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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 -
Frontiers in Public Health 2021We performed a meta-analysis to systematically review the risk factors of mortality from non-HIV-related pneumonia (PcP) and provide the theoretical basis for managing... (Meta-Analysis)
Meta-Analysis
We performed a meta-analysis to systematically review the risk factors of mortality from non-HIV-related pneumonia (PcP) and provide the theoretical basis for managing non-HIV-related PcP. PubMed, Embase, Web of Science, the Cochrane Library and CNKI databases were searched. A meta-analysis of the risk factors of mortality from non-HIV-related PcP was conducted. A total of 19 studies and 1,310 subjects were retrieved and included in the meta-analysis, including 485 and 825 patients in the non-survivor and survivor groups, respectively. In the primary analysis, age, concomitant with other pulmonary diseases at diagnosis of PcP, solid tumors, cytomegalovirus(CMV) co-infection, lactate dehydrogenase (LDH), lymphocyte count, invasive ventilation during hospitalization, and pneumothorax were associated with mortality from non-HIV-related PcP, whereas sex, albumin, PcP prophylaxis, use of corticosteroids after admission, and time from onset of symptoms to treatment were not associated with mortality from non-HIV-related PcP. The mortality rate of non-HIV-infected patients with PcP was still high. Age, concomitant with other pulmonary diseases at diagnosis of PcP, solid tumors, CMV co-infection, LDH, lymphocyte count, invasive ventilation during hospitalization, and pneumothorax were risk factors of mortality from non-HIV-related PcP. Improved knowledge of prognostic factors is crucial to guide early treatment.
Topics: Coinfection; Cytomegalovirus Infections; Humans; Pneumocystis; Pneumonia, Pneumocystis; Risk Factors
PubMed: 34222179
DOI: 10.3389/fpubh.2021.680108 -
Journal of Fungi (Basel, Switzerland) Mar 2023Trimethoprim-sulfamethoxazole (TMP-SMX) is a first-line pneumonia (PCP) prophylaxis agent, but monthly intravenous pentamidine (IVP) is used in immunocompromised hosts... (Review)
Review
BACKGROUND
Trimethoprim-sulfamethoxazole (TMP-SMX) is a first-line pneumonia (PCP) prophylaxis agent, but monthly intravenous pentamidine (IVP) is used in immunocompromised hosts without human immunodeficiency virus (HIV) infection because IVP is not associated with cytopenia and delayed engraftment.
METHOD
We performed a systematic review and meta-analysis to estimate breakthrough PCP incidence and adverse reactions in HIV-uninfected immunocompromised patients receiving IVP. MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from their inception until 15 December 2022.
RESULTS
The pooled incidence of breakthrough PCP with IVP was 0.7% (95% CI, 0.3-1.4%, 16 studies, 3025 patients) and was similar when used as first-line prophylaxis (0.5%; 95% CI, 0.2-1.4%, 7 studies, 752 patients). The pooled incidence of adverse reactions was 11.3% (95% CI, 6.7-18.6%, 14 studies, 2068 patients). The pooled adverse event-related discontinuation was 3.7% (95% CI, 1.8-7.3%, 11 studies, 1802 patients), but was lower in patients receiving IVP monthly (2.0%; 95% CI 0.7-5.7%, 7 studies, 1182 patients).
CONCLUSION
Monthly IVP is an appropriate second-line agent for PCP prophylaxis in certain non-HIV immunocompromised hosts, especially in patients with hematologic malignancies and hematopoietic stem cell transplant recipients. Using IVP for PCP prophylaxis as an alternative to oral TMP-SMX while patients are unable to tolerate enteral medication administration is feasible.
PubMed: 37108861
DOI: 10.3390/jof9040406 -
Journal of Global Health Feb 2023Knowledge of the risk factors for and causes of treatment failure and mortality in childhood pneumonia is important for prevention, diagnosis, and treatment at an...
BACKGROUND
Knowledge of the risk factors for and causes of treatment failure and mortality in childhood pneumonia is important for prevention, diagnosis, and treatment at an individual and population level. This review aimed to identify the most important risk factors for mortality among children aged under ten years with pneumonia.
METHODS
We systematically searched MEDLINE, EMBASE, and PubMed for observational and interventional studies reporting risk factors for mortality in children (aged two months to nine years) in low- and middle-income countries (LMICs). We screened articles according to specified inclusion and exclusion criteria, assessed risk of bias using the EPHPP framework, and extracted data on demographic, clinical, and laboratory risk factors for death. We synthesized data descriptively and using Forest plots and did not attempt meta-analysis due to the heterogeneity in study design, definitions, and populations.
FINDINGS
We included 143 studies in this review. Hypoxaemia (low blood oxygen level), decreased conscious state, severe acute malnutrition, and the presence of an underlying chronic condition were the risk factors most strongly and consistently associated with increased mortality in children with pneumonia. Additional important clinical factors that were associated with mortality in the majority of studies included particular clinical signs (cyanosis, pallor, tachypnoea, chest indrawing, convulsions, diarrhoea), chronic comorbidities (anaemia, HIV infection, congenital heart disease, heart failure), as well as other non-severe forms of malnutrition. Important demographic factors associated with mortality in the majority of studies included age <12 months and inadequate immunisation. Important laboratory and investigation findings associated with mortality in the majority of studies included: confirmed Pneumocystis jirovecii pneumonia (PJP), consolidation on chest x-ray, pleural effusion on chest x-ray, and leukopenia. Several other demographic, clinical and laboratory findings were associated with mortality less consistently or in a small numbers of studies.
