Medicine Surgery

Orthopedic Infections and Treatments

Description

This cluster of papers focuses on the diagnosis, treatment, and management of prosthetic joint infections, including periprosthetic joint infections associated with orthopedic implants. It covers topics such as osteomyelitis, antibiotic prophylaxis, biofilm infections, diagnostic imaging techniques, and surgical approaches. The papers also discuss infection risk factors and the economic burden of periprosthetic joint infections.

Keywords

Prosthetic Joint Infections; Periprosthetic Joint Infection; Orthopedic Implants; Osteomyelitis; Implant-Associated Infections; Antibiotic Prophylaxis; Biofilm Infections; Diagnostic Imaging; Surgical Management; Infection Risk Factors

INTRODUCTION Jon Terry Mader (Fig 1) was born on March 21, 1944 in Madison, WI. He earned his BA and MD degrees at Wabash College at Indiana University in 1966 … INTRODUCTION Jon Terry Mader (Fig 1) was born on March 21, 1944 in Madison, WI. He earned his BA and MD degrees at Wabash College at Indiana University in 1966 and 1970, respectively. He trained in Internal Medicine at the University of Texas Medical Branch in Galveston, TX and made his career there in the Division of Infectious Disease in the Department of Internal Medicine. At the time of his death on October 25, 2002, he had risen to the positions of Professor of Medicine, Professor of Pathology, and Adjunct Professor of Orthopaedic Surgery. During his life, he published more than 145 peerreviewed papers on osteomyelitis, antibiotic therapy, hyperbaric oxygen, joint infections, the foot in patients with diabetes, and the use of the Ilizarov technique for the treatment of musculoskeletal infections. He also was the principle investigator in numerous funded research projects and the coauthor of Musculo-Skeletal Infection. He died when the book was in its final stages of production.Fig 1.: John T. Mader, MDIn addition, Dr. Mader was a gifted athlete, Eagle Scout, captain in the U.S. Naval Reserve, and regarded with respect and affection by his patients and colleagues. Henry H. Sherk, MD At the University of Texas Medical Branch (UTMB) in Galveston, Texas, the adult osteomyelitis service now treats ten new cases of osteomyelitis each month. Since January 1981, 425 patients have been evaluated and 900 procedures performed to treat 240 lesions. In our experience, the treatment of adult osteomyelitis is influenced by four factors: the condition of the host, the functional impairment caused by the disease, the site of involvement, and the extent of bony necrosis. Without reference to these factors, it is difficult to compare the results of different treatment protocols 1–5 and the effectiveness of new therapeutic modalities. 6–9 The UTMB classification of adult osteomyelitis 10 combines four anatomic types (the disease) with three physiologic classes (the host) to define 12 clinical stages (Table I). A distinction between the acute and chronic process has not been necessary. 11 The classification system incorporates the four prognostic factors, delineates treatment for progressive stages of the disease, and provides guidelines for the use of adjunctive therapies.TABLE I: The UTMB Staging System for Adult OsteomyelitisTHE UTMB TREATMENT PROTOCOL FOR ADULT OSTEOMYELITIS ( TABLE II)TABLE II: UTMB Treatment Protocol for Adult OsteomyelitisTABLE II: UTMB Treatment Protocol for Adult Osteomyelitis (Continued)The UTMB prospective study of adult osteomyelitis began in June 1981. The methods have remained unchanged except for the antibiotic recommendations for emergency coverage and for acrylic bead mixtures. The protocol itself is unique: patient selection and medical/surgical treatment are predetermined by the clinical staging system; the preoperative antibiotic program is based on outpatient biopsy data, and the patient follow-up system correlates a clinical and biologic response to therapy. Patient Evaluation Condition of the host. Host deficiencies influence treatment options, prognosis, and the interpretation of treatment results. Following debridement surgery, the host must be able to impede infection, resist contamination, heal surgical wounds, and tolerate the metabolic stress of sequential surgeries. A list of factors influencing the ability of the host to elicit an effective response to infection and treatment is found in Table III. Local factors lead to a vascular compromise of bone and soft tissue. Systemic compromise affects immune surveillance, metabolism, leukocyte function, and/or large vessel disease. Local and systemic factors may combine (e.g., diabetes mellitus).TABLE III: Systemic or Local Factors that Affect Immune Surveillance, Metabolism, and Local VascularityDisability of the patient. The functional impairment caused by the disease, the reconstruction options, and the metabolic consequences of aggressive therapy influence the selection of treatment candidates. A draining sinus with minimal pain and/or dysfunction is not, by itself, an indication for surgical treatment. At times, the procedures required to arrest or palliate the disease are of such magnitude that treatment can lead to loss of function, limb, or life. In these latter instances, quality of life is the major factor influencing the decision to pursue therapy. Physiologic Classification (Host). At UTMB, the condition of the host and the relative disability caused by the disease are combined in a physiologic classification (Table I). A patient with a normal physiologic response to infection and surgery is designated an A-Host; a compromised patient is classified a B-Host and will have either local (BL), systemic (BS) or combined (BL,S) deficiency in wound healing (Table III). When the treatment or results of treatment are more compromising to the patient than the disability caused by the disease itself, the patient is classified a C-Host. Thus, the selection of surgical candidates may vary from institution to institution until there has been a standardization of concepts, methods, and techniques. Disease Assessment Persistent osteomyelitis is a surgical disease. Since debridement is the unchallenged cornerstone of successful therapy, a classification of osteomyelitis based on the site of necrosis will have specific implications for surgical management. Using such a system, four anatomically defined types of osteomyelitis become apparent: medullary, superficial, localized, and diffuse (Fig. 1). However, the condition of the host, regional vascularity, local milieu, and extent of necrosis will influence the natural history of the disease. 11Fig. 1: Anatomic classification of adult osteomyelitis.Anatomic classification. The medullary and superficial types of osteomyelitis share a pathophysiologic component: soft tissue compromise. In medullary osteomyelitis the primary lesion is endosteal. The etiology of the disease is variable but the nidus remains constant: ischemic scar, chronic granulations, and splinter sequestra within the medullary canal. In superficial osteomyelitis the problem is on the surface of the bone. This is a true contiguous focus lesion. A compromised soft tissue envelope either begins or perpetuates an exposure of the bone. The involved surface may be on an old saucerization, and healed Papineau graft, the prominent callus of a healed open fracture, or the metatarsal head in a neuropathic foot ulcer. The hallmark of localized osteomyelitis is full-thickness, cortical sequestration and/or cavitation. It is a discrete lesion within a stable bony segment. Although localized osteomyelitis usually follows trauma, it often has the combined features of medullary and superficial osteomyelitis and may even result as an extension of either of these two entities. Diffuse osteomyelitis is a permeative, circumferential, or through-and-through disease of hard and soft tissue. In this type, an intercalary segment of the skeletal unit must be removed in order to resect all the compromised tissue. Instability is present either before or after a thorough debridement. Stabilization is an essential factor in the treatment and separates the diffuse lesion from the other types of osteomyelitis. Infected nonunions, end-stage septic joints, and through-and-through metaphyseal/epiphyseal lesions of the proximal femur are examples of this type of osteomyelitis. Clinical staging of adult osteomyelitis. The four anatomic types of osteomyelitis are numerically ordered according to the complexity of the disease and/or its treatment: I—medullary; II—superficial; III—localized; IV—diffuse (Table I). In our classification system, the anatomic type (I-IV) is combined with the physiologic class (A-C) to designate one of 12 clinical stages of adult osteomyelitis. The clinical stage can change during the course of treatment (Table IV).TABLE IV: Clinical Stage ManipulationMicrobiology The bacteria responsible for the infection may be reliably isolated in two ways: preoperative biopsies, or from tissue sampled at the time of debridement surgery. 15 All isolated pockets of granulation tissue or necrosis must be sampled. Whenever possible, an antibiotic regime tailored to the sensitivities of all organisms isolated from biopsy material obtained in the outpatient setting is begun prior to debridement. 16 At the first and all subsequent debridements, multiple biopsies are obtained again for aerobic/anaerobic cultures and histologic evaluation. During therapy, antibiotic coverage may be changed or modified on the basis of clinical findings, serial debridement isolates and their sensitivities, inadequate serum bactericidal levels, abnormal laboratory studies, and/or patient intolerance. Antibiotics are given for six weeks after the last major debridement surgery. 16 At UTMB, all isolated organisms are placed in defibrinated sheep blood and stored at −70°C for future reference. Outpatient intravenous antibiotic therapy is utilized once serum bactericidal levels and/or surgical wounds permit. 13 Surgical Treatment Osteomyelitis surgery is disciplined and demanding. The average number of operations for a limb-salvage patient in our 1983 series as 3.8 procedures. Depending on the clinical stage of the disease and the planned reconstruction, the diagnostic biopsies, debridements, and reconstructions may be combined or performed separately. Biopsies are usually performed in the outpatient setting under local anesthesia. The organisms are thereby established, and questionable areas of involvement are assessed histologically. Debridement. As in musculoskeletal tumor surgery, careful preoperative planning is critical to achieve a high rate of success and to minimize wound complications in the patient with osteomyelitis. The debridement is direct, atraumatic, and executed with the reconstruction in mind. Whenever possible, the incisions are laced between myocutaneous territories, at times disregarding previous incisions. Soft tissue retraction is minimized by careful wound planning. Sinus tracts are excised if present for more than one year. All dead or ischemic hard and soft tissues are excised unless a palliative procedure has been chosen from the start. The extent of the debridement is predictable from the preliminary assessment. 16 If complete excision will threaten stability, external fixation and/or a bypass graft may be necessary prior to or during debridement surgery. At UTMB, the instruments used in the debridement procedures include scalpels, curettes, straight stem and angled dental mirrors, and a pneumatic bone scalpel. Because of the speed and gentle efficiency of this pneumatic system, osteotomes are rarely used. Tetracycline labeling, fluorescein, and other dyes have not been useful. The debridement process begins in a centrifugal fashion. This technique retains an outer ring of bone that shares its circulation with the attached soft tissues. This shell of bleeding bone is dressed with either bone grafts, antibiotic beads, or soft tissue at the time on reconstruction. The residual cortical and cancellous bone must bleed uniformly (Fig. 6). Definitive wound management usually takes place five to seven days after the last debridement. In the interim, the wound usually is left open.Fig. 6: Tangential excision with the bone scalpel is carried down to uniform haversian or cancellous bleeding (the paprika sign 17).Dead space management. The techniques of managing the dead space created by debridement surgery are illustrated in Fig. 7. Secondary intention healing is discouraged; the scar tissue that fills the defect later becomes avascular and may lead to recurrent drainage. Similarly, suction/drainage systems are rarely used. The goal of surgery is to replace dead bone and scar with durable, vascularized tissue.Fig. 7: Methods of dead space management.A complete wound closure is secured whenever possible. Cancellous bone grafts are placed beneath local or transferred tissues when structural augmentation is necessary or a significant dead space will otherwise persist in the bone. Bypass grafts are performed when an in situ reconstruction will prove inadequate or is not feasible (Fig. 8). Open cancellous grafts 14 are used sparingly as the epithelial coverage is not durable and may lead to superficial ulceration following minor trauma or persistent venous stasis. 18 They are, however, simple to do, effective, and particularly useful when a free or local tissue transfer is not an option.Fig. 8: Bone graft techniques.Antibiotic-impregnated acrylic beads 6 have been used to sterilize and/or temporarily maintain a dead space created by debridement surgery. In our experience, any patient-compatible, powdered antibiotic may be safely delivered in this manner; it must first be adequately pulverized and then thoroughly mixed with the powdered cement prior to adding the monomer. 10 Thermal stability of the antibiotic(s) is not necessary when the beads are fashioned in the dough phase. 19 Two or three antibiotics may be combined in a single mix. Before using this technique, the debridement must first be thorough and the wound flora ideally sensitive to the antibiotic mixed with the cement. The beads usually are removed within two to four weeks and replaced with cancellous bone grafts. If strung on a line, 6,20 the beads are removed in ten to 12 days. The five antibiotics most commonly used in beads and their mixing ratios are listed in Table V. If the volumetric ratio of the powders exceeds 24cc/120cc (antibiotic/40gm cement), the cement will not harden reliably.TABLE V: Antibiotic Bead Cocktails June 1984Application Stage IA,B,C: Medullary Osteomyelitis ( Fig. 9A, 9B)Fig. 9A: Stage I classification of osteomyelitis.Fig. 9B: Treatment algorithm for Stages IA and IB.Once the medullary process extends into the soft tissues, the usefulness of medical management alone will depend on the site and extent of the process, the physiologic class of the patient, and the functional disability expected from disease and treatment. The majority of the patients with Stage I osteomyelitis are systemically compromised hosts and suffer stage progression to Stage IIIB or IVB. When extension occurs, the process usually becomes intraarticular and the subchondral bone and articular cartilages sequester. Protection (stick, cast, or orthosis) usually is necessary until remodeling occurs and/or bone grafts mature. This stage often is debrided and closed on the first look. Closure over the obliterated dead space frequently can be achieved with simple approximation of the soft tissues. The organism is obtained preoperatively, and wound closure is protected by appropriate antibiotic coverage. 23 To completely excise the infected contents of the medullary canal, a small unroofing of the cortex is required. This minimal access to the canal is sufficient for an extended curettage 21 and/or medullary reaming. 