Medicine › Epidemiology

Pneumocystis jirovecii pneumonia detection and treatment

Works Count: 42037

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Description

This cluster of papers focuses on the epidemiology, pathogenesis, diagnosis, and treatment of Pneumocystis pneumonia, particularly in the context of HIV infection and immunocompromised patients. It covers topics such as opportunistic infections, colonization by Pneumocystis, impact of antiretroviral therapy, and the clinical significance of Pneumocystis colonization.

Keywords

Pneumocystis; Pneumonia; HIV; Opportunistic Infections; Antiretroviral Therapy; Colonization; Diagnosis; Treatment; Immunocompromised Patients; Epidemiology

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America

2009-01-01

Jonathan E. Kaplan , Constance A. Benson , King K. Holmes +3 more

This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons … This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.

A New Name forPneumocystisfrom Humans and New Perspectives on the Host-Pathogen Relationship

2002-09-01

James R. Stringer , Charles B. Beard , Robert F. Miller +1 more

Abstract The disease known as Pneumocystis carinii pneumonia (PCP) is a major cause of illness and death in persons with impaired immune systems. While the genus Pneumocystis has been known … Abstract The disease known as Pneumocystis carinii pneumonia (PCP) is a major cause of illness and death in persons with impaired immune systems. While the genus Pneumocystis has been known to science for nearly a century, understanding of its members remained rudimentary until DNA analysis showed its extensive diversity. Pneumocystis organisms from different host species have very different DNA sequences, indicating multiple species. In recognition of its genetic and functional distinctness, the organism that causes human PCP is now named Pneumocystis jiroveci Frenkel 1999. Changing the organism’s name does not preclude the use of the acronym PCP because it can be read “Pneumocystis pneumonia.” DNA varies in samples of P. jiroveci, a feature that allows reexamination of the relationships between host and pathogen. Instead of lifelong latency, transient colonization may be the rule.

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Pneumocystis Pneumonia—Los Angeles

1996-10-02

Gottlieb Ms , Schanker Hm , Fan Pt +3 more

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor … Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal

Pneumocystis cariniiPneumonia: Differences in Lung Parasite Number and Inflammation in Patients with and without AIDS

1989-11-01

Andrew H. Limper , Kenneth P. Offord , Thomas F. Smith +1 more

Pneumocystis carinii pneumonia has emerged as a significant cause of morbidity and mortality in immunocompromised patients with and without AIDS. To determine differences in P. carinii pneumonia in patients with … Pneumocystis carinii pneumonia has emerged as a significant cause of morbidity and mortality in immunocompromised patients with and without AIDS. To determine differences in P. carinii pneumonia in patients with and without AIDS, the P. carinii parasite numbers, lung inflammatory cell populations, gas exchange, and survival were assessed in a series of 75 consecutive patients with P. carinii pneumonia. Bronchoalveolar lavage was used to quantify the parasite and inflammatory cell numbers in these patients. The data from this study indicate: (1) patients with P. carinii pneumonia and AIDS have significantly greater numbers of P. carinii per ml of lavage compared to other immunocompromised patients with P. carinii pneumonia (p less than 0.0001); (2) patients with P. carinii pneumonia and AIDS also have significantly fewer neutrophils recovered in the lavage compared to other immunocompromised patients with P. carinii pneumonia (p = 0.0001); (3) patients with AIDS and P. carinii pneumonia have higher arterial oxygen tensions than those patients with P. carinii pneumonia in conditions other than AIDS (p = 0.008); and (4) increased lavage neutrophils (rather than parasite number) correlate with poorer oxygenation and poorer patient survival (p = 0.01). This investigation demonstrates substantial differences in lung inflammation and parasite number during P. carinii pneumonia in patients with and without AIDS. The data further suggest that lung inflammation contributes substantially to respiratory impairment in patients with P. carinii pneumonia.

The mortality and pathology of HIV infection in a West African city

1993-12-01

Sebastian Lucas , A. Hounnou , Christopher S. Peacock +7 more

Background: HIV disease is epidemic in Africa, but associated mortality, underlying pathology and CD4+ T-lymphocyte counts have not previously been evaluated in a representative study. Such data help to determine … Background: HIV disease is epidemic in Africa, but associated mortality, underlying pathology and CD4+ T-lymphocyte counts have not previously been evaluated in a representative study. Such data help to determine the management of HIV-positive people. Both HIV-1 and HIV-2 infections are prevalent in Côte d'lvoire, and the pathology of HIV-2 infection in Africa is unclear. Methods: Consecutive adult medical admissions to a large city hospital in Côte d'lvoire were studied in 1991, and a sample of HIV-positive deaths autopsied. Results: Of 5401 patients evaluated, 50% were HIV-positive; 38% of these died, with a median survival of 1 week. At autopsy (n=294, including 24% of HIV-positive deaths in hospital), tuberculosis (TB), bacteraemia (predominantly Gram-negative rods) and cerebral toxoplasmosis caused 53% of deaths. TB was seen in 54% of cadavers with AIDS-defining pathology and Pneumocystis pneumonia in 4%. The median CD4+ T-lymphocyte counts in those who died was <90×106/l. Compared with HIV-1-positives, patients with HIV-2-positivity had a greater frequency of severe cytomegalovirus infection, HIV encephalitis and cholangitis. Conclusions: In this population, HIV-positive adults present to hospital with advanced disease associated with high mortality. The three major underlying pathologies (TB, toxoplasmosis and bacteraemia) are either preventable or treatable. TB is an underestimated cause of the 'slim' syndrome in Africa. The patterns of pathology in HIV-2-positive patients suggest a more prolonged terminal course compared with HIV-1. There is an urgent need for attention towards the issues of therapy and care for HIV disease in developing countries. AIDS 1993, 7:1569–1579

Adverse Reactions to Trimethoprim-Sulfamethoxazole in Patients with the Acquired Immunodeficiency Syndrome

1984-04-01

Fred M. Gordin

We reviewed the charts of 38 patients with the acquired immunodeficiency syndrome who were treated for Pneumocystis carinii pneumonia. Only 5 of 37 patients started on trimethoprim-sulfamethoxazole were able to … We reviewed the charts of 38 patients with the acquired immunodeficiency syndrome who were treated for Pneumocystis carinii pneumonia. Only 5 of 37 patients started on trimethoprim-sulfamethoxazole were able to complete treatment; in 29 patients drug toxicity occurred and in 19 treatment was changed due to adverse reactions that included rash, fever, neutropenia, thrombocytopenia, and transaminase elevation. Pentamidine was given to 30 patients (1 as initial treatment); toxicity occurred in 13 but only 4 required a change in drug. Adverse reactions from pentamidine included fever, rash, neutropenia, transaminase elevation, azotema, and hypoglycemia. Patients received trimethoprim-sulfamethoxazole a median of 9.5 days, and pentamidine, a median of 12.5 days. Toxicity from trimethoprim-sulfamethoxazole appeared earlier than toxicity associated with pentamidine (7.5 versus 9.5 days of treatment). In patients with the acquired immunodeficiency syndrome, trimethoprim-sulfamethoxazole has a higher incidence of adverse reactions than pentamidine (p < 0.005).

The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials

1997-06-01

Heiner C. Bucher , Gordon Guyatt , Lauren E. Griffith +1 more

Quantitation of HIV-1 RNA in Plasma Predicts Outcome after Seroconversion

1995-04-15

John W. Mellors

To investigate the relation between the quantity of human immunodeficiency virus type 1 (HIV-1) RNA in plasma and the risk for the acquired immunodeficiency syndrome (AIDS) or a decline in … To investigate the relation between the quantity of human immunodeficiency virus type 1 (HIV-1) RNA in plasma and the risk for the acquired immunodeficiency syndrome (AIDS) or a decline in the CD4+ T-cell count after seroconversion.Prospective study.62 homosexual men with documented HIV-1 seroconversion.University outpatient setting.Clinical status, CD4+ T-cell counts, and plasma and serum samples were obtained every 6 months. Human immunodeficiency virus RNA in plasma was quantitated with a branched-DNA (bDNA) assay. Serum samples were assayed for neopterin, beta 2-microglobulin, and immune complex dissociated HIV-1 p24 antigen.18 of 62 (29%) men developed AIDS; 21 (34%) had a significant decline in the CD4+ T-cell count without AIDS; and 23 (37%) had a stable CD4+ T-cell count. For each participant, HIV-1 RNA results were categorized into one of four groups: 1) detection of HIV-1 RNA (> 1 x 10(4) genome equivalents/mL [Eq/mL]) in all samples; 2) detection in most samples (> or = 50%); 3) detection in fewer than 50% of samples; and 4) detection in none of the samples. Detection of HIV-1 RNA in all or most samples was strongly associated with AIDS (16 of 18 patients) and a decline in the CD4+ T-cell count (13 of 21 patients) compared with a stable CD4+ T-cell count (4 of 23 patients; P < 0.001). Conversely, the absence of HIV-1 RNA (< 1 x 10(4) Eq/mL) in all or most samples was associated with stable CD4+ T-cell counts (19 of 23 patients) and a lower risk for AIDS or decline in the CD4+ T-cell count (10 of 39 patients; P < 0.001). In multivariate analysis of all laboratory values at the seroconversion visit, a plasma HIV-1 RNA level greater than 1 x 10(5) Eq/mL was the most powerful predictor of AIDS (odds ratio, 10.8; P = 0.01).Plasma HIV-1 RNA is a strong, CD4+ T-cell-independent predictor of a rapid progression to AIDS after HIV-1 seroconversion.

Pulmonary Complications of the Acquired Immunodeficiency Syndrome

1984-06-21

John F. Murray , Charles P. Felton , Stuart M. Garay +4 more

Under the sponsorship of the Division of Lung Diseases of the National Heart, Lung, and Blood Institute, a two-day workshop on the pulmonary complications of the acquired immunodeficiency syndrome (AIDS) … Under the sponsorship of the Division of Lung Diseases of the National Heart, Lung, and Blood Institute, a two-day workshop on the pulmonary complications of the acquired immunodeficiency syndrome (AIDS) was held in Bethesda, Md., on October 13 and 14, 1983. The meeting was organized to bring together representatives from six institutions who had had considerable experience with AIDS and who had agreed to share their findings. The purposes of the workshop were threefold: (1) to collate and analyze the experience from the six centers concerning the types and incidence of the pulmonary complications of AIDS, how to diagnose, treat, . . .

