Duration of Pivalate-conjugated Antibiotics and Blood Glucose Levels Among Pediatric Inpatients: Causal Mediation Analyses and Systematic Review.

Abstract

Several cases of hypoglycemia potentially induced by pivalate-conjugated antibiotics have been reported. However, no observational studies have investigated the associations among children. A retrospective cohort study was conducted on 814 consecutive inpatients < 15 years of age with lower respiratory infections. We investigated whether the duration of lower respiratory symptoms and antibiotic use on blood glucose levels and their mediating/moderating effects using multivariable linear regression models and causal mediation analyses. Additionally, we performed a systematic review of the literature that reported the potential associations between pivalate-conjugated antibiotics and hypoglycemia. Multivariable linear regression models showed that the duration of respiratory symptoms and fever had independent relationships with the reduction in blood glucose levels, whereas duration of pivalate-conjugated antibiotic use did not. Causal mediation analyses found that the controlled direct effects of respiratory symptom duration contributed to the reduction in blood glucose levels, but the mediating/moderating effects through antibiotic use did not. A systematic review of the literature included 7 reports written in English and 14 reports written in Japanese. No reports were observational studies; therefore, we were unable to conduct a meta-analysis. Our study failed to demonstrate an association between duration of pivalate-conjugated antibiotic use and blood glucose levels. Further studies are required to illuminate the relationship.