22 When using the latter technique, the disease must be situated within an isthmus or limited to the tract of an intramedullary nail, otherwise a combination of reaming and unroofing will be necessary. The bony entry should be placed slightly askew of the anticipated soft tissue closure to prevent inversion of the wound margins and persistent drainage. The operations for treating Stage I lesions apply whenever medullary involvement is present (Fig. 10).Fig. 10: Debridement techniques are unique to each stage but combine as the complexity of the disease increases.Stage IIA,B,C: Superficial Osteomyelitis ( Fig. 11A, 11B)Fig. 11A: Stage II classification of osteomyelitis.Fig. 11B: Treatment algorithm for Stages IIA and IIBThe management of superficial osteomyelitis requires considerable experience with complex soft tissue transfers. Ischemic soft tissues are excised and the exposed bony surface is tangentially removed (decortication) until the paprika sign 17 is observed. A pedicle flap or free tissue transfer is performed at the same sitting or as a delayed procedure. The key to the success of this method is a live and clean prior to soft tissue coverage. (sic) If the Stage II lesion is caught in the acute or subacute stage, treatment with pressure garments, orthoses, and/or local wound care may be sufficient. The wounds heal unless tissue oxygen tensions, local mechanical factors, or patient cooperation are not favorable. At UTMB, the septic joint is classified as a superficial osteomyelitis (osteochondritis). The soft tissue component of the process is the compromised synovium. The disease progresses and responds to treatment as do the other Stage II lesions; they resolve with early host alteration and progress to cavitation and full-thickness sequestration (subchondral), if untreated. The operations for treating Stage II lesions apply whenever superficial involvement is present (Stage II, III, IV). Stage IIIA,B,C: Localized Osteomyelitis ( Fig. 12A, 12B)Fig. 12A: Stage III classification of osteomyelitis.Fig. 12B: Treatment algorithm for Stages IIIA and IIIB.The hallmark of this process is cortical sequestration and cavitation. Debridement surgery usually involves sequestrectomy, saucerization, medullary decompression, scar excision, and superficial decortication. The reconstruction will depend on the dead space created, the integrity of the residual bone, and the site of involvement. The procedures include viable hard and soft tissue transfers, cancellous bone grafts, bypass procedures, and simple wound approximation. Prophylactic stabilization is provided when the extent of the debridement places the bone at risk for fracture. 24,25 Most Stage III lesions are posttraumatic and satellite or skip foci of infection may be present within the treatment zone secondary to prior surgeries (internal or external fixations). The preliminary evaluation (protocol steps I, II, III) usually identifies these lesions and directs an appropriate staging and treatment. 16 The operations for treating Stage III lesions apply whenever cavitation occurs (Stage III, IV) and often include procedures from Stage I and II treatment protocols (Fig. 11B) Stage IVA,B,C: Diffuse Osteomyelitis ( Fig. 13A, 13B)Fig. 13A: Stage IV classification of osteomyelitis.Fig. 13B: Treatment algorithm for Stage IV.B-Hosts and segmental defects are common in this stage and potentiate the risk for developing a wound healing disturbance, i.e., nonunion, central bone graft necrosis, opportunistic infections, and stress fractures. The techniques used in managing Stage IV osteomyelitis are conceived and executed with a stabilization procedure in mind. The preoperative planning must be precise and exhaustive to avoid tissue devitalization, unnecessary hardware in the wound, and in inefficient use of cancellous bone reserves. External fixation devices, medullary rods, and cortical plates are used selectively and are listed according to our preference and frequency of application. In our experience, external fixation is the safest and most versatile system. Extent of Necrosis When the host is unable to resorb or expel infected, nonviable tissues, the infection becomes chronic. The nidus will persist until the pathophysiology of the process is reversed by appropriate therapy. Although debridement surgery usually is the treatment of choice, some lesions consistently respond to alternate forms of therapy. The common denominator in these wounds is infected scar tissue, not bone sequestration. This entity is called minimal necrosis osteomyelitis. Manipulation of host parameters frequently is the treatment of choice rather than debridement surgery. Vertebral osteomyelitis. Hematogenous osteomyelitis of the vertebral column is an example of osteomyelitis with minimal necrosis. When the Stage I lesion progresses to Stage IV in the spine, the process usually becomes intraarticular and the disc sequesters within the septic joint. The rich blood supply and high cancellous to cortical bone ratio favor a rapid resorption of subchondral bone and medullary debris. The disease will arrest if motion is curtailed and the host augmented with appropriate antibiotic therapy. The disc is a resorbable sequestrum. Deep/superficial osteomyelitis. There is a deep Stage II lesion with minimal necrosis. Often these lesions are failures in management of Stages III or IV where treatment involved a suction-irrigation system or secondary intention healing. In the preliminary evaluation, no dead bone can be identified to account for a chronic sinus. Here the ischemic soft tissue adjacent to deep bony surfaces is the nidus that leads to persistent disease. Therapeutic options include exploration and soft tissue manipulation, hyperbaric oxygen therapy, or skillful neglect. Infected nonunion with minimal bony necrosis. In this lesion, the problem again is infected scar tissue. Surface resorption and union are impeded by constant motion and the resultant local compromise. 26 Immobilization and/or bypass surgery will relieve the soft tissue compromise, promote union, and enhance autosequestrectomy. 27 If the necrosis is more than superficial in septic pseudarthrosis, drainage often recurs despite bony union. THE UTMB EXPERIENCE—A PRELIMINARY REPORT From June 1981 to December 1983, 357 patients with adult osteomyelitis were evaluated and staged on our service. 10 Definitive treatment was given to 189 patients with 192 lesions, and 747 surgical procedures were performed (Table VI). There were 46 amputations: 41 were a first procedure; five followed a limb-salvage attempt. Of the primary amputations 90% (37/41) were in B-Hosts: 86% Stage IVB, 14% Stage IIB. Two of the patients with late amputations were disease-free at nine and 12 months but were unsuccessfully rehabilitated. These two patients were a young woman (Stage IIIA) with Munchausen's syndrome and a young man (Stage IVBS/L) with an ipsilateral sciatofemoral palsy. During the first six months of therapy there were three deaths, including one (IVBL) due to trauma at four months, one (IVBS) from hypoglycemia at three months, and the third (IIBS/L) from an induced bleeding diasthesis at three weeks.TABLE VI: Classification of 192 Sites of Adult Osteomyelitis Treated Surgically at UTMB (1981–1983)Of the patients evaluated, 15% (54/357) were C-Hosts. The remaining 110 of the 164 patients not treated by our service were either outside the consultations (46), IIB or IVB lesions we referred for amputations (50), or osteomyelitis with minimal necrosis (14). RESULTS Sixty-three patients entered our limb-salvage protocol and were followed for a minimum of two years (Table VII). Among these limb-salvage candidates, 93.6% (59/63) were disease-free and ambulating without assistance at 24 months. Two patients had more than one lesion, bringing the total number of sites treated to 65. Treatment led to an arrest in 95.4% (62/65) of the lesions.TABLE VII: Sixty-three Patients Followed ≥ Two Years (Clinical and Laboratory Evaluations at 24 Months) (A & B Hosts Combined)There were nine treatment failures (Table VIII): eight initial, one late, and four overall. These failures were defined by recurrent drainage (5/9), infected nonunion with minimal necrosis (2/9), tumor contamination (1/9), and unsuccessful rehabilitation (1/9). The reasons for initial failure included inadequate debridement (6), poor fixation (1), and stress fracture (1). Of the initial treatment failure group, 62% (5/8) were arrested with retreatment. Three of the four overall treatment failures were in the initial failure group: an occult carcinoma was undiagnosed until the third debridement/biopsy, and two compromised patients suffered stage progression and underwent a below-knee amputation after completing a limb-salvage protocol. The other overall failure (IIIA-Munchausen's) had an ablation elsewhere at 12 months despite disease arrest (pathology report).TABLE VIII: Sixty-three Patients Followed ≥ Two Years Treatment FailuresAll 65 lesions were indium-positive prior to treatment. Since there were four amputations, only 61 sites were available for followup. Six of these 61 lesions (10%) had a normal sedimentation rate and an abnormal indium scan at 18 months (one IIIA, three IVA, and two IVB lesions). Three of these same six patients were still indium-positive with normal sedimentation rates at 24 months (one IVA and the two IVB lesions). One palliative procedure was performed in the original group of 63 patients (C.W.-IVBL); this patient's sedimentation rate and indium scan are still abnormal at 54 months. The organisms isolated in 50 consecutive patients are listed in Table IX. Staphylococcus aureus was the most commonly isolated bacteria. More than two organisms were present in 46% of our patients. The number and type of organisms had no bearing on the outcome of treatment, providing an adequate debridement was performed. In all cases, appropriate antibiotic coverage was gained and maintained for the duration of the treatment protocols.TABLE IX: Microbial Spectrum in 50 Consecutive PatientsRepresentative sedimentation rate profiles for Stage IA/B, IIA, IIIA, and IVA are seen in Figs. 14A–14D. The Stage I profile is a composite of A and B hosts to illustrate the problem that occurs in using a sedimentation rate to follow compromised patients. These hosts are plagued by minor illnesses and peripheral sores that affect this index. In Stage IIA, the sedimentation rate did not fall before three months, a profile identical to soft tissue infections. The profiles for Stages IIIA and IVA reflect the wound healing disturbances associated with bone grafts, internal hardware, pin tract infections, and nonunion.Fig. 14: Representative sedimentation rate profiles for Stage IA/B, IIA, IIIA, and IVA. Most Type I lesions are in B-hosts. Sedimentation rate is an inadequate follow-up index in these patients, secondary to frequent illnesses (A-arrows). The response of the only A-host in the StageIA/B group (patient I.A.) mimicked a patient with a StageIIIA osteomyelitis.DISCUSSION The clinical stages of adult osteomyelitis may interplay during both their natural history and their response to therapy (Fig. 15). An anatomic or physiologic stage progression (upstaging) increases the difficulty of treatment. The prognosis for disease arrest without ablation is improved when a downstaging of the process can be accomplished by therapy.Fig. 15: Cavitation and reclassification to Stage III or IV will occur whenever Stages I and II appear simultaneously.Patients with Stage IV lesions suffer the greatest number of complications and represent the majority of treatment failures. The Stage IVB sedimentation rate profile (Fig. 16) represents a composite of B-hosts with type IV lesions whose deficiencies were corrected with successful host alteration (Table II). The sedimentation rates and arrest rate in these patients have mimicked the Stage IVA responses. These encouraging results have strengthened our commitment to the diagnosis and treatment of host deficiencies. The B-host challenges the frontiers of modern medicine and brings the search for effective adjunctive therapies to the forefront. 6–9,28–33Fig. 16: The sedimentation rate profile of three B-hosts with Type IV lesions who underwent physiological downstaging to Class A by host alteration.In our experience, indium-111 chloride imaging has been accurate in localizing persistent osteomyelitis in adults. 34 The cytokinetics of this imaging technique have not been established. Detailed anatomic mappings of specimens amputated 24 hours after indium chloride injection have demonstrated heavy indium concentration in tissues laden with histiocytes, macrophages, plasma cells, and lymphocytes as well as those with leukocytic infiltrates. This scan is not limited to acute and subacute processes 35 and appears to have a limited affinity for noninfected, reactive bone. 36 The methods used in the management of osteomyelitic wounds have influenced our long-term results. All of the amputation stumps reverted to normal indium studies by 12 months. Similarly, 94% of the wounds managed with primary closure (Fig. 7) in Stages II and III displayed normal indium concentrations at one year. The biology of wound healing in complex reconstructions lends support to the gradual resolution in the indium scan sequence depicted in the follow-up protocol. Eighty-seven percent of the Stage I, III, and IV lesions were indium-positive at 12 months if dead space management included cancellous bone grafts and/or an osteosynthesis. However, this percentage decreased to 12% and 6% at 18 and 24 months, respectively. Two of our overall treatment failures had at least one normal sedimentation rate prior to a recurrence of disease at seven and 12 months. No patient with a positive-turned-negative indium scan has experienced recurrence. Our prospective study should help define the role of sequential indium-111 chloride imaging in following treated cases of adult osteomyelitis. CONCLUSIONS The treatment and prognosis of adult osteomyelitis correlate with the clinical stage of the disease. The UTMB staging system provides guidelines for the use of adjunctive therapies and a basis for comparing treatment protocols from institution to institution. Serial indium-111 chloride scans may prove a sensitive index for following patients with treated osteomyelitis.
The direct examination of tissue and biomaterials from prosthesis-related infections of twenty-five patients showed that the causative bacteria grew in glycocalyx-enclosed biofilms that were adherent to surfaces of biomaterials and … The direct examination of tissue and biomaterials from prosthesis-related infections of twenty-five patients showed that the causative bacteria grew in glycocalyx-enclosed biofilms that were adherent to surfaces of biomaterials and tissues in 76 per cent. This high rate of recovery of adherent biofilm-mediated growth suggests that the process occurs commonly in the presence of a foreign body or biomaterial-related infection. Because of the adherent mode of growth of the infecting organisms, accurate microbiological sampling was difficult. The analysis of joint fluids or of swabs of excised tissue and of prosthetic surfaces often yielded only one species from what was a polymicrobial population based on electron microscopic studies. We adapted direct quantitative sampling methods from environmental microbiology in order to recover a large number of species from these infections, but comparison of the organisms isolated by these techniques with the morphological types that were seen by electron microscopy indicated that in some instances all bacterial components of the biofilms were still not being recovered.
