Toshihiro Matsui

Background: Aeromonas species can cause bacteremia, but their epidemiology and clinical significance in pediatric liver transplant (LT) recipients are unclear. We evaluated the incidence, clinical features, management, and outcomes of Aeromonas bacteremia in this population. Methods: We performed a retrospective observational study at a tertiary pediatric LT center from November 2005 to April 2023. Patients who underwent LT before 18 years of age were reviewed, and cases of Aeromonas bacteremia were analyzed in detail. Results: Among 746 children who underwent LT, five episodes of Aeromonas bacteremia were identified. The incidence was 0.82 cases per 1000 person‐years. Median age at LT was 2 years, and median interval from LT to bacteremia was 6 years (range, 2 months–24 years). All patients were receiving maintenance immunosuppression without neutropenia or significant liver dysfunction, and none were receiving antibiotics, including trimethoprim–sulfamethoxazole prophylaxis at the time of Aeromonas bacteremia. No patient had recent hepatobiliary procedures or biliary obstruction. All presented with fever; three had fever without source, and three reported freshwater exposure. Blood cultures yielded A. hydrophila / caviae ( n = 3) or A. sobria (currently A. veronii biovar sobria) ( n = 2). All isolates were susceptible to the empiric antibiotic regimens. Definitive therapy consisted of cefotaxime or cefepime, with or without metronidazole. All patients survived without progression to life‐threatening sepsis or relapse. Conclusions: In pediatric LT recipients, Aeromonas bacteremia can occur late after transplantation under mild immunosuppression and without recognizable biliary risk factors. Early recognition and appropriate antibiotic therapy may contribute to favorable outcomes.

Summary: Since 2023, macrolide-resistant Bordetella pertussis (MRBP) has surged worldwide. Six infants aged <2 months completed a 14-day course of trimethoprim-sulfamethoxazole for suspected MRBP infection without significant adverse events. Trimethoprim-sulfamethoxazole may be a tolerable option in infants in MRBP-dominant settings.

Background.: Valganciclovir (VGCV) is the first-line therapeutic agent for cytomegalovirus (CMV) infection following pediatric liver transplantation (LT). The dosage for pediatric patients is either determined by body weight (BW dose) or body surface area (BSA) and renal function (7 × BSA [m ² ] × creatinine clearance (CrCl) [mL/min/1.73 m ² ]) (BSA dose). However, the optimal dosing strategy for achieving target drug exposure for CMV treatment remains unclear. Methods.: We conducted a prospective pharmacokinetic study in pediatric LT patients. The area under the concentration-time curve (AUC _0–24 ) was estimated using previously reported pediatric population pharmacokinetic parameters. An AUC _0–24 of 80–120 µg·h/mL was defined as the therapeutic target. The primary endpoint was to compare the achievement rate of target AUC between BW and BSA doses. Although BW dose is the standard at our institution, a hypothetical BSA dose was estimated proportionally for comparison with BW dose. Results.: Fourteen patients with a median age of 1.1 y were included. The median VGCV dose was 15.3 mg/kg, whereas the hypothetical median BSA dose was 24.5 mg/kg. The estimated AUC _0–24 in BW and BSA dose groups were as follows: 120 µg·h/mL, 0.0% and 21.4% ( P = 0.027). There was a negative correlation between AUC _0–24 and the duration of CMV viremia, indicating that higher AUC values were associated with faster viral clearance (ρ = −0.72, P = 0.003). Conclusions.: Based on our estimation, BSA dosing may be more likely to achieve the target AUC _0–24 compared with BW dosing in infant/toddler LT recipients. Higher AUC values correlated with faster viral clearance.

In 2022–23, several European countries reported paediatric acute liver failure (ALF) with enterovirus infection. In August–November 2024, three neonatal cases of ALF with echovirus 11 (E11) were reported in Tokyo, Japan. All neonates developed irreversible multiple-organ failure and died. The E11 strain belonged to the new lineage 1, which was the same as strains isolated from neonatal ALF cases in Europe in 2022–23.

