-
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 -
The American Journal of Tropical... May 2024Surveillance for genetic markers of resistance can provide valuable information on the likely efficacy of antimalarials but needs to be targeted to ensure optimal use of...
Surveillance for genetic markers of resistance can provide valuable information on the likely efficacy of antimalarials but needs to be targeted to ensure optimal use of resources. We conducted a systematic search and review of publications in seven databases to compile resistance marker data from studies in India. The sample collection from the studies identified from this search was conducted between 1994 and 2020, and these studies were published between 1994 and 2022. In all, Plasmodium falciparum Kelch13 (PfK13), P. falciparum dihydropteroate synthase, and P. falciparum dihydrofolate reductase (PfDHPS) genotype data from 2,953, 4,148, and 4,222 blood samples from patients with laboratory-confirmed malaria, respectively, were extracted from these publications and uploaded onto the WorldWide Antimalarial Resistance Network molecular surveyors. These data were fed into hierarchical geostatistical models to produce maps with a predicted prevalence of the PfK13 and PfDHPS markers, and of the associated uncertainty. Zones with a predicted PfDHPS 540E prevalence of >15% were identified in central, eastern, and northeastern India. The predicted prevalence of PfK13 mutants was nonzero at only a few locations, but were within or adjacent to the zones with >15% prevalence of PfDHPS 540E. There may be a greater probability of artesunate-sulfadoxine-pyrimethamine failures in these regions, but these predictions need confirmation. This work can be applied in India and elsewhere to help identify the treatments most likely to be effective for malaria elimination.
Topics: Plasmodium falciparum; Pyrimethamine; Sulfadoxine; India; Drug Resistance; Antimalarials; Drug Combinations; Humans; Malaria, Falciparum; Artemisinins; Tetrahydrofolate Dehydrogenase; Genetic Markers; Dihydropteroate Synthase; Protozoan Proteins
PubMed: 38574550
DOI: 10.4269/ajtmh.23-0631 -
Annals of Clinical Microbiology and... Mar 2024Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most appropriate antibiotic to treat S. maltophilia infection is a major challenge.
AIM
The current meta-analysis aimed to investigate the global prevalence of antibiotic resistance among S. maltophilia isolates to the develop more effective therapeutic strategies.
METHOD
A systematic literature search was performed using the appropriate search syntax after searching Pubmed, Embase, Web of Science and Scopus databases (May 2023). Statistical analysis was performed using Pooled and the random effects model in R and the metafor package. A total of 11,438 articles were retrieved. After a thorough evaluation, 289 studies were finally eligible for inclusion in this systematic review and meta-analysis.
RESULT
Present analysis indicated that the highest incidences of resistance were associated with doripenem (97%), cefoxitin (96%), imipenem and cefuroxime (95%), ampicillin (94%), ceftriaxone (92%), aztreonam (91%) and meropenem (90%) which resistance to Carbapenems is intrinsic. The lowest resistance rates were documented for minocycline (3%), cefiderocol (4%). The global resistance rate to TMP-SMX remained constant in two periods before and after 2010 (14.4% vs. 14.6%). A significant increase in resistance to tigecycline and ceftolozane/tazobactam was observed before and after 2010.
CONCLUSIONS
Minocycline and cefiderocol can be considered the preferred treatment options due to low resistance rates, although regional differences in resistance rates to other antibiotics should be considered. The low global prevalence of resistance to TMP-SMX as a first-line treatment for S. maltophilia suggests that it remains an effective treatment option.
