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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 -
OBM Genetics 2018Over the past decade, there has been rising interest in the interaction of with the environment. This interest has arisen in part from the demonstration that...
BACKGROUND
Over the past decade, there has been rising interest in the interaction of with the environment. This interest has arisen in part from the demonstration that environmental factors have important effects on the viability and transmission of microbes, including . Environmental factors include climatological factors such as temperature, humidity, and precipitation, and air pollution factors including carbon monoxide, nitrogen dioxide, sulfur dioxide, and particulate matter.
METHODS
We undertook a systematic review in order to identify environmental factors associated with infection or PCP, and their effects on human and animal hosts.
RESULTS
The systematic review found evidence of associations between infection in animal and human hosts, and climatological and air pollution factors. Data from human studies infers that rather than a seasonal association, presentation with PCP appears to be highest when the average temperature is between 10 and 20°C. There was evidence of an association with hospitalization with PCP and ambient air pollution factors, as well as evidence of an effect of air pollution on both systemic and bronchoscopic lavage fluid humoral responses to . Interpretation of human studies was confounded by possible genetically-determined predisposition to, or protection from infection.
CONCLUSIONS
This systematic review provides evidence of associations between infection in both animal and human hosts, and climatological and environmental air pollution factors. This information may lead to an improved understanding of the conditions involved in transmission of in both animal and human hosts. Such knowledge is critical to efforts aimed at prevention.
PubMed: 30815637
DOI: 10.21926/obm.genet.1804045 -
Journal of Infection in Developing... Oct 2018Pneumocystis jirovecii (PJ) pneumonia (PJP) is an important opportunistic infection affecting various types of immunocompromised patients and is associated with an...
INTRODUCTION
Pneumocystis jirovecii (PJ) pneumonia (PJP) is an important opportunistic infection affecting various types of immunocompromised patients and is associated with an increased risk of mortality. PJ is a unique fungal pathogen which is increasingly common and maybe associated with a higher mortality rate in patients without AIDS. We present the characteristics of PJP, diagnosis, and treatment outcomes between AIDS and non-AIDS patients.
METHODOLOGY
We conducted a review of studies of AIDS and non-AIDS patients with PJP using PubMed to search for studies until December 2017.
RESULTS
The annual incidence of AIDS-PJP decreased from 13.4 to 3.3 per 1000 person-years in industrialized countries, while the incidence of non-AIDS-PJP varied widely. Both groups had similar clinical manifestations and radiological features, but the non-AIDS-PJP group potentially had a more fulminant course, more diffuse ground glass opacities, and fewer cystic lesions. The mortality rate decreased in the AIDS-PJP group after the advent of antiretroviral therapy; however, the mortality rate remained high in both groups. A laboratory diagnosis was usually nonspecific; CD4+ T-cell < 200 cells/mL or < 14% favored AIDS-PJP. Serum 1,3-β-D-glucan (BDG) had a high diagnostic odds ratio. Combining BDG and lactic dehydrogenase improved the diagnosis of AIDS-PJP. Histopathological staining and polymerase chain reactions could not discriminate infection from colonization when the result was positive. The use of antibiotics, prophylaxis, and adjunctive corticosteroids was controversial.
CONCLUSIONS
Early diagnosis and treatment can be achieved through vigilance, thereby improving the survival rate for PJP in immunocompromised patients.
Topics: AIDS-Related Opportunistic Infections; Case-Control Studies; Early Diagnosis; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Survival Rate
PubMed: 32004150
DOI: 10.3855/jidc.10357 -
American Journal of Hematology Mar 2018Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of... (Meta-Analysis)
Meta-Analysis
Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of estimating the risk of infections in patients treated with ruxolitinib. Studies were identified by electronic search of MEDLINE and EMBASE database. Differences in the incidence of infectious events between ruxolitinib and comparison groups were expressed as odds ratios (ORs) and 95% confidence intervals (95% CI). Five phase III randomized clinical trials (RCTs) (3 phase IIIa with their extended phase and 2 phase IIIb), 6 phase IV studies and 28 case reports were included in this systematic review. Ruxolitinib was associated with a statistically significant increased risk of herpes zoster infection compared to control group in 3 RCTs including patients with polycythemia vera (OR 7.39 [1.33, 41.07]) and in a pooled analysis of the extended phase IIIa RCTs (OR 5.20 [95%CI 1.27, 21.18]). In the larger phase IV post-marketing study, the incidence of the most frequent infections was 8% for herpes zoster, 6.1% for bronchitis and 6% for urinary tract infections. In the published case reports, the most frequent infections were tuberculosis (N = 10), hepatitis B reactivation (N = 5) and pneumocystis jeroveci infection (N = 2). Evidence is not solid enough to accurately estimate the risk of infection in ruxolitinib-treated patients. However, published data clearly suggest that the infection risk may be clinically relevant. Well-designed studies are warranted to evaluate the risk of ruxolitinib-associated infection, in order to identify the most appropriate antimicrobial prophylactic strategy.
