-
Journal of Infection and Chemotherapy :... Nov 2022Fidaxomicin (FDX) has received considerable attention as a novel therapeutic alternative agent to vancomycin (VCM) for Clostridioides difficile infection (CDI). However,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fidaxomicin (FDX) has received considerable attention as a novel therapeutic alternative agent to vancomycin (VCM) for Clostridioides difficile infection (CDI). However, the superiority and efficacy profile of FDX are not sufficiently determined by high-quality evidence. This study aimed to clarify the superiority of FDX for CDI treatment through a systematic review and meta-analysis.
METHODS
We conducted a meta-analysis of randomized controlled trials (RCTs) which evaluated the efficacy and safety of FDX and VCM in patients with CDI. Electronic databases (PubMed, Cochrane Library, Web of Science, and Clinicaltrials.gov) were searched for studies published until October 15, 2021. The primary endpoint was global cure. The secondary endpoints were clinical cure, recurrence, and adverse event. Risk ratios (RRs), risk differences (RDs), and 95% confidence intervals were calculated using Mantel-Haenszel random-effects model. The risk of bias was assessed using Cochrane Handbook for Systematic Reviews of Interventions and Assessment Criteria.
RESULTS
Six RCTs were included in this meta-analysis. Compared to VCM, FDX was associated with significantly higher global cure rates (RR = 1.18, P < 0.00001; RD = 0.11, 95% CI = 0.07-0.16). In addition, clinical cure rates were comparable between FDX and VCM (P = 0.31). FDX was associated with significantly lower recurrence rates compared to VCM (RR = 0.59, P < 0.0001). In addition, adverse event rates were not significantly different between the drugs (P = 0.41).
CONCLUSION
FDX achieves significantly higher global cure rates and lower recurrence rates and is comparable to VCM in clinical cure rates and adverse event rates in patients with CDI. Collectively, FDX is superior to VCM as a therapeutic agent for CDI.
Topics: Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Fidaxomicin; Humans; Randomized Controlled Trials as Topic; Vancomycin
PubMed: 35964806
DOI: 10.1016/j.jiac.2022.08.008 -
Journal of Global Antimicrobial... Dec 2020Vancomycin combined with β-lactams (Combo therapy) has been encouraged in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of the efficacy and safety of vancomycin combined with β-lactam antibiotics in the treatment of methicillin-resistant Staphylococcus aureus bloodstream infections.
OBJECTIVE
Vancomycin combined with β-lactams (Combo therapy) has been encouraged in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) in recent years, but its efficacy and safety have not been systematically evaluated. This is a systematic review and meta-analysis to clarify the efficacy and safety of Combo therapy in patients with MRSA BSIs.
METHODS
Relevant articles reporting on the clinical or microbiology outcomes of Combo treatment in adult patients with MRSA bacteraemia throughout November 2019 were searched in PubMed, EMBASE and Cochrane Library databases. Summary odds ratios (ORs) or mean differences (MDs) and 95% confidence intervals (CIs) were evaluated using a fixed- or random-effects model.
RESULTS
Six articles (806 patients) consisting of one RCT and five retrospective cohort studies were included in this study. The pooled data showed that Combo therapy could significantly reduce the risk of microbiological failure (OR = 0.54, 95% CI 0.35-0.83, I 40%, P = 0.005) and persistent bacteraemia (OR=0.48, 95% CI 0.30-0.77, I 13%, P = 0.002), as well as shorten the duration of bacteraemia (MD = -1.06, 95% CI -1.53 to -0.60, I 0%, P < 0.00001). In addition, it did not significantly increase the incidence of nephrotoxicity (OR = 1.17, 95% CI 0.64-2.13, I 0%, P = 0.61). However, no significant difference was detected between the groups regarding 28/30-day mortality, MRSA-related mortality, bacteraemia relapse or length of hospitalization.
CONCLUSIONS
These results demonstrate that Combo therapy clears the pathogenic bacteria of MRSA bacteraemia but does not improve the clinical prognosis. As the sample size was small and most of the studies were retrospective cohort studies with substantial heterogeneity, there is a need for further studies encompassing large-scale multicentre RCTs to validate our results.