Background: Total hip arthroplasty is a commonly performed procedure in the United States and Canada that is associated with a definite risk of postoperative infection. Moreover, diagnosing an infection after … Background: Total hip arthroplasty is a commonly performed procedure in the United States and Canada that is associated with a definite risk of postoperative infection. Moreover, diagnosing an infection after total hip arthroplasty can present a challenge as there are no preoperative tests that are consistently sensitive and specific for infection in patients who need a revision arthroplasty. The present prospective study was performed to evaluate a variety of investigations for the diagnosis of infection at the site of a previous arthroplasty in order to determine if any combination of diagnostic studies could be used to determine which patients are at risk for a postoperative wound infection.Methods: We prospectively analyzed the preoperative and intraoperative investigations used for the diagnosis of infection in 178 patients who had a total of 202 revision hip replacements. Clinical data were collected preoperatively. Investigations to determine the presence or absence of infection included a white blood-cell count, measurement of the erythrocyte sedimentation rate, measurement of the level of C-reactive protein, preoperative aspiration of the joint, intraoperative gram-staining and culture of periprosthetic tissue, a white blood-cell count in synovial fluid, and examination of intraoperative frozen sections. Frozen sections were analyzed in a blinded fashion without knowledge of clinical or laboratory data. Patients receiving antibiotics at the time of aspiration or collection of specimens for intraoperative culture were excluded from the analysis of those investigations, regardless of the results of the cultures. A positive result (suggestive of infection) was clearly defined for each of the investigations.Results: Thirty-five hips (17 percent) were determined to be infected on the basis of clinical findings and positive results, according to the defined criteria, of investigations. With inflammatory conditions excluded, the sensitivity, specificity, positive predictive value, and negative predictive value were 0.82, 0.85, 0.58, and 0.95, respectively, for the erythrocyte sedimentation rate and 0.96, 0.92, 0.74, and 0.99, respectively, for the level of C-reactive protein. All patients who had a periprosthetic infection had an elevated erythrocyte sedimentation rate or level of C-reactive protein, but not always both. When patients who were receiving antibiotics were excluded, the results of aspiration of the joint were 0.86 for sensitivity, 0.94 for specificity, 0.67 for the positive predictive value, and 0.98 for the negative predictive value. Intraoperative studies revealed sensitivities, specificities, positive predictive values, and negative predictive values of 0.19, 0.98, 0.63, and 0.89, respectively, for gram-staining of specimens of the most inflamed-appearing tissue; 0.36, 0.99, 0.91, and 0.90, respectively, for the white blood-cell count in synovial fluid; and 0.89, 0.85, 0.52, and 0.98, respectively, for a neutrophil count in synovial fluid of more than 80 percent. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.80, 0.94, 0.74, and 0.96, respectively, for the frozen sections and 0.94, 0.97, 0.77, and 0.99, respectively, for the intraoperative cultures.Conclusions: The combination of a normal erythrocyte sedimentation rate and C-reactive protein level is reliable for predicting the absence of infection. Aspiration should be used when the erythrocyte sedimentation rate or the C-reactive protein level is elevated or when a clinical suspicion of infection remains. We found the gram stain to be unreliable. Examination of intraoperative frozen sections is useful in equivocal cases or when hematological markers may be falsely elevated because of an inflammatory or other condition.
Background: A child who has an acutely irritable hip can pose a diagnostic challenge. The purposes of this study were to determine the diagnostic value of presenting variables for differentiating … Background: A child who has an acutely irritable hip can pose a diagnostic challenge. The purposes of this study were to determine the diagnostic value of presenting variables for differentiating between septic arthritis and transient synovitis of the hip in children and to develop an evidence-based clinical prediction algorithm for this differentiation.Methods: We retrospectively reviewed the cases of children who were evaluated at a major tertiary-care children's hospital between 1979 and 1996 because of an acutely irritable hip. Diagnoses of true septic arthritis, presumed septic arthritis, and transient synovitis were explicitly defined on the basis of the white blood-cell count in the joint fluid, the results of cultures of joint fluid and blood, and the clinical course. Univariate analysis and multiple logistic regression analysis were used to compare groups. A probability algorithm for differentiation between septic arthritis and transient synovitis on the basis of independent multivariate predictors was constructed and tested.Results: Patients who had septic arthritis differed significantly (p < 0.05) from those who had transient synovitis with regard to the erythrocyte sedimentation rate, serum white blood-cell count and differential, weight-bearing status, history of fever, temperature, evidence of effusion on radiographs, history of chills, history of recent antibiotic use, hematocrit, and gender. Patients who had true septic arthritis differed significantly (p < 0.05) from those who had presumed septic arthritis with regard to history of recent antibiotic use, history of chills, temperature, erythrocyte sedimentation rate, history of fever, gender, and serum white blood-cell differential. Four independent multivariate clinical predictors were identified to differentiate between septic arthritis and transient synovitis: history of fever, non-weight-bearing, erythrocyte sedimentation rate of at least forty millimeters per hour, and serum white blood-cell count of more than 12,000 cells per cubic millimeter (12.0 x 109 cells per liter). The predicted probability of septic arthritis was determined for all sixteen combinations of these four predictors and is summarized as less than 0.2 percent for zero predictors, 3.0 percent for one predictor, 40.0 percent for two predictors, 93.1 percent for three predictors, and 99.6 percent for four predictors. The chi-square test for trend and the area under the receiver operating characteristic curve indicated excellent diagnostic performance of this group of multivariate predictors in identifying septic arthritis.Conclusions: Although several variables differed significantly between the group that had septic arthritis and the group that had transient synovitis, substantial overlap in the intermediate ranges made differentiation difficult on the basis of individual variables alone. However, by combining variables, we were able to construct a set of independent multivariate predictors that, together, had excellent diagnostic performance in differentiating between septic arthritis and transient synovitis of the hip in children.
The results of eleven two-stage reimplantations to salvage eleven infected total knee arthroplasties in ten women (seven with osteoarthritis and three with rheumatoid arthritis) were evaluated after an average follow-up … The results of eleven two-stage reimplantations to salvage eleven infected total knee arthroplasties in ten women (seven with osteoarthritis and three with rheumatoid arthritis) were evaluated after an average follow-up of thirty-four months. The staged procedures included removal of all of the components of the prosthesis and all cement, then six weeks of parenteral antibiotic therapy (monitored by maintaining serum bactericidal levels at a peak dilution of 1:8), and finally reimplantation with a total condylar-type prosthesis. All antibiotics were discontinued after reimplantation. At follow-up, no patient had had a recurrence of the original infection, but one had a hematogenous infection with a different organism secondary to an infected bunion. The results after reimplantation were rated excellent in five knees, good in four, and fair in two. Weakness of the extensor mechanism with an extension lag was the most frequent complication. We do not believe that antibiotic therapy alone is adequate for the management of an infection around a prosthesis. The method described appears to be effective but it is costly and time-consuming. The surgical procedures and medical management are technically difficult, often special equipment and a custom-made prosthesis are required, and there are no shortcuts.
Staphylococcus comprises up to two-thirds of all pathogens in orthopedic implant infections and they are the principal causative agents of two major types of infection affecting bone: septic arthritis and … Staphylococcus comprises up to two-thirds of all pathogens in orthopedic implant infections and they are the principal causative agents of two major types of infection affecting bone: septic arthritis and osteomyelitis, which involve the inflammatory destruction of joint and bone. Bacterial adhesion is the first and most important step in implant infection. It is a complex process influenced by environmental factors, bacterial properties, material surface properties and by the presence of serum or tissue proteins. Properties of the substrate, such as chemical composition of the material, surface charge, hydrophobicity, surface roughness and the presence of specific proteins at the surface, are all thought to be important in the initial cell attachment process. The biofilm mode of growth of infecting bacteria on an implant surface protects the organisms from the host immune system and antibiotic therapy. The research for novel therapeutic strategies is incited by the emergence of antibiotic-resistant bacteria. This work will provide an overview of the mechanisms and factors involved in bacterial adhesion, the techniques that are currently being used studying bacterial-material interactions as well as provide insight into future directions in the field.
Six thousand four hundred eighty-nine knee replacements were done in 6120 patients at the authors' institution between 1993 and 1999. Operations were done in a theater with vertical laminar flow … Six thousand four hundred eighty-nine knee replacements were done in 6120 patients at the authors' institution between 1993 and 1999. Operations were done in a theater with vertical laminar flow and with the surgical team using body exhaust suits. Of these knee replacements, 116 knees became infected and 113 were available for followup. One hundred of the infections occurred in patients undergoing primary knee replacement, whereas the remaining infections occurred in patients undergoing revision knee replacement. Ninety-seven of these knees (86%) had deep periprosthetic infections and the remaining 16 knees had superficial wound infections. One third of the deep infections occurred within the first 3 months after surgery and the remaining 2/3 occurred after 3 months. The overall early deep infection rate for patients undergoing a primary knee replacement was 0.39%, whereas the rate for patients undergoing a revision knee replacement was 0.97%. A cohort of noninfected knee replacements from patients matched for gender, age, and month of surgery was used as a control group. Those comorbidities that were statistically significant in increasing the risk of infection were prior open surgical procedures, immunosuppressive therapy, poor nutrition, hypokalemia, diabetes mellitus, obesity, and a history of smoking. Patients undergoing revision procedures had a statistically higher risk of infection than did patients undergoing primary surgeries. If the surgery took longer than 2.5 hours, the risk of infection was increased significantly. There was no change in the infection rate when the perioperative antibiotic prophylaxis was decreased from 48 to 24 hours after surgery. The predominant infectious organisms were gram-positive (Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus Group B). Twenty percent of the knees that were infected clinically had no organisms that could be identified. In each case, the patient had been treated empirically at another institution with antibiotics before a culture of the joint was obtained.
Propionibacterium acnes is known primarily as a skin commensal. However, it can present as an opportunistic pathogen via bacterial seeding to cause invasive infections such as implant-associated infections. These infections … Propionibacterium acnes is known primarily as a skin commensal. However, it can present as an opportunistic pathogen via bacterial seeding to cause invasive infections such as implant-associated infections. These infections have gained more attention due to improved diagnostic procedures, such as sonication of explanted foreign materials and prolonged cultivation time of up to 14 days for periprosthetic biopsy specimens, and improved molecular methods, such as broad-range 16S rRNA gene PCR. Implant-associated infections caused by P. acnes are most often described for shoulder prosthetic joint infections as well as cerebrovascular shunt infections, fibrosis of breast implants, and infections of cardiovascular devices. P. acnes causes disease through a number of virulence factors, such as biofilm formation. P. acnes is highly susceptible to a wide range of antibiotics, including beta-lactams, quinolones, clindamycin, and rifampin, although resistance to clindamycin is increasing. Treatment requires a combination of surgery and a prolonged antibiotic treatment regimen to successfully eliminate the remaining bacteria. Most authors suggest a course of 3 to 6 months of antibiotic treatment, including 2 to 6 weeks of intravenous treatment with a beta-lactam. While recently reported data showed a good efficacy of rifampin against P. acnes biofilms, prospective, randomized, controlled studies are needed to confirm evidence for combination treatment with rifampin, as has been performed for staphylococcal implant-associated infections.
Modern techniques have reduced the frequency of infections that are associated with prosthetic joints, but such infections continue to pose difficult problems in clinical management. Advances in understanding biofilms and … Modern techniques have reduced the frequency of infections that are associated with prosthetic joints, but such infections continue to pose difficult problems in clinical management. Advances in understanding biofilms and the pathogenesis of microbial interactions with the implant have led to more rational approaches to therapy. This review offers guidance in establishing the diagnosis correctly and an algorithm summarizing the appropriate medical and surgical options.
ALTHOUGH osteomyelitis often falls into the purview of the orthopedic surgeon, the internist and pediatrician are also very frequently involved in the initial diagnosis and the subsequent antibiotic management of … ALTHOUGH osteomyelitis often falls into the purview of the orthopedic surgeon, the internist and pediatrician are also very frequently involved in the initial diagnosis and the subsequent antibiotic management of patients with bone infections. The wide spectrum of manifestations of disease related to the site of involvement, the infecting organism, the initiating event and the acute or chronic course of the illness provides many questions not yet fully answered. Has the frequency of the disease continued to change two decades after the introduction of antimicrobial agents? Is the bacteriology of osteomyelitis the same as in the preantibiotic era, or does . . .
Periprosthetic joint infection is one of the most challenging complications of joint arthroplasty. We identified current risk factors of periprosthetic joint infection after modern joint arthroplasty, and determined the incidence … Periprosthetic joint infection is one of the most challenging complications of joint arthroplasty. We identified current risk factors of periprosthetic joint infection after modern joint arthroplasty, and determined the incidence and timing of periprosthetic joint infection. We reviewed prospectively collected data from our database on 9245 patients undergoing primary hip or knee arthroplasty between January 2001 and April 2006. Periprosthetic joint infections developed in 63 patients (0.7%). Sixty-five percent of periprosthetic joint infections developed within the first year of the index arthroplasty. The infecting organism was isolated in 57 of 63 cases (91%). The most common organisms identified were Staphylococcus aureus and Staphylococcus epidermidis. We identified the following independent predictors for periprosthetic joint infection: higher American Society of Anesthesiologists score, morbid obesity, bilateral arthroplasty, knee arthroplasty, allogenic transfusion, postoperative atrial fibrillation, myocardial infarction, urinary tract infection, and longer hospitalization. This study confirmed some previously implicated factors and identified new variables that predispose patients to periprosthetic joint infection.Level II, prognostic study.
A 62-year-old woman with osteoarthritis presents with a 7-month history of progressively worsening left hip pain radiating to the groin, 8 months after undergoing total left-hip arthroplasty. Physical examination reveals … A 62-year-old woman with osteoarthritis presents with a 7-month history of progressively worsening left hip pain radiating to the groin, 8 months after undergoing total left-hip arthroplasty. Physical examination reveals a sinus tract overlying her left hip. A radiograph shows loosening of the prosthesis at the bone–cement interface. How should her case be managed?
Abstract These guidelines are intended for use by infectious disease specialists, orthopedists, and other healthcare professionals who care for patients with prosthetic joint infection (PJI). They include evidence-based and opinion-based … Abstract These guidelines are intended for use by infectious disease specialists, orthopedists, and other healthcare professionals who care for patients with prosthetic joint infection (PJI). They include evidence-based and opinion-based recommendations for the diagnosis and management of patients with PJI treated with debridement and retention of the prosthesis, resection arthroplasty with or without subsequent staged reimplantation, 1-stage reimplantation, and amputation.
SUMMARY Prosthetic joint infection (PJI) is a tremendous burden for individual patients as well as the global health care industry. While a small minority of joint arthroplasties will become infected, … SUMMARY Prosthetic joint infection (PJI) is a tremendous burden for individual patients as well as the global health care industry. While a small minority of joint arthroplasties will become infected, appropriate recognition and management are critical to preserve or restore adequate function and prevent excess morbidity. In this review, we describe the reported risk factors for and clinical manifestations of PJI. We discuss the pathogenesis of PJI and the numerous microorganisms that can cause this devastating infection. The recently proposed consensus definitions of PJI and approaches to accurate diagnosis are reviewed in detail. An overview of the treatment and prevention of this challenging condition is provided.