Topics: Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Minocycline; Stenotrophomonas maltophilia; Microbial Sensitivity Tests; Anti-Bacterial Agents; Cefiderocol; Drug Resistance, Microbial; Gram-Negative Bacterial Infections
PubMed: 38504262
DOI: 10.1186/s12941-024-00685-4 -
The American Journal of Tropical... Jan 2024Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in... (Meta-Analysis)
Meta-Analysis
Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in 2012 and has been implemented in 13 countries in the Sahel, reaching more than 30 million children annually. Malaria control programs implementing SMC have asked the WHO to consider expanding the age range or number of monthly cycles. We conducted a systematic review and meta-analysis of SMC among children up to 15 years of age and up to six monthly cycles. Twelve randomized studies were included, with outcomes stratified by age (< 5/≥ 5 years), by three or four versus five or six cycles, and by drug where possible. Drug regimens included sulfadoxine-pyrimethamine + amodiaquine, amodiaquine-artesunate, and sulfadoxine-pyrimethamine + artesunate. Included studies were all conducted in Sahelian countries in which high-grade resistance to sulfadoxine-pyrimethamine was rare and in zones with parasite prevalence ranging from 1% to 79%. Seasonal malaria chemoprevention resulted in substantial reductions in uncomplicated malaria incidence measured during that transmission season (rate ratio: 0.27, 95% CI: 0.25-0.29 among children < 5 years; rate ratio: 0.27, 95% CI: 0.25-0.30 among children ≥ 5 years) and in the prevalence of malaria parasitemia measured within 4-6 weeks from the final SMC cycle (risk ratio: 0.38, 95% CI: 0.34-0.43 among children < 5 years; risk ratio: 0.23, 95% CI: 0.11-0.48 among children ≥ 5 years). In high-transmission zones, SMC resulted in a moderately reduced risk of any anemia (risk ratio: 0.77, 95% CI: 0.72-0.83 among children < 5 years; risk ratio: 0.70, 95% CI: 0.52-0.95 among children ≥ 5 years [one study]). Children < 10 years of age had a moderate reduction in severe malaria (risk ratio: 0.53, 95% CI: 0.37-0.76) but no evidence of a mortality reduction. The evidence suggests that in areas in which sulfadoxine-pyrimethamine and amodiaquine remained efficacious, SMC effectively reduced malaria disease burden among children both < 5 and ≥ 5 years old and that the number of cycles should be commensurate with the length of the transmission season, up to six cycles.
Topics: Child; Child, Preschool; Humans; Amodiaquine; Antimalarials; Artesunate; Chemoprevention; Drug Combinations; Malaria; Pyrimethamine; Seasons; Sulfadoxine; Adolescent
PubMed: 38081050
DOI: 10.4269/ajtmh.23-0481 -
Malaria Journal Oct 2023Malaria infection during pregnancy is an important cause of maternal and infant mortality and morbidity with the greatest effect being concentrated in sub-Saharan... (Meta-Analysis)
Meta-Analysis
Safety and tolerability of repeated doses of dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in pregnancy: a systematic review and an aggregated data meta-analysis of randomized controlled trials.
BACKGROUND
Malaria infection during pregnancy is an important cause of maternal and infant mortality and morbidity with the greatest effect being concentrated in sub-Saharan Africa. In areas of moderate to high malaria transmission, the World Health Organization (WHO) recommends the administration of intermittent preventive treatment of malaria in pregnancy (IPTp) using sulfadoxine-pyrimethamine (SP) to be given to all pregnant women at each scheduled antenatal care visit at monthly intervals. However, there is concern that increased resistance has compromised its effectiveness. This has led to a need for evaluation of alternatives to SP for IPTp with dihydroartemisinin-piperaquine (DP) emerging as a very promising candidate. Thus, this systematic review and aggregated data meta-analysis was conducted to establish the safety and tolerability of repeated doses with DP in IPTp.
METHODS
A systematic review and aggregated data meta-analysis of randomized controlled trials (RCTs) was performed by searching electronic databases of PubMed, Science Direct, ClinicalTrials.gov and Google Scholar. RCTs comparing IPTp DP versus recommended standard treatment for IPTp with these outcome measures were analyzed; change in QTc interval, serious adverse events (SAE), grade 3 or 4 adverse events possibly related to study drug and vomiting within 30 min after study drug administration. The search was performed up to 24th June 2023. Data was extracted from eligible studies and an aggregated data meta-analysis was carried out with data pooled as risk ratio (RR) with a 95% confidence interval (CI), using RevMan software (5.4). This study is registered with PROSPERO, CRD42022310041.
RESULTS
Six RCTs involving 7969 participants were included in this systematic review and aggregated data meta-analysis. The pooled analysis showed that DP was associated with a change from baseline of the QTc interval although this change was not associated with cardiotoxicity. There was no statistically significant difference in the risk of occurrence of SAEs among participants in both treatment groups (RR = 0.80, 95% CI [0.52-1.24], P = 0.32). However, significant difference was observed in grade 3 or 4 AEs possibly related to study drug where analysis showed that subjects on IPT DP were statistically significantly more likely to experience an AE possibly related to study drug than subjects on IPT SP (RR = 6.65, 95% CI [1.18-37.54], P = 0.03) and in vomiting within 30 min after study drug administration where analysis showed that the risk of vomiting is statistically significantly higher in subjects receiving IPT DP than in subjects receiving IPT SP (RR = 1.77, 95% CI [1.02-3.07], P = 0.04).
