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Surgery Nov 2023Despite guideline recommendations, routine application of topical antibiotic agents to sternal edges after cardiac surgery is seldom done. Recent randomized controlled... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite guideline recommendations, routine application of topical antibiotic agents to sternal edges after cardiac surgery is seldom done. Recent randomized controlled trials have also questioned the effectiveness of topical vancomycin in sternal wound infection prophylaxis.
METHODS
We screened multiple databases for observational studies and randomized controlled trials assessing the effectiveness of topical vancomycin. Random effects meta-analysis and risk-profile regression were performed, and randomized controlled trials and observational studies were analyzed separately. The primary endpoint was sternal wound infection; other wound complications were also analyzed. Risk ratios served as primary statistics.
RESULTS
Twenty studies (N = 40,871) were included, of which 7 were randomized controlled trials (N = 2,187). The risk of sternal wound infection was significantly reduced by almost 70% in the topical vancomycin group (risk ratios [95% confidence intervals]: 0.31 (0.23-0.43); P < .00001) and was comparable between randomized controlled trials (0.37 [0.21-0.64]; P < .0001) and observational studies (0.30 [0.20-0.45]; P < .00001; P = .57). Topical vancomycin significantly reduced the risk of superficial sternal wound infections (0.29 [0.15-0.53]; P < .00001) and deep sternal wound infections (0.29 [0.19-0.44]; P < .00001). A reduction in the risk of mediastinitis and sternal dehiscence risks was also demonstrated. Risk profile meta-regression showed a significant relationship between a higher risk of sternal wound infection and a higher benefit accrued with topical vancomycin (ß-coeff. = -0.00837; P < .0001). The number needed to treat was 58.2. A significant benefit was observed in patients with diabetes mellitus (risk ratios 0.21 [0.11-0.39]; P < .00001). There was no evidence of vancomycin or methicillin resistance; on the contrary, the risk of gram-negative cultures was reduced by over 60% (risk ratios 0.38 [0.22-0.66]; P = .0006).
CONCLUSION
Topical vancomycin effectively reduces the risk of sternal wound infection in cardiac surgery patients.
Topics: Humans; Vancomycin; Surgical Wound Infection; Anti-Bacterial Agents; Cardiac Surgical Procedures; Sternum
PubMed: 37414589
DOI: 10.1016/j.surg.2023.05.031 -
European Spine Journal : Official... Mar 2015Post-operative spine surgical site infections are associated with substantial morbidity, mortality, and economic burden. Intrawound vancomycin may prevent infections... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Post-operative spine surgical site infections are associated with substantial morbidity, mortality, and economic burden. Intrawound vancomycin may prevent infections after spine surgery, but recent studies have reported conflicting results. The objectives of this systematic review and meta-analysis were to determine: (1) In patients undergoing spine surgery, does the application of intrawound vancomycin lead to reduced rates of post-operative surgical site infections? (2) Are there differences in the estimates of effect between observational studies and randomized trials? (3) What adverse events are reported in the literature?
METHODS
All published comparative studies of intrawound vancomycin in spine surgery were included. Two reviewers independently screened eligible articles and assessed study quality. Observational studies and randomized trials were pooled separately using a random-effects model.
RESULTS
Eight observational studies and one randomized controlled trial met the inclusion criteria. Across observational studies, the odds of infection with intrawound vancomycin was 0.19 times the odds of infection without intrawound vancomycin (95 % CI 0.08-0.47, p = 0.0003, I (2) = 52 %). The single randomized controlled trial produced a conflicting result (OR 0.96, 95 % CI 0.34-2.66, p = 0.93). There were no adverse events attributable to intrawound vancomycin. The quality of the evidence was low or very low.
CONCLUSIONS
There is a lack of high-quality evidence to inform the use of intrawound vancomycin in spine surgery. Surgeons should be cautious before widely adopting this intervention and should be vigilant in monitoring for adverse effects. Further investigation with additional randomized controlled trials is justified.
Topics: Anti-Bacterial Agents; Humans; Spine; Surgical Wound Infection; Treatment Outcome; Vancomycin
PubMed: 24838506
DOI: 10.1007/s00586-014-3357-0 -
The Journal of the Egyptian Public... Apr 2023Vancomycin-resistant Enterococci (VRE) represent a critical medical and public health concerns due to their association with serious nosocomial infections and a high... (Review)
Review
BACKGROUND
Vancomycin-resistant Enterococci (VRE) represent a critical medical and public health concerns due to their association with serious nosocomial infections and a high risk of mortality. We aimed to reveal the pooled prevalence of VRE and antimicrobial resistance profiles among enterococci clinical isolates in Egypt.
METHODS
A PubMed, Scopus, Google Scholar, and Web of Science literature search was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Only published studies documenting the prevalence of VRE between 2010 and 2022 were included. Using the random effects model and the 95% confidence intervals, the pooled estimate of VRE was calculated by MedCalc Version 20.113. Cochran's Q and I tests were used to evaluate the degree of heterogeneity, and publication bias was examined by visually examining the funnel plot and its associated tests (Begg's and Egger's tests).
