-
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 -
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 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 -
Frontiers in Pharmacology 2022Interstitial lung disease (ILD) is a common pulmonary disease often associated with significant morbidity and mortality in patients with connective tissue diseases...
Interstitial lung disease (ILD) is a common pulmonary disease often associated with significant morbidity and mortality in patients with connective tissue diseases (CTD). Currently, no gold-standard therapies are available for CTD-ILD. Recently, several studies have proposed that rituximab (RTX) may be effective for the treatment of CTD-ILD. This study aimed to systematically evaluate the efficacy and safety of RTX for the treatment of CTD-ILD. Studies were selected from PubMed, Embase, and Cochrane Library, up to 20 July 2022. Improvement and stable rates were extracted as the main outcomes and pooled using the weighted mean proportion with fixed or random-effects models, in case of significant heterogeneity ( > 50%). Safety analysis was performed based on the adverse events reported in all of the studies. Thirteen studies (312 patients) were included in the meta-analysis. The follow-up durations ranged from 6 to 36 months. The pooled improvement rate was 35.0% (95% CI: 0.277-0.442), while the pooled stable rate was 59.2% (95% CI: 0.534-0.656). Anti-synthetase syndrome associated with ILD [ASS-ILD, 48.1% (95% CI, 0.373-0.620)] and idiopathic inflammatory myopathies associated with ILD [IIM-ILD, non-ASS, 47.4% (95% CI, 0.266-0.846)] had higher improvement rates than the other types. A total of 106 adverse events associated with RTX or progressive ILD were reported among the 318 patients, 55.7% of which were mild. Among 19 deaths, 17 were due to ILD progression, one to severe pulmonary arterial hypertension, and one to infection. RTX, which exhibits a satisfactory safety profile, is an effective treatment option for CTD-ILD, even in patients who fail to respond to other therapies. Further randomized trials are needed to assess the efficacy of rituximab compared to other treatments for CTD-ILD. PROSPERO, identifier (CRD42022363403).
PubMed: 36386239
DOI: 10.3389/fphar.2022.1019915 -
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 -
Seminars in Arthritis and Rheumatism Feb 2023Pneumocystis jiroveci pneumonia (PJP) is an opportunistic fungal infection that affects immunocompromised patients. The objective of this study was to describe the...
BACKGROUND
Pneumocystis jiroveci pneumonia (PJP) is an opportunistic fungal infection that affects immunocompromised patients. The objective of this study was to describe the incidence of PJP among patients with giant cell arteritis (GCA) or polymyalgia rheumatica (PMR).
METHODS
A retrospective cohort study of incident cases of GCA and PMR was conducted using claims data from the TriNetX database to describe the incidence of PJP during the first 6 months of therapy. Additionally, a systematic review was performed to identify other publications describing PJP among patients with GCA or PMR.
RESULTS
During 547 patient-years of follow-up time, no cases of PJP were identified among 1,168 cases of GCA (incident rate 0 per 1,000 person-years); during 7,446 patient-years of follow up time, one case of PJP was identified out of 15,575 cases of PMR (incident rate 0.07 cases per 1,000 patient-years). This patient was alive at last follow up. Our systematic review identified 1 case-control study, 4 cohort studies, and 18 case series / case reports of PJP among patients with GCA or PMR. The incident rate of PJP was reported from one additional study for GCA and was estimated at 0.08 cases per 1,000 person years; no additional cohort studies were identified for patients with PMR. Over the entirety of the published literature, the total number of cases identified among case series and case reports was 33, from which 4 total deaths were identified.
CONCLUSIONS
Patients with newly diagnosed GCA or PMR rarely develop PJP. Existing data does not support routine prescribing of PJP prophylaxis for either group of patients.
Topics: Humans; Giant Cell Arteritis; Polymyalgia Rheumatica; Pneumocystis carinii; Case-Control Studies; Retrospective Studies; Pneumonia, Pneumocystis
PubMed: 36563422
DOI: 10.1016/j.semarthrit.2022.152154 -
Respiratory Investigation Jan 2020We evaluated immune reconstitution inflammatory syndrome (IRIS) in the lung in non-human immunodeficiency virus (HIV) patients.
BACKGROUND
We evaluated immune reconstitution inflammatory syndrome (IRIS) in the lung in non-human immunodeficiency virus (HIV) patients.
METHODS
We reviewed articles related to IRIS occurrence in the lung in non-HIV patients using a PubMed search. The keywords used for the search were "immune reconstitution syndrome" and "non-HIV." Only patients with lung involvement were included. Those with suggested IRIS caused by white blood cell recovery were excluded.
RESULTS
There were 37 cases of IRIS in the lung in non-HIV patients. Complicating infections included tuberculosis (n = 17), histoplasmosis (n = 9), aspergillosis (n = 5), cryptococcosis (n = 4), and Pneumocystis pneumonia (n = 2). We also evaluated the underlying diseases, IRIS pathogenesis, management, and prognosis. IRIS was most commonly encountered in patients treated with anti-tumor necrosis factor (TNF) antibody who developed disseminated or extrapulmonary tuberculosis, leading to treatment discontinuation.
CONCLUSIONS
The diagnosis and management of IRIS in the lung in non-HIV patients should be investigated further, especially in the era of anti-TNF treatment.
Topics: Humans; Immune Reconstitution Inflammatory Syndrome; Tumor Necrosis Factor-alpha
PubMed: 31791908
DOI: 10.1016/j.resinv.2019.11.001 -
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 -
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 -
International Journal of Rheumatic... Jul 2021Systemic lupus erythematosus (SLE) is a more common autoimmune rheumatic disease in the Asia-Pacific region. The prognosis of SLE remains unsatisfactory in some Asian...
Systemic lupus erythematosus (SLE) is a more common autoimmune rheumatic disease in the Asia-Pacific region. The prognosis of SLE remains unsatisfactory in some Asian countries because of delayed diagnosis, limited access to medications, increased complications and issues of tolerability and adherence to treatment. The Asia-Pacific League of Associations for Rheumatology SLE special interest group has recently published a set of consensus recommendations on the management of SLE for specialists, family physicians, specialty nurses, and other healthcare professionals in the Asia-Pacific region. This article reports a systematic literature review of the infective complications of SLE in Asia and evidence for prevention of these infections by pre-emptive antimicrobial therapy and vaccination.
Topics: Anti-Infective Agents; Consensus; Humans; Immunocompromised Host; Lupus Erythematosus, Systemic; Opportunistic Infections; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Treatment Outcome; Vaccination
PubMed: 33999518
DOI: 10.1111/1756-185X.14125