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The American Journal of Tropical... Dec 2020A rapid increase of nosocomial vancomycin-resistant enterococci (VRE) from 23.3% in 2009 to 44.5% in 2018 among all the medical centers in Taiwan was found. The aim of...
A rapid increase of nosocomial vancomycin-resistant enterococci (VRE) from 23.3% in 2009 to 44.5% in 2018 among all the medical centers in Taiwan was found. The aim of the study was to explore the relationship between antimicrobial usage and prevalence of VRE. We conducted the study between January 2010 and December 2019 in a tertiary teaching hospital in Taiwan. Antibiotic consumption was expressed as defined daily doses (DDDs) per 1,000 patient-days (PDs). The trend in antibiotic consumption and VRE prevalence were analyzed by regression analysis with yearly data. Pearson's correlation analysis was used to determine the relationship between antibiotic consumption and the prevalence of VRE. The total consumption of antibiotics increased significantly from 450.6 DDDs/1,000 PDs in 2010 to 520.1 DDDs/1,000 PDs in 2019 (P = 0.013). Positive correlations were found between the prevalence of vancomycin-resistant Enterococcus faecium and the consumption of amoxicillin/clavulanate, vancomycin, and carbapenems, which included meropenem (P < 0.05). The increase in total VRE prevalence was significantly correlated with increased consumption of vancomycin and carbapenems, which included meropenem (P < 0.05). This 10-year study in a hospital demonstrated changes in antimicrobial use, which may have affected VRE prevalence in the hospital. We found a rise in nosocomial VRE prevalence was associated with the use of specific antimicrobial agents.
Topics: Anti-Infective Agents; Carrier State; Cross Infection; Enterococcus; Gram-Positive Bacterial Infections; Humans; Taiwan; Vancomycin; Vancomycin Resistance
PubMed: 33319735
DOI: 10.4269/ajtmh.20-0842 -
Therapeutic Drug Monitoring Aug 2014Optimal monitoring of vancomycin in children needs evaluation using the exposure target with area under the curve (AUC) of the serum concentrations versus time over 24...
BACKGROUND
Optimal monitoring of vancomycin in children needs evaluation using the exposure target with area under the curve (AUC) of the serum concentrations versus time over 24 hours. Our study objectives were to: (1) compare the accuracy and precision of vancomycin AUC estimations using 2 sampling strategies-1 serum concentration sample (1S, near trough) versus 2 samples (2S, near peak and trough) against the rich sample (RS) method; and (2) determine the performance of these strategies in predicting future AUC against an internal validation sample (VS).
METHODS
This was a retrospective cohort study using population-based pharmacokinetic modeling with Bayesian post hoc individual estimations in nonlinear mixed effects modeling (version 7.2). Pediatric subjects 3 months-21 years of age who received vancomycin ≥48 hours and had more than 3 drug samples within the first ≤96 hours of therapy were enrolled. Outcome measures were the accuracy, precision, and internal predictive performance of AUC estimations using 2 monitoring strategies (ie, 1S versus 2S) against the RS (which was derived from modeling all serum vancomycin concentrations obtained anytime during therapy) and VS (from serum concentrations obtained after 96 hours of therapy).
RESULTS
Analysis included 138 subjects with 712 vancomycin serum concentrations. Median age was 6.1 (interquartile range, 2.2-12.2) years, weight 22 (13-38) kg, and baseline serum creatinine 0.37 (0.30-0.50) mg/dL. Both accuracy and precision were improved with the 2S, compared with 1S, for AUC estimations (-2.0% versus -7.6% and 10.3% versus 12.8%, respectively) against the RS. Improved accuracy and precision were also observed for 2S when evaluated against VS in predicting future AUC.
CONCLUSIONS
Compared with 1S, the 2S sampling strategy for vancomycin monitoring improved accuracy and precision in estimating and predicting future AUC. Evaluating 2 drug concentrations in children may be prudent to ensure adequate drug exposure.
Topics: Adolescent; Anti-Bacterial Agents; Area Under Curve; Bayes Theorem; Child; Child, Preschool; Drug Monitoring; Humans; Male; Models, Biological; Retrospective Studies; Vancomycin
PubMed: 24452067
DOI: 10.1097/FTD.0000000000000039 -
Journal of Infection and Public Health Jan 2020Augmented renal clearance (ARC) refers to enhanced renal elimination of circulating solute has attracted attention widely and in recent years increasing attention has...
BACKGROUND
Augmented renal clearance (ARC) refers to enhanced renal elimination of circulating solute has attracted attention widely and in recent years increasing attention has been paid to patients with ARC. A population pharmacokinetic (PPK) analysis was performed to provide a reference for clinical individual therapy of vancomycin in in ARC patients.