HIV Infection–Associated Tuberculosis: The Epidemiology and the Response

2010-04-16

Haileyesus Getahun , Christian Gunneberg , Reuben Granich +1 more

Of the 33.2 million persons infected with human immunodeficiency virus (HIV), one-third are estimated to also be infected with Mycobacterium tuberculosis. In 2008, there were an estimated 1.4 million new … Of the 33.2 million persons infected with human immunodeficiency virus (HIV), one-third are estimated to also be infected with Mycobacterium tuberculosis. In 2008, there were an estimated 1.4 million new cases of tuberculosis (TB) among persons with HIV infection, and TB accounted for 26% of AIDS-related deaths. The relative risk of TB among HIV-infected persons, compared with that among HIV-uninfected persons, ranges from 20- and 37-fold, depending on the state of the HIV epidemic. In 2008, 1.4 million patients with TB were tested globally for HIV, and 81 countries tested more than half of their patients with TB for HIV. Only 4% of all persons infected with HIV were screened for TB in the same year. Decentralization of HIV treatment services and strengthening of its integration with TB services are essential. Use of the highly decentralized TB services as an entry point to rapidly expand access to antiretroviral therapy and methods for prevention of HIV infection must be pursued aggressively.

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Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the Fungi

1988-08-01

Jeffrey C. Edman , Joseph A. Kovacs , Henry Masur +3 more

Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene

1997-02-01

Dominique Sanglard , Françoise Ischer , Michel Monod +1 more

Resistance to azole antifungal agents in Candida albicans can be mediated by multidrug efflux transporters. In a previous study, we identified at least two such transporters, Cdr1p and Benp, which … Resistance to azole antifungal agents in Candida albicans can be mediated by multidrug efflux transporters. In a previous study, we identified at least two such transporters, Cdr1p and Benp, which belong to the class of A TP- b inding c assette (ABC) transporters and of major facilitators, respectively. To isolate additional factors potentially responsible for resistance to azole antifungal agents in C. albicans, the hypersusceptibility of a Saccharomyces cerevisiae multidrug transporter mutant, δ pdr5 , to these agents was complemented with a C. albicans genomic library. Several new genes were isolated, one of which was a new ABC transporter gene called CDR2 ( C andida d rug r esistance). The protein Cdr2p encoded by this gene exhibited 84% identity with Cdr1p and could confer resistance to azole antifungal agents, to other antifungals (terbinafine, amorolfine) and to a variety of metabolic inhibitors. The disruption of CDR2 in the C. albicans strain CAF4-2 did not render cells more susceptible to these substances. When the disruption of CDR2 was performed in the background of a mutant in which CDR1 was deleted, the resulting double δ cdr1 δ cdr2 mutant was more susceptible to these agents than the single δ cdr1 mutant. The absence of hypersusceptibility of the single δ cdr2 mutant could be explained by the absence of CDR2 mRNA in azole-susceptible C albicans strains. CDR2 was overexpressed, however, in clinical C. albicans isolates resistant to azole antifungal agents as described previously for CDR1, but to levels exceeding or equal to those reached by CDR1. Interestingly, CDR2 expression was restored in δ cdr1 mutants reverting spontaneously to wild-type levels of susceptibility to azole antifungal agents. These data demonstrate that CDR2 plays an important role in mediating the resistance of C. albicans to azole antifungal agents.

Phase equilibria of rock-forming ferromagnesian silicates in granitic systems

1983-12-01

M.T. Naney

BACKGROUND--Infection with Pneumocystis carinii typically results in a pneumonia which histologically is seen to consist of an eosinophilic foamy alveolar exudate associated with a mild plasma cell interstitial infiltrate. Special … BACKGROUND--Infection with Pneumocystis carinii typically results in a pneumonia which histologically is seen to consist of an eosinophilic foamy alveolar exudate associated with a mild plasma cell interstitial infiltrate. Special stains show that cysts of P carinii lie within the alveolar exudate. Atypical histological appearances may occasionally be seen, including a granulomatous pneumonia and diffuse alveolar damage. In these patients the clinical presentation may be atypical and results of investigations negative unless lung biopsies are performed and tissue obtained for histological examination. METHODS--The incidence and mode of presentation of histologically atypical pneumocystis pneumonia was studied in a cohort of HIV-I antibody positive patients. RESULTS--Over a 30 month period 138 patients had pneumocystis pneumonia, of whom eight (6%) had atypical histological appearances which were diagnosed (after negative bronchoalveolar lavage) by open lung biopsy in five, percutaneous biopsy in one, and at post mortem examination in two. Atypical appearances included granulomatous inflammation in four patients, "pneumocystoma" in two (one also had extrapulmonary pneumocystosis), bronchiolitis obliterans organising pneumonia in one patient, diffuse alveolar damage and subpleural cysts in one (who also had intrapulmonary cytomegalovirus infection), and extrapulmonary pneumocystosis in two patients. CONCLUSIONS--Various atypical histological appearances may be seen in pneumocystis pneumonia. Lung biopsy (either percutaneous or open) should be considered when bronchoalveolar lavage is repeatedly negative and evidence of P carinii should be sought, by use of special stains, in all lung biopsy material from HIV-I antibody positive patients.

Pneumocystis carinii Pneumonia in Patients Without Acquired Immunodeficiency Syndrome: Associated Illnesses and Prior Corticosteroid Therapy

1996-01-01

Steven H. Yale , Andrew H. Limper

Relationship of the Manifestations of Tuberculosis to CD4 Cell Counts in Patients with Human Immunodeficiency Virus Infection

1993-11-01

Brenda E. Jones , S M Young , Diana Antoniskis +3 more

To evaluate the relationship between the clinical presentation of tuberculosis and the CD4 cell count in patients with human immunodeficiency virus (HIV) infection, we evaluated clinical and laboratory features of … To evaluate the relationship between the clinical presentation of tuberculosis and the CD4 cell count in patients with human immunodeficiency virus (HIV) infection, we evaluated clinical and laboratory features of 97 HIV-infected patients with tuberculosis in whom CD4 cell counts were available. Extrapulmonary tuberculosis was found in 30 (70%) of 43 patients with ⩽ 100 CD4 cells/µL, 10 (50%) of 20 patients with 101 to 200 CD4 cells/µL, seven (44%) of 16 patients with 201 to 300 CD4 cells/µL, and five (28%) of 18 patients with > 300 CD4 cells/µL (p = 0.02). Mycobacteremia was found in 18 (49%) of 37 patients with ⩽ 100 CD4 cells/ µL, three (20%) of 15 patients with 101 to 200 CD4 cells/µL, one (7%) of 15 patients with 201 to 300 CD4 cells/µL, and none of eight patients with > 300 CD4 cells/µL (p = 0.002). Acid-fast smears were more often positive in patients with low CD4 cell counts. Positive tuberculin skin tests were more common in patients with high CD4 counts. On chest roentgenograms, mediastinal adenopathy was noted in 20 (34%) of 58 patients with ⩽ 200 CD4 cells/µL and four (14%) of 29 patients with > 200 CD4 cells/µL (p = 0.04). Pleural effusions were noted in six (10%) of 58 patients with ⩽ 200 CD4 cells/µL and eight (28%) of 29 patients with > 200 CD4 cells/µL (p = 0.04). The CD8 cell counts did not correlate with the manifestations of tuberculosis. We conclude that, in HIV-infected patients, markers of severe tuberculosis, such as mycobacteremia and positive acid-fast smears, are more common in those with low CD4 cell counts. Features dependent on delayed-type hypersensitivity responses, such as positive tuberculin skin tests and tuberculous pleuritis, are more common in patients with higher CD4 cell counts. These findings suggest that CD4 cells play a central role in limiting the severity of tuberculosis.

Acquired Immunodeficiency Syndrome (AIDS) Associated with Transfusions

1984-01-12

James W. Curran , Dale N. Lawrence , Harold W. Jaffe +7 more

Of 2157 patients with the acquired immunodeficiency syndrome (AIDS) whose cases were reported to the Centers for Disease Control by August 22, 1983, 64 (3 per cent) with AIDS and … Of 2157 patients with the acquired immunodeficiency syndrome (AIDS) whose cases were reported to the Centers for Disease Control by August 22, 1983, 64 (3 per cent) with AIDS and Pneumocystis carinii pneumonia had no recognized risk factors for AIDS. Eighteen of these (28 per cent) had received blood components within five years before the onset of illness. These patients with transfusion-associated AIDS were more likely to be white (P = 0.00008) and older (P = 0.0013) than other patients with no known risk factors. They had received blood 15 to 57 months (median, 27.5) before the diagnosis of AIDS, from 2 to 48 donors (median, 14). At least one high-risk donor was identified by interview or T-cell-subset analysis in each of the seven cases in which investigation of the donors was complete; five of the six high-risk donors identified during interview also had low T-cell helper/suppressor ratios, and four had generalized lymphadenopathy according to history or examination. These findings strengthen the evidence that AIDS may be transmitted in blood.

Uptake of Pneumocystis carinii mediated by the macrophage mannose receptor

1991-05-01

R. Alan B. Ezekowitz , D. Williams , Henry Koziel +4 more

AIDS virus-specific cytotoxic T lymphocytes in lung disorders

1987-07-01

Fernando Plata , Brigitte Autran , Livia Pedroza-Martins +6 more

Immune restoration disease after antiretroviral therapy

2004-07-27

Martyn A. French , Patricia Price , Shelley F. Stone

Suppression of HIV replication by highly active antiretroviral therapy (HAART) often restores protective pathogen-specific immune responses, but in some patients the restored immune response is immunopathological and causes disease [immune … Suppression of HIV replication by highly active antiretroviral therapy (HAART) often restores protective pathogen-specific immune responses, but in some patients the restored immune response is immunopathological and causes disease [immune restoration disease (IRD)]. Infections by mycobacteria, cryptococci, herpesviruses, hepatitis B and C virus, and JC virus are the most common pathogens associated with infectious IRD. Sarcoid IRD and autoimmune IRD occur less commonly. Infectious IRD presenting during the first 3 months of therapy appears to reflect an immune response against an active (often quiescent) infection by opportunistic pathogens whereas late IRD may result from an immune response against the antigens of non-viable pathogens. Data on the immunopathogenesis of IRD is limited but it suggests that immunopathogenic mechanisms are determined by the pathogen. For example, mycobacterial IRD is associated with delayed-type hypersensitivity responses to mycobacterial antigens whereas there is evidence of a CD8 T-cell response in herpesvirus IRD. Furthermore, the association of different cytokine gene polymorphisms with mycobacterial or herpesvirus IRD provides evidence of different pathogenic mechanisms as well as indicating a genetic susceptibility to IRD. Differentiation of IRD from an opportunistic infection is important because IRD indicates a successful, albeit undesirable, effect of HAART. It is also important to differentiate IRD from drug toxicity to avoid unnecessary cessation of HAART. The management of IRD often requires the use of anti-microbial and/or anti-inflammatory therapy. Investigation of strategies to prevent IRD is a priority, particularly in developing countries, and requires the development of risk assessment methods and diagnostic criteria.

