Dataset Information

Clinical and Molecular Characteristics of qacA- and qacB-Positive Methicillin-Resistant Staphylococcus aureus Causing Bloodstream Infections.

ABSTRACT: The increasing use of chlorhexidine for methicillin-resistant Staphylococcus aureus (MRSA) decolonization has raised concerns about the emergence of resistance to these agents. However, the clinical significance of MRSA positive for the qacA and qacB chlorhexidine tolerance genes has not been established. We investigated the clinical features and predictive factors of MRSA bloodstream infection (BSI) isolates, caused by qacA- and qacB-positive MRSA, from 2010 to 2016 at a tertiary hospital in South Korea. A total of 246 MRSA BSI isolates were included; 71 (28.9%) isolates carried qacA/B The annual frequency of qacA- and qacB-positive MRSA bacteremia did not change significantly over the study period. Patients infected with qacA- and qacB-positive MRSA had common risk factors for health care-associated infections, including prior antibiotic use, central venous catheterization in situ, intensive care unit-acquired bacteremia, and nosocomial infection. The qacA- and qacB-positive isolates were also associated with an increasing chlorhexidine MIC and resistance to non-?-lactam antibiotics. The qacA- and qacB-positive isolates were more likely to belong to sequence type 5 (ST5), which is a common health care-associated MRSA strain in South Korea. In multivariable analyses, qacA- and qacB-positive MRSA isolates were found to be associated with agr dysfunction (adjusted odds ratio [aOR], 6.45; 95% confidence interval [CI], 2.59 to 16.10), ST5 MRSA strain (aOR, 4.96; 95% CI, 1.85 to 13.26), nosocomial infection (aOR, 4.88; 95% CI, 2.20 to 10.83), and antibiotic use within the previous 3?months (aOR, 2.59; 95% CI, 1.20 to 5.59). These findings suggest that the microbiological features of qacA and qacB carriage provide a selective advantage for specific MRSA strains in hospital environments.

SUBMITTER: Hong SI

PROVIDER: S-EPMC6437476 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Clinical and Molecular Characteristics of qacA- and qacB-Positive Methicillin-Resistant Staphylococcus aureus Causing Bloodstream Infections.

Hong Sun In SI Lee Yu-Mi YM Park Ki-Ho KH Ryu Byung-Han BH Hong Kyung-Wook KW Kim Sunjoo S Bae In-Gyu IG Cho Oh-Hyun OH

Antimicrobial agents and chemotherapy 20190327 4

The increasing use of chlorhexidine for methicillin-resistant Staphylococcus aureus (MRSA) decolonization has raised concerns about the emergence of resistance to these agents. However, the clinical significance of MRSA positive for the qacA and qacB chlorhexidine tolerance genes has not been established. We investigated the clinical features and predictive factors of MRSA bloodstream infection (BSI) isolates, caused by qacA- and qacB-positive MRSA, from 2010 t ...[more]

PMID: 30718251

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Project description:BackgroundBloodstream infections due to Staphylococcus aureus cause significant patient morbidity and mortality worldwide. Of major concern is the emergence and spread of methicillin-resistant S. aureus (MRSA) in bloodstream infections, which are associated with therapeutic failure and increased mortality.MethodsWe generated high quality draft genomes from 323 S. aureus blood culture isolates from patients diagnosed with bloodstream infection at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA in 2010-2018.ResultsIn silico detection of antimicrobial resistance genes revealed that 133/323 isolates (41.18%) carry horizontally acquired genes conferring resistance to at least three antimicrobial classes, with resistance determinants for aminoglycosides, beta-lactams and macrolides being the most prevalent. The most common resistance genes were blaZ and mecA, which were found in 262/323 (81.11%) and 104/323 (32.20%) isolates, respectively. Majority of the MRSA (102/105 isolates or 97.14%) identified using in vitro screening were related to two clonal complexes (CC) 5 and 8. The two CCs emerged in the New Hampshire population at separate times. We estimated that the time to the most recent common ancestor of CC5 was 1973 (95% highest posterior density (HPD) intervals: 1966-1979) and 1946 for CC8 (95% HPD intervals: 1924-1959). The effective population size of CC8 increased until the late 1960s when it started to level off until late 2000s. The levelling off of CC8 in 1968 coincided with the acquisition of SCCmec Type IV in majority of the strains. The plateau in CC8 also coincided with the acceleration in the population growth of CC5 carrying SCCmec Type II in the early 1970s, which eventually leveled off in the early 1990s. Lastly, we found evidence for frequent recombination in the two clones during their recent clonal expansion, which has likely contributed to their success in the population.ConclusionsWe conclude that the S. aureus population was shaped mainly by the clonal expansion, recombination and co-dominance of two major MRSA clones in the last five decades in New Hampshire, USA. These results have important implications on the development of effective and robust strategies for intervention, control and treatment of life-threatening bloodstream infections.

