scholarly journals Emergence of Linezolid-Resistant Mutants in a Susceptible-Cell Population of Methicillin-Resistant Staphylococcus aureus

2011 ◽  
Vol 55 (5) ◽  
pp. 2466-2468 ◽  
Author(s):  
Yurika Ikeda-Dantsuji ◽  
Hideaki Hanaki ◽  
Taiji Nakae ◽  
Yoshio Takesue ◽  
Kazunori Tomono ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Population ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Rrna Genes ◽  
Chloramphenicol Resistance ◽  
Methicillin Resistant ◽  
Content Type ◽  
Susceptible Cell ◽  
Linezolid Therapy ◽  
Resistant Mutants

ABSTRACTMethicillin-resistantStaphylococcus aureuswith a MIC of linezolid of 4 μg/ml, isolated from a patient who had undergone unsuccessful linezolid therapy, yielded linezolid-resistant mutants in blood agar at 48 h of incubation. The resistant clones showed a MIC of linezolid ranging from 8 to 64 μg/ml and accumulated the T2500A mutation(s) of the rRNA genes. Emergence of these resistant clones appears to be facilitated by a cryptic mutation or mutations associated with chloramphenicol resistance.

scholarly journals Complete Genome Sequences of Methicillin-Resistant Staphylococcus aureus Strains 110900 and 128254, Two Representatives of the CRISPR-Cas-Carrying Sequence Type 630/spa Type t4549 Lineage

2020 ◽  
Vol 9 (41) ◽  
Author(s):  
Raphael N. Sieber ◽  
Søren Overballe-Petersen ◽  
Hülya Kaya ◽  
Anders R. Larsen ◽  
Andreas Petersen
Keyword(s):  
Staphylococcus Aureus ◽  
Complete Genome ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Nordic Countries ◽  
Sequence Type ◽  
Genome Sequences ◽  
Methicillin Resistant ◽  
Content Type ◽  
Spa Type

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) sequence type 630 (ST630) and spa type t4549 is an emerging lineage in Nordic countries, and some representatives carry the CRISPR-Cas system. Here, the complete genome sequences of two isolates from this lineage are presented, comprising chromosomes of 2,918,239 and 2,877,083 nucleotides, respectively, and a 2,473-nucleotide plasmid carrying erm(C).

scholarly journals Complete Genome Sequence of Systemically Disseminated Sequence Type 8 Staphylococcal Cassette Chromosome mec Type IVl Community-Acquired Methicillin-Resistant Staphylococcus aureus

2017 ◽  
Vol 5 (35) ◽  
Author(s):  
Junzo Hisatsune ◽  
Hideharu Hagiya ◽  
Sumiko Shiota ◽  
Motoyuki Sugai
Keyword(s):  
Staphylococcus Aureus ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Sequence Type ◽  
Methicillin Resistant ◽  
Content Type ◽  
Staphylococcal Cassette Chromosome ◽  
Epidermal Cell Differentiation

ABSTRACT Staphylococcus aureus JH4899, a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate collected from a patient with systematically disseminated infection, is classified as sequence type 8 and carries the staphylococcal cassette chromosome mec type IVl (SCCmecIVl). It produces TSST-1, SEC, a newly discovered enterotoxin (SE1), and epidermal cell differentiation inhibitor A (EDIN-A). Here, we present the complete genome sequence of the chromosome and a plasmid harboring the se1 and ednA genes.

scholarly journals β-Lactam Antibiotics Targeting PBP1 Selectively Enhance Daptomycin Activity against Methicillin-Resistant Staphylococcus aureus