In patients who present with an acutely painful and swollen joint, prompt identification and treatment of septic arthritis can substantially reduce morbidity and mortality.To review the accuracy and precision of … In patients who present with an acutely painful and swollen joint, prompt identification and treatment of septic arthritis can substantially reduce morbidity and mortality.To review the accuracy and precision of the clinical evaluation for the diagnosis of nongonococcal bacterial arthritis.Structured PubMed and EMBASE searches (1966 through January 2007), limited to human, English-language articles and using the following Medical Subject Headings terms: arthritis, infectious, physical examination, medical history taking, diagnostic tests, and sensitivity and specificity.Studies were included if they contained original data on the accuracy or precision of historical items, physical examination, serum, or synovial fluid laboratory data for diagnosing septic arthritis.Three authors independently abstracted data from the included studies.Fourteen studies involving 6242 patients, of whom 653 met the gold standard for the diagnosis of septic arthritis, satisfied all inclusion criteria. Two studies examined risk factors and found that age, diabetes mellitus, rheumatoid arthritis, joint surgery, hip or knee prosthesis, skin infection, and human immunodeficiency virus type 1 infection significantly increase the probability of septic arthritis. Joint pain (sensitivity, 85%; 95% confidence interval [CI], 78%-90%), a history of joint swelling (sensitivity, 78%; 95% CI, 71%-85%), and fever (sensitivity, 57%; 95% CI, 52%-62%) are the only findings that occur in more than 50% of patients. Sweats (sensitivity, 27%; 95% CI, 20%-34%) and rigors (sensitivity, 19%; 95% CI, 15%-24%) are less common findings in septic arthritis. Of all laboratory findings readily available to the clinician, the 2 most powerful were the synovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells from arthrocentesis. The summary likelihood ratio (LR) increased as the synovial fluid WBC count increased (for counts <25,000/microL: LR, 0.32; 95% CI, 0.23-0.43; for counts > or =25,000/microL: LR, 2.9; 95% CI, 2.5-3.4; for counts >50,000/microL: LR, 7.7; 95% CI, 5.7-11.0; and for counts >100,000/microL: LR, 28.0; 95% CI, 12.0-66.0). On the same synovial fluid sample, a polymorphonuclear cell count of at least 90% suggests septic arthritis with an LR of 3.4 (95% CI, 2.8-4.2), while a polymorphonuclear cell count of less than 90% lowers the likelihood (LR, 0.34; 95% CI, 0.25-0.47).Clinical findings identify patients with peripheral, monoarticular arthritis who might have septic arthritis. However, the synovial WBC and percentage of polymorphonuclear cells from arthrocentesis are required to assess the likelihood of septic arthritis before the Gram stain and culture test results are known.
Introduction Periprosthetic joint infection (PJI) is one of the most challenging and frequent complications after lower-extremity joint (hip and knee) arthroplasty. However, there is no single accepted set of diagnostic … Introduction Periprosthetic joint infection (PJI) is one of the most challenging and frequent complications after lower-extremity joint (hip and knee) arthroplasty. However, there is no single accepted set of diagnostic criteria for PJI. Various definitions have been proposed; however, none have been widely adopted. Furthermore, some of these definitions disagree with each other [14]. Therefore, a workgroup convened by the Musculoskeletal Infection Society (MSIS) analyzed the available evidence to propose a new definition for PJI. A summary of recommendations of those in attendance at a premeeting workshop of the 21st Annual Meeting of the MSIS on August 4, 2011, pertaining to the definition of PJI is outlined below. Existing published data on the definition of PJI was discussed by e-mail in the preceding 6 months by the executive members of the MSIS and a group of experts with known interest in this field. The intention of this proposal is to have a "gold standard" definition for PJI that can be universally adopted by all physicians, surveillance authorities (including the Centers for Disease Control, medical and surgical journals, the medicolegal community), and all involved in management of PJI. The panel acknowledged, in certain low-grade infections (ie, Propionibacterium acnes), several of these criteria may not be routinely met despite the presence of PJI. Using this definition, clinicians can be confident in their diagnosis and therefore provide appropriate treatment. Additionally, adoption of this definition for research purposes will allow for consistency between studies and potential improvement of the quality of the published body of evidence. Definition of Periprosthetic Joint Infection Based on the proposed criteria, definite PJI exists when: There is a sinus tract communicating with the prosthesis; or A pathogen is isolated by culture from at least two separate tissue or fluid samples obtained from the affected prosthetic joint; or Four of the following six criteria exist: Elevated serum erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) concentration, Elevated synovial leukocyte count, Elevated synovial neutrophil percentage (PMN%), Presence of purulence in the affected joint, Isolation of a microorganism in one culture of periprosthetic tissue or fluid, or Greater than five neutrophils per high-power field in five high-power fields observed from histologic analysis of periprosthetic tissue at ×400 magnification. PJI may be present if fewer than four of these criteria are met. Considerations Microbiologic Testing It is imperative that tissue for culture be obtained from representative periprosthetic tissue or fluid. To limit the risk of contamination, each sample should be taken with separate, sterile instruments. The definition of phenotypically identical organisms should be based on phenotypic similarities and in vitro antimicrobial susceptibility testing since confirmation of genetic identity is not routinely performed on clinical isolates. We recommend that at least three and no more than five periprosthetic specimen culture samples are taken and incubated in an aerobic and anaerobic environment. Fungal and mycobacterial cultures should not be performed routinely and reserved to higher-risk scenarios. The time of culture incubation has not been standardized yet. Isolation of a single low-virulence pathogen such as coagulase-negative Staphylococcus, P. acnes, or Corynebacteria in the absence of other criteria is not believed to represent a definite infection. Isolation of a single virulent organism such as S. aureus may represent a PJI. Furthermore, recent evidence has identified that certain tests, such as Gram stain, of periprosthetic tissue or fluid are not sensitive in diagnosing PJI [7]. Serum Tests Based on previous publications, an ESR of greater than 30 mm/hour and a CRP of greater than 10 mg/L would represent elevated levels [11, 15]. However, it is important to note there are variations in measuring these markers between laboratories. Furthermore, the level of these serum markers is affected by age, sex, and medical comorbidities of the patient. It has also been reported these markers can be elevated for approximately 30 to 60 days in the immediate postoperative period [3, 9]. Synovial Tests Multiple studies have provided thresholds for synovial leukocyte count and PMN% in the differential. In the chronically infected knee arthroplasty, these values have been reported from 1100 to 4000 cells/μL and 64% to 69%, respectively [5, 8, 16]. In patients with acute infections, the levels of synovial cell count and PMN% are much higher (approximately 20,000 cells/μL and 89%, respectively). Acute infections are defined as less than 3 months from index surgery or from the onset of symptoms [1]. The levels of synovial cell count and PMN% in the infected hip arthroplasty are not well delineated. A sole study has provided a threshold of 3000 cells/μL for leukocytes and 80% for PMN% for the infected hip arthroplasty [15]. None of these studies have included patients with underlying inflammatory arthropathies and related diseases. Current research is proceeding to provide more definitive thresholds for all patients. Histology Examination of periprosthetic tissues for evidence of neutrophils has been traditionally conducted by specially trained musculoskeletal pathologists. Histologic examination consequently may be operator dependent. It is therefore incumbent on surgeons to ensure their pathologists are in agreement with the diagnostic criteria for PJI. When examining for the presence of neutrophils, the histopathologist should disregard neutrophils entrapped in superficial fibrin or adherent to endothelium or small veins. Also, caution should be exercised in analyzing this test in cases where elevated neutrophil count might be expected, such as recent periprosthetic fractures or inflammatory arthropathy. Future Developments This proposed definition was based on current evidence supporting the role of various tests in diagnosis of PJI that are available in the literature. We recognize there are numerous other tests currently being evaluated, including measurement of CRP from the synovial fluid [12], synovial leukocyte esterase [13], sonication of explanted prosthetics [17], and molecular techniques such as PCR [10] and other molecular markers such as IL-6 [2, 4, 6]. As these or other techniques become validated and widely available, the currently proposed definition may require modification. Acknowledgments We thank the following individuals for their involvement and invaluable input throughout the development of this document: Robert Barrack MD, Keith Berend MD, Sandra Berrios-Torres (from Centers for Disease Control and Prevention), Kevin Bozic MD, John Esterhai MD, Ryan Fagan (from Centers for Disease Control and Prevention), Thomas Fehring MD, Terry Gioe MD, Teresa Horan (from Centers for Disease Control and Prevention), Steven Kurtz PhD, Bas Masri MD, Arvind Nana MD, Douglas Osmon MD, John Segreti MD, and Mark Spangehl MD.
Context.— Rifampin-containing regimens are able to cure staphylococcal implant-related infections based on in vitro and in vivo observations. However, this evidence has not been proven by a controlled clinical trial. … Context.— Rifampin-containing regimens are able to cure staphylococcal implant-related infections based on in vitro and in vivo observations. However, this evidence has not been proven by a controlled clinical trial. Objective.— To evaluate the clinical efficacy of a rifampin combination in staphylococcal infections associated with stable orthopedic devices. Design.— A randomized, placebo-controlled, double-blind trial conducted from 1992 through 1997. Setting.— Two infectious disease services in tertiary care centers in collaboration with 5 orthopedic surgeons in Switzerland. Patients.— A total of 33 patients with culture-proven staphylococcal infection associated with stable orthopedic implants and with a short duration of symptoms of infection (exclusion limit &lt;1 year; actual experience 0-21 days). Intervention.— Initial debridement and 2-week intravenous course of flucloxacillin or vancomycin with rifampin or placebo, followed by either ciprofloxacin-rifampin or ciprofloxacin-placebo long-term therapy. Main Outcome Measures.— Cure was defined as (1) lack of clinical signs and symptoms of infection, (2) C-reactive protein level less than 5 mg/L, and (3) absence of radiological signs of loosening or infection at the final follow-up visit at 24 months. Failure was defined as (1) persisting clinical and/or laboratory signs of infection or (2) persisting or new isolation of the initial microorganism. Results.— A total of 18 patients were allocated to ciprofloxacin-rifampin and 15 patients to the ciprofloxacin-placebo combination. Twenty-four patients fully completed the trial with a follow-up of 35 and 33 months. The cure rate was 12 (100%) of 12 in the ciprofloxacin-rifampin group compared with 7 (58%) of 12 in the ciprofloxacin-placebo group (P=.02). Nine of 33 patients dropped out due to adverse events (n=6), noncompliance (n=1), or protocol violation (n=2). Seven of the 9 patients who dropped out were subsequently treated with rifampin combinations, and 5 of them were cured without removal of the device. Conclusion.— Among patients with stable implants, short duration of infection, and initial debridement, patients able to tolerate long-term (3-6 months) therapy with rifampin-ciprofloxacin experienced cure of the infection without removal of the implant.
To the Editor: The Transverse Myelitis Consortium Working Group should be congratulated for the proposed diagnostic criteria and nosology of acute transverse myelitis (ATM).1 However, in the differential diagnosis only … To the Editor: The Transverse Myelitis Consortium Working Group should be congratulated for the proposed diagnostic criteria and nosology of acute transverse myelitis (ATM).1 However, in the differential diagnosis only scarce attention was given to fibrocartilaginous embolization from nucleus pulposus embolism (NPE), a condition that is often undiagnosed and frequently confused—clinically and pathologically—with ATM.2 For instance, Bots et al.3 reexamined a teaching specimen of so-called ATM and found an acute transverse myelopathy due to NPE. Although the exclusion criterion of <4 hours from onset to nadir would effectively exclude most vascular cases, in our review of the natural history of NPE,2 we found that at least 42% of the cases had progressed for periods of ≥4 hours; furthermore, a prodromal history of intermittent back pain is not uncommon, lasting for periods of weeks to up to 4 months.4 …
We review recent advances in the prevention, diagnosis and treatment of infections associated with joint prostheses and internal fixation devices.The perioperative antimicrobial prophylaxis should be administered 60-30 min before incision … We review recent advances in the prevention, diagnosis and treatment of infections associated with joint prostheses and internal fixation devices.The perioperative antimicrobial prophylaxis should be administered 60-30 min before incision or before inflation of the tourniquet. New diagnostic approaches include sonication of removed implants to dislodge adherent microorganisms growing in biofilms and the use of molecular techniques to improve diagnostic yield. Treatment of implant-associated infections without removal of the device is an established option for selected patients. Treatment with rifampin combinations in staphylococcal infections is crucial for success. As demonstrated in vitro, in animal studies and in clinical trials, quinolones are suitable combination agents with rifampin against susceptible staphylococci, but increasing antimicrobial resistance requires evaluation of alternative combination agents, such as quinpristin-dalfopristin, linezolid, and daptomycin, although clinical experience is limited. New antimicrobial agents, such as dalbavancin, tigecycline, iclaprim, and novel rifamycin derivatives are studied.Better understanding of the interaction between microorganisms, the implant and the host may improve our current approach to the diagnosis and treatment of implant-associated infections. The treatment modality depends on duration of infection, stability of the implant, antimicrobial susceptibility of the pathogen and condition of the surrounding soft tissue.
THE high success rate observed with antibiotic therapy in most bacterial diseases contrasts with the substantial failure rate in the treatment of bone infections. This discrepancy can be partly accounted … THE high success rate observed with antibiotic therapy in most bacterial diseases contrasts with the substantial failure rate in the treatment of bone infections. This discrepancy can be partly accounted for by a variety of specific problems pertaining to the diagnosis and treatment of this type of infection, discussed in the Journal 10 years ago.1 Since then, continued interest in osteomyelitis has provided new insight into its pathogenesis, diagnosis, and therapy; it is our aim to put this new information into perspective. Other, more conventional aspects of osteomyelitis, made familiar by previous studies, will be dealt with more briefly, and . . .
Abstract These guidelines are intended for use by infectious disease specialists, orthopedists, and other healthcare professionals who care for patients with prosthetic joint infection (PJI). They include evidence-based and opinion-based … Abstract These guidelines are intended for use by infectious disease specialists, orthopedists, and other healthcare professionals who care for patients with prosthetic joint infection (PJI). They include evidence-based and opinion-based recommendations for the diagnosis and management of patients with PJI treated with debridement and retention of the prosthesis, resection arthroplasty with or without subsequent staged reimplantation, 1-stage reimplantation, and amputation.
