scholarly journals Predictors ofagrDysfunction in Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates among Patients with MRSA Bloodstream Infections

2011 ◽  
Vol 55 (12) ◽  
pp. 5433-5437 ◽  
Author(s):  
Jill M. Butterfield ◽  
Brian T. Tsuji ◽  
Jack Brown ◽  
Elizabeth Dodds Ashley ◽  
Dwight Hardy ◽  
...  
Keyword(s):  
New York ◽  
Staphylococcus Aureus ◽  
Severity Of Illness ◽  
Bloodstream Infections ◽  
Bivariate Analysis ◽  
Beta Lactam ◽  
Accessory Gene ◽  
Cross Sectional ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACTDespite emerging evidence that dysfunction in the accessory gene regulator (agr) locus is associated with deleterious outcomes among patients treated with vancomycin for methicillin-resistantStaphylococcus aureus(MRSA) infections, factors predictive ofagrdysfunction have not been evaluated. This study describes the epidemiology ofagrdysfunction, identifies predictors ofagrdysfunction in MRSA isolates among those with MRSA bloodstream infections, and describes the relationship betweenagrdysfunction and other microbiologic phenotypes. A cross-sectional study of patients with MRSA bloodstream infections at two institutions in upstate New York was performed. Clinical data on demographics, comorbidities, disease severity, hospitalization history, and antibiotic history were collected. Microbiologic phenotypes, includingagrdysfunction, MIC values by broth microdilution (BMD) and Etest, and vancomycin heteroresistance (hVISA) were tested. Multivariable analyses were performed to identify factors predictive ofagrdysfunction. Among 200 patients with an MRSA bloodstream infection, the proportion of strains withagrdysfunction was 31.5%. The distribution of MICs determined by both BMD and Etest were equivalent acrossagrgroups, and there was no association betweenagrdysfunction and the presence of hVISA. Severity of illness, comorbidities, and hospitalization history were comparable betweenagrgroups. In the multivariate analysis, prior antibiotic exposure was the only factor of variables studied found to be predictive ofagrdysfunction. This relationship was predominantly driven by prior beta-lactam and fluoroquinolone administration in the bivariate analysis. Identifying these institution-specific risk factors can be used to develop a process to assess the risk ofagrdysfunction and guide empirical antibiotic therapy decisions.

scholarly journals Toxic Shock Syndrome Toxin 1-Producing Methicillin-Resistant Staphylococcus aureus of Clonal Complex 5, the New York/Japan Epidemic Clone, Causing a High Early-Mortality Rate in Patients with Bloodstream Infections

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Dokyun Kim ◽  
Jun Sung Hong ◽  
Eun-Jeong Yoon ◽  
Hyukmin Lee ◽  
Young Ah Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
New York ◽  
Staphylococcus Aureus ◽  
Mortality Rate ◽  
Clonal Complex ◽  
Bloodstream Infections ◽  
Early Mortality ◽  
Epidemic Clone ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACT This study was performed to evaluate the clinical impacts of putative risk factors in patients with Staphylococcus aureus bloodstream infections (BSIs) through a prospective, multicenter, observational study. All 567 patients with S. aureus BSIs that occurred during a 1-year period in six general hospitals were included in this study. Host- and pathogen-related variables were investigated to determine risk factors for the early mortality of patients with S. aureus BSIs. The all-cause mortality rate was 15.0% (85/567) during the 4-week follow-up period from the initial blood culture, and 76.5% (65/85) of the mortality cases occurred within the first 2 weeks. One-quarter (26.8%, 152/567) of the S. aureus blood isolates carried the tst-1 gene, and most (86.2%, 131/152) of them were identified to be clonal complex 5 agr type 2 methicillin-resistant S. aureus (MRSA) strains harboring staphylococcal cassette chromosome mec type II, belonging to the New York/Japan epidemic clone. A multivariable logistic regression showed that the tst-1 positivity of the causative S. aureus isolates was associated with an increased 2-week mortality rate both in patients with S. aureus BSIs (adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 0.90 to 2.88) and in patients with MRSA BSIs (aOR, 2.61; 95% CI, 1.19 to 6.03). Two host-related factors, an increased Pitt bacteremia score and advanced age, as well as a pathogen-related factor, carriage of tst-1 by causative MRSA isolates, were risk factors for 2-week mortality in patients with BSIs. Careful management of patients with BSIs caused by the New York/Japan epidemic clone is needed to improve clinical outcomes.

