-
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 -
JBJS Reviews Dec 2023To determine whether there is any difference in graft rerupture rates and clinical outcomes between cases having vancomycin graft presoaking vs. no vancomycin presoaking... (Meta-Analysis)
Meta-Analysis
Vancomycin Graft Presoaking in Anterior Cruciate Ligament Reconstruction Surgery Is Associated with a Lower Risk of Graft Rerupture as Compared With No Vancomycin Presoaking: Systematic Review and Meta-analysis.
BACKGROUND
To determine whether there is any difference in graft rerupture rates and clinical outcomes between cases having vancomycin graft presoaking vs. no vancomycin presoaking in anterior cruciate ligament (ACL) reconstruction (ACLR).
METHODS
Systematic review and meta-analysis. PubMed, Embase, CINAHL, and Cochrane CENTRAL were searched. Full published studies reporting on the relation between vancomycin graft presoaking and rates of graft rerupture and/or clinical outcomes in ACLR surgery vs. no vancomycin graft presoaking were included. Data extraction and quality appraisal were performed. Meta-analysis was conducted using a random effects model. The study's protocol was prospectively registered with PROSPERO (CRD42021290608).
RESULTS
The literature search identified 907 records. After removing duplicates and those not meeting inclusion criteria, 8 studies were included. Meta-analysis showed that the estimated risk of hamstring graft rerupture was lower in cases presoaked with vancomycin vs. those having no presoaking (3.2% vs. 6.2% rerupture rate, risk ratio [RR] = 0.507, 95% CI, 0.39-0.737, p < 0.001). Similarly, the estimated risk of graft rerupture was lower in cases presoaked with vancomycin vs. those having no presoaking when the analysis included various ACL graft types (2.7% vs. 3.9% rerupture rate, RR = 0.557, 95% confidence interval [CI], 0.403-0.771, p < 0.001). Meta-analysis also showed that vancomycin graft presoaking was associated with similar International Knee Documentation Committee scores as compared with no presoaking when looking at hamstring grafts (estimated mean difference 0.112, 95% CI, -2.359 to 2.582, p = 0.929) or when considering various graft types (estimated mean difference 0.933, 95% CI, -0.140 to 2.006, p = 0.088).
CONCLUSION
Vancomycin graft presoaking is a safe practice and does not compromise ACL graft rerupture rates or clinical outcomes.
LEVEL OF EVIDENCE
Level IV. See Instructions for Authors for a complete description of levels of evidence.
Topics: Humans; Vancomycin; Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Knee Joint
PubMed: 38117914
DOI: 10.2106/JBJS.RVW.23.00145 -
Techniques in Coloproctology Dec 2023Newer antibiotics that specifically target Clostridioides difficile while preserving the host microbiome have emerged to treat C. difficile infection (CDI): cadazolid,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Newer antibiotics that specifically target Clostridioides difficile while preserving the host microbiome have emerged to treat C. difficile infection (CDI): cadazolid, fidaxomicin, ridinilazole, and surotomycin. The aim of the present study was to perform a systematic review and meta-analysis of efficacy for each antibiotic.
METHODS
Only randomized clinical trials of patients being treated for Clostridioides disease infection were included. Studies were sought in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organization clinical trials register portal (up to December 9, 2022). Sustained clinical cure was the outcome of treatment comparison, defined as the resolution of diarrhea without recurrence. Vancomycin was the standard treatment comparator. Meta-analysis was performed for each antibiotic. The overall certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-classified as either high, moderate, low, or very low.
RESULTS
Fourteen eligible studies were included in the meta-analysis with 4837 patients from 773 sites. Cadazolid did not increase sustained clinical cure relative to vancomycin (risk ratio (RR) 1.04, 95% confidence intervals (CI) 0.96-1.13; moderate-certainty evidence). Fidaxomicin demonstrated a significant increase (RR 1.14, 95% CI 1.07-1.21; low-certainty evidence). In one phase 2 study, ridinilazole demonstrated a significant increase in sustained clinical cure (RR 1.71, 95% CI 1.01-2.91; very low-quality evidence). Surotomycin did not show significant improvement (RR 1.05, 95% CI 0.96-1.14; moderate-certainty evidence).
