Activity of quinupristin/dalfopristin and its components against Haemophilus influenzae

Abstract

Quinupristin/dalfopristin is an injectable streptogramin antibiotic that is constituted in a 30:70 (w/w) ratio of the two components. Quinupristin and dalfopristin are thought to act synergically by binding to two separate sites on the bacterial 50S ribosomal subunit. The in-vitro activities of the two components separately and together in different ratios were determined for a collection of 100 Haemophilus influenzae strains representing various antimicrobial resistance phenotypes. The NCCLS microdilution susceptibility testing procedure incorporating Haemophilus test medium (HTM) broth was used to determine MICs of quinupristin, dalfopristin and seven other antimicrobial agents. The MIC50 and MIC90 values were 4 and 8, 4 and 16, and 64 and 128 mg/L for quinupristin/dalfopristin (30:70), dalfopristin and quinupristin, respectively. MICs of quinupristin and dalfopristin were also determined in Mueller-Hinton lysed horse blood broth and by HTM agar dilution testing. Compared with HTM broth-derived results, the MICs of quinupristin/dalfopristin and its components were the same or one dilution higher in lysed horse blood and HTM agar incubated in air, and were equivalent or one dilution lower in HTM agar incubated in a CO2 atmosphere. The MICs of quinupristin and dalfopristin separately or together were directly proportional to erythromycin MICs, but were otherwise unaffected by any of the resistance mechanisms represented in these strains. MICs of quinupristin and dalfopristin combined in ratios of 10:90, 70:30 and 90:10 did not differ significantly from those of the 30:70 ratio. Thus, unlike the synergic activity noted against Gram-positive bacteria, the activity of quinupristin/dalfopristin against H. influenzae appears to be due almost entirely to the dalfopristin component of the combination.