scholarly journals Evaluation of Ceftaroline Alone and in Combination against Biofilm-Producing Methicillin-Resistant Staphylococcus aureus with Reduced Susceptibility to Daptomycin and Vancomycin in anIn VitroPharmacokinetic/Pharmacodynamic Model

2015 ◽  
Vol 59 (8) ◽  
pp. 4497-4503 ◽  
Author(s):  
Katie E. Barber ◽  
Jordan R. Smith ◽  
Cortney E. Ireland ◽  
Blaise R. Boles ◽  
Warren E. Rose ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Medical Device ◽  
Bloodstream Infections ◽  
Methicillin Resistant ◽  
Content Type ◽  
Elimination Half ◽  
Antimicrobial Protection ◽  
Mrsa Strains ◽  
Post Hoc

ABSTRACTAnnually, medical device infections are associated with >250,000 catheter-associated bloodstream infections (CLABSI), with up to 25% mortality.Staphylococcus aureus, a primary pathogen in these infections, is capable of biofilm production, allowing organism persistence in harsh environments, offering antimicrobial protection. With increases inS. aureusisolates with reduced susceptibility to current agents, ceftaroline (CPT) offers a therapeutic alternative. Therefore, we evaluated whether CPT would have a role against biofilm-producing methicillin-resistantS. aureus(MRSA), including those with decreased susceptibilities to alternative agents. In this study, we investigated CPT activity alone or combined with daptomycin (DAP) or rifampin (RIF) against 3 clinical biofilm-producing MRSA strains in anin vitrobiofilm pharmacokinetic/pharmacodynamic (PK/PD) model. Simulated antimicrobial regimens were as follows: 600 mg of CPT every 8 h (q8h) (free maximum concentration of drug [fCmax], 17.04 mg/liter; elimination half-life [t1/2], 2.66 h), 12 mg/kg of body weight/day of DAP (fCmax, 14.7 mg/liter;t1/2, 8 h), and 450 mg of RIF q12h (fCmax, 3.5 mg/liter;t1/2, 3.4 h), CPT plus DAP, and CPT plus RIF. Samples were obtained and plated to determine colony counts. Differences in log10CFU/cm2were evaluated by analysis of variance with Tukey'spost hoctest. The strains were CPT and vancomycin susceptible and DAP nonsusceptible (DNS). CPT displayed activity throughout the experiment. DAP demonstrated initial activity with regrowth at 24 h in all strains. RIF was comparable to the drug-free control, and little benefit was observed when combined with CPT. CPT plus DAP displayed potent activity, with an average log10CFU/cm2reduction of 3.33 ± 1.01 from baseline. CPT demonstrated activity against biofilm-producing DNS MRSA. CPT plus DAP displayed therapeutic enhancement over monotherapy, providing a potential option for difficult-to-treat medical device infections.

scholarly journals Novel Combinations of Vancomycin plus Ceftaroline or Oxacillin against Methicillin-Resistant Vancomycin-Intermediate Staphylococcus aureus (VISA) and Heterogeneous VISA

2013 ◽  
Vol 57 (5) ◽  
pp. 2376-2379 ◽  
Author(s):  
B. J. Werth ◽  
C. Vidaillac ◽  
K. P. Murray ◽  
K. L. Newton ◽  
G. Sakoulas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Inverse Correlation ◽  
Fluorescent Dye ◽  
Beta Lactam ◽  
Significant Inverse Correlation ◽  
Methicillin Resistant ◽  
Content Type ◽  
Time Kill ◽  
Wall Interactions

ABSTRACTWe demonstrated a significant inverse correlation between vancomycin and beta-lactam susceptibilities in vancomycin-intermediateStaphylococcus aureus(VISA) and heterogeneous VISA (hVISA) isolates. Using time-kill assays, vancomycin plus oxacillin or ceftaroline was synergistic against 3 of 5 VISA and 1 of 5 hVISA isolates or 5 of 5 VISA and 4 of 5 hVISA isolates, respectively. Beta-lactam exposure reduced overall vancomycin-Bodipy (dipyrrometheneboron difluoride [4,4-difluoro-4-bora-3a,4a-diaza-s-indacene] fluorescent dye) binding but may have improved vancomycin-cell wall interactions to improve vancomycin activity. Further research is warranted to elucidate the mechanism behind vancomycin and beta-lactam synergy.

scholarly journals Blurred molecular epidemiological lines between the two dominant methicillin-resistant Staphylococcus aureus clones

