-
Clinical Infectious Diseases : An... Jun 2024This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different...
BACKGROUND
This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different respiratory tract samples, in both human immunodeficiency virus (HIV) and non-HIV populations.
METHODS
A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group definition of proven PCP was examined.
RESULTS
Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%-99.5%), adequate specificity of 89.3% (95% CI, 84.4%-92.7%), negative likelihood ratio (LR-) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%-99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%-88.3%), LR- of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%-96.5%), high specificity of 90.5% (95% CI, 80.9%-95.5%), LR- of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients.
CONCLUSIONS
On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested.
PubMed: 38860786
DOI: 10.1093/cid/ciae239 -
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 -
Clinical Transplantation May 2024Pneumocystis jirovecii pneumonia (PJP), an opportunistic infection, often leads to an increase in hospitalization time and mortality rates in kidney transplant (KT)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Pneumocystis jirovecii pneumonia (PJP), an opportunistic infection, often leads to an increase in hospitalization time and mortality rates in kidney transplant (KT) recipients. However, the risk factors associated with PJP in KT recipients remain debatable. Therefore, we conducted this meta-analysis to identify risk factors for PJP, which could potentially help to reduce PJP incidence and improve outcome of KT recipients.
METHODS
We systematically retrieved relevant studies in PubMed, EMBASE, and the Cochrane Library up to November 2023. Pooled odds ratios (ORs) or mean differences (MDs) and the corresponding 95% confidence intervals (CIs) were calculated to assess the impact of potential risk factors on the occurrence of PJP.
RESULTS
27 studies including 42383 KT recipients were included. In this meta-analysis, age at transplantation (MD = 3.48; 95% CI = .56-6.41; p = .02), cytomegalovirus (CMV) infection (OR = 4.00; 95% CI = 2.53-6.32; p = .001), BK viremia (OR = 3.38; 95% CI = 1.70-6.71; p = .001), acute rejection (OR = 3.66; 95% CI = 2.44-5.49; p = .001), ABO-incompatibility (OR = 2.51; 95% CI = 1.57-4.01; p = .001), estimated glomerular filtration rate (eGFR) (MD = -14.52; 95% CI = -25.37- (-3.67); p = .009), lymphocyte count (MD = -.54; 95% CI = -.92- (-.16); p = .006) and anti-PJP prophylaxis (OR = .53; 95% CI = .28-.98; p = .04) were significantly associated with PJP occurrence.
CONCLUSION
Our findings suggest that transplantation age greater than 50 years old, CMV infection, BK viremia, acute rejection, ABO-incompatibility, decreased eGFR and lymphopenia were risk factors for PJP.
Topics: Humans; Kidney Transplantation; Pneumonia, Pneumocystis; Risk Factors; Prognosis; Pneumocystis carinii; Postoperative Complications; Graft Rejection
PubMed: 38690617
DOI: 10.1111/ctr.15320 -
Journal of Fungi (Basel, Switzerland) Nov 2023A systematic literature search on in 276 pet, farm, zoo, and wild mammal species resulted in 124 publications originating from 38 countries that were analyzed...
A systematic literature search on in 276 pet, farm, zoo, and wild mammal species resulted in 124 publications originating from 38 countries that were analyzed descriptively and statistically, for which inclusion and exclusion criteria were exactly defined. The range of recorded prevalence was broad, yet in half of the citations a prevalence of ≤25% was documented. Prevalence was significantly dependent on the method used for detection, with PCR revealing the highest percentages. Pet animals showed the lowest median prevalence, followed by farm, wild, and zoo animals. In contrast, pet and farm animals showed higher proportions of high-grade infection levels compared to zoo and wild mammals. Only in individual cases, all of them associated with severe pneumonia, was an underlying immunosuppression confirmed. Acquired immunosuppression caused by other diseases was frequently discussed, but its significance, especially in highly immunosuppressive cases, needs to be clarified. This meta-analysis supported a potential influence of the social and environmental factors of the host on transmission in wildlife, which must be further elucidated, as well as the genetic diversity of the fungus.
PubMed: 37998885
DOI: 10.3390/jof9111081 -
Seminars in Arthritis and Rheumatism Dec 2023Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and mortality. We attempted to determine the potential risk factors associated with IFIs in CTD.
METHODS
We systematically searched PubMed, Embase, and the Cochrane Library databases for relevant articles published from the database inception to February 1, 2023.