METHODS
Patients hospitalized in the First Affiliated Hospital of China Medical University from July 2013 to December 2015 and suspected or confirmed infection caused by gram-positive bacteria were enrolled in this study. The serum concentrations were determined by enzyme multiplied immunoassay technique. A nonlinear mixed effects model (NONMEM) was used to evaluate the influence of covariates on vancomycin pharmacokinetics and obtain the PPK model. Bootstrap, visual predictive checks and normalized prediction distribution errors were used to evaluate the estabolishe model.
RESULTS
A total of 186 vancomycin serum samples from 95 patients, including 24 females and 71 males were studied. The final model was as follows: [Formula: see text] and [Formula: see text] . The final PPK model in ARC patients was proved to be robust and reliable. Age was identified as the most significant covariate in the final model.
CONCLUSIONS
In this study, a simple population pharmacokinetic (PPK) model of vancomycin in Chinese patients with ARC was established using a nonlinear mixed-effects model (NONMEM). The final PPK model could achieve a good predictive effect, which provides a reference for clinical individual therapy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Asian People; Child; China; Female; Gram-Positive Bacterial Infections; Humans; Kidney; Male; Middle Aged; Nonlinear Dynamics; Vancomycin; Young Adult
PubMed: 31277936
DOI: 10.1016/j.jiph.2019.06.016 -
Antimicrobial Agents and Chemotherapy Nov 2015We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of Clostridium difficile infection (CDI)...
We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of Clostridium difficile infection (CDI) in patients hospitalized during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (P = 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly associated with decreased recurrence (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.12 to 0.93). The total lengths of stay of readmitted patients were 183 days for vancomycin and 87 days for fidaxomicin, with costs of $454,800 and $196,200, respectively. Readmissions for CDI were reimbursed on the basis of the severity of CDI, totaling $151,136 for vancomycin and $107,176 for fidaxomicin. Fidaxomicin drug costs totaled $62,112, and vancomycin drug costs were $6,646. We calculated that the hospital lost an average of $3,286 per fidaxomicin-treated patient and $6,333 per vancomycin-treated patient, thus saving $3,047 per patient with fidaxomicin. Fidaxomicin use for CDI treatment prevented readmission and decreased hospital costs compared to use of oral vancomycin.
Topics: Aminoglycosides; Clostridioides difficile; Clostridium Infections; Fidaxomicin; Humans; Retrospective Studies; Vancomycin
PubMed: 26324268
DOI: 10.1128/AAC.00939-15 -
Journal of Infection and Public Health Apr 2020The clinical use of intermittent infusion of vancomycin (IIV) and continuous infusion of vancomycin (CIV) is controversial. The aim of this study was to assess the... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
The clinical use of intermittent infusion of vancomycin (IIV) and continuous infusion of vancomycin (CIV) is controversial. The aim of this study was to assess the effectiveness and safety of IIV and CIV by using a meta-analysis for cohort studies and randomized controlled trials.
METHODS
We compared the probabilities of target attainment (PTA) for the measured concentration (C) ≥the target concentration (C), the PTA for the area under the drug concentration curve/minimal inhibitory concentration (AUC/MIC) ≥400, the duration of treatment, nephrotoxicity, and overall mortality after vancomycin treatment as reported in PubMed, Embase, Cochrane, and Web of Science.
RESULTS
A total of 14 studies with 1640 patients were included in the meta-analysis. For IIV, the PTA of C≥C (RR=0.72, 95% CI=0.60-0.88), and nephrotoxicity (RR=1.70, 95% CI=1.34-2.14) were significantly different from those of CIV. The treatment duration (SMD=0.08, 95% CI=-0.08-0.25), the PTA of AUC/MIC ≥ 400 (RR=0.84, 95% CI=0.70-1.00) and mortality (RR=0.94, 95% CI=0.72-1.25) were not significantly different from those of CIV.
CONCLUSIONS
The results showed that CIV was easier to achieve C and safer than IIV. Additional randomized controlled trials focusing on the concentration of vancomycin are needed for further analysis.
Topics: Anti-Bacterial Agents; Drug Administration Schedule; Gram-Positive Bacterial Infections; Humans; Infusions, Intravenous; Vancomycin
PubMed: 31530441
DOI: 10.1016/j.jiph.2019.09.001 -
Proceedings of the National Academy of... Apr 2023The alarming rise in superbugs that are resistant to drugs of last resort, including vancomycin-resistant enterococci and staphylococci, has become a significant global...