Sulfonamide resistance: mechanisms and trends

2000-06-01

Ola Sköld

Resistance to Trimethoprim-Sulfamethoxazole

2001-06-01

George M. Eliopoulos , Pentti Huovinen

Sulfonamides have a glorious history. In 1935, they were the first class of true antimicrobial agents with life-saving potency. Today, 66 years later, increased bacterial resistance to sulfonamides and to … Sulfonamides have a glorious history. In 1935, they were the first class of true antimicrobial agents with life-saving potency. Today, 66 years later, increased bacterial resistance to sulfonamides and to trimethoprim (TMP), a synthetic antimicrobial agent that is 30 years younger than sulfonamides, has limited their use to only a few indications. In the treatment and prophylaxis of patients with urinary tract infections, trimethoprim-sulfamethoxazole (TMP-SMZ) or TMP alone is still considered the first-line drug of choice, although increased bacterial resistance to these agents has been linked with treatment failure. TMP-SMZ has a possible role as a second- or third-line treatment for patients who have respiratory tract infections. In the developing world, where this inexpensive drug is widely used as first-line treatment, bacterial resistance has caused problems, especially with regard to the treatment of patients with severe respiratory tract infections. Use of TMP-SMZ as prophylaxis for Pneumocystis carinii infection has rapidly increased the multidrug resistance of bacterial pathogens found in human immunodeficiency virus-infected patients. Today, detailed and reliable knowledge on the resistance of bacterial pathogens to both TMP-SMZ and TMP is an essential requirement for the safe and effective use of these drugs in all clinical settings.

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Accelerated course of human immunodeficiency virus infection after tuberculosis.

1995-01-01

Christopher Whalen , C. Robert Horsburgh , D. Hom +3 more

To determine the effect of active tuberculosis on survival and the incidence of opportunistic infections in HIV-infected patients, we performed a retrospective cohort study at four U.S. medical centers to … To determine the effect of active tuberculosis on survival and the incidence of opportunistic infections in HIV-infected patients, we performed a retrospective cohort study at four U.S. medical centers to compare the survival and incidence rate of opportunistic infections in 106 HIV-infected patients with active tuberculosis (cases) with that of 106 HIV-infected patients without tuberculosis (control subjects) but with a similar level of immunosuppression (measured by the absolute CD4+ lymphocyte count) as the cases. Cases and control subjects were similar with regard to age, sex, race, previous opportunistic infection, and use of antiretroviral therapy, but they were more likely than control subjects to have a history of intravenous drug use (49 versus 19%). The mean CD4+ counts were similar for cases and control subjects (154 versus 153 cells/microliters, respectively). The incidence rate of new AIDS-defining opportunistic infections in cases was 4.0 infections per 100 person-months compared with 2.8 infections per 100 person-months in control subjects for an incidence rate ratio (RR) of 1.42 (95% confidence interval: 0.94-2.11). Cases also had a shorter overall survival than did controls subjects (p = 0.001). Active tuberculosis was associated with an increased risk for death (odds ratio = 2.17), even when controlling for age, intravenous drug use, previous opportunistic infection, baseline CD4+ count, and antiretroviral therapy. Although active tuberculosis may be an independent marker of advanced immunosuppression in HIV-infected patients, it may also act as a cofactor to accelerate the clinical course of HIV infection.

Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters

1995-11-01

Dominique Sanglard , Karl Kuchler , Françoise Ischer +3 more

Azole antifungal agents, and especially fluconazole, have been used widely to treat oropharyngeal candidiasis in patients with AIDS. An increasing number of cases of clinical resistance against fluconazole, often correlating … Azole antifungal agents, and especially fluconazole, have been used widely to treat oropharyngeal candidiasis in patients with AIDS. An increasing number of cases of clinical resistance against fluconazole, often correlating with in vitro resistance, have been reported. To investigate the mechanisms of resistance toward azole antifungal agents at the molecular level in clinical C. albicans isolates, we focused on resistance mechanisms related to the cellular target of azoles, i.e., cytochrome P450(14DM) (14DM) and those regulating the transport or accumulation of fluconazole. The analysis of sequential isogenic C. albicans isolates with increasing levels of resistance to fluconazole from five AIDS patients showed that overexpression of the gene encoding 14DM either by gene amplification or by gene deregulation was not the major cause of resistance among these clinical isolates. We found, however, that fluconazole-resistant C. albicans isolates failed to accumulate 3H-labelled fluconazole. This phenomenon was reversed in resistant cells by inhibiting the cellular energy supply with azide, suggesting that resistance could be mediated by energy-requiring efflux pumps such as those described as ATP-binding cassette (ABC) multidrug transporters. In fact, some but not all fluconazole-resistant clinical C. albicans isolates exhibited up to a 10-fold relative increase in mRNA levels for a recently cloned ABC transporter gene called CDR1. In an azole-resistant C. albicans isolate not overexpressing CDR1, the gene for another efflux pump named BENr was massively overexpressed. This gene was cloned from C. albicans for conferring benomyl resistance in Saccharomyces cerevisiae. Therefore, at least the overexpression or the deregulation of these two genes potentially mediates resistance to azoles in C. albicans clinical isolates from AIDS patients with oropharyngeal candidiasis. Involvement of ABC transporters in azole resistance was further evidenced with S. cerevisiae mutants lacking specific multidrug transporters which were rendered hypersusceptible to azole derivatives including fluconazole, itraconazole, and ketoconazole.

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Integration of Antiretroviral Therapy with Tuberculosis Treatment

2011-10-19

Salim S. Abdool Karim , Kogieleum Naidoo , Anneke Grobler +7 more

We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, the timing for the initiation of ART during tuberculosis treatment remains unresolved.We conducted a three-group, open-label, … We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, the timing for the initiation of ART during tuberculosis treatment remains unresolved.We conducted a three-group, open-label, randomized, controlled trial in South Africa involving 642 ambulatory patients, all with tuberculosis (confirmed by a positive sputum smear for acid-fast bacilli), human immunodeficiency virus infection, and a CD4+ T-cell count of less than 500 per cubic millimeter. Findings in the earlier-ART group (ART initiated within 4 weeks after the start of tuberculosis treatment, 214 patients) and later-ART group (ART initiated during the first 4 weeks of the continuation phase of tuberculosis treatment, 215 patients) are presented here.At baseline, the median CD4+ T-cell count was 150 per cubic millimeter, and the median viral load was 161,000 copies per milliliter, with no significant differences between the two groups. The incidence rate of the acquired immunodeficiency syndrome (AIDS) or death was 6.9 cases per 100 person-years in the earlier-ART group (18 cases) as compared with 7.8 per 100 person-years in the later-ART group (19 cases) (incidence-rate ratio, 0.89; 95% confidence interval [CI], 0.44 to 1.79; P=0.73). However, among patients with CD4+ T-cell counts of less than 50 per cubic millimeter, the incidence rates of AIDS or death were 8.5 and 26.3 cases per 100 person-years, respectively (incidence-rate ratio, 0.32; 95% CI, 0.07 to 1.13; P=0.06). The incidence rates of the immune reconstitution inflammatory syndrome (IRIS) were 20.1 and 7.7 cases per 100 person-years, respectively (incidence-rate ratio, 2.62; 95% CI, 1.48 to 4.82; P<0.001). Adverse events requiring a switching of antiretroviral drugs occurred in 10 patients in the earlier-ART group and 1 patient in the later-ART group (P=0.006).Early initiation of ART in patients with CD4+ T-cell counts of less than 50 per cubic millimeter increased AIDS-free survival. Deferral of the initiation of ART to the first 4 weeks of the continuation phase of tuberculosis therapy in those with higher CD4+ T-cell counts reduced the risks of IRIS and other adverse events related to ART without increasing the risk of AIDS or death. (Funded by the U.S. President's Emergency Plan for AIDS Relief and others; SAPIT ClinicalTrials.gov number, NCT00398996.).

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Timing of Antiretroviral Therapy for HIV-1 Infection and Tuberculosis

2011-10-19

Diane V. Havlir , Michelle A. Kendall , Prudence Ive +7 more

Antiretroviral therapy (ART) is indicated during tuberculosis treatment in patients infected with human immunodeficiency virus type 1 (HIV-1), but the timing for the initiation of ART when tuberculosis is diagnosed … Antiretroviral therapy (ART) is indicated during tuberculosis treatment in patients infected with human immunodeficiency virus type 1 (HIV-1), but the timing for the initiation of ART when tuberculosis is diagnosed in patients with various levels of immune compromise is not known.We conducted an open-label, randomized study comparing earlier ART (within 2 weeks after the initiation of treatment for tuberculosis) with later ART (between 8 and 12 weeks after the initiation of treatment for tuberculosis) in HIV-1 infected patients with CD4+ T-cell counts of less than 250 per cubic millimeter and suspected tuberculosis. The primary end point was the proportion of patients who survived and did not have a new (previously undiagnosed) acquired immunodeficiency syndrome (AIDS)-defining illness at 48 weeks.A total of 809 patients with a median baseline CD4+ T-cell count of 77 per cubic millimeter and an HIV-1 RNA level of 5.43 log(10) copies per milliliter were enrolled. In the earlier-ART group, 12.9% of patients had a new AIDS-defining illness or died by 48 weeks, as compared with 16.1% in the later-ART group (95% confidence interval [CI], -1.8 to 8.1; P=0.45). Among patients with screening CD4+ T-cell counts of less than 50 per cubic millimeter, 15.5% of patients in the earlier-ART group versus 26.6% in the later-ART group had a new AIDS-defining illness or died (95% CI, 1.5 to 20.5; P=0.02). Tuberculosis-associated immune reconstitution inflammatory syndrome was more common with earlier ART than with later ART (11% vs. 5%, P=0.002). The rate of viral suppression at 48 weeks was 74% and did not differ between the groups (P=0.38).Overall, earlier ART did not reduce the rate of new AIDS-defining illness and death, as compared with later ART. In persons with CD4+ T-cell counts of less than 50 per cubic millimeter, earlier ART was associated with a lower rate of new AIDS-defining illnesses and death. (Funded by the National Institutes of Health and others; ACTG A5221 ClinicalTrials.gov number, NCT00108862.).

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Opportunistic Infections in Patients with and Patients without Acquired Immunodeficiency Syndrome

2002-04-15

Kent A. Sepkowitz

In the next decade, longer survival of patients with cancer and more-aggressive therapies applied to common conditions, such as asthma and rheumatoid arthritis, will result in a larger population with … In the next decade, longer survival of patients with cancer and more-aggressive therapies applied to common conditions, such as asthma and rheumatoid arthritis, will result in a larger population with significant immune system defects. Many in this population will be at risk for opportunistic infections, which are familiar to doctors who have treated people infected with human immunodeficiency virus (HIV). However, the epidemiology, presentation, and outcome of these infections in patients with an immune system defect, other than that caused by HIV infection, may be different than those encountered in patients with acquired immunodeficiency syndrome. Reviewed are 4 common opportunistic infections: Pneumocystis carinii pneumonia, cryptococcosis, atypical mycobacterial infection, and cytomegalovirus infection. Emphasized are the important differences among these groups at risk.