CONCLUSION
DP was associated with a higher risk of grade 3 or 4 AEs possibly related to study drug and a higher risk of vomiting within 30 min after study drug administration. However, these were experienced in a very small percentage of women and did not affect adherence to study drugs. DP was also better tolerated in these studies as compared to most alternatives that have been proposed to replace SP which have proved to be too poorly tolerated in IPTp use.
Topics: Pregnancy; Infant; Female; Humans; Antimalarials; Pregnancy Complications, Parasitic; Randomized Controlled Trials as Topic; Malaria; Pyrimethamine; Sulfadoxine; Drug Combinations; Vomiting
PubMed: 37865784
DOI: 10.1186/s12936-023-04757-2 -
Clinical Microbiology and Infection :... Feb 2024Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. (Meta-Analysis)
Meta-Analysis Review
Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients: systematic review and individual patient data meta-analysis.
BACKGROUND
Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial.
OBJECTIVES
To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection.
METHODS
A systematic review and individual patient data meta-analysis.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023.
STUDY ELIGIBILITY CRITERIA
(a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis.
PARTICIPANTS
SOT recipients.
INTERVENTION
TMP-SMX prophylaxis versus no prophylaxis.
ASSESSMENT OF RISK OF BIAS
Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies.
METHODS OF DATA SYNTHESIS
For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92-100).
CONCLUSIONS
In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.
Topics: Humans; Breakthrough Infections; Nocardia Infections; Organ Transplantation; Retrospective Studies; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 37865337
DOI: 10.1016/j.cmi.2023.10.008 -
BMC Infectious Diseases Sep 2023Tuberculosis, along with HIV, is the leading cause of mortality and morbidity globally. Despite the fact that several primary studies have been conducted on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis, along with HIV, is the leading cause of mortality and morbidity globally. Despite the fact that several primary studies have been conducted on the incidence rate of tuberculosis in HIV-infected people in Sub-Saharan Africa, the regional-level tuberculosis incidence rate remains unknown. The objective of this study is to determine the tuberculosis incidence rate and its associated factors in HIV-infected people in Sub-Saharan Africa.
METHODS
A systematic review and meta-analysis were conducted by searching four databases for studies published in English between January 1, 2000, and November 25, 2022. The study was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. To assess the quality of the studies, the Joanna Briggs Institute critical appraisal checklist was used. A random-effects model meta-analysis was used to determine the pooled incidence of tuberculosis using STATA version 15. The I heterogeneity test was used to assess heterogeneity. Subgroup and sensitivity analyses were performed. Funnel plots and Egger's regression tests were used to investigate publication bias. The pooled estimate predictors of tuberculosis incidence rate with a 95% confidence interval were also determined using the hazard ratio of each factor (HR).
RESULTS
Out of a total of 3339 studies, 43 were included in the analysis. The overall pooled incidence rate of tuberculosis in HIV-infected people was 3.49 per 100 person-years (95% CI: 2.88-4.17). In the subgroup analysis, the pooled incidence rate of tuberculosis in HIV-infected children was 3.42 per 100 person-years (95% CI: 1.78, 5.57), and it was 3.79 per 100 person-years (95% CI: 2.63, 5.15) in adults. A meta-analysis revealed that underweight (AHR = 1.79, 95% CI: 1.61-1.96), low CD4 count (AHR = 1.23, 95% CI: 1.13-1.35), male gender (AHR = 1.43, 95% CI: 1.22-1.64), advanced WHO clinical stages (AHR = 2.29, 95% CI: 1.34-3.23), anemia (AHR = 1.73, 95% CI: 1.34-2.13), bedridden or ambulatory (AHR = 1.87, 95%), lack of isoniazid preventive therapy (AHR = 3.32, 95% CI: 1.08-2.28), and lack of cotrimoxazole (AHR = 1.68, 95% CI: 1.08-2.28) were risk factors for tuberculosis incidence. HIV patients who received antiretroviral therapy had a 0.53 times higher risk of acquiring tuberculosis than HIV patients who did not receive antiretroviral therapy (AHR = 0.53; 95% CI: 0.3-0.77).
CONCLUSION
In this systematic review and meta-analysis study, the incidence rate of tuberculosis among HIV-positive people was higher than the WHO 2022 Africa regional estimated report. To reduce the incidence of tuberculosis among HIV patients, HIV patients should take isoniazid prevention therapy (IPT), cotrimoxazole prophylaxis, and antiretroviral therapy (ART) without interruption, as well as increase the frequency and diversity of their nutritional intake. Active tuberculosis screening should be increased among HIV-infected people.
