133. Ceftriaxone-resistant Haemophilus influenzae in Korean children

BACKGROUND: Haemophilus influenzae is known to develop resistance to β-lactam antibiotics by either producing β-lactamase or modifying structure of penicillin-binding protein 3 (PBP3) by ftsI gene mutation. Since 2017, H. influenzae with ceftriaxone resistance has been continuously appearing in our hospital, and the genotypic characteristics of these strains was analyzed. METHODS: Among a total of 69 H. influenzae isolated from the patients who admitted to Asan Medical Center Children’s Hospital from March 2014 to April 2019, 23 isolates resistant to ceftriaxone by EUCAST disk diffusion method were included. The ceftriaxone MIC was checked again with the E-test and ceftriaxone MIC ≤ 0.125 mg/L were categorized as susceptible. As test for β-lactamase production, the cefinase test and PCR amplification for bla(TEM-1) and bla(ROB-1) were performed. The sequencing of the ftsI encoding PBP3 amplified by PCR was performed, and amino acid sequences were compared with H. influenzae Rd KW20. RESULTS: Among total 23 ceftriaxone-resistant isolates by disk diffusion method, 21 isolates restored for further molecular characterization were included, and 19% (4/21) were reported as susceptible by E-test. Among the 21 ceftriaxone-resistant isolates, 76.2% (16/21) were non-susceptible to amoxicillin/clavulanate, and one of them were resistant to meropenem. The prevalence of b-lactamase-producers was 57.1% (12/21), all of which were positive for bla(TEM-1.) For ftsI gene sequencing, either R517H or N526K amino acid substitution was observed, and none had both. The number of isolates having S385T was 17, of which 15 isolates accompanied with both M377I and L389F. The median ceftriaxone MIC of 3 isolates with only N526K was 0.012 ug/ml (range 0.008-0.125 ug/ml), and 12 isolates with N526K, M377I, S385T, and L389F was 0.19 ug/ml (0.19-0.25 ug/ml). Lastly, the three isolates with R517H, M377I, S385T, and L389F showed the highest median ceftriaxone MIC with 0.25 ug/ml (0.19-0.75 ug/ml). CONCLUSION: Ceftriaxone-resistant H. influenzae isolates in Korea seems to be related to the combination of R517H, M377I, S385T, and L389F by ftsI gene mutation. Although clinical concerns about treatment failure may be low, continuous monitoring of the emergence of highly resistant strains is necessary. DISCLOSURES: All Authors: No reported disclosures.