Factors predicting and reducing mortality in patients with invasive Staphylococcus aureus disease in a developing country

Abstract

Background: Invasive Staphylococcus aureus infection is increasingly recognised as an important cause of serious sepsis across the developing world, with mortality rates higher than those in the developed world. The factors determining mortality in developing countries have not been identified.

Methods: A prospective, observational study of invasive S. aureus disease was conducted at a provincial hospital in northeast Thailand over a 1-year period. All-cause and S. aureus-attributable mortality rates were determined, and the relationship was assessed between death and patient characteristics, clinical presentations, antibiotic therapy and resistance, drainage of pus and carriage of genes encoding Panton-Valentine Leukocidin (PVL).

Principal findings: A total of 270 patients with invasive S. aureus infection were recruited. The range of clinical manifestations was broad and comparable to that described in developed countries. All-cause and S. aureus-attributable mortality rates were 26% and 20%, respectively. Early antibiotic therapy and drainage of pus were associated with a survival advantage (both p<0.001) on univariate analysis. Patients infected by a PVL gene-positive isolate (122/248 tested, 49%) had a strong survival advantage compared with patients infected by a PVL gene-negative isolate (all-cause mortality 11% versus 39% respectively, p<0.001). Multiple logistic regression analysis using all variables significant on univariate analysis revealed that age, underlying cardiac disease and respiratory infection were risk factors for all-cause and S. aureus-attributable mortality, while one or more abscesses as the presenting clinical feature and procedures for infectious source control were associated with survival.

Conclusions: Drainage of pus and timely antibiotic therapy are key to the successful management of S. aureus infection in the developing world. Defining the presence of genes encoding PVL provides no practical bedside information and draws attention away from identifying verified clinical risk factors and those interventions that save lives.

Figure 1. Higher all-cause mortality associated with methicillin-resistant S. aureus (MRSA) but not with Panton-Valentine Leukocidin (PVL).

Patients infected by MRSA had a greater all-cause mortality compared with patients infected by methicillin-susceptible S. aureus (MSSA) (p<0.001). Conversely, patients infected by PVL gene-positive S. aureus had a lower all-cause mortality compared with patients infected by PVL gene-negative S. aureus (p<0.001), an association that remained after adjustment for MRSA (p = 0.001).

Figure 2. Timely effective antibiotic therapy and procedures for infectious source control significantly improved outcome.

Administration of an effective antibiotic on the same day as the positive culture was taken significantly reduced all-cause mortality (p<0.001), as did undergoing a procedure for infectious source control (p<0.001).