-
Clinical Journal of the American... Dec 2016Vancomycin has been in use for more than half a century, but whether it is truly nephrotoxic and to what extent are still highly controversial. The objective of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Vancomycin has been in use for more than half a century, but whether it is truly nephrotoxic and to what extent are still highly controversial. The objective of this study was to determine the risk of AKI attributable to intravenous vancomycin.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We conducted a systematic review of randomized, controlled trials and cohort studies that compared patients treated with intravenous vancomycin with a control group of patients given a comparator nonglycopeptide antibiotic and in which kidney function or kidney injury outcomes were reported. PubMed and Cochrane Library were searched from 1990 to September of 2015. Two reviewers extracted data and assessed study risk of bias, and one reviewer adjudicated the assessments. A meta-analysis was conducted on seven randomized, controlled trials (total of 4033 patients).
RESULTS
Moderate quality evidence suggested that vancomycin treatment is associated with a higher risk of AKI, with a relative risk of 2.45 (95% confidence interval, 1.69 to 3.55). The risk of kidney injury was similar in patients treated for skin and soft tissue infections compared with those treated for nosocomial pneumonia and other complicated infections. There was an uncertain risk of reporting bias, because kidney function was not a prespecified outcome in any of the trials. The preponderance of evidence was judged to be indirect, because the majority of studies compared vancomycin specifically with linezolid.
CONCLUSIONS
Our findings suggest that there is a measurable risk of AKI associated with vancomycin, but the strength of the evidence is moderate. A randomized, controlled trial designed to study kidney function as an outcome would be needed to draw unequivocal conclusions.
Topics: Acute Kidney Injury; Administration, Intravenous; Anti-Bacterial Agents; Humans; Linezolid; Risk Factors; Vancomycin
PubMed: 27895134
DOI: 10.2215/CJN.05920616 -
Antibiotics (Basel, Switzerland) Apr 2023Vancomycin (VCM) and daptomycin (DAP) are standard therapies for methicillin-resistant (MRSA) bacteremia, despite concerns regarding clinical utility and growing... (Review)
Review
Vancomycin (VCM) and daptomycin (DAP) are standard therapies for methicillin-resistant (MRSA) bacteremia, despite concerns regarding clinical utility and growing resistance. Linezolid (LZD) affords superior tissue penetration to VCM or DAP and has been successfully used as salvage therapy for persistent MRSA bacteremia, indicating its utility as a first-choice drug against MRSA bacteremia. In a systematic review and meta-analysis, we compared the effectiveness and safety of LZD with VCM, teicoplanin (TEIC), or DAP in patients with MRSA bacteremia. We evaluated all-cause mortality as the primary effectiveness outcome, clinical and microbiological cure, hospital length of stay, recurrence, and 90-day readmission rates as secondary effectiveness outcomes, and drug-related adverse effects as primary safety outcomes. We identified 5328 patients across 2 randomized controlled trials (RCTs), 1 pooled analysis of 5 RCTs, 1 subgroup analysis (1 RCT), and 5 case-control and cohort studies (CSs). Primary and secondary effectiveness outcomes were comparable between patients treated with LZD versus VCM, TEIC, or DAP in RCT-based studies and CSs. There was no difference in adverse event incidence between LZD and comparators. These findings suggest that LZD could be a potential first-line drug against MRSA bacteremia as well as VCM or DAP.
PubMed: 37107059
DOI: 10.3390/antibiotics12040697 -
British Journal of Clinical Pharmacology Sep 2022This systematic literature review and meta-analysis aimed to evaluate the risk factors for vancomycin-associated acute kidney injury (AKI) incidence. (Meta-Analysis)
Meta-Analysis Review
AIMS
This systematic literature review and meta-analysis aimed to evaluate the risk factors for vancomycin-associated acute kidney injury (AKI) incidence.
METHODS
This study assessed risk factors for vancomycin-associated AKI in adult patients by searching studies from PubMed, the Cochrane Library and Embase. Random effect models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
Fifty-three studies were included in our meta-analysis. For patient factors, black race (OR 1.47, 95% CI: 1.16-1.87), Caucasian (OR 0.72, 95% CI: 0.58-0.90) and obesity (OR 1.46, 95% CI: 1.12-1.90) were associated with an increase in vancomycin-associated AKIs. In terms of vancomycin-related factors, longer treatment duration (>14 d; OR 1.73, 95% CI: 1.06-2.83), serum vancomycin trough level >15 μg/mL (OR 2.10, 95% CI: 1.43-3.07) and vancomycin trough level >20 μg/mL (OR 2.84, 95% CI: 1.48-5.44) increased the risks of vancomycin-associated AKI. For comorbidities and clinical factors, renal disease (OR 2.19, 95% CI: 1.51-3.17) showed the highest odds of vancomycin-associated AKI, followed by hepatic disease, intensive care unit admission, heart failure, sepsis, coronary heart disease and diabetes mellitus. For concomitant nephrotoxic drugs, amphotericin B (OR 5.21, 95% CI: 3.44-7.87) showed the highest odds of vancomycin-associated AKI, followed by acyclovir (OR 3.22, 95% CI: 1.39-7.46), vasopressors, loop diuretics, piperacillin-tazobactam and aminoglycoside. The use of any concomitant nephrotoxic agent (OR 1.74, 95% CI: 1.17-2.58) increased the odds of vancomycin-associated AKI.
