Risk of death from methicillin-resistant Staphylococcus aureus bacteraemia: a meta-analysis

To the Editor: I write to offer a re-analysis of the data presented by Whitby and colleagues.1 They reported a meta-analysis of crude estimates and relative risk of death derived from nine published studies for Staphylococcus aureus bacteraemia. They concluded that bacteraemia caused by methicillin-resistant S. aureus (MRSA) is associated with a "real increase in risk of death" compared with bacteraemia caused by methicillin-sensitive S. aureus (MSSA), with a relative risk of 2.12. However, they failed to explore fully the possible confounding effect of the patients' underlying diseases and treatment in their analysis.

With this in mind, I offer a re-analysis of their data using regression analysis. Mortality rates versus median length of stay in hospital before bacteraemia (LOS) are shown in the Box (next page) for the five studies for which these data were presented by Whitby et al (in Boxes 1 and 2). The four studies without LOS data were combined, using the median LOS from the other five studies in the figure and the regression model.

The regression analysis was performed with and without the weights provided by Whitby et al (Box 2), and also with and without the four studies for which LOS data were not available.

Regression analysis revealed a significant association between mortality rate and LOS (P < 0.005). However, the addition of group status (MRSA or MSSA) failed to achieve significance in any iteration of the regression, while LOS remained a significant predictor of mortality risk.

This suggests that, with S. aureus bacteraemia, mortality rate increases with length of time in hospital before the bacteraemia. The likely explanation is that patients residing in hospital for longer periods are sicker. Moreover, they are more likely to have been exposed to antibiotics, leading to increased risk of acquiring an S. aureus strain that is methicillin-resistant. The mortality risk is no different for MRSA versus MSSA bacteraemia if LOS, a surrogate marker for severity of patient illness, is taken into account. The difference that Whitby et al observed between the groups of patients with MRSA and MSSA bacteraemia could be accounted for by the difference in LOS between these groups.

Mortality rate versus hospital length of stay before bacteraemia (LOS) in patients with MRSA or MSSA bacteraemia