Topics: Antibiotic Prophylaxis; Bacterial Infections; Clinical Trials, Phase III as Topic; Confidence Intervals; Disease Susceptibility; Herpes Zoster; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Infections; Janus Kinase 1; Janus Kinase 2; Mycoses; Nitriles; Odds Ratio; Product Surveillance, Postmarketing; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Risk
PubMed: 29150886
DOI: 10.1002/ajh.24976 -
Open Access Macedonian Journal of... Apr 2017Methotrexate (MTX) is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA); however, it causes many side effects, including... (Review)
Review
BACKGROUND
Methotrexate (MTX) is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA); however, it causes many side effects, including pulmonary lesions. In this review, we characterised the histopathological features of MTX-induced pulmonary lesions in RA patients.
AIM
We carried out an electronic search of the relevant literature published during the period from 1990 to 2016. We included only the cases with definitive histo-pathological findings caused by MTX therapy.
MATERIAL AND METHODS
The total number of cases is 27. Male: female ratio was 1:3, and ages ranged from 48 to 87 years old, with a mean (SD) = 65.7 (1.0). The cases were originally from Asia (55%), Europe (41%), and America (4%). The major complications of methotrexate therapy were lymphoproliferative disorders (42%) followed by interstitial fibrosis (33), and infections (25%). The incidence of these complications significantly increases with the duration of MTX treatment (p = 0.044). Among the infections, the most common causative organism was pneumocystis jiroveci. The majority of patients who developed infections following methotrexate therapy were from Europe whereas the majority of those who developed lymphoproliferative disorders were from Asia (p = 0.003).
CONCLUSION
In conclusion, methotrexate therapy in rheumatoid arthritis patients causes different types pulmonary complications.
PubMed: 28507640
DOI: 10.3889/oamjms.2017.049 -
Transplantation Direct Mar 2017Randomized trials show a mortality benefit to adjunctive corticosteroids for human immunodeficiency virus (HIV)-related pneumonia (HIV-PCP). Guidelines for non-HIV PCP...
BACKGROUND
Randomized trials show a mortality benefit to adjunctive corticosteroids for human immunodeficiency virus (HIV)-related pneumonia (HIV-PCP). Guidelines for non-HIV PCP (NH-PCP) recommend adjunctive corticosteroids based on expert opinion. We conducted a systematic review and meta-analysis characterizing adjunctive corticosteroids for NH-PCP.
METHODS
We searched MEDLINE from 1966 through 2015. Data on clinical outcomes from NH-PCP were extracted with a standardized instrument. Heterogeneity was assessed with the I index. Pooled odds ratios and 95% confidence interval were calculated using a fixed effects model.
RESULTS
Our search yielded 5044 abstracts, 277 articles were chosen for full review, and 6 articles described outcomes in moderate to severe NH-PCP. Studies were limited by variable definitions, treatment selection bias, concomitant infections and small sample size. Individual studies reported shorter intensive care unit stay and duration of mechanical ventilation of patients given adjunctive corticosteroids. There was no association between corticosteroids and survival in NH-PCP (odds ratio, 0.66; 95% confidence interval, 0.38-1.15; = 0.14).
CONCLUSIONS
The literature does not support an association between adjunctive corticosteroids and survival from NH-PCP but data are limited and findings should not be considered conclusive. Further research with improved methodology is needed to better understand the role of adjunctive corticosteroids for NH-PCP.
PubMed: 28361121
DOI: 10.1097/TXD.0000000000000642 -
BMC Infectious Diseases Sep 2016Seroprevalence data and clinical studies in children suggest that the burden of pneumocystis pneumonia (PCP) in Africa may be underestimated. We performed a systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Seroprevalence data and clinical studies in children suggest that the burden of pneumocystis pneumonia (PCP) in Africa may be underestimated. We performed a systematic review to determine the prevalence and attributable mortality of PCP amongst HIV-infected adults in sub-Saharan Africa.
METHODS
We searched Pubmed, Web of Science, Africa-Wide: NiPAD and CINAHL, from Jan 1 1995 to June 1 2015, for studies that reported the prevalence, mortality or case fatality of PCP in HIV-infected adults living in sub-Saharan African countries. Prevalence data from individual studies were combined by random-effects meta-analysis according to the Mantel-Haenszel method. Data were stratified by clinical setting, diagnostic method, and study year.