CONCLUSIONS
Fidaxomicin (in seven studies) demonstrated significant improvement in achieving sustained clinical cure. A limitation of this study may that more studies are needed to compare fidaxomicin with other antibiotics.
Topics: Humans; Anti-Bacterial Agents; Vancomycin; Fidaxomicin; Clostridioides difficile; Clostridium Infections
PubMed: 38112980
DOI: 10.1007/s10151-023-02878-z -
Clinical Microbiology and Infection :... Mar 2024To prioritize healthcare investments, ranking of infections caused by antibiotic-resistant bacteria should be based on accurate incidence data. (Meta-Analysis)
Meta-Analysis Review
Frequency of bloodstream infections caused by six key antibiotic-resistant pathogens for prioritization of research and discovery of new therapies in Europe: a systematic review.
BACKGROUND
To prioritize healthcare investments, ranking of infections caused by antibiotic-resistant bacteria should be based on accurate incidence data.
OBJECTIVES
We performed a systematic review to estimate frequency measures of antimicrobial resistance for six key bacteria causing bloodstream infections (BSI) in European countries.
DATA SOURCES
We searched PubMed, Web of Science, Embase databases, and the ECRAID-Base Epidemiological-Network platform.
STUDY ELIGIBILITY CRITERIA
We included studies and surveillance systems assessing resistance-percentage, prevalence, or incidence-density of BSI because of carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli, third-generation cephalosporins-resistant E. coli and K. pneumoniae, vancomycin-resistant Enterococcus faecium, and methicillin-resistant Staphylococcus aureus.
METHODS
Reviewers independently assessed published data and evaluated study quality with the modified Joanna Briggs Institute critical appraisal tool. Pooled estimates were determined using random effects meta-analysis. Consistency of data was assessed using random effects meta-regression (Wald test, p > 0.05).
RESULTS
We identified 271 studies and 52 surveillance systems from 32 European countries. Forty-five studies (16%) reported on BSI, including 180 frequency measures most commonly as resistance-percentage (88, 48.9%). Among 309 frequency measures extracted from 24 (46%) surveillance systems, 278 (89%) were resistance-percentages. Frequency measures of methicillin-resistant S. aureus and vancomycin-resistant E. faecium BSI were more frequently reported from Southern Europe and Western Europe (80%), whereas carbapenem-resistant P. aeruginosa BSI from Northern Europe and Western Europe (88%). Highest resistance-percentages were detected for carbapenem-resistant A. baumannii (66% in Central Eastern Europe) and carbapenem-resistant K. pneumoniae (62.8% in Southern Europe). Pooled estimates showed lower resistance-percentages in community versus healthcare-associated infections and in children versus adults. Estimates from studies and surveillance systems were mostly consistent among European regions. The included data was of medium quality.
DISCUSSION
Pathogen-specific frequency measures of antimicrobial resistance in BSI are insufficient to inform antibiotic stewardship and research and development strategies. Improving data collection and standardization of frequency measures is urgently needed.
Topics: Child; Adult; Humans; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus; Vancomycin; Escherichia coli; Bacteremia; Drug Resistance, Bacterial; Bacteria; Carbapenems; Sepsis; Europe; Klebsiella pneumoniae; Microbial Sensitivity Tests
PubMed: 38007387
DOI: 10.1016/j.cmi.2023.10.019 -
Microorganisms Nov 2023The aim of this review was to assess the efficacy and safety of GG (LGG) (previously known as GG) for the eradication of vancomycin-resistant (VREfm) in colonized... (Review)
Review
The aim of this review was to assess the efficacy and safety of GG (LGG) (previously known as GG) for the eradication of vancomycin-resistant (VREfm) in colonized carriers. We searched Cochrane Central, EMBASE, and the PubMed Library from inception to 21 August 2023, for randomized controlled trials (RCTs) investigating the effectiveness of LGG for the eradication of gastrointestinal carriage of VREfm. An initial screening was performed followed by a full-text evaluation of the papers. Out of 4076 articles in the original screening, six RCTs (167 participants) were included in the review. All were placebo-controlled RCTs. The meta-analysis was inconclusive with regard to the effect of LGG for clearing VREfm colonization. The overall quality of the evidence was low due to inconsistency and the small number of patients in the trials. We found insufficient evidence to support the use of LGG for the eradication of VREfm in colonized carriers. There is a need for larger RCTs with a standardized formulation and dosage of LGG in future trials.
