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Microbial Drug Resistance (Larchmont,... Aug 2021Several and studies demonstrated that adding a β-lactam to vancomycin (VAN) or daptomycin (DAP) can provide synergy against methicillin-resistant (MRSA). However,... (Meta-Analysis)
Meta-Analysis
Several and studies demonstrated that adding a β-lactam to vancomycin (VAN) or daptomycin (DAP) can provide synergy against methicillin-resistant (MRSA). However, the results from clinical studies were controversial. The objective of this systematic review and meta-analysis was to compare the efficacy and safety of using VAN or DAP plus a β-lactam (combination therapy) and using VAN or DAP alone (monotherapy) in MRSA bloodstream infections. We included randomized controlled trials and observational studies evaluating whether combination therapy can improve clinical and microbiological outcomes and safety compared to monotherapy with VAN or DAP in MRSA-related bacteremia. Literature search identified 3 randomized clinical trials and 10 observational studies involving at least 1,796 patients. There were no significant associations between the combination therapy and risk of mortality within 30 days (risk ratios [RRs], 1.10, 95% confidence interval [CI], 0.82-1.46), in-hospital mortality (RR, 0.59, 95% CI, 0.31-1.13) and mortality within 60-90 days (RR, 0.91, 95% CI, 0.64-1.29). There was also no evidence that there was a difference in length of hospital stay between the combination therapy and monotherapy (mean difference, -0.41 days, 95% CI, -3.41 to 2.59). However, compared with monotherapy, combination therapy seemed to have a shorter duration of bacteremia(mean difference, -1.06 days, 95% CI, -1.53 to -0.60), a lower risk of persistent bacteremia (RR, 0.63, 95% CI, 0.51-0.79) and a lower risk of bacteremia recurrence within 60-90 days (RR, 0.61, 95% CI, 0.40-0.92). There were no statistically significant differences in the total number of adverse events, including acute kidney injury (AKI) (RR, 1.52, 95% CI, 0.84-2.73), thrombocytopenia (RR, 1.13, 95% CI, 0.74-1.73), and diarrhea (RR, 1.36, 95% CI, 0.70-2.65), between patients with combination therapy and monotherapy. In subgroup analysis, when the analysis was limited to the studies comparing using DAP plus ceftaroline with monotherapy, we found that the former had a lower risk of mortality within 30 days. In addition, a subgroup analysis limited to randomized clinical trials showed that the combination therapy was associated with a higher risk of AKI compared with using VAN or DAP alone. Although adding a β-lactam to standard therapy seemed to experience a higher clearance compared with monotherapy in patients with MRSA bacteremia, the combination therapy did not increase survival benefits. Based on the available evidence, the combination therapy was not supported as the routine management of MRSA-related bacteremia, and both its harms and benefits should be taken into account.
Topics: Anti-Bacterial Agents; Bacteremia; Daptomycin; Drug Therapy, Combination; Humans; Length of Stay; Methicillin-Resistant Staphylococcus aureus; Observational Studies as Topic; Randomized Controlled Trials as Topic; Staphylococcal Infections; Vancomycin; beta-Lactams
PubMed: 33728980
DOI: 10.1089/mdr.2020.0350 -
The Cochrane Database of Systematic... Jan 2016The morbidity and treatment costs associated with skin and soft tissue infections (SSTIs) are high. Linezolid and vancomycin are antibiotics that are commonly used in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The morbidity and treatment costs associated with skin and soft tissue infections (SSTIs) are high. Linezolid and vancomycin are antibiotics that are commonly used in treating skin and soft-tissue infections, specifically those infections due to methicillin-resistant Staphylococcus aureus (MRSA).
OBJECTIVES
To compare the effects and safety of linezolid and vancomycin for treating people with SSTIs.
SEARCH METHODS
For this first update of this review we conducted searches of the following databases: Cochrane Wounds Group Specialised Register (searched 24 March 2015; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also contacted manufacturers for details of unpublished and ongoing trials. We scrutinised citations within all obtained trials and major review articles to identify any additional trials.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing linezolid with vancomycin in the treatment of SSTIs.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed risk of bias and extracted data. The primary outcomes were clinical cure, microbiological cure, and SSTI-related and treatment-related mortality. We performed subgroup analyses according to age, and whether the infection was due to MRSA.