2013 ◽  
Vol 57 (10) ◽  
pp. 5005-5012 ◽  
Author(s):  
Andrew D. Berti ◽  
George Sakoulas ◽  
Victor Nizet ◽  
Ryan Tewhey ◽  
Warren E. Rose
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Division ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Binding Protein ◽  
Membrane Insertion ◽  
Penicillin Binding Protein ◽  
Compensatory Response ◽  
Binding Profile ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACTThe activity of daptomycin (DAP) against methicillin-resistantStaphylococcus aureus(MRSA) is enhanced in the presence of subinhibitory concentrations of antistaphylococcal β-lactam antibiotics by an undefined mechanism. Given the variability in the penicillin-binding protein (PBP)-binding profiles of different β-lactam antibiotics, the purpose of this study was to examine the relative enhancement of DAP activity against MRSA by different β-lactam antibiotics to determine if a specific PBP-binding profile is associated with the ability to enhance the anti-MRSA activity of DAP. We determined that both broad- and narrow-spectrum β-lactam antibiotics known to exhibit PBP1 binding demonstrated potent enhancement of DAP anti-MRSA activity, whereas β-lactam antibiotics with minimal PBP1 binding (cefoxitin, ceftriaxone, cefaclor, and cefotaxime) were less effective. We suspect that PBP1 disruption by β-lactam antibiotics affects pathways of cell division inS. aureusthat may be a compensatory response to DAP membrane insertion, resulting in DAP hypersusceptibility.

scholarly journals Iron Sequestrant DIBI, a Potential Alternative for Nares Decolonization of Methicillin-Resistant Staphylococcus aureus, Is Anti-infective and Inhibitory for Mupirocin-Resistant Isolates

2020 ◽  
Vol 64 (3) ◽  
Author(s):  
David S. Allan ◽  
Maria del Carmen Parquet ◽  
Kimberley A. Savage ◽  
Bruce E. Holbein
Keyword(s):  
Staphylococcus Aureus ◽  
Developmental Stage ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Opportunistic Infections ◽  
Major Health ◽  
Methicillin Resistant ◽  
Content Type ◽  
Health Burden ◽  
Potential Alternative ◽  
Infective Agent

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) opportunistic infections are a major health burden. Decolonization of hospitalized patients with mupirocin (MUP) has reduced the incidence of infection but has led to MUP resistance. DIBI is a developmental-stage anti-infective agent that sequesters bacterial iron and bolsters innate host iron-withdrawal defenses. Clinical isolates possessing low, high, or no MUP resistance all had similarly high susceptibilities to DIBI. Intranasal DIBI reduced nares bacterial burdens in mice to the same extent as MUP. No resistance was found after exposure to DIBI.

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 Linezolid Attenuates Lethal Lung Damage during Postinfluenza Methicillin-Resistant Staphylococcus aureus Pneumonia

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Atul K. Verma ◽  
Christopher Bauer ◽  
Vijaya Kumar Yajjala ◽  
Shruti Bansal ◽  
Keer Sun
Keyword(s):  
Staphylococcus Aureus ◽  
Therapeutic Effect ◽  
Critical Role ◽  
Lung Damage ◽  
Alpha Toxin ◽  
Methicillin Resistant ◽  
Content Type ◽  
Linezolid Therapy ◽  
Staphylococcus Aureus Pneumonia ◽  
The Impact

ABSTRACT Postinfluenza methicillin-resistant Staphylococcus aureus (MRSA) infection can quickly develop into severe, necrotizing pneumonia, causing over 50% mortality despite antibiotic treatments. In this study, we investigated the efficacy of antibiotic therapies and the impact of S. aureus alpha-toxin in a model of lethal influenza virus and MRSA coinfection. We demonstrate that antibiotics primarily attenuate alpha-toxin-induced acute lethality, even though both alpha-toxin-dependent and -independent mechanisms significantly contribute to animal mortality after coinfection. Furthermore, we found that the protein synthesis-suppressing antibiotic linezolid has an advantageous therapeutic effect on alpha-toxin-induced lung damage, as measured by protein leak and lactate dehydrogenase (LDH) activity. Importantly, using a Panton-Valentine leucocidin (PVL)-negative MRSA isolate from patient sputum, we show that linezolid therapy significantly improves animal survival from postinfluenza MRSA pneumonia compared with vancomycin treatment. Rather than improved viral or bacterial control, this advantageous therapeutic effect is associated with a significantly attenuated proinflammatory cytokine response and acute lung damage in linezolid-treated mice. Together, our findings not only establish a critical role of alpha-toxin in the extreme mortality of secondary MRSA pneumonia after influenza but also provide support for the possibility that linezolid could be a more effective treatment than vancomycin to improve disease outcomes.