PubMed: 38004815
DOI: 10.3390/microorganisms11112804 -
European Journal of Clinical... Jan 2024Vancomycin-resistant enterococci (VRE) are a leading cause of hospital-acquired infections with limited therapeutic options. Combination of at least two antimicrobials... (Review)
Review
PURPOSE
Vancomycin-resistant enterococci (VRE) are a leading cause of hospital-acquired infections with limited therapeutic options. Combination of at least two antimicrobials is a possible strategy to obtain rapid and sustained bactericidal effects and overcome the emergence of resistance. We revised the literature on linezolid synergistic properties from in vitro studies to assess its activity in combination with molecules belonging to other antibiotic classes against Enterococcus spp.
METHODS
We performed a systematic review of the literature from three peer-reviewed databases including papers evaluating linezolid synergistic properties in vitro against Enterococcus spp. isolates.
RESULTS
We included 206 Enterococcus spp. isolates (92 E. faecalis, 90 E. faecium, 2 E. gallinarum, 3 E. casseliflavus, 19 Enterococcus spp.) from 24 studies. When an isolate was tested with different combinations, each combination was considered independently for further analysis. The most frequent interaction was indifferent effect (247/343, 72% of total interactions). The highest synergism rates were observed when linezolid was tested in combination with rifampin (10/49, 20.4% of interactions) and fosfomycin (16/84, 19.0%, of interactions). Antagonistic effect accounted for 7/343 (2.0%) of total interactions.
CONCLUSION
Our study reported overall limited synergistic in vitro properties of linezolid with other antibiotics when tested against Enterococcus spp. The clinical choice of linezolid in combination with other antibiotics should be guided by reasoned empiric therapy in the suspicion of a polymicrobial infection or targeted therapy on microbiological results, rather than on an intended synergistic effect of the linezolid-based combination.
Topics: Humans; Anti-Bacterial Agents; Enterococcus faecalis; Enterococcus faecium; Fosfomycin; Gram-Positive Bacterial Infections; Linezolid; Microbial Sensitivity Tests; Rifampin; Vancomycin-Resistant Enterococci
PubMed: 37975976
DOI: 10.1007/s10096-023-04704-8 -
Neurology India 2023Surgical site infection (SSI) rates (1-9%) remain high despite the widespread adoption of infection control bundles. Topical vancomycin has emerged as an effective... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Surgical site infection (SSI) rates (1-9%) remain high despite the widespread adoption of infection control bundles. Topical vancomycin has emerged as an effective strategy to reduce the rate of SSI in patients undergoing spinal surgery including instrumentation. However, its use and efficiency in cranial neurosurgery is not well established. The aim of this study is to study the efficacy of topical vancomycin in cranial neurosurgery.
METHODS
A systematic search was performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Data regarding type of surgery, use of implants, the dose of vancomycin, technique of administration in each study, outcomes, rate of SSI, and the interval between surgery and SSI; possible complications related to antibiotic use were collected.
RESULTS
A total of 12 studies were included in the qualitative analysis with 3,446 patients. SSI developed in 1.6% of the patients in the vancomycin group as compared to 5.28% in the control group. The pooled risk ratio was 0.24 with 95% CI: 0.12-0.51 (P-value: <0.00001). The difference between the subgroups was significant (P-value: < 0.00001). The number needed to treat (NNT) was 27.2. The studies showed low heterogeneity with an I of 24%. Meta-regression analysis showed that the number of patients in a study, duration of follow-up, and year of publication did not contribute significantly to effect size.
CONCLUSION
The limited systemic absorption of vancomycin and broad-spectrum led to its widespread applicability in the prevention of SSI in all types of cranial neurosurgery. Cases with implantable pulse generators, cranioplasty, and cerebrospinal fluid (CSF) diversion procedures have all demonstrated their unequivocal effectiveness.
