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Therapeutic Drug Monitoring Feb 2020Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug...
Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and neuropathy, which are more prevalent with higher exposures and longer treatment durations. Although linezolid is traditionally administered at a standard 600 mg dose every 12 hours, the resulting exposure can vary greatly between patients and can lead to treatment failure or toxicity. The efficacy and toxicity of linezolid are determined by the exposure achieved in the patient; numerous clinical and population pharmacokinetics (popPK) studies have identified threshold measurements for both parameters. Several special populations with an increased need for linezolid dose adjustments have also been identified. Therapeutic Drug Monitoring (TDM) is a clinical strategy that assesses the response of an individual patient and helps adjust the dosing regimen to maximize efficacy while minimizing toxicity. Adaptive feedback control and model-informed precision dosing are additional strategies that use Bayesian algorithms and PK models to predict patient-specific drug exposure. TDM is a very useful tool for patient populations with sparse clinical data or known alterations in pharmacokinetics, including children, patients with renal insufficiency or those receiving renal replacement therapy, and patients taking co-medications known to interact with linezolid. As part of the clinical workflow, clinicians can use TDM with the thresholds summarized from the current literature to improve linezolid dosing for patients and maximize the probability of treatment success.
Topics: Anti-Bacterial Agents; Bayes Theorem; Drug Dosage Calculations; Drug Interactions; Drug Monitoring; Half-Life; Humans; Linezolid; Liver Failure; Metabolic Clearance Rate; Microbial Sensitivity Tests; Models, Biological; Pediatrics; Renal Insufficiency; Renal Replacement Therapy; Tuberculosis
PubMed: 31652190
DOI: 10.1097/FTD.0000000000000710 -
Jornal de Pediatria 2024To investigate the effectiveness of linezolid and vancomycin for the treatment of nosocomial infections in children under 12 years old. (Review)
Review
OBJECTIVE
To investigate the effectiveness of linezolid and vancomycin for the treatment of nosocomial infections in children under 12 years old.
DATA SOURCES
This is a systematic review in which five randomized clinical trials about the effectiveness of linezolid and vancomycin, involving a total of 429 children with nosocomial infections, were evaluated. They were searched in scientific databases: PubMed, Bvs, and SciELO.
SUMMARY OF FINDINGS
The main nosocomial infections that affected children were bacteremia, skin, and soft tissue infections followed by nosocomial pneumonia. Most infections were caused by Gram-positive bacteria, which all studies showed infections caused by Staphylococcus aureus, with methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci strains being isolated. Both linezolid and vancomycin showed high therapeutic efficacy against different types of nosocomial infections, ranging from 84.4% to 94% for linezolid and 76.9% to 90% for vancomycin. Patients receiving linezolid had lower rates of rash and red man syndrome compared to those receiving vancomycin. However, despite the adverse reactions, antimicrobials can be safely administered to children to treat nosocomial infections caused by resistant Gram-positive bacteria.
CONCLUSION
Both linezolid and vancomycin showed good efficacy in the treatment of bacterial infections caused by resistant Gram-positive bacteria in hospitalized children. However, linezolid stands out regarding its pharmacological safety. Importantly, to strengthen this conclusion, further clinical trials are needed to provide additional evidence.
Topics: Humans; Linezolid; Cross Infection; Vancomycin; Child; Anti-Bacterial Agents; Randomized Controlled Trials as Topic; Child, Preschool; Methicillin-Resistant Staphylococcus aureus; Infant; Staphylococcal Infections; Gram-Positive Bacterial Infections
PubMed: 38145631
DOI: 10.1016/j.jped.2023.08.011 -
Porto Biomedical Journal 2021Enterococci are opportunistic pathogens and are one of the most important bacteria in hospital-acquired infections. Their resistance to antibiotics such as vancomycin... (Review)
Review
BACKGROUND
Enterococci are opportunistic pathogens and are one of the most important bacteria in hospital-acquired infections. Their resistance to antibiotics such as vancomycin has led to life-threatening and difficult-to-treat nosocomial infections. The true prevalence in clinical settings in Nigeria is not well known due to the lack of a comprehensive antibiotic surveillance system. This study aims to estimate the prevalence of vancomycin-resistant enterococci (VRE) in clinical infections in Nigeria.
