Yoshichika Arakawa

Several studies have reported clinical isolates of Streptococcus mitis, Streptococcus oralis, and their related species (S. mitis/oralis group) with reduced carbapenem susceptibility. However, to date, no simple and accurate methods of detecting S. mitis/oralis group isolates with reduced carbapenem susceptibility have been reported. The meropenem ETEST misinterpreted 3 of 25 (12 %) meropenem-non-susceptible S. mitis/oralis group isolates as susceptible to meropenem. Therefore, we screened 38 disks containing 38 different β-lactams to detect S. mitis/oralis group strains with reduced carbapenem susceptibility using the disk-diffusion method. Additionally, using the agar dilution method to determine susceptibility, we identified the optimal antibiotic concentrations in agar medium to enable selective culture of meropenem-non-susceptible S. mitis/oralis group by culturing 25 meropenem-non-susceptible (meropenem minimum inhibitory concentration [MIC] >0.5 μg/mL) and 24 meropenem-susceptible (meropenem MIC ≤0.5 μg/mL) S. mitis/oralis group isolates on agar containing different concentrations of six β-lactams. Meropenem-susceptible and non-susceptible S. mitis/oralis group isolates were successfully differentiated using oxacillin- and cefoxitin-containing disks. Moreover, cefdinir-, flomoxef-, meropenem-, and doripenem-containing disks showed clear differences in the growth inhibitory zone diameter between the meropenem-susceptible and meropenem-non-susceptible S. mitis/oralis group isolates. Media containing 2 μg/mL oxacillin, 4-16 μg/mL cefoxitin, 2 μg/mL cefdinir, 2-4 μg/mL flomoxef, 0.06-0.25 μg/mL meropenem, and 0.06-0.12 μg/mL doripenem allowed selective culture of meropenem-non-susceptible S. mitis/oralis group strains. The disk-diffusion method using six β-lactam-containing disks and selective culture agar medium are the first-reported simple and accurate methods of detecting meropenem-non-susceptible S. mitis/oralis group suitable for use in clinical microbiology laboratories.

INTRODUCTION: Antimicrobial resistance in Pseudomonas aeruginosa is one of the global health concerns. Like many countries, Japan monitors multidrug-resistant P. aeruginosa (MDRP) infections through a national sentinel surveillance system, which has shown a recent decline in MDRP reports. We evaluated this surveillance system to verify the validity of this trend and explore future directions. METHODS: We conducted a cross-sectional mixed-method study based mainly on the guidelines published by the United States Centers for Disease Control and Prevention in 2001. As a quantitative method, we analyzed characteristics of reports on MDRP infections from designated sentinel sites (DSSs) between 2013-2022. A questionnaire was sent to identifiable DSSs (target DSSs) requesting data on accurate numbers of MDRP infections between 2018-2022 to assess attributes such as geographical representativeness. Additionally, we conducted as a qualitative method face-to-face, semi-structured key informant interviews with surveillance system stakeholders to assess its usefulness and challenges. RESULTS: From 2013 to 2022, 1,666 cases of MDRP infections were reported by 463 target DSSs, which were scattered across the county. We obtained valid responses to the questionnaire survey from 231 target DSSs (49.9%). From 2018 to 2022, these sites reported 277 cases as MDRP infections, while 184 cases were accurate cases of MDRP infection, with both numbers declining over time. False reporting and underreporting of MDRP infections were common, resulting in a positive predictive value of 0.45 and a sensitivity of 0.65 for the reports of MDRP infections to the surveillance system. The interviews highlighted the difficulties in timely detection, accurate reporting, and international data comparison. CONCLUSION: Our evaluation indicated that the current sentinel surveillance system for MDRP infections partially captured the true decreasing trend in Japan. However, as the epidemiology of drug-resistant P. aeruginosa is changing, national policy and surveillance strategies would need to address changing public health needs.

ABSTRACT Streptococcus mitis/oralis group isolates with reduced carbapenem susceptibility have been reported, but its isolation rate in Japan is unknown. We collected 356 clinical α-hemolytic streptococcal isolates and identified 142 of them as S. mitis/oralis using partial sodA sequencing. The rate of meropenem non-susceptibility was 17.6% (25/142). All 25 carbapenem-non-susceptible isolates harbored amino acid substitutions in/near the conserved motifs in PBP1A, PBP2B, and PBP2X. Carbapenem non-susceptibility is common among S. mitis/oralis group isolates in Japan.