RESULTS
Twenty-six studies were included in this systematic review and meta-analysis. Risk factors identified for IFIs were diabetes (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.00 to 2.64), pulmonary diseases (OR 3.43; 95% CI 2.49 to 4.73), interstitial lung disease (ILD; OR, 4.06; 95% CI, 2.22 to 7.41), renal disease (OR, 4.41; 95% CI, 1.84 to 10.59), glucocorticoid (GC) use (OR, 4.15; 95% CI, 2.74 to 6.28), especially moderate to high-dose GC, azathioprine (AZA) use (OR, 1.50; 95% CI, 1.12 to 2.01), calcineurin inhibitor (CNI) use (OR, 2.49; 95% CI, 1.59 to 3.91), mycophenolate mofetil (MMF) use (OR, 2.83; 95% CI, 1.59 to 5.03), cyclophosphamide (CYC) use (OR, 3.35; 95% CI, 2.47 to 4.54), biologics use (OR, 3.43; 95% CI, 2.36 to 4.98), and lymphopenia (OR, 4.26; 95% CI, 2.08 to 8.73). Hydroxychloroquine (HCQ) use reduced risk of IFIs (OR, 0.67; 95% CI, 0.54 to 0.84). Furthermore, 17 of the 26 studies only reported risk factors for Pneumocystis jiroveci pneumonia (PJP) in patients with CTD. Pulmonary disease; ILD; and the use of GC, CNIs, CYC, methotrexate (MTX), MMF and biologics, and lymphopenia increased the risk of PJP, whereas the use of HCQ reduced its risk.
CONCLUSION
Diabetes, pulmonary disease, ILD, renal disease, use of GC (especially at moderate to high dose) and immunosuppressive drugs, and lymphopenia were found to be associated with significant risk for IFIs (especially PJP) in patients with CTD. Furthermore, the use of HCQ may reduce the risk of IFIs in patients with CTD.
Topics: Humans; Connective Tissue Diseases; Cyclophosphamide; Lung Diseases, Interstitial; Mycophenolic Acid; Glucocorticoids; Risk Factors; Diabetes Mellitus; Lymphopenia; Biological Products; Invasive Fungal Infections
PubMed: 37633041
DOI: 10.1016/j.semarthrit.2023.152257 -
Pediatric Blood & Cancer Jan 2024Initially developed as immunosuppressive agents, mammalian target of rapamycin (mTOR) inhibitors are currently used widely in the management of vascular malformations... (Review)
Review
BACKGROUND AND OBJECTIVES
Initially developed as immunosuppressive agents, mammalian target of rapamycin (mTOR) inhibitors are currently used widely in the management of vascular malformations and tumors. The incidence of infectious complications in the vascular anomalies (VA) population is not well defined. The goal of this systematic review was to better define the types and severity of reported infectious complications in patients with VAs treated with mTOR inhibition.
METHODS
This was a systematic review conducted following PRISMA guidelines evaluating all research articles focused on infectious complications in patients with VAs treated with sirolimus or everolimus. Thirty articles including 1182 total patients and 316 infections (in 291 unique patients) were ultimately included.
RESULTS
The majority of infections were viral upper respiratory (n = 137, 54%), followed by pneumonia (n = 53, 20%), and cutaneous infections (n = 20, 8%). There were six total infection-related fatalities, which all occurred in patients younger than 2 years. Two cases of Pneumocystis jirovecii pneumonia (PJP) were reported. These were infants with kaposiform hemangioendothelioma (KHE) who were also treated with steroids and did not receive PJP prophylaxis. Almost one-third (n = 96, 32%) of infectious complications were graded 3-4 according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. Details of patient age, subtype of VA, and timing of infection were lacking from many reports.
CONCLUSIONS
Most infectious complications reported in patients with VA on mTOR inhibitors were viral respiratory infections and non-severe. Bacteremia, infectious fatalities, and PJP are exceedingly rare. Future studies are needed to clarify the spectrum of infectious risks in VA patients and to provide guidance for infection prevention.
Topics: Infant; Humans; Sirolimus; Immunosuppressive Agents; Everolimus; Pneumonia, Pneumocystis; Vascular Malformations; TOR Serine-Threonine Kinases
PubMed: 37933207
DOI: 10.1002/pbc.30758 -
Open Forum Infectious Diseases Apr 2024The performance of chest x-ray (CXR) features for pneumonia (PCP) diagnosis has been evaluated in small studies. We conducted a systematic review and meta-analysis to...
BACKGROUND
The performance of chest x-ray (CXR) features for pneumonia (PCP) diagnosis has been evaluated in small studies. We conducted a systematic review and meta-analysis to describe CXR changes in adults with HIV-associated laboratory-confirmed PCP, comparing these with non-PCP respiratory disease.