CONCLUSION
Our results may help predict the risk of vancomycin-associated AKI in the clinical setting.
Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Retrospective Studies; Risk Factors; Vancomycin
PubMed: 35665530
DOI: 10.1111/bcp.15429 -
Antimicrobial Resistance and Infection... Feb 2022Healthcare-associated infections (HAI) are one of the gravest threats to patient safety worldwide. The importance of the hospital environment has recently been revalued... (Review)
Review
BACKGROUND
Healthcare-associated infections (HAI) are one of the gravest threats to patient safety worldwide. The importance of the hospital environment has recently been revalued in infection prevention and control. Though the literature is evolving rapidly, many institutions still do not consider healthcare environmental hygiene (HEH) very important for patient safety. The evidence for interventions in the healthcare environment on patient colonization and HAI with multidrug-resistant microorganisms (MDROs) or other epidemiologically relevant pathogens was reviewed.
METHODS
We performed a systematic review according to the PRISMA guidelines using the PubMed and Web of Science databases. All original studies were eligible if published before December 31, 2019, and if the effect of an HEH intervention on HAI or patient colonization was measured. Studies were not eligible if they were conducted in vitro, did not include patient colonization or HAI as an outcome, were bundled with hand hygiene interventions, included a complete structural rebuild of the healthcare facility or were implemented during an outbreak. The primary outcome was the comparison of the intervention on patient colonization or HAI compared to baseline or control. Interventions were categorized by mechanical, chemical, human factors, or bundles. Study quality was assessed using a specifically-designed tool that considered study design, sample size, control, confounders, and issues with reporting. The effect of HEH interventions on environmental bioburden was studied as a secondary outcome.
FINDINGS
After deduplication, 952 records were scrutinized, of which 44 were included for full text assessment. A total of 26 articles were included in the review and analyzed. Most studies demonstrated a reduction of patient colonization or HAI, and all that analyzed bioburden demonstrated a reduction following the HEH intervention. Studies tested mechanical interventions (n = 8), chemical interventions (n = 7), human factors interventions (n = 3), and bundled interventions (n = 8). The majority of studies (21/26, 81%) analyzed either S. aureus, C. difficile, and/or vancomycin-resistant enterococci. Most studies (23/26, 88%) reported a decrease of MDRO-colonization or HAI for at least one of the tested organisms, while 58% reported a significant decrease of MDRO-colonization or HAI for all tested microorganisms. Forty-two percent were of good quality according to the scoring system. The majority (21/26, 81%) of study interventions were recommended for application by the authors. Studies were often not powered adequately to measure statistically significant reductions.
INTERPRETATION
Improving HEH helps keep patients safe. Most studies demonstrated that interventions in the hospital environment were related with lower HAI and/or patient colonization. Most of the studies were not of high quality; additional adequately-powered, high-quality studies are needed. Systematic registration number: CRD42020204909.