Topics: Adult; Child; Male; Humans; Incidence; Isoniazid; HIV Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Africa South of the Sahara
PubMed: 37723415
DOI: 10.1186/s12879-023-08533-0 -
Clinical Cardiology Jan 2024
Topics: Humans; Furosemide; Torsemide; Randomized Controlled Trials as Topic; Heart Failure; Sulfonamides; Diuretics
PubMed: 37608566
DOI: 10.1002/clc.24088 -
Annals of Clinical Microbiology and... Aug 2023Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. The two stages of melioidosis treatment are the intense intravenous phase and the... (Review)
Review
BACKGROUND
Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. The two stages of melioidosis treatment are the intense intravenous phase and the oral eradication phase. Although co-trimoxazole has been in use for several years, the literature does not demonstrate uniformity of the drug doses, combinations, or durations suitable for the eradication phase of melioidosis. The safety profile of co-trimoxazole was not documented in the literature, nor have systematic studies of its effectiveness been done. This systematic review sought to study on the dose, duration and combination of co-trimoxazole therapy in view of clinical efficacy and safety in the eradication phase of melioidosis.
MAIN BODY
This systematic review included all of the published articles that employed co-trimoxazole in the eradication phase after 1989, including, randomized clinical trials, case-control studies, cohorts, case reports, and case series. Throughout the eradication (maintenance) phase, co-trimoxazole usage was permissible in any dose for any period. A total of 40 results were included in the analysis which contained six clinical trials, one cohort study, one Cochrane review, and thirty-two case series/case reports. Clinical and microbial relapse rates are low when co-trimoxazole is used in single therapy than in combination. There were several adverse events of co-trimoxazole, however, a quantitative analysis was not conducted as the data did not include quantitative values in most studies.
SHORT CONCLUSION
The dose of co-trimoxazole, duration of the eradication phase, and other combinations used in the treatment was varying between studies. Compared to combined therapy patients treated with co-trimoxazole alone the mortality and relapse rates were low. The lowest relapse rate and lowest mortality rate occur when using co-trimoxazole 1920 mg twice daily. The duration of therapy varies on the focus of melioidosis and it is ranged from 2 months to one year and minimum treatment duration associated with low relapse rate is 3 months. The use of co-trimoxazole over the maintenance phase of melioidosis is associated with clinical cure but has adverse effects.
Topics: Humans; Melioidosis; Cohort Studies; Administration, Intravenous; Case-Control Studies; Drug-Related Side Effects and Adverse Reactions; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 37592339
DOI: 10.1186/s12941-023-00620-z -
BMC Microbiology Jul 2023While trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line therapy of Stenotrophomonas maltophilia infections, colistin is one of the therapeutic options in cases... (Meta-Analysis)
Meta-Analysis
While trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line therapy of Stenotrophomonas maltophilia infections, colistin is one of the therapeutic options in cases of allergy or resistance to TMP-SMX. However, understanding the global status of resistance to colistin amongst S. maltophilia isolates could be helpful for appropriate antibiotic prescription. This study aimed to conduct a systematic review and meta-analysis to examine the prevalence of colistin resistance in clinical S. maltophilia isolates worldwide. According to eligibility criteria, a total of 61 studies were included in the analysis. The pooled prevalence for colistin resistance was 42% (95% CI: 35-49%), ranging from 0.1 to 97%. Subgroups analysis indicated that, the pooled prevalence of colistin resistance was 44% (95% CI: 29-60%) in 15 studies during 2000-2010, and it was estimated to be 41% (95% CI: 33-50%) in 46 articles from 2011 to 2021. It was 46% (95% CI: 35-58%) in the studies that used broth microdilution method, and 39% (95% CI: 30-49%) in the studies with other used methods. The resistance rate in Asian countries was 45% (95% CI: 31-60%), in European countries was 45% (95% CI: 34-56%) and in the countries of North and South America was 33% (95% CI: 20-46%). Our review showed notable resistance to colistin in clinical S. maltophilia isolates. Given the estimated resistance rates, alternative antibiotics could be preferred to treat serious infections due to S. maltophilia.
Topics: Humans; Colistin; Trimethoprim, Sulfamethoxazole Drug Combination; Stenotrophomonas maltophilia; Prevalence; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests; Anti-Bacterial Agents
PubMed: 37507660
DOI: 10.1186/s12866-023-02950-6