Vancomycin MIC creep in MRSA isolates from 1997 to 2008 in a healthcare region in Hong Kong

Ho, Pak‐Leung; Lo, P. W.; Chow, Kin-Hung; Lau, Eric H. Y.; Lai, Eileen L.; Cheng, Vincent Chi-Chung; Kao, Ryt

doi:10.1016/j.jinf.2009.11.011

Cited by 68 publications

(41 citation statements)

References 30 publications

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“…In the present study, the simulation approach demonstrated that the doses of 90 mg/kg/day for infants and of 80 mg/kg for children and adolescents allow nearly 50% of patients to achieve the AUC/ MIC target, with the standard MIC susceptibility breakpoint of 1 mg/liter which was clinically validated primarily in adult pneumonia studies in MRSA. However, according to recent data, there is a trend to a decrease in vancomycin efficacy, linked to the increase in the vancomycin MIC during MRSA infection (22,23). Indeed, to obtain similar efficacy, treatment of MSRA with a higher MIC would require a higher AUC.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease

Zhao

Zhang

Fakhoury

et al. 2014

Antimicrob Agents Chemother

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e An increase in vancomycin dose has been proposed in adults with malignant hematological disease. As pediatric data are limited, our aim was to evaluate the population pharmacokinetics of vancomycin in order to define the appropriate dosing regimen in children with malignant hematological disease. Vancomycin concentrations were collected prospectively during therapeutic monitoring. Population pharmacokinetic analysis was performed using NONMEM software. Seventy children (age range, 0.3 to 17.7 years) were included. With the current recommended dosing regimen of 40 to 60 mg/kg/day, 53 children (76%) had subtherapeutic steady-state trough concentrations (C ss/min of <10 mg/liter). A one-compartment model with first-order elimination was developed. Systematic covariate analysis identified that weight significantly influenced clearance (CL) and volume of distribution (V) with power functions of 0.677 for CL and 0.838 for V. Vancomycin CL also significantly increased with increases in creatinine clearance and seemed to be higher in children with malignant hematological disease than in the general pediatric population. The model was validated internally. Its predictive performance was further confirmed in an external validation by Bayesian estimation. A patient-tailored dosing regimen was developed based on the final pharmacokinetic model and showed that a higher proportion of patients reached the target C ss/min than with the traditional mg/kg-basis dose (60% versus 49%) and that the risks associated with underdosing or overdosing were reduced. This is the first population pharmacokinetic study of vancomycin in children with malignant hematological disease. An optimized dosing regimen, taking into account patient weight, creatinine clearance, and susceptibility of the pathogens involved, could routinely be used to individualize vancomycin therapy in this vulnerable population.

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Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease

Zhao

Zhang

Fakhoury

et al. 2014

Antimicrob Agents Chemother

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“…12 Unless appropriate testing methods are used and the data carefully analyzed, such subtle changes in the MIC trend within the susceptible range (MIC creep) would be missed. 13 It has been reported that vancomycin MICs generated by Etest were consistently one twofold dilution higher than those determined by Clinical and Laboratory Standards Institute (CLSI) broth dilution method. 14,15 In addition, the BHIA plates being recommended to screen the S. aureus reduced susceptibility to vancomycin in the CLSI.…”

Section: Introductionmentioning

confidence: 95%

Vancomycin MICs of the resistant mutants of S. aureus ATCC43300 vary based on the susceptibility test methods used

Mei

et al. 2012

J Antibiot

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“…Review of references in these papers identified 3 other studies. Both studies performed at the time of isolation suggested evidence of vancomycin MIC creep; however, creep was less consistently found by Etest or broth microdilution (BMD) after storage, although heterogeneity in study population and size was noted (see the supplemental material) (1,2,6,11,13,14,20,23,26,29,35,36).…”

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confidence: 99%

Effects of Storage on Vancomycin and Daptomycin MIC in Susceptible Blood Isolates of Methicillin-Resistant Staphylococcus aureus

et al. 2012

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b B y repeating Etests on 36 blood isolates of methicillin-resistant Staphylococcus aureus (MRSA) over 9 months, we explored the effects of isolate storage on vancomycin and daptomycin MICs. We identified overall declines in vancomycin and daptomycin MICs taken from the same isolates at 3-month intervals (P Ͻ 0.001). Declines of Ն1 doubling dilution were observed in 75% and 67% of isolates for vancomycin and daptomycin MICs, respectively. Effects of storage should be considered in evidence of MIC "creep."Decreasing effectiveness of vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections has been linked to increasing vancomycin MIC within the susceptibility range (Յ2 mg/liter) (5). Subinhibitory vancomycin exposure may also be a risk factor for daptomycin heterogenous susceptibility (18,22,28). However, evidence of MIC "creep" is mixed (24), and the implications for treatment decisions of a vancomycin MIC that is high but still within the susceptibility range are uncertain (5). We previously demonstrated that detection of vancomycin and daptomycin MIC creep may be method dependent (7). In this study, we further explored the hypothesis that isolate storage may explain divergent results in investigations of susceptibility trends.A prospective repeated-measure design involved susceptibility testing of MRSA bloodstream isolates (BSI) at the time of isolation and at 3-month intervals. A 9-month follow-up period was chosen on the basis of previous data suggesting that changes in susceptibility occurred within this time. Our sample included all nonreplicate MRSA BSI identified in adult, nonobstetric patients at Aberdeen Royal Infirmary (Scotland) between January and March 2011. Susceptibility testing at the time of isolation was by Etest performed in accordance with the manufacturer's guidelines on Mueller-Hinton agar (Oxoid), and results were read blind in duplicate. Each isolate was then stored in a Cryobank storage container (Mast Diagnostics), which contained glycerol, peptones, sucrose, and saline, at Ϫ70°C. Isolates were recovered from storage at 3, 6, and 9 months and subcultured twice prior to repeat Etests. Assessors were blinded to previous MIC results.Interobserver agreement was assessed by weighted Cohen's kappa (). Friedman tests were used to test for overall difference in MICs across repeated readings, with post hoc analyses by Wilcoxon signed-rank tests with Bonferroni adjustment (␣ ϭ 0.0083). Variation in trends was investigated by independent-sample t test to assess differences in means of slopes for isolates grouped by "high" (Ͼmedian) or "low" (Ͻmedian) baseline MICs. All analyses were repeated with MICs from Etest converted to doubling dilutions by rounding up intermediate increments.To evaluate the potential for systematic bias arising from differences in storage of isolates before susceptibility testing in stud-

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Vancomycin MIC creep in MRSA isolates from 1997 to 2008 in a healthcare region in Hong Kong

Cited by 68 publications

References 30 publications

Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease

Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease

Vancomycin MICs of the resistant mutants of S. aureus ATCC43300 vary based on the susceptibility test methods used

Effects of Storage on Vancomycin and Daptomycin MIC in Susceptible Blood Isolates of Methicillin-Resistant Staphylococcus aureus

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