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Medicine Oct 2019The clinical significance of using vancomycin loading dose remains controversial. A systematic review and meta-analysis were performed to assess the clinical efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical significance of using vancomycin loading dose remains controversial. A systematic review and meta-analysis were performed to assess the clinical efficacy and safety of vancomycin loading dose in the treatment of infections.
METHODS
The Pubmed, Embase, Web of Science, and Cochrane Library databases were searched from their inception up to 5 May 2019. Randomized controlled trials (RCTs) and other observational studies were included if they provided clinical outcomes or trough concentrations of vancomycin loading dose (20-30 mg/kg) and conventional-dose (10-20 mg/kg) in the treatment of infections. Achievement of therapeutic concentration (serum trough concentrations of vancomycin reached 15-20 mg/L before the second dose), clinical response (clinical improvement or culture-negative), nephrotoxicity (serum creatinine increase ≥0.5 mg/dL or ≥50% increasing from the baseline), other adverse events (including pruritus, flushing, rash, and/or red man syndrome), and mortality were analyzed. Heterogeneity was identified using the Cochrane I statistic, and P-value <.10 or I-values >50% indicated significant heterogeneity. Pooled estimates of the intervention effects were determined by the odds ratios (ORs) and 95% confidence intervals (CIs) in Review Manager program, version 5.3.5.
RESULTS
Two RCTs and 7 cohort studies including 2816 infected patients were selected for the analysis, in which serum trough concentrations of vancomycin following the use of vancomycin loading dose or other outcomes were available. Loading dose group had a significantly higher compliance rate of serum trough concentration of 15 to 20 mg/L (OR = 3.06; 95% CI = 1.15-8.15; P = .03) and significantly lower incidence of nephrotoxicity (OR = 0.59, 95% CI = 0.40-0.87; P = .008; I = 29%) compared with control group. No significant difference was noted between loading dose group and control group in terms of other adverse events and clinical response (OR = 1.98, 95% CI = 0.80-4.93; P = .14; I = 0%). The use of vancomycin loading doses in patients can indeed increase the achievement of therapeutic concentration.
CONCLUSION
Vancomycin loading dose increases the achievement of therapeutic concentration without bringing extra risk of nephrotoxicity. However, well-designed large-scale RCTs remain needed to validate the clinical efficacy of vancomycin loading dose and to further evaluate other adverse reactions and mortality.PROSPERO registration number CRD42018093927.
Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Administration Schedule; Humans; Treatment Outcome; Vancomycin
PubMed: 31651882
DOI: 10.1097/MD.0000000000017639 -
Surgical Infections Dec 2015Current recommendations suggest that vancomycin dosing utilize actual rather than ideal body weight in obese patients. Thus, obese patients may be at greater risk for...
BACKGROUND
Current recommendations suggest that vancomycin dosing utilize actual rather than ideal body weight in obese patients. Thus, obese patients may be at greater risk for nephrotoxicity. The purpose of this study was to compare the incidence of nephrotoxicity in vancomycin-treated obese and lean patients at our institution, where unadjusted, actual body weight-based dosing (capped at 2 g per dose twice daily) is used. We expected obese patients to experience a greater incidence of nephrotoxicity than lean patients.
METHODS
This study examined a retrospective cohort of patients treated with vancomycin for gram-positive or mixed infections in our facility from 2005-2009 who were not receiving hemodialysis at the time of admission. Patients were stratified by body mass index (BMI; obese ≥30 kg/m(2) vs. lean <30 kg/m(2)). Relative risk (RR), 95% confidence intervals (CIs), and p values were computed using a generalized estimating equation to accommodate a correlated data structure corresponding to multiple episodes of infection per individual. Multivariable analysis was performed.
