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PloS One 2021Pneumocystis pneumonia (PCP) has a significant impact on the mortality of immunocompromised patients. It is not known whether the prophylactic application of... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of pneumocystis pneumonia in human immunodeficiency virus-negative immunodeficient patients: A systematic review and meta-analysis.
BACKGROUND
Pneumocystis pneumonia (PCP) has a significant impact on the mortality of immunocompromised patients. It is not known whether the prophylactic application of trimethoprim-sulfamethoxazole (TMP-SMZ) can reduce the incidence of PCP and mortality in the human immunodeficiency virus (HIV)-negative immunodeficient population. The safety profile is also unknown. There have been few reports on this topic. The aim of this study was to systematically evaluate the efficacy and safety of the use of TMP-SMZ for the prevention of PCP in this population of patients from the perspective of evidence-based medicine.
METHODS
A comprehensive search without restrictions on publication status or other parameters was conducted. Clinical randomized controlled trials (RCTs) or case-control trials (CCSs) of TMP-SMZ used for the prevention of PCP in HIV-negative immunocompromised populations were considered eligible. A meta-analysis was performed using the Mantel-Haenszel fixed-effects model or Mantel-Haenszel random-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and reported.
RESULTS
Of the 2392 records identified, 19 studies (n = 4135 patients) were included. The efficacy analysis results indicated that the PCP incidence was lower in the TMP-SMZ group than in the control group (OR = 0.27, 95% CI (0.10, 0.77), p = 0.01); however, the rate of drug discontinuation was higher in the TMP-SMZ group than in the control group (OR = 14.31, 95% CI (4.78, 42.91), p<0.00001). In addition, there was no statistically significant difference in the rate of mortality between the two groups (OR = 0.54, 95% CI (0.21, 1.37), p = 0.19). The safety analysis results showed that the rate of adverse events (AEs) was higher in the TMP-SMZ group than in the control group (OR = 1.92, 95% CI (1.06, 3.47), p = 0.03).
CONCLUSIONS
TMP-SMZ has a better effect than other drugs or the placebo with regard to preventing PCP in HIV-negative immunocompromised individuals, but it may not necessarily reduce the rate of mortality, the rate of drug discontinuation or AEs. Due to the limitations of the research methodologies used, additional large-scale clinical trials and well-designed research studies are needed to identify more effective therapies for the prevention of PCP.
Topics: Adolescent; Adult; Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Immunologic Deficiency Syndromes; Male; Middle Aged; Pneumonia, Pneumocystis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 33765022
DOI: 10.1371/journal.pone.0248524 -
Systematic Reviews Mar 2021Even when resting pulse oximetry is normal in the patient with acute Covid-19, hypoxia can manifest on exertion. We summarise the literature on the performance of...
BACKGROUND
Even when resting pulse oximetry is normal in the patient with acute Covid-19, hypoxia can manifest on exertion. We summarise the literature on the performance of different rapid tests for exertional desaturation and draw on this evidence base to provide guidance in the context of acute Covid-19.
MAIN RESEARCH QUESTIONS
1. What exercise tests have been used to assess exertional hypoxia at home or in an ambulatory setting in the context of Covid-19 and to what extent have they been validated? 2. What exercise tests have been used to assess exertional hypoxia in other lung conditions, to what extent have they been validated and what is the applicability of these studies to acute Covid-19?
METHOD
AMED, CINAHL, EMBASE MEDLINE, Cochrane and PubMed using LitCovid, Scholar and Google databases were searched to September 2020. Studies where participants had Covid-19 or another lung disease and underwent any form of exercise test which was compared to a reference standard were eligible. Risk of bias was assessed using QUADAS 2. A protocol for the review was published on the Medrxiv database.
RESULTS
Of 47 relevant papers, 15 were empirical studies, of which 11 described an attempt to validate one or more exercise desaturation tests in lung diseases other than Covid-19. In all but one of these, methodological quality was poor or impossible to fully assess. None had been designed as a formal validation study (most used simple tests of correlation). Only one validation study (comparing a 1-min sit-to-stand test [1MSTST] with reference to the 6-min walk test [6MWT] in 107 patients with interstitial lung disease) contained sufficient raw data for us to calculate the sensitivity (88%), specificity (81%) and positive and negative predictive value (79% and 89% respectively) of the 1MSTST. The other 4 empirical studies included two predictive studies on patients with Covid-19, and two on HIV-positive patients with suspected pneumocystis pneumonia. We found no studies on the 40-step walk test (a less demanding test that is widely used in clinical practice to assess Covid-19 patients). Heterogeneity of study design precluded meta-analysis.