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Pneumocystis carinii Pneumonia: A Comparison Between Patients with the Acquired Immunodeficiency Syndrome and Patients with Other Immunodeficiencies

1984-05-01

Joseph A. Kovacs

Clinical features of 49 episodes of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome were compared with those of 39 episodes in patients with other immunosuppressive diseases. At … Clinical features of 49 episodes of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome were compared with those of 39 episodes in patients with other immunosuppressive diseases. At presentation patients with the syndrome were found to have a longer median duration of symptoms (28 days versus 5 days, p = 0.0001), lower mean respiratory rate (23.4 versus 30, p = 0.005), and higher median room air arterial oxygen tension (69 mm Hg versus 52 mm Hg, p = 0.0002). The survival rate from 1979 to 1983 was similar for the two groups (57% and 50% respectively). Patients with the syndrome had a higher incidence of adverse reactions to trimethoprim-sulfamethoxazole (22 of 34 versus 2 of 17, p = 0.0007). Survivors with the syndrome at initial presentation had a significantly lower respiratory rate, and higher room air arterial oxygen tension, lymphocyte count, and serum albumin level compared to nonsurvivors. Pneumocystis carinii pneumonia presents as a more insidious disease process in patients with the syndrome, and drug therapy in these patients is complicated by frequent adverse reactions.

Variations in the Care of HIV-Infected Adults in the United States

1999-06-23

Martin F. Shapiro , Sally C. Morton , Daniel F. McCaffrey +7 more

Studies of selected populations suggest that not all persons infected with human immunodeficiency virus (HIV) receive adequate care. Studies of selected populations suggest that not all persons infected with human immunodeficiency virus (HIV) receive adequate care.

Effect of isoniazid prophylaxis on incidence of active tuberculosis and progression of HIV infection

1993-07-01

Jean W. Pape , SIMONE S. JEAN , John L. Ho +2 more

SummaryTuberculosis occurring with human immunodeficiency virus (HIV) infection is a serious and growing public health problem. We have carried out a randomised clinical trial of a 12-month course of isoniazid … SummaryTuberculosis occurring with human immunodeficiency virus (HIV) infection is a serious and growing public health problem. We have carried out a randomised clinical trial of a 12-month course of isoniazid plus vitamin B6 versus vitamin B6 alone in Port-au-Prince, Haiti, to assess the efficacy of isoniazid in preventing active tuberculosis in symptom-free HIV-infected individuals. The effect of prophylaxis on the development of HIV disease, AIDS, and death was also investigated.118 subjects were assigned treatment with isoniazid plus B6 (n=58) or B6 alone (n=60) between 1986 and 1989. The treatment groups were similar at study entry in demographic, clinical, and immunological characteristics. Interim analysis in 1990 revealed no significant difference in tuberculosis outcome measures. Follow-up was continued until 1992, at which time significant protection by isoniazid against the development of tuberculosis was apparent, both for the whole study population and for subjects positive for purified protein derivative of tuberculin (PPD). The incidence of tuberculosis was lower in isoniazid recipients than in patients who received B6 alone (2·2 vs 7·5 per 100 person-years). The relative risk of tuberculosis was 3·4 (95% CI 1·1-10·6) for B6 alone versus isoniazid plus B6 (p<0·05). Isoniazid also delayed progression to HIV disease and AIDS and death. Thus isoniazid effectively decreases the incidence of tuberculosis and delays the onset of HIV-related disease in symptom-free HIV-seropositive individuals. Isoniazid prophylaxis should be considered for HIV-seropositive, PPD-positive subjects, and may also be appropriate for PPD-negative patients in areas where tuberculosis is highly endemic.

CD4 Counts as Predictors of Opportunistic Pneumonias in Human Immunodeficiency Virus (HIV) Infection

1989-08-01

Henry Masur

Study Objective: To determine if circulating CD4+ lymphocyte counts are predictive of specific infectious or neoplastic processes causing pulmonary dysfunction. Design: Retrospective, consecutive sample study. Setting: Referral-based clinic and wards. … Study Objective: To determine if circulating CD4+ lymphocyte counts are predictive of specific infectious or neoplastic processes causing pulmonary dysfunction. Design: Retrospective, consecutive sample study. Setting: Referral-based clinic and wards. Patients: We studied 100 patients infected with human immunodeficiency virus (HIV) who had had 119 episodes of pulmonary dysfunction within 60 days after CD4 lymphocyte determinations. Measurements and Main Results: Circulating CD4 counts were less than 0.200 X 109 cells/L (200 cells/mm3) before 46 of 49 episodes of Pneumocystis pneumonia, 8 of 8 episodes of cytomegalovirus pneumonia, and 7 of 7 episodes and 19 of 21 episodes of infection with Cryptococcus neoformans and Mycobacterium avium-intracellulare, respectively. In contrast, circulating CD4 counts before episodes of non-specific interstitial pneumonia were quite variable: Of 41 episodes, 11 occurred when CD4 counts were greater than 0.200 X 109 cells/L. The percent of circulating lymphocytes that were CD4+ had a predictive value equal to that of CD4 counts. Serum p24 antigen levels had no predictive value. Conclusions: Pneumocystis pneumonia, cytomegalovirus pneumonia, and pulmonary infection caused by C. neoformans or M. avium-intracellulare are unlikely to occur in HIV-infected patients who have had a CD4 count above 0.200 to 0.250 X 109 cells/L (200 to 250 cells/mm3) or a CD4 percent above 20% to 25% in the 60 days before pulmonary evaluation. Patients infected with HIV who have a CD4 count below 0.200 X 109 cells/L (or less than 20% CD4 cells) are especially likely to benefit from antipneumocystis prophylaxis.

Cryptococcosis in the Acquired Immunodeficiency Syndrome

1985-10-01

Joseph A. Kovacs

The clinical course and response to therapy of 27 patients with cryptococcosis and the acquired immunodeficiency syndrome were reviewed. Cryptococcosis was the initial manifestation of the syndrome in 7 patients, … The clinical course and response to therapy of 27 patients with cryptococcosis and the acquired immunodeficiency syndrome were reviewed. Cryptococcosis was the initial manifestation of the syndrome in 7 patients, and the initial opportunistic infection in an additional 7. Meningitis was the commonest clinical feature (18 patients). Blood cultures and serum cryptococcal antigen were frequently positive. In patients with meningitis, leukocyte count, protein level, and glucose level in cerebrospinal fluid were frequently normal; cerebrospinal fluid India ink test (82%), culture (100%), and cryptococcal antigen (100%) were usually positive. Only 10 of 24 patients had no evidence of clinical activity of cryptococcal infection after completion of therapy; 6 of these 10 had relapses shown by clinical findings or at autopsy. Standard courses of amphotericin B alone or combined with flucytosine were ineffective. Cryptococcosis in patients with the syndrome is a debilitating disease that does not respond to conventional therapy; earlier diagnosis or long-term suppressive therapy may improve the prognosis.

Tuberculosis in Patients with the Acquired Immunodeficiency Syndrome: Clinical Features, Response to Therapy, and Survival

1987-08-01

Richard E. Chaisson , Gisela Schecter , Charles P. Theuer +3 more

Tuberculosis has been reported previously in patients with acquired immunodeficiency syndrome who are at increased risk of prior infection with Mycobacterium tuberculosis. We performed a population-baaed study of AIDS and … Tuberculosis has been reported previously in patients with acquired immunodeficiency syndrome who are at increased risk of prior infection with Mycobacterium tuberculosis. We performed a population-baaed study of AIDS and tuberculosis in San Francisco using the tuberculosis and AIDS Registries of the San Francisco Department of Public Health. Of 287 cases of tuberculosis in non-Asian-born males 15 to 60 yr of age reported from 1981 through 1885, 35 (12%) also had AIDS, including 23 American-born whites. Patients with tuberculosis and AIDS were more likely to be nonwhite and heterosexual intravenous drug users than were AIDS patients without tuberculosis. Fifty-one percent had tuberculosis diagnosed before AIDS, and 37 percent had AIDS diagnosed at least 1 month prior to the diagnosis of tuberculosis. Although the lungs were the most frequent site of tuberculosis in both AIDS and non-AIDS patients, 60% of the AIDS group had at least 1 extrapulmonary site of disease compared to 28% of the non-AIDS group (p < 0.001). Nonsignificant tuberculin skin teats were more common in AIDS patients (14 of 23 patients tested) than in non-AIDS patients (12 of 128 patients tested; p < 0.0001). Cheat radiographs In AIDS patients showed predominantly diffuse or miliary infiltrates (60%), whereas non-AIDS patl.nts had predominantly focal infiltrates and/or cavitation (68%). Response to antituberculosis therapy was favorable in AIDS patients although adverse drug reactions occurred more frequently than in non-AIDS patients (p < 0.02). Overall mortality was high, was almost always caused by AIDS, and did not differ when measured from time of tuberculosis diagnosis or from time of AIDS diagnosis. These data confirm that tuberculosis is an AIDS-related opportunistic infliction characterized by atypical clinical features and poor survival, and that tuberculosis may appear after AIDS is diagnosed in patients with a low likelihood of prior tuberculous infection.

Epidemiology of Human Immunodeficiency Virus–Associated Opportunistic Infections in the United States in the Era of Highly Active Antiretroviral Therapy

2000-04-01

Jonathan E. Kaplan , Debra L. Hanson , Mark S. Dworkin +5 more

The incidence of nearly all AIDS-defining opportunistic infections (OIs) decreased significantly in the United States during 1992-1998; decreases in the most common OIs (Pneumocystis carinii pneumonia ¿PCP, esophageal candidiasis, and … The incidence of nearly all AIDS-defining opportunistic infections (OIs) decreased significantly in the United States during 1992-1998; decreases in the most common OIs (Pneumocystis carinii pneumonia ¿PCP, esophageal candidiasis, and disseminated Mycobacterium avium complex ¿MAC disease) were more pronounced in 1996-1998, during which time highly active antiretroviral therapy (HAART) was introduced into medical care. Those OIs that continue to occur do so at low CD4+ T lymphocyte counts, and persons whose CD4+ counts have increased in response to HAART are at low risk for OIs, a circumstance that suggests a high degree of immune reconstitution associated with HAART. PCP, the most common serious OI, continues to occur primarily in persons not previously receiving medical care. The most profound effect on survival of patients with AIDS is conferred by HAART, but specific OI prevention measures (prophylaxis against PCP and MAC and vaccination against Streptococcus pneumoniae) are associated with a survival benefit, even when they coincide with the administration of HAART. Continued monitoring of incidence trends and detection of new syndromes associated with HAART are important priorities in the HAART era.