Topics: Adult; Anti-Bacterial Agents; Bacteremia; Humans; Methicillin-Resistant Staphylococcus aureus; Retrospective Studies; Staphylococcal Infections; Vancomycin; beta-Lactams
PubMed: 33045437
DOI: 10.1016/j.jgar.2020.09.024 -
Archives of Disease in Childhood Sep 2022Vancomycin is a recognised cause of drug-induced acute kidney injury (AKI).
INTRODUCTION
Vancomycin is a recognised cause of drug-induced acute kidney injury (AKI).
OBJECTIVE
The aim of this systematic review was to summarise the incidence of, and the risk factors for, vancomycin-associated AKI (v-AKI) in children.
DESIGN
A systematic search was performed in November 2020 on the search engines PubMed, Web of Science and Medline, using predefined search terms. The inclusion criteria were primary paediatric studies, intervention with vancomycin and studies that included AKI as an outcome. Study quality was assessed using the relevant Critical Appraisal Skills Programme checklist. The data are reported using descriptive statistics.
RESULTS
890 studies were identified and screened with 25 studies suitable for inclusion. A cohort of 12 730 patients with v-AKI were included and the incidence of v-AKI in children was found to be 11.8% (1.6%-27.2%). The median age of the cohort was 2.5 years (range 0-23) and 57% were male patients. Risk factors that increased the likelihood of v-AKI were concomitant use of nephrotoxic medications, increased trough concentrations and, to a lesser extent, increased dose, longer duration of treatment, impaired renal function and if the patient required paediatric intensive care.
CONCLUSIONS
The incidence of v-AKI in children is significant and methods to reduce this risk should be considered. Further prospective interventional studies to understand the mechanisms of nephrotoxicity from vancomycin are needed and targeting risk factors may make vancomycin administration safer.
PubMed: 35210220
DOI: 10.1136/archdischild-2021-323429 -
Clinical Microbiology and Infection :... Mar 2024Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined.
OBJECTIVES
We evaluated pathogen-specific excess health burden of drug-resistant bloodstream infections (BSIs) in Europe.
METHODS
A systematic review and meta-analysis.
DATA SOURCES
MEDLINE, Embase, and grey literature for the period January 1990 to May 2022.
STUDY ELIGIBILITY CRITERIA
Studies that reported burden data for six key drug-resistant pathogens: carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, third-generation cephalosporin or CR Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Excess health outcomes compared with drug-susceptible BSIs or uninfected patients. For MRSA and third-generation cephalosporin E. coli and K. pneumoniae BSIs, five or more European studies were identified. For all others, the search was extended to high-income countries.
PARTICIPANTS
Paediatric and adult patients diagnosed with drug-resistant BSI.
INTERVENTIONS
Not applicable.
ASSESSMENT OF RISK OF BIAS
An adapted version of the Joanna-Briggs Institute assessment tool.
METHODS OF DATA SYNTHESIS
Random-effect models were used to pool pathogen-specific burden estimates.
RESULTS
We screened 7154 titles, 1078 full-texts and found 56 studies on BSIs. Most studies compared outcomes of drug-resistant to drug-susceptible BSIs (46/56, 82.1%), and reported mortality (55/56 studies, 98.6%). The pooled crude estimate for excess all-cause mortality of drug-resistant versus drug-susceptible BSIs ranged from OR 1.31 (95% CI 1.03-1.68) for CR P. aeruginosa to OR 3.44 (95% CI 1.62-7.32) for CR K. pneumoniae. Pooled crude estimates comparing mortality to uninfected patients were available for vancomycin-resistant Enterococcus and MRSA BSIs (OR of 11.19 [95% CI 6.92-18.09] and OR 6.18 [95% CI 2.10-18.17], respectively).
CONCLUSIONS
Drug-resistant BSIs are associated with increased mortality, with the magnitude of the effect influenced by pathogen type and comparator. Future research should address crucial knowledge gaps in pathogen- and infection-specific burdens to guide development of novel interventions.
