Relationship between Vancomycin MIC and Failure among Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia Treated with Vancomycin

Department of Pharmacy Practice, Albany College of Pharmacy, Albany, New York 12208-3492, USA.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 06/2008; 52(9):3315-20. DOI: 10.1128/AAC.00113-08
Source: PubMed


There is growing concern that vancomycin has diminished activity for methicillin-resistant Staphylococcus aureus (MRSA) infections, with vancomycin MICs at the high end of the CLSI susceptibility range. Despite this growing concern, there are limited clinical data to support this notion. To better elucidate this, a retrospective cohort study was conducted among patients with MRSA bloodstream infections who were treated with vancomycin between January 2005 and May 2007. The inclusion criteria were as follows: at least 18 years old, nonneutropenic, with an MRSA culture that met the CDC criteria for bloodstream infection, had received vancomycin therapy within 48 h of the index blood culture, and survived >24 h after vancomycin administration. Failure was defined as 30-day mortality, bacteremia >or=10 days on vancomycin therapy, or a recurrence of MRSA bacteremia within 60 days of vancomycin discontinuation. Classification and regression tree (CART) analysis identified the vancomycin MIC breakpoint associated with an increased probability of failure. During the study period, 92 patients met the inclusion criteria. The vancomycin MIC breakpoint derived by CART analysis was >or=1.5 mg/liter. The 66 patients with vancomycin MICs of >or=1.5 mg/liter had a 2.4-fold increase in failure compared to patients with MICs of <or=1.0 mg/liter (36.4% and 15.4%, respectively; P = 0.049). In the Poisson regression, a vancomycin MIC of >or=1.5 mg/liter was independently associated with failure (adjusted risk ratio, 2.6; 95% confidence interval, 1.3 to 5.4; P = 0.01). These data strongly suggest that patients with MRSA bloodstream infections with vancomycin MICs of >or=1.5 mg/liter respond poorly to vancomycin. Alternative anti-MRSA therapies should be considered for these patients.