Topics: Clostridioides difficile; Cross Infection; Delivery of Health Care; Humans; Hygiene; Staphylococcus aureus
PubMed: 35183259
DOI: 10.1186/s13756-022-01075-1 -
Pharmacotherapy Sep 2022Vancomycin is commonly used to treat methicillin-resistant Staphylococcus aureus infections and is known to cause nephrotoxicity. Previous Vancomycin Consensus... (Meta-Analysis)
Meta-Analysis Review
Vancomycin is commonly used to treat methicillin-resistant Staphylococcus aureus infections and is known to cause nephrotoxicity. Previous Vancomycin Consensus Guidelines recommended targeting trough concentrations but the 2020 Guidelines suggest monitoring vancomycin area under the curve (AUC) given the reduced risk of acute kidney injury (AKI) at similar levels of efficacy. This meta-analysis compares vancomycin-induced AKI incidence using AUC-guided dosing strategies versus trough-based monitoring. Literature was queried from Medline (Ovid), Web of Science, and Google Scholar from database inception through November 5, 2021. Interventional or observational studies reporting the incidence of vancomycin-induced AKI between AUC- and trough-guided dosing strategies were included. In the primary analysis, the Vancomycin Consensus Guidelines definition for AKI was used if reported; otherwise, the Risk, Injury, and Failure; and Loss, and End-stage kidney disease (RIFLE) or Kidney Disease Improving Global Outcomes (KDIGO) definitions were used. The incidence of nephrotoxicity was evaluated between the two strategies using a Mantel-Haenszel random-effects model, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses for adjusted ORs and AKI definitions were performed. Heterogeneity was identified using Cochrane's Q test and I statistics. A total of 10 studies with 4231 patients were included. AUC-guided dosing strategies were associated with significantly less vancomycin-induced AKI than trough-guided strategies [OR 0.625, 95% CI (0.469-0.834), p = 0.001; I = 25.476]. A subgroup analysis of three studies reporting adjusted ORs yielded similar results [OR 0.475, 95% CI (0.261-0.863), p = 0.015]. Stratification by AKI definition showed a significant reduction in AKI with the Vancomycin Consensus Guidelines definition [OR 0.552, 95% CI (0.341-0.894), p = 0.016] but failed to find significance in the alternative definitions. Area under the curve-guided dosing strategies are associated with a lower incidence of vancomycin-induced AKI versus trough-guided dosing strategies (GRADE, low). Limitations included the variety of AKI definitions and the potential for confounding bias.
Topics: Humans; Acute Kidney Injury; Anti-Bacterial Agents; Area Under Curve; Electrolytes; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Retrospective Studies; Vancomycin
PubMed: 35869689
DOI: 10.1002/phar.2722 -
JAMA Jan 2015Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased. (Review)
Review
IMPORTANCE
Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased.
OBJECTIVE
To review current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age ≥ 18 years).
EVIDENCE REVIEW
Ovid MEDLINE and Cochrane databases were searched using keywords relevant to the diagnosis and treatment of CDI in adults. Articles published between January 1978 and October 31, 2014, were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a guideline, systematic review, or meta-analysis published within the past 10 years. Of 4682 articles initially identified, 196 were selected for full review. Of these, the most pertinent 116 articles were included. Clinical trials, large observational studies, and more recently published articles were prioritized in the selection process.
FINDINGS
Laboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C difficile. Diagnostic approaches are complex due to the availability of multiple testing strategies. Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single-step PCR on liquid stool samples have the best test performance characteristics (for multistep: sensitivity was 0.68-1.00 and specificity was 0.92-1.00; and for single step: sensitivity was 0.86-0.92 and specificity was 0.94-0.97). Vancomycin and metronidazole are first-line therapies for most patients, although treatment failures have been associated with metronidazole in severe or complicated cases of CDI. Recent data demonstrate clinical success rates of 66.3% for metronidazole vs 78.5% for vancomycin for severe CDI. Newer therapies show promising results, including fidaxomicin (similar clinical cure rates to vancomycin, with lower recurrence rates for fidaxomicin, 15.4% vs vancomycin, 25.3%; P = .005) and fecal microbiota transplantation (response rates of 83%-94% for recurrent CDI).
CONCLUSIONS AND RELEVANCE
Diagnostic testing for CDI should be performed only in symptomatic patients. Treatment strategies should be based on disease severity, history of prior CDI, and the individual patient's risk of recurrence. Vancomycin is the treatment of choice for severe or complicated CDI, with or without adjunctive therapies. Metronidazole is appropriate for mild disease. Fidaxomicin is a therapeutic option for patients with recurrent CDI or a high risk of recurrence. Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established.
Topics: Adult; Anti-Bacterial Agents; Clostridioides difficile; Enterocolitis, Pseudomembranous; Humans
PubMed: 25626036
DOI: 10.1001/jama.2014.17103 -
BMC Infectious Diseases Feb 2021This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety.
METHODS
We conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
Adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 μg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47-0.85). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 μg/mL compared to those at 15-20 μg/mL (OR 2.39, 95% CI 1.78-3.20). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18-0.45). The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13-3.89). Our meta-analysis of differences in monitoring strategies included four studies. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28-1.01); however, it was not significant in the analysis of mortality.
CONCLUSIONS
We identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.
Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Area Under Curve; Bacteremia; Drug Monitoring; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Odds Ratio; Safety; Staphylococcal Infections; Treatment Failure; Vancomycin
PubMed: 33549035
DOI: 10.1186/s12879-021-05858-6 -
Clinical Microbiology and Infection :... Mar 2023COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises.
OBJECTIVE
We aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings.
DATA SOURCE
A search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022.
STUDY ELIGIBILITY
Studies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted.
METHODS
Pooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed.
RESULTS
Of 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67-1.47) or proportion (risk ratio 0.91, 95% CI: 0.55-1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92-2.92; risk ratio 1.08, 95% CI: 0.91-1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03-1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40).