scholarly journals AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Ximena Castañeda ◽  
Cristina García-de-la-Mària ◽  
Oriol Gasch ◽  
Juan M. Pericas ◽  
Yolanda Armero ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Good Predictor ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Area Under The Curve ◽  
Methicillin Resistant ◽  
Bacterial Counts ◽  
Content Type ◽  
Treatment Groups ◽  
Mrsa Strains

ABSTRACT The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) (P = 0.343), while the medians (interquartile ranges [IQRs]) for log10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) (P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis.

scholarly journals Efficacy of Fosfomycin Compared to Vancomycin in Treatment of Implant-Associated Chronic Methicillin-Resistant Staphylococcus aureus Osteomyelitis in Rats

2014 ◽  
Vol 58 (9) ◽  
pp. 5111-5116 ◽  
Author(s):  
Wolfgang Poeppl ◽  
Tilman Lingscheid ◽  
Dominik Bernitzky ◽  
Uwe Y. Schwarze ◽  
Oliver Donath ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Drug Control ◽  
Once Daily ◽  
Methicillin Resistant ◽  
Content Type ◽  
Titanium Wire ◽  
Experimental Rat Model ◽  
Vancomycin Group ◽  
Emergence Of Resistance

ABSTRACTFosfomycin monotherapy was compared to therapy with vancomycin for the treatment of implant-associated methicillin-resistantStaphylococcus aureus(MRSA) osteomyelitis in an experimental rat model. The proximal tibiae were inoculated with 15 μl of a suspension containing 1 × 108to 5 × 108CFU/ml of a clinical isolate of MRSA with simultaneous insertion of a titanium wire. Four weeks later, treatment was started for 28 days with either 50 mg/kg of body weight vancomycin intraperitoneally twice daily (n= 11) or 75 mg/kg fosfomycin intraperitoneally once daily (n= 10). Eleven animals were left untreated. After treatment, quantitative cultures from bone were found to be positive for MRSA in all animals in the untreated group (median, 3.29 × 106CFU/g of bone) and the vancomycin group (median, 3.03 × 105CFU/g of bone). In the fosfomycin group, MRSA was detectable in 2 out of 10 (20%) animals (3.42 × 102and 1.51 × 103CFU/g of bone). Vancomycin was superior to the no-drug control (P= 0.002), and fosfomycin was superior to the no-drug control and vancomycin (P< 0.001). The cultures from the wires were positive in all untreated animals (median, 2.5 × 103CFU/implant), in 10 animals in the vancomycin group (median, 1.15 × 103CFU/implant), and negative in all animals in the fosfomycin group. Based on the bacterial counts from the implants, vancomycin was not superior to the no-drug control (P= 0.324), and fosfomycin was superior to the no-drug control and vancomycin (P< 0.001). No emergence of resistance was observed. In conclusion, it was demonstrated that fosfomycin monotherapy is highly effective for the treatment of experimental implant-associated MRSA osteomyelitis.

scholarly journals β-Lactamase Inhibitors Enhance the Synergy between β-Lactam Antibiotics and Daptomycin against Methicillin-Resistant Staphylococcus aureus

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Karl Evans R. Henson ◽  
Juwon Yim ◽  
Jordan R. Smith ◽  
George Sakoulas ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Synergistic Effect ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Time Kill ◽  
Lactamase Inhibitor

ABSTRACT The evidence for using combination therapy for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections is growing. In this study, we investigated the synergistic effect of daptomycin (DAP) combined with piperacillin-tazobactam and ampicillin-sulbactam against MRSA in time-kill experiments. Six of eight strains demonstrated synergy between DAP and the β-lactam–β-lactamase inhibitor (BLI) combination. In 5/8 strains, the synergy occurred only in the presence of the BLI, highlighting a role for BLIs in peptide–β-lactam synergy.

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