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    • "The susceptibility breakpoint for vancomycin has been set at ≤2 ␮g/mL and on this basis the frequency of in vitro resistance to vancomycin remains low in most institutions. However, multiple reports have been published on the occurrence of elevated minimum inhibitory concentrations (MICs) among MRSA strains and the associated detrimental effect on the efficacy of vancomycin [2] [3]. Indeed, a recent meta-analysis reported a vancomycin MIC ≥ 1 ␮g/mL as a factor independently predictive of treatment failure [odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.60–4.51] "
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    ABSTRACT: Elevated minimum inhibitory concentrations (MICs) of vancomycin against meticillin-resistant Staphylococcus aureus (MRSA) and the emergence of heteroresistant S. aureus strains have led to increased use of anti-MRSA antibiotics other than vancomycin. Ceftaroline fosamil is a novel cephalosporin with activity against MRSA, but there are limited clinical data on its use for MRSA bacteraemia (MRSAB) and against strains exhibiting high vancomycin MICs (2–4 μg/mL). This multicentre, retrospective, case–control study compared the microbiological and clinical effectiveness of ceftaroline used after vancomycin failure with that of vancomycin-treated controls for the treatment of MRSA with vancomycin MICs ≥ 2 μg/mL. In total, 32 patients were matched 1:1 with respect to vancomycin MIC, age and origin of bacteraemia. In the ceftaroline group, patients received prior MRSA therapy for a median of 5 days [interquartile range (IQR), 3–15.8 days] prior to switching to ceftaroline. Median time to eradication of MRSA was significantly less after treatment with ceftaroline compared with vancomycin [4 days (IQR, 3–7.5 days) vs. 8 days (IQR, 5.8–19.5 days); P = 0.02]. Both clinical success at the end of treatment and recurrence of MRSA at Day 7 were trending towards being inferior in the vancomycin group, although the results did not attain statistical significance [81% vs. 44% (P = 0.06) and 6% vs. 38% (P = 0.08), respectively]. Ceftaroline added at the point of vancomycin failure resolves MRSAB more rapidly and with a higher rate of clinical success, therefore ceftaroline should be considered as an alternative for these difficult-to-treat infections.
    International Journal of Antimicrobial Agents 09/2014; 44(6). DOI:10.1016/j.ijantimicag.2014.07.024 · 4.30 Impact Factor
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    • "Vancomycin, a tricyclic glycopeptide, is the standard first-line treatment for patients with MRSA bacteremia. However, studies have linked vancomycin treatment failure in MRSA with higher vancomycin MICs even at MICs below the Clinical and Laboratory Standards Institute (CLSI) susceptibility breakpoints for S. aureus (≤2 ug/ml) [8-11]. Recent consensus guidelines recommend that clinicians consider using alternative agents for MRSA infection when the vancomycin MIC is greater than 1 ug/ml [12,13], especially if there is evidence of clinical failure with regards to vancomycin treatment. "
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    ABSTRACT: Background: Vancomycin is the standard first-line treatment for methicillin-resistant Staphylococcus aureus bacteremia. However, recent consensus guidelines recommend that clinicians consider using alternative agents such as daptomycin when the vancomycin minimum inhibitory concentration is greater than 1 ug/ml. To date however, there have been no head-to-head randomized trials comparing the safety and efficacy of daptomycin and vancomycin in the treatment of such infections. The primary aim of our study is to compare the efficacy of daptomycin versus vancomycin in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations (greater than or equal to 1.5 ug/ml) in terms of reducing all-cause 60-day mortality. Methods/design: The study is designed as a multicenter prospective open label phase IIB pilot randomized controlled trial. Eligible participants will be inpatients over 21-years-old with a positive blood culture for methicillin-resistant Staphylococcus aureus with vancomycin minimum inhibitory concentration of greater than or equal to 1.5 ug/ml. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. We aim to recruit 50 participants over a period of two years. Participants randomized to the active control arm will receive vancomycin dose-while those randomized to the intervention arm will receive daptomycin. Participants will receive a minimum of 14 days study treatment.The primary analysis will be conducted on the intention-to-treat principle. The Fisher's exact test will be used to compare the 60-day mortality rate from index blood cultures (primary endpoint) between the two treatment arms, and the exact two-sided 95% confidence interval will be calculated using the Clopper and Pearson method. Primary analysis will be conducted using a two sided alpha of 0.05. Discussion: If results from this pilot study suggest that daptomycin shows significant efficacy in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations, we aim to proceed with a larger scale confirmatory study. This would help guide clinicians and inform practice guidelines on the optimal treatment for such infections. Trial registration: The trial is listed on (NCT01975662, date of registration: 29 October 2013).
    Trials 06/2014; 15(1):233. DOI:10.1186/1745-6215-15-233 · 1.73 Impact Factor
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    • "Meanwhile, isolates with heteroresistance (hVISA) are emerging and the clinical importance of such isolates is uncertain. Vancomycin treatment failures were reported in patients infected with susceptible isolates with MIC values of 1.5 to 2 μg/ml [1,2,17]. Besides, the presence of VISA and hVISA has been associated with worse clinical outcomes [18-20]. "
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    ABSTRACT: The aim of this study was to determine the distribution of vancomycin and daptomycin MICs among methicillin-resistant Staphylococcus aureus (MRSA) blood isolates, the prevalence of heterogeneous vancomycin-intermediate S. aureus (hVISA) and the relationship between hVISA and vancomycin MIC values. A total of 175 MRSA blood isolates were collected from seven university hospitals in Turkey. All isolates were tested for susceptibility to vancomycin and daptomycin by reference broth microdilution (BMD) and by standard Etest method. BMD test was performed according to CLSI guidelines and Etest was performed according to the instructions of the manufacturer. All isolates were screened for the presence of the hVISA by using macro Etest (MET) and population analysis profile-area under the curve (PAP-AUC) methods. The vancomycin MIC50, MIC90 and MIC ranges were 1, 2, and 0.5-2 mug/ml, respectively, by both of BMD and Etest. The daptomycin MIC50, MIC90 and MIC ranges were 0.5, 1 and 0.125 -1 mug/ml by BMD and 0.25, 0.5 and 0.06-1 mug/ml by Etest, respectively. The vancomycin MIC for 40.6% (71/175) of the MRSA isolates tested was >1 mug/ml by BMD. No vancomycin and daptomycin resistance was found among MRSA isolates. Percent agreement of Etest MICs with BMD MICs within +/-1 doubling dilution was 100% and 73.1% for vancomycin and daptomycin, respectively. The prevalence of hVISA among MRSA blood isolates was 13.7% (24/175) by PAP-AUC method. MET identified only 14 of the hVISA strains (sensitivity, 58.3%), and there were 12 strains identified as hVISA that were not subsequently confirmed by PAP-AUC (specificity, 92.1%). Agreement between BMD and Etest MICs is high both for vancomycin and daptomycin. Daptomycin was found to be highly active against MRSA isolates including hVISA. A considerable number of isolates are determined as hVISA among blood isolates. As it is impractical to use the reference method (PAP-AUC) for large numbers of isolates, laboratory methods for rapid and accurate identification of hVISA need to be developed.
    BMC Infectious Diseases 12/2013; 13(1):583. DOI:10.1186/1471-2334-13-583 · 2.61 Impact Factor
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