368 - New Emergence of Macrolide-Resistant Bordetella pertussis among Children in Japan

Publication Number: 2357.368

Yu Kuramochi, Tokyo Metropolitan Children’s Medical Center, Fuchu City, Tokyo, Japan; Kazue Kinoshita, Tokyo Metropolitan Children’s Medical Center, Fuchu City, Tokyo, Japan; Tomoyuki Tame, Tokyo Metropolitan Children’s Medical Center, Fuchu City, Tokyo, Japan; Meiwa Shibata, Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo, Japan; Hanako Funakoshi, Tokyo Metropolitan Children's Medical Center, Mitaka-shi, Tokyo, Japan; Hiroshi Sakakibara, Tokyo Metropolitan Children's Medical Center, Fuchu-shi, Tokyo, Japan; Osamu Saito, Tokyo Metropolitan children`s medical center, Fuchu, Tokyo, Japan; Yuho Horikoshi, Tokyo metropolitan children's medical center, Fuchu, Tokyo, Japan

Background: Sporadic cases of macrolide-resistant Bordetella pertussis (MRBP) have been reported globally, becoming predominant in China since the 2010s, but remained extremely rare in Japan. Following the COVID-19 pandemic, pertussis resurged worldwide, beginning in late 2024 in Japan. During this resurgence, several MRBP cases were identified; however, their prevalence and clinical characteristics remained unclear.

Objective: To determine the prevalence and clinical features of MRBP among children.

Design/Methods: A retrospective observational study was conducted from January 2024 to October 2025 at Tokyo Metropolitan Children’s Medical Center. Patients aged < 20 years with symptomatic pertussis confirmed by nasopharyngeal PCR and/or culture were included. Duplicate episodes within the same illness were excluded. Demographic, immunization, microbiological, treatment, and outcome data were collected from electronic medical records. Isolates were tested for the 23S rRNA A2047G mutation conferring macrolide resistance. Minimum inhibitory concentrations (MICs) for erythromycin and sulfamethoxazole–trimethoprim (SMX-TMP) were determined using gradient diffusion strips.

Results: Forty-two cases were identified (median age, 6 years; IQR, 2 months–10 years); 64% were male. Thirty (71%) required hospitalization and seven (16%) required PICU admission. Underimmunized patients (0, 1, and 2 doses) comprised 26%, 10%, and 0%, respectively. Among 42 PCR-positive cases, B. pertussis grew in 29/40 (73%) cultures. Confirmation testing for the 23S rRNA A2047G mutation and susceptibility testing ware performed in 28 isolates (one subculture failure). The A2047G mutation was detected in 22/28(79%). Erythromycin MICs were ≤0.016 µg/mL in 6 (21%) and >256 µg/mL in 22 (79%). SMX-TMP MIC was ≤ 0.32 µg/mL for all isolates. Among PICU patients, 57% had positive cultures, all MRBP. Empirical regimens included macrolides (17%), SMX-TMP (45%), macrolide + SMX-TMP (36%), and minocycline + piperacillin (2%). One fatal and one relapsed case occurred, both involving MRBP treated with macrolides or minocycline + piperacillin, respectively.

Conclusion(s): MRBP has newly emerged as the predominant B. pertussis strain among pediatric pertussis cases in Tokyo, including one fatal case of macrolide treatment failure, underscoring the need for continued surveillance and alternative treatment strategies.