Teicoplanin and daptomycin bactericidal activities in the presence of albumin or serum under controlled conditions of pH and ionized calcium

Self Cite

We adapted an in vitro pharmacodynamic model of infection to incorporate simulated endocardial vegetations. The bactericidal activities of teicoplanin, vancomycin, gentamicin, and various combinations of these drugs were studied against a strain of methicillin-susceptible Staphylococcus aureus obtained from a patient being treated for endocarditis at Detroit Receiving Hospital. Bacteria were grown overnight, concentrated, and added to a mixture of cryoprecipitate (80%o)

Section: In Vitro Model Of Endocarditis a One-compartment In Vitromentioning

confidence: 69%

Bactericidal activities of teicoplanin, vancomycin, and gentamicin alone and in combination against Staphylococcus aureus in an in vitro pharmacodynamic model of endocarditis

McGrath

Kang

Kaatz

et al. 1994

Self Cite

“…Mueller-Hinton broth II (MHB II; Difco, Detroit, MI) with 25 mg/liter of calcium and 12.5 g/ml magnesium was used for susceptibility testing and in vitro pharmacodynamic simulated endocardial vegetation (SEV) models. Due to the dependency of daptomycin on calcium for antimicrobial activity, supplemented MHB II (SMHB II) containing 50 g/ml of calcium was used for susceptibility testing, and that containing 75 g/ml of calcium (50 and 75 SMHB, respectively) was used for in vitro SEV model experiments (due to binding of calcium by albumin) (25). Colony counts were determined using brain heart infusion agar (BHA; Difco, Detroit, MI).…”

Section: Methodsmentioning

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

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...

“…The mechanism of action differs from that of the glycopeptides, involving the disruption of amino acid transport by the cell membrane and alterations of the cytoplasmic membrane potential (1)(2)(3). The bactericidal activity of daptomycin is concentration dependent and is influenced by pH and ionized calcium concentrations (9). Like teicoplanin, daptomycin is highly protein bound (94%), and its in vitro activity is altered in the presence of serum or albumin.…”

mentioning

confidence: 99%

“…However, clinical trials were suspended when treatment failures were noted in patients with S. aureus endocarditis (Eli Lilly & Co., personal communication). Possible reasons for failure included the high degree of protein binding and the degree of penetration into cardiac vegetations (9). Experimental animal endocarditis studies replicating clinical trial dosages and achievable concentrations demonstrated that slightly higher dosage regimens of daptomycin were as effective as or more effective than vancomycin in reducing vegetative bacterial densities (8).…”

mentioning

confidence: 99%

In Vitro Activities of Daptomycin, Vancomycin, Linezolid, and Quinupristin-Dalfopristin against Staphylococci and Enterococci, Including Vancomycin- Intermediate and -Resistant Strains

Rybak

Hershberger

Moldovan

et al. 2000

328

210

The in vitro activity of daptomycin was compared with those of vancomycin, linezolid, and quinupristindalfopristin against a variety (n ‫؍‬ 203) of gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and S. epidermidis (MRSA and MRSE, respectively), vancomycin-resistant enterococci (VRE), and vancomycin-intermediate S. aureus (VISA). Overall, daptomycin was more active against all organisms tested, except Enterococcus faecium and VISA, against which its activity was similar to that of quinupristin-dalfopristin. In time-kill studies with MRSA, MRSE, VRE, and VISA, daptomycin demonstrated greater bactericidal activity than all other drugs tested, killing >3 log CFU/ml by 8 h. Daptomycin may be a potential alternative drug therapy for multidrug-resistant gram-positive organisms and warrants further investigation.