METHODS
Databases (PubMed, , and Google scholar) were searched following the Preferred Reporting Items for Systematic review and meta-analysis protocols (PRISMA-P) 2015 statements for articles reporting VRE prevalence, and were published before August 5, 2020. Data from the studies were extracted and analyzed using Microsoft Excel and Comprehensive Meta-Analysis (CMA 3.0), respectively. The pooled prevalence of VRE was estimated with the random-effects model and the 95% confidence interval (CI). The heterogeneity level was assessed using Cochran Q and tests.
RESULTS
A total of 35 articles were scanned for eligibility, among which 7 were included in the study after fulfilling the eligibility criteria. The studies analyzed a total of 832 enterococci isolates and 90 VRE strains. The prevalence of and in this study are 361 (59.3%) and 248 (40.7%), respectively, among which 41 (63.1%) of the and 24 (36.9%) of the were vancomycin resistant. The pooled prevalence of VRE was estimated at (95% CI; 10.0-53.9%; = 93.50%; < .001). The highest prevalence of VRE was reported from western Nigeria, 14.6% (95% CI; = 97.27; < .001).
CONCLUSION
The prevalence of VRE in Nigeria according to the reports from this study is relatively high. The report of this study should help policymakers to put in place measures that will help curb the spread of VRE and associated resistant genes to other important clinical pathogens like .
PubMed: 33884321
DOI: 10.1097/j.pbj.0000000000000125 -
International Journal of Antimicrobial... Feb 2022Neonatal infections caused by Gram-positive bacteria are commonly treated with vancomycin. However, there is a lack of agreement on the optimal vancomycin dosing regimen...
INTRODUCTION
Neonatal infections caused by Gram-positive bacteria are commonly treated with vancomycin. However, there is a lack of agreement on the optimal vancomycin dosing regimen and corresponding vancomycin exposure to correlate with efficacy and toxicity.
OBJECTIVES
This review aimed to evaluate dosing of vancomycin in neonates, therapeutic target attainment and clinical toxicity and efficacy outcomes.
METHODS
Two electronic databases - Embase and PubMed (Medline) - were systematically searched between 1995-2020. Studies that reported dosing regimens, drug concentrations, toxicity, and efficacy of vancomycin in neonates were eligible for inclusion. Descriptive analysis and a narrative synthesis were performed.
RESULTS
The systematic review protocol was registered with the PROSPERO International Prospective Register of Systematic reviews in 2020 (registration number: CRD42020219568). Twenty-four studies were included for final analysis. Overall, the data from the included studies showed a great degree of heterogeneity. Therapeutic drug monitoring practices were different between institutions. Although most studies used trough concentration with a target range of 10-20 mg/L, target attainment was different across the studies. The probability of target attainment was < 80% in all tested dosing algorithms. Few studies reported on vancomycin efficacy and toxicity.
CONCLUSION
This is a comprehensive overview of dosing strategies of vancomycin in neonates. There was inadequate evidence to propose an optimal therapeutic regimen in the newborn population, based on the data obtained, due to the heterogeneity in the design and objectives of the included studies. Consistent and homogeneous comparative randomised clinical trials are needed to identify a dosing regimen with a probability of target attainment of > 90% without toxicity.
Topics: Humans; Infant, Newborn; Anti-Bacterial Agents; Drug Monitoring; Retrospective Studies; Vancomycin
PubMed: 35031450
DOI: 10.1016/j.ijantimicag.2021.106515 -
Journal of Burn Care & Research :... 2015Vancomycin pharmacokinetics are significantly altered following burn injury, requiring a higher total daily dose to achieve adequate serum concentrations. Wide... (Review)
Review
Vancomycin pharmacokinetics are significantly altered following burn injury, requiring a higher total daily dose to achieve adequate serum concentrations. Wide interpatient variability necessitates close, frequent monitoring of serum concentrations for efficacy and safety. The aim of this study is to systematically evaluate published data regarding vancomycin pharmacokinetic alterations in burn patients, to determine whether evidence-based recommendations for dosing and monitoring can be formulated, and to identify future research opportunities. The systematic review included studies published in English, involved human subjects with at least a 10% TBSA burn who received vancomycin intravenously, and obtained serum concentration(s). Database searches returned 130 titles for review. Twelve studies met a priori inclusion criteria. The most common dosing regimens in adult and pediatric patients were 5 to 20 mg/kg/dose every 6 to 8 hours. Mean trough concentrations were 7.24 ± 1.5 mg/L. Only 12.5% of reported trough concentrations were within the currently recommended range of 10 to 20 mg/L. Although no consistent dosing recommendations were provided, all studies recommended close monitoring of trough concentrations. Based on limited clinical outcomes data, standardized recommendations for vancomycin dosing and monitoring in burn patients cannot be made. Higher total daily doses (40-70 mg/kg/day) and increased dosing frequency (every 6-12 hr in adults) may be necessary to achieve current target trough concentrations. Future research goals include prospective investigation of clinical outcomes related to initial doses, loading doses, monitoring peak and trough concentrations, and adverse effects. Further data on the effects of burn size, concomitant diseases, inhalation injury, and time since injury may improve the accuracy of vancomycin dosing in burn patients.
