Multistaie population-based assessment of drug resistant S. pneumoniae mortality

Background: Emergence of drug resistant Streptococcus pneumoniae (SP) has raised concern about the impact of resistance on clinical outcome. We evaluated factors associated with mortality among patients hospitalized with invasive SP infections. Methods: All hospital and reference labs within 9 areas of N. America (pop. 19 million) reported all sterile-she SP isolates from residents during 1995-96. Isolates underwent susceptibility testing by broth microdilution in reference laboratories. The following breakpoints were used: penicillin resistant (R) MIC ≥ 2 μg/ml, intermediate (I) MIC .12-1.2 μg/ml; cefotaxime R MIC ≥ 2 μg/ml, I, MIC 1 μg/ml. We defined underlying illnesses as one previously associated with SP mortality. Nosocomial infections were excluded. Results: Of 4515 invasive SP cases, 534 (11.8%) were fatal. Mortality for meningitis, pneumonia and primary bacteremia by age group were as follows: < 18 years-5.9%, 4.0%, 2.4%; 18-64years-21.4%, 10.0%, 10.5%;>64years-22.9%, 17.5%, 19.8%. Inasubset of patients who had supplemental clinical data, multivariate logistic regression showed that fatal infections were strongly associated with older age, geographic area and underlying illness. Controlling for these variables, the associations between β-lactam susceptibility and mortality are shown. pneumonia (N=896) bacteremia (N=375) adjusted odds ratio (95% confidence intervals) penicillin R (N=57) 4.2(1.7-10) .86(21-3.4) penicillin I (N=93) 1.2 (.56-2.6) 1.5 (.47-5.0) cefotaxime R (N=20) 2.5 (.48-13) undefined cefotaxime I (N=31) 4.0(1.1-14) .89 (.16-5.0) Too few cases of meningitis were available in this subset to analyze. Conclusions: Age, geographic location, underlying illness and clinical pneumococcal syndrome influence mortality from invasive SP disease, β-lactam-nonsusceptible SP strains were associated with increased mortality for pneumonia. However, unmeasured factors like severity of presenting illness may confound the findings. Further studies are needed to determine the impact of drug resistance on clinical outcomes.