2018 ◽  
Author(s):  
Amy C. Dupper ◽  
Mitchell J. Sullivan ◽  
Kieran I. Chacko ◽  
Aaron Mishkin ◽  
Brianne Ciferri ◽  
...  
Keyword(s):  
New York ◽  
Staphylococcus Aureus ◽  
Medical Center ◽  
Data Extraction ◽  
Age Groups ◽  
Bloodstream Infections ◽  
Methicillin Resistant ◽  
Peripheral Intravenous Catheter ◽  
Life Threatening ◽  
Healthcare Associated

AbstractBackgroundMethicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening infections in both community and hospital settings and is a leading cause of healthcare-associated infections (HAIs). We sought to describe the molecular epidemiological landscape of patients with MRSA bloodstream infections (BSIs) at an urban medical center by evaluating the clinical characteristics associated with the two dominant endemic clones.MethodsComprehensive clinical data extraction from the electronic health records of 227 hospitalized patients ≥18 years old with MRSA BSI over a 33-month period in New York City were collected. The descriptive epidemiology and mortality associated with the two dominant clones was compared using logistic regression.ResultsMolecular analysis revealed that 91% of all single-patient MRSA BSIs were due to two equally represented genotypes, clonal complex (CC) 5 (N=117) and CC8 (N=110). MRSA BSIs were associated with a 90-day mortality of 27%. CC8 caused disease more frequently in younger age groups (56 ± 17 vs 67 ± 17 years old; p<0.001) and in non-White race (OR=3.45 95% CI [1.51-7.87]; p=0.003), with few other major distinguishing features. Morbidity and mortality also did not differ significantly between the two clones. CC8 caused BSIs more frequently in the setting of peripheral intravenous catheters (OR=5.96; 95% CI [1.51-23.50]; p=0.01).ConclusionThe clinical features distinguishing dominant MRSA clones continue to converge. The association of CC8 with peripheral intravenous catheter infections underscores the importance of classical community clones causing hospital-onset infections. Ongoing monitoring and analysis of the dynamic epidemiology of this endemic pathogen is crucial to inform management to prevent disease.

scholarly journals Genetic Characterization of Methicillin-Resistant Staphylococcus aureus Isolates from Human Bloodstream Infections: Detection of MLSB Resistance

Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 375
Author(s):  
Vanessa Silva ◽  
Sara Hermenegildo ◽  
Catarina Ferreira ◽  
Célia M. Manaia ◽  
Rosa Capita ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bloodstream Infections ◽  
Disk Diffusion ◽  
Diffusion Method ◽  
Accessory Gene ◽  
Spa Typing ◽  
Disk Diffusion Method ◽  
Methicillin Resistant

In this study we aimed to characterize antimicrobial resistance in methicillin-resistant Staphylococcus aureus (MRSA) isolated from bloodstream infections as well as the associated genetic lineages of the isolates. Sixteen MRSA isolates were recovered from bacteremia samples from inpatients between 2016 and 2019. The antimicrobial susceptibility of these isolates was tested by the Kirby–Bauer disk diffusion method against 14 antimicrobial agents. To determine the macrolide–lincosamide–streptogramin B (MLSB) resistance phenotype of the isolates, erythromycin-resistant isolates were assessed by double-disk diffusion (D-test). The resistance and virulence genes were screened by polymerase chain reaction (PCR). All isolates were characterized by multilocus sequence typing (MLST), spa typing, staphylococcal chromosomal cassette mec (SCCmec) typing, and accessory gene regulator (agr) typing. Isolates showed resistance to cefoxitin, penicillin, ciprofloxacin, erythromycin, fusidic acid, clindamycin, and aminoglycosides, confirmed by the presence of the blaZ, ermA, ermC, mphC, msrA/B, aac(6’)-Ie-aph(2’’)-Ia, and ant(4’)-Ia genes. Three isolates were Panton–Valentine-leukocidin-positive. Most strains (n = 12) presented an inducible MLSB phenotype. The isolates were ascribed to eight spa-types (t747, t002, t020, t1084, t008, t10682, t18526, and t1370) and four MLSTs (ST22, ST5, ST105, and ST8). Overall, most (n = 12) MRSA isolates had a multidrug-resistance profile with inducible MLSB phenotypes and belonged to epidemic MRSA clones.

scholarly journals Vancomycin Tolerance in Methicillin-Resistant Staphylococcus aureus: Influence of Vancomycin, Daptomycin, and Telavancin on Differential Resistance Gene Expression

