Yoshichika Arakawa

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.

The number and type of metallo-β-lactamase (MΒL) are increasing over time. Carbapenem resistance conferred by MΒL is a significant threat to our antibiotic regimen, and the development of MΒL inhibitors is urgently required to restore carbapenem efficacy. Microbial natural products have served as important sources for developing antimicrobial agents targeting pathogenic bacteria since the discovery of antibiotics in the mid-20th century. MΒL inhibitors derived from microbial natural products are still rare compared to those derived from chemical compound libraries. Hydroxyhexylitaconic acids (HHIAs) produced by members of the genus Aspergillus have potent inhibitory activity against clinically relevant IMP-type MBL. HHIAs may be good lead compounds for the development of MBL inhibitors applicable for controlling carbapenem resistance in IMP-type MBL-producing Enterobacterales .