MAIN RESULTS
No new trials were identified for this first update. We included nine RCTs (3144 participants). Linezolid was associated with a significantly better clinical (RR 1.09, 95% CI 1.03 to 1.16) and microbiological cure rate in adults (RR 1.08, 95% CI 1.01 to 1.16). For those infections due to MRSA, linezolid was significantly more effective than vancomycin in clinical (RR 1.09, 95% CI 1.03 to 1.17) and microbiological cure rates (RR 1.17, 95% CI 1.04 to 1.32). No RCT reported SSTI-related and treatment-related mortality. There was no significant difference in all-cause mortality between linezolid and vancomycin (RR 1.44, 95% CI 0.75 to 2.80). There were fewer incidents of red man syndrome (RR 0.04, 95% CI 0.01 to 0.29), pruritus (RR 0.36, 95% CI 0.17 to 0.75) and rash (RR 0.27, 95% CI 0.12 to 0.58) in the linezolid group compared with vancomycin, however, more people reported thrombocytopenia (RR 13.06, 95% CI 1.72 to 99.22), and nausea (RR 2.45, 95% CI 1.52 to 3.94) when treated with linezolid. It seems, from the available data, that length of stay in hospital was shorter for those in the linezolid group than the vancomycin group. The daily cost of outpatient therapy was less with oral linezolid than with intravenous vancomycin. Although inpatient treatment with linezolid cost more than inpatient treatment with vancomycin per day, the median length of hospital stay was three days shorter with linezolid. Thus, total hospital charges per patient were less with linezolid treatment than with vancomycin treatment.
AUTHORS' CONCLUSIONS
Linezolid seems to be more effective than vancomycin for treating people with SSTIs, including SSTIs caused by MRSA. The available evidence is at high risk of bias and is based on studies that were supported by the pharmaceutical company that makes linezolid. Further well-designed, independently-funded, RCTs are needed to confirm the available evidence.
Topics: Adult; Anti-Bacterial Agents; Drug Eruptions; Humans; Length of Stay; Linezolid; Pruritus; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Soft Tissue Infections; Thrombocytopenia; Vancomycin
PubMed: 26758498
DOI: 10.1002/14651858.CD008056.pub3 -
Antimicrobial Agents and Chemotherapy Aug 2022To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases,... (Meta-Analysis)
Meta-Analysis
To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases, including PubMed, Elsevier, Web of Science, EMBASE, Medline, clinicaltrials.gov, the Cochrane Library, and three Chinese databases (Wanfang Data, China National Knowledge Infrastructure, and SINOMED), were comprehensively searched to obtain research articles on vancomycin use in children from inception through December 2021. All studies were screened and evaluated using the Cochrane systematic review method. Then, the feature information was extracted for meta-analysis. The evaluated results included clinical efficacy, vancomycin-associated nephrotoxicity, hepatotoxicity, ototoxicity, mortality, and microbial clearance. A total of 35 studies involving 4820 children were included in the analysis. The meta-analysis showed that compared with children with vancomycin trough concentrations <10 μg/mL, those with vancomycin trough concentrations ≥10 μg/mL had a higher clinical efficacy rate [OR: 2.23, 95% CI: 1.29 to 3.84, = 0.004] and higher incidences of nephrotoxicity [OR: 2.76, 95% CI: 1.51 to 5.07, = 0.001], ototoxicity [OR: 1.87, 95% CI: 1.08 to 3.23, = 0.02] and microbial clearance [OR: 2.36, 95% CI: 1.53 to 3.64, = 0.0001]. All-cause mortality [OR: 1.07, 95% CI: 0.45 to 2.53, = 0.88] and hepatotoxicity [OR: 0.84, 95% CI: 0.46 to 1.53, = 0.57] were similar between the two groups. Subgroup analysis showed that compared with children with vancomycin trough concentrations of 10 to 15 μg/mL, those with vancomycin trough concentrations >15 μg/mL had a higher incidence of nephrotoxicity [OR: 2.64, 95% CI: 1.28 to 5.43, = 0.008], but there was no significant difference in clinical efficacy [OR: 0.85, 95% CI: 0.30 to 2.44, = 0.76]. A vancomycin trough concentration of 10 to 15 μg/mL can improve clinical efficacy in children. Additionally, avoidance of trough concentrations >15 μg/mL can reduce the incidence of adverse reactions.
Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Child; Humans; Ototoxicity; Renal Insufficiency; Retrospective Studies; Vancomycin
PubMed: 35862741
DOI: 10.1128/aac.00138-22 -
The Annals of Pharmacotherapy Dec 2022To assess the success rates of off-label uses of ceftaroline for infections caused by methicillin-resistant (MRSA) and evaluate emerging ceftaroline resistance. (Review)
Review
OBJECTIVE
To assess the success rates of off-label uses of ceftaroline for infections caused by methicillin-resistant (MRSA) and evaluate emerging ceftaroline resistance.
DATA SOURCES
We queried PubMed/MEDLINE, with the search term "Ceftaroline." Articles were restricted to the English language and year of publication (January 1, 2009-January 31, 2022).
