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[Pharmacokinetics and clinical efficacy of imipenem/cilastatin sodium in neonates]
S Azagami1, Y Kusumoto, T Oikawa
1Department of Pediatrics, School of Medicine, Keio University.
Insights
Imipenem/cilastatin sodium (IPM/CS) is effective and safe for treating severe neonatal bacterial infections. This antibiotic combination demonstrated good clinical responses and manageable side effects in newborns.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Infectious Diseases
Background:
- Imipenem/cilastatin sodium (IPM/CS) is a broad-spectrum beta-lactam antibiotic combined with a dehydropeptidase-I inhibitor.
- Its clinical pharmacology, efficacy, and safety in newborns require thorough investigation due to unique physiological differences.
Observation:
- Peak serum concentrations and mean serum half-lives of imipenem (IPM) and cilastatin (CS) were determined in neonates and premature infants at different age groups.
- A dose-response relationship was observed between 10 mg/10 mg/kg and 20 mg/20 mg/kg doses.
- Urinary recovery rates for both IPM and CS were quantified.
Findings:
- IPM/CS achieved therapeutic serum levels with dose-dependent pharmacokinetics in neonates.
- Clinical efficacy was observed in 7 out of 9 patients with excellent or good responses.
- Adverse reactions, including hematuria, leukopenia, thrombocytopenia, and eosinophilia, were transient and resolved post-treatment.
Implications:
- IPM/CS demonstrates significant utility in treating severe bacterial infections in neonates, particularly those caused by beta-lactamase resistant strains or polymicrobial infections.
- The favorable safety profile and efficacy support the use of IPM/CS in neonatal intensive care settings.
- Further research may refine dosing strategies for optimal outcomes in diverse neonatal populations.
Abstract:
Clinical pharmacology and clinical efficacy and safety of imipenem/cilastatin sodium (IPM/CS), a beta-lactam antibiotic with a carbapenem nucleus and a dehydropeptidase-I inhibitor, were investigated in newborns. 1. Peak serum concentrations of IPM/CS at a dose of 20 mg/20 mg/kg were achieved at the end of 60-minute infusion. Maximum serum levels of IPM and CS were 44.2 micrograms/ml and 70.0 micrograms/ml, respectively, in neonates with ages 0-3 days. IPM and CS peak levels in premature infants with ages 0-3 days were 47.2 micrograms/ml and 56.1 micrograms/ml, respectively. IPM and CS peak levels in neonates 4 day-old or older were 35.0 micrograms/ml and 41.5 micrograms/ml, respectively, and in premature infants of similar ages were 45.7 micrograms/ml and 65.3 micrograms/ml, respectively. 2. Mean serum half-lives of IPM and CS in 0-3 day-old neonates were 1.6 hours and 3.1 hours, respectively, and the mean serum half-lives in premature infants were 2.1 hours and 4.6 hours, respectively. In neonates 4 day-old or older, the mean serum half-lives of IPM and CS were 1.6 hours and 2.6 hours, respectively, and in premature infants they were 1.5 hours and 1.9 hours, respectively. 3. A dose response was evident between doses of 10 mg/10 mg/kg and 20 mg/20 mg/kg of IPM and CS. 4. Urinary recovery rates of IPM for the 0- to 6-hour post IPM/CS infusion period ranged between 27.2 and 46.6%. For CS, urinary recovery rates for the 0- to 6-hour post IPM/CS infusion period ranged between 25.3 and 100.8%. 5. Clinical efficacy was evaluated in 9 patients and 7 patients showed excellent or good responses. 6. Of 14 patients who received IPM/CS treatment, 1 patient showed hematuria, leukopenia and thrombocytopenia, and 3 patients showed eosinophilia. However, these adverse reactions improved after the completion of therapy. 7. IPM has excellent antimicrobial activity against aerobic and anaerobic Gram-positive and Gram-negative bacteria. In this study, coadministration of IPM and CS produced good clinical responses and no serious adverse reactions. It is hence concluded that IPM/CS sodium is very useful for the treatment of severe bacterial infections in neonates, especially in the presence of beta-lactamase resistant strains and in polymicrobial infections.