Topics: Adult; Age Factors; Burns; Child; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Injury Severity Score; Male; Monitoring, Physiologic; Prospective Studies; Retrospective Studies; Risk Assessment; Treatment Outcome; Vancomycin; Wound Infection
PubMed: 25423436
DOI: 10.1097/BCR.0000000000000191 -
International Journal of Antimicrobial... Oct 2023To evaluate the safety and efficacy of vancomycin with the other anti-Gram-positive bacteria antibiotics in the treatment of Staphylococcus aureus bacteraemia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate the safety and efficacy of vancomycin with the other anti-Gram-positive bacteria antibiotics in the treatment of Staphylococcus aureus bacteraemia.
METHODS
We searched the PubMed, MEDLINE, Embase and Cochrane Library databases until August 2022 for studies that compared vancomycin with other antibiotic regimens for treating Staphylococcus aureus bacteraemia. Clinical and microbiological responses, adverse events, relapse rate and mortality were considered.
RESULTS
Fifteen randomized controlled trials and nine retrospective studies were included. The efficacy and safety data of vancomycin differed from those of the comparators group. After subgroup analysis, the differences came mainly from the trials compared with daptomycin. Compared to daptomycin, vancomycin showed a lower microbiological cure rate (OR = 0.58, 95% CI = 0.41∼0.82, I = 0%, P = 0.002) and clinical cure rate (OR = 0.53, 95% CI = 0.42∼0.68, I = 3%, P < 0.00001), as well as more adverse events (OR = 3.21, 95% CI = 1.43∼7.19, I = 59%, P = 0.005).
CONCLUSION
The efficacy of vancomycin in treating Staphylococcus aureus bacteraemia is still excellent but slightly inferior in adverse events. However, this does not affect its use as a first-line drug. Daptomycin is expected to be a better antimicrobial drug.
Topics: Humans; Vancomycin; Staphylococcal Infections; Daptomycin; Bacteremia; Retrospective Studies; Treatment Outcome; Staphylococcus aureus; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus
PubMed: 37543121
DOI: 10.1016/j.ijantimicag.2023.106946 -
Journal of Global Antimicrobial... Dec 2020Epidemiological surveillance is one critical approach to estimate and fight the burden of antibiotic resistance (AR). Here we summarise the characteristics of... (Review)
Review
OBJECTIVES
Epidemiological surveillance is one critical approach to estimate and fight the burden of antibiotic resistance (AR). Here we summarise the characteristics of surveillance systems devoted to the surveillance of AR worldwide and published in the literature.
METHODS
We performed a systematic review of the literature available on PubMed from January 2007 to July 2019 (12.5 years). The keywords ('surveillance system' OR 'laboratory-based surveillance' OR 'syndromic surveillance' OR 'sentinel surveillance' OR 'integrated surveillance' OR 'population-based surveillance') AND ('antibiotic resistance' OR 'antimicrobial resistance') were used. This research was completed with AR monitoring systems available on websites.
RESULTS
We identified 71 AR surveillance systems described by 90 publications from 35 countries, including 64 (90.1%) national and 7 (9.9%) multinational surveillance systems. Two regions accounted for ∼72% of systems: European region (37; 52.1%) and Region of the Americas (14; 19.7%). Fifty-three focused on AR surveillance in humans, 12 studied both humans and animals, and 6 focused only on animals. The two most common bacterial species reported were Staphylococcus aureus (42; 59.2%) and Escherichia coli (39; 54.9%). Of the 71 AR surveillance systems, 20 (28.2%) used prevalence as an indicator, 3 (4.2%) used incidence and 7 (9.9%) used both. Methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococcus spp., S. aureus and Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, and extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant E. coli and Klebsiella pneumoniae were monitored.
CONCLUSIONS
Our results showed heterogeneous surveillance systems. A 'One Health' approach is needed to monitor AR, with reference to the WHO Global Action Plan.