2012 ◽  
Vol 56 (8) ◽  
pp. 4422-4427 ◽  
Author(s):  
Warren E. Rose ◽  
Michael Fallon ◽  
John J. M. Moran ◽  
Joshua P. Vanderloo
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Gene Regulation ◽  
Cell Envelope ◽  
Differential Resistance ◽  
Accessory Gene ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Strains ◽  
Time Kill

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) isolates that are susceptible to vancomycin but are tolerant to its killing effect may present a potential challenge for effective treatment. This study compared the microbiologic characteristics of clinical vancomycin-tolerant (VT-MRSA) and vancomycin-susceptible (VS-MRSA) strains using phenotypic and gene regulation studies. MRSA isolates collected from vancomycin-treated patients with bacteremia over a 5-year period were analyzed for vancomycin, daptomycin, and telavancin susceptibility, as well as accessory gene regulator (agr) group and function. Vancomycin tolerance was defined by a minimum bactericidal concentration (MBC)/minimum inhibitor concentration (MIC) ratio of ≥32 mg/liter. VT-MRSA isolates were compared to VS-MRSA isolates for differences in antimicrobial susceptibility, time-kill activity, and gene expression of key cell envelope response genesvraSR,dltA, andmprF. All 115 isolates evaluated were susceptible to vancomycin, daptomycin, and telavancin. Seven isolates (6%) were VT-MRSA.agrgroup II was more prevalent in isolates with vancomycin MBC/MIC ratios of ≥8. In time-kill analyses, VT-MRSA had reduced vancomycin killing, but daptomycin and telavancin activities were maintained. Significantly greater gene expression was observed in VT-MRSA after 72 h of subinhibitory antibiotic exposures. Vancomycin most notably increasedvraSRexpression (P= 0.002 versus VS-MRSA strains). Daptomycin and telavancin increased expression of all genes studied, most significantlymprFexpression (P< 0.001). Longer durations of antibiotic exposure (72 h versus 24 h) resulted in substantial increases in gene expression in VT-MRSA. Although the clinical impact of VT-MRSA is not fully recognized, these data suggest that VT-MRSA strains, while still susceptible, have altered gene regulation to adapt to the antimicrobial effects of glyco- and lipopeptides that may emerge during prolonged durations of exposure.

scholarly journals Full-Genome Sequencing Identifies in the Genetic Background Several Determinants That Modulate the Resistance Phenotype in Methicillin-Resistant Staphylococcus aureus Strains Carrying the Novel mecC Gene

2017 ◽  
Vol 61 (3) ◽  
Author(s):  
Catarina Milheiriço ◽  
Hermínia de Lencastre ◽  
Alexander Tomasz
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Genetic Background ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
Content Type ◽  
Resistance Phenotype ◽  
Beta Lactam Antibiotics ◽  
Oxacillin Resistance ◽  
Mrsa Strains

ABSTRACT Most methicillin-resistant Staphylococcus aureus (MRSA) strains are resistant to beta-lactam antibiotics due to the presence of the mecA gene, encoding an extra penicillin-binding protein (PBP2A) that has low affinity for virtually all beta-lactam antibiotics. Recently, a new resistance determinant—the mecC gene—was identified in S. aureus isolates recovered from humans and dairy cattle. Although having typically low MICs to beta-lactam antibiotics, MRSA strains with the mecC determinant are also capable of expressing high levels of oxacillin resistance when in an optimal genetic background. In order to test the impact of extensive beta-lactam selection on the emergence of mecC-carrying strains with high levels of antibiotic resistance, we exposed the prototype mecC-carrying MRSA strain, LGA251, to increasing concentrations of oxacillin. LGA251 was able to rapidly adapt to high concentrations of oxacillin in growth medium. In such laboratory mutants with increased levels of oxacillin resistance, we identified mutations in genes with no relationship to the mecC regulatory system, indicating that the genetic background plays an important role in the establishment of the levels of oxacillin resistance. Our data also indicate that the stringent stress response plays a critical role in the beta-lactam antibiotic resistance phenotype of MRSA strains carrying the mecC determinant.

scholarly journals Methicillin-Resistant Staphylococcus aureus Control in the 21st Century: Laboratory Involvement Affecting Disease Impact and Economic Benefit from Large Population Studies

2016 ◽  
Vol 54 (11) ◽  
pp. 2647-2654 ◽  
Author(s):  
Lance R. Peterson ◽  
Donna M. Schora
Keyword(s):  
Health Care ◽  
Staphylococcus Aureus ◽  
Disease Control ◽  
Clinical Laboratory ◽  
Large Population ◽  
Bloodstream Infections ◽  
Control Plan ◽  
Methicillin Resistant ◽  
Content Type ◽  
Program Cost

