Monitoring quinolone resistance due to Haemophilus influenzae mutations (2012-17)

Abstract

Among drug-resistant bacteria of recent concern, we determined minimum inhibitory concentrations (MICs) of six different quinolone antibacterial agents in Haemophilus influenzae and performed molecular genetic analysis in addition to the exploration for {beta}-lactamase-producing and {beta}-lactamase negative ampicillin-resistant H. influenzae (BLNAR). A total of 144 clinical H. influenzae strains isolated at the Showa University Hospital between 2012 and 2017 were subjected to MIC determination for penicillin/quinolone antibacterial agents using the nitrocefin method and the Clinical and Laboratory Standards Institute broth microdilution method. Moreover, amino acid mutations in the quinolone resistance-determining regions (QRDRs) were analyzed in the isolates showing MIC value of [≥] 0.25 {micro}g/ml of quinolone antibacterial agents. Increasing proportions of BLNAR were noted, with 15% in 2015 to 43.5% in 2016 and 63.6% in 2017. Among quinolone antibacterial agents, all isolates remained susceptible to sitafloxacin (STFX), and STFX showed strong inhibitory potencies against both DNA gyrase and topoisomerase IV. For moxifloxacin (MXF), however, strains with MIC value of 0.5 {micro}g/ml were detected every year since 2013 except 2015. Amino acid mutations were investigated in 17 isolates (11.8%) with MXF MIC value of [≥]0.25 {micro}g/ml, and confirmed in 11 isolates (7.6%), of which mutations of GyrA were found in 9 isolates. Future antibacterial drug regimens may need to address the emergence of quinolone-resistant H. influenzae.