Carboxyamidotriazole

Establishing the precise epidemiology of antimicrobial use (AMU) is essential to promote antimicrobial stewardship. However, data on AMU for pediatric inpatients in Japanese hospitals are lacking. In this study, we performed a subgroup analysis focusing on pediatric patients from a point prevalence survey.

A multicenter point prevalence survey was conducted in Aichi Prefecture in 2020. This subgroup analysis included pediatric patients (≦18 years old) and assessed AMU and their indications: community-acquired infections (CAIs), healthcare-associated infections (HAIs), medical prophylaxis (MP), and surgical prophylaxis (SP). Details of infections and interventions by the antimicrobial stewardship teams (AST) were also surveyed.

Of the 736 patients from 23 hospitals included in this study, 241 patients (32.7 %, 95 % confidence interval [95 % CI]: 29.4-36.3) received a total of 399 antimicrobials. The prevalence of HAI was 6.0 % (95 % CI: 4.4-7.9). The number of antimicrobials administered per 100 patients ranged from 24.1 in small hospitals to 109.6 in university hospitals. CAI treatment was the most common indication in community hospitals, SP in specific centers, and MP in university hospitals. The most commonly prescribed antimicrobials were cefotaxime for CAI, meropenem for HAI, trimethoprim-sulfamethoxazole for MP, and cefazolin for SP. A total of 78 CAIs and 46 HAIs were identified, with AST intervention rates of 2.5 % and 34.8 %, respectively.

This subgroup analysis provides the first demographic data on AMU among pediatric inpatients at Japanese hospitals. The distinct distribution of AMU suggests that different approaches are necessary to promote antimicrobial stewardship in hospital settings.

The HIV-1 capsid protein (CA) is essential for viral replication and serves as a validated antiviral drug target. Traditional purification of CA relies on multi-step chromatographic protocols, which are time-consuming and labor-intensive. In this study, we established a rapid, column-free purification strategy using a cleavable self-aggregating tag (cSAT) to produce functional wild-type CA protein from E. coli with >95 % purity within a single day. The workflow is compatible with high-throughput formats and scalable from microplates to fermenters, offering significant advantages over conventional purification methods. The purified CA retained full biological activity, as demonstrated by its ability to assemble into higher-order structures in a salt- and protein concentration-dependent manner in vitro. We further evaluated the effects of two well-characterized capsid modulators: CAI, a peptide inhibitor, and lenacapavir (LEN), a clinically approved capsid-targeting drug. Turbidity-based assembly assays confirmed that CAI inhibited and LEN enhanced CA assembly in a dose-dependent manner. When co-administered, CAI and LEN exhibited mutually antagonistic effects. Preincubation with CAI abolished LEN-mediated enhancement, indicating a potential conformational lock imposed by CAI. These findings demonstrate that the column-free strategy enables efficient production of functionally active CA protein suitable for downstream biochemical and inhibitor screening assays. The approach provides a practical tool for accelerating HIV-1 capsid research and antiviral discovery.