Tatebe et al. used JMDC’s database to analyze the relationship between hypoglycemia and pivalateconjugated antibiotics in pediatric patients aged between 1 month and 5 years during the period January
2011 to December 2013.7 In this study, 454,153 consultations in the group prescribed pivalate-conjugated
antibiotics were analyzed, along with 417,287 consultations of pediatric patients prescribed another
antimicrobial. Hypoglycemia was diagnosed in 3,356 consultations (0.74% [0.71-0.76]) and 2,605
consultations (0.62% [0.60-0.65]), respectively. Multivariate logistic regression analysis revealed that the
odds of developing hypoglycemia in the pivalate-conjugated antibiotics group were 1.19 [1.13-1.25] times
higher than in the group prescribed other antimicrobials (Table 87). The adjusted odds ratios for
hypoglycemia risk were 1.17 [1.11-1.24] within 7 days of administration, 1.22 [1.05-1.41] within 8-14 days
of administration, and 1.57 [0.90-2.69] 15 days or more after administration.
Table 87 Results of multivariate analysis for risk factors associated with hypoglycemia
Reference

Odds ratio
(95% confidence
interval)

Adjusted odds ratio
(95% confidence
interval)

p-value

Control group

1.19 (1.13-1.25)

1.18 (1.12-1.24)

<0.001

Female

1.14 (1.08-1.20)

1.14 (1.08-1.20)

<0.001

1-2 years

Infants

1.00 (0.90-1.12)

1.00 (0.96-1.10)

0.938

3-4 years

Infants

1.37 (1.23-1.53)

1.36 (1.22-1.52)

<0.001

5 years and older

Infants

1.32 (1.18-1.49)

1.31 (1.17-1.48)

<0.001

Variable
Antimicrobial
Administration of
pivalate-conjugated
antibiotics
Sex
Male
Age

Number of days drug supplied
8-14 days

Up to 7 days

1.05 (0.97-1.13)

1.06 (0.98-1.15)

0.132

15 days or more

Up to 7 days

0.93 (0.71-1.20)

0.96 (0.75-1.28)

0.623

[Summary]
Respiratory tract infections in both children and adults are an important target for antimicrobial
stewardship. The usage of third-generation cephalosporins and macrolides in children and adults alike
stands out, along with usage of fluoroquinolones in adults, suggesting that efforts to reduce the use of these
antimicrobials are required. Two reports have been published that consider the effects of political measures
on antimicrobial stewardship; these studies will be important when deciding on future policies. Ongoing
investigation will be required, as the age range to which the pediatric outpatient antimicrobial stewardship
fee has been extended upward. Furthermore, a report was published on a large study of the risk of
hypoglycemia from pivalate-conjugated antibiotics. Most third-generation cephalosporins typically used in
Japan contain pivalate-conjugated antibiotics and ascertaining their side-effects is an issue closely related
to supporting stewardship. Further research focused on antimicrobial side-effects would be desirable.

76