RESULTS
We included 48 unique study populations comprising 6884 individuals from 18 countries in sub-Saharan Africa. The pooled prevalence of PCP among 6018 patients from all clinical settings was 15 · 4 % (95 % CI 12 · 9-18 · 0), and was highest amongst inpatients, 22 · 4 % (95 % CI 17 · 2-27 · 7). More cases were identified by bronchoalveolar lavage, 21 · 0 % (15 · 0-27 · 0), compared with expectorated, 7 · 7 % (4 · 4-11 · 1), or induced sputum, 11 · 7 % (4 · 9-18 · 4). Polymerase chain reaction (PCR) was used in 14 studies (n = 1686). There was a trend of decreasing PCP prevalence amongst inpatients over time, from 28 % (21-34) in the 1990s to 9 % (8-10) after 2005. The case fatality rate was 18 · 8 % (11 · 0-26 · 5), and PCP accounted for 6 · 5 % (3 · 7-9 · 3) of study deaths.
CONCLUSIONS
PCP is an important opportunistic infection amongst HIV-infected adults in sub-Saharan Africa, particularly amongst patients admitted to hospital. Although prevalence appears to be decreasing, improved access to antiretroviral therapy and non-invasive diagnostics, such as PCR, are needed.
Topics: AIDS-Related Opportunistic Infections; Africa; Africa South of the Sahara; HIV Infections; Humans; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prevalence; Seroepidemiologic Studies; Sputum
PubMed: 27612639
DOI: 10.1186/s12879-016-1809-3 -
Clinical Infectious Diseases : An... Jun 2016To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral... (Meta-Analysis)
Meta-Analysis Review
Incidence of Opportunistic Infections and the Impact of Antiretroviral Therapy Among HIV-Infected Adults in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis.
BACKGROUND
To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral therapy (ART) on incidence of key opportunistic infections (OIs) in human immunodeficiency virus (HIV)-infected adults in low- and middle-income countries (LMICs).
METHODS
Eligible studies describing the cumulative incidence of OIs and proportion on ART from 1990 to November 2013 were identified using multiple databases. Summary incident risks for the ART-naive period, and during and after the first year of ART, were calculated using random-effects meta-analyses. Summary estimates from ART subgroups were compared using meta-regression. The number of OI cases and associated costs averted if ART was initiated at a CD4 count ≥200 cells/µL were estimated using Joint United Nations Programme on HIV/AIDS (UNAIDS) country estimates and global average OI treatment cost per case.
RESULTS
We identified 7965 citations, and included 126 studies describing 491 608 HIV-infected persons. In ART-naive patients, summary risk was highest (>5%) for oral candidiasis, tuberculosis, herpes zoster, and bacterial pneumonia. The reduction in incidence was greatest for all OIs during the first 12 months of ART (range, 57%-91%) except for tuberculosis, and was largest for oral candidiasis, Pneumocystis pneumonia, and toxoplasmosis. Earlier ART was estimated to have averted 857 828 cases in 2013 (95% confidence interval [CI], 828 032-874 853), with cost savings of $46.7 million (95% CI, $43.8-$49.4 million).
CONCLUSIONS
There was a major reduction in risk for most OIs with ART use in LMICs, with the greatest effect seen in the first year of treatment. ART has resulted in substantial cost savings from OIs averted.
Topics: AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Developing Countries; HIV Infections; Humans; Incidence; Tuberculosis
PubMed: 26951573
DOI: 10.1093/cid/ciw125 -
Journal of Thoracic Disease Dec 2015The (1-3)-β-D-Glucan (BG) assay has been approved for making a diagnosis of invasive fungal disease. However, the role of serum-BG assay for the diagnosis of...
BACKGROUND
The (1-3)-β-D-Glucan (BG) assay has been approved for making a diagnosis of invasive fungal disease. However, the role of serum-BG assay for the diagnosis of pneumocystis pneumonia (PCP) is controversial, especially between patients with human immunodeficiency virus (HIV) and non-HIV. We conducted a meta-analysis to determine the difference of the overall accuracy of serum-BG assay for the diagnosis of PCP in immunocompromised patients with and without HIV.
METHODS
After a systematic review of English-language studies and manual researching, sensitivity (Se), specificity (Sp), and other measures of accuracy of serum-BG for the diagnosis of PCP were pooled using random-effects models for bivariate meta-analysis. Summary receiver operating characteristic (SROC) curve was used to summarize overall test performance. Subgroup analyses were performed to explore the heterogeneity in Se and Sp.
RESULTS
Thirteen studies met our inclusion criteria. The summary estimates for serum-BG assay for definite PCP were as follows: Se, 0.91 [95% confidence interval (CI), 0.88-0.93]; Sp, 0.75 (95% CI, 0.68-0.81). As for the patients with and without HIV, the Se and Sp were 0.92 and 0.78, 0.85 and 0.73, respectively. Significant heterogeneity between Se was presented (P=0.04).
CONCLUSIONS
Contrary to the results of the previous meta-analysis, a negative result of serum-BG determination is sufficient for ruling out PCP only in HIV cases. For non-HIV patients, the results should be interpreted in parallel with clinical and radiological findings. Besides, further prospective studies with larger sample size are needed to confirm the diagnosis strategy of BG detection.
PubMed: 26793343
DOI: 10.3978/j.issn.2072-1439.2015.12.27 -
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