Importance of appropriate empirical antibiotic therapy for methicillin-resistant Staphylococcus aureus bacteraemia.

OBJECTIVES: To document the effects of appropriate and inappropriate empirical antibiotic therapy on mortality in a cohort of patients with bacteraemia due to methicillin-resistant Staphylococcus aureus (MRSA) and to summarize effects with previous studies. METHODS: In the retrospective cohort study, episodes of clinically significant MRSA bacteraemia during a 15 year period were included. Polymicrobial episodes were excluded unless MRSA was isolated in more than one bottle and co-pathogens were given appropriate empirical antibiotic treatment. Appropriate empirical treatment was defined as matching in vitro susceptibility and started within 48 h of blood-culture taking, except for single aminoglycosides or rifampicin. We assessed univariate and multivariate associations between appropriate empirical therapy and 30 day all-cause mortality. Multivariable analysis was conducted using backward stepwise logistic regression. We reviewed all studies assessing the effects of appropriate empirical antibiotic treatment on mortality for MRSA infections and compiled adjusted odds ratios (ORs) using a random effects meta-analysis. RESULTS: Five hundred and ten episodes of MRSA bacteraemia were included. There were no cases of community-acquired infection. The 30 day mortality was 43.9% (224/510) and was stable throughout the study period. Mortality was significantly higher among patients receiving inappropriate (168/342, 49.1%) compared with those receiving appropriate (56/168, 33.3%) empirical antibiotic treatment, P = 0.001. In the adjusted analysis the OR was 2.15 [95% confidence interval (CI) 1.34-3.46]. Pooling of six studies using adequate methodology for the adjusted analysis resulted in an OR of 1.98 (95% CI 1.62-2.44). CONCLUSIONS: Appropriate empirical antibiotic treatment has a significant survival benefit in MRSA bacteraemia. Treatment guidelines should consider this benefit.

Use of the NOW Streptococcus pneumoniae urinary antigen test in cerebrospinal fluid for rapid diagnosis of pneumococcal meningitis.

Streptococcus pneumoniae is one of the most common pathogens in bacterial meningitis. Rapid diagnosis is critical for effective treatment. The aim of this study was to assess the accuracy of the NOW S. pneumoniae Urinary Antigen Test, (Binax, Portland, ME, USA) originally developed for urine testing, in detecting the S. pneumoniae antigen in cerebrospinal fluid (CSF). The study included 519 patients with suspected meningitis. CSF, blood and urine samples were cultured according to standard methods. CSF viral culture was also performed. CSF and urine specimens were tested for pneumococcal antigen with the NOW S. pneumoniae test.S. pneumoniae was isolated from the CSF of 22 patients. The direct antigen test was positive in CSF in 21/22 patients (95.4% sensitivity), and in urine, in 12/21 (57.1% sensitivity). Direct CSF smear was positive in 15/22 (68% sensitivity). CSF samples that cultured negative for S. pneumoniae (n = 470) or positive for other bacteria (n = 27) were also negative on the NOW test (100% specificity). By contrast, urine samples of 63/470 of patients with negative CSF culture were positive on the NOW test, as were 5/27 urine samples of patients with CSF culture positive for other bacteria (p = 0.45). The NOW S. pneumoniae antigen test in CSF yields a rapid and very reliable diagnosis of pneumococcal meningitis, enabling prompt and adequate treatment. Its low sensitivity in urine indicates that this mode of testing is not useful for the diagnosis of pneumococcal meningitis. These data have been included in the FDA application for approval of the NOW test for use in the CSF for the diagnosis of pneumococcal meningitis.