Antimicrob Agents Chemother. 2016 Jul 11. pii: AAC.00863-16. [Epub ahead of print]
Solithromycin is a fourth generation macrolide with in-vitro activity against multidrug-resistantStreptococcus pneumoniae (SP) and non-typeable Haemophilus influenzae (NTHi).
The objective was to evaluate pharmacokinetics (PK), middle ear fluid (MEF) concentrations, and microbiologic efficacy in a chinchilla model of EOM due to isolates of SP or NTHi.
Plasma PK (Cmax and AUC0-24) and MEF concentrations were determined. Isolates with specified antimicrobial susceptibility patterns were inoculated directly into the middle ear (ME). Plasma and MEF were collected for PK and MEF cultures performed to determine efficacy.
Solithromycin at 150 mg/kg/day resulted in: Cmax and AUC 0-24 of 2.2 μg/mL and 27.4 μg⋅h/mL in plasma and 1.7 μg/mL and 28.2 μg⋅h/mL, in extracellular MEF on day 1. By day 3, Cmax and AUC 0-24 increased to 4.5 μg/mL and 54 μg⋅h/mL in plasma and 4.8 μg/mL and 98.6 μg⋅h/mL in extracellular MEF.For NTHi EOM, three isolates with MIC/MBC [BCH1:0.5/1; 1247: 2/2 and 1213: 4/4 μg/mL] were selected. The MEF of > 85% of animals infected with BCH1 and 1247 was sterilized. For NTHi 1213, > 85% of MEF cultures remained positive. For SP EOM, 3 isolates with MIC/MBC [SP 331: 0.06/0.125; SP CP-645 (MLSB phenotype):0.125/1 and CP-712(mefA subclass mefA resistance): 0.5/2 μg/mL] were selected. Solithromycin sterilized MEF in 100% of animals infected with SP 331 and SP CP-645. ME infection persisted in 60% of animals infected with CP-712.
In a model of EOM, solithromycin sterilized MEF in >85% of animals challenged with NTHi with MIC≤ 2 μg/mL and 100% of ME infected with SP with MIC≤ 0.125 μg/mL.
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