DISCUSSION
Exertional desaturation tests have not yet been validated in patients with (or suspected of having) Covid-19. A stronger evidence base exists for the diagnostic accuracy of the 1MSTST in chronic long-term pulmonary disease; the relative intensity of this test may raise safety concerns in remote consultations or unstable patients. The less strenuous 40-step walk test should be urgently evaluated.
Topics: COVID-19; Dyspnea; Exercise; Exercise Test; Humans; Hypoxia; Lung Diseases; Oxygen; Physical Exertion; Predictive Value of Tests; SARS-CoV-2; Sensitivity and Specificity
PubMed: 33726854
DOI: 10.1186/s13643-021-01620-w -
Journal of Fungi (Basel, Switzerland) Feb 2021The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases...
Performance of Existing Definitions and Tests for the Diagnosis of Invasive Fungal Diseases other than Invasive Candidiasis and Invasive Aspergillosis in Critically Ill, Adult Patients: A Systematic Review with Qualitative Evidence Synthesis.
The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases (IFDs) in critically ill, adult patients, including invasive aspergillosis (IA), invasive candidiasis (IC), pneumonia (PJP), and other non-IA, non-IC IFDs. The first step of the project was the conduction of separated systematic reviews of the characteristics and applicability to critically ill, adult patients outside classical populations at risk (hematology patients, solid organ transplant recipients) of available definitions and diagnostic tests for IFDs. We report here the results of two systematic reviews exploring the performance of available definitions and tests, for PJP and for other non-IA, non-IC IFDs. Starting from 2585 and 4584 records for PJP and other IFDs, respectively, 89 and 61 studies were deemed as eligible for full-text evaluation. However, only two studies for PJP and no studies for other IFDs met the FUNDICU protocol criteria for inclusion in qualitative synthesis. Currently, there is no sufficient solid data for directly evaluating the performance of existing definitions and laboratory tests for the diagnosis of PJP and other non-IA, non-IC IFDs in critically ill adult patients outside classical populations at risk.
PubMed: 33670864
DOI: 10.3390/jof7030176 -
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 -
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 -
Open Forum Infectious Diseases May 2020pneumonia (PJP) remains a common and highly morbid infection for immunocompromised patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the antimicrobial treatment of...
BACKGROUND
pneumonia (PJP) remains a common and highly morbid infection for immunocompromised patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the antimicrobial treatment of choice. However, treatment with TMP-SMX can lead to significant dose-dependent renal and hematologic adverse events. Although TMP-SMX is conventionally dosed at 15-20 mg/kg/d of trimethoprim for the treatment of PJP, reduced doses may be effective and carry an improved safety profile.
METHODS
We conducted a systematic search in the Medline, Embase, and Cochrane Library databases from inception through March 2019 for peer-reviewed studies reporting on reduced doses of TMP-SMX (15 mg/kg/d of trimethoprim or less) for the treatment of PJP. PRISMA, MOOSE, and Cochrane guidelines were followed. Gray literature was excluded.
RESULTS
Ten studies were identified, and 6 were included in the meta-analysis. When comparing standard doses with reduced doses of TMP-SMX, there was no statistically significant difference in mortality (absolute risk difference, -9% in favor of reduced dose; 95% confidence interval [CI], -27% to 8%). When compared with standard doses, reduced doses of TMP-SMX were associated with an 18% (95% CI, -31% to -5%) absolute risk reduction of grade ≥3 adverse events.
CONCLUSIONS
In this systematic review, treatment of PJP with doses of ≤10 mg/kg/d of trimethoprim was associated with similar rates of mortality when compared with standard doses and with significantly fewer treatment-emergent severe adverse events. Although limited by the observational nature of the studies included, this review provides the most current available evidence for the optimal dosing of TMP-SMX in the treatment of PJP.
PubMed: 32391402
DOI: 10.1093/ofid/ofaa112