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[Pharmacokinetic, bacteriological and clinical studies on imipenem/cilastatin sodium in neonates]
Insights
This study shows imipenem/cilastatin sodium (IPM/CS) is effective and safe for treating bacterial infections in neonates, with 100% clinical efficacy. Pharmacokinetic data indicate differences in drug metabolism in neonates compared to adults.
Area of Science:
- Neonatal Medicine
- Infectious Diseases
- Pharmacology
Background:
- Bacterial infections pose significant risks to neonates.
- Imipenem/cilastatin sodium (IPM/CS) is a broad-spectrum antibiotic combination.
- Limited data exist on IPM/CS pharmacokinetics and efficacy in neonates.
Purpose of the Study:
- To evaluate the clinical efficacy and safety of IPM/CS in neonates.
- To assess the bacteriological response to IPM/CS treatment.
- To determine the pharmacokinetic profile of IPM/CS in neonatal populations.
Main Methods:
- Clinical study involving 27 neonates (17 mature, 10 immature) treated with IPM/CS (20 mg/20 mg/kg/dose, 3 times daily).
- Bacteriological evaluation included MIC testing of imipenem against clinical isolates.
- Pharmacokinetic analysis of imipenem (IPM) and cilastatin (CS) serum levels and half-lives.
Main Results:
- 100% clinical efficacy observed in 10 neonates with bacterial infections (sepsis, pneumonia, UTI, omphalitis).
- All 5 identified causative organisms were eradicated.
- Adverse reactions (rash, diarrhea) and transient elevations in liver enzymes (GOT, GPT) were noted in 2 patients.
- Imipenem demonstrated good activity against Streptococcus agalactiae but poor activity against methicillin-resistant Staphylococcus aureus.
- Pharmacokinetic parameters, including peak serum levels and half-lives of IPM and CS, differed between mature and immature neonates and from adult data, with generally longer half-lives in younger infants.
Conclusions:
- IPM/CS is a safe and effective treatment option for bacterial infections in neonates.
- Neonatal pharmacokinetics of IPM/CS differ significantly from those in adults and older children.
- Further research into optimized dosing regimens for neonates may be warranted based on pharmacokinetic findings.
Abstract:
Pharmacokinetic, bacteriological and clinical studies on imipenem/cilastatin sodium (IPM/CS) were performed in neonates. The results were as follow: 1. A total of 27 patients consisting of 17 mature and 10 immature infants were treated with IPM/CS. Each dose was 20 mg/20 mg/kg, and it was administered 2 approximately 3 times daily, in a 1-hour intravenous drip infusion for 3 approximately 12 days. The clinical efficacy of IPM/CS in 10 patients with bacterial infections (2 with sepsis, 3 with suspected sepsis, 2 with pneumonia, 2 with urinary tract infection and 1 with acute omphalitis) was evaluated as excellent in all patients, with an efficacy rate of 100%. All 5 causative organisms found in 5 patients (Staphylococcus aureus in 1, Staphylococcus epidermidis in 1, Escherichia coli in 2 and Flavobacterium meningosepticum in 1) were eradicated. Among 27 patients administered IPM/CS, adverse reactions were observed in 2 patients. These were rash and diarrhea. As for abnormal laboratory test values, elevations of GOT and GPT were observed. 2. MICs of IPM against 14 clinical isolates (S. epidermidis 1, S. aureus 6, Streptococcus agalactiae 4, E. coli 1, Enterobacter cloacae 1 and F. meningosepticum 1) from neonatal patients with bacterial infections were examined. IPM showed good antibacterial activity comparable to that of cefotaxime against S. agalactiae; however, the activity against methicillin-resistant S. aureus was poor. 3. Serum levels of IPM and CS were investigated in a total of 22 patients consisting of 15 mature and 7 immature infants after 20 mg/20 mg/kg of IPM/CS was administered. IPM and CS produced peak serum levels at the end of the drip infusion. In mature infants, peak serum levels of IPM and CS were 31.8 micrograms/ml (17.1 approximately 59.0 micrograms/ml) and 59.9 micrograms/ml (35.6 approximately 99.0 micrograms/ml), respectively. In low birth weight infants, these were 25.0 micrograms/ml (16.8 approximately 41.8 micrograms/ml) and 55.2 micrograms/ml (33.8 approximately 82.4 micrograms/ml), respectively. Half-lives of IPM and CS were 1.0 approximately 2.7 hrs. and 0.9 approximately 7.4 hrs. in mature infants, and 1.6 approximately 3.0 hrs. and 1.3 approximately 9.7 hrs. in immature infants, respectively. Generally the longer half-lives were observed in the younger neonates. Serum levels of CS remained higher and half-lives of CS were longer than those of IPM. The pharmacokinetics in neonates were different from those in adults or children.(ABSTRACT TRUNCATED AT 400 WORDS)