STUDY SELECTION AND DATA EXTRACTION
Clinical trials, observational studies, and case reports that reported efficacy, safety, pharmacokinetics, use in MRSA infections other than acute bacterial skin infection and community-acquired pneumonia, and ceftaroline resistance were selected.
DATA SYNTHESIS
The search pooled 103 publications and all abstracts were reviewed. Forty-six articles that reported efficacy, safety, pharmacokinetics, or off-label use in multiple patients and 7 articles on ceftaroline resistance are used in this review. Ceftaroline has been approved for treatment of acute skin/soft tissue infection and community-acquired pneumonia. Ceftaroline's efficacy in off-label infections ranged from 66.7% to 87.3% depending on the types of infection. There were 14 documented cases of ceftaroline resistance associated with PBP2a changes.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Case series and observational studies have documented success with ceftaroline alone or in combination with vancomycin or daptomycin for treatment of MRSA bone and joint, endovascular, diabetic foot infections, and bacteremia from other causes.
CONCLUSION
Despite the lack of randomized controlled trials, ceftaroline is used as salvage therapy for different MRSA infections. The data from case series and observational studies are promising but ceftaroline should be used judiciously as ceftaroline-resistant MRSA begin to emerge.
Topics: Anti-Bacterial Agents; Cephalosporins; Community-Acquired Infections; Daptomycin; Drug Resistance; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Vancomycin; Ceftaroline
PubMed: 35300514
DOI: 10.1177/10600280221082326 -
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 -
Journal of Personalized Medicine Aug 2022several blood-based biomarkers have been proposed for predicting vancomycin-associated kidney injury (VIKI). However, no systematic analysis has compared their... (Review)
Review
Blood Biomarkers and Metabolomic Profiling for the Early Diagnosis of Vancomycin-Associated Acute Kidney Injury: A Systematic Review and Meta-Analysis of Experimental Studies.
BACKGROUND
several blood-based biomarkers have been proposed for predicting vancomycin-associated kidney injury (VIKI). However, no systematic analysis has compared their prognostic value.
OBJECTIVE
this systematic review and meta-analysis was designed to investigate the role of blood biomarkers and metabolomic profiling as diagnostic and prognostic predictors in pre-clinical studies of VIKI.
METHODS
a systematic search of PubMed was conducted for relevant articles from January 2000 to May 2022. Animal studies that administered vancomycin and studied VIKI were eligible for inclusion. Clinical studies, reviews, and non-English literature were excluded. The primary outcome was to investigate the relationship between the extent of VIKI as measured by blood biomarkers and metabolomic profiling. Risk of bias was assessed with the CAMARADES checklist the SYRCLE's risk of bias tool. Standard meta-analysis methods (random-effects models) were used.
RESULTS
there were four studies for the same species, dosage, duration of vancomycin administration and measurement only for serum creatine and blood urea nitrogen in rats. A statistically significant increase was observed between serum creatinine in the vancomycin group compared to controls (pooled = 0.037; Standardized Mean Difference: 2.93; 95% CI: 0.17 to 5.69; I = 92.11%). Serum BUN levels were not significantly different between control and vancomycin groups (pooled = 0.11; SMD: 3.05; 95% CI: 0.69 to 6.8; I = 94.84%). We did not identify experimental studies using metabolomic analyses in animals with VIKI.
CONCLUSIONS
a total of four studies in rodents only described outcomes of kidney injury as defined by blood biomarkers. Blood biomarkers represented included serum creatinine and BUN. Novel blood biomarkers have not been explored.
PubMed: 36143182
DOI: 10.3390/jpm12091397 -
Pharmaceutics Mar 2022This systematic review and meta-analysis compares the efficacy of daptomycin and vancomycin in adult patients with bacteremia by methicillin-resistant Staphylococcus... (Review)
Review
Efficacy and Safety of Daptomycin versus Vancomycin for Bacteremia Caused by Methicillin-Resistant Staphylococcus aureus with Vancomycin Minimum Inhibitory Concentration > 1 µg/mL: A Systematic Review and Meta-Analysis.
