In vitro bactericidal activity of ceftobiprole against hospital- and community-associated methicillin-resistant Staphylococcus aureus

2010 ◽  
Vol 65 (3) ◽  
pp. 591-594 ◽  
Author(s):  
S. Borbone ◽  
F. Campanile ◽  
D. Bongiorno ◽  
S. Stefani
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant

scholarly journals ComparativeIn VitroActivities of Oritavancin, Dalbavancin, and Vancomycin against Methicillin-Resistant Staphylococcus aureus Isolates in a Nondividing State

2016 ◽  
Vol 60 (7) ◽  
pp. 4342-4345 ◽  
Author(s):  
Adam Belley ◽  
David Lalonde Seguin ◽  
Francis Arhin ◽  
Greg Moeck
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Antibacterial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Skin Structure ◽  
Persistent Infections ◽  
Time Kill

ABSTRACTAntibacterial agents that kill nondividing bacteria may be of utility in treating persistent infections. Oritavancin and dalbavancin are bactericidal lipoglycopeptides that are approved for acute bacterial skin and skin structure infections in adults caused by susceptible Gram-positive pathogens. Using time-kill methodology, we demonstrate that oritavancin exerts bactericidal activity against methicillin-resistantStaphylococcus aureus(MRSA) isolates that are maintained in a nondividing statein vitro, whereas dalbavancin and the glycopeptide vancomycin do not.

scholarly journals Evaluation of Ceftaroline, Vancomycin, Daptomycin, or Ceftaroline plus Daptomycin against Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus in anIn VitroPharmacokinetic/Pharmacodynamic Model of Simulated Endocardial Vegetations

2014 ◽  
Vol 58 (6) ◽  
pp. 3177-3181 ◽  
Author(s):  
Brian J. Werth ◽  
Katie E. Barber ◽  
Cortney E. Ireland ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Active Agent ◽  
Minimum Concentration ◽  
Ceftaroline Fosamil ◽  
Methicillin Resistant ◽  
Content Type ◽  
Sustained Activity

ABSTRACTInfective endocarditis (IE) caused by methicillin-resistantStaphylococcus aureus(MRSA) with reduced susceptibility to vancomycin and daptomycin has few adequate therapeutic options. Ceftaroline (CPT) is bactericidal against daptomycin (DAP)-nonsusceptible (DNS) and vancomycin-intermediate MRSA, but supporting data are limited for IE. This study evaluated the activities of ceftaroline, vancomycin, daptomycin, and the combination of ceftaroline plus daptomycin against DNS MRSA in a pharmacokinetic/pharmacodynamic (PK/PD) model of simulated endocardial vegetations (SEVs). Simulations of ceftaroline-fosamil (600 mg) every 8 h (q8h) (maximum concentration of drug in serum [Cmax], 21.3 mg/liter; half-life [t1/2], 2.66 h), daptomycin (10 mg/kg of body weight/day) (Cmax, 129.7 mg/liter;t1/2, 8 h), vancomycin (1 g) q8h (minimum concentration of drug in serum [Cmin], 20 mg/liter;t1/2, 5 h), and ceftaroline plus daptomycin were evaluated against 3 clinical DNS, vancomycin-intermediate MRSA in a two-compartment,in vitro, PK/PD SEV model over 96 h with a starting inoculum of ∼8 log10CFU/g. Bactericidal activity was defined as a ≥3-log10CFU/g reduction from the starting inoculum. Therapeutic enhancement of combinations was defined as ≥2-log10CFU/g reduction over the most active agent alone. MIC values for daptomycin, vancomycin, and ceftaroline were 4 mg/liter, 4 to 8 mg/liter, and 0.5 to 1 mg/liter, respectively, for all strains. At simulated exposures, vancomycin was bacteriostatic, but daptomycin and ceftaroline were bactericidal. By 96 h, ceftaroline monotherapy offered significantly improved killing compared to other agents against one strain. The combination of DAP plus CPT demonstrated therapeutic enhancement, resulting in significantly improved killing versus either agent alone against 2/3 (67%) strains. CPT demonstrated bactericidal activity against DNS, vancomycin-intermediate MRSA at high bacterial densities. Ceftaroline plus daptomycin may offer more rapid and sustained activity against some MRSA in the setting of high-inoculum infections like IE and should also be considered.