Topics: Humans; Vancomycin; Surgical Wound Infection; Anti-Bacterial Agents; Neurosurgical Procedures
PubMed: 37929420
DOI: 10.4103/0028-3886.388107 -
Antimicrobial Resistance and Infection... Nov 2023
PubMed: 37924142
DOI: 10.1186/s13756-023-01327-8 -
European Journal of Pediatrics Jan 2024The optimal duration of antibiotic treatment for the most common bacterial meningitis etiologies in the pediatric population, namely Streptococcus pneumoniae,... (Meta-Analysis)
Meta-Analysis Review
The optimal duration of antibiotic treatment for the most common bacterial meningitis etiologies in the pediatric population, namely Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, is not well-established in the literature. Therefore, we aimed to perform an updated meta-analysis comparing shorter versus longer antibiotic treatment in children with meningitis. PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials (RCTs) that compared shorter (up to 7 days) versus longer (10 days or double the days of the equivalent short course) duration of antibiotic treatment in children with meningitis and reported the outcomes of treatment failure, death, neurologic sequelae, non-neurologic complications, hearing impairment, nosocomial infection, and relapse. Heterogeneity was examined with I statistics. RevMan 5.4.1 was used for statistical analysis and RoB-2 (Cochrane) for risk of bias assessment. Of 684 search results, 6 RCTs were included, with a cohort of 1333 children ages 3 weeks to 15.5 years, of whom 49.51% underwent a short antibiotic course. All RCTs included monotherapy with ceftriaxone, except one, which added vancomycin as well. No differences were found comparing the short and long duration of therapy concerning treatment failure, relapse, mortality, and neurologic complications at discharge and at follow-up. Conclusion: Because no statistically significant differences were found between groups for the analyzed outcomes, the results of this meta-analysis support shorter therapy. However, generalizing these results to complicated meningitis and infections caused by other pathogens should be made with caution. (PROSPERO identifier: CRD42022369843). What is Known: • Current recommendations on the duration of antibiotic therapy for bacterial meningitis are mostly based on clinical practice. • Defining an optimal duration of antibiotic therapy is essential for antimicrobial stewardship achievement, improving patient outcomes, and minimizing adverse effects. What is New: • There are no differences between shorter versus longer antibiotic treatment duration in regard to treatment failure, relapse, mortality, neurologic complications, and hearing impairment at discharge and at follow-up.
Topics: Child; Humans; Anti-Bacterial Agents; Meningitis, Bacterial; Ceftriaxone; Hearing Loss; Recurrence
PubMed: 37870611
DOI: 10.1007/s00431-023-05275-8 -
European Respiratory Review : An... Dec 2023Methicillin-resistant (MRSA) is responsible for an array of problematic community- and healthcare-acquired infections, including pneumonia, and is frequently associated... (Review)
Review
Methicillin-resistant (MRSA) is responsible for an array of problematic community- and healthcare-acquired infections, including pneumonia, and is frequently associated with severe disease and high mortality rates. Standard recommended treatments for empiric and targeted coverage of suspected MRSA in patients with community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), are vancomycin and linezolid. However, adverse events such as acute kidney injury and infection have been associated with these antibiotics. Ceftaroline fosamil is a β-lactam/extended-spectrum cephalosporin approved for the treatment of adults and children with CAP and complicated skin and soft tissue infections. Ceftaroline has activity against a range of common Gram-positive bacteria and is distinct among the β-lactams in retaining activity against MRSA. Due to the design of the pivotal randomised controlled trials of ceftaroline fosamil, outcomes in patients with MRSA CAP were not evaluated. However, various reports of real-world outcomes with ceftaroline fosamil for pneumonia caused by MRSA, including CAP and HAP/VAP, been published since its approval. A systematic literature review and qualitative analysis of relevant publications was undertaken to collate and summarise relevant published data on the efficacy and safety of ceftaroline fosamil in patients with MRSA pneumonia. While relatively few real-world outcomes studies are available, the available data suggest that ceftaroline fosamil is a possible alternative to linezolid and vancomycin for MRSA pneumonia. Specific scenarios in which ceftaroline fosamil might be considered include bacteraemia and complicating factors such as empyema.
Topics: Adult; Child; Humans; Methicillin-Resistant Staphylococcus aureus; Linezolid; Vancomycin; Cephalosporins; Anti-Bacterial Agents; Community-Acquired Infections; Pneumonia, Ventilator-Associated; Ceftaroline
PubMed: 37852658
DOI: 10.1183/16000617.0117-2023