Topics: Anti-Bacterial Agents; Escherichia coli; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcus aureus
PubMed: 33176216
DOI: 10.1016/j.jgar.2020.10.009 -
Hospital Pharmacy Dec 2023Simultaneous administration of vancomycin and piperacillin-tazobactam (VPT) poses significant challenges related to physical and chemical compatibility, as well as... (Review)
Review
Simultaneous administration of vancomycin and piperacillin-tazobactam (VPT) poses significant challenges related to physical and chemical compatibility, as well as clinical practice. A systematic review of available literature related to VPT Y-site compatibility was performed. Data was collected from primary and tertiary sources. Seven articles were included in addition to one internal assessment and one review article and information from tertiary drug databases. The literature supports the simultaneous administration via Y-site of piperacillin-tazobactam 33.75 mg/mL in normal saline (NS) and vancomycin 4 to 8 mg/mL in NS. The same drug products at differing concentrations, diluents, storage conditions, or preparations outside of this recommendation should be considered incompatible.
PubMed: 38560538
DOI: 10.1177/00185787231169455 -
Antibiotics (Basel, Switzerland) Sep 2020Vancomycin-Resistant Enterococci (VRE) are on the rise worldwide. Here, we report the first prevalence of VRE in Nigeria using systematic review and meta-analysis.... (Review)
Review
Vancomycin-Resistant Enterococci (VRE) are on the rise worldwide. Here, we report the first prevalence of VRE in Nigeria using systematic review and meta-analysis. International databases MedLib, PubMed, International Scientific Indexing (ISI), Web of Science, Scopus, Google Scholar, and African journals online (AJOL) were searched. Information was extracted by two independent reviewers, and results were reviewed by the third. Two reviewers independently assessed the study quality using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. OpenMeta analyst was used. The random effect was used, and publication bias was assessed using a funnel plot. Between-study heterogeneity was assessed, and the sources were analysed using the leave-one-out meta-analysis, subgroup analysis, and meta-regression. Nineteen studies met the eligibility criteria and were added to the final meta-analysis, and the study period was from 2009-2018. Of the 2552 isolates tested, 349 were VRE, and was reported the most. The pooled prevalence of VRE in Nigeria was estimated at 25.3% (95% CI; 19.8-30.8%; = 96.26%; < 0.001). Between-study variability was high ( = 0.011; heterogeneity = 96.26% with heterogeneity chi-square (Q) = 480.667, degrees of freedom (df) = 18, and = 0.001). The funnel plot showed no publication bias, and the leave-one-out forest plot did not affect the pooled prevalence. The South-East region had a moderate heterogeneity though not significant ( = 51.15%, = 0.129). Meta-regression showed that all the variables listed contributed to the heterogeneity except for the animal isolate source ( = 0.188) and studies that were done in 2013 ( = 0.219). Adherence to proper and accurate antimicrobial usage, comprehensive testing, and continuous surveillance of VRE are required.
PubMed: 32882963
DOI: 10.3390/antibiotics9090565 -
Antibiotics (Basel, Switzerland) Mar 2021Vancomycin is commonly used as a treatment for neonatal infections. However, there is a lack of consensus establishing the optimal vancomycin therapeutic regimen and... (Review)
Review
Vancomycin is commonly used as a treatment for neonatal infections. However, there is a lack of consensus establishing the optimal vancomycin therapeutic regimen and defining the most appropriate PK/PD parameter correlated with the efficacy. A recent guideline recommends AUC-guided therapeutic dosing in treating serious infections in neonates. However, in clinical practice, trough serum concentrations are commonly used as a surrogate PKPD index for AUC24. Despite this, target serum concentrations in a neonatal population remain poorly defined. The objective is to describe the relationship between therapeutic regimens and the achievement of clinical or pharmacokinetic outcomes in the neonatal population. The review was carried out following PRISMA guidelines. A bibliographic search was manually performed for studies published on PubMed and EMBASE. Clinical efficacy and/or target attainment and the safety of vancomycin treatment were evaluated through obtaining serum concentrations. A total of 476 articles were identified, of which 20 met the inclusion criteria. All of them evaluated the target attainment, but only two assessed the clinical efficacy. The enormous variability concerning target serum concentrations is noteworthy, which translates into a difficulty in determining which therapeutic regimen achieves the best results. Moreover, there are few studies that analyze clinical efficacy results obtained after reaching predefined trough serum concentrations, this information being essential for clinical practice.
PubMed: 33805874
DOI: 10.3390/antibiotics10040347