RESULTS
A total of 530 patients (207 obese; 323 lean) with 1,007 episodes of infection were treated with vancomycin. Patient demographics, co-morbidities, sites of infection, and infecting organisms were similar in the two groups. Female gender (p=0.042), diabetes mellitus (DM) (p=0.018), and hypertension (HTN) (p=0.0009) were more often associated with obesity, whereas allografts (p=0.022) and peripheral vascular disease (p=0.036) were more often present in lean patients. The Acute Physiology and Chronic Health Evaluation II score >21 was the only variable associated with nephrotoxicity (p=0.039). After adjusting for statistically significant variables, obesity was found not to be associated with a greater risk of nephrotoxicity (RR=0.98; 95% CI=0.93-1.04; p=0.59).
CONCLUSION
No difference in nephrotoxicity was observed between lean and obese patients treated with vancomycin at our institution.
Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Humans; Incidence; Male; Middle Aged; Obesity; Retrospective Studies; Vancomycin
PubMed: 26324996
DOI: 10.1089/sur.2014.198 -
Drug Design, Development and Therapy 2021This study aimed to establish an optimal model to predict vancomycin trough concentrations by using machine learning.
PURPOSE
This study aimed to establish an optimal model to predict vancomycin trough concentrations by using machine learning.
PATIENTS AND METHODS
We enrolled 407 pediatric patients (age < 18 years) who received vancomycin intravenously and underwent therapeutic drug monitoring from June 2013 to April 2020 at Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine. The median (interquartile range) age and weight of the patients were 2 (0.63-5) years and 12 (7.8-19) kg. Vancomycin trough concentrations were considered as the target variable, and eight different algorithms were used for predictive performance comparison. The whole dataset (407 cases) was divided into training group and testing group at the ratio of 80%: 20%, which were 325 and 82 cases, respectively.
RESULTS
Ultimately, five algorithms (XGBoost, GBRT, Bagging, ExtraTree and decision tree) with high (0.657, 0.514, 0.468, 0.425 and 0.450, respectively) were selected and further ensembled to establish the final model and achieve an optimal result. For missing data, through filling the missing values and model ensemble, we obtained =0.614, MAE=3.32, MSE=24.39, RMSE=4.94 and a prediction accuracy of 51.22% (predicted trough concentration within ±30% of the actual trough concentration). In comparison with the pharmacokinetic models ( =0.3), the machine learning model works better in model fitting and has better prediction accuracy.
CONCLUSION
Therefore, the ensemble model is useful for the vancomycin concentration prediction, especially in the population of children with great individual variation. As machine learning methods evolve, the clinical value of the ensemble model will be demonstrated in the clinical practice.
Topics: Algorithms; Child, Preschool; Female; Humans; Infant; Injections, Intravenous; Machine Learning; Male; Vancomycin
PubMed: 33883878
DOI: 10.2147/DDDT.S299037 -
PloS One 2023We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of...
OBJECTIVES
We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of antibiotic therapy.
MATERIALS AND METHODS
Rats were implanted a polyethylene graft in the common carotid artery, pre-inoculated with approx. 6 log10 colony forming units (CFU) of methicillin resistant Staphylococcus aureus. Ten days after surgery, rats were randomized to either: 0.9% NaCl (n = 8), vancomycin (n = 8), vancomycin + tPA (n = 8), vancomycin + rifampicin (n = 18) or vancomycin + rifampicin + tPA (n = 18). Treatment duration was seven days. Approximately 36 hours after the end of treatment, the rats were euthanized, and grafts and organs were harvested for CFU enumeration.
RESULTS
All animals in the control group had significantly higher CFU at the time of euthanization compared to bacterial load found on the grafts prior to inoculation (6.45 vs. 4.36 mean log10 CFU/mL, p = 0.0011), and both the procedure and infection were well tolerated. Vancomycin and rifampicin treatment were superior to monotherapy with vancomycin, as it lead to a marked decrease in median bacterial load on the grafts (3.50 vs. 6.56 log10 CFU/mL, p = 0.0016). The addition of tPA to vancomycin and rifampicin combination treatment did not show a further decrease in bacterial load (4.078 vs. 3.50 log10 CFU/mL, p = 0.26). The cure rate was 16% in the vancomycin + rifampicin group vs. 37.5% cure rate in the vancomycin + rifampicin + tPA group. Whilst interesting, this trend was not significant at our sample size (p = 0.24).