Topics: Adult; Humans; Child; Methicillin-Resistant Staphylococcus aureus; Bacteremia; Escherichia coli; Vancomycin; Anti-Bacterial Agents; Europe; Sepsis; Cephalosporins; Drug Resistance, Bacterial
PubMed: 37802750
DOI: 10.1016/j.cmi.2023.09.001 -
Biology of Sex Differences May 2021Vancomycin-resistant enterococci (VRE) have emerged in the healthcare setting worldwide. Infections with these pathogens, i.e., bloodstream infections (BSI), are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vancomycin-resistant enterococci (VRE) have emerged in the healthcare setting worldwide. Infections with these pathogens, i.e., bloodstream infections (BSI), are accompanied with an impaired patient outcome. Diverse factors comprising patient characteristics, therapeutic strategies, and infection control measures are positively or negatively associated with VRE BSI occurrence. However, whether sex-specific differences influence the frequency of VRE BSI is yet unknown. The aim of this systematic review was to comprehensively summarize and analyze sex prevalence in VRE BSI patients.
MAIN TEXT
A systematic search for relevant articles was conducted in PubMed and Web of Science. After screening for eligibility, data extraction from included articles and risk of bias assessment were processed. The prevalence of male/female sex in VRE BSI patients and 95% CI were calculated for each study and summarized as pooled estimated effect. In total, nine articles met the inclusion criteria. Risk of bias assessment resulted in low (six studies) to moderate bias (three studies). The pooled prevalence of male patients suffering from VRE BSI was 59% resulting in a 1.4 male/female prevalence ratio.
CONCLUSIONS
Current literature suggests sex differences with male preference (59%) in the distribution of VRE BSI cases. Further primary studies should address the question of male-specific factors favoring the enhanced frequency of VRE BSI.
Topics: Anti-Bacterial Agents; Bacteremia; Female; Gram-Positive Bacterial Infections; Humans; Male; Sex Characteristics; Vancomycin-Resistant Enterococci
PubMed: 34001270
DOI: 10.1186/s13293-021-00380-5 -
Alimentary Pharmacology & Therapeutics Jan 2023Primary sclerosing cholangitis (PSC) is a progressive liver disease with poor prognosis and no effective therapies to prevent progression. An aetiopathological link... (Review)
Review
BACKGROUND
Primary sclerosing cholangitis (PSC) is a progressive liver disease with poor prognosis and no effective therapies to prevent progression. An aetiopathological link between PSC and gastrointestinal microbial dysbiosis has been suggested.
AIM
To evaluate all potential medical therapies which may exert their effect in PSC by modulation of the gut-liver axis.
METHODS
We conducted a comprehensive scoping review of PubMed and Cochrane Library, including all articles evaluating an intervention aimed at manipulating the gastrointestinal microbiome in PSC.
RESULTS
A wide range of therapies proposed altering the gastrointestinal microbiome for the treatment of PSC. In particular, these considered antibiotics including vancomycin, metronidazole, rifaximin, minocycline and azithromycin. However, few therapies have been investigated in randomised, placebo-controlled trials. Vancomycin has been the most widely studied antibiotic, with improvement in alkaline phosphatase reported in two randomised controlled trials, but with no data on disease progression. Unlike antibiotics, strategies such as faecal microbiota transplantation and dietary therapy can improve microbial diversity. However, since these have only been tested in small numbers of patients, robust efficacy data are currently lacking.
CONCLUSIONS
The gut-liver axis is increasingly considered a potential target for the treatment of PSC. However, no therapies have been demonstrated to improve transplant-free survival. Innovative and well-designed clinical trials of microbiome-targeted therapies with long-term follow-up are required for this orphan disease.
Topics: Humans; Cholangitis, Sclerosing
PubMed: 36324251
DOI: 10.1111/apt.17251 -
British Journal of Clinical Pharmacology Feb 2023The aim was to quantify the relationship between pharmacist intervention and vancomycin-associated acute kidney injury (AKI). (Meta-Analysis)
Meta-Analysis Review
AIMS
The aim was to quantify the relationship between pharmacist intervention and vancomycin-associated acute kidney injury (AKI).
METHODS
Electronic databases were searched up to August 2020 for meta-analyses of cohort studies and/or randomized controlled trials. Studies that compared the incidence of AKI in patients between post- and prepharmacist intervention were investigated. The primary outcome was incidence of AKI. We also evaluated the influence of pharmacist intervention in risk factors of vancomycin-associated AKI.
