Staphylococcus aureus Bacteraemia in a Tropical Setting: Patient Outcome and Impact of Antibiotic Resistance

Background: Most information on invasive Staphylococcus aureus infections comes from temperate countries. There are considerable knowledge gaps in epidemiology, treatment, drug resistance and outcome of invasive S. aureus infection in the tropics. Methods: A prospective, observational study of S. aureus bacteraemia was conducted in a 1000-bed regional hospital in northeast Thailand over 1 year. Detailed clinical data were collected and final outcomes determined at 12 weeks, and correlated with antimicrobial susceptibility profiles of infecting isolates. Principal Findings: Ninety-eight patients with S. aureus bacteraemia were recruited. The range of clinical manifestations was similar to that reported from temperate countries. The prevalence of endocarditis was 14%. The disease burden was highest at both extremes of age, whilst mortality increased with age. The all-cause mortality rate was 52%, with a mortality attributable to S. aureus of 44%. Methicillin-resistant S. aureus (MRSA) was responsible for 28% of infections, all of which were healthcare-associated. Mortality rates for MRSA and methicillin-susceptible S. aureus (MSSA) were 67% (18/27) and 46% (33/71), respectively (p = 0.11). MRSA isolates were multidrug resistant. Only vancomycin or fusidic acid would be suitable as empirical treatment options for suspected MRSA infection. Conclusions: S. aureus is a significant pathogen in northeast Thailand, with comparable clinical manifestations and a similar endocarditis prevalence but higher mortality than industrialised countries. S. aureus bacteraemia is frequently associated with exposure to healthcare settings with MRSA causing a considerable burden of disease. Further studies are required to define setting-specific strategies to reduce mortality from S. aureus bacteraemia, prevent MRSA transmission, and to define the burden of S. aureus disease and emergence of drug resistance throughout the developing world. © 2009 Nickerson et al

<i>S. aureus</i> attributable deaths occur more rapidly than non-attributable deaths.

<p>Kaplan-Meier survival curves comparing <i>S. aureus</i> attributable deaths and non-attributable deaths (p = 0.001).</p

Impact of MRSA on effective antibiotic prescribing.

*1<p>MSSA, methicillin-susceptible <i>S. aureus</i>; MRSA, methicillin-resistant <i>S. aureus</i>.</p>*2<p>p value comparing MSSA and MRSA groups.</p>*3<p>Optimal therapy defined as cloxacillin for MSSA infection and vancomycin for MRSA infection. Alternative therapy used included ceftriaxone, cefazolin, cefoxitin, ceftazidime, augmentin and ampicillin combined with gentamicin.</p>*4<p>Denominator is patients who survived to day of culture result. A total of 25 patients (21 with MSSA and 4 with MRSA) died or were discharged moribund prior to culture results becoming available.</p

The burden of S. aureus bacteraemia is highest at the extremes of age, whilst mortality increased with age.

<p>Age distribution and age-specific mortality rates and disease burden for 98 cases of <i>S. aureus</i> bacteraemia studied in Ubon Ratchathani, NE Thailand. Overall mortality increased significantly with age (p<0.001), analysing age as a continuous variable.</p

Antibiotic resistance rates for infecting isolates.

*1<p>MSSA, methicillin-susceptible <i>S. aureus</i>; MRSA, methicillin-resistant <i>S. aureus</i>.</p

Patient characteristics.

*1<p>Two patients were from Lao PDR.</p>*2<p>History of any underlying chronic medical condition documented in the medical notes.</p>*3<p>Immunosuppression from chemotherapy (n = 4), untreated leukaemia (n = 1), HIV (n = 3, none of whom were on anti-retroviral therapy or any prophylactic antibiotics) or immunosuppressive medication including prednisolone >30 mg/day for >1 week (n = 4; one of these additionally on chemotherapy).</p>*4<p>Denominator is number of sites (n = 73) since some patients had >1 site of infection.</p>*5<p>Intravenous catheters (central n = 3, peripheral n = 2, umbilical n = 1), pacemakers (n = 3) and arteriovenous graft (n = 1).</p>*6<p>Vegetations on transthoracic echocardiography (n = 7); or strong clinical evidence in intravenous drug user (n = 1).</p>*7<p>Following mitral valve replacement (n = 3), or coronary artery bypass graft (n = 1).</p>*8<p>Empyema (n = 2), septic emboli to the lungs (n = 1), lung abscesses (n = 1).</p>*9<p>Liver (n = 2), spleen (n = 1).</p

Survival from <i>S. aureus</i> bacteraemia is worse in adults than in children.

<p>Kaplan-Meier survival curves comparing adult and paediatric patients with respect to <i>S. aureus</i> attributable deaths (p = 0.01). Non-attributable deaths were censored.</p