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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 -
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 -
Transplant Infectious Disease : An... Apr 2017In recent years, the incidence of Pneumocystis jirovecii pneumonia (PJP) has increased in immunocompromised patients without human immunodeficiency virus (HIV)... (Review)
Review
The role of CD4 cell count as discriminatory measure to guide chemoprophylaxis against Pneumocystis jirovecii pneumonia in human immunodeficiency virus-negative immunocompromised patients: A systematic review.
BACKGROUND
In recent years, the incidence of Pneumocystis jirovecii pneumonia (PJP) has increased in immunocompromised patients without human immunodeficiency virus (HIV) infection. Chemoprophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is highly effective in preventing PJP in both HIV-positive and -seronegative patients. In HIV-positive patients, the risk of PJP is strongly correlated with decreased CD4 cell count. The role of CD4 cell count in the pathogenesis of PJP in non-HIV immunocompromised patients is less well studied. For most immunosuppressive conditions, no clear guidelines indicate whether to start TMP-SMX.
METHOD
We conducted a systematic literature review with the aim to provide a comprehensive overview on the role of CD4 cell counts in managing the risk of PJP in HIV-seronegative patients.
RESULTS
Of the 63 individual studies retrieved, 14 studies report on CD4 cell counts in a variety of immunosuppressive conditions. CD4 cell count were <200/μL in 73.1% of the patients.
CONCLUSION
CD4 cell count <200/μL is a sensitive biomarker to identify non-HIV immunocompromised patients who are at risk for PJP. Measuring CD4 cell counts could help clinicians identify patients who may benefit from TMP-SMX prophylaxis.
Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotic Prophylaxis; CD4 Lymphocyte Count; HIV Seronegativity; Humans; Immunocompromised Host; Kidney Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 28035717
DOI: 10.1111/tid.12651 -
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 -
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... Sep 2015Lower respiratory tract infections (LRTIs) in young children account for 1.4 million deaths annually worldwide. Antibiotics could be beneficial in preventing LRTIs in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lower respiratory tract infections (LRTIs) in young children account for 1.4 million deaths annually worldwide. Antibiotics could be beneficial in preventing LRTIs in high-risk children, and may also help prevent school absenteeism and work days missed by children and/or carers. While it is well documented that the efficacy of antibiotic prophylaxis for RTIs decreases over time, there are no reviews that describe the use of antibiotic prophylaxis to prevent LRTIs in high-risk children aged 12 years and under.
OBJECTIVES
To assess the effectiveness and safety of antibiotic prophylaxis in the prevention of bacterial LRTIs in high-risk children aged 12 years and under.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 1) and the Database of Abstracts of Reviews of Effects (DARE), MEDLINE and MEDLINE In-Process (OvidSP) (1946 to 13 February 2015), EMBASE (OvidSP) (1974 to 12 February 2015), Science Citation Index Expanded (1945 to 13 February 2015) and Conference Proceedings Citation Index-Science (Web of Science Core Collection) (1990 to 13 February 2015). We searched for ongoing studies on ClinicalTrials.gov and the World Health Organization ICTRP. We handsearched the bibliographies of retrieved full texts of relevant studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing oral or intravenous antibiotics versus placebo or no treatment to prevent infections in high-risk children aged 12 years and under. We used a combination of the Centers for Disease Control and Prevention (CDC), National Health Service (NHS), American Academy of Paediatrics (AAP) and National Institute for Health and Care Excellence (NICE) guidelines to define conditions at higher risk of complications. Our primary outcome was the incidence of bacterial lower respiratory infections. Secondary outcomes included clinical function, hospital admission, mortality, growth, use of secondary antibiotics, time off school or parental work, quality of life and adverse events.
DATA COLLECTION AND ANALYSIS
We extracted data using a customised data extraction sheet, assessed the risk of bias of included studies using the Cochrane 'Risk of bias' criteria, and used the GRADE criteria to rate the quality of the evidence. We used a random-effects model for meta-analysis. We presented the results narratively where we could not statistically combine data.
