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Clinical Microbiology and Infection :... Jul 2024Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Comparative efficacy and safety of Pneumocystis jirovecii pneumonia prophylaxis regimens for people living with HIV: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone.
OBJECTIVES
To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis.
METHODS
DATA SOURCES: Embase, MEDLINE, and CENTRAL from inception to June 21, 2023.
STUDY ELIGIBILITY CRITERIA
Comparative randomized controlled trials (RCTs).
PARTICIPANTS
PWH.
INTERVENTIONS
Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo.
ASSESSMENT OF RISK OF BIAS
Cochrane risk-of-bias tool for RCTs 2.
METHODS OF DATA SYNTHESIS
Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed.
RESULTS
A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36-0.83) and AP (RR = 0.53; 95% CI, 0.36-0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64-0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01-1.54) and AP (7.20; 95% CI, 5.37-9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups.
CONCLUSIONS
TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity.
Topics: Humans; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Network Meta-Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Pneumocystis carinii; HIV Infections; AIDS-Related Opportunistic Infections; Dapsone; Pentamidine; Atovaquone; Antifungal Agents; Treatment Outcome
PubMed: 38583518
DOI: 10.1016/j.cmi.2024.03.037 -
BMJ Open Oct 2023We aimed to identify exercise tests that have been validated to support a safe discharge to home in patients with or without COVID-19. (Review)
Review
OBJECTIVES
We aimed to identify exercise tests that have been validated to support a safe discharge to home in patients with or without COVID-19.
STUDY DESIGN
Scoping review, using PRISMA-ScR reporting standards. Medline, PubMed, AMED, Embase, CINAHL and LitCovid databases were searched between 16 and 22 February 2021, with studies included from any publication date up to and including the search date.
INTERVENTION
Short exercise tests.
PRIMARY OUTCOME MEASURES
Safe discharge from hospital, readmission rate, length of hospital stay, mortality. Secondary outcomes measures: safety, feasibility and reliability.
RESULTS
Of 1612 original records screened, 19 studies were included in the analysis. These used a variety of exercise tests in patients with chronic obstructive pulmonary disease, suspected pulmonary embolism and pneumocystis carinii pneumonia, heart failure or critical illness. Only six studies had examined patients with COVID-19, of these two were still recruiting to evaluate the 1 min sit-to-stand test and the 40-steps test. There was heterogeneity in patient populations, tests used and outcome measures. Few exercise tests have been validated to support discharge decisions. There is currently no support for short exercise tests for triage of care in patients with COVID-19.
CONCLUSIONS
Further research is needed to aid clinical decision-making at discharge from hospital.
Topics: Humans; COVID-19; Patient Discharge; Exercise Test; Reproducibility of Results; Hospitals
PubMed: 37907292
DOI: 10.1136/bmjopen-2022-068169 -
Pharmacotherapy Nov 2022Patients with inflammatory bowel disease (IBD) are at increased risk of developing Pneumocystis jirovecii pneumonia (PJP) than the general population. Many medications... (Review)
Review
Patients with inflammatory bowel disease (IBD) are at increased risk of developing Pneumocystis jirovecii pneumonia (PJP) than the general population. Many medications utilized for the treatment of IBD affect the immune system, potentially further increasing the risk of PJP. Recommendations for prophylaxis against PJP in this patient population are based upon limited evidence, and risk factors for PJP development are not well-agreed upon. The purpose of this systematic review was to consolidate and evaluate the evidence for PJP prophylaxis in patients with IBD. An electronic literature search was performed, and 29 studies were included in the review, of which 24 were case reports or case series. Combined data from five cohort studies showed an absolute risk of developing PJP to be 0.07%. The majority of patients who developed PJP were receiving corticosteroids at the time of diagnosis (76%). The number of concomitant immunosuppressants received at time of PJP diagnosis varied from one to four. All studies reporting treatment of PJP utilized sulfamethoxazole-trimethoprim. Of the 27 studies reporting mortality data, 19% of patients died. Given the lack of conclusive data regarding risk factors for PJP development and the overall low incidence of PJP in patients with IBD, it is recommended to assess the patient's risk on a case-by-case basis to determine whether PJP prophylaxis is warranted.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination; Inflammatory Bowel Diseases; Immunosuppressive Agents
PubMed: 36222368
DOI: 10.1002/phar.2733 -
Health Science Reports May 2022Bendamustine, a bifunctional mechlorethamine alkylating agent, is used in the treatment of patients with hematologic malignancies. Myelosuppression and cytotoxic effect... (Review)
Review
BACKGROUND
Bendamustine, a bifunctional mechlorethamine alkylating agent, is used in the treatment of patients with hematologic malignancies. Myelosuppression and cytotoxic effect arises quite often after bendamustine treatment. To date, there have been no recommendations for routine chemoprophylaxis for pneumonia (PCP) in patients under treatment with this agent. The present systematic review aimed to evaluate the existing data on bendamustine effects on pneumocystis pneumonia.