ACQUIRED IMMUNODEFICIENCY SYNDROME IN A HETEROSEXUAL POPULATION IN ZAIRE

1984-07-01

Peter Piot , Henri Taelman , Kapita Bila Minlangu +7 more

Trimethoprim and sulfonamide resistance

1995-02-01

Pentti Huovinen , Lars Sundström , Göte Swedberg +1 more

Free access1 February 1995 Share on Trimethoprim and sulfonamide resistanceAuthors: P Huovinen, L Sundström, G Swedberg, O SköldAuthors Info & AffiliationsDOI: https://doi.org/10.1128/AAC.39.2.279 PDF/EPUB Free access1 February 1995 Share on Trimethoprim and sulfonamide resistanceAuthors: P Huovinen, L Sundström, G Swedberg, O SköldAuthors Info & AffiliationsDOI: https://doi.org/10.1128/AAC.39.2.279 PDF/EPUB

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Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans

2006-12-10

Shinobu Saijo , Noriyuki Fujikado , Takahisa Furuta +7 more

Pulmonary Aspergillosis in the Acquired Immunodeficiency Syndrome

1991-03-07

David W. Denning , Stephen Follansbee , Michael J. Scolaro +3 more

Symptomatic pulmonary aspergillosis has rarely been reported in patients with the acquired immunodeficiency syndrome (AIDS). We describe the predisposing factors, the clinical and radiologic features, and the therapeutic outcomes in … Symptomatic pulmonary aspergillosis has rarely been reported in patients with the acquired immunodeficiency syndrome (AIDS). We describe the predisposing factors, the clinical and radiologic features, and the therapeutic outcomes in 13 patients with pulmonary aspergillosis, all of whom had human immunodeficiency virus (HIV) infection and 12 of whom had AIDS.

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A Controlled Trial of Early Adjunctive Treatment with Corticosteroids forPneumocystis cariniiPneumonia in the Acquired Immunodeficiency Syndrome

1990-11-22

Samuel A. Bozzette , Fred R. Sattler , Joseph Chiu +7 more

Pneumocystis carinii pneumonia remains a common cause of serious morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). The extensive lung injury that accompanies pneumocystis-associated respiratory failure and … Pneumocystis carinii pneumonia remains a common cause of serious morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). The extensive lung injury that accompanies pneumocystis-associated respiratory failure and the reports of clinical benefit from the use of adjunctive corticosteroids provided the rationale for this prospective multicenter trial.

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A Prospective Study of the Risk of Tuberculosis among Intravenous Drug Users with Human Immunodeficiency Virus Infection

1989-03-02

Peter A. Selwyn , Diana Hartel , Victor Lewis +5 more

To determine the risk of active tuberculosis associated with human immunodeficiency virus (HIV) infection, we prospectively studied 520 intravenous drug users enrolled in a methadone-maintenance program. Tuberculin skin testing and … To determine the risk of active tuberculosis associated with human immunodeficiency virus (HIV) infection, we prospectively studied 520 intravenous drug users enrolled in a methadone-maintenance program. Tuberculin skin testing and testing for HIV antibody were performed in all subjects. Forty-nine of 217 HIV-seropositive subjects (23 percent) and 62 of 303 HIV-seronegative subjects (20 percent) had a positive response to skin testing with purified protein derivative (PPD) tuberculin before entry into the study. The rates of conversion from a negative to a positive PPD test were similar for seropositive subjects (15 of 131; 11 percent) and seronegative subjects (26 of 202; 13 percent) who were retested during the follow-up period (mean, 22 months). Active tuberculosis developed in eight of the HIV-seropositive subjects (4 percent) and none of the seronegative subjects during the study period (P<0.002). Seven of the eight cases of tuberculosis occurred in HIV-seropositive subjects with a prior positive PPD test (7.9 cases per 100 person-years, as compared with 0.3 case per 100 person-years among seropositive subjects without a prior positive PPD test; rate ratio, 24.0; P<0.0001). We conclude that, although the prevalence and incidence of tuberculous infection were similar for both HIV-seropositive and HIV-seronegative intravenous drug users, the risk of active tuberculosis was elevated only for seropositive subjects. These data also suggest that in HIV-infected persons tuberculosis most often results from the reactivation of latent tuberculous infection; our results lend support to recommendations for the aggressive use of chemoprophylaxis against tuberculosis in patients with HIV infection and a positive PPD test. (N Engl J Med 1989; 320:545–50.)

Successful Chemoprophylaxis forPneumocystis cariniiPneumonitis

1977-12-29

Walter T. Hughes , Shirley Kuhn , Subhash Chaudhary +5 more

In a randomized, double-blind, placebo-controlled study to evaluate the efficacy of trimethoprim–sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia, we studied 160 patients with cancer who were at high risk … In a randomized, double-blind, placebo-controlled study to evaluate the efficacy of trimethoprim–sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia, we studied 160 patients with cancer who were at high risk for this pneumonia over a two-year period. Seventeen of the 80 patients receiving a placebo acquired P. carinii pneumonitis, whereas none of the 80 given 150 mg of trimethoprim and 750 mg of sulfamethoxazole per square meter per day had the infection (P<0.01). Bacterial sepsis, pneumonia other than that caused by P. carinii, acute otitis media, upper-respiratory-tract infections, sinusitis and cellulitis occurred less frequently in recipients of the drug than in the placebo group (P<0.01 in each case). Oral candidiasis was the only adverse effect encountered from trimethoprim–sulfamethoxazole administration. The study shows the combination to be highly effective in the prevention of P. carinii pneumonitis. (N Engl J Med 297:1419–1426, 1977)

The Risk ofPneumocystis cariniiPneumonia among Men Infected with Human Immunodeficiency Virus Type 1

1990-01-18

John Phair , Álvaro Muñoz , Roger Detels +3 more

We assessed the risk of pneumonia due to Pneumocystis carinii in 1665 participants in the Multicenter AIDS Cohort Study who were seropositive for human immunodeficiency virus type 1 (HIV-1) but … We assessed the risk of pneumonia due to Pneumocystis carinii in 1665 participants in the Multicenter AIDS Cohort Study who were seropositive for human immunodeficiency virus type 1 (HIV-1) but did not have the acquired immunodeficiency syndrome (AIDS) and were not receiving prophylaxis against P. carinii. During 48 months of follow-up, 168 participants (10.1 percent) had a first episode of P. carinii pneumonia.

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Bacterial Pneumonia in Persons Infected with the Human Immunodeficiency Virus

1995-09-28

Robert E. Hirschtick , Jeffrey Glassroth , Matthew Carey Jordan +7 more

Patients with human immunodeficiency virus (HIV) infection are at increased risk for bacterial pneumonia in addition to opportunistic infection. However, the risk factors for bacterial pneumonia and its incidence in … Patients with human immunodeficiency virus (HIV) infection are at increased risk for bacterial pneumonia in addition to opportunistic infection. However, the risk factors for bacterial pneumonia and its incidence in this population are not well defined.

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Pneumocystis cariniiPneumonia and Mucosal Candidiasis in Previously Healthy Homosexual Men

1981-12-10

Michael S. Gottlieb , Robert W. Schroff , H SCHANKER +4 more

Four previously healthy homosexual men contracted Pneumocystis carinii pneumonia, extensive mucosal candidiasis, and multiple viral infections. In three of the patients these infections followed prolonged fevers of unknown origin. In … Four previously healthy homosexual men contracted Pneumocystis carinii pneumonia, extensive mucosal candidiasis, and multiple viral infections. In three of the patients these infections followed prolonged fevers of unknown origin. In all four cytomegalovirus was recovered from secretions. Kaposi's sarcoma developed in one patient eight months after he presented with esophageal candidiasis. All patients were anergic and lymphopenic; they had no lymphocyte proliferative responses to soluble antigens, and their responses to phytohemagglutinin were markedly reduced. Monoclonal-antibody analysis of peripheral-blood T-cell subpopulations revealed virtual elimination of the Leu-3+ helper/inducer subset, an increased percentage of the Leu-2+ suppressor/cytotoxic subset, and an increased percentage of cells bearing the thymocyte-associated antigen T10. The inversion of the T helper to suppressor/cytotoxic ratio suggested that cytomegalovirus infection was an important factor in the pathogenesis of the immunodeficient state. A high level of exposure of male homosexuals to cytomegalovirus-infected secretions may account for the occurrence of this immune deficiency. (N Engl J Med. 1981; 305:1425–31.)

An Outbreak of Community-AcquiredPneumocystis cariniiPneumonia

1981-12-10

Henry Masur , Michael F. Michelis , Jeffrey B. Greene +7 more

Eleven cases of community-acquired Pneumocystis carinii pneumonia occurred between 1979 and 1981 and prompted clinical and immunologic evaluation of the patients. Young men who were drug abusers (seven patients), homosexuals … Eleven cases of community-acquired Pneumocystis carinii pneumonia occurred between 1979 and 1981 and prompted clinical and immunologic evaluation of the patients. Young men who were drug abusers (seven patients), homosexuals (six), or both (two) presented with pneumonia. Immunologic testing revealed that absolute lymphocyte counts, T-cell counts, and lymphocyte proliferation were depressed, and that humoral immunity was intact. Of the 11 patients, one was found to have Kaposi's sarcoma, and another had angioimmunoblastic lymphadenopathy. Eight patients died. In the remaining three, no diagnosis of an immunosuppressive disease was established, despite persistence of immune defects. These cases of pneumocystosis suggest the importance of cell-mediated immune function in the defense against P. carinii. The occurrence of this infection among drug abusers and homosexuals indicates that these groups may be at high risk for this infection. (N Engl J Med. 1981; 305:1431–8.)

Treatment of Tuberculosis in Patients with Advanced Human Immunodeficiency Virus Infection

1991-01-31

Peter M. Small , Gisela Schecter , Philip C. Goodman +3 more

Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, … Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988.

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Survival with the Acquired Immunodeficiency Syndrome

1987-11-19

Richard Rothenberg , Mary Lou Woelfel , Rand Stoneburner +3 more

In a cohort of 5833 subjects in whom the acquired immunodeficiency syndrome (AIDS) was diagnosed in New York City before 1986, the cumulative probability of survival (mean +/- SE) was … In a cohort of 5833 subjects in whom the acquired immunodeficiency syndrome (AIDS) was diagnosed in New York City before 1986, the cumulative probability of survival (mean +/- SE) was 48.8 +/- 0.7 percent at one year and 15.2 +/- 1.8 percent at five years. The group with the most favorable survival rate--white homosexual men 30 to 34 years old who presented with Kaposi's sarcoma only--had a one-year cumulative probability of survival of 80.5 percent; that group was used as the reference group in assessing the effect of five variables: sex, race or ethnic background, age, probable route of acquiring AIDS (risk group), and manifestations of AIDS at diagnosis. The range in the mortality rate was greater than threefold, depending on these variables. Black women who acquired the disease through intravenous drug abuse, for example, had a particularly poor prognosis. The manifestations of disease at diagnosis had the most influence on survival, accounting on average for 56.3 percent of the excess risk. This variable was followed in importance by age (12.2 percent), race or ethnicity (10.6 percent), risk group (8.4 percent), and sex (8.0 percent), with 4.5 percent of the risk attributable to interactions between variables. When we compared subcohorts based on the year of diagnosis (1981 through 1985), we found a significant improvement in the one-year cumulative probability of survival among subjects with Pneumocystis carinii pneumonia, but not among subjects without P. carinii pneumonia.

