Severity of invasive pneumococcal disease in children caused by susceptible and nonsusceptible isolates.

Abstract

To the Editors: In the post-pneumococcal conjugate vaccine era, there has been an increase in nonvaccine serotypes causing invasive pneumococcal disease (IPD), including penicillin nonsusceptible Streptococcus pneumoniae (PNSP). The prevalence of PNSP causing IPD is increasing,1 and antimicrobial resistance of these isolates has been hypothesized to provide a survival advantage.2 Multidrug-resistant strains have also been associated with a 500% increase in cases of acute mastoiditis, and such cases were more likely to present with subperiosteal abscess and to require intraoperative mastoidectomy.3 We hypothesized that PNSP may also correlate with increased severity of IPD. We analyzed data of childhood IPD in Massachusetts that was based on state laboratory surveillance data from 2007 to 2012. Outcomes compared were characteristics of IPD, including patient demographics, clinical features, microbiologic features and comorbidities. A case of IPD was defined by a positive culture for S. pneumoniae from a normally sterile site. Penicillin intermediate and resistant isolates, based on current Clinical Laboratory Standards Institute breakpoints, were grouped as PNSP. We compared outcomes of PNSP cases with cases caused by penicillin-susceptible S. pneumoniae (PSSP). Patient characteristics were compared using the Fisher’s Exact test for categorical variables, and the Wilcoxon or Kruskal–Wallis test for continuous variables. This study was approved by the Institutional Review Boards of the University of Minnesota and the Massachusetts Department of Public Health. There were 253 cases of IPD from 2007 to 2012 in Massachusetts children ≤5 years of age. Penicillin susceptibility results were available for 239 of 253 isolates (94.5%): 183 were PSSP (76.6%) and 56 were PNSP (23.4%). Of these, 56.4% of patients with IPD caused by PSSP were hospitalized compared with 56.6% of patients with IPD caused by PNSP (P = 1.000). Length of hospitalization was a median of 1 day (range 0–42 days) for PSSP IPD cases, compared with a median of 2 days (range 0–14 days) for PNSP IPD cases (P = 0.931). There was also no difference in comorbidity (P = 0.46), mortality (P = 0.69), the number of cases who were readmitted (P = 0.44) or who were up-to-date on pneumococcal immunization (P = 0.35), between the 2 groups. Our analysis supports that children with IPD because of PNSP have similar outcomes to cases caused by PSSP. This is similar to findings in other studies where there was no difference in clinical presentation and outcome between patients with PSSP and PNSP isolates.4 In addition, neither comorbidity nor pneumococcal conjugate vaccine immunization appear to be risk factors for invasive disease caused by a PNSP isolate. Although our study is limited by missing data within the cohorts, our study’s strength is that it is based on statewide, population-based data that suggest that IPD outcome is not associated with penicillin susceptibility. ACKNOWLEDGMENTS The authors thank Massachusetts Department of Health laboratory and epidemiology staff for their work in compiling data for this study. The authors thank the laboratory staff in Stephen Pelton’s lab for providing antimicrobial susceptibility data. The authors also thank Molly Crockett, MPH, Noelle Cocoros, DSc, MPH, and Kerry O’Brien, MPH, for their assistance on data collection for this project and Michael J O’Connell and Philippe Gaillaird, PhD, for their assistance with statistical analysis. Pui-Ying Iroh Tam, MD Brandon Coombes, MS University of Minnesota, Minneapolis, MN Lawrence Madoff, MD Massachusetts Department of Public Health, Boston, MA Stephen I. Pelton, MD University of Minnesota, Minneapolis, MN