RESULTS
The pooled prevalence of VRE among enterococci clinical isolates in Egypt was estimated to be 26% (95% CI 16.9 to 36.3). E. faecalis had a greater pooled prevalence than E. faecium, with 61.22% (95% CI 53.65 to 68.53) and 32.47% (95% CI 27 to 38.2), respectively. The VanA gene is more frequent than the VanB gene among VRE, with a pooled prevalence of 63.3% (95% CI 52.1 to 73.7) and 17.95% (95% CI 7.8 to 31), respectively. The pooled resistance rate of linezolid was substantially lower than that of ampicillin and high-level gentamicin (HLG) 5.54% (95% CI 2.33 to 10%), 65.7% (95% CI 50.8 to 79.2%), and 61.1% (95% CI 47.4 to 73.9), respectively.
CONCLUSION
The prevalence of VRE is alarmingly high in Egypt. It is imperative that antimicrobial stewardship activities and infection control programs are strictly adhered to and implemented to prevent further escalation of the problem.
PubMed: 37037955
DOI: 10.1186/s42506-023-00133-9 -
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 -
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 -
The Pediatric Infectious Disease Journal Jul 2018Vancomycin is frequently used to treat methicillin-resistant Staphylococcus aureus infections in pediatric patients. Vancomycin exposure may lead to an increase in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vancomycin is frequently used to treat methicillin-resistant Staphylococcus aureus infections in pediatric patients. Vancomycin exposure may lead to an increase in frequency of nephrotoxicity. Our aim was to conduct a systematic review to describe predictors of nephrotoxicity associated with vancomycin, including documented trough concentrations ≥15 mg/L. We also aimed to use a meta-analysis to assess the impact of a vancomycin trough ≥15 mg/L on nephrotoxicity.
METHODS
A literature search was performed using PubMed, Cochrane Library, Embase and Web of Sciences database. We included randomized clinical trials and observational studies evaluating the relationship between vancomycin troughs and nephrotoxicity in pediatric-age patients. Studies not measuring troughs or defining a different cut-off point than 15 mg/L were excluded. Data on age, exclusion criteria, nephrotoxicity definition, risk factors for nephrotoxicity and vancomycin trough levels were extracted from selected papers.
RESULTS
Ten studies were identified for meta-analysis. All subjects had comparatively normal baseline serum creatinine values. Common risk factors identified included elevated (≥15 mg/L) trough levels, renal impairment, hypovolemia and concurrent use of nephrotoxic medications. Troughs ≥15 mg/L increased nephrotoxicity by 2.7-fold (odds ratio (OR), 2.71; 95% confidence interval: 1.82-4.05; I(2) = 40%; Q = 0.09). These odds were further increased among patients in the pediatric intensive care unit (OR, 3.61; 95% confidence interval: 1.21-10.74; I(2) = 45%; Q = 0.18).
CONCLUSIONS
Though the rate of vancomycin-induced nephrotoxicity is increased in pediatric patients with higher vancomycin troughs, other factors such as intensive care unit admission, hypovolemia and concurrent nephrotoxic drug use appear to contribute to the development of nephrotoxicity.
Topics: Anti-Bacterial Agents; Child; Humans; Intensive Care Units; Kidney; Kidney Diseases; Methicillin-Resistant Staphylococcus aureus; Observational Studies as Topic; Odds Ratio; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Staphylococcal Infections; Vancomycin
PubMed: 29280786
DOI: 10.1097/INF.0000000000001882 -
Paediatric Drugs Apr 2018In adults, the area under the concentration-time curve (AUC) divided by the minimum inhibitory concentration (MIC) is associated with better clinical and bacteriological... (Review)
Review
BACKGROUND
In adults, the area under the concentration-time curve (AUC) divided by the minimum inhibitory concentration (MIC) is associated with better clinical and bacteriological response to vancomycin in patients with methicillin-resistant Staphylococcus aureus who achieve target AUC/MIC ≥ 400. This target is often extrapolated to pediatric patients despite the lack of similar evidence. The impracticalities of calculating the AUC in practice means vancomycin trough concentrations are used to predict the AUC/MIC.
OBJECTIVE
This review aimed to determine the relationship between vancomycin trough concentrations and AUC/MIC in pediatric patients.
METHODS
We searched the MEDLINE and Embase databases, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials using the medical subject heading (MeSH) terms vancomycin and AUC and pediatric* or paediatric*. Articles were included if they were published in English and reported a relationship between vancomycin trough concentrations and AUC/MIC.
