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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 -
Rheumatology International Aug 2021The incidence of Pneumocystis jirovecii pneumonia (PJP) has increased over recent years in patients with systemic autoimmune rheumatic diseases (SARD). PJP prognosis is...
Is cotrimoxazole prophylaxis against Pneumocystis jirovecii pneumonia needed in patients with systemic autoimmune rheumatic diseases requiring immunosuppressive therapies?
The incidence of Pneumocystis jirovecii pneumonia (PJP) has increased over recent years in patients with systemic autoimmune rheumatic diseases (SARD). PJP prognosis is poor in those receiving immunosuppressive therapy and glucocorticoids in particular. Despite the effectiveness of cotrimoxazole against PJP, the risk of adverse effects remains significant, and no consensus has emerged regarding the need for PJP prophylaxis in SARD patients undergoing immunosuppressor therapies.Objective: To evaluate the efficacy and safety of cotrimoxazole prophylaxis against PJP in SARD adult patients receiving immunosuppressive therapies. Methods: We performed a systematic review, consulting MEDLINE, EMBASE, and Cochrane Library databases up to April 2020. Outcomes covered prevention of PJP, other infections, morbidity, mortality, and safety. The information obtained was summarized with a narrative review and results were tabulated. Of the 318 identified references, 8 were included. Two were randomized controlled trials and six observational studies. The quality of studies was moderate or low. Despite disparities in the cotrimoxazole prophylaxis regimens described, results were consistent in terms of efficacy, particularly with glucocorticoid doses > 20 mg/day. However, cotrimoxazole 400 mg/80 mg/day, prescribed three times/ week, or 200 mg/40 mg/day or in dose escalation, exhibited similar positive performances. Conversely, cotrimoxazole 400 mg/80 mg/day showed higher incidences of withdrawals and adverse effects. Cotrimoxazole prophylaxis against PJP exhibited efficacy in SARD, mainly in patients taking glucocorticoids ≥ 20 mg/day. All cotrimoxazole regimens exposed seemed equally efficacious, although, higher quality trials are needed. Adverse effects were observed 2 months after initiation, particularly with the 400 mg/80 mg/day regimen. Conversely, escalation dosing or 200 mg/40 mg/day regimens appeared better tolerated.
Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Rheumatic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 33656582
DOI: 10.1007/s00296-021-04808-4 -
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 -
Transplantation Oct 2021There is no consensus guidance on when to reinitiate Pneumocystis jirovecii pneumonia (PJP) prophylaxis in solid organ transplant (SOT) recipients at increased risk. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is no consensus guidance on when to reinitiate Pneumocystis jirovecii pneumonia (PJP) prophylaxis in solid organ transplant (SOT) recipients at increased risk. The 2019 American Society of Transplantation Infectious Diseases Community of Practice (AST IDCOP) guidelines suggested to continue or reinstitute PJP prophylaxis in those receiving intensified immunosuppression for graft rejection, cytomegalovirus (CMV) infection, higher dose of corticosteroids, or prolonged neutropenia.
METHODS
A literature search was conducted evaluating all literature from existence through April 22, 2020, using MEDLINE and EMBASE. (The International Prospective Register of Systematic Reviews registration number: CRD42019134204).
RESULTS
A total of 30 studies with 413 276 SOT recipients were included. The following factors were associated with PJP development: acute rejection (pooled odds ratio [pOR], 2.35; 95% confidence interval [CI], 1.69-3.26); study heterogeneity index [I2] = 23.4%), CMV-related illnesses (pOR, 3.14; 95% CI, 2.30-4.29; I2 = 48%), absolute lymphocyte count <500 cells/mm3 (pOR, 6.29; 95% CI, 3.56-11.13; I2 = 0%), BK polyomavirus-related diseases (pOR, 2.59; 95% CI, 1.22-5.49; I2 = 0%), HLA mismatch ≥3 (pOR, 1.83; 95% CI, 1.06-3.17; I2 = 0%), rituximab use (pOR, 3.03; 95% CI, 1.82-5.04; I2 = 0%), and polyclonal antibodies use for rejection (pOR, 3.92; 95% CI, 1.87-8.19; I2 = 0%). On the other hand, sex, CMV mismatch, interleukin-2 inhibitors, corticosteroids for rejection, and plasmapheresis were not associated with developing PJP.
CONCLUSIONS
PJP prophylaxis should be considered in SOT recipients with lymphopenia, BK polyomavirus-related infections, and rituximab exposure in addition to the previously mentioned risk factors in the American Society of Transplantation Infectious Diseases Community of Practice guidelines.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Opportunistic Infections; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 33323766
DOI: 10.1097/TP.0000000000003576 -
The British Journal of Radiology Feb 2021Chest imaging is often used as a complementary tool in the evaluation of coronavirus disease 2019 (COVID-19) patients, helping physicians to augment their clinical...
Chest imaging is often used as a complementary tool in the evaluation of coronavirus disease 2019 (COVID-19) patients, helping physicians to augment their clinical suspicion. Despite not being diagnostic for COVID-19, chest CT may help clinicians to isolate high suspicion patients with suggestive imaging findings. However, COVID-19 findings on CT are also common to other pulmonary infections and non-infectious diseases, and radiologists and point-of-care physicians should be aware of possible mimickers. This state-of-the-art review goal is to summarize and illustrate possible etiologies that may have a similar pattern on chest CT as COVID-19. The review encompasses both infectious etiologies, such as non-COVID viral pneumonia, , , and pulmonary granulomatous infectious, and non-infectious disorders, such as pulmonary embolism, fat embolism, cryptogenic organizing pneumonia, non-specific interstitial pneumonia, desquamative interstitial pneumonia, and acute and chronic eosinophilic pneumonia.
