scholarly journals Susceptibility of Methicillin-Resistant Staphylococcus aureus to Five Quinazolinone Antibacterials

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Sara Ceballos ◽  
Choon Kim ◽  
Yuanyuan Qian ◽  
Shahriar Mobashery ◽  
Mayland Chang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Amino Acid ◽  
Binding Proteins ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Penicillin Binding Proteins

ABSTRACT The in vitro activities of five quinazolinone antibacterials, compounds Q1 to Q5, were tested against 210 strains of methicillin-resistant Staphylococcus aureus (MRSA). The MIC50/MIC90 values (in μg/ml) were as follows: Q1, 0.5/2; Q2, 1/4; Q3, 2/4; Q4, 0.06/0.25; and Q5, 0.125/0.5. Several strains with high MIC values (from 8 to >32 μg/ml) for some of these compounds exhibited amino acid changes in the penicillin-binding proteins, which are targeted by these antibacterials.

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 New Transposon Tn6133in Methicillin-Resistant Staphylococcus aureus ST398 Containsvga(E), a Novel Streptogramin A, Pleuromutilin, and Lincosamide Resistance Gene

2011 ◽  
Vol 55 (10) ◽  
pp. 4900-4904 ◽  
Author(s):  
Sybille Schwendener ◽  
Vincent Perreten
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistance ◽  
Amino Acid ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Transporter Family ◽  
Acid Protein ◽  
Mrsa St398 ◽  
Amino Acid Protein

ABSTRACTA novel streptogramin A, pleuromutilin, and lincosamide resistance determinant, Vga(E), was identified in porcine methicillin-resistantStaphylococcus aureus(MRSA) ST398. Thevga(E) gene encoded a 524-amino-acid protein belonging to the ABC transporter family. It was found on a multidrug resistance-conferring transposon, Tn6133, which was comprised of Tn554with a stably integrated 4,787-bp DNA sequence harboringvga(E). Detection of Tn6133in several porcine MRSA ST398 isolates and its ability to circularize suggest a potential for dissemination.

scholarly journals Classical β-Lactamase Inhibitors Potentiate the Activity of Daptomycin against Methicillin-Resistant Staphylococcus aureus and Colistin against Acinetobacter baumannii

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
George Sakoulas ◽  
Warren Rose ◽  
Andrew Berti ◽  
Joshua Olson ◽  
Jason Munguia ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Acinetobacter Baumannii ◽  
Murine Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Peptide Antibiotic ◽  
Peptide Antibiotics ◽  
Methicillin Resistant ◽  
Content Type ◽  
Host Defense Peptide

ABSTRACT We asked whether beta-lactamase inhibitors (BLIs) increased the activity of daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA), the peptide antibiotic colistin (COL) against the emerging Gram-negative nosocomial pathogen Acinetobacter baumannii, and the human host defense peptide cathelicidin LL37 against either pathogen. DAP and LL37 kill curves were performed with or without BLIs against MRSA, vancomycin-intermediate S. aureus (VISA), and heterogeneous VISA (hVISA). COL and LL37 kill curves were performed against A. baumannii. Boron-dipyrromethene (BODIPY)-labeled DAP binding to MRSA grown with the BLI tazobactam (TAZ) was assessed microscopically. The combination of COL plus TAZ was studied in a murine model of A. baumannii pneumonia. TAZ alone lacked in vitro activity against MRSA or A. baumannii. The addition of TAZ to DAP resulted in a 2- to 5-log10 reduction in recoverable MRSA CFU at 24 h compared to the recoverable CFU with DAP alone. TAZ plus COL showed synergy by kill curves for 4 of 5 strains of A. baumannii tested. Growth with 20 mg/liter TAZ resulted in 2- to 2.5-fold increases in the intensity of BODIPY-DAP binding to MRSA and hVISA strains. TAZ significantly increased the killing of MRSA and A. baumannii by LL37 in vitro. TAZ increased the activity of COL in a murine model of A. baumannii pneumonia. Classical BLIs demonstrate synergy with peptide antibiotics. Since BLIs have scant antimicrobial activity on their own and are thus not expected to increase selective pressure toward antibiotic resistance, their use in combination with peptide antibiotics warrants further study.

Cloning and characterization of the fmt gene which affects the methicillin resistance level and autolysis in the presence of triton X-100 in methicillin-resistant Staphylococcus aureus.