MAIN RESULTS
We included 10 RCTs of high-risk children using antibiotics (azithromycin, ciprofloxacin, co-trimoxazole, isoniazid, oral penicillin V or vancomycin) to prevent LRTIs. Three studies included HIV-infected children (n = 1345), four cystic fibrosis (n = 429) and one each sickle cell disease (n = 219), cancer (n = 160) and low birth weight neonates with underlying respiratory disorders (n = 40). The study duration ranged from seven days to three years. The quality of the evidence from studies including children with HIV infection, cystic fibrosis or cancer was moderate. Due to inadequate data, we were unable to rate the quality of the evidence for two studies: one in children with sickle cell disease (low risk of bias), and another in low birth weight neonates with underlying respiratory disorders (high risk of bias).In HIV-infected children receiving continuous isoniazid prophylaxis, there was no significant difference in the incidence of pulmonary tuberculosis (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.32 to 1.29, I(2) statistic = 47%, P value = 0.21). There was no significant effect on mortality with co-trimoxazole or isoniazid prophylaxis (RR 0.82, 0.46 to 1.46, I(2) statistic = 76%, P value = 0.58); however, analysis of one study that used co-trimoxazole showed a significant reduction in mortality (RR 0.67, 95% CI 0.53 to 0.85, P value = 0.001). There was a significant decrease in the rates of hospital admission per child-year of follow-up with co-trimoxazole prophylaxis in one study (P value = 0.01). There was no evidence of increased adverse events due to antibiotic prophylaxis (RR 1.10, 95% CI 0.75 to 1.64, I(2) statistic = 22%, P value = 0.28); however, there was scant reporting of antibiotic resistance - the one study that did assess this found no increase.In two studies of children with cystic fibrosis receiving ciprofloxacin prophylaxis, there was no significant difference in Pseudomonas infections (RR 0.76, 0.44 to 1.31, I(2) statistic = 0%, P value = 0.33). In two studies assessing the benefit of azithromycin prophylaxis, there was a significant reduction in the frequency of pulmonary exacerbations (RR 0.60, 95% CI 0.48 to 0.76, I(2) statistic = 0%, P value < 0.0001). The effect of antibiotic prophylaxis on growth in children with cystic fibrosis was inconsistent across the studies. There was an increased risk of emergence of pathogenic strains with either azithromycin or ciprofloxacin prophylaxis in two studies reporting this outcome. There was no significant difference in the quality of life (one study). In three studies, there was no significant increase in the frequency of adverse events with prophylaxis with azithromycin (two studies) or ciprofloxacin (one study). There was no evidence of increased antibiotic resistance in two studies.In the one study of children with sickle cell disease, a significantly lesser proportion of children with pneumococcal septicaemia was reported with penicillin V prophylaxis (P value = 0.0025).In the one study of children with cancer there was a significant decrease in Pneumocystis carinii pneumonia with trimethoprim-sulfamethoxazole prophylaxis (RR 0.03, 95% CI 0.00 to 0.47, P value < 0.01). There was no significant increase in the frequency of adverse events with antibiotic prophylaxis.In low birth weight children with underlying respiratory disorders, there was no significant difference in the proportion of children with pulmonary infection with vancomycin prophylaxis (P value = 0.18).No included studies reported time off school or carer time off work.
AUTHORS' CONCLUSIONS
There is inconclusive evidence that antibiotic prophylaxis in certain groups of high-risk children can reduce pneumonia, exacerbations, hospital admission and mortality in certain conditions. However, limitations in the evidence base mean more clinical trials assessing the effectiveness of antibiotics for preventing LRTIs in children at high risk should be conducted. Specifically, clinical trials assessing the effectiveness of antibiotics for preventing LRTIs in congenital heart disease, metabolic disease, endocrine and renal disorders, neurological disease or prematurity should be a priority.
Topics: Anemia, Sickle Cell; Anti-Bacterial Agents; Child; Child, Preschool; Cystic Fibrosis; HIV Infections; Humans; Infant; Infant, Newborn; Randomized Controlled Trials as Topic; Respiratory Tract Infections
PubMed: 26408070
DOI: 10.1002/14651858.CD011530.pub2 -
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