Thirty-seven patients who were clinically suspected of having vertebral osteomyelitis were prospectively evaluated with magnetic resonance (MR), radiography, and radionuclide studies. These findings were correlated with the final clinical, microbiologic, … Thirty-seven patients who were clinically suspected of having vertebral osteomyelitis were prospectively evaluated with magnetic resonance (MR), radiography, and radionuclide studies. These findings were correlated with the final clinical, microbiologic, or histologic diagnoses. Based on the results of these latter studies, 23 patients were believed to have osteomyelitis. MR examinations consisted of at least a sagittal image (TE = 30 msec, TR = 0.5 sec) and an image obtained at TE = 120 msec, TR = 2-3 sec. All patients underwent radiographic and MR examinations, 36 underwent technetium 99m-HDP bone scanning, and 20 patients underwent gallium 67 scanning. Nineteen patients underwent both bone and gallium scanning. The imaging studies were reviewed independently by investigators blinded to the final diagnoses. MR had a sensitivity of 96%, specificity of 92%, and accuracy of 94%. Combined gallium and bone scan studies (19 cases) had a sensitivity of 90%, specificity of 100%, and accuracy of 94%. Bone scans alone had a sensitivity of 90%, specificity of 78%, and accuracy of 86%. Plain radiographs had a sensitivity of 82%, specificity of 57%, and accuracy of 73%. The MR appearance of vertebral osteomyelitis in this study was characteristic, and MR was as accurate and sensitive as radionuclide scanning in the detection of osteomyelitis.
SUMMARY Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial … SUMMARY Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of the host immune response and the adherence factors, toxins, and immunoavoidance strategies of the invading pathogen. Neisseria gonorrhoeae and Staphylococcus aureus are used in discussing the host-pathogen interaction in the pathogenesis of acute septic arthritis. While diagnosis rests on isolation of the bacterial species from synovial fluid samples, patient history, clinical presentation, laboratory findings, and imaging studies are also important. Acute nongonococcal septic arthritis is a medical emergency that can lead to significant morbidity and mortality. Therefore, prompt recognition, rapid and aggressive antimicrobial therapy, and surgical treatment are critical to ensuring a good prognosis. Even with prompt diagnosis and treatment, high mortality and morbidity rates still occur. In contrast, gonococcal arthritis is often successfully treated with antimicrobial therapy alone and demonstrates a very low rate of complications and an excellent prognosis for full return of normal joint function. In the case of prosthetic joint infections, the hardware must be eventually removed by a two-stage revision in order to cure the infection.
Exchange operation is recommended as the treatment of choice for most deep infections involving a total hip replacement. This revision arthroplasty comprises, in one stage, excision of soft tissue, removal … Exchange operation is recommended as the treatment of choice for most deep infections involving a total hip replacement. This revision arthroplasty comprises, in one stage, excision of soft tissue, removal of implant and cement, replacement with an appropriate implant using Palacos R acrylic cement loaded with an appropriate antibiotic and, more recently, systemic antibiotics. During our first 10 years without systemic antibiotics we have achieved an overall 77 per cent success rate from a first attempt in 583 patients and a 90 per cent success rate after subsequent exchange procedures. Morbidity is significant but acceptable. Success is defined as control of infection, no loosening, and useful function. The factors associated with failures include, in particular, specific infections (Pseudomonas group, Streptococcus group D, Proteus group, and Escherichia coli), delay in operation and inadequate antibiotic dosage in the cement.
Objectives: Implantable devices are major risk factors for hospital-acquired infection. Biomaterials coated with silver oxide or silver alloy have all been used in attempts to reduce infection, in most cases … Objectives: Implantable devices are major risk factors for hospital-acquired infection. Biomaterials coated with silver oxide or silver alloy have all been used in attempts to reduce infection, in most cases with controversial or disappointing clinical results. We have developed a completely new approach using supercritical carbon dioxide to impregnate silicone with nanoparticulate silver metal. This study aimed to evaluate the impregnated polymer for antimicrobial activity.
We conducted a matched case-control study to determine risk factors for the development of prosthetic joint infection. Cases were patients with prosthetic hip or knee joint infection. Controls were patients … We conducted a matched case-control study to determine risk factors for the development of prosthetic joint infection. Cases were patients with prosthetic hip or knee joint infection. Controls were patients who underwent total hip or knee arthroplasty and did not develop prosthetic joint infection. A multiple logistic regression model indicated that risk factors for prosthetic joint infection were the development of a surgical site infection not involving the prosthesis (odds ratio [OR], 35.9; 95% confidence interval [CI], 8.3-154.6), a National Nosocomial Infections Surveillance (NNIS) System surgical patient risk index score of 1 (OR, 1.7; 95% CI, 1.2-2.3) or 2 (OR, 3.9; 95% CI, 2.0-7.5), the presence of a malignancy (OR, 3.1; 95% CI, 1.3-7.2), and a history of joint arthroplasty (OR, 2.0; 95% CI, 1.4-3.0). Our findings suggest that a surgical site infection not involving the joint prosthesis, an NNIS System surgical patient risk index score of 1 or 2, the presence of a malignancy, and a history of a joint arthroplasty are associated with an increased risk of prosthetic joint infection.
Deep surgical site infection following total knee arthroplasty is a devastating complication. Patient and surgical risk factors for this complication have not been thoroughly examined. The purpose of this study … Deep surgical site infection following total knee arthroplasty is a devastating complication. Patient and surgical risk factors for this complication have not been thoroughly examined. The purpose of this study was to evaluate risk factors associated with deep surgical site infection following total knee arthroplasty in a large U.S. integrated health-care system.A retrospective review of a prospectively followed cohort of primary total knee arthroplasties recorded in a total joint replacement registry from 2001 to 2009 was conducted. Records were screened for deep surgical site infection with use of a validated algorithm, and the results were adjudicated by chart review. Patient factors, surgical factors, and surgeon and hospital characteristics were identified with use of the total joint replacement registry. Cox regression models were used to assess risk factors associated with deep surgical site infection.A total of 56,216 total knee arthroplasties were identified; 63.0% were done in women, the average age of the patients was 67.4 years (standard deviation [SD] = 9.6), and the average body mass index (BMI) was 32 kg/m2 (SD = 6). The incidence of deep surgical site infection was 0.72% (404/56,216). In a fully adjusted model, patient factors associated with deep surgical site infection included a BMI of ≥35 (hazard ratio [HR] = 1.47), diabetes mellitus (HR = 1.28), male sex (HR = 1.89), an American Society of Anesthesiologists (ASA) score of ≥3 (HR = 1.65), a diagnosis of osteonecrosis (HR = 3.65), and a diagnosis of posttraumatic arthritis (HR = 3.23). Hispanic race was protective (HR = 0.69). Protective surgical factors included use of antibiotic irrigation (HR = 0.67), a bilateral procedure (HR = 0.51), and a lower annual hospital volume (HR = 0.33). Surgical risk factors included quadriceps-release exposure (HR = 4.76) and the use of antibiotic-laden cement (HR = 1.53). In a subanalysis, operative time was a risk factor, with a 9% increased risk per fifteen-minute increment.Use of a comprehensive infection surveillance system, combined with a total joint replacement registry, identified patient and surgical factors associated with infection following total knee arthroplasty in a large sample. High-risk patients should be counseled, and modifiable clinical conditions should be optimized. Use of antibiotic irrigation should be encouraged, but antibiotic-laden cement may not be useful.Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Culturing of samples of periprosthetic tissue is the standard method used for the microbiologic diagnosis of prosthetic-joint infection, but this method is neither sensitive nor specific. In prosthetic-joint infection, microorganisms … Culturing of samples of periprosthetic tissue is the standard method used for the microbiologic diagnosis of prosthetic-joint infection, but this method is neither sensitive nor specific. In prosthetic-joint infection, microorganisms are typically present in a biofilm on the surface of the prosthesis. We hypothesized that culturing of samples obtained from the prosthesis would improve the microbiologic diagnosis of prosthetic-joint infection.
ABSTRACT A prospective study was performed to establish criteria for the microbiological diagnosis of prosthetic joint infection at elective revision arthroplasty. Patients were treated in a multidisciplinary unit dedicated to … ABSTRACT A prospective study was performed to establish criteria for the microbiological diagnosis of prosthetic joint infection at elective revision arthroplasty. Patients were treated in a multidisciplinary unit dedicated to the management and study of musculoskeletal infection. Standard multiple samples of periprosthetic tissue were obtained at surgery, Gram stained, and cultured by direct and enrichment methods. With reference to histology as the criterion standard, sensitivities, specificities, and likelihood ratios (LRs) were calculated by using different cutoffs for the diagnosis of infection. We performed revisions on 334 patients over a 17-month period, of whom 297 were evaluable. The remaining 37 were excluded because histology results were unavailable or could not be interpreted due to underlying inflammatory joint disease. There were 41 infections, with only 65% of all samples sent from infected patients being culture positive, suggesting low numbers of bacteria in the samples taken. The isolation of an indistinguishable microorganism from three or more independent specimens was highly predictive of infection (sensitivity, 65%; specificity, 99.6%; LR, 168.6), while Gram staining was less useful (sensitivity, 12%; specificity, 98%; LR, 10). A simple mathematical model was developed to predict the performance of the diagnostic test. We recommend that five or six specimens be sent, that the cutoff for a definite diagnosis of infection be three or more operative specimens that yield an indistinguishable organism, and that because of its low level of sensitivity, Gram staining should be abandoned as a diagnostic tool at elective revision arthroplasty.
Background: Periprosthetic joint infection continues to potentially complicate an otherwise successful joint replacement. The treatment of this infection often requires multiple surgical procedures associated with increased complications and morbidity. This … Background: Periprosthetic joint infection continues to potentially complicate an otherwise successful joint replacement. The treatment of this infection often requires multiple surgical procedures associated with increased complications and morbidity. This study examined the relationship between periprosthetic joint infection and mortality and aimed to determine the effect of periprosthetic joint infection on mortality and any predictors of mortality in patients with periprosthetic joint infection. Methods: Four hundred and thirty-six patients with at least one surgical intervention secondary to confirmed periprosthetic joint infection were compared with 2342 patients undergoing revision arthroplasty for aseptic failure. The incidence of mortality at thirty days, ninety days, one year, two years, and five years after surgery was assessed. Multivariate analysis was used to assess periprosthetic joint infection as an independent predictor of mortality. In the periprosthetic joint infection population, variables investigated as potential risk factors for mortality were evaluated. Results: Mortality was significantly greater (p < 0.001) in patients with periprosthetic joint infection compared with those undergoing aseptic revision arthroplasty at ninety days (3.7% versus 0.8%), one year (10.6% versus 2.0%), two years (13.6% versus 3.9%), and five years (25.9% versus 12.9%). After controlling for age, sex, ethnicity, number of procedures, involved joint, body mass index, and Charlson Comorbidity Index, revision arthroplasty for periprosthetic joint infection was associated with a fivefold increase in mortality compared with revision arthroplasty for aseptic failures. In the periprosthetic joint infection population, independent predictors of mortality included increasing age, higher Charlson Comorbidity Index, history of stroke, polymicrobial infections, and cardiac disease. Conclusions: Although it is well known that periprosthetic joint infection is a devastating complication that severely limits joint function and is consistently difficult to eradicate, surgeons must also be cognizant of the systemic impact of periprosthetic joint infection and its major influence on fatal outcome in patients. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
The value of microbiological culture to diagnose late periprosthetic infection is limited, especially because standard methods may fail to detect biofilm-forming sessile or other fastidious bacteria. There is no agreement … The value of microbiological culture to diagnose late periprosthetic infection is limited, especially because standard methods may fail to detect biofilm-forming sessile or other fastidious bacteria. There is no agreement on the appropriate cultivation period, although this period is a crucial factor. This study was designed to assess the duration of culture that is necessary for reliable detection.Ten periprosthetic tissue specimens each were obtained during revision from 284 patients with suspected late hip or knee arthroplasty infection. Five samples were examined by microbiological culture over a 14-day period, and 5 were subjected to histologic analysis. To define infection, a pre-established algorithm was used; this included detection of indistinguishable organisms in >/=2 tissue samples or growth in 1 tissue sample and a positive result of histologic analysis (>5 neutrophils in at least 10 high-power fields). The time to detection of organisms was monitored.Infection was diagnosed in 110 patients. After 7 days (the longest incubation period most frequently reported), the detection rate via culture was merely 73.6%. Organisms indicating infection were found for up to 13 days. "Early"-detected species (mostly staphylococci) emerged predominantly during the first week, whereas "late"-detected agents (mostly Propionibacterium species) were detected mainly during the second week. In both populations, an unequivocal correlation between the number of culture-positive tissue samples and positive results of histologic analysis was noted, which corroborated the evidence that true infections were detected over the entire cultivation period.Prolonged microbiological culture for 2 weeks is promising because it yields signs of periprosthetic infection in a significant proportion of patients that would otherwise remain unidentified.
Background: Massive endoprostheses provide orthopaedic oncologists with many reconstructive options after tumor resection, although failure rates are high. Because the number of these procedures is limited, failure of these devices … Background: Massive endoprostheses provide orthopaedic oncologists with many reconstructive options after tumor resection, although failure rates are high. Because the number of these procedures is limited, failure of these devices has not been studied or classified adequately. This investigation is a multicenter review of the use of segmental endoprostheses with a focus on the modes, frequency, and timing of failure. Methods: Retrospective reviews of the operative databases of five institutions identified 2174 skeletally mature patients who received a large endoprosthesis for tumor resection. Patients who had failure of the endoprosthesis were identified, and the etiology and timing of failure were noted. Similar failures were tabulated and classified on the basis of the risk of amputation and urgency of treatment. Statistical analysis was performed to identify dependent relationships among mode of failure, anatomic location, and failure timing. A literature review was performed, and similar analyses were done for these data. Results: Five hundred and thirty-four failures were identified. Five modes of failure were identified and classified: soft-tissue failures (Type 1), aseptic loosening (Type 2), structural failures (Type 3), infection (Type 4), and tumor progression (Type 5). The most common mode of failure in this series was infection; in the literature, it was aseptic loosening. Statistical dependence was found between anatomic location and mode of failure and between mode of failure and time to failure. Significant differences were found in the incidence of failure mode Types 1, 2, 3, and 4 when polyaxial and uniaxial joints were compared. Significant dependence was also found between failure mode and anatomic location in the literature data. Conclusions: There are five primary modes of endoprosthetic failure, and their relative incidences are significantly different and dependent on anatomic location. Mode of failure and time to failure also show a significant dependence. Because of these relationships, cumulative reporting of segmental failures should be avoided because anatomy-specific trends will be missed. Endoprosthetic design improvements should address failure modes specific to the anatomic location. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.