RESULTS
The search strategy retrieved 1744 studies and 34 studies with 19 298 participants were included (22 published articles and 12 abstracts from conference proceedings). Compared with the preintervention group, the postintervention group patients had a significantly lower incidence of vancomycin-associated AKI: 7.3% for post- and 9.6% for preintervention (odds ratio [OR] 0.52, 95% confidence interval [CI]; 0.41, 0.67], P < .00001). The rate of attaining target concentration was significantly higher in the post- than preintervention group (OR 2.86, 95% CI [2.23, 3.67], P < .00001). The postintervention group significantly improved the percentage of serum creatinine laboratory tests than preintervention group (OR = 3.24, 95% CI 2.02, 5.19], P < .00001). Patients postintervention had markedly lower risk of mortality than preintervention patients (OR 0.47, 95% CI [0.31, 0.72], P = .0004).
CONCLUSION
Pharmacist intervention in vancomycin treatment significantly decreased the rate of vancomycin-associated AKI, while improving efficacy and reducing mortality. We speculate that this is because the pharmacist interventions optimized the rationality of vancomycin therapy, monitoring of vancomycin trough concentration and the monitoring of patients' renal function.
Topics: Humans; Vancomycin; Anti-Bacterial Agents; Pharmacists; Retrospective Studies; Acute Kidney Injury; Creatinine
PubMed: 35285970
DOI: 10.1111/bcp.15301 -
Clinical Microbiology and Infection :... Mar 2024Quantifying the resource use and cost of antimicrobial resistance establishes the magnitude of the problem and drives action. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Quantifying the resource use and cost of antimicrobial resistance establishes the magnitude of the problem and drives action.
OBJECTIVES
Assessment of resource use and cost associated with infections with six key drug-resistant pathogens in Europe.
METHODS
A systematic review and Bayesian meta-analysis.
DATA SOURCES
MEDLINE (Ovid), Embase (Ovid), Econlit databases, and grey literature for the period 1 January 1990, to 21 June 2022.
STUDY ELIGIBILITY CRITERIA
Resource use and cost outcomes (including excess length of stay, overall costs, and other excess in or outpatient costs) were compared between patients with defined antibiotic-resistant infections caused by carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, CR or third-generation cephalosporin Escherichia coli (3GCREC) and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium, and patients with drug-susceptible or no infection.
PARTICIPANTS
All patients diagnosed with drug-resistant bloodstream infections (BSIs).
INTERVENTIONS
NA.
ASSESSMENT OF RISK OF BIAS
An adapted version of the Joanna Briggs Institute assessment tool, incorporating case-control, cohort, and economic assessment frameworks.
METHODS OF DATA SYNTHESIS
Hierarchical Bayesian meta-analyses were used to assess pathogen-specific resource use estimates.
RESULTS
Of 5969 screened publications, 37 were included in the review. Data were sparse and heterogeneous. Most studies estimated the attributable burden by, comparing resistant and susceptible pathogens (32/37). Four studies analysed the excess cost of hospitalization attributable to 3GCREC BSIs, ranging from -€ 2465.50 to € 6402.81. Eight studies presented adjusted excess length of hospital stay estimates for methicillin-resistant S. aureus and 3GCREC BSIs (4 each) allowing for Bayesian hierarchical analysis, estimating means of 1.26 (95% credible interval [CrI], -0.72 to 4.17) and 1.78 (95% CrI, -0.02 to 3.38) days, respectively.
CONCLUSIONS
Evidence on most cost and resource use outcomes and across most pathogen-resistance combinations was severely lacking. Given the importance of this evidence for rational policymaking, further research is urgently needed.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Bayes Theorem; Anti-Bacterial Agents; Anti-Infective Agents; Escherichia coli; Pseudomonas aeruginosa; Drug Resistance, Bacterial
PubMed: 38128781
DOI: 10.1016/j.cmi.2023.12.013 -
Clinical Microbiology and Infection :... Jan 2024Current practice guidelines favour fidaxomicin over vancomycin and exclude metronidazole from the recommended standard regimen for Clostridioides difficile infection... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current practice guidelines favour fidaxomicin over vancomycin and exclude metronidazole from the recommended standard regimen for Clostridioides difficile infection (CDI), based on lower recurrence rates with fidaxomicin, giving little weight to mortality or the clinical implications of recurrences.