This systematic review and meta-analysis compares the efficacy of daptomycin and vancomycin in adult patients with bacteremia by methicillin-resistant Staphylococcus aureus (MRSA) with vancomycin minimum inhibitory concentration (MIC) > 1 µg/mL. We searched the PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov databases on 12 May 2020. All-cause mortality (primary outcome) and treatment success rates were compared and subgroups stratified by infection source risk level and method of vancomycin susceptibility testing were also analyzed. Seven studies (n = 907 patients) were included in this efficacy analysis. Compared with vancomycin, daptomycin treatment was associated with significantly lower mortality (six studies, odds ratio (OR) 0.53, 95% confidence interval (CI) 0.29−0.98) and higher treatment success (six studies, OR 2.20, 95% CI 1.63−2.96), which was consistent regardless of the vancomycin MIC test method used. For intermediate-risk sources, daptomycin was a factor increasing treatment success compared with vancomycin (OR 4.40, 95% CI 2.06−9.40), and it exhibited a trend toward a higher treatment success rate for high-risk sources. In conclusion, daptomycin should be considered for the treatment of bacteremia caused by MRSA with vancomycin MIC > 1 µg/mL, especially in patients with intermediate- and high-risk bacteremia sources.
PubMed: 35456548
DOI: 10.3390/pharmaceutics14040714 -
Therapeutic Drug Monitoring Jun 2020Studies comparing the clinical outcomes between vancomycin intermittent infusion (InI) and continuous infusion (CoI) treated patients are generally underpowered....
BACKGROUND
Studies comparing the clinical outcomes between vancomycin intermittent infusion (InI) and continuous infusion (CoI) treated patients are generally underpowered. Moreover, due to large differences in the design and efficacy end points in these studies, a meta-analysis of the currently available data is not feasible. Therefore, this systematic review aimed to compare the exposure variability and target attainment with vancomycin during InI and CoI.
PATIENTS AND METHODS
A literature search was performed, and clinical studies reporting on vancomycin-treated populations were selected. After exclusion of reviews, case reports, and articles not published in the English language, 505 articles were screened for reported data on vancomycin serum concentrations. A total of 34 studies were included in the review. Relative standard deviations reported in the included studies were assessed, and vancomycin serum concentration variability and target attainment were compared between vancomycin InI and CoI.
RESULTS
The variability in serum concentrations was significantly larger for InI than for CoI (relative standard deviations 46.5% and 32.1%, respectively; P = 0.001). Notably, variability appeared to be independent of the study population or design. Studies directly comparing target attainment between both modes of administration denoted higher and faster target attainment with CoI in all instances.
CONCLUSIONS
In conclusion, CoI was associated with lower variabilities in the serum concentration and favorable target attainment rates compared with InI. These findings are important because vancomycin exposure is considered a major predictor of the patients' clinical outcomes. However, the role of lower serum concentration variability and higher target attainment rates in achieving better clinical outcomes needs to be evaluated in patients treated with vancomycin CoI compared with InI.
Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Drug Administration Schedule; Drug Monitoring; Healthy Volunteers; Humans; Infusions, Intravenous; Intensive Care Units; Vancomycin
PubMed: 32432845
DOI: 10.1097/FTD.0000000000000755 -
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 -
PloS One 2016A target AUC0-24/MIC ratio of 400 has been associated with its clinical success when treating Staphylococcus aureus infections but is not currently supported by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A target AUC0-24/MIC ratio of 400 has been associated with its clinical success when treating Staphylococcus aureus infections but is not currently supported by state-of-the-art evidence-based research.
OBJECTIVE
This current systematic review aimed to evaluate the available evidence for the association between the AUC0-24/MIC ratio of vancomycin and its clinical effectiveness on hospitalized patients and to confirm the existing target value of 400.
METHODS
PubMed, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were systematically searched. Manual searching was also applied. Both RCTs and observational studies comparing the clinical outcomes of high AUC0-24/MIC groups versus low AUC0-24/MIC groups were eligible. Two reviewers independently extracted the data. The primary outcomes were mortality and infection treatment failure. Risk ratios (RRs) with 95% confidence intervals (95%CIs) were calculated.
RESULTS
No RCTs were retrieved. Nine cohort studies were included in the meta-analysis. Mortality rates were significantly lower in high AUC0-24/MIC groups (RR = 0.47, 95%CI = 0.31-0.70, p<0.001). The rates of infection treatment failure were also significantly lower in high AUC/MIC groups and were consistent after correcting for heterogeneity (RR = 0.39, 95%CI = 0.28-0.55, p = 0.001). Subgroup analyses showed that results were consistent whether MIC values were determined by broth microdilution (BMD) method or Etest method. In studies using the BMD method, breakpoints of AUC0-24/MIC all fell within 85% to 115% of 400.
CONCLUSIONS
This meta-analysis demonstrated that achieving a high AUC0-24/MIC of vancomycin could significantly decrease mortality rates by 53% and rates of infection treatment failure by 61%, with 400 being a reasonable target.
Topics: Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Staphylococcal Infections; Treatment Outcome; Vancomycin
PubMed: 26731739
DOI: 10.1371/journal.pone.0146224