The alarming rise in superbugs that are resistant to drugs of last resort, including vancomycin-resistant enterococci and staphylococci, has become a significant global health hazard. Here, we report the click chemistry synthesis of an unprecedented class of shapeshifting vancomycin dimers (SVDs) that display potent activity against bacteria that are resistant to the parent drug, including the ESKAPE pathogens, vancomycin-resistant (VRE), methicillin-resistant (MRSA), as well as vancomycin-resistant (VRSA). The shapeshifting modality of the dimers is powered by a triazole-linked bullvalene core, exploiting the dynamic covalent rearrangements of the fluxional carbon cage and creating ligands with the capacity to inhibit bacterial cell wall biosynthesis. The new shapeshifting antibiotics are not disadvantaged by the common mechanism of vancomycin resistance resulting from the alteration of the C-terminal dipeptide with the corresponding d-Ala-d-Lac depsipeptide. Further, evidence suggests that the shapeshifting ligands destabilize the complex formed between the flippase MurJ and lipid II, implying the potential for a new mode of action for polyvalent glycopeptides. The SVDs show little propensity for acquired resistance by enterococci, suggesting that this new class of shapeshifting antibiotic will display durable antimicrobial activity not prone to rapidly acquired clinical resistance.
Topics: Vancomycin; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus; Vancomycin-Resistant Enterococci; Microbial Sensitivity Tests
PubMed: 37011186
DOI: 10.1073/pnas.2208737120 -
Antimicrobial Agents and Chemotherapy May 2018Strains of methicillin-resistant (MRSA), particularly those belonging to the USA300 pulsotype, have been well described to cause severe osteoarticular infections...
Association of Vancomycin MIC and Molecular Characteristics with Clinical Outcomes in Methicillin-Susceptible Staphylococcus aureus Acute Hematogenous Osteoarticular Infections in Children.
Strains of methicillin-resistant (MRSA), particularly those belonging to the USA300 pulsotype, have been well described to cause severe osteoarticular infections (OAIs). A vancomycin MIC of ≥1.5 μg/ml has been demonstrated to contribute to disease severity in adults with MRSA and even methicillin-susceptible (MSSA) bacteremia. Little data exist describing the outcomes of MSSA OAIs in terms of molecular characteristics and vancomycin MIC. All patients/isolates were chosen from a surveillance study at Texas Children's Hospital (TCH). OAI isolates were identified from 2011 to 2016 and subjected to vancomycin Etests, pulsed-field gel electrophoresis (PFGE), and PCR to determine Panton-Valentine leucocidin (PVL) production and group. Two hundred fifty-two cases of OAI were identified; 183 cases were MSSA (72.6%). During the study period, a decrease in the proportion of cases secondary to MRSA was observed, declining from 37.8% to 15.9% ( = 0.02). Of the MSSA isolates, 26.2% and 23.5% were USA300 and PVL positive, respectively. An increase in the proportion of MSSA isolates with a vancomycin MIC of ≥1.5 μg/ml occurred in the study period ( = 0.004). In MSSA, an elevated vancomycin MIC was associated with multiple surgical procedures and venous thromboses, even when adjusting for empirical β-lactam use. An increase in vancomycin MIC was noted among isolates belonging to group 4 during the study period. Methicillin resistance is declining among OAI isolates at TCH. Simultaneously, vancomycin Etest MICs are increasing among MSSA isolates. Vancomycin MICs of ≥2 μg/ml are associated with adverse clinical outcomes in MSSA irrespective of antibiotic choice, suggesting that this may be a surrogate for organism virulence.
Topics: Bone Diseases, Infectious; Child; Child, Preschool; Humans; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; Vancomycin
PubMed: 29530845
DOI: 10.1128/AAC.00084-18 -
Pharmacological Reports : PR Aug 2023Bacterial resistance is defined as a microorganism's capacity to develop mechanisms for resisting a determined antimicrobial. Gram-positive bacteria, such as...
BACKGROUND
Bacterial resistance is defined as a microorganism's capacity to develop mechanisms for resisting a determined antimicrobial. Gram-positive bacteria, such as Staphylococcus aureus (S. aureus) and Enterococcus faecalis (E. faecalis), are internationally recognized among the isolates with this resistance profile. In this context, the demand for new medicines has risen, and silver nanoparticles (AgNPs) have been highlighted, especially for their anti-bacterial effects. To develop a nano-antibiotic for treating these Gram-positive strains, we herein report synthesizing and characterizing a nano-antibiotic based on AgNPs functionalized with the complex vancomycin-cysteamine.
METHODS
AgNPs were produced using the bottom-up methodology and functionalized with vancomycin modified by the carbodiimide chemistry, forming Ag@vancomycin. Susceptibility tests were performed using S. aureus and E. faecalis strains to assess the bacteriostatic and bactericidal potential of the developed nano-antibiotic.