Topics: Adult; Aged; COVID-19; Community-Acquired Infections; Diagnosis, Differential; Embolism, Fat; Female; Granulomatous Disease, Chronic; Humans; Lung Diseases; Lung Diseases, Interstitial; Male; Middle Aged; Pneumonia, Mycoplasma; Pneumonia, Pneumocystis; Pneumonia, Viral; Pulmonary Embolism; Pulmonary Eosinophilia; Radiography, Thoracic; Time Factors; Tomography, X-Ray Computed
PubMed: 33296607
DOI: 10.1259/bjr.20200703 -
Journal of Clinical Pharmacy and... Dec 2020Pneumocystis jiroveci (P jiroveci) is an important opportunistic fungus and causes pneumocystis jiroveci pneumonia (PJP) in kidney transplant recipients (KTRs). By using...
WHAT IS KNOWN AND OBJECTIVE
Pneumocystis jiroveci (P jiroveci) is an important opportunistic fungus and causes pneumocystis jiroveci pneumonia (PJP) in kidney transplant recipients (KTRs). By using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, the objective of this study was to evaluate the quality of PJP prophylaxis clinical practice guidelines (CPGs), and to help develop, update or improve guideline.
METHODS
A search was conducted for PJP prophylaxis CPGs using PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), WanFang data, VIP Database, Google and guideline websites (until 18 January 2020). Data extraction and quality assessment were independently assessed by two appraisers, and the intra-class correlation coefficient (ICC) was used to assess interrater reliability. The specific recommendations were evaluated based on the quality results.
RESULTS AND DISCUSSION
A total of 6 CPGs were included. The highest median scores were in the clarity of presentation domain (92%), and the lowest median scores were in the applicability domain (25%). The Kidney Disease Improving Global Outcome (KDIGO) and Renal Association (RA)/British Transplantation Society (BTS) CPGs were strongly recommended. The specific recommendations were inconsistent, such as the dose, frequency and duration.
WHAT IS NEW AND CONCLUSION
The KDIGO and RA/BTS CPGs were strongly recommended. Not only the quality of the PJP prophylaxis CPGs needs to be improved during the development progress, but also the specific recommendations should be further refined.
Topics: Humans; Kidney Transplantation; Observer Variation; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Reproducibility of Results
PubMed: 32710453
DOI: 10.1111/jcpt.13213 -
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 -
European Journal of Clinical... Nov 2019Although there is controversy, some evidences proposed increased risk of post-transplant Pneumocystis carinii pneumonia (PCP) in patients receiving mammalian target of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Although there is controversy, some evidences proposed increased risk of post-transplant Pneumocystis carinii pneumonia (PCP) in patients receiving mammalian target of rapamycin (mTOR) inhibitors. This study aimed to examine the association between m-TOR inhibitors and the risk of developing PCP in solid organ transplant (SOT) recipients.
METHODS
A comprehensive search was performed to find the eligible studies that investigated the incidence of PCP in patients treated with mTOR inhibitors after SOT. Random effect model was applied for meta-analysis.
RESULTS
Combination of 15 effect sizes showed a significant positive association between mTOR inhibitor administration and the risk of PCP (OR = 1.90, 95%CIs = 1.44, 2.75). There was no heterogeneity between studies (I = 3.5%). Subgroup analysis revealed increased risk of PCP after the first year of transplantation (P < 0.001).
CONCLUSION
In conclusion, administration of mTOR inhibitors is a potential risk factor for late-onset PCP after SOT. Targeted PCP prophylaxis based on recipients' risk factors rather universal prophylaxis may lessen the risk.
Topics: Humans; Organ Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Factors; TOR Serine-Threonine Kinases
PubMed: 31377892
DOI: 10.1007/s00228-019-02730-0 -
Journal of Infection in Developing... Oct 2018Pneumocystis jirovecii (PJ) pneumonia (PJP) is an important opportunistic infection affecting various types of immunocompromised patients and is associated with an...
INTRODUCTION
Pneumocystis jirovecii (PJ) pneumonia (PJP) is an important opportunistic infection affecting various types of immunocompromised patients and is associated with an increased risk of mortality. PJ is a unique fungal pathogen which is increasingly common and maybe associated with a higher mortality rate in patients without AIDS. We present the characteristics of PJP, diagnosis, and treatment outcomes between AIDS and non-AIDS patients.
METHODOLOGY
We conducted a review of studies of AIDS and non-AIDS patients with PJP using PubMed to search for studies until December 2017.
RESULTS
The annual incidence of AIDS-PJP decreased from 13.4 to 3.3 per 1000 person-years in industrialized countries, while the incidence of non-AIDS-PJP varied widely. Both groups had similar clinical manifestations and radiological features, but the non-AIDS-PJP group potentially had a more fulminant course, more diffuse ground glass opacities, and fewer cystic lesions. The mortality rate decreased in the AIDS-PJP group after the advent of antiretroviral therapy; however, the mortality rate remained high in both groups. A laboratory diagnosis was usually nonspecific; CD4+ T-cell < 200 cells/mL or < 14% favored AIDS-PJP. Serum 1,3-β-D-glucan (BDG) had a high diagnostic odds ratio. Combining BDG and lactic dehydrogenase improved the diagnosis of AIDS-PJP. Histopathological staining and polymerase chain reactions could not discriminate infection from colonization when the result was positive. The use of antibiotics, prophylaxis, and adjunctive corticosteroids was controversial.
CONCLUSIONS
Early diagnosis and treatment can be achieved through vigilance, thereby improving the survival rate for PJP in immunocompromised patients.
Topics: AIDS-Related Opportunistic Infections; Case-Control Studies; Early Diagnosis; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Survival Rate
PubMed: 32004150
DOI: 10.3855/jidc.10357