METHODS
We searched databases for studies reporting CXR changes in people >15 years old with HIV and laboratory-confirmed PCP and those with non-PCP respiratory disease. CXR features were grouped using consensus terms. Proportions were pooled and odds ratios (ORs) generated using random-effects meta-analysis, with subgroup analyses by CD4 count, study period, radiology review method, and study region.
RESULTS
Fifty-one studies (with 1821 PCP and 1052 non-PCP cases) were included. Interstitial infiltrate (59%; 95% CI, 52%-66%; 36 studies, n = 1380; = 85%) and ground-glass opacification (48%; 95% CI, 15%-83%; 4 studies, n = 57; = 86%) were common in PCP. Cystic lesions, central lymphadenopathy, and pneumothorax were infrequent. Pleural effusion was rare in PCP (0%; 95% CI, 0%-2%). Interstitial infiltrate (OR, 2.3; 95% CI, 1.4-3.9; = 60%), interstitial-alveolar infiltrate (OR, 10.2; 95% CI, 3.2-32.4; = 0%), and diffuse CXR changes (OR, 7.3; 95% CI, 2.7-20.2; = 87%) were associated with PCP diagnosis. There was loss of association with alveolar infiltrate in African studies.
CONCLUSIONS
Diffuse CXR changes and interstitial-alveolar infiltrates indicate a higher likelihood of PCP. Pleural effusion, lymphadenopathy, and focal alveolar infiltrates suggest alternative causes. These findings could be incorporated into clinical algorithms to improve diagnosis of HIV-associated PCP.
PubMed: 38628951
DOI: 10.1093/ofid/ofae146 -
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 -
Medical Mycology Jun 2024This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to...
Features and global impact of invasive fungal infections caused by Pneumocystis jirovecii: A systematic review to inform the World Health Organization fungal priority pathogens list.
This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%-30%, while in studies of persons without HIV, mortality ranged from 4% to 76%. Risk factors for disease principally include immunosuppression from HIV, but other types of immunosuppression are increasingly recognised, including solid organ and haematopoietic stem cell transplantation, autoimmune and inflammatory disease, and chemotherapy for cancer. Although prophylaxis is available and generally effective, burdensome side effects may lead to discontinuation. After a period of decline associated with improvement in access to HIV treatment, new risk groups of immunosuppressed patients with PJP are increasingly identified, including solid organ transplant patients.
Topics: Humans; Pneumocystis carinii; Invasive Fungal Infections; World Health Organization; Immunocompromised Host; Risk Factors; Global Health; Pneumonia, Pneumocystis; Antifungal Agents; Incidence
PubMed: 38935910
DOI: 10.1093/mmy/myae038 -
PloS One 2024The epidemiology of Human Immunodeficiency Virus (HIV)-associated pneumocystosis (HAP) is poorly described on a worldwide scale. We searched related databases between... (Meta-Analysis)
Meta-Analysis
The epidemiology of Human Immunodeficiency Virus (HIV)-associated pneumocystosis (HAP) is poorly described on a worldwide scale. We searched related databases between January 2000 and December 2022 for studies reporting HAP. Meta-analysis was performed using StatsDirect (version 2.7.9) and STATA (version 17) according to the random-effects model for DerSimonian and Laird method and metan and metaprop commands, respectively. Twenty-nine studies with 38554 HIV-positive, 79893 HIV-negative, and 4044 HAP populations were included. The pooled prevalence of HAP was 35.4% (95% CI 23.8 to 47.9). In contrast, the pooled prevalence of PCP among HIV-negative patients was 10.16% (95% CI 2 to 25.3). HIV-positive patients are almost 12 times more susceptible to PCP than the HIV-negative population (OR: 11.710; 95% CI: 5.420 to 25.297). The mortality among HAP patients was 52% higher than non-PCP patients (OR 1.522; 95% CI 0.959 to 2.416). HIV-positive men had a 7% higher chance rate for PCP than women (OR 1.073; 95% CI 0.674 to 1.706). Prophylactic (OR: 6.191; 95% CI: 0.945 to 40.545) and antiretroviral therapy (OR 3.356; 95% CI 0.785 to 14.349) were used in HAP patients six and three times more than HIV-positive PCP-negatives, respectively. The control and management strategies should revise and updated by health policy-makers on a worldwide scale. Finally, for better management and understanding of the epidemiology and characteristics of this coinfection, designing further studies is recommended.
Topics: Male; Humans; Female; HIV; Pneumonia, Pneumocystis; Prevalence; HIV Infections; HIV Seropositivity
PubMed: 38526997
DOI: 10.1371/journal.pone.0297619