1997 ◽  
Vol 41 (11) ◽  
pp. 2355-2361 ◽  
Author(s):  
H Komatsuzawa ◽  
M Sugai ◽  
K Ohta ◽  
T Fujiwara ◽  
S Nakashima ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Proteins ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Insertion Mutant ◽  
Resistance Level ◽  
Methicillin Resistant ◽  
Penicillin Binding Proteins ◽  
Oxacillin Resistance ◽  
Mrsa Strains ◽  
Triton X

In methicillin-resistant Staphylococcus aureus (MRSA) strains, Triton X-100 reduced the oxacillin resistance level, although the degree of reduction varied from strain to strain. To study the responses of MRSA strains to Triton X-100, we isolated a Tn551 insertion mutant of the COL strain that became more susceptible to oxacillin in the presence of 0.02% Triton X-100. The Tn551 insertion of the mutant was transduced back to the parent strain, other MRSA strains (strains KSA8 and NCTC 10443), and methicillin-susceptible strain RN450. All transductants of MRSA strains had reduced levels of resistance to oxacillin in the presence of 0.02% Triton X-100, while those of RN450 did not. Tn551 mutants of KSA8 and NCTC 10443 also had reduced levels of resistance in the absence of 0.02% Triton X-100. The autolysis rates of the transductants in the presence of 0.02% Triton X-100 were significantly increased. Amino acid analysis of peptidoglycan and testing of heat-inactivated cells for their susceptibilities to several bacteriolytic enzymes showed that there were no significant differences between the parents and the respective Tn551 mutants. The Tn551 insertion site mapped at a location different from the previously identified fem and llm sites. Cloning and sequencing showed that Tn551 had inserted at the C-terminal region of a novel gene designated fmt. The putative Fmt protein showed a hydropathy pattern similar to that of S. aureus penicillin-binding proteins and contained two of the three conserved motifs shared by penicillin-binding proteins and beta-lactamases, suggesting that fmt may be involved in cell wall synthesis.

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 Rapid Detection of Methicillin-Resistant Staphylococcus aureus and Methicillin-Susceptible S. aureus Directly from Positive Blood Cultures by Use of the BD Max StaphSR Assay

2015 ◽  
Vol 53 (12) ◽  
pp. 3900-3904 ◽  
Author(s):  
Justin A. Ellem ◽  
Tom Olma ◽  
Matthew V. N. O'Sullivan
Keyword(s):  
Staphylococcus Aureus ◽  
Predictive Value ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Direct Detection ◽  
Blood Cultures ◽  
Coagulase Negative Staphylococcus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Standard Culture

The BD Max StaphSR assay is an automated qualitativein vitrodiagnostic test for the direct detection and differentiation of methicillin-susceptibleStaphylococcus aureus(MSSA) and methicillin-resistantS. aureus(MRSA). A total of 460 specimens were tested, and the results were compared with standard culture-based identification. MRSA was detected in 48 samples (sensitivity of 100%; positive predictive value [PPV] of 100%). MSSA was detected in 112 samples (sensitivity of 99.1%; PPV of 100%), and 299 samples containing coagulase-negative staphylococcus and nonstaphylococcal species were negative by the BD Max StaphSR assay (specificity of 100%; negative predictive value [NPV] of 99.7 to 100%).

scholarly journals Antibacterial Properties of MagnesiumIn Vitroand in anIn VivoModel of Implant-Associated Methicillin-Resistant Staphylococcus aureus Infection

2014 ◽  
Vol 58 (12) ◽  
pp. 7586-7591 ◽  
Author(s):  
Yang Li ◽  
Guangwang Liu ◽  
Zanjing Zhai ◽  
Lina Liu ◽  
Haowei Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Formation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Periprosthetic Infection ◽  
Antibacterial Properties ◽  
Methicillin Resistant ◽  
Content Type ◽  
Aureus Infection

ABSTRACTPeriprosthetic infection remains a challenging clinical complication. We investigated the antibacterial properties of pure (99.9%) magnesium (Mg)in vitroand in anin vivorat model of implant-related infection. Mg was highly effective against methicillin-resistantStaphylococcus aureus-induced osteomyelitis and improved new peri-implant bone formation. BacterialicaAandagrRNAIII transcription levels were also assessed to characterize the mechanism underlying the antibacterial properties of the Mg implant.

scholarly journals Activity of Daptomycin with or without 25 Percent Ethanol Compared to Combinations of Minocycline, EDTA, and 25 Percent Ethanol against Methicillin-Resistant Staphylococcus aureus Isolates Embedded in Biofilm

2013 ◽  
Vol 57 (4) ◽  
pp. 1998-2000 ◽  
Author(s):  
R. Estes ◽  
J. Theusch ◽  
A. Beck ◽  
D. Pitrak ◽  
Kathleen M. Mullane
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bloodstream Infections ◽  
Central Line ◽  
Methicillin Resistant ◽  
Content Type ◽  
Lock Therapy ◽  
Antibiotic Lock ◽  
Mrsa Colonization

ABSTRACTCentral venous catheters commonly develop central line-associated bloodstream infections.In vitroantibiotic lock therapy (ALT) was simulated on 10 methicillin-resistantStaphylococcus aureus(MRSA) clinical isolates imbedded in biofilm-coated silicon disks. Five days of 4-h daily exposures to daptomycin (2.5 mg/ml) in 25% ethanol or minocycline (3 mg/ml) plus 25% ethanol and 30 mg/ml EDTA resulted in significantly greater elimination of MRSA colonization than treatment with minocycline alone.

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