METHOD
English papers were systematically reviewed using Web of Science, Embase, Google Scholar, PubMed, and Cochrane library. There was no time constraint for the paper search. The used keywords included "Pneumonia, Pneumocystis"or "Pneumocystis Pneumonia"or "Pneumocystis jirovecii" and "Bendamustine hydrochloride or Bendamustine. "Through our search, 113 papers were found, 26 of which were chosen following a review of the titles and abstracts; ultimately, 10 were included in the research.
RESULT
A total of 10 studies (out of 113 studies) were retrieved. The papers were classified into seven case reports, two clinical trials, and one retrospective analysis study. The case reports included 14 patients diagnosed with PCP after bendamustine administration between 2003 and 2019. The patients' mean age was with a range of 66.8. Non-Hodgkin's lymphoma (including diffuse large B-cell lymphoma and mantle cell lymphoma) ( = 9, 60%), chronic lymphocytic leukemia ( = 4, 26.6%), and breast cancer ( = 2, 13.4%) were the most prevalent types of malignancy. Bendamustine, along with rituximab, were the most commonly prescribed chemotherapy regimens during the treatments. Finally, the mortality rate among the patients whose results were reported ( = 9) was 44.44% ( = 4).
CONCLUSION
The present review described PCP infection in patients with malignancies after the treatment with bendamustine, a chemotherapeutic agent associated with lymphopenia. Further research is required to determine the PCP risk in patients with bendamustine treatment and identify individuals who may benefit from prophylaxis.
PubMed: 35509412
DOI: 10.1002/hsr2.610 -
Clinical Microbiology and Infection :... Jan 2022Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection commonly affecting immunocompromised people. Diagnosis usually requires invasive techniques to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection commonly affecting immunocompromised people. Diagnosis usually requires invasive techniques to obtain respiratory specimens. Minimally invasive detection tests have been proposed, but their operating characteristics are poorly described.
OBJECTIVES
To systematically review and meta-analyse the performance of minimally invasive PCP detection tests to inform diagnostic algorithms.
DATA SOURCES
Medline, Embase, Cochrane Library (inception to 15 October 2020).
STUDY ELIGIBILITY CRITERIA
Studies of minimally invasive PCP detection tests were included if they contained a minimum of ten PCP cases.
PARTICIPANTS
Adults at risk of PCP.
TESTS
Non-invasive PCP detection tests.
REFERENCE STANDARD
Diagnosis using the combination of clinical and radiographical features with invasive sampling.
ASSESSMENT OF RISK BIAS
Using the QUADAS-2 tool.
METHODS
We used bivariate and, when necessary, univariate analysis models to estimate diagnostic test sensitivity and specificity.
RESULTS
Fifty-two studies were included; most studies (40) comprised exclusively human immunodeficiency virus (HIV) -infected individuals; nine were mixed (HIV and non-HIV), two were non-HIV and one study did not report HIV status. Sampling sites included induced sputum, nasopharyngeal aspirate, oral wash and blood. The four testing modalities evaluated were cytological staining, fluorescent antibody, PCR and lactate dehydrogenase. Induced sputum had the most data available; this modality was both highly sensitive at 99% (95% CI 51%-100%) and specific at 96% (95% CI 88%-99%). Induced sputum cytological staining had moderate sensitivity at 50% (95% CI 39%-61%) and high specificity at 100% (95% CI 100%-100%), as did fluorescent antibody testing with sensitivity 74% (95% CI 62%-87%) and specificity 100% (95% CI 91%-100%).
CONCLUSION
There are several promising minimally invasive PCP diagnostic tests available, some of which may reduce the need for invasive respiratory sampling. Understanding the operating characteristics of these tests can augment current diagnostic strategies and help establish a more confident clinical diagnosis of PCP. Further studies in non-HIV infected populations are needed.