Project description:Since 2010, methicillin-resistant Staphylococcus aureus (MRSA) ST59 began to increase in prevalence in China, gradually replacing ST239 and has become the dominant clone in most hospitals in China. Here, we investigated the changing epidemiology, phylogenetic reconstruction, and genomic characterization of MRSA clones in China to identify the genomic driving factors in the prevalence of ST59. Most MRSA isolates were identified as ST59 (36.98%; 277/749), which increased from 25.09% in 2014 to 35.53% in 2019. The phylogenetic analysis of the 749 MRSA isolates showed a high level of diversity and the copresence of hospital-associated, community-associated, livestock-associated, and hypervirulent clones. Furthermore, minimum spanning trees revealed that ST59 MRSA clones from different hospitals and regions were integrated, suggesting that frequent exchanges had occurred between regions and hospitals. ST59 clones displayed higher susceptibility to antimicrobials than did ST239 and ST5 MRSA clones, indicating that resistance to non-β-lactam and fluoroquinolone antibiotics may be not critical for the epidemic success of ST59 clones. Virulence factors detection showed that sak and chp genes enriched in MRSA ST59 may be associated with the enhanced spreading success of ST59, whereas qacA may have contributed to the predominance of ST5 in East China. Our refined analysis of different clones among ST239, ST5, ST59, and ST398 demonstrated the existence of potential driving factors for the evolution of nosocomial MRSA populations and diversity of the evolutionary events surrounding clonal replacement. IMPORTANCE As a developing country, China has an unbalanced health care system due to regional differences in economic development. However, China is also a country worthy of study with regard to the population dynamics of MRSA within the more resource-rich health care systems. In this study, we carried out genomic analysis to investigate the genomic epidemiology and characterization of MRSA isolated from bloodstream infections over a timespan of 6 years. Our refined analysis of different MRSA clones among ST59, ST5, ST239, and ST398 demonstrated the existence of driving factors for the evolution of nosocomial MRSA populations and diversity of the evolutionary events surrounding clonal replacement.

Project description:Vancomycin remains the mainstay treatment for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) despite increased treatment failures. Daptomycin has been shown to improve clinical outcomes in patients with BSIs caused by MRSA isolates with vancomycin MICs of >1 mg/liter, but these studies relied on automated testing systems. We evaluated the outcomes of BSIs caused by MRSA isolates for which vancomycin MICs were determined by standard broth microdilution (BMD). A retrospective, matched cohort of patients with MRSA BSIs treated with vancomycin or daptomycin from January 2010 to March 2015 was completed. Patients were matched using propensity-adjusted logistic regression, which included age, Pitt bacteremia score, primary BSI source, and hospital of care. The primary endpoint was clinical failure, which was a composite endpoint of the following metrics: 30-day mortality, bacteremia with a duration of ?7 days, or a change in anti-MRSA therapy due to persistent or worsening signs or symptoms. Secondary endpoints included MRSA-attributable mortality and the number of days of MRSA bacteremia. Independent predictors of failure were determined through conditional backwards-stepwise logistic regression with vancomycin BMD MIC forced into the model. A total of 262 patients were matched. Clinical failure was significantly higher in the vancomycin cohort than in the daptomycin cohort (45.0% versus 29.0%; P = 0.007). All-cause 30-day mortality was significantly higher in the vancomycin cohort (15.3% versus 6.1%; P = 0.024). These outcomes remained significant when stratified by vancomycin BMD MIC. There was no significant difference in the length of MRSA bacteremia. Variables independently associated with treatment failure included vancomycin therapy (adjusted odds ratio [aOR] = 2.16, 95% confidence interval [CI] = 1.24 to 3.76), intensive care unit admission (aOR = 2.46, 95% CI = 1.34 to 4.54), and infective endocarditis as the primary source (aOR = 2.33, 95% CI = 1.16 to 4.68). Treatment of MRSA BSIs with daptomycin was associated with reduced clinical failure and 30-day mortality; these findings were independent of vancomycin BMD MIC.

Dataset Information

Clinical and Molecular Characteristics of qacA- and qacB-Positive Methicillin-Resistant Staphylococcus aureus Causing Bloodstream Infections.

Publications

Clinical and Molecular Characteristics of <i>qacA</i>- and <i>qacB</i>-Positive Methicillin-Resistant <i>Staphylococcus aureus</i> Causing Bloodstream Infections.

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