scholarly journals Epinecidin-1 Protects against Methicillin Resistant Staphylococcus aureus Infection and Sepsis in Pyemia Pigs

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 693
Author(s):  
Han-Ning Huang ◽  
Chieh-Yu Pan ◽  
Bor-Chyuan Su ◽  
Hung-Yi Wu ◽  
Jyh-Yih Chen
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Analysis ◽  
Diabetic Patients ◽  
Methicillin Resistant ◽  
Antibiotic Drug

Methicillin resistant Staphylococcus aureus (MRSA) may be found on the skin, nose, and throats of long-term hospitalized patients. While MRSA infections are usually minor, serious infections and death may occur in immunocompromised or diabetic patients, or after exposure of MRSA to blood. This report demonstrates that the antimicrobial peptide (AMP) epinecidin-1 (Epi-1) efficiently protects against MRSA infection in a pyemia pig model. We first found that Epi-1 exhibits bactericidal activity against MRSA. Next, pharmacokinetic analysis revealed that Epi-1 was stable in serum for 4 h after injection, followed by a gradual decrease. This pharmacokinetic profile suggested Epi-1 may bind serum albumin, which was confirmed in vitro. Harmful effects were not observed for doses up to 100 mg/kg body weight in pigs. When Epi-1 was supplied as a curative agent 30 min post-infection, MRSA-induced abnormalities in blood uric acid (UA), blood urea nitrogen (BUN), creatine (CRE), GOT, and GPT levels were restored to normal levels. We further showed that the bactericidal activity of Epi-1 was higher than that of the antibiotic drug vancomycin. Epi-1 significantly decreased MRSA counts in the blood, liver, kidney, heart, and lungs of infected pigs. Elevated levels of serum C reactive protein (CRP), proinflammatory cytokine IL6, IL1β, and TNFα were also attenuated by Epi-1 treatment. Moreover, the MRSA genes, enterotoxin (et)-A, et-B, intrinsic methicillin resistance A (mecA), and methicillin resistance factor A (femA), were significantly reduced or abolished in MRSA-infected pigs after treatment with Epi-1. Hematoxylin and eosin staining of heart, liver, lung, and kidney sections indicated that Epi-1 attenuated MRSA toxicity in infected pigs. A survival study showed that the pyemia pigs infected with MRSA alone died within a week, whereas the pigs post-treated with 2.5 mg/kg Epi-1 were completely protected against death. The present investigation, thus, demonstrates that Epi-1 effectively protects pyemia pigs against pathogenic MRSA without major toxic side effects.

In Vitro Bactericidal Activity of Sulbactam plus Ampicillin Against Methicillin-Resistant Staphylococcus aureus

1986 ◽  
Vol 8 (Supplement_5) ◽  
pp. S549-S554 ◽  
Author(s):  
Antoine Kazmierczak ◽  
Jean-Marie Duez ◽  
Andre Pecbinot ◽  
Patrice Nordmann ◽  
Roger Labia
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant

scholarly journals Novel Daptomycin Combinations against Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus in an In Vitro Model of Simulated Endocardial Vegetations

2010 ◽  
Vol 54 (12) ◽  
pp. 5187-5192 ◽  
Author(s):  
Molly E. Steed ◽  
Celine Vidaillac ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Analysis Of Variance ◽  
Bactericidal Activity ◽  
In Vitro Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Unique Combination ◽  
Methicillin Resistant ◽  
Vitro Model ◽  
Post Hoc