CONCLUSION
We developed the first functional model of an arterial prosthetic vascular graft infection in rats. Antibiotic combination therapy with vancomycin and rifampicin was superior to vancomycin monotherapy, and the addition of tPA did not significantly reduce bacterial load, nor significantly increase cure rate.
Topics: Animals; Rats; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Tissue Plasminogen Activator; Vancomycin
PubMed: 37463137
DOI: 10.1371/journal.pone.0287671 -
Saudi Medical Journal Feb 2019To assess the appropriateness of vancomycin dosing and monitoring at Lebanese hospitals.
OBJECTIVES
To assess the appropriateness of vancomycin dosing and monitoring at Lebanese hospitals.
METHODS
This was a multicenter retrospective study conducted at 3 Lebanese hospitals between January and March 2018. Patients 18 years of age and older treated with vancomycin for a systemic infection or prophylaxis were eligible for study enrollment. Consistency with the Infectious Diseases Society of America guidelines was evaluated to determine whether the dose of vancomycin was appropriate, as well as for the time of trough measurement, and the target concentration obtained.
RESULTS
From a total of 120 patients who met the inclusion criteria, only 11 (12%) were given the appropriate maintenance dose of vancomycin with respect to actual body weight. The trough levels were monitored for 67 (55.8%) patients, with 20 (29.9%) of these patients achieving appropriate therapeutic trough levels of 15-20 mg/l. The trough concentration time measurement before the fourth dose was only carried out in 28 (41.8%) of the 67 patients.
CONCLUSION
This study reveals a gap between the appropriate utilization of vancomycin with respect to the international guidelines in the studied Lebanese hospitals. It highlights the need for dosing and monitoring protocols suitable for vancomycin utilization in these hospitals.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Body Weight; Creatinine; Drug Monitoring; Drug Utilization Review; Female; Guideline Adherence; Hospitals; Humans; Lebanon; Male; Middle Aged; Practice Guidelines as Topic; Retrospective Studies; Vancomycin; Young Adult
PubMed: 30723860
DOI: 10.15537/smj.2019.2.23872 -
Hepatology International Apr 2022Gut microbiota and microbe-derived metabolites are involved in the development of HCC. Bile acids (BAs) are the most important gut microbiota-modulated endogenous...
BACKGROUND
Gut microbiota and microbe-derived metabolites are involved in the development of HCC. Bile acids (BAs) are the most important gut microbiota-modulated endogenous signaling molecules.
METHODS
We tested serum bile acid levels and gut microbiome compositions in patients with HCC, chemical-induced HCC mouse models (DEN-HCC mice) and mouse orthotopic implanted liver tumor models with vancomycin treatment (vancomycin-treated mice). Then, we screened an important kind of HCC-related BAs, and verified its effect on the growth of HCC in vivo and in vitro.
RESULTS
We found that the remarkably decreasing percentages of serum secondary BAs in the total bile acids of patients and DEN-HCC mice, especially, conjugated deoxycholic acids (DCA). The relative abundance of the bile salt hydrolase (BSH)-rich bacteria (Bifidobacteriales, Lactobacillales, Bacteroidales, and Clostridiales) was decreased in the feces of patients and DEN-HCC mice. Then, in vancomycin-treated mice, vancomycin treatment induced a reduction in the BSH-rich bacteria and promoted the growth of liver tumors. Similarly, the percentage of conjugated DCA after vancomycin treatment was significantly declined. We used a kind of conjugated DCA, Glyco-deoxycholic acid (GDCA), and found that GDCA remarkably inhibited the growth of HCC in vivo and in vitro.
CONCLUSIONS
We conclude that the remarkably decreasing percentages of serum conjugated DCA may be closely associated with HCC, which may be induced by the reducing gut BSH-rich bacteria. The mechanisms may be correlated with conjugated DCA directly inhibiting the growth and migration of HCC cells.