American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America

2003-02-14

Henry M. Blumberg , William J. Burman , Richard E. Chaisson +7 more

Pneumocystis Pneumonia

2004-06-09

Charles F. Thomas , Andrew H. Limper

Pneumocystis pneumonia remains the most prevalent opportunistic infection in patients infected with the human immunodeficiency virus. Molecular techniques have provided new insights into the complex cell biology of this fungus. … Pneumocystis pneumonia remains the most prevalent opportunistic infection in patients infected with the human immunodeficiency virus. Molecular techniques have provided new insights into the complex cell biology of this fungus. The authors summarize advances that have resulted from studies of the cell biology, biochemistry, and genetics of pneumocystis in the past several years and provide recommendations for the diagnosis of pneumocystis pneumonia and for prophylaxis and treatment.

Pulmonary Alveolar Proteinosis

1958-06-05

Samuel H. Rosen , Benjamin Castleman , Averill A. Liebow +2 more

WITHIN the past five years, and at an increasing rate within recent months, we have encountered 27 cases of a remarkable disease of the lung that consists of the filling … WITHIN the past five years, and at an increasing rate within recent months, we have encountered 27 cases of a remarkable disease of the lung that consists of the filling of the alveoli by a PAS-positive proteinaceous material, rich in lipid. This material appears to be produced by the lining cells, which slough into the lumen, ultimately becoming necrotic and yielding granules and variable laminated bodies to the alveolar content. The condition bears certain resemblances to pneumocystis infection of the lung,1 2 3 4 5 6 7 8 9 and, indeed, the possibility was considered that it represented a "burnt-out" phase of this disease. Several cases that we . . .

MPAM (Mycoplasma PneumoniaeAssociated Mucositis): chi è costei?

2025-06-24

Sara Zannoni , Alessandra Iacono , C Radice +2 more | Medico e Bambino

The paper reports the case of an 11-year-old boy with aphthous lesions in the oral cavity caused by a Mycoplasma pneumoniae infection, which may present with severe mucositis, mimicking more … The paper reports the case of an 11-year-old boy with aphthous lesions in the oral cavity caused by a Mycoplasma pneumoniae infection, which may present with severe mucositis, mimicking more serious conditions such as Stevens-Johnson syndrome.

The Maximum-Tolerated Dose and Pharmacokinetics of ISFP10 a Novel Inhibitor of Fungal Phosphoglucomutase (PGM)

2025-06-22

Theodore J. Kottom , Andrew H. Limper | bioRxiv (Cold Spring Harbor Laboratory)

ABSTRACT Background The newly identified small molecule ISFP10 has demonstrated the ability to inhibit fungal phosphoglucomutases (PGM), leading to decreased fungal growth and survival. Exhibiting 50 times greater selectivity for … ABSTRACT Background The newly identified small molecule ISFP10 has demonstrated the ability to inhibit fungal phosphoglucomutases (PGM), leading to decreased fungal growth and survival. Exhibiting 50 times greater selectivity for fungal PGM compared to the human homolog, ISFP10 shows promise as a broad-spectrum antifungal and a candidate for preliminary testing in rodent models of fungal infections, including Pneumocystis pneumonia (PCP). In preparation for targeted and relevant administration of the drug in fungal mouse models of infection, the current study describes the maximum-tolerated-dose (MTD) and pharmacokinetics (PK) of ISFP10 in mice. Methods For the MTD study, 24 C57BL/6 mice were randomly distributed into 6 groups (2M/2F per group): Placebo (vehicle; 10% DMSO with 90% of 0.5% methylcellulose in 0.9% NaCl) at various doses (12.5, 25, 50, 100, 200 mg/kg), were administered twice daily by intraperitoneally (IP) for 7 consecutive days. For the PK study, 108 mice were administered either vehicle or ISFP10 in single-dose intraperitoneal (IP) injections twice daily for 7 consecutive days at concentrations of 0, 12.5, 25, 50, and 100 mg/kg. Pharmacokinetics were assessed in plasma, and epithelial lining fluid (ELF). Analysis of this test compound was performed using LC-MS/MS for PK evaluation on blood samples drawn from mice at multiple time points. Results IP administered, ISFP10 did not produce significant changes in body weight, food consumption or adverse events in the MTD up to 100 mg/kg dosing. The plasma PK study demonstrated T max values ranging from 2 to 8 h. Non-compartmental analysis (NCA) yielded elimination half-life values, t 1/2 , of 4.39 and 5.31 h for the 12.5 and 50 mg/kg dose groups. Concentration dependent peak-blood concentration (C max ) at the dosing and length tested ranged from 3.450-5.140 ug/ml. Conclusions In conclusion, ISFP10, administered intraperitoneally to mice twice daily at doses up to 100 mg/kg, exhibited no inherent safety concerns based on the analyzed parameters. Pharmacokinetic analysis revealed slow absorption and distribution kinetics, with plasma T max values ranging from 2 to 8 hours and elimination half-lives of approximately 4–5 hours at lower doses. These data support broader in vivo testing of the inhibitor as potential novel antifungal in fungal diseases including PCP.

Pneumocystis Pneumonia in a Non-HIV Patient With Advanced Liver Cirrhosis and No History of Immunosuppression: A Case Report

2025-06-22

Yuta Isomura , Yuichiro Ogura , Hiroyuki Tamiya | Cureus

Basiliximab/Cotrimoxazole/Mycophenolate-mofetil

2025-06-21

| Reactions Weekly

Cotrimoxazole

2025-06-21

| Reactions Weekly

Cefiderocol/Daptomycin

2025-06-21

| Reactions Weekly

Inhalable Artificial Polymeric Nucleases Degrading Neutrophil Extracellular Trap‐DNAs and Alleviating Pulmonary Fibrosis

2025-06-20

Yibo Du , Chenxu Zhu , Ruifeng Wang +5 more | Advanced Science

Abstract Pulmonary fibrosis resulting from recurrent lung inflammation due to pathogen infection may lead to serious problems and death. Neutrophil extracellular traps (NETs), consisting of DNAs and proteins released by … Abstract Pulmonary fibrosis resulting from recurrent lung inflammation due to pathogen infection may lead to serious problems and death. Neutrophil extracellular traps (NETs), consisting of DNAs and proteins released by neutrophils in response to infection, are major pathogenesis factors for pathogen‐associated pulmonary fibrosis. By mimicking nucleic acid hydrolase, polymeric artificial DNases bearing imidazole units (PEG‐PIm) are developed to degrade the DNAs and thus deconstruct NETs, inhibiting pulmonary fibrosis. By tailoring the PIm segments with varied imidazole units, the polymer hydrolase with a defined number of imidazole units outperforms other samples in the cleavage of DNAs and inhibits the transition of pulmonary fibroblasts to myofibroblasts. This polymer digests the DNAs complexed with cationic peptides, unlike natural DNase I. By aerosol inhalation, it reduces NET infiltration in lungs and significantly alleviates inflammatory cytokines and fibrosis. Molecular dynamics simulations indicate that the optimized polymer may expose more effective imidazole units to the DNA backbones and thus enhance the affinity and hydrolysis of phosphodiester linkages. The function is also confirmed by systematic administration of PEG‐PIm to rheumatoid arthritis. Thus, a strategy is provided for treating pulmonary fibrosis that can be applied in a pandemic to reduce high mortality because of pathogen infection.

Outcomes and risk factors in HIV-positive patients with sepsis: a retrospective study

2025-06-19

Qiang Gao , Tingting Wang , Shun Tan +2 more | European journal of medical research

The aim of this study was to assess the outcomes and risk factors for in-hospital mortality and further explore a predictive model for forecasting in-hospital mortality in HIV-positive patients with … The aim of this study was to assess the outcomes and risk factors for in-hospital mortality and further explore a predictive model for forecasting in-hospital mortality in HIV-positive patients with sepsis. A retrospective cohort study of 203 hospitalized HIV-positive patients with sepsis was conducted at Chongqing Public Health Medical Center, a tertiary-level infectious disease hospital, from January 2021 to December 2023. Patients were divided into two groups according to survival status (survival and death). The patients' baseline characteristics, laboratory findings and outcomes were collected for comprehensive analysis. The in-hospital mortality rate was 18.7%. Independent risk factors for in-hospital mortality in HIV-positive patients with sepsis were acute respiratory failure (OR 3.654, 95% CI 1.303-10.248, p = 0.014), septic shock (OR 9.542, 95% CI 3.614-25.197, p < 0.001), chronic liver disease (OR 4.330, 95% CI 1.348-13.910, p = 0.014) and lactate (OR 1.570, 95% CI 1.195-2.062, p = 0.001). The AUC for the RF model to predict in-hospital death was 0.853, and the threshold was -1.553 with a sensitivity of 73.7% and a specificity of 84.8%. Acute respiratory failure, septic shock, chronic liver disease and lactate were independent risk factors for in-hospital mortality in HIV-positive patients with sepsis. The prediction model based on these four risk factors demonstrated good effectiveness in predicting in-hospital mortality among HIV-positive patients with sepsis.

Design and Synthesis of Bimetallic Cu(II) Compounds as Potent Antibacterial and Antibiofilm Agents with Metallo‐ β ‐Lactamase Inhibitory Activityagainst Multidrug Resistant Pseudomonas aeruginosa

2025-06-19

Samik Biswas , Sujan Sk , Sangita Das +6 more | Chemistry - A European Journal

In this research, a novel class of biologically active bimetallic Cu(II) compounds have been discovered as cutting‐edge antibiofilm agents with metallo‐β‐lactamase (MBL) inhibitory activity against the clinically isolated multidrug resistant … In this research, a novel class of biologically active bimetallic Cu(II) compounds have been discovered as cutting‐edge antibiofilm agents with metallo‐β‐lactamase (MBL) inhibitory activity against the clinically isolated multidrug resistant (MDR) gram‐negative bacterium, Pseudomonas aeruginosa (Pa‐CI‐1). Thus, the 2,6‐bis[N‐{N‐(carboxymethyl)‐N‐(pyridylmethyl)amine}methyl]‐4‐methylphenol (H3L)‐incorporated three bimetallic Cu(II) compounds, [Cu2L(H2O)(Cl)]∙H2O (1), [Cu2L(H2O)(NO3)]∙H2O (2) and [Cu2L(H2O)(CH3CO2)]∙H2O (3) have been strategically designed and synthesized with unsymmetrical coordination arrangement that synergistically modifies the electronic environment of Cu centres for the enhancement of antibacterial and antibiofilm activity. The standard nitrocefin assay disclosed that 1‐3 significantly inhibited the activity of MBLs produced by Pa‐CI‐1 at their 1/2 MIC doses. Molecular docking study revealed an excellent propensity of these Cu compounds for binding with different MBL‐producing proteins. All three Cu(II) compounds displayed significantly high antibacterial and antibiofilm activity as established by multiple bioassays, including ex‐vivo applicability studies. They showed an exceptional combinatorial activity when examined with commercially accessible five different β‐lactam‐based antibiotics such as amoxicillin (AMX), chloramphenicol (CHL), cefotaxime (CTX), ceftriaxone (CTR) and Cefoxitin (CX) against Pa‐CI‐1. Our study disclosed that 1‐3 could be the emergent drug leads and attract great attention to the inorganic, material and biological chemists, combating antimicrobial resistance.