RESULTS
Of 122 articles retrieved, 11 met the inclusion criteria. One trial reported a relationship between vancomycin trough concentrations, AUC/MIC, and clinical outcomes but was likely underpowered. Five studies found troughs 6-10 mg/l were sufficient to attain an AUC/MIC > 400 in most general hospitalized pediatric patients. One study in patients undergoing cardiothoracic surgery found a trough of 18.4 mg/l achieved an AUC/MIC > 400. Two oncology studies reported troughs ≥ 15 mg/l likely attained an AUC/MIC ≥ 400. In critical care patients: one study found a trough of 9 mg/l did not attain the AUC/MIC target; another found 7 mg/l corresponded to an AUC/MIC of 400.
CONCLUSIONS
Potential vancomycin targets varied based on the population studied but, for general hospitalized pediatric patients, troughs of 6-10 mg/l are likely sufficient to achieve AUC/MIC ≥ 400. For MIC ≥ 2 mg/l, higher troughs are likely necessary to achieve an AUC/MIC ≥ 400. More research is needed to determine the relationships between vancomycin trough concentrations, AUC/MIC, and clinical outcomes.
Topics: Anti-Bacterial Agents; Area Under Curve; Child; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Qualitative Research; Staphylococcal Infections; Vancomycin
PubMed: 29344778
DOI: 10.1007/s40272-018-0282-4 -
International Journal of Antimicrobial... Feb 2018Although the exposure-dependent efficacy thresholds of vancomycin have been probed, less is known about acute kidney injury (AKI) thresholds for this drug. Sensitive... (Review)
Review
BACKGROUND
Although the exposure-dependent efficacy thresholds of vancomycin have been probed, less is known about acute kidney injury (AKI) thresholds for this drug. Sensitive urinary biomarkers, such as kidney injury molecule 1 (KIM-1), have shown high sensitivity and specificity for vancomycin-associated AKI. The aims of the study were to determine if there were dose-response curves with urinary KIM-1, and to evaluate the impact of therapy duration and sex on observed relationships.
METHODS
A systematic review was conducted via PubMed/MEDLINE. Data were compiled from preclinical studies that reported individual subject data for urinary KIM-1 concentrations, vancomycin dose (mg/kg), duration of treatment, and sex. Sigmoidal Hill-type models were fit to the individual dose-response data.
RESULTS
A total of 15 studies were identified, 6 of which reported vancomycin dose and KIM-1 data. Of these, three included individual animal-level data suitable for analysis. For all pooled rats, increasing total daily vancomycin doses displayed a dose-response curve with urinary KIM-1 concentrations (50% maximal toxic response=130.4 mg/kg/day). Dose-response curves were shifted left for females vs. males (P = 0.05) and for long (i.e. ≥7 days) vs. short (i.e. <4 days) duration of vancomycin therapy (P=0.02).
CONCLUSIONS
The collective findings demonstrate a clear dose-response relationship between vancomycin dose and AKI. As these analyses focused exclusively on dose-response relationships, additional preclinical data are needed to more clearly define vancomycin exposures that predict the onset of AKI.
Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Female; Hepatitis A Virus Cellular Receptor 1; Humans; Male; Rats; Vancomycin
PubMed: 28803934
DOI: 10.1016/j.ijantimicag.2017.08.012 -
The Journal of Arthroplasty Jul 2022Periprosthetic joint injection (PJI) is a rare, but life-altering complication of total joint arthroplasty (TJA). Though intrawound vancomycin powder (IVP) has been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Periprosthetic joint injection (PJI) is a rare, but life-altering complication of total joint arthroplasty (TJA). Though intrawound vancomycin powder (IVP) has been studied in other orthopedic subspecialties, its efficacy and safety in TJA has not been established.
METHODS
PubMed and MEDLINE databases were used to identify studies utilizing IVP in primary and revision total hip (THA) and knee arthroplasty (TKA). Postoperative PJI data were pooled using random effect models with results reported as odds ratios (ORs) and 95% confidence intervals (CIs). Studies were weighted by the inverse variance of their effect estimates.
RESULTS
Overall, 16 of the 1871 studies identified were pooled for final analysis, yielding 33,731 patients totally. Of these, 17 164 received IVP. In aggregate, patients who received IVP had a decreased rate of PJI (OR 0.46, P < .05). Separately, TKA and THA patients who received IVP had lower rates of PJI (OR 0.41, P < .05 and OR 0.45, P < .05, respectively). Aggregate analysis of primary TKA and THA patients also revealed a decreased PJI rate (OR 0.44, P < .05). Pooled revision TKA and THA patients had a similar decrease in PJI rates (OR 0.30, P < .05). Although no publication bias was appreciated, these findings are limited by the low-quality evidence available.
CONCLUSION
While IVP may reduce the risk of PJI in primary and revision TJA, its widespread use cannot be recommended until higher-quality data, such as that obtained from randomized control trials, are available. This study underscores the continued need for more rigorous studies before general adoption of this practice by arthroplasty surgeons.
Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Humans; Odds Ratio; Prospective Studies; Prosthesis-Related Infections; Randomized Controlled Trials as Topic; Retrospective Studies; Vancomycin
PubMed: 35314283
DOI: 10.1016/j.arth.2022.03.047 -
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