Linezolid-daptomycin combinations against total and resistant Staphylococcus aureus populations: in vitro model studies

ABSTRACT Platelets contribute to antimicrobial host defense against infective endocarditis (IE) by releasing platelet microbicidal proteins (PMPs). We investigated the influence of thrombin-stimulated human platelets on the evolution of simulated IE in the presence and absence of vancomycin or nafcillin. Staphylococcus aureus strains differing in intrinsic susceptibility to PMPs or antibiotics were studied: ISP479C (thrombin-induced PMP-1 [tPMP-1] susceptible; nafcillin and vancomycin susceptible), ISP479R (tPMP-1 resistant; nafcillin and vancomycin susceptible), and GISA-NJ (tPMP-1 intermediate-susceptible; vancomycin intermediate-susceptible). Platelets were introduced and thrombin activated within the in vitro IE model 30 min prior to inoculation with S. aureus. At 0 to 24 h postinoculation, bacterial densities in chamber fluid and simulated endocardial vegetations (SEVs) were quantified and compared among groups. Activated platelets alone, or in combination with antibiotics, inhibited the proliferation of ISP479C in chamber fluid or SEVs over the initial 4-h period (P < 0.05 versus controls). Moreover, nafcillin-containing regimens exerted inhibitory effects beyond 4 h against ISP479C in both model phases. By comparison, activated platelets inhibited GISA-NJ proliferation in SEVs but not in chamber fluid. The combination of platelets plus nafcillin or vancomycin significantly inhibited proliferation of the GISA-NJ strain in SEVs compared to the effect of platelets or antibiotics alone (P < 0.05). In contrast, platelets did not significantly alter the antistaphylococcal efficacies of nafcillin or vancomycin against ISP479R. These data support our hypothesis that a beneficial antimicrobial effect may result from the interaction among platelets, PMPs, and anti-infective agents against antibiotic-susceptible or -resistant staphylococci that exhibit a tPMP-1-susceptible or -intermediate-susceptible phenotype.

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In Vitro Evaluation of the Activities of Telavancin, Cefazolin, and Vancomycin against Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus in Peritoneal Dialysate

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00435-07 ◽

2007 ◽

Vol 51 (12) ◽

pp. 4521-4524 ◽

Cited By ~ 8

Author(s):

Frances L. Clouse ◽

Laurie B. Hovde ◽

John C. Rotschafer

Keyword(s):

Staphylococcus Aureus ◽

Peritoneal Dialysis ◽

In Vitro Model ◽

Methicillin Resistant Staphylococcus Aureus ◽

Dialysis Fluid ◽

Methicillin Resistant ◽

Peritoneal Dialysate ◽

Peritoneal Dialysis Fluid ◽

Vitro Model

ABSTRACT This study compared the ability of telavancin to the ability of cefazolin and vancomycin to eliminate staphylococci from peritoneal dialysis fluid by using a static in vitro model to simulate the conditions of peritoneal dialysis. The results showed that telavancin exhibited statistically significantly better kill (P < 0.05) against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

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Effects of antioxidant agents in protecting the brain against ischemia-reperfusion injury: In vivo and in vitro model studies

Free Radical Biology and Medicine ◽

10.1016/0891-5849(90)90734-z ◽

1990 ◽

Vol 9 ◽

pp. 156 ◽

Cited By ~ 1

Author(s):

Atsuhiro Sakamoto ◽

S.Tsuyoshi Ohnishi ◽

Ryo Ogawa

Keyword(s):

Reperfusion Injury ◽

In Vitro Model ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Model Studies ◽

Antioxidant Agents ◽

Vitro Model ◽

The Brain

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Ceftaroline pharmacodynamic activity versus community-associated and healthcare-associated methicillin-resistant Staphylococcus aureus, heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus using an in vitro model

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkr110 ◽

2011 ◽

Vol 66 (6) ◽

pp. 1301-1305 ◽

Cited By ~ 18

Author(s):

G. G. Zhanel ◽

E. Rossnagel ◽

K. Nichol ◽

L. Cox ◽

J. A. Karlowsky ◽

...

Keyword(s):

Staphylococcus Aureus ◽

In Vitro Model ◽

Methicillin Resistant Staphylococcus Aureus ◽

Methicillin Resistant ◽

Vancomycin Resistant ◽

Vitro Model ◽

Healthcare Associated

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Impact of sarA on Antibiotic Susceptibility of Staphylococcus aureus in a Catheter-Associated In Vitro Model of Biofilm Formation

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01432-08 ◽

2009 ◽

Vol 53 (6) ◽

pp. 2475-2482 ◽

Cited By ~ 33

Author(s):

Elizabeth C. Weiss ◽

Horace J. Spencer ◽

Sonja J. Daily ◽

Brian D. Weiss ◽

Mark S. Smeltzer

Keyword(s):

Staphylococcus Aureus ◽

Clinical Isolate ◽

Antimicrobial Susceptibility ◽

Antibiotic Susceptibility ◽

Biofilm Formation ◽

In Vitro Model ◽

Susceptibility Testing ◽

Specific Context ◽

Vitro Model

ABSTRACT Mutation of the staphylococcal accessory regulator (sarA) in Staphylococcus aureus limits but does not abolish the capacity of the organism to form a biofilm. As a first step toward determining whether this limitation is therapeutically relevant, we carried out in vitro studies comparing the relative susceptibility of an S. aureus clinical isolate (UAMS-1) and its isogenic sarA mutant (UAMS-929) in the specific context of a catheter-associated biofilm. The antibiotics tested were daptomycin, linezolid, and vancomycin, all of which were evaluated by using concentrations based on the MIC defined as the breakpoint for a susceptible strain of S. aureus (≤1.0, ≤2.0, and ≤4.0 μg/ml for daptomycin, vancomycin, and linezolid, respectively). Mutation of sarA had no significant impact on the MIC of UAMS-1 for any of the targeted antibiotics, as defined by Etest antimicrobial susceptibility testing. However, mutation of sarA did result in a significant increase in antimicrobial susceptibility to all targeted antibiotics when they were tested in the specific context of a biofilm. Additionally, whether susceptibility was assessed by using UAMS-1 or its sarA mutant, daptomycin was found to be more effective against established S. aureus biofilms than either linezolid or vancomycin.

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