Voriconazole pharmacokinetics (PK) are known to be affected by genetic polymorphisms of drug-metabolizing enzymes such as CYP2C19; however, such information is limited for the pediatric population. This was a single-center population PK study. Information regarding patient background, laboratory test data, voriconazole serum concentration, voriconazole dosing status, and concurrent medications were extracted from electronic medical records. CYP2C19 genotypes was assessed by whole genome genotyping and defined as follows: *1/*1, *1/*17: normal metabolizer [NM], *1/*2, *1/*3: intermediate metabolizer [IM], and *2/*2, *2/*3, *3/*3: poor metabolizer [PM]. Population PK analysis was performed using Phoenix NLME (v8.3.0). The voriconazole serum concentration profile was described by a two-compartment model with first-order absorption, mixed linear and nonlinear (Michaelis-Menten) elimination, and allometric scaling, as described in previous reports. Covariates were examined using a stepwise method and included to the model when the objective function [-2LL (log-likelihood)] by the maximum likelihood method decreased significantly (Δ-2LL > 6.63, p < 0.01 by likelihood ratio test). Voriconazole concentration data were available from 60 patients with a median age of 5.3 years. In total, 526 measurements were available for population PK analysis. The phenotypes predicted from CYP2C19 genotypes were NM in 22 patients, IM in 27 patients, and PM in 11 patients. Underlying diseases included 40 patients with malignancy (66.7%), 18 patients with inborn errors of immunity (30.0%), and 2 patients with other comorbidities. Among the CYP2C19 phenotypes, PM was predicted to show complete inhibition (the degree of Vmax inhibition (Vmax,inh) = 100%; Vmax= 0). The estimated parameters of Vmax,inh were +0.8 higher in patients with γ-GTP Grade 2 or higher compared with those with Grade 1 or lower. The increase in Vmax,inh was shown to be caused by an increase in C-reactive protein (CRP); the estimated parameters of Vmax,inh were +2.7 higher when CRP was 2.0 mg/dL or higher. CYP2C19 genetic polymorphisms (PM), γ-GTP, and CRP affect Vmax,inh of voriconazole in Japanese children with malignancy or inborn errors in immunity Kensuke Shoji, MD, PhD, AstraZeneca K.K.: Honoraria|Gilead Sciences, Inc.: Honoraria|KYORIN Pharmaceutical Co.,Ltd.: Honoraria|Meiji Seika Pharma Co., Ltd.: Honoraria|Nippon Becton Dickinson Company, Ltd.: Honoraria|Novartis Pharma Co., Ltd.: Honoraria|Viatrs, Inc: Honoraria Motohiro Kato, MD, PhD, Amgen: Honoraria|Bayer: Honoraria|Chugai Pharm: Honoraria|CSL Behring: Honoraria|Daiichi Sankyo: Grant/Research Support|Konica Minolta REALM: Honoraria|Kyowa KIRIN: Honoraria|Maruho: Honoraria|Nippon Shinyaku: Honoraria|Novartis: Honoraria|Ohara Pharma: Honoraria|Riken Genesis: Honoraria|Sanofi: Honoraria|Sumitomo Pharma: Honoraria|Takeda Pharma: Honoraria Toshinao Kawai, MD, PhD, Novartis Pharmaceuticals: Honoraria|Takeda Pharmaceutical Company: Advisor/Consultant|Takeda Pharmaceutical Company: Honoraria Hidefumi Nakamura, MD, PhD, Asahi Kasei Corporation: Stocks/Bonds|Bristol Myers Squibb Company: Honoraria|Chugai Pharmaceutical Co., Ltd.: Honoraria|Daiichi Sankyo Company, Ltd.: Advisor/Consultant|Pfizer Global Supply Japan Inc.: Advisor/Consultant|Pfizer R&D Japan G.K.: Advisor/Consultant|Sato Pharmaceutical Co., Ltd.: Advisor/Consultant|Shionogi & Co., Ltd.: Honoraria|Taisho Pharmaceutical Holdings Co., Ltd: Advisor/Consultant Isao Miyairi, MD, PhD, Astrazeneca: Honoraria|Mitsubishi-Tanabe: Honoraria|Pfeizer: Honoraria|Sanofi: Advisor/Consultant|Shionogi: Honoraria Taisei Mushiroda, PhD, Zenyaku Kogyo Company, Limited: Grant/Research Support

Osteomyelitis in childhood is often hematogenous and neonates are generally prone to bacteremia because of immature immunity. Neonatal osteomyelitis occurs even in the absence of apparent immunological or perinatal abnormalities.