Topics: Adult; HIV Infections; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Sensitivity and Specificity; Sputum
PubMed: 34464734
DOI: 10.1016/j.cmi.2021.08.017 -
Medical Mycology Jul 2021The epidemiology of Pneumocystis jirovecii, known to colonize the respiratory tract and cause a life-threatening HIV-associated pneumonia (PCP), is poorly described in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The epidemiology of Pneumocystis jirovecii, known to colonize the respiratory tract and cause a life-threatening HIV-associated pneumonia (PCP), is poorly described in Africa. We conducted a systematic review to evaluate P. jirovecii prevalence in African HIV-positive adults with or without respiratory symptoms.
METHODS
We searched Medline, Embase, Cochrane library, Africa-Wide, and Web of Science for studies employing PCR and/or microscopy for P. jirovecii detection in respiratory samples from HIV-positive adults in Africa between 1995 and 2020. Prevalence with respiratory symptoms was pooled using random-effect meta-analysis, and stratified by laboratory method, sample tested, study setting, CD4 count, and trimethoprim/sulfamethoxazole prophylaxis. Colonization prevalence in asymptomatic adults and in adults with non-PCP respiratory disease was described, and quantitative PCR (qPCR) thresholds to distinguish colonization from microscopy-confirmed PCP reviewed.
RESULTS
Thirty-two studies were included, with 27 studies (87%) at high risk of selection bias. P. jirovecii was detected in 19% [95% confidence interval (CI): 12-27%] of 3583 symptomatic and in 9% [95% CI: 0-45%] of 140 asymptomatic adults. Among symptomatic adults, prevalence was 22% [95% CI: 12-35%] by PCR and 15% [95% CI: 9-23%] by microscopy. Seven percent of 435 symptomatic adults had PCR-detected Pneumocystis colonization without evidence of PCP [95% CI: 5-10%, four studies]. One study established a qPCR cutoff of 78 copies/5μl of DNA in 305 induced sputum samples to distinguish Pneumocystis colonization from microscopy-confirmed PCP.
CONCLUSION
Despite widened access to HIV services, P. jirovecii remains common in Africa. Prevalence estimates and qPCR-based definitions of colonization are limited, and overall quality of studies is low.
Topics: Adult; Africa; Asymptomatic Infections; HIV Infections; Humans; Pneumocystis Infections; Pneumocystis carinii; Prevalence
PubMed: 33578417
DOI: 10.1093/mmy/myab002 -
The Cochrane Database of Systematic... Jul 2020Invasive fungal infections (IFIs) are life-threatening opportunistic infections that occur in immunocompromised or critically ill people. Early detection and treatment...
BACKGROUND
Invasive fungal infections (IFIs) are life-threatening opportunistic infections that occur in immunocompromised or critically ill people. Early detection and treatment of IFIs is essential to reduce morbidity and mortality in these populations. (1→3)-β-D-glucan (BDG) is a component of the fungal cell wall that can be detected in the serum of infected individuals. The serum BDG test is a way to quickly detect these infections and initiate treatment before they become life-threatening. Five different versions of the BDG test are commercially available: Fungitell, Glucatell, Wako, Fungitec-G, and Dynamiker Fungus.
OBJECTIVES
To compare the diagnostic accuracy of commercially available tests for serum BDG to detect selected invasive fungal infections (IFIs) among immunocompromised or critically ill people.
SEARCH METHODS
We searched MEDLINE (via Ovid) and Embase (via Ovid) up to 26 June 2019. We used SCOPUS to perform a forward and backward citation search of relevant articles. We placed no restriction on language or study design.
SELECTION CRITERIA
We included all references published on or after 1995, which is when the first commercial BDG assays became available. We considered published, peer-reviewed studies on the diagnostic test accuracy of BDG for diagnosis of fungal infections in immunocompromised people or people in intensive care that used the European Organization for Research and Treatment of Cancer (EORTC) criteria or equivalent as a reference standard. We considered all study designs (case-control, prospective consecutive cohort, and retrospective cohort studies). We excluded case studies and studies with fewer than ten participants. We also excluded animal and laboratory studies. We excluded meeting abstracts because they provided insufficient information.