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a global health care problem. Large studies (e.g., >25,000 patients) show that active surveillance testing (AST) followed by contact precautions for positive patients is an effective approach for MRSA disease control. With this approach, the clinical laboratory will be asked to select what AST method(s) to use and to provide data monitoring outcomes of the infection prevention interventions. This minireview summarizes evidence for MRSA disease control, reviews the involvement of the laboratory, and provides examples of how to undertake a program cost analysis. Health care organizations with total MRSA clinical infections of >0.3/1,000 patient days or bloodstream infections of >0.03/1,000 patient days should implement a MRSA control plan.

Molecular Study of Immune Evasion Cluster Genes in Clinical Isolates of Staphylococcus aureus

2021 ◽  
Vol 10 ◽  
Author(s):  
Maysaa El Sayed Zaki ◽  
Samah Sabry El-Kazzaz
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Evasion ◽  
Clinical Isolates ◽  
Diffusion Method ◽  
Beta Lactam ◽  
Sensitivity Testing ◽  
Cross Sectional ◽  
Methicillin Resistant ◽  
Beta Lactam Antibiotics ◽  
Immune Evasion Cluster

Aims: The aim of the present research was to highlight the prevalence of immune evasion cluster genes (IEC) sak, chp, scn, sea, sep among Staphylococcus aureus (S. aureus) clinical isolates. Background: The present study was a cross-sectional retrospective study, included one hundred isolates of S. aureus that were isolated from patients with nosocomial infections. S. aureus isolates were subjected to full microbiological identification and antibiotics sensitivity testing by the disc diffusion method. The presence of IEC genes scn, sea, sak, sep, chp was determined by polymerase chain reaction (PCR). Methods: The current study included 100 S. aureus isolates; 40% were classified as methicillin resistant. The isolates exhibited marked resistance to beta lactams antibiotics, the lowest resistance was to erythromycin, ciprofloxacin and vancomycin. The presence of one or more IEC was determined in 89 isolates. The prevalence of chp, sak, sea, sep and scn was 54%, 53%, 8%, 7% and 30%, respectively. Results: S. aureus isolates with IEC genes had increased resistance rates to the studied antibiotics; however, this increase was statistically insignificant either to beta-lactam antibiotics, such as amoxacillin/clavulinic acid (P=0.794), ampicillin (P=0.561), cefotaxim (P=0.271), ceftazidime (P=0.145), imipenem (P=0.589) or non beta-lactam antibiotics, such as amikacin (P=0.955) and trimethoprim/sulfamethoxazale (P=0.974). From 40 methicillin resistant Staphylococcus aureus (MRSA) strains, 37 isolates harbor one or more immune evasion cluster genes. Conclusion: The high prevalence of these genes among MRSA may explain its pathogenesis. There is a need for studies with a high number of isolates to verify the present findings.

scholarly journals Genetic Determinants of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Maria Pardos de la Gandara ◽  
Vitor Borges ◽  
Marilyn Chung ◽  
Catarina Milheiriço ◽  
João Paulo Gomes ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Phenotypic Expression ◽  
Beta Lactam ◽  
Genetic Determinants ◽  
Methicillin Resistant ◽  
Content Type ◽  
Clonal Type ◽  
Oxacillin Resistance ◽  
Resistant Phenotype ◽  
Six Genes

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) strains carry either a mecA - or a mecC -mediated mechanism of resistance to beta-lactam antibiotics, and the phenotypic expression of resistance shows extensive strain-to-strain variation. In recent communications, we identified the genetic determinants associated with the stringent stress response that play a major role in the antibiotic resistant phenotype of the historically earliest “archaic” clone of MRSA and in the mecC -carrying MRSA strain LGA251. Here, we sought to test whether or not the same genetic determinants also contribute to the resistant phenotype of highly and homogeneously resistant (H*R) derivatives of a major contemporary MRSA clone, USA300. We found that the resistance phenotype was linked to six genes ( fruB , gmk , hpt , purB , prsA , and relA ), which were most frequently targeted among the analyzed 20 H*R strains (one mutation per clone in 19 of the 20 H*R strains). Besides the strong parallels with our previous findings (five of the six genes matched), all but one of the repeatedly targeted genes were found to be linked to guanine metabolism, pointing to the key role that this pathway plays in defining the level of antibiotic resistance independent of the clonal type of MRSA.

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