The impact of penicillin resistance on short-term mortality in hospitalized adults with pneumococcal pneumonia: A systematic review and meta-analysis

Background. The clinical impact of penicillin resistance on the outcome of pneumococcal pneumonia has remained controversial. We performed a meta-analysis of prospective cohort studies to examine the association between penicillin resistance and short-term all-cause mortality for pneumococcal pneumonia. Methods. We retrieved studies published in any language by a comprehensive search of the Medline, Current Contents, and Embase databases for all appropriate articles published up to January 2005. We also manually reviewed bibliographies of retrieved articles, recent national treatment guidelines, and review articles. We included prospective cohort studies that involved adult subjects, and we examined the association between penicillin resistance and short-term mortality for pneumococcal pneumonia. Two reviewers independently extracted data on crude and adjusted risk estimates of all-cause mortality for pneumococcal infections with different levels of penicillin resistance and assessed the methodological quality of selected studies. We also contacted authors to obtain additional information. We performed meta-analyses using a random-effect model. Results. Of 1152 articles identified in the search, 10 studies that involved 3430 patients (most of whom were hospitalized) were included. The mortality rate was 19.4% in the penicillin-nonsusceptible Streptococcus pneumoniae group and 15.7% in the penicillin-susceptible S. pneumoniae group. The combined relative risks of all-cause mortality for the penicillin-nonsusceptible, -intermediate, and -resistant S. pneumoniae groups, compared with the penicillin-susceptible S. pneumoniae group, were 1.31 (95% confidence interval [CI], 1.08-1.59), 1.34 (95% CI, 1.13-1.60), and 1.29 (95% CI, 1.01-1.66), respectively. The combined adjusted relative risks of mortality for penicillin-nonsusceptible versus penicillin-susceptible S. pneumoniae group was 1.29 (95% CI, 1.04-1.59) for the 6 studies that adjusted for age, comorbidities, and severity of illness. There was minimal between-study heterogeneity in these analyses. Conclusion. Penicillin resistance is associated with a higher mortality rate than is penicillin susceptibility in hospitalized patients with pneumococcal pneumonia. Additional efforts are needed to understand the mechanisms of this association.