CONCLUSIONS
Risk assessment for children with pneumonia should include routine evaluation for hypoxaemia (pulse oximetry), decreased conscious state (e.g. AVPU), malnutrition (severe, moderate, and stunting), and the presence of an underlying chronic condition as these are strongly and consistently associated with increased mortality. Other potentially useful risk factors include the presence of pallor or anaemia, chest indrawing, young age (<12 months), inadequate immunisation, and leukopenia.
Topics: Humans; Child; Infant; Developing Countries; HIV Infections; Pallor; Pneumonia; Risk Factors; Malnutrition; Hypoxia
PubMed: 36825608
DOI: 10.7189/jogh.13.05003 -
Antibiotics (Basel, Switzerland) May 2022Although combination therapy using trimethoprim-sulfamethoxazole (TMP-SMX) plus echinocandins has been reported to reduce the mortality of patients with pneumocystis...
Efficacy of Trimethoprim-Sulfamethoxazole in Combination with an Echinocandin as a First-Line Treatment Option for Pneumocystis Pneumonia: A Systematic Review and Meta-Analysis.
Although combination therapy using trimethoprim-sulfamethoxazole (TMP-SMX) plus echinocandins has been reported to reduce the mortality of patients with pneumocystis pneumonia (PCP), it remains unclear whether it is more effective than TMP-SMX monotherapy, the current first-line treatment for this disease. Hence, we performed a systematic review and meta-analysis to compare the efficacies of these treatment options for PCP. The Scopus, EMBASE, PubMed, CINAHL, and Ichushi databases were searched for studies (up to January 2022) reporting the mortality and positive response rates (fewer clinical symptoms, improved partial pressure of arterial oxygen, and resolution of pneumonitis on chest imaging) of PCP patients receiving monotherapy or combination therapy. Four studies met the inclusion criteria. All four presented mortality data and one had positive response rates. Compared with the monotherapy, the combination therapy resulted in significantly lower mortality and higher positive response rates (mortality: odds ratio (OR) 2.20, 95% confidence interval (CI) 1.46-3.31; positive response rate: OR 2.13, 95%CI 1.41-3.23), suggesting it to be an effective and promising first-line therapy for PCP. However, further safety evaluations are needed to establish this as a fact.
PubMed: 35740126
DOI: 10.3390/antibiotics11060719 -
Frontiers in Endocrinology 2023Hypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical...
OBJECTIVE
Hypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical characteristics, risk factors, treatment, and prognosis of TMP-SMX-induced hypoglycemia.
METHODS
Case reports and series of TMP-SMX-induced hypoglycemia were systematically searched using Chinese and English databases. Primary patient and clinical information were extracted for analysis.
RESULTS
A total of 34 patients were reported from 31 studies (16 males and 18 females). The patients had a median age of 64 years (range 0.4-91), and 75.8% had renal dysfunction. The median duration of a hypoglycemic episode was six days (range 1-20), and the median minimum glucose was 28.8 mg/dL (range 12-60). Thirty-two patients (97.0%) showed neuroglycopenic symptoms, with consciousness disturbance (30.3%) and seizure (24.2%), sweating (18.2%), confusion (15.2%), asthenia (12.1%) being the most common symptoms. Fifteen patients (44.1%) had elevated serum insulin levels, with a median of 31.8 μU/mL (range 3-115.3). C-peptide increased in 13 patients (38.2%), with a median of 7.7 ng/mL (range 2.2-20). Complete recovery from symptoms occurred in 88.2% of patients without sequelae. The duration of hypoglycemia symptoms was 8 hours to 47 days after the intervention. Interventions included discontinuation of TMP-SMX, intravenous glucose, glucagon, and octreotide.
CONCLUSION
Hypoglycemia is a rare and serious adverse effect of TMP-SMX. Physicians should be aware of this potential adverse effect, especially in patients with renal insufficiency, increased drug doses, and malnutrition.
Topics: Male; Female; Humans; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Trimethoprim, Sulfamethoxazole Drug Combination; Risk Factors; Hypoglycemia; Renal Insufficiency; Glucose
PubMed: 36843590
DOI: 10.3389/fendo.2023.1059522 -
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 -
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 -
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 Journal of International Medical... Mar 2022The aim of this study was to describe the clinical characteristics and prognostic factors of patients treated with rituximab (RTX) who developed severe pneumonia in the...
OBJECTIVE
The aim of this study was to describe the clinical characteristics and prognostic factors of patients treated with rituximab (RTX) who developed severe pneumonia in the intensive care unit (ICU).
METHODS
We systematically reviewed the medical records of 40 patients who received RTX and developed severe pneumonia in the ICU at our hospital from January 2009 to January 2019 to evaluate the underlying conditions, clinical course, and possible prognostic factors.
RESULTS
Most patients had underlying hematologic malignancies (n = 21, 52.5%), followed by rheumatologic diseases (n = 17, 42.5%). The most frequent causative pathogens were fungi (n = 11, 27.5%), followed by bacteria (n = 9, 22.5%) and pneumonia (n = 8, 20%). Thirty patients (75%) died, and the other 10 patients (25%) survived. Compared with survivors, patients who died were significantly older (60.6 ± 10.6 vs 44.4 ± 18.3 years) and had chronic lung disease (40% vs 0%).
CONCLUSION
Older age and chronic lung disease were significantly associated with mortality in patients treated with RTX.
Topics: Humans; Intensive Care Units; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Rituximab
PubMed: 35350908
DOI: 10.1177/03000605211063281