CONCLUSION
The COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Methicillin-Resistant Staphylococcus aureus; COVID-19; Carbapenems
PubMed: 36509377
DOI: 10.1016/j.cmi.2022.12.006 -
The Cochrane Database of Systematic... Nov 2021Hospital-acquired pneumonia is one of the most common hospital-acquired infections in children worldwide. Most of our understanding of hospital-acquired pneumonia in... (Review)
Review
BACKGROUND
Hospital-acquired pneumonia is one of the most common hospital-acquired infections in children worldwide. Most of our understanding of hospital-acquired pneumonia in children is derived from adult studies. To our knowledge, no systematic review with meta-analysis has assessed the benefits and harms of different antibiotic regimens in neonates and children with hospital-acquired pneumonia.
OBJECTIVES
To assess the beneficial and harmful effects of different antibiotic regimens for hospital-acquired pneumonia in neonates and children.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, three other databases, and two trial registers to February 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included randomised clinical trials comparing one antibiotic regimen with any other antibiotic regimen for hospital-acquired pneumonia in neonates and children.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were all-cause mortality and serious adverse events; our secondary outcomes were health-related quality of life, pneumonia-related mortality, non-serious adverse events, and treatment failure. Our primary time point of interest was at maximum follow-up.
MAIN RESULTS
We included four randomised clinical trials (84 participants). We assessed all trials as having high risk of bias. We did not conduct any meta-analyses, as the included trials did not compare similar antibiotic regimens. Each of the four trials assessed a different comparison, as follows: cefepime versus ceftazidime; linezolid versus vancomycin; meropenem versus cefotaxime; and ceftobiprole versus cephalosporin. Only one trial reported our primary outcomes of all-cause mortality and serious adverse events. Three trials reported our secondary outcome of treatment failure. Two trials primarily included community-acquired pneumonia and hospitalised children with bacterial infections, hence the children with hospital-acquired pneumonia constituted subgroups of the total sample sizes. Where outcomes were reported, the certainty of the evidence was very low for each of the comparisons. We are unable to draw meaningful conclusions from the numerical results. None of the included trials assessed health-related quality of life, pneumonia-related mortality, or non-serious adverse events.
AUTHORS' CONCLUSIONS
The relative beneficial and harmful effects of different antibiotic regimens remain unclear due to the very low certainty of the available evidence. The current evidence is insufficient to support any antibiotic regimen being superior to another. Randomised clinical trials assessing different antibiotic regimens for hospital-acquired pneumonia in children and neonates are warranted.
Topics: Adult; Anti-Bacterial Agents; Child; Hospitals; Humans; Infant, Newborn; Pneumonia; Quality of Life; Randomized Controlled Trials as Topic; Vancomycin
PubMed: 34727368
DOI: 10.1002/14651858.CD013864.pub2 -
Revista Do Instituto de Medicina... 2021The aim of this study was to establish an evidence-based guideline for the antibiotic treatment of Corynebacterium striatum infections. Several electronic databases were...
The aim of this study was to establish an evidence-based guideline for the antibiotic treatment of Corynebacterium striatum infections. Several electronic databases were systematically searched for clinical trials, observational studies or individual cases on patients of any age and gender with systemic inflammatory response syndrome, harboring C. striatum isolated from body fluids or tissues in which it is not normally present. C. striatum had to be identified as the only causative agent of the invasive infection, and its isolation from blood, body fluids or tissues had to be confirmed by one of the more advanced diagnostic methods (biochemical methods, mass spectrometry and/or gene sequencing). This systematic review included 42 studies that analyzed 85 individual cases with various invasive infections caused by C. striatum. More than one isolate of C. striatum exhibited 100% susceptibility to vancomycin, linezolid, teicoplanin, piperacillin-tazobactam, amoxicillin-clavulanate and cefuroxime. On the other hand, some strains of this bacterium showed a high degree of resistance to fluoroquinolones, to the majority majority of β-lactams, aminoglycosides, macrolides, lincosamides and cotrimoxazole. Despite the antibiotic treatment, fatal outcomes were reported in almost 20% of the patients included in this study. Gene sequencing methods should be the gold standard for the identification of C. striatum, while MALDI-TOF and the Vitek system can be used as alternative methods. Vancomycin should be used as the antibiotic of choice for the treatment of C. striatum infections, in monotherapy or in combination with piperacillin-tazobactam. Alternatively, linezolid, teicoplanin or daptomycin may be used in severe infections, while amoxicillin-clavulanate may be used to treat mild infections caused by C. striatum.
Topics: Aminoglycosides; Anti-Bacterial Agents; Corynebacterium; Corynebacterium Infections; Humans; Microbial Sensitivity Tests
PubMed: 34161555
DOI: 10.1590/S1678-9946202163049