Daptomycin for the treatment of vancomycin-resistant enterococcal infections

Grim, Shellee A.; Hong, Irene S.; Freeman, Joseph W.; Edwards, Christopher; Clark, Nina M.

doi:10.1093/jac/dkn478

Cited by 11 publications

(13 citation statements)

References 6 publications

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“…The simulated effective dose to achieve 80% maximal kill activity was 3 mg/kg for the two staphylococcal isolates (MICs of 0.125 and 0.25 g/ml) and 6.8 mg/kg for the two Enterococcus faecium isolates (MICs of 2 and 4 g/ml) (9). Based on the available data, the current Food and Drug Administration-approved dose of 6 mg/kg/day for Staphylococcus aureus bacteremia and right-sided infective endocarditis infections is likely suboptimal for infections caused by most enterococcus due to the higher MIC values and leads to the logical conclusion that higher daptomycin doses (i.e., Ͼ6 mg/kg/day) will be required to adequately treat these infections.Clinical experience with daptomycin for the treatment of enterococcal infections is limited to several retrospective, observational studies of patients with enterococcal bacteremia (12,14,17,18,20,21,28,29,31,32). Success rates in these series vary from 58.1% to 90% depending on the severity of illness of the included patients and the inclusion of clinical or microbiological results in the definition of success.…”

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confidence: 99%

“…Clinical experience with daptomycin for the treatment of enterococcal infections is limited to several retrospective, observational studies of patients with enterococcal bacteremia (12,14,17,18,20,21,28,29,31,32). Success rates in these series vary from 58.1% to 90% depending on the severity of illness of the included patients and the inclusion of clinical or microbiological results in the definition of success.…”

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Evaluation of Standard- and High-Dose Daptomycin versus Linezolid against Vancomycin-Resistant Enterococcus Isolates in an In Vitro Pharmacokinetic/Pharmacodynamic Model with Simulated Endocardial Vegetations

Hall

Steed

Arias

et al. 2012

Antimicrob Agents Chemother

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Daptomycin MICs for enterococci are typically 1-to 2-fold higher than those for Staphylococcus aureus, and there is an imminent need to establish the optimal dose for appropriate treatment of enterococcal infections. We investigated the bactericidal activity of daptomycin at various dose exposures compared to that of linezolid against vancomycin-resistant enterococcus (VRE) in an in vitro pharmacokinetic/pharmacodynamic model utilizing simulated endocardial vegetations over 96 h. Daptomycin at doses of 6, 8, 10, and 12 mg/kg of body weight/day and linezolid at a dose of 600 mg every 12 h were evaluated against two clinical vancomycin-resistant Enterococcus faecium strains (EFm11499 and 09-184D1051), one of which was linezolid resistant (09-184D1051), and one clinical vancomycin-resistant Enterococcus faecalis strain (EFs11496). Daptomycin MICs were 4, 2, and 0.5 g/ml for EFm11499, 09-184D1051, and EFs11496, respectively. Bactericidal activity, defined as a >3 log 10 CFU/g reduction from the initial colony count, was demonstrated against all three isolates with all doses of daptomycin; however, bactericidal activity was not sustained with the daptomycin 6-and 8-mg/kg/day regimens. Linezolid was bacteriostatic against EFm11499 and displayed no appreciable activity against 09-184D1051 or EFs11496. Concentration-dependent killing was displayed with more sustained reduction in colony count (3.58 to 6.46 and 5.89 to 6.56 log 10 CFU/g) at 96 h for the simulated regimen of daptomycin at doses of 10 and 12 mg/kg/day, respectively (P < 0.012). No E. faecium mutants with reduced susceptibility were recovered at any dosage regimen; however, the E. faecalis strain developed reduced daptomycin susceptibility with daptomycin at 6, 8, and 10 but not at 12 mg/kg/day. Daptomycin displayed a dose-dependent response against three VRE isolates, with high-dose daptomycin producing sustained bactericidal activity. Further research is warranted. D aptomycin (DAP) is a lipopeptide antibiotic with concentration-dependent activity against Gram-positive bacteria that is currently approved for the treatment of staphylococcus bacteremia and right-sided endocarditis at a dose of 6 mg/kg of body weight/day (7). Daptomycin also displays in vitro activity against almost all Enterococcus spp., including those resistant to other antibiotics, such as vancomycin, linezolid (LZD), and quinupristindalfopristin (3, 22, 38). Daptomycin exhibits a lower potency against enterococci than that against staphylococci, demonstrating higher Clinical Laboratory and Standards Institute (CLSI) breakpoints (Յ4 g/ml versus Յ1 g/ml), MIC 50 values (1 to 2 g/ml versus 0.25 g/ml), and MIC 90 values (1 to 2 g/ml versus 0.5 g/ml) (11, 38). Based on in vivo neutropenic mice infection models, maximum concentration (C max )/MIC and area under the concentration-time curve (AUC)/MIC ratios are the best predictors for efficacy of daptomycin against infections caused by both Staphylococcus spp. and Enterococcus spp. (39) Additionally, in vitro pharmacokinetic/pharmacodynamic (P...

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confidence: 99%

mentioning

confidence: 99%

Evaluation of Standard- and High-Dose Daptomycin versus Linezolid against Vancomycin-Resistant Enterococcus Isolates in an In Vitro Pharmacokinetic/Pharmacodynamic Model with Simulated Endocardial Vegetations

Hall

Steed

Arias

et al. 2012

Antimicrob Agents Chemother

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“…54,85 Despite the theoretical concern, 6 mg/kg is still the most common dosing scheme used in trials and clinical practice. 39,[62][63][64][65]67 Real-world experience is limited at doses >6 mg/kg. A study by Moise et al 66 analyzed the efficacy of daptomycin administered at doses ≥8 mg/kg (median dose was 8 mg/kg) for a variety of Gram-positive infections.…”

Section: Clinical Trials Experience With Daptomycin Median Doses >6 Mmentioning

confidence: 99%

“…The remaining 2 studies did not find a higher success rate with higher doses. 64,68 The interpretation of these results is limited by relatively small sample sizes and unbalanced baseline characteristics. Additionally, because patients were not randomized to daptomycin dose groups, dose escalation of daptomycin may have been performed in the patients who were more critically ill or doing poorly.…”

Section: Studies Comparing Outcomes Among Patients Who Received Daptomentioning

confidence: 99%

“…Additionally, because patients were not randomized to daptomycin dose groups, dose escalation of daptomycin may have been performed in the patients who were more critically ill or doing poorly. 64 It is also possible that patients having a very high burden of disease, and concomitant immunosuppression may have diluted the true benefit possible with high-dose daptomycin. Although these studies add to the collective experience with high-dose daptomycin, further prospective comparative studies are needed to fully understand the optimal dosing of daptomycin in treating infections caused by VRE and whether higher doses may be of value in specific subsets of patients.…”

Section: Studies Comparing Outcomes Among Patients Who Received Daptomentioning

confidence: 99%

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