ABSTRACT Reduced susceptibility to daptomycin has been reported in patients with infections due to methicillin-resistant Staphylococcus aureus (MRSA). Although infections with daptomycin-nonsusceptible (DNS) MRSA are infrequent, optimal therapy of these strains has not been determined. We investigated the killing effects of novel antibiotic combinations with daptomycin (DAP) against two clinical DNS MRSA isolates (SA-684 and R6003) in a 72-h in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated endocardial vegetations (SEV). Simulated regimens included DAP at 6 mg/kg every 24 h (q24h) alone or in combination with trimethoprim-sulfamethoxazole (TMP/SMX) at 160/800 mg q12h, linezolid (LIN) at 600 mg q12h, cefepime (CEF) at 2 g q12h, and nafcillin (NAF) at 4 g q4h. Bactericidal activity was defined as a ≥3-log10 CFU/g kill. Differences in CFU/g were evaluated between 4 and 72 h by analysis of variance with the Bonferroni post hoc test. DAP MICs were 4 and 2 mg/liter for SA-684 and R6003, respectively. In the PK/PD model, DAP alone was slowly bactericidal, achieving a 3-log10 kill at 24 and 50 h for SA-684 and R6003, respectively. Against SA-684, DAP plus TMP/SMX, CEF, LIN, or NAF was bactericidal at 4, 4, 8, and 8 h, respectively, and maintained this activity for the 72-h study duration. DAP plus TMP/SMX or CEF exhibited superior killing than DAP alone against SA-684 between 4 and 72 h, and overall this was significant (P < 0.05). Against R6003, DAP plus TMP/SMX was bactericidal (8 h) and superior to DAP alone between 8 and 72 h (P < 0.001). The unique combination of DAP plus TMP/SMX was the most effective and rapidly bactericidal regimen against the two isolates tested and may provide a clinical option to treat DNS S. aureus infections.

scholarly journals Telavancin Demonstrates Activity against Methicillin-Resistant Staphylococcus aureus Isolates with Reduced Susceptibility to Vancomycin, Daptomycin, and Linezolid in Broth Microdilution MIC and One-Compartment Pharmacokinetic/Pharmacodynamic Models

2015 ◽  
Vol 59 (9) ◽  
pp. 5529-5534 ◽  
Author(s):  
Jordan R. Smith ◽  
Katie E. Barber ◽  
Jessica Hallesy ◽  
Animesh Raut ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Clinical Research ◽  
Bactericidal Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Broth Microdilution ◽  
Model Data ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) isolates have arisen with reduced susceptibility to several anti-MRSA agents. Telavancin (TLV), a novel anti-MRSA agent, retains low MICs against these organisms. Our objective was to determine the MICs for TLV, daptomycin (DAP), vancomycin (VAN), and linezolid (LZD) against daptomycin-nonsusceptible (DNS)S. aureus, vancomycin-intermediateS. aureus(VISA), heteroresistant VISA (hVISA), and linezolid-resistant (LZDr)S. aureus. We also evaluated these agents against each phenotype in pharmacokinetic/pharmacodynamic (PK/PD) models. Seventy DNS, 100 VISA, 180 hVISA, and 25 LZDrMRSA isolates were randomly selected from our library and tested to determine their MICs against TLV, DAP, VAN, and LZD via broth microdilution and a Trek panel. Four isolates were randomly selected for 168-hin vitromodels to evaluate treatment with TLV at 10 mg/kg of body weight/day, DAP at 10 mg/kg/day, VAN at 1 g every 12 h (q12h), and LZD at 600 mg q12h. The MIC50/90for TLV, DAP, VAN, and LZD against 70 DNSS. aureusisolates were 0.06/0.125 μg/ml, 2/4 μg/ml, 1/2 μg/ml, and 2/2 μg/ml, respectively. Against 100 VISA isolates, the MIC50/90were 0.06/0.125 μg/ml, 1/1 μg/ml, 4/8 μg/ml, and 1/2 μg/ml, respectively. Against 170 hVISA isolates, the MIC50/90were 0.06/0.125 μg/ml, 0.5/1 μg/ml, 1/2 μg/ml, and 1/2 μg/ml, respectively. Against 25 LZDrisolates, the MIC50/90were 0.03/0.06 μg/ml, 1/1 μg/ml, 2/2 μg/ml, and 8/8 μg/ml, respectively. The TLV MIC was >0.125 μg/ml for 10/365 (2.7%) isolates. In PK/PD models, TLV was universally bactericidal at 168 h and statistically superior to all antibiotics against DNSS. aureusstrain R2334. These data further establish the potency of TLV against resistant MRSA. The model data demonstratein vitrobactericidal activity of TLV against hVISA, VISA, DNSS. aureus, and LZDrS. aureusstrains. Further clinical research is warranted.

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