DATA COLLECTION AND ANALYSIS
We followed the standard procedures outlined in the Cochrane Handbook for Diagnostic Test Accuracy Reviews. Two review authors independently screened studies, extracted data, and performed a quality assessment for each study. For each study, we created a 2 × 2 matrix and calculated sensitivity and specificity, as well as a 95% confidence interval (CI). We evaluated the quality of included studies using the Quality Assessment of Studies of Diagnostic Accuracy-Revised (QUADAS-2). We were unable to perform a meta-analysis due to considerable variation between studies, with the exception of Candida, so we have provided descriptive statistics such as receiver operating characteristics (ROCs) and forest plots by test brand to show variation in study results.
MAIN RESULTS
We included in the review 49 studies with a total of 6244 participants. About half of these studies (24/49; 49%) were conducted with people who had cancer or hematologic malignancies. Most studies (36/49; 73%) focused on the Fungitell BDG test. This was followed by Glucatell (5 studies; 10%), Wako (3 studies; 6%), Fungitec-G (3 studies; 6%), and Dynamiker (2 studies; 4%). About three-quarters of studies (79%) utilized either a prospective or a retrospective consecutive study design; the remainder used a case-control design. Based on the manufacturer's recommended cut-off levels for the Fungitell test, sensitivity ranged from 27% to 100%, and specificity from 0% to 100%. For the Glucatell assay, sensitivity ranged from 50% to 92%, and specificity ranged from 41% to 94%. Limited studies have used the Dynamiker, Wako, and Fungitec-G assays, but individual sensitivities and specificities ranged from 50% to 88%, and from 60% to 100%, respectively. Results show considerable differences between studies, even by manufacturer, which prevented a formal meta-analysis. Most studies (32/49; 65%) had no reported high risk of bias in any of the QUADAS-2 domains. The QUADAS-2 domains that had higher risk of bias included participant selection and flow and timing.
AUTHORS' CONCLUSIONS
We noted considerable heterogeneity between studies, and these differences precluded a formal meta-analysis. Because of wide variation in the results, it is not possible to estimate the diagnostic accuracy of the BDG test in specific settings. Future studies estimating the accuracy of BDG tests should be linked to the way the test is used in clinical practice and should clearly describe the sampling protocol and the relationship of time of testing to time of diagnosis.
Topics: Aspergillosis; Biomarkers; Candidiasis, Invasive; Case-Control Studies; Critical Illness; Humans; Immunocompromised Host; Invasive Fungal Infections; Pneumocystis Infections; Pneumocystis carinii; Prospective Studies; ROC Curve; Retrospective Studies; Sensitivity and Specificity; beta-Glucans
PubMed: 32693433
DOI: 10.1002/14651858.CD009833.pub2 -
Clinical Microbiology and Infection :... Sep 2020Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring semi-invasive respiratory sampling. The serum 1,3-β-D-glucan (BDG) assay has been proposed as a minimally invasive test for the presumptive diagnosis of PJP.
METHOD
We carried out a systematic review and meta-analysis using articles in the English language published between January 1960 and September 2019. We estimated the pooled sensitivity and specificity of BDG testing using a bivariate random effects approach and compared test performance in human immunodeficiency virus (HIV) and non-HIV subgroups with meta-regression. Data from the pooled sensitivity and specificity were transformed to generate pre- and post-test probability curves.
RESULTS
Twenty-three studies were included. The pooled sensitivity and specificity of serum BDG testing for PJP were 91% (95%CI 87-94%) and 79% (95%CI 72-84%) respectively. The sensitivity in patients with HIV was better than in patients without (94%, 95%CI 91-96%) versus 86% (95%CI 78-91%) (p 0.02), with comparable specificity (83%, 95%CI 69-92% versus 83%, 95%CI 72-90%) (p 0.10). A negative BDG was only associated with a low post-test probability of PJP (≤5%) when the pre-test probability was low to intermediate (≤20% in non-HIV and ≤50% in HIV).
CONCLUSIONS
Among patients with a higher likelihood of PJP, the pooled sensitivity of BDG is insufficient to exclude infection. Similarly, for most cases, the pooled specificity is inadequate to diagnose PJP. Understanding the performance of BDG in the population being investigated is therefore essential to optimal clinical decision-making.
Topics: Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Sensitivity and Specificity; Serologic Tests; beta-Glucans
PubMed: 32479781
DOI: 10.1016/j.cmi.2020.05.024