Hospital Acquired MRSA pays no attention to vancomycin effectiveness

Image: PD/CDC. MRSA 

Key study points: 

1. Hospital-acquired MRSA (HA-MRSA) infections have worse outcomes than community-acquired MRSA (CA-MRSA) infections regardless of their susceptibility to vancomycin.

2. Worse outcomes from HA-MRSA infections may be due to unidentified virulence factors.

Primer: Methicillin-resistant Staphylococcus aureus (MRSA) has become an increasingly prevalent cause of infection worldwide. Methicillin resistance is conferred by the mecA gene, which is found on a mobile genetic element called staphylococcal chromosome cassette (SCCmec).  MecA encodes the peptidoglycan cross-linking protein PBP-2a to which most beta-lactams are unable to bind.  Six major mecA clones (SCCmec I-VI) have been identified.

HA-MRSA species generally contain the SCCmec type I, II, or III genes and are associated with higher rates of mortality and worse clinical outcomes while CA-MRSA generally possess SCCmec types IV and V and generally cause less severe infections.

To better understand why HA-MRSA causes more severe infections, this study’s authors examined how drug-susceptibility correlated with clinical outcome.  Specifically, the authors examined whether minimum inhibitory concentration (MIC) for vancomycin of different MRSA isolates correlated with treatment failure.

Of note, the clinical distinctions between CA and HA-MRSA have become less clear as patients are being colonized in one setting and developing infections in another; therefore this study defined HA-MRSA as isolates containing SCCmec type I,II or III and CA-MRSA isolates as containing types IV or V.

More background reading: 

1. Ganga R, Riederer K, Sharma M, et al. Role of SCCmec type in outcome of Staphylococcus aureus bacteremia in a single medical center. J Clin Microbiol 2009;47:590-5. 

2. Hota B, Lyles R, Rim J, et al. Predictors of clinical virulence in community-onset methicillin-resistant Staphylococcus aureus infections: the importance of USA300 and pneumonia. Clin Infect Dis 2011;53:757-65.

This [retrospective cohort] study by Chen et. al. pooled data from a prior study and examined records of all patients >15 years of age who were diagnosed with MRSA bacteremia, for a total of 291 patients in the study.  The SCCmec elements and MIC’s for vancomycin were identified for the different isolates.  The primary outcome for the study was treatment failure, which the authors defined as (1) all cause 30 day mortality; (2) persistent bacteremia after 7 days of treatment; or (3) recurrent MRSA bacteremia within 30 days of completing treatment with an appropriate anti-MRSA agent.

Patients were then categorized into groups: low vancomycin-MIC CA-MRSA (111), low-vancomycin-MIC HA-MRSA (127), and high vancomycin-MIC HA-MRSA (47). Low vancomycin-MIC was defined as </=1ug/ml, while high vancomycin-MIC was defined as >/=2ug/ml.

Analysis showed that HA-MRSA had a significantly higher treatment failure risk than CA-MRSA (aOR 1.98, 95% CI 1.131-3.496).  Additionally, the risk for treatment failure was higher for both low and high vancomycin-MIC HA-MRSA than for low vancomycin-MIC CA-MRSA patients (aOR 1.853 95% CI 1.0006 – 3.413 and aOR 2.393 95% CI 1.079-5.309 respectively).

In sum: This study suggests that the higher rates of treatment failure associated with HA-MRSA strains do not stem from vancomycin resistance.  The authors propose the existence of strain-specific virulence factors that affect clinical outcome.  The generalizability of this study requires clarification, however, as patient data was tracked from only a single center.  Additionally, retrospective cohort studies are subject to information bias.

The prospect of unidentified virulence factors affecting treatment outcome is compelling.  Further studies should attempt to identify these factors, and also to potentially seek targeted treatments to improve patient outcomes.

Click to read the study in Clinical Infectious Diseases  

By [AS] and [MP]

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