The impact of multidrug resistance in healthcare-associated and nosocomial Gram-negative bacteraemia on mortality and length of stay: cohort study.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging public health threat. Accurate estimates of their clinical impact are vital for justifying interventions directed towards preventing or managing infections caused by these pathogens. A retrospective observational cohort study was conducted between 1 January 2007 and 31 July 2009, involving subjects with healthcare-associated and nosocomial Gram-negative bacteraemia at two large Singaporean hospitals. Outcomes studied were mortality and length of stay post-onset of bacteraemia in survivors (LOS). There were 675 subjects (301 with MDR-GNB) matching study inclusion criteria. On multivariate analysis, multidrug resistance was not associated with 30-day mortality, but it was independently associated with longer LOS in survivors (coefficient, 0.34; 95% CI, 0.21-0.48; p < 0.001). The excess LOS attributable to multidrug resistance after adjustment for confounders was 6.1 days. Other independent risk factors for higher mortality included male gender, higher APACHE II score, higher Charlson comorbidity index, intensive care unit stay and presence of concomitant pneumonia. Concomitant urinary tract infection and admission to a surgical discipline were associated with lower risk of mortality. Appropriate empirical antibiotic therapy was neither associated with 30-day mortality nor LOS, although the study was not powered to assess this covariate adequately. Our study adds to existing evidence that multidrug resistance per se is not associated with higher mortality when effective antibiotics are used for definitive therapy. However, its association with longer hospitalization justifies the use of control efforts.

Economic and clinical impact of nosocomial meticillin-resistant Staphylococcus aureus infections in Singapore: a matched case-control study.

We performed a prospective matched case-control study, with six-month follow-up for discharged subjects, to evaluate the direct clinical and financial impact of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) infections in Singaporean hospitals. Consecutive nosocomial MRSA-infected cases at both tertiary public sector hospitals in Singapore were matched for age, specialty service, major surgical procedure (if applicable) and Charlson comorbidity index with up to two non-infected controls each. Chart reviews and subject interviews were performed during hospitalisation and also upon six months post-discharge for survivors. The outcomes analysed were: mortality, length of hospitalisation (LOS), healthcare-associated financial costs, and health-related quality of life. The last was evaluated via an interviewer-administered EuroQol-5D questionnaire on discharge, with conversion to a single health state summary index. Attributable outcomes were ascertained by conditional logistic and linear regression. There were 181 cases and 351 controls. MRSA infection was independently associated with in-hospital death [14.4% vs 1.4%; odds ratio (OR): 5.54; 95% confidence interval (CI): 1.63-18.79, P=0.006], longer LOS (median of 32 days vs 7 days; coefficient: 1.21; 95% CI: 1.02-1.40, P<0.001), higher hospitalisation costs (median of US$18,129.89 vs US$4,490.47; coefficient: 1.14; 95% CI: 0.93-1.35; P<0.001), higher post-discharge healthcare-associated financial costs (median of US$337.24 vs US$259.29; coefficient: 0.39; 95% CI: 0.06-0.72; P=0.021), and poorer health-related quality of life (coefficient: -0.14; 95% CI: -0.21 to -0.08; P<0.001). Outcomes were not significantly different between both hospitals. The attributable individual, institutional and societal impact of MRSA infections is considerable in Singapore. Preventing such infections will result in substantial improvements in patient outcomes and healthcare delivery.