Pneumocystis jirovecii pneumonia in AIDS patient with atypical lung ct images：a case report

2025-06-17

G. Wan , Yujiao Duan | Research Square (Research Square)

<title>Abstract</title> We report a case of AIDS complicated with cytomegalovirus retinitis whose lung CT screening revealed multiple small nodules and patchy shadow lesions mainly in the peripheral of both lungs. … <title>Abstract</title> We report a case of AIDS complicated with cytomegalovirus retinitis whose lung CT screening revealed multiple small nodules and patchy shadow lesions mainly in the peripheral of both lungs. The treatment against bacteria and aspergillus was ineffective. Finally, we performed a lung biopsy on the patient and both the pathology and NGS confirmed it as Pneumocystis jirovecii pneumonia. This case reminds clinicians to pay attention to the atypical manifestations of common diseases to avoid misdiagnosis and missed diagnoses.

Relationship between clinical, laboratory, and radiological parameters with polymerase chain reaction positivity sputum in adult HIV patients with suspicion of pneumocystis jirovecii pneumonia

2025-06-17

Kadek Surya Atmaja , I Ketut Agus Somia , I Desak Putu Agung Krisdanti +3 more | Edelweiss Applied Science and Technology

Pneumocystis jirovecii pneumonia (PCP) is a fungal infection of the lungs caused by P. jirovecii, usually affecting patients with Human Immunodeficiency Virus (HIV). The polymerase chain reaction (PCR) test is … Pneumocystis jirovecii pneumonia (PCP) is a fungal infection of the lungs caused by P. jirovecii, usually affecting patients with Human Immunodeficiency Virus (HIV). The polymerase chain reaction (PCR) test is used in the diagnosis of PCP and has good sensitivity, but it is not available in all healthcare facilities. Clinical, laboratory, and radiological parameters can serve as alternatives to support the diagnosis of PCP in HIV patients. This study is an analytical observational study with a cross-sectional design. The assessment of clinical, laboratory, and radiological parameters of PCP patients was conducted from June to December 2024. Variables were compared using the Independent T-test if normally distributed or the Mann-Whitney test if not normally distributed. Nominal variables were compared using the Chi-square test. Multivariate analysis employed logistic regression analysis. A total of 80 patients participated in the study. From the multivariate analysis, clinical parameters such as low-grade fever (PR 23.9; 95% CI 4.086–141.01; p < 0.001), non-productive cough (PR 7.108; 95% CI 1.25–40.1; p = 0.027), and oral candidiasis (PR 8.81; 95% CI 1.62–47.8; p = 0.012) were significant. Laboratory parameters such as lymphocyte count ≤1.2×10³/µL (PR 19.4; 95% CI 2.5–149.3; p = 0.004), albumin ≤ 3.1 g/dL (PR 5.59; 95% CI 1.062–29.4; p = 0.042), and CD4 count ≤ 200 cells/µL (PR 14.3; 95% CI 2.06–99.69; p = 0.007) were also significant. Typical radiological parameters (PR 20.6; 95% CI 2.9–144.2; p = 0.02) and atypical radiological parameters (PR 5.43; 95% CI 1.47–20.05; p = 0.02) showed a significant relationship with sputum PCR positivity for PCP in HIV patients. Low-grade fever, non-productive cough, oral candidiasis, lymphocyte count ≤1.2×10³/µL, albumin ≤ 3.1 g/dL, CD4 count ≤ 200 cells/µL, and typical and atypical chest X-ray images are associated with sputum PCR positivity in HIV patients suspected of having PCP.

Extracellular Vesicle-Mediated Delivery of Genetic Material for Transformation and CRISPR/Cas9-based Gene Editing inPneumocystis murina

2025-06-17

Steven G. Sayson , Alan Ashbaugh , L. I. de Bauer +1 more | bioRxiv (Cold Spring Harbor Laboratory)

ABSTRACT Pneumocystis species are obligate fungal pathogens that cause severe pneumonia, particularly in immunocompromised individuals. The absence of robust genetic manipulation tools has impeded our mechanistic understanding of Pneumocystis biology … ABSTRACT Pneumocystis species are obligate fungal pathogens that cause severe pneumonia, particularly in immunocompromised individuals. The absence of robust genetic manipulation tools has impeded our mechanistic understanding of Pneumocystis biology and the development of novel therapeutic strategies. Herein, we describe a novel method for the stable transformation and CRISPR/Cas9-mediated genetic editing of Pneumocystis murina utilizing extracellular vesicles (EVs) as a delivery vehicle. Building upon our prior investigations demonstrating EV-mediated delivery of exogenous material to Pneumocystis , we engineered mouse lung EVs to deliver plasmid DNA encoding reporter genes and CRISPR/Cas9 components. Our initial findings demonstrated successful in vitro transformation and subsequent expression of mNeonGreen and Dhps ARS in P. murina organisms. Subsequently, we established stable in vivo expression of mNeonGreen in mice infected with transformed P. murina for a duration of up to 5 weeks. Furthermore, we designed and validated a CRISPR/Cas9 system targeting the P. murina Dhps gene, confirming its in vitro cleavage efficiency. Ultimately, we achieved successful in vivo CRISPR/Cas9-mediated homologous recombination, precisely introducing a Dhps ARS mutation into the P. murina genome, which was confirmed by Sanger sequencing across all tested animals. Here, we establish a foundational methodology for genetic manipulation in Pneumocystis , thereby opening avenues for functional genomics, drug target validation, and the generation of genetically modified strains for advanced research and potential therapeutic applications. IMPORTANCE Pneumocystis species are obligate fungal pathogens and major causes of pneumonia in immunocompromised individuals. However, their strict dependence on the mammalian lung environment has precluded the development of genetic manipulation systems, limiting our ability to interrogate gene function, study antifungal resistance mechanisms, or validate therapeutic targets. Here, we report the first successful approach for stable transformation and CRISPR/Cas9-based genome editing of Pneumocystis murina , achieved through in vivo delivery of engineered extracellular vesicles (EVs) containing plasmid DNA and encoding CRISPR/Cas9 components. We demonstrate sustained transgene expression and precise modification of the dhps locus via homology-directed repair. This modular, scalable platform overcomes a long-standing barrier in the field and establishes a foundation for functional genomics in Pneumocystis and other obligate, host-adapted microbes.

Unanticipated Global Emergence of Multiple Pneumocystis jirovecii Mutants Selected by Mycophenolic Acid Driving Increasing Outbreaks in Solid Organ Transplant Recipients

2025-06-17

Liang Ma , Ming Hao , Weizhong Chang +7 more | medRxiv (Cold Spring Harbor Laboratory)

Background: Classified by the WHO as one of the 19 most dangerous fungal pathogens, Pneumocystis jirovecii has been associated with increasing outbreaks of Pneumocystis pneumonia (PCP) among solid organ transplant … Background: Classified by the WHO as one of the 19 most dangerous fungal pathogens, Pneumocystis jirovecii has been associated with increasing outbreaks of Pneumocystis pneumonia (PCP) among solid organ transplant (SOT) recipients worldwide. Mycophenolic acid (MPA), an inosine monophosphate dehydrogenase (IMPDH) inhibitor commonly used as an immunosuppressant to prevent organ rejection, is a risk factor for PCP. However, MPA also displays antifungal activity, potentially protecting against PCP, despite not being used to treat it. Therefore the underlying factors driving these outbreaks remain undefined. Methods: In this international multicenter retrospective observational study, P. jirovecii samples were collected from 96 SOT patients (including 94 from nine separate outbreaks and 84 on MPA therapy) and 67 non-transplant controls (none on MPA), between 1986 and 2020 across six countries in Europe, North America and Asia. All samples underwent extensive targeted sequencing of the P. jirovecii inosine monophosphate dehydrogenase (impdh) gene and multiple genetic markers, with selected samples further analyzed for complete mitogenome and restriction fragment length polymorphisms. Computational modeling was employed to predict the effects of IMPDH mutations on protein structure and MPA binding. Results: Six impdh mutations (including one previously reported) were identified, with frequencies of 4-21% each in SOT patients and 0-1% in controls. These mutations were strongly associated with prior MPA exposure and showed marked geographic segregation and temporal shifts. Four mutations were each linked to multiple distinct genotype profiles, representing separate P. jirovecii strains. Structure modeling predicted that these four mutations reduced protein stability and binding affinity to MPA. Conclusions: This study suggests that the widespread use of MPA in SOT recipients has unexpectedly driven the emergence of multiple impdh mutations in P. jirovecii, each presumably arising independently in multiple strains worldwide. These mutations likely confer drug resistance and provide a selective survival advantage to P. jirovecii in SOT recipients exposed to MPA, thereby facilitating transmission and outbreaks. These findings have significant implications for the prevention and clinical management of PCP in SOT recipients, highlighting a rare example of how antimicrobial resistance can emerge through unexpected pathways, transcending conventional antimicrobial use and emphasizing the need for increased vigilance and strategic adaptation in clinical practice.

