Hypoglycemia associated with pivalate-conjugated antibiotics in young children: A retrospective study using a medical and pharmacy claims database in Japan

Acute bacterial infectious diseases are major causes for outpatient visits for young children. Pivalate-conjugated antibiotics (PCAs) are frequently prescribed for these situations in Japan, while several literatures have shown a potential risk of hypoglycemia associated with PCAs. This study aimed to evaluate the incidence of PCA-induced hypoglycemia in children, compared with other oral beta-lactam antibiotics. This retrospective cohort study using a Japanese medical and pharmacy claims database was performed on children aged 1 month to 5 years old with at least once prescription of PCAs or other oral beta-lactam antibiotics from January 2011 to December 2013. Hypoglycemia was defined based on diagnostic codes or the prescription of 10% or 20% glucose injection. We examined the prevalence of hypoglycemic events and performed multivariate analysis to investigate the risk of hypoglycemia with PCAs compared with the control oral beta-lactam antibiotics. We identified 179,594 eligible patients in this population. In the PCA and control groups, there were 454,153 and 417,287 prescriptions and 3356 (0.74%, 95% confidence intervals [CI] 0.71–0.76) and 2605 (0.62%, 95% CI 0.60–0.65) hypoglycemic events, respectively. Multivariate analysis revealed that PCAs were associated with hypoglycemia (adjusted odds ratios [OR] 1.18, 95% CI 1.12–1.24), and even a shorter duration of PCAs prescribing (≤7 days) was significantly associated with hypoglycemia (adjusted OR 1.17, 95% CI 1.11–1.24). These results suggest that in young children PCA use, even for a short period, is a risk factor of hypoglycemia.