Imipenem/Cilastatin for the Treatment of Infections in Hospitalized Children

Clinical pharmacology of imipenem and cilastatin in premature infants during the first week of life

“…Similar to other P-lactam antibiotics, imipenem is bactericidal against susceptible bacteria in vitro because it inhibits bacterial cell wall synthesis. Studies of imipenem in vitro have demonstrated a broad spectrum of antibacterial activity, including activity against many ,Blactam and aminoglycoside-resistant pathogens as well as the majority of pathogens associated with infections during the neonatal period (1,4,8,14,15,19). The trans conformation of the hydroxyethyl side chain and hydrogens protects the parent P-lactam structure from inactivation by both penicillinase and cephalosporinase, whereas the alkylthio moiety enhances the compound's in vitro antipseudomonal activity.…”

“…Initial disposition evaluations of imipenem in both animals and humans described stable systemic profiles, although they revealed highly variable drug concentrations in urine (1,4,8,(13)(14)(15)19). Further studies revealed the rapid and efficient hydrolysis of the imipenem P-lactam ring by the renal brush border enzyme dehydropeptidase I. Cilastatin, a compound that possesses no inherent antibacterial activity and that is a competitive inhibitor of renal dehydropeptidase I (1, 4, 8, 14, 15, 19), is administered concurrently with imipenem to circumvent this renal inactivation.…”

“…To provide for adequate antibacterial therapy against these pathogens, initial empiric regimens for these infants routinely require a combination of antibiotics. Although antibiotic combinations that include an aminoglycoside and a P-lactam or an expanded-spectrum cephalosporin and a penicillin have frequently been successful in the treatment of infections in these infants, drug-related toxicities and the development of resistant microorganisms underscore the importance for continual evaluation of more effective, less toxic compounds (1,8,(13)(14)(15)19).Imipenem, the stable derivative of thienamycin, represents the first of a new class of ,-lactam antibiotics (14). The drug possesses potent in vitro activity against a broad spectrum of aerobic and anaerobic gram-positive and gramnegative bacteria, including the majority of pathogens responsible for neonatal infections (4,14).…”

Clinical Pharmacology of Imipenem/Cilastatin

“…This treatment is well-tolerated in 87.1% of patients, moderately well-tolerated in 12.9% of patients, and the overall clinical outcome is favourable in 95% or more patients [24], patients had intraabdominal infection caused by Staphylococcus epidermidis, Moraxella morganii, or by Fusobacterium varium and received imipenem/cilastatin intravenously at a daily dose of 1.5 grams and the frequency of clinical cure or improvement is obtained in 91.2% of patients [25], patients with bacterial pneumonia received either ciprofloxacin administered intravenously at a daily dose of 800 to 1,200 mg or imipenem/cilastatin administered intravenously at a daily dose of 2 to 4 grams and the success-rate is generally good with both treatments [26], children had infection caused by Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, or by Pseudomonas aeruginosa. Children aged < 3 years received imipenem/cilastatin intravenously at a daily dose of 100 mg/kg and children aged > 3 years received imipenem/cilastatin intravenously at a daily dose of 60 mg/kg and the treatment is well-tolerated and children respond favourably to this treatment [27], infants and children had bronchopneumonia with or without empyema, peritonitis complicating appendicitis, skin infection, soft-tissue abscessus, bacterial septicaemia, and miscellaneous infections and the infective agents were Proteus mirabilis, Salmonella typhi, Streptococcus aureus, or Escherichia coli. Children aged up to 3 years received imipenem/cilastatin intravenously at a daily dose of 100 mg/kg and older children received imipenem/cilastatin at a daily dose of 60 mg/kg and the treatment is well-tolerated and has excellent clinical efficacy [28], children were hospitalized for appendectomy and the appendix was perforated in 24.8% of children.…”

“…All children respond favourably to treatment, no serious adverse-effects are observed, and the infective bacteria are eradicated in all children. Thus Imipenem/cilastatin is well-tolerated and effectively treats the infections [27]. One-hundred-four infants and children, aged 22 days to 15 years, with bacterial infection were enrolled.…”