Risk of hypoglycemia induced by pivalate-conjugated antibiotics in young children: A population-based retrospective study in Japan

Infection is a common cause for an outpatient visit for young children. Pivalate-conjugated antibiotics (PCAs) are often used for these patients in Japan. However, a few case reports have shown that PCAs can provoke hypoglycemia in children, but no larger study has shown that PCAs increase the risk of hypoglycemia. The current study was performed as a retrospective review of children aged 1 month to 5 years old with at least once prescription of PCAs or other beta-lactam antibiotics from January 2011 to December 2013, using a medical and pharmacy claims database. Hypoglycemia was defined based on the International Statistical Classification of Diseases and Related Health Problems 10th Revision code or prescription of 10% or 20% glucose injection, and the incidence of hypoglycemic events was investigated. Logistic regression analysis was performed to examine the risk of hypoglycemia with PCAs compared with control antibiotics. The study cohort contained 179,594 eligible patients (male: 52.2%, mean age: 3.2 years). The numbers of prescriptions were 454,153 and 417,287 for PCAs and control antibiotics, respectively. Multivariate analysis showed that PCAs were associated with hypoglycemia (adjusted OR 1.18, 95% CI 1.12 to 1.24, P < 0.01), and the risk of hypoglycemia was also significantly increased with use of PCAs for ≤7 days (adjusted OR 1.17, 95% CI 1.11 to 1.24, P < 0.01). These results suggest that prescription of PCAs to young children should be avoided, even for a short time period.