2031. Efficacy of Tedizolid in Experimental Myonecrosis caused by Erythromycin/Clindamycin-Sensitive and -Resistant Group A Streptococcus
Session: Poster Abstract Session: Antimicrobial Resistant Infections: Treatment
Saturday, October 29, 2016
Room: Poster Hall
Background: Resistance to clindamycin (ClinR) and erythromycin (ErmR) is increasing in group A streptococcal (GAS) strains causing invasive disease and other protein synthesis inhibitor antibiotics are urgently needed. Tedizolid (Tzd) is a newer oxazolidinone with improved potency and safety over the first drug in this class, linezolid (Lzd). We compared Tzd and Lzd efficacy in experimental murine myonecrosis caused by ErmS/ClinS and ErmR/ClinR GAS.

Methods: Adult female Swiss Webster outbred mice (10/group) were infected intramuscularly with 109, 108 or 107 ErmS/ClinS GAS (ATCC 12384; M-type 3) or an ErmR/ClinR GAS from invasive human infection (VA15-003; emm type 1, ermB+). Treatments began 4 h post-infection and continued for 72 h. Saline, penicillin (Pen), Clin and Erm were given q 6 h. Tzd and Lzd (40, 20,10 mg/kg) were given q 12 h. Survival was followed for 14 d; mice were scored daily from 0-4 for severity of local infection or systemic illness.

Results: Both GAS strains were sensitive to Pen, Lzd and Tzd. ErmR/ClinR was confirmed for GAS 15-003. Blood levels of Lzd40 and Tzd40 were 30.9 ± 4.0 and 21.9 ± 5.3 ug/mL, respectively. ErmS/ClinS GAS Infection: Without treatment, ≥107 GAS was rapidly lethal. Clin and Erm significantly improved 14-d survival (60–100%). Pen was protective (90% survival) only at the 108 or 107 infection doses. Tzd and Lzd significantly delayed mortality, but 90-100% of Lzd-treated mice ultimately succumbed to 109 GAS whereas Tzd was protective. ErmR/ClinR GAS Infection: ≥108 GAS was 100% lethal in saline-, Clin- and Erm-treated mice by 50 h; 107 GAS was not uniformly lethal and was not studied further. Lzd significantly delayed mortality, but protection (50% survival) was afforded only to mice infected with 108 GAS who received Lzd40. Survivals of Tzd40, 20, 10-treated mice infected with 109 or 108 GAS were 30-70% and 80%, respectively, while 90% of all Pen-treated mice survived. The 14-d mean infection severity scores in Pen- vs Tzd40-treated mice infected with 108 GAS were .46 vs 1.98.

Conclusion: Tzd is markedly superior to Lzd for the treatment of experimental GAS myonecrosis, including that caused by ErmR/ClinR GAS. Penicillin’s unexpected efficacy against ErmR/ClinR GAS requires further study but may be related to strain-specific differences in exotoxin profile or penicillin-binding protein expression.

Amy Bryant, PhD, Michael Aldape, PhD, Clifford Bayer, BS, Eric Mcindoo, BS and Dennis Stevens, MD, PhD, Infectious Diseases, Veterans Affairs Medical Center, Boise, ID


A. Bryant, Merck & Co.: Grant Investigator , Research grant

M. Aldape, None

C. Bayer, None

E. Mcindoo, None

D. Stevens, None

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