Secular trends in incidence of invasive beta-hemolytic streptococci and efficacy of adjunctive therapy in Quebec, Canada, 1996-2016

Objectives To examine secular changes in the incidence of invasive beta-hemolytic streptococcal infections, and to assess the efficacy of immunoglobulins and clindamycin as adjunctive therapies in the management of Streptococcus pyogenes infections. Methods Retrospective cohort study of all cases of invasive group A (GAS), B (GBS), C or G (GCGS) streptococcal infections managed in a Canadian tertiary center from 1996-2016. Population incidence was measured for diabetics and non-diabetics. Adjusted odds ratios (AOR) and their 95% confidence intervals (CI) were calculated by logistic regression. Results 741 cases were identified (GAS: 249; GBS: 304; GCGS: 188). While the incidence of invasive GAS infections fluctuated with no clear trend, incidence of invasive GBS and GCGS increased over time and were 8.4 and 6.3 times higher in diabetics. Mortality of invasive GAS infections decreased from 16% (6/37) in 1996-2001 to 4% (4/97) in 2011-15. Among patients with GAS infections, clindamycin administered concomitantly with a beta-lactam within 24 hours of admission decreased mortality (AOR: 0.04, 95%CI: 0.003-0.55, P= 0.02. Immunoglobulins had no such effect (AOR: 1.66, 95%CI: 0.16-17.36, P= 0.67). The protective effect of clindamycin was similar in patients with pneumonia/empyema compared to all others. Conclusion Incidence of GBS and GCGS infections increased due to an expansion of the high-risk population (elderly diabetics), but also rose in non-diabetics. No such secular change was seen for invasive GAS infections. The decrease in mortality in patients with invasive GAS infections presumably reflects better case-management. Adjunctive clindamycin reduced mortality in invasive GAS infections; immunoglobulins did not, but power was limited. The highest mortality was seen in patients with GAS pneumonia/empyema, for whom clindamycin was protective but underused.