Topics: Animals; Bile Acids and Salts; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Mice; Microbiota; Vancomycin
PubMed: 35211843
DOI: 10.1007/s12072-022-10299-7 -
British Journal of Clinical Pharmacology Nov 2019Vancomycin is frequently used in critically ill children in whom the drug pharmacokinetics are significantly altered as a result of changes in renal clearance and volume...
AIMS
Vancomycin is frequently used in critically ill children in whom the drug pharmacokinetics are significantly altered as a result of changes in renal clearance and volume of distribution. Therapeutic drug monitoring (TDM) is recommended to achieve vancomycin trough concentrations between 10 and 20 mg/L. In this study we reviewed vancomycin dosing, TDM and treatment outcomes in paediatric and neonatal intensive care unit patients.
METHODS
We reviewed the medical records of all patients receiving intravenous vancomycin in a tertiary paediatric and neonatal intensive care unit over a 10-month period. Demographic, vancomycin dosing, TDM and drug-related adverse effects data were collected.
RESULTS
In total, 115 children received 126 courses of vancomycin and had at least 1 TDM blood sample taken at steady state. In only 38/126 (30%) courses was the target concentration (10-20 mg/L) achieved at the initial steady state trough sample. Of the 88 courses that had initial trough concentrations outside the target range, the dose was adjusted in only 49 (56%). Overall, minimum doses of 30 mg/kg/day in neonates with a corrected gestational age of <35 weeks, and 50 mg/kg/day in older children, were required to achieve target vancomycin concentrations. Vancomycin-attributable nephrotoxicity occurred in 10/126 (8%) courses and there were no episodes of red man syndrome.
CONCLUSION
In critically ill children, individualised dosing is needed. In the absence of Bayesian model-based dosing, in children with normal renal function, empiric vancomycin doses of at least 30 mg/kg/day in neonates of <35 weeks corrected gestational age, and 50 mg/kg/day in older children, should be considered. Optimisation of TDM practices through the development of protocols, ideally built into electronic medical records, should be considered.
Topics: Administration, Intravenous; Adolescent; Age Factors; Anti-Bacterial Agents; Child; Child, Preschool; Critical Illness; Dose-Response Relationship, Drug; Drug Dosage Calculations; Drug Monitoring; Female; Gestational Age; Humans; Infant; Infant, Extremely Premature; Infant, Newborn; Intensive Care Units, Neonatal; Kidney; Kidney Diseases; Male; Medical Records; Retrospective Studies; Sepsis; Vancomycin
PubMed: 31378957
DOI: 10.1111/bcp.14084 -
Microbiology Spectrum Feb 2023Enterococci can cause various infectious diseases, including urinary tract infection, wound infection, and life-threatening endocarditis and meningitis. The emergence...
Enterococci can cause various infectious diseases, including urinary tract infection, wound infection, and life-threatening endocarditis and meningitis. The emergence and transmission of vancomycin-resistant enterococci (VRE) have presented a challenge to clinical treatment. There is an urgent need to develop new strategies to fight against this pathogen. This study investigated the antibacterial and anti-biofilm activity of celastrol (CEL), a natural product originating from against enterococci, and its adjuvant capacity of restoring the susceptibility of VRE to vancomycin and . CEL inhibited all enterococcus strains tested, with MICs ranging from 0.5 to 4 μg/mL. More than 50% of biofilm was eliminated by CEL at 16 μg/mL after 24 h of exposure. The combination of CEL and vancomycin showed a synergistic effect against all 23 strains tested in checkerboard assays. The combination of sub-MIC levels of CEL and vancomycin showed a synergistic effect in a time-kill assay and exhibited significant protective efficacy in Galleria mellonella larval infection model compared with either drug used alone. The underlying mechanisms of CEL were explored by conducting biomolecular binding interactions and an enzyme inhibition assay of CEL on bacterial cell-division protein FtsZ. CEL presented strong binding and suppression ability to FtsZ, with K and IC values of 2.454 μM and 1.04 ± 0.17 μg/mL, respectively. CEL exhibits a significant antibacterial and synergic activity against VRE and and has the potential to be a new antibacterial agent or adjuvant to vancomycin as a therapeutic option in combating VRE. The emergence and transmission of VRE pose a significant medical and public health challenge. CEL, well-known for a wide range of biological activities, has not previously been investigated for its synergistic effect with vancomycin against VRE. In the present study, CEL exhibited antibacterial activity against enterococci, including VRE strains, and restored the activity of vancomycin against VRE and . Hence, CEL has the potential to be a new antibacterial adjuvant to vancomycin and could provide a promising therapeutic option in combating VRE.
