Activity of linezolid and high-dose daptomycin, alone or in combination, in an in vitro model of Staphylococcus aureus biofilm

Parra-Ruiz, Jorge; Molina, Ana Rodríguez; Peña-Monje, Alejandro; Hernández-Quero, José

doi:10.1093/jac/dks272

Cited by 68 publications

(35 citation statements)

References 23 publications

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“…This highlights the importance of pharmacodynamic interactions with combination therapy, even for antibiotics with a completely dif- ferent spectrum of activity. Of interest, one study demonstrated the activity of daptomycin and linezolid in combination against MRSA, but in contrast to our study, this study tested formed biofilms on coupons (28).…”

contrasting

confidence: 58%

Observed Antagonistic Effect of Linezolid on Daptomycin or Vancomycin Activity against Biofilm-Forming Methicillin-Resistant Staphylococcus aureus in an In Vitro Pharmacodynamic Model

Luther

LaPlante

2015

Antimicrob Agents Chemother

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c Pharmacodynamic activity in antibiotic combinations of daptomycin, vancomycin, and linezolid was investigated in a 48-h in vitro pharmacodynamic model. Using human-simulated free drug concentrations, activity against clinical biofilm-forming methicillin-resistant Staphylococcus aureus isolates was evaluated. Linezolid antagonized vancomycin activity at 24 and 48 h. Linezolid antagonized daptomycin at 24 and 48 h depending on dose and strain. Adding daptomycin increased vancomycin activity at 48 h (P < 0.03). These results may be strain dependent and require further clinical investigation. There is recent increased interest in the activity of protein synthesis inhibitors in combination with cell wall-active agents. Some combination regimens are being used clinically but lack data to support their combined use (1). High-dose daptomycin and linezolid were recommended for use as a combination therapy in the Infectious Diseases Society of America 2011 methicillinresistant Staphylococcus aureus (MRSA) treatment guidelines for persistent bacteremia or vancomycin failure (2). However, other in vitro studies have demonstrated antagonism with combinations of linezolid and vancomycin (3, 4). To date, there have been limited investigations of daptomycin and linezolid in combination (5, 6). The combined use of these agents prompted an investigation into pharmacokinetic and pharmacodynamic activity and possible interactions when using combinations of bactericidal and bacteriostatic antimicrobials as previously described (7,8).(A portion of these results were presented as a poster at the 53rd annual Interscience Conference on Antimicrobial Agents and Chemotherapy [ICAAC], Denver, CO, 10 September 2013.) Two randomly selected clinical MRSA blood isolates (L31 and L328) from the LaPlante Laboratory at the Providence Veterans Affairs Medical Center were selected for analysis. The two isolates are known biofilm-producing strains, previously isolated from patients with catheter-related bloodstream infections (9). Biofilm formation was determined as previously described (9, 10). Daptomycin (lot CDC271; Cubist Pharmaceuticals, Inc., Lexington, MA), linezolid (lot 11C10U10, 13F05U09; Pfizer, New York, NY), and vancomycin (lot 12070DD, 382553A; Hospira, Lake Forest, IL) were tested. Mueller-Hinton broth (MHB) (Becton Dickinson, Sparks, MD, USA) supplemented with calcium and adjusted to 25 mg/liter calcium chloride (for daptomycin studies, 50 mg/ml of calcium chloride, ionized Ca, and 1.03 to 1.23 mmol/liter) and 12.5 mg/liter magnesium was used for all assays for MICs, minimum bactericidal concentrations (MBCs), and in vitro pharmacodynamic (IVPD) infection models (11-13). Colony counts were determined using tryptic soy agar (TSA) (BD Difco).A previously described IVPD model was used to evaluate several antibiotic regimens against MRSA (7). Briefly, a 0.5 McFarland standard of planktonic bacteria from overnight growth on TSA was diluted in a one-compartment model (250-ml working volume) to a starting inoculum of ϳ10 6 CFU/ml. (14); ...

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confidence: 58%

Observed Antagonistic Effect of Linezolid on Daptomycin or Vancomycin Activity against Biofilm-Forming Methicillin-Resistant Staphylococcus aureus in an In Vitro Pharmacodynamic Model

Luther

LaPlante

2015

Antimicrob Agents Chemother

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“…Due to the practical limitations of in vitro modeling, we simulated one-compartment pharmacokinetics of the study drugs, which may have slightly overestimated their average clinical exposures. The simplification of multicompartmental clinical pharmacokinetics is common in in vitro modeling, even when the investigators use a two-compartment model, such as a simulated endocardial vegetation model or a hollow-fiber model (58)(59)(60). While these strategies may modestly overestimate the drug exposures in the model, due to the short distribution phase of these drugs, which was not simulated, we do not believe this had a significant impact on the results.…”

Section: Discussionmentioning

confidence: 98%

Fosfomycin Enhances the Activity of Daptomycin against Vancomycin-Resistant Enterococci in an In Vitro Pharmacokinetic-Pharmacodynamic Model

Snyder

Werth

Nonejuie

et al. 2016

Antimicrob Agents Chemother

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“…A combination of linezolid and high-dose daptomycin was more effective than each agent alone in an in vitro model of biofi lm-producing Staphylococcus aureus infection (Parra-Ruiz et al 2012 ).…”

Section: The Role Of Antibiotic Therapymentioning

confidence: 91%

The Fight Against the Slime: Can We Ever Win?

Lisanti

Piolanti

Tagliaferri

et al. 2014

Perioperative Medical Management for Total Joint Arthroplasty

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Activity of linezolid and high-dose daptomycin, alone or in combination, in an in vitro model of Staphylococcus aureus biofilm

Cited by 68 publications

References 23 publications

Observed Antagonistic Effect of Linezolid on Daptomycin or Vancomycin Activity against Biofilm-Forming Methicillin-Resistant Staphylococcus aureus in an In Vitro Pharmacodynamic Model

Observed Antagonistic Effect of Linezolid on Daptomycin or Vancomycin Activity against Biofilm-Forming Methicillin-Resistant Staphylococcus aureus in an In Vitro Pharmacodynamic Model

Fosfomycin Enhances the Activity of Daptomycin against Vancomycin-Resistant Enterococci in an In Vitro Pharmacokinetic-Pharmacodynamic Model

The Fight Against the Slime: Can We Ever Win?

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