OBJECTIVES
To compile the effects of metronidazole, glycopeptides (vancomycin or teicoplanin), and fidaxomicin for CDI on mortality and other patient-relevant outcomes.
DATA SOURCES
PubMed, the Cochrane Library, ClinicalTrials.gov, conference proceedings, and Google Scholar, until August 2023.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials (RCTs).
PARTICIPANTS
Adult patients experiencing primary or recurrent CDI.
INTERVENTIONS
Glycopeptides versus fidaxomicin or metronidazole (comparators).
ASSESSMENT OF RISK OF BIAS
We used the Risk of Bias 2 (RoB 2) tool for randomized trials, focusing on the outcome of all-cause mortality.
METHODS OF DATA SYNTHESIS
Random effects meta-analyses were performed for dichotomous outcomes. Outcomes were summarized preferentially for all randomly assigned patients.
RESULTS
Thirteen trials were included. There was no significant difference in all-cause mortality (risk ratio [RR] < 1 favouring the comparator) between vancomycin and fidaxomicin (RR 0.86, 95% CI 0.64-1.14, 8 RCTs, 1951 patients) or metronidazole (RR 0.78, 95% CI 0.46-1.32, 4 RCTs, 808 patients), with low and very low certainty of evidence, respectively. No significant difference in initial treatment failure between fidaxomicin and vancomycin was found, however, initial treatment failure was higher with metronidazole (RR 1.58, 95% CI 1.10-2.27, 5 RCTs, 843 patients). No study reported on symptomatic recurrence necessitating re-treatment among all randomly assigned patients. Among initially cured patients, symptomatic recurrence necessitating re-treatment was lower with fidaxomicin than with vancomycin (RR 0.54, 95% CI 0.42-0.71, 6 RCTs, 1617 patients). None of the studies reported on other CDI complications or the burden of infection on daily activities.
CONCLUSIONS
Setting patient-relevant outcomes for CDI independently of the RCT definitions and results might lead to less confidence in the guidance for CDI management.
Topics: Adult; Humans; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Fidaxomicin; Metronidazole; Randomized Controlled Trials as Topic; Recurrence; Vancomycin
PubMed: 37690610
DOI: 10.1016/j.cmi.2023.09.002 -
The optimal trough-guided monitoring of vancomycin in children: Systematic review and meta-analyses.Journal of Infection and Chemotherapy :... May 2021We carried out a systematic review and meta-analysis exploring the relationship between vancomycin (VCM) trough concentrations and its effectiveness and nephrotoxicity... (Meta-Analysis)
Meta-Analysis
We carried out a systematic review and meta-analysis exploring the relationship between vancomycin (VCM) trough concentrations and its effectiveness and nephrotoxicity in pediatric patients. We conducted our analysis using MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials as electronic databases (June 29, 2019). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. We identified 16 studies that were eligible for the meta-analysis. A total of 351 and 3,266 patients were included in the analysis for effectiveness and nephrotoxicity, respectively. Pediatric MRSA infection patients with VCM trough concentrations ≥ 10 μg/mL had significantly lower treatment failure rates (OR 0.54, 95% CI 0.30-0.96). The incidence of nephrotoxicity was significantly higher in trough concentrations ≥ 15 μg/mL than when they were < 15 μg/mL (OR 3.02, 95% CI 2.08-4.38). We identified the optimal VCM trough concentrations associated with effectiveness and nephrotoxicity in pediatric patients with MRSA infection. Further prospective studies are needed to find optimal dosing and monitoring strategy on VCM in pediatric population.
Topics: Anti-Bacterial Agents; Child; Humans; Methicillin-Resistant Staphylococcus aureus; Prospective Studies; Renal Insufficiency; Retrospective Studies; Vancomycin
PubMed: 33563525
DOI: 10.1016/j.jiac.2021.01.015