Sameer S. Kadria, Ahmed Babikerb c, Yi Ling Laid, Xiaobai Lie, Sadia Hussaina f, Jeffrey R. Stricha, John P. Dekkerg, Robert L. Dannera
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Clindamycin demonstrates anti-toxin effects and its cidality, unlike b-lactams, is independent of bacterial load and growth kinetics. Clindamycin has been strongly recommended as an adjunct to b-lactams in severe invasive Group A streptococcal (GAS) infections. However, evidence favoring clindamycin is predominantly derived from in vitro and animal studies; clinical studies, limited to single-center series or active surveillance, have yielded mixed results. Clinical characteristics, in vitro susceptibility and antibiotic therapy were examined for unique inpatient encounters with GAS bacteremia in the Cerner Healthfacts Database. All b-lactam treated cases that received clindamycin were matched 1:1 to non-clindamycin cases using nearest neighbor propensity matching and adjusted for residual confounding with logistic regression. Adjusted Odds Ratios (aOR) of in-hospital mortality were calculated for all matched pairs as well as for subsets with median baseline SOFA score ≤2 and >2 respectively (sensitivity analysis). Of 1152 inpatients with GAS bacteremia at 134 hospitals between 2000 and 2014, 388 (34%) received adjunctive clindamycin. The prevalence of clindamycin resistance among GAS bloodstream isolates was 5%. Clindamycin use in GAS bacteremia increased over time. Compared with non-clindamycin counterparts, clindamycin recipients were younger, had lower comorbidity indices, greater ICU use and comparable median SOFA scores. Propensity matching yielded 356 case-pairs with good covariate balance. Mortality between matched pairs was not significantly different (13% clindamycin vs. 17% non-clindamycin; P = 0.14; aOR 0.66 [0.40, 1.10]). The aOR of mortality for subsets with a median SOFA score ≤2 was 0.53 [0.17, 1.62] and >2 was 0.59 [0.33, 1.06] respectively. A third of patients with GAS bacteremia receive adjunctive clindamycin. Our study was unable to demonstrate statistically significant survival benefit of adjunctive clindamycin in GAS bacteremia. Notably, survival benefit approached significance in the subgroup of patients with worse baseline acute organ failure. Larger cohorts that encompass bacteremic and non-bacteremic severe invasive GAS infections warrant further study All authors: No reported disclosures.