ABSTRACT There has been a dramatic increase in the emergence of antibiotic‐resistant bacterial strains, which has made antibiotic choices for infection control increasingly limited and more expensive. In the U.S. … ABSTRACT There has been a dramatic increase in the emergence of antibiotic‐resistant bacterial strains, which has made antibiotic choices for infection control increasingly limited and more expensive. In the U.S. alone, antibiotic‐resistant bacteria cause at least 2 million infections and 23,000 deaths a year resulting in a $55–70 billion per year economic impact. Antibiotics are critical to the success of surgical procedures including orthopedic prosthetic surgeries, and antibiotic resistance is occurring in nearly all bacteria that infect people, including the most common bacteria that cause orthopedic infections, such as Staphylococcus aureus ( S. aureus ). Most clinical cases of orthopedic surgeries have shown that patients infected with antibiotic‐resistant bacteria, such as methicillin‐resistant S. aureus (MRSA), are associated with increased morbidity and mortality. This paper reviews the severity of antibiotic resistance at the global scale, the consequences of antibiotic resistance, and the pathways bacteria used to develop antibiotic resistance. It highlights the opportunities and challenges in limiting antibiotic resistance through approaches like the development of novel, non‐drug approaches to reduce bacteria functions related to orthopedic implant‐associated infections. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:22–32, 2018.
The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication.
Known since antiquity,1 osteomyelitis is a difficult-to-treat infection characterized by the progressive inflammatory destruction and new apposition of bone.24 This review focuses on current knowledge of the disease and the … Known since antiquity,1 osteomyelitis is a difficult-to-treat infection characterized by the progressive inflammatory destruction and new apposition of bone.24 This review focuses on current knowledge of the disease and the progress being made in understanding its pathogenesis, diagnosis, and treatment.PathogenesisThe pathogenesis of osteomyelitis has been explored in various animal models5; these studies have found that normal bone is highly resistant to infection, which can only occur as a result of very large inocula, trauma, or the presence of foreign bodies.6,7 Certain major causes of infection, such as Staphylococcus aureus, adhere to bone by expressing receptors . . .
Abstract Bdellovibrio bacteriovorus is an agent that stands out with its predatory properties and has recently been used against pathogens that are frequently resistant to antibiotics. The study was conducted … Abstract Bdellovibrio bacteriovorus is an agent that stands out with its predatory properties and has recently been used against pathogens that are frequently resistant to antibiotics. The study was conducted experimentally to determine the effect of dressing application containing Bdellovibrio bacteriovorus on superficial incisional surgical site infection caused by Staphylococcus aureus in mice. In the study, mice were divided into 6 different groups, BB: B. bacteriovorus ; NC: Negative Control; PC: Positive Control Methicillin Resistant S. aureus ; MRSA + BB: Methicillin Resistant S. aureus + B. bacteriovorus dressing; MRSA + V: Methicillin Resistant S. aureus + Vancomycin; MRSA + BB + V: Methicillin Resistant S. aureus + B. bacteriovorus dressing + Vancomycin group. The treatment procedures were applied over a period of 3 days. Infection symptoms were monitored and recorded at the 24th, 48th, and 72nd hours. In the Staphylococcus aureus + Vancomycin group, all mice developed edema, redness, and fever at 24 h. At 48 h, all mice exhibited edema and redness, with 50% showing fever. At 72 h, 70% of the mice showed edema and redness, and 10% showed fever. In the Staphylococcus aureus + Bdellovibrio bacteriovorus + Vancomycin combined treatment group, all mice exhibited edema, redness, and fever at 24 h. At 48 h, only 20% of the mice showed redness. At 72 h, no edema, redness, fever, purulent discharge, or suture dehiscence was observed. Sepsis developed in 2 of 10 mice in the Staphylococcus aureus + Bdellovibrio bacteriovorus + Vancomycin group. The most effective treatment was in the Staphylococcus aureus + Bdellovibrio bacteriovorus + Vancomycin group. It was determined that sepsis findings were the least in the Staphylococcus aureus + Bdellovibrio bacteriovorus + Vancomycin group. B. bacteriovorus holds the potential to be an effective control agent in preventing or slowing resistance development.
Background: Orthopaedic implant infections (ODRI) remain a significant clinical challenge due to their association with persistent biofilm formation, which complicates treatment. 1.2 Objective: This study aimed to investigate the biofilm-forming … Background: Orthopaedic implant infections (ODRI) remain a significant clinical challenge due to their association with persistent biofilm formation, which complicates treatment. 1.2 Objective: This study aimed to investigate the biofilm-forming potential of Gram-positive and Gram-negative pathogens isolated from orthopaedic implant infections in a tertiary care setting. Methods: A retrospective cross-sectional study was conducted at the Krishna Institute of Medical Sciences, Secunderabad, India, from February 2023 to January 2024. Clinical samples from orthopaedic implant infections, were processed for bacterial culture and biofilm formation using the Tissue Culture Plate (TCP) method in triplicates. Bacterial identification was performed using the Vitek 2 Compact system. Results: Of 87 patients diagnosed with orthopaedic implant infections, 62 (71.26%) were culture-positive, with 35 (56.45%) Gram-negative bacilli and 27 (43.54%) Gram-positive cocci. Biofilm formation was observed in 59.25% of Gram-positive isolates, with 18.51% strong biofilm producers, 40.74% moderate producers, and 40.74% weak/non-producers. Among Gram-negative isolates, 31.42% were biofilm producers, with 5.71% strong, 25.71% moderate, and 68.57% weak/non-producers. A higher prevalence of biofilm production was noted in Gram-positive organisms compared to Gram-negative bacteria. Conclusion: The study highlights the higher propensity of Gram-positive bacteria to form biofilms, which may contribute to the persistence and chronicity of orthopaedic implant infections.
Background: A subset of children with acute haematogenous osteomyelitis become severely ill. This study aimed to define a severe and standard course and identify potential risk factors on admission for … Background: A subset of children with acute haematogenous osteomyelitis become severely ill. This study aimed to define a severe and standard course and identify potential risk factors on admission for a severe course as well as the cumulative incidence. Methods: This retrospective cohort study included all children under 16 years with acute haematogenous osteomyelitis between January 2018 and September 2021. The outcome parameters included &gt;2 surgical debridements, C-reactive protein level not halving in 48 h, extraosseous involvement and hospital stay &gt;14 days. Predictor variables (delayed presentation (&gt;5 days), C-reactive protein &gt;250 mg/L on admission, &gt;1 bone segment and need for intensive care unit on admission) were tested against the outcome of a severe clinical course using univariate logistic regression analysis (using p &lt; 0.2). Results: One hundred and twenty-one patients were included. Thirty-nine patients (32.2%) had a complicated course. Patients admitted to intensive care unit had a 2.8-times higher risk of a severe course compared to those not requiring intensive care unit (risk ratio 2.8; 95% confidence interval 1.6–4.8); having a C-reactive protein &gt;250 mg/L on admission increased the risk of a severe course 1.7 times (risk ratio 1.71, 95% confidence interval 1.3–2.3). Having more than one bone segment involved and a delayed presentation of &gt;5 days increased risk of a severe course by 2.4 (risk ratio 2.4, 95% confidence interval 1.6–3.6) and 1.3 times (risk ratio 1.3, 95% confidence interval 1.3–1.3), respectively, compared to the alternative. The cumulative incidence of acute haematogenous osteomyelitis ranged between 4.0% and 5.0% per year. Conclusion: Four risk factors present on admission were identified and are suggested to modify the risk of a severe disease as well as change treatment protocols.
Pseudomonas aeruginosa (PA)-associated periprosthetic joint infection (PJI) is notoriously difficult to treat due to biofilm formation and poor antibiotic penetration into joint tissues. This study investigates the efficacy of combined … Pseudomonas aeruginosa (PA)-associated periprosthetic joint infection (PJI) is notoriously difficult to treat due to biofilm formation and poor antibiotic penetration into joint tissues. This study investigates the efficacy of combined intravenous (IV) and intra-articular (IA) levofloxacin administration in targeting PA biofilms in PJI. A retrospective cohort of nine knee PJI patients received daily IV (500 mg) and IA (100 mg) levofloxacin post-revision surgery. Patients were followed for ≥2 years for their long-term clinical outcomes, with synovial and serum levofloxacin concentrations analyzed to assess minimum biofilm eradication concentration (MBEC) attainment. Physiologically based pharmacokinetic (PBPK) modeling simulated levofloxacin distribution in plasma, synovial fluid, and synovium. In vitro studies quantified biofilm biomass and metabolic activity reduction, while scanning electron microscopy (SEM) evaluated biofilm disruption on 3D-printed knee implants. Over two years, no patients required reoperation, experienced mortality, or needed ongoing antibiotic suppression. Daily living activities and Knee Society Scores improved, with no major adverse events. On postoperative day 7, synovial levofloxacin concentrations reached 110.20 ± 39.20 mg/L, exceeding the MBEC for 80% of PA isolates. Serum levofloxacin concentrations were measured at 1.76 ± 0.37 mg/L, showing only a marginal increase compared to the levels specified in FDA-approved labeling. In vitro, levofloxacin reduced biofilm biomass to 28.65 ± 5.12% and metabolic activity to 39.66 ± 4.28% of baseline. SEM confirmed reduced bacterial cell counts and disrupted biofilm structure on 3D printed implants. PBPK modeling demonstrated elevated levofloxacin concentrations in synovial fluid and synovium, with minimal systemic exposure. Combined IV and IA levofloxacin effectively targets PA biofilms in PJI without significant safety concerns, offering a promising therapeutic strategy for PA-induced PJI.
While two-stage exchange arthroplasty is the gold standard for treating periprosthetic joint infections (PJIs), it results in a prolonged treatment period with the potential for complications and non-planned additional procedures, … While two-stage exchange arthroplasty is the gold standard for treating periprosthetic joint infections (PJIs), it results in a prolonged treatment period with the potential for complications and non-planned additional procedures, limited joint function during the interstage period, and emotional stress for patients. The primary objective of this systematic literature review was to evaluate outcomes associated with two-stage exchange arthroplasty for treating total hip arthroplasty (THA) and total knee arthroplasty (TKA) PJIs. This literature review analyzed U.S. data on the timing and health consequences associated with the interstage period and outcomes following reimplantation in patients undergoing two-stage exchange arthroplasty. A search of U.S. studies published between January 2014 and January 2024 was conducted using PubMed and Embase databases. Sixty-five studies reporting data on 26,354 patients undergoing two-stage exchange arthroplasty were included. There were 29.0% and 68.6% of patients who underwent THA and TKA respectively, with 2.4% patients not having the affecting joint identified. The mean interstage period was 141.4 ± 74.2 days with 16.9 ± 12.2% patients not re-implanted. The mean infection eradication was 74.2 ± 10.5% and the average reinfection rate was 15.7 ± 7.1%. Complications and additional procedures were common during the interstage and post-implant periods. Only four studies utilized Musculoskeletal Infection Society (MSIS) Outcomes Reporting Tool. Patients undergoing treatment for TKA PJIs had less successful MSIS outcomes compared to those being treated for THA PJIs. This includes a lower rate of infection control (46.0% vs. 65.5%), a higher rate of reoperation, revision, and/or spacer retention (40.6% vs. 25.2%) and a higher death rate (13.4% vs. 9.4%), respectively. Two-stage exchange arthroplasty treatment of PJIs is associated with major morbidity and often requires additional surgical procedures to address complications. The prolonged duration of the interstage period contributes to morbidity and negatively impacts patients' quality of life and increases the risk of mortality.
Despite advancements in surgical techniques and implant designs, Periprosthetic joint infection (PJI) continues to be one of the commonest and most devastating causes of failure in total joint arthroplasty. PJIs … Despite advancements in surgical techniques and implant designs, Periprosthetic joint infection (PJI) continues to be one of the commonest and most devastating causes of failure in total joint arthroplasty. PJIs are associated with significant morbidity and mortality, placing a multifactorial burden on patients, caregivers, surgeons, hospitals, health systems, and economies. The incidence of PJI ranges from 0.5% to 2.3% based on current literature. Mortality rates in PJI subsequent to a primary total hip arthroplasty (THA) range from 4% to 8% after one year. The common treatment for PJI is a two-stage revision THA, which itself is associated with significant morbidity and mortality. The economic burden of PJI is substantial, with treatment costs 3 to 5.6 times higher than primary THA. Patients with PJI experience inferior hip function, lower health-related quality of life scores, and higher odds of developing new onset depression. PJI's negatively impacts on a patient's capacity to work and conduct everyday activities. Orthopaedic surgeons also face significant psychological stress due to the challenges in managing PJI, including feelings of incompetence, insecurity, and frustration. Continued research and innovation are essential to optimize THA outcomes and reduce the need for revision surgeries. Improved prevention strategies, multidisciplinary cooperation, and comprehensive care and support for both patients and surgeons are crucial. It is paramount that every orthopaedic surgeon remains cognisant of this complication to institute better prevention strategies, promote better multi-disciplinary cooperation and enhance patient pre-operative care.