Topics: Vancomycin; Anti-Bacterial Agents; Pentacyclic Triterpenes; Vancomycin-Resistant Enterococci; Microbial Sensitivity Tests
PubMed: 36622182
DOI: 10.1128/spectrum.03699-22 -
Comparative Immunology, Microbiology... Jul 2022The objective of this study was to evaluate local antimicrobial delivery from temperature-responsive hydrogels for preventing infection in a rat model of intra-abdominal...
The objective of this study was to evaluate local antimicrobial delivery from temperature-responsive hydrogels for preventing infection in a rat model of intra-abdominal infection (IAI), and to determine whether delivery of tobramycin and vancomycin in combination is effective against IAI pathogens. Rats received intraperitoneal inoculation of E. coli, rat cecal contents, or cecal contents supplemented with E. coli, and received either no treatment, subcutaneous cefoxitin, or local delivery from hydrogels containing vancomycin, tobramycin, or both antimicrobials. Only the hydrogel with tobramycin and vancomycin significantly increased the infection free-rate compared to no treatment for all inocula (E. coli: 13/17, p < 0.0001; cecal contents: 11/17, p = 0.0013; cecal contents + E. coli: 15/19, p < 0.0001). Additionally, tobramycin and vancomycin displayed no synergy or antagonism against clinical isolates in vitro. Local delivery of tobramycin and vancomycin from temperature-responsive hydrogels provides broad coverage and high antimicrobial concentrations for several hours that may be effective for preventing IAIs.
Topics: Animals; Anti-Bacterial Agents; Escherichia coli; Hydrogels; Incidence; Intraabdominal Infections; Rats; Temperature; Tobramycin; Vancomycin
PubMed: 35636372
DOI: 10.1016/j.cimid.2022.101823 -
Journal of Infection in Developing... Nov 2018Vancomycin is the cornerstone of parenteral therapy for serious methicillin resistant Staphylococcus aureus infections. Optimal dosing of vancomycin is patient specific... (Observational Study)
Observational Study
INTRODUCTION
Vancomycin is the cornerstone of parenteral therapy for serious methicillin resistant Staphylococcus aureus infections. Optimal dosing of vancomycin is patient specific due to its narrow therapeutic window. The objective of this study is to evaluate the appropriate use of vancomycin focusing on the indication, dose, and therapeutic level monitoring.
METHODOLOGY
A prospective observational study was conducted in a tertiary care hospital over a 3- month period. A data collection form was used to gather information on 93 patients receiving vancomycin. Study outcomes were assessment of the appropriateness of vancomycin indication, dose, and therapeutic trough level.
RESULTS
The use of vancomycin both empirically and after culture results was appropriate in 78.5 % of the patients. More than half of the patients (51.6 %) were given an inappropriate dose of vancomycin per actual body weight, creatinine clearance, and indication. Regarding therapeutic vancomycin monitoring, 69.0 % had inappropriate trough level monitoring. Only 15.7 % of the 166 measured troughs were within the target therapeutic level for the corresponding indication.
CONCLUSION
This study demonstrates the high level of inappropriate use of vancomycin. This is mainly attributed to inappropriate dose and trough level monitoring. Interventions to improve vancomycin prescribing and monitoring practices are needed. The presence of an interdisciplinary team may improve the appropriate use of medications with a narrow therapeutic index such as vancomycin.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Inappropriate Prescribing; Infant; Male; Middle Aged; Prospective Studies; Vancomycin; Young Adult
PubMed: 32012127
DOI: 10.3855/jidc.9800