Pediatr Infect Dis J. 2024 Oct 10. doi: 10.1097/INF.0000000000004582. Online ahead of print.
ABSTRACT
BACKGROUND: Rates of carbapenem-resistant Acinetobacter baumannii are rising in Thailand. Although high-dose (HD) sulbactam is recommended for treating carbapenem-resistant A. baumannii infections, data on plasma sulbactam concentrations in children are limited. We aimed to evaluate plasma sulbactam concentrations and pharmacokinetic-pharmacodynamic (PK-PD) target achievement in pediatric patients.
METHODS: Prospective study data (January-November 2023) on children (1 month-18 years) who received sulbactam every 6-8 hours were analyzed. Mid-dosing (Cmid, 50% fT) and trough (Ctrough, 100% fT) concentrations were evaluated. PK-PD target achievement [50% fT > minimum inhibitory concentration (MIC), 100% fT > MIC] was evaluated using Clinical and Laboratory Standards Institute 2024 MIC cutoffs and MIC data of isolates of Acinetobacter calcoaceticus-baumannii complex from this study.
RESULTS: Thirty-five patients (median age 50 months) were categorized into standard-dose (SD) or HD groups. The geometric mean Cmid was higher in the HD (41.3 mg/L) versus SD (19.5 mg/L) groups (P = 0.006). Among 101 isolates of Acinetobacter calcoaceticus-baumannii complex, the MIC50 and MIC90 (concentrations that inhibit 50% and 90% of isolates of the A. calcoaceticus-baumannii complex) were 16 and 128 mg/L, respectively. The HD group achieved Cmid >MIC50 in 87.5% of the patients compared with 63.6% in SD (P = 0.17). Within the HD group, patients with augmented renal clearance (ARC) had lower Cmid (geometric mean 31.9 mg/L) compared with non-ARC (geometric mean 63.4 mg/L) (P = 0.04).
CONCLUSIONS: HD sulbactam resulted in higher Cmid and PK-PD achievement. ARC significantly compromised plasma sulbactam concentration. HD sulbactam may be preferable for treating critically ill pediatric patients and those with ARC, especially during the empirical period.
PMID:39724654 | DOI:10.1097/INF.0000000000004582