Aims Successful identification of bacteria in tissue samples requires careful consideration of multiple factors, including sample type and quality, the type of bacteria being detected, and the sensitivity and specificity … Aims Successful identification of bacteria in tissue samples requires careful consideration of multiple factors, including sample type and quality, the type of bacteria being detected, and the sensitivity and specificity of the detection method. Here, we address the issues of detecting a small number of bacteria, often found in biofilms and heterogeneously distributed in a large volume (the surgical site with suspected infection). Specifically, the study seeks to address the difficulties in detecting small numbers of bacteria, and to evaluate the impact of bacterial aggregation on the probability of successful detection. Methods We present simple formulae for the probability of detecting bacteria in different infection scenarios where the number of bacteria and size of bacterial aggregates are incorporated as variables. We define a critical aggregation parameter, above which the probability of sampling bacteria decreases dramatically. Results Our calculations demonstrate that aggregation of bacteria in tissues can strongly impact the probability of detection, where an increase in aggregate size results in a reduced probability of obtaining a positive biopsy. Our calculations underscore the challenges in effectively sampling tissue for diagnostic purposes, particularly in low-grade infections characterized by small bacterial quantities within aggregates. Below the critical aggregation parameter, obtaining five tissue specimens is associated with a high probability of detecting infection, but at a higher aggregation level, increasing the number of specimens is rendered ineffective, resulting in culture-negative diagnoses. Conclusion We hypothesize that the high false-negative rate in diagnosing orthopaedic surgical site infections, such as periprosthetic joint infections, could be partly influenced by the heterogeneous bacterial distribution and the sampling complexities of such populations outlined here. Homogenization of tissue specimens is a technique to enhance the surface area which potentially could increase the detection of heterogeneously distributed bacteria. Cite this article: Bone Joint Res 2025;14(6):560–567.
Introduction Periprosthetic joint infections are relatively rare complications of total joint replacements. The standard of care for these infections involves the placement of a temporary spacer made of poly (methyl … Introduction Periprosthetic joint infections are relatively rare complications of total joint replacements. The standard of care for these infections involves the placement of a temporary spacer made of poly (methyl methacrylate) (PMMA) bone cement combined with antibiotics. The rate of major complication can be as high as 12% for PMMA spacers. Therefore, this study was designed to identify an alternative resin material that could be 3D printed, provide mechanical support necessary for ambulation, and deliver a therapeutic dose of antibiotics over an extended period. Methods Test substrates were photochemically printed out of Biomed Clear (BMC) loaded with up to 16% gentamicin or 10% vancomycin (wt%). PMMA and BMC composites were characterized using differential scanning calorimetry, dynamic mechanical analysis, compression testing, and a 30-day antibiotic elution study. Results The thermoset properties of the BMC allowed for the compressive properties to remain unchanged (post-elution = compressive strength 84–94 MPa) as antibiotics were added to the resin (0–16 wt%). However, antibiotic elution was influenced by the type and concentration of the antibiotic in the composite. In contrast, the thermoplastic properties of PMMA led to a decrease in compressive properties with the addition of antibiotics, but PMMA was able to elute relatively more antibiotics. Discussion This study described a novel method to 3D print load bearing materials that can release antibiotics over 30 days. BMC composites have some advantages and disadvantages compared to PMMA that need to be considered when developing new treatments for orthopaedic infections.
ABSTRACT Background Rates of childhood bone and joint infection (BJI) in New Zealand (NZ) are among the highest in the world, with a disproportionate burden experienced by Māori and Pacific … ABSTRACT Background Rates of childhood bone and joint infection (BJI) in New Zealand (NZ) are among the highest in the world, with a disproportionate burden experienced by Māori and Pacific children. Eczema, also inequitably distributed by ethnicity, is a potential risk factor for BJI. This study describes the recent incidence of BJI and investigates disease risk secondary to eczema. Methods BJI cases were children aged &lt;/= 15 years admitted with acute haematogenous osteomyelitis (AHO) or septic arthritis (SA) between 2018 and 2023 in the Auckland region. Data were obtained on eczema status, ethnicity and area‐based socioeconomic deprivation. BJI incidence was estimated using the 2018 Census. A retrospective case–control study was undertaken to determine the association between eczema and BJI. Ethnicity‐matched controls were identified from the nationally representative NZ Health Survey. Results This study identified 563 cases and 8840 ethnicity‐matched controls. Incidence of AHO remains higher for Māori (26.7/100 000) and Pacific (38.5/100 000) compared with European children (17/100 000). Eczema was seen more frequently in BJI cases (30% of BJI cases vs. 24% of NZHS controls ( p = 0.0007)). For NZ Māori and Pacific children, a diagnosis of eczema increased the odds of developing BJI (Pacific aOR = 1.6, 95% CI: 1.1–2.3, Māori aOR = 1.6, 1.1–2.4). Pacific children with BJI were more likely than controls to reside in areas of greater socioeconomic deprivation (aOR 1.88, 95% CI: 1.3–2.5). European children were more likely to reside in areas of least socioeconomic deprivation (OR 2.3, 95% CI: 1.7–3.1). Conclusions Childhood BJI remains inequitably distributed by ethnicity. Eczema may be a suitable focus for strategies to lower disease risk.
ABSTRACT Natural lakes and ponds typically feature green areas where people engage in recreational and sporting activities. In Italy, these areas are often inhabited by non‐native freshwater turtles, even at … ABSTRACT Natural lakes and ponds typically feature green areas where people engage in recreational and sporting activities. In Italy, these areas are often inhabited by non‐native freshwater turtles, even at high densities. However, freshwater turtles have been identified as natural carriers for various pathogens that can be transmitted to humans, making their sanitary monitoring crucial to prevent accidental transmission through direct or indirect contact. In this study, we investigated the presence of three potentially zoonotic pathogens, namely Salmonella , Leptospira and Cryptosporidium , in a group of 83 freshwater turtles ( Trachemys scripta ) captured in Piedmont, Northwest Italy. Overall infection prevalence was 9.6%. Salmonella spp. was detected in ten specimens of T. s. elegans and Cryptosporidium ducismarci in one specimen of T. s. scripta . Salmonella enterica subsp. diarizonae was confirmed in ten freshwater turtles. No Leptospira DNA was detected. Our findings highlight that turtles, as asymptomatic carriers of zoonotic pathogens, contribute to environmental contamination and public health risks, underscoring the need for sanitary monitoring of invasive alien species under a ‘One Health’ approach.
Background: Implant-associated infections (IAIs) require aggressive debridement to eliminate microbial bioburden. The use of irrigants may improve microbial killing during debridement. This study compared the efficacy of surgical irrigants in … Background: Implant-associated infections (IAIs) require aggressive debridement to eliminate microbial bioburden. The use of irrigants may improve microbial killing during debridement. This study compared the efficacy of surgical irrigants in vitro against Staphylococcus aureus alone and in combination with Candida albicans , in both planktonic and biofilm states. Methods: Full-strength Dakin’s solution, 0.35% povidone-iodine (PI), 10% PI, 3% hydrogen peroxide (HP), a 1:1 combination of 10% PI and 3% HP (PI + HP), Irrisept, XPERIENCE, Bactisure, and normal saline solution were tested. For planktonic testing, 1 × 10 6 colony-forming units (CFUs) of S. aureus and C. albicans were utilized, and biofilms were grown in these conditions on 0.8 × 10-mm titanium alloy Kirschner wires for 48 hours. Killing assays were performed using 5-minute dwell times. Success was defined by complete eradication of planktonic or biofilm CFUs. Results: PI + HP and Bactisure were the only irrigants to eradicate S. aureus in both planktonic and biofilm states. PI + HP was the only irrigant to eradicate polymicrobial S. aureus + C. albicans bioburden in both states. Conclusions: PI + HP and Bactisure were superior irrigants against S. aureus, eliminating it in planktonic and biofilm states. PI + HP was the only irrigant to eradicate polymicrobial S. aureus + C. albicans bioburden in both states. In vivo studies are needed to evaluate the clinical effectiveness. Clinical Relevance: Surgical irrigants have variable efficacy in eradicating microbes depending on their state of existence (planktonic versus biofilm). In this study, the most effective eradication of polymicrobial S. aureus + C. albicans bioburden was a 1:1 combination of 10% PI and 3% HP, which is of nominal cost.
Abstract Antimicrobial stewardship programs (ASP) reduce the inappropriate use of antimicrobial agents. Traditionally, paediatric osteoarticular infections have been treated with prolonged intravenous antibiotics; however, evidence suggests that shorter intravenous therapy … Abstract Antimicrobial stewardship programs (ASP) reduce the inappropriate use of antimicrobial agents. Traditionally, paediatric osteoarticular infections have been treated with prolonged intravenous antibiotics; however, evidence suggests that shorter intravenous therapy followed by oral narrow-spectrum antibiotics is effective. The aim of this study is to assess the impact of an ASP on the treatment of acute haematogenous bone and joint infections (AH-BJI) in children.We performed a single-centre quasi-experimental study comparing antibiotic use in paediatric [0–18 years] inpatients with AH-BJI before (2015–2016 period 1 [P1]) and after (2017-june 2023 period 2 [P2]) the implementation of a multifaceted hospital ASP with post-prescription review with feedback as the primary strategy. ASP also promoted a first-line empiric antibiotics change in the local protocol in June 2020. The study describes and compares the demographic and clinical characteristics among patients who were recruited prospectively during their hospital admission or in outpatient clinics. The primary outcomes were the length of antibiotic therapy, length of hospital stay, sequelae, readmission and fatality rates. Two-hundred-eighty-five patients were included (60 in P1 and 225 in P2). The length of parenteral antibiotic treatment and the length of hospital stay were significantly lower in P2 (median [IQR] days, P1: 8.5[7.0–12.0] vs P2: 7[4.5–8.0], p &lt; 0.001; and P1: 8.5[7.0–11.0] vs P2: 7[5.0–9.0], p &lt; 0.001, respectively). After June 2020, 3rd generation cephalosporin use decreased in patients &lt; 5 years old (96/119[81%] vs 6/57[10%] cases; p &lt; 0.001). The rates of sequelae, readmission (2/60[3.3%] in P1 and 8/225[3.6%] in P2) and mortality remained unchanged. Conclusion : After ASP implementation, the length of parenteral antibiotic treatment, length of hospital stay, and 3rd generation cephalosporin use in children with AH-BJI were reduced safely. What is Known: • Antimicrobial Stewardship Programmes (ASPs) have been shown to be effective for optimising antibiotic prescriptions and reducing antimicrobial resistance. There is still limited literature about ASPs in the paediatric population. • Paediatric bone and joint infections were traditionally treated with prolonged intravenous antibiotics. However, current evidence suggests that shorter intravenous therapy followed by oral narrow-spectrum antibiotics is equally effective. What is New: • Implementing an ASP with post-prescription review with feedback as main strategy, in a tertiary paediatric hospital, safely reduced the duration of intravenous treatment and length of hospital stay for children with acute haematogenous bone and joint infections (AH-BJI). • The ASP helped to reduce the use of 3rd generation cephalosporin in children with AH-BJI.
Septic arthritis is a serious infection that can lead to joint destruction, sepsis, and high mortality rates, particularly in elderly patients and those with comorbid conditions. Comorbidities such as diabetes, … Septic arthritis is a serious infection that can lead to joint destruction, sepsis, and high mortality rates, particularly in elderly patients and those with comorbid conditions. Comorbidities such as diabetes, rheumatoid arthritis, chronic kidney disease, and liver disease can complicate the diagnosis, treatment, and overall prognosis of the disease. These conditions may impair immune function, delay diagnosis, and hinder effective antimicrobial therapy, thereby increasing the risk of severe complications and poor outcomes. This review explores the impact of comorbidities on the prognosis of patients with septic arthritis, emphasizing the need for tailored management strategies to improve outcomes in this vulnerable population. Understanding the interplay between comorbid conditions and septic arthritis is essential for optimizing treatment approaches and enhancing patient care.
Background: Accurate and timely differential diagnosis of hip prosthesis failures remains a major clinical challenge. Radiographic examination remains the most cost-effective and common first-line imaging modality for hip prostheses, and … Background: Accurate and timely differential diagnosis of hip prosthesis failures remains a major clinical challenge. Radiographic examination remains the most cost-effective and common first-line imaging modality for hip prostheses, and integrating deep learning has the potential to improve its diagnostic accuracy and efficiency. Methods: A deep learning-based clinical classification system (Hip-Net) was developed to classify multiple causes of total hip arthroplasty failure, including periprosthetic joint infection (PJI), aseptic loosening, dislocation, periprosthetic fracture, and polyethylene wear. Hip-Net employed a dual-channel ensemble of 4 deep learning models trained on 2,908 routine dual-view (anteroposterior and lateral) radiographs for 1,454 patients (Asian) across 3 medical centers. An interpretive subnetwork generated spatially resolved disease probability maps. Discrimination performance and interpretability were tested in external and prospective cohorts, respectively. The correlation between model-generated individual PJI risk and inflammatory biomarkers was assessed. Results: Hip-Net demonstrated strong generalizability across different settings, effectively distinguishing between 5 common types of hip prosthesis failures with an accuracy of 0.904 (95% confidence interval [CI], 0.894 to 0.914) and an area under the receiver operating characteristic curve (AUC) of 0.937 (95% CI, 0.925 to 0.948) in the external cohort. The spatially resolved disease-probability maps for PJI closely aligned with intraoperative and pathological findings. The model-generated individual PJI risk scores exhibited a positive correlation with the C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR). Conclusions: Hip-Net provided a clinically applicable strategy for accurately classifying and characterizing multiple etiologies of hip prosthesis failure. Such an approach is highly beneficial for providing interpretable, pathology-aligned probability maps that enhance the understanding of PJI. Its integration into clinical workflows may streamline decision-making and improve patient outcomes. Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.