RESULTS
Fourier transform infrared spectroscopy measurements showed the efficacy of vancomycin chemical modification, and the characteristic bands of AgNPs functionalization with the antibiotic. The increase in the nano-antibiotic average hydrodynamic diameter observed by dynamic light scattering proved the presence of vancomycin at the surface of AgNPs. The data from the minimum inhibitory concentration and minimal bactericidal concentration assays tested on standard and clinical planktonic strains of S. aureus and E. faecalis presented excellent performance.
CONCLUSION
The results indicate the promising development of a new nano-antibiotic in which the functionalization potentiates the bacteriostatic action of AgNPs and vancomycin with greater efficacy against Gram-positive strains.
Topics: Anti-Bacterial Agents; Vancomycin; Staphylococcus aureus; Enterococcus faecalis; Silver; Cysteamine; Metal Nanoparticles; Microbial Sensitivity Tests
PubMed: 37171518
DOI: 10.1007/s43440-023-00491-3 -
Scientific Reports Mar 2019In the presented study, transportan 10 (TP10), an amphipathic cell penetrating peptide (CPP) with high translocation activity, was conjugated with vancomycin (Van),...
In the presented study, transportan 10 (TP10), an amphipathic cell penetrating peptide (CPP) with high translocation activity, was conjugated with vancomycin (Van), which is known for poor access to the intracellular bacteria and the brain. The antibacterial activity of the conjugates was tested on selected clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus sp. It turned out that all of them had superior antimicrobial activity in comparison to that of free Van, which became visible particularly against clinical MRSA strains. Furthermore, one of the conjugates was tested against MRSA - infected human cells. With respect to them, this compound showed high bactericidal activity. Next, the same conjugate was screened for its capacity to cross the blood brain barrier (BBB). Therefore, qualitative and quantitative analyses of the conjugate's presence in the mouse brain slices were carried out after its iv administration. They indicated the conjugate's presence in the brain in amount >200 times bigger than that of Van. The conjugates were safe with respect to erythrocyte toxicity (erythrocyte lysis assay). Van in the form of a conjugate with TP10 acquires superior pharmacodynamic and pharmacokinetic.
Topics: Amino Acid Sequence; Animals; Anti-Bacterial Agents; Cell-Penetrating Peptides; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Erythrocytes; HEK293 Cells; Hemolysis; Humans; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Molecular Weight; Recombinant Fusion Proteins; Sheep; Tissue Distribution; Vancomycin
PubMed: 30824786
DOI: 10.1038/s41598-019-40103-w -
Pharmacotherapy Dec 2013Vancomycin treatment failure has been associated with low serum vancomycin trough concentrations, prompting recommendations to increase the daily doses in adults and...
BACKGROUND
Vancomycin treatment failure has been associated with low serum vancomycin trough concentrations, prompting recommendations to increase the daily doses in adults and children. Despite more aggressive vancomycin dosing, there continues to be significant variability in vancomycin trough concentrations in pediatric patients.
METHODS
To determine if vancomycin trough concentrations in pediatric patients differ by age and weight, we reviewed records of hospitalized patients who received vancomycin between 2008 and 2012. Patients were divided into groups that received vancomycin 40 mg/kg/day (2008-2009) or 60 mg/kg/day (2010-2012). Vancomycin trough concentrations were compared between groups and within the 60 mg/kg/day group, stratified by patient age and weight.
RESULTS
After increasing the vancomycin dose from 40 to 60 mg/kg/day, initial trough concentrations increased significantly in patients younger than 2 and greater than 6 years of age, but not in patients between the ages of 2 and 5 years. In the 60 mg/kg/day group, only 16.7% of patients between 2 and 5 years of age had initial trough concentrations in the therapeutic range (10-20 μg/ml). Initial trough concentrations were therapeutic in a greater proportion of patients ages 6-12 years (38.7%) and 13-18 years (63.0%). Patients between the ages of 13 and 18 had the highest proportion of supratherapeutic initial vancomycin trough concentrations (14.8%). Patients weighing over 50 kg had significantly higher trough concentrations than patients 50 kg or less (17.1 μg/ml vs 9.3 μg/ml, p<0.001).
CONCLUSION
Although increasing the vancomycin dose from 40 to 60 mg/kg/day led to a significant increase in vancomycin trough concentrations, a large proportion of patients receiving 60 mg/kg/day of vancomycin had trough concentrations outside of the therapeutic range. Specifically, patients younger than 6 years tended to have low trough concentrations, whereas adolescents and children over 50 kg were more likely to have elevated trough concentrations. Vancomycin dosing strategies in pediatric patients should consider age and weight as well as renal function and indication.
Topics: Adolescent; Age Factors; Anti-Bacterial Agents; Body Weight; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Infant; Male; Retrospective Studies; Vancomycin
PubMed: 23864541
DOI: 10.1002/phar.1331