An AIDS Patient With Pneumocystis jiroveci Pneumonia

2025-06-17

Nicholas R Munoz , Armin Hojjat , A. Adial | Cureus

An Update on the Clinical Management of HIV and Tuberculosis Co-Infection in Pregnancy: TB Preventative Therapy, Long-Acting ARVs, and Bedaquiline-Based Regimens

2025-06-16

Tim Crocker-Buqué , Michael A Moso , Justin T. Denholm +1 more | Current HIV/AIDS Reports

Mortality of Pneumocystis jirovecii pneumonia in intensive care units: a post-hoc analysis of an international multicenter study by ESGCIP and EFISG

2025-06-14

Daniele Roberto Giacobbe , Silvia Dettori , Vincenzo Di Pilato +7 more | Annals of Medicine

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening disease. In the intensive care unit (ICU), PJP is most frequently observed among patients with several conditions not related to the human immunodeficiency … Pneumocystis jirovecii pneumonia (PJP) is a life-threatening disease. In the intensive care unit (ICU), PJP is most frequently observed among patients with several conditions not related to the human immunodeficiency virus (HIV) infection. The primary objective of the present post-hoc analysis of a multicenter, multinational, retrospective study was to assess factors impacting prognosis in ICU patients with PJP through univariable and multivariable analyses. A total of 107 patients were included; 28 had proven PJP (26.2%), and 79 had presumptive PJP (73.8%). The overall 30-day mortality was 52.7% (95% confidence interval [CI] 42.1-62.2). In the multivariable analysis, metastatic solid tumor (hazard ratio [HR] 3.49; 95% CI 1.71-7.13, p < 0.001) and chronic liver disease (HR 2.44; 95% CI 1.03-5.80, p = 0.044) showed an independent association with 30-day mortality. The direction of effect remained consistent when center was added to the multivariable model as random effect. PJP mortality remains high in ICU patients. Conditions other than HIV infection are emerging not only as non-classical risk factors for PJP development, but also as important mortality predictors. A better understanding of the reasons underlying this evolving landscape could be crucial to improve PJP management and survival.

Antenatal screening for TB disease: a systematic review and meta-analysis

2025-06-13

A.J. Morton , Niamh Meagher , Gerry Tonkin‐Hill +3 more | Deleted Journal

<sec><title>OBJECTIVES</title>TB disease during pregnancy is associated with poor maternal and neonatal outcomes, and is a leading non-obstetric cause of maternal death. However, optimal detection strategies remain uncertain. We aimed to … <sec><title>OBJECTIVES</title>TB disease during pregnancy is associated with poor maternal and neonatal outcomes, and is a leading non-obstetric cause of maternal death. However, optimal detection strategies remain uncertain. We aimed to identify the optimal screening approach for TB disease in pregnant women.</sec><sec><title>METHODS</title>We searched Ovid MEDLINE, Embase + Embase Classic, Web of Science, and CENTRAL to identify antenatal screening studies for TB disease. The yield, number needed to screen (NNS), and positive predictive value (PPV) were calculated for each method. Pooled estimates were generated using random-effects meta-analyses. Narrative synthesis was conducted to summarise secondary outcomes.</sec><sec><title>RESULTS</title>We included 33 studies. Pooled yield for symptom screening (SS) was 7.26 [95% CI: 0.70, 19.25] cases per 1,000 versus 5.12 [95% CI: 0.79, 12.39] for TST/IGRA. NNS was 138 [95% CI: 51.95, 1,428.57] for SS versus 1,667 [95% CI: 537.63, 1,000,000] for TST/IGRA. SS pooled PPV was 3.85% [95% CI: 1.23–7.57%], and <0.01% [95% CI: <0.01–0.05%] for TST/IGRA. Narrative synthesis indicated antenatal SS is low-cost, feasible, and acceptable but poorly implemented.</sec><sec><title>CONCLUSION</title>In pregnancy, symptom screening demonstrates highest yield and lowest NNS, is low-cost, feasible and acceptable. While currently optimal, the low PPV underscores the need for TB screening tools tailored to pregnant populations.</sec>

Immunopathogenesis of Pneumocystis Pneumonia (PCP) and Its Clinical Implications

2025-06-13

A Malik , Heidy Agustin , Fariz Nurwidya +1 more | Respiratory Science

Pneumocystis pneumonia (PCP) is a serious lung infection caused by Pneumocystis jirovecii, primarily affecting immunocompromised individuals. It remains a major health concern, especially in HIV/AIDS patients and those undergoing immunosuppressive … Pneumocystis pneumonia (PCP) is a serious lung infection caused by Pneumocystis jirovecii, primarily affecting immunocompromised individuals. It remains a major health concern, especially in HIV/AIDS patients and those undergoing immunosuppressive therapy. This review discusses how the immune system responds to P. jirovecii and why immunocompromised individuals are more vulnerable. In healthy individuals, CD4+ T cells, B cells, and macrophages help control the infection. However, in immunocompromised individuals, a weakened immune response allows fungal overgrowth, leading to severe lung damage. The review also covers symptoms, diagnosis, and treatment options. TMP-SMX is the preferred treatment, while alternative drugs are available for those who cannot tolerate it. Understanding the immune response to PCP can help improve treatment and patient care.

Pharmacokinetics of Isavuconazole During Extracorporeal Membrane Oxygenation Support in Critically Ill Patients: A Case Series

2025-06-12

Laura Doménech Moral , Sonia García-García , Alba Pau‐Parra +7 more | Antibiotics

Background/Objectives: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO … Background/Objectives: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO patients are limited. Our objective is to evaluate Isavuconazole exposure and variability in critically ill COVID-19 patients receiving ECMO. Methods: We conducted a pharmacokinetic analysis of Isavuconazole in critically ill patients receiving Veno-Venous ECMO for respiratory support. Plasma concentrations were measured using therapeutic drug monitoring (TDM) at multiple time points, including sampling before and after the membrane oxygenator. PK parameters—Area Under Curve (AUC0–24), Minimum Plasma Concentration (Cmin), Elimination Half-Life (T1/2), volume of distribution (Vd), and clearance (CL)—were estimated and compared with published data in non-ECMO populations. Results: Five patients were included. The median AUC0–24 was 227.3 µg·h/mL (IQR 182.4–311.35), higher than reported in non-ECMO patients. The median Vd was 761 L (727–832), suggesting extensive peripheral distribution and potential drug sequestration in the ECMO circuit. CL was increased (1.6 L/h, IQR 1.5–3.4). Two patients with recently replaced ECMO circuits exhibited significant drug loss across the membrane. Obesity and hypoalbuminemia were identified as factors associated with altered drug exposure. Conclusions: Isavuconazole pharmacokinetics show marked variability in critically ill ECMO patients. Increased AUC and Vd, along with reduced clearance, highlight the need for individualized dosing.

The Lung

2025-06-05

Bruce Kirenga , Jamie Rylance | Cambridge University Press eBooks

Refining scores for non-invasive diagnosis of PCP

2025-06-01

Rajeev Soman , Tanu Singhal , Camilla Rodrigues +1 more | CMI Communications

ABS0296 ARTHRITIS FOLLOWING BCG INSTILLATION IN BLADDER CANCER: STILL REACTIVE OR AN IMMUNE-RELATED ADVERSE EFFECT A NATIONAL STUDY BASED ON THE FRENCH PHARMACOVIGILANCE DATABASE

2025-06-01

Simon Cadiou , François Robin , A. Faÿsse +7 more | Annals of the Rheumatic Diseases

Sulfasalazine as a Prophylactic for Pneumocystis Pneumonia in Patients With Rheumatoid Arthritis: A Cohort Study

2025-06-01

Masaru Yoshimura , Nobuya Abe , Michihito Kono +5 more | International Journal of Rheumatic Diseases

ABSTRACT Aim We investigated the potential of sulfasalazine (SSZ), one of the conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs), as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis … ABSTRACT Aim We investigated the potential of sulfasalazine (SSZ), one of the conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs), as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA). Methods In this longitudinal cohort study, we enrolled patients with RA who started receiving new RA treatment. A treatment episode was defined as a period of 1 year from the start or increase of DMARDs dose, or starting prednisolone > 10 mg/day, and the incidence of PCP in this period was assessed. All treatment episodes were classified into two groups based on the presence of SSZ at baseline. The PCP incidence rate in the two groups was evaluated using a negative binomial regression model. Results A total of 848 treatment episodes were recorded in 594 RA patients: 181 and 667 in the SSZ and control groups, respectively. During the 850.6 person‐years of observation, 21 patients developed PCP, and three died of PCP. Multivariable adjusted analysis using Firth's method showed that the 1‐year incidence of PCP was significantly reduced with SSZ treatment ( p = 0.003, rate ratio = 0.05; 95% CI 0.00–0.34). Furthermore, the log‐rank test in the propensity score‐matched population confirmed this result. Regarding safety, 45 adverse drug reactions related to SSZ occurred (4.34/100 person‐years; 95% CI 3.26–5.78). Only one serious adverse reaction (drug‐induced hypersensitivity syndrome) was observed, which resolved after discontinuation of SSZ. Conclusion We demonstrated the preventive efficacy of SSZ on PCP. The pleiotropic effect of this traditional DMARD may impact RA treatment, providing another option for PCP prophylaxis.

Post-COVID-19 severe Pneumocystis jirovecii pneumonia in a non-HIV and immunocompetent patient: A case report and literature review

2025-06-01

Zhiyang Xu , Wei Ouyang , Jinliang Liu +2 more | Journal of International Medical Research

Pneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. The clinical manifestations of pneumonia caused by severe acute respiratory syndrome coronavirus 2 and P. jirovecii are similar, … Pneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. The clinical manifestations of pneumonia caused by severe acute respiratory syndrome coronavirus 2 and P. jirovecii are similar, posing a significant challenge in the diagnosis of P. jirovecii pneumonia or coronavirus disease 2019. Herein, we report a case of P. jirovecii pneumonia diagnosed through bronchoalveolar lavage and sputum smear analyses. The patient recovered successfully and was discharged following combination therapy with trimethoprim/sulfamethoxazole and corticosteroids. Early diagnosis and prompt treatment are of vital importance in managing P. jirovecii pneumonia, particularly in individuals with related risk factors for P. jirovecii pneumonia development.

Chronic Obstructive Pulmonary Disease in People with HIV: an Evidence-Based Review

2025-06-01

Alan Read , Jane Akodu , Tristan Barber +5 more | HIV/AIDS - Research and Palliative Care

HIV co-infection is a risk factor for the development of COPD. HIV enhances the deleterious effects of exposures such as tobacco smoking, as well as interacting with other drivers of … HIV co-infection is a risk factor for the development of COPD. HIV enhances the deleterious effects of exposures such as tobacco smoking, as well as interacting with other drivers of COPD such as pulmonary tuberculosis, air pollution and biomass fuel burning. Recent work demonstrates that HIV also contributes independently to COPD pathogenesis by promoting oxidative stress, chronic inflammation, abnormal innate and adaptive immune responses, microbial dysbiosis, and epigenetic alterations within the lung. Consequently, people with HIV develop COPD younger, more often, and with faster rates of lung function decline compared to seronegative individuals. They may also have distinct patterns of lung function abnormalities compared to other etiotypes of COPD. Understanding the natural and pathogenetic history of HIV-associated COPD is important as its assessment, prevention and treatment are currently extrapolated from the general population. Whilst smoking cessation remains vital, further understanding may help guide unique management strategies for HIV-associated COPD. In this review, we explore its epidemiology and pathophysiology and discuss prevention and treatment approaches in this increasingly common disease.