ABSTRACT The BioFire Joint Infection (JI) Panel is a multiplex polymerase chain reaction assay developed for rapid pathogen detection in synovial fluid, particularly for suspected prosthetic joint infections (PJI). However, … ABSTRACT The BioFire Joint Infection (JI) Panel is a multiplex polymerase chain reaction assay developed for rapid pathogen detection in synovial fluid, particularly for suspected prosthetic joint infections (PJI). However, its diagnostic sensitivity varies by clinical context and pathogen, and the impact of prior antibiotic exposure on sample quality and PJI stewardship remains unclear. This prospective study evaluated the diagnostic performance of the Investigational Use Only JI Panel versus conventional synovial fluid culture, using Musculoskeletal Infection Society criteria and symptom onset within 3 weeks to define acute PJI. Fifty-four fresh synovial fluid samples from patients with suspected knee PJI were analyzed. In acute PJI, the JI Panel demonstrated comparable sensitivity to synovial fluid culture (80% vs. 95%; P = 0.096), while significantly reducing time to pathogen identification (mean 18.2 vs. 84.6 hours, P &lt; 0.001), enabling earlier targeted antibiotic therapy in 83.3% of cases. Overall sensitivity across all PJI cases was moderate (50%) and significantly lower in chronic PJI (16.7%), reflecting limited panel coverage and reduced detection in prolonged infections. Prior antibiotic exposure reduced sensitivity for both methods, though not significant ( P = 0.127). The absence of key pathogens such as Staphylococcus epidermidis and Cutibacterium acnes further limited diagnostic yield in chronic cases. The JI Panel offers a rapid and clinically impactful tool for diagnosing acute PJI and guiding antibiotic stewardship. However, its limitations in chronic PJI and susceptibility to antibiotic pretreatment restrict its standalone diagnostic utility. Therefore, it should complement, not replace, traditional culture methods, particularly in chronic PJI cases. IMPORTANCE The JI Panel demonstrates high sensitivity for acute PJI but lower sensitivity for chronic infections. The ability of the JI Panel to rapidly identify pathogens in acute cases plays a significant role in improving antibiotic stewardship, ensuring timely and appropriate treatment. Given the lower sensitivity for chronic PJI, further research could focus on improving the detection of pathogens that are commonly involved in chronic infections. While the JI Panel is a promising tool for acute PJI diagnosis and supports rapid antibiotic stewardship, its limitations in chronic cases and under antibiotic exposure must be addressed to maximize its clinical utility.
Background: We report the successful formulation of a bone-targeted vancomycin-loaded liposomal carrier. Method: The basic liposomal structure is composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and dicetyl phosphate (DCP) in a molar … Background: We report the successful formulation of a bone-targeted vancomycin-loaded liposomal carrier. Method: The basic liposomal structure is composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and dicetyl phosphate (DCP) in a molar ratio of 3:1:0.25, respectively. The dehydration-rehydration method was used to maximize the liposomal-encapsulation efficiency of vancomycin after the initial preparation using thin-film hydration. Results: Sodium alendronate was used as a targeting moiety and was successfully conjugated to DSPE-PEG-COOH via carbodiimide chemistry, as was confirmed using IR spectroscopy. The resulting conjugate, DSPE-PEG-alendronate, was subsequently used in the formulation of bone-targeting vancomycin-loaded liposomes. In vitro binding assays with hydroxyapatite demonstrated preferential binding of the surface-modified liposomes to hydroxyapatite crystals. Furthermore, ex vivo studies revealed that the surface-modified liposomes exhibited enhanced binding affinity to the tibial bone tissue of 4-week-old male CD1 mice, in comparison to unmodified liposomes. Conclusions: The successfully formulated surface-modified vancomycin loaded liposomes showed enhanced bone affinity with a great potential for targeting the antibiotic to infected bones.
Background: Management of total knee arthroplasty (TKA) periprosthetic joint infection (PJI) can prompt knee fusion or transfemoral amputation, both associated with poor mobility. The titanium transcutaneous osseointegrated nail (TiTON) provides … Background: Management of total knee arthroplasty (TKA) periprosthetic joint infection (PJI) can prompt knee fusion or transfemoral amputation, both associated with poor mobility. The titanium transcutaneous osseointegrated nail (TiTON) provides superior mobility versus traditional socket prostheses but has been minimally studied for amputees with prior TKA PJI. Purpose: This study investigated the complications and mobility experience of 9 transfemoral osseointegration patients whose initial amputation was for TKA PJI management. Methods: A retrospective review of a prospectively maintained registry was conducted of 9 patients whose unilateral transfemoral osseointegration was performed following TKA PJI. Complications associated with the implantation of the titanium implant were noted, specifically antibiotic prescription or any additional surgery. K-level mobility performance before and after osseointegration was also compared. Results: Three patients (33.3%) had management for an infectious concern: 2 had a 10-day course of oral doxycycline for periportal drainage, and 1 had operative debridement with implant retention. No other complications (periprosthetic fracture, implant removal, and additional amputation) occurred. Eight patients (88.9%) improved their K-level, while 1 remained at K3. None declined. All achieved at least K2. Three patients were wheelchair-bound (K0) before osseointegration and achieved K3 or better. Conclusions: While infection may occur in patients who have TiTON following TKA PJI, our findings suggest that it does not seem inevitable, severe, or likely to further disable the patient. We noted meaningful mobility improvement that was common and lasting. Although our sample was small, we suggest that TiTON seems safe and reasonable to offer to patients seeking improved mobility and quality of life after amputation for TKA PJI management. Further study is warranted.
Background/Objectives: Accurate detection of periprosthetic joint infection (PJI) in patients with inflammatory arthritis (IA), including rheumatoid arthritis (RA), remains challenging due to overlapping inflammatory parameters and the influence of immunosuppressive … Background/Objectives: Accurate detection of periprosthetic joint infection (PJI) in patients with inflammatory arthritis (IA), including rheumatoid arthritis (RA), remains challenging due to overlapping inflammatory parameters and the influence of immunosuppressive regimens. Methods: A narrative review was conducted using PubMed/MEDLINE (2010-2025). Search terms included "periprosthetic joint infection", "inflammatory arthritis", "rheumatoid arthritis", "diagnosis", "biomarkers", "synovial fluid", and "immunosuppression". Eventually, 50 studies were included. Results: IA patients diagnosed with PJI are more frequently younger, female, and present with a higher burden of comorbidities and an increased rate of false-positive histological findings and culture-negative infections. Standard biomarkers, such as serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), as well as synovial fluid white blood cell count and polymorphonuclear leukocyte percentage, have a low to moderate value for diagnosing PJI in patients with IA. Optimal thresholds for these tests differ from those recommended by the Musculoskeletal Infection Society (MSIS). Alpha-defensin has demonstrated superior diagnostic performance among synovial fluid biomarkers included in MSIS criteria. Novel markers, such as serum bactericidal permeability-increasing protein (BPI) and neutrophil elastase-2 (ELA-2), as well as synovial C-reactive protein and calprotectin, along with molecular techniques like polymerase chain reaction (PCR), are showing increasing potential. Conclusions: Disease and treatment-related confounders hinder PJI diagnosis in IA. Adjusted thresholds and IA-specific approaches are needed. Further research should validate emerging biomarkers, among which BPI, ELA-2, and synovial CRP show the greatest diagnostic potential and guide perioperative immunosuppressive strategies.
Background: Surgical Site Infection (SSI) is among the most common healthcare-associated infections worldwide. Both patient-related and surgical factors contribute to its incidence. Prevention and management of SSI require a multidisciplinary, … Background: Surgical Site Infection (SSI) is among the most common healthcare-associated infections worldwide. Both patient-related and surgical factors contribute to its incidence. Prevention and management of SSI require a multidisciplinary, comprehensive approach, supported by accurate epidemiological data to enhance healthcare quality and patient outcomes. Methods: This study was retrospective descriptive design. Data were obtained using total sampling from medical records of all patients with SSI post clean surgery with Implant in the Department of Orthopaedic and Traumatology at Dr. Soetomo Hospital from July 2021 to July 2022. Results: This study showed that SSI occurred in 47 patients. Most patients with SSI were male (61.70%) and elderly (51.06%). Obesity (Obesity I and II) was the most common Body Mass Index (BMI) category (46.81%). Anemia was the most prevalent comorbidity (36.17%). American Society of Anesthesiologists (ASA) score II was most frequently found (65.96%). Most patients had no postoperative complications (93.61%). Prophylactic antibiotics were consistently administered using cefazolin. Elective procedures were the predominant surgery type (85.11%). The duration of surgery exceeding four hours was common (55.32%). Conclusion: This study concluded that SSI most frequently occurred in elderly male patients. The majority of SSI were associated with elective surgical procedures. These findings highlight the need for targeted preventive strategies.
Hematogenously disseminated osteomyelitis in children and adolescents is an acute disease with a substantial threat to the health of a child or adolescent. Due to the destruction of bones or … Hematogenously disseminated osteomyelitis in children and adolescents is an acute disease with a substantial threat to the health of a child or adolescent. Due to the destruction of bones or joints within hours to days and the risk of bacterial sepsis, it is a feared pediatric emergency that requires hospitalization in a children's hospital and rapid action. The standard radiological procedures are X‑ray, sonography and magnetic resonance imaging (MRI). Contrast-enhanced MRI has established itself as the gold standard for the detection of osteomyelitis. It is characterized by a very high sensitivity and high specificity. If there is a clinical suspicion of bacterial osteomyelitis, an MRI diagnosis must be carried out quickly.
Background/Objectives: Periprosthetic joint infection (PJI) is a severe complication that follows arthroplasty and occurs in approximately 2% of all cases. One of several cornerstones of therapy is an optimized antibiotic … Background/Objectives: Periprosthetic joint infection (PJI) is a severe complication that follows arthroplasty and occurs in approximately 2% of all cases. One of several cornerstones of therapy is an optimized antibiotic regimen. Early administration of rifampicin-together with a combination of an antibiotic to which the specific microorganism is susceptible-accompanying a two-stage revision surgery, remained controversial due to the potential risk of emerging resistance. However, the exact time to start rifampicin treatment often remains unclear and might be crucial in the treatment regimen. Methods: In a retrospective study design, a total of 212 patients receiving a two-stage revision surgery after a diagnosis of PJI (60.8% THA, 39.2% TKA) received an individual rifampicin combination therapy after initial debridement and removal of all foreign material, starting rifampicin on the second day postoperatively. Results: At the time of spacer explantation, two patients had developed rifampicin resistance (0.9%). At follow-up (M = 55.4 ± 21.8 months) after reimplantation, three patients had developed rifampicin resistance (1.4%). Concerning the development of reinfection, in general, in the study group and the necessity for further treatment, a total of 25 patients showed signs of reinfection (11.8%). Conclusions: Only 0.9% after the first stage and 1.4% at follow-up after the second stage of all 212 patients with accompanying long-term rifampicin combination therapy developed a rifampicin resistance. Therefore, rifampicin administration could be started on the second postoperative day when sufficient concentrations of the accompanying antibiotics can be expected.
Background: The purpose of this study was to determine the normative perioperative plasmatic levels of presepsin in patients undergoing primary total hip arthroplasty (THA), and to evaluate whether presepsin measurements … Background: The purpose of this study was to determine the normative perioperative plasmatic levels of presepsin in patients undergoing primary total hip arthroplasty (THA), and to evaluate whether presepsin measurements can effectively distinguish the presence of periprosthetic joint infection (PJI) following THA. Methods: In study 1, we evaluated multiple inflammatory markers before and at several time points after surgery in 31 primary THA patients. The Kruskal-Wallis test was used to compare sequential changes in each variable followed by the Sheffe post hoc comparison. In study 2, we evaluated the diagnostic accuracy of the inflammatory markers for PJI using five cases with confirmed PJI without bacteremia. ROC curve analysis was performed comparing these PJI cases with the 31 preoperative cases from study 1. Results: In study 1, presepsin levels were not significantly different from the baseline throughout the monitoring period. In study 2, the AUCs of CRP (1.0, p < 0.001) and ESR-1h (0.83, p < 0.05) in the ROC curve were able to discriminate PJI, but those of presepsin (0.51, p = 0.96) and WBC (0.65, p = 0.28) failed to discriminate PJI. Conclusions: Our findings suggest that presepsin levels remain stable following THA and may have limited utility in detecting periprosthetic joint infection, particularly in the absence of systemic infection.
Osteomyelitis is a complex infectious bone disease involving pathogen invasion, host immune responses, and dysregulation of the local microenvironment. As a critical component of the innate immune system, macrophages play … Osteomyelitis is a complex infectious bone disease involving pathogen invasion, host immune responses, and dysregulation of the local microenvironment. As a critical component of the innate immune system, macrophages play a pivotal role in inflammatory responses and tissue repair. Their polarization states (M1/M2) directly influence disease progression, while mitochondrial metabolism, as the central hub of cellular energy metabolism, has recently been shown to play a key role in macrophage polarization and functional regulation. However, how mitochondrial metabolism regulates macrophage polarization to affect the pathological mechanisms of osteomyelitis, and how to develop novel therapeutic strategies based on this mechanism, remain critical scientific questions to be addressed. This review systematically summarizes the molecular mechanisms by which mitochondrial metabolism regulates macrophage polarization and its role in osteomyelitis, with a focus on the impact of mitochondrial dynamics (fission/fusion), metabolic reprogramming, and reactive oxygen species (ROS) generation on macrophage polarization. Additionally, potential therapeutic strategies targeting mitochondrial metabolism are analyzed. For the first time, this review integrates the interplay between mitochondrial metabolism and macrophage polarization in osteomyelitis, revealing how mitochondrial dysfunction exacerbates inflammation and bone destruction through metabolic reprogramming. Based on these findings, we propose novel therapeutic strategies targeting mitochondrial metabolism, offering new perspectives and directions for understanding the pathogenesis and clinical treatment of osteomyelitis.
Antibiotic-loaded calcium sulphate beads (ALCSB) have been effectively used in revision arthroplasty for prosthetic joint infections (PJI), but their use in primary arthroplasty as a prophylactic measure remains limited. This … Antibiotic-loaded calcium sulphate beads (ALCSB) have been effectively used in revision arthroplasty for prosthetic joint infections (PJI), but their use in primary arthroplasty as a prophylactic measure remains limited. This study presents the first reported experience using ALCSB in bacteremic patients undergoing hip hemiarthroplasty (HA) for displaced femoral neck fractures—a group at high risk for PJI. Four elderly patients (mean age 71.5) with confirmed preoperative bacteremia from various sources (pneumonia, infected ulcer, endocarditis) received ALCSB during HA. Beads were loaded with vancomycin and/or tobramycin based on microbial sensitivities and placed around the joint capsule and gluteal muscles. Over a mean follow-up of 18 months, none of the patients developed PJI, required revision, or experienced persistent wound drainage. One patient died postoperatively due to unrelated cardiac causes. The findings highlight the potential of ALCSB as a localized prophylactic strategy in high-risk HA patients, especially where systemic infection is present preoperatively. Although the sample size is limited, the absence of infection or wound complications supports the feasibility of this approach. Larger studies are needed to validate these findings and assess cost-effectiveness.