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Risk factors for methicillin-resistant Staphylococcus aureus bacteraemia differ depending on the control group chosen.

ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia cause significant morbidity and mortality in hospitalized patients. Using a nested case-control design, 204 MRSA bacteraemia cases were compared to 301 unmatched methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia controls and were matched 1:2 with non-infected controls. The independent risk factors for MRSA bacteraemia compared to MSSA bacteraemia were older age (P = 0·048), major organ transplant during current hospital stay (P = 0·016) and quinolone use (P = 0·016). Cases were more likely than non-infected controls to have renal failure (P = 0·003), cirrhosis (P = 0·013), and a central venous catheter (P = 0·003) after controlling for other risk factors. This large case-control study made it possible to assess risk factors for MRSA bacteraemia using two sets of controls and showed that risk factors differed greatly depending on the control group chosen. These results confirm the need for careful selection of appropriate control groups and the need to carefully adjust for underlying severity of illness.

SUBMITTER: Pogorzelska-Maziarz M

PROVIDER: S-EPMC4065413 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Risk factors for methicillin-resistant Staphylococcus aureus bacteraemia differ depending on the control group chosen.

Pogorzelska-Maziarz M M Furuya E Y EY Larson E L EL

Epidemiology and infection 20130221 11

Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia cause significant morbidity and mortality in hospitalized patients. Using a nested case-control design, 204 MRSA bacteraemia cases were compared to 301 unmatched methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia controls and were matched 1:2 with non-infected controls. The independent risk factors for MRSA bacteraemia compared to MSSA bacteraemia were older age (P = 0·048), major organ transplant during current hospita ...[more]

PMID: 23425708

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Project description:BackgroundClinical risk factors for nephrotoxicity in Staphylococcus aureus bacteraemia remain largely undetermined, despite its common occurrence and clinical significance. In an international, multicentre, prospective clinical trial (CAMERA2), which compared standard therapy (vancomycin monotherapy) to combination therapy (adding an anti-staphylococcal beta-lactam) for methicillin-resistant S. aureus bacteraemia, significantly more people in the combination therapy arm experienced acute kidney injury compared with those in the monotherapy arm (23% vs 6%).ObjectiveThe aim of this post hoc analysis was to explore in greater depth the risk factors for acute kidney injury from the CAMERA2 trial.MethodsAmong participants of the CAMERA2 trial, demographic-related, infection-related and treatment-related risk factors were assessed for their relationship with acute kidney injury by univariable and multivariable logistic regression. Acute kidney injury was defined by a modified-KDIGO (Kidney Disease: Improving Global Outcomes) criteria (not including urinary output).ResultsOf the 266 participants included, age (p = 0.04), randomisation to combination therapy (p = 0.002), vancomycin area under the concentration-time curve (p = 0.03) and receipt of (flu)cloxacillin as the companion beta-lactam (p < 0.001) were significantly associated with acute kidney injury. On a multivariable analysis, concurrent use of (flu)cloxacillin increased the risk of acute kidney injury over four times compared with the use of cefazolin or no beta-lactam. The association of vancomycin area under the concentration-time curve with acute kidney injury also persisted in the multivariable model.ConclusionsFor participants receiving vancomycin for S. aureus bacteraemia, use of (flu)cloxacillin and increased vancomycin area under the concentration-time curve were risk factors for acute kidney injury. These represent potentially modifiable risk factors for nephrotoxicity and highlight the importance of avoiding the use of concurrent nephrotoxins.

Project description:Methicillin resistant Staphylococcus aureus (MRSA) infection is becoming refractory to existing antibiotic therapy owing to the inherent ability of S. aureus to develop rapid resistance and is considered a major threat to public health. We found that a natural isolate of Bacillus pumilus from the Columbia River Estuary produces a strong anti-MRSA compound, amicoumacin A. As amicoumacin A has been reported to exhibit anti-microbial, anti-inflammatory, and anti-ulcer activities, we sought to uncover its mechanism of action. Genome-wide transcriptome analysis of S. aureus COL in response to amicoumacin A showed alteration in the expression of genes involved in several cellular processes including cell envelope turnover, cross-membrane transport, virulence, metabolism, and general stress response. The most highly induced gene was lrgA, encoding an antiholin-like product, which has been shown to be induced in response to a collapse of membrane potential. In order to gain further insight into the mechanism of action of amicoumacin A, a whole genome comparison of wild-type COL and amicoumacin A-resistant mutants isolated by serial passage method was carried out. Single point mutations resulting in codon substitutions were uncovered in several distinct genes: ksgA, RNA dimethyltranferase; fusA, elongation factor G; dnaG, primase, ; lacD, tagatose 1,6-bisphosphate aldolase, ; and SACOL0611, encoding a putative glycosyl transferase gene. Based on these results, a candidate approach was undertaken to recreate the same amino acid substitution individually in FusA and KsgA, each of which resulted in two-fold resistance towards amicoumacin A. The fusA gene is known as the site for fusidic acid- resistant mutations; however the codon substitutions in EF-G that cause amicoumacin A resistance and fusidic acid resistance occur in separate domains and do not bring about cross resistance. Taken together, these results suggest that amicoumacin A might cause perturbation of the cell membrane and lead to energy dissipation. Decreased rates of cellular metabolism including protein synthesis and DNA replication in resistant strains might allow cells to compensate for membrane dysfunction and thus increase cell survivability.

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Risk factors for methicillin-resistant Staphylococcus aureus bacteraemia differ depending on the control group chosen.

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Risk factors for methicillin-resistant Staphylococcus aureus bacteraemia differ depending on the control group chosen.

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