Clinical and Pharmacokinetic Evaluation of Parenteral Cefoxitin in Infants and Children

Abstract

Thirty-two infants and children ranging in age from 3 to 151 months (mean, 26 months) were treated with parenteral cefoxitin (150 mg/kg per day). Ten patients with isolates of Haemophilus influenzae (six with cellulitis, two with arthritis, and two with mastoiditis), four with Staphylococcus aureus (one with lymphadenitis, one with septicemia, and two with abscess), and three patients with Streptococcus pneumoniae (one each with cellulitis, abscess, and arthritis), were clinically and bacteriologically cured by therapy. Two additional patients with septic arthritis and facial cellulitis developed meningitis with H. influenzae type b and S. pneumoniae, respectively. Minimal inhibitory and bactericidal concentrations were c5 jig/ml for 15 isolates. Minimal bactericidal concentrations were >20 ,ug/ml for one strain of S. aureus and one of H. influenzae type b. The mean peak serum levels were 81.9 and 68.5 ,Ag/ml 15 min after intravenous or intramuscular doses, respectively. The mean elimination half-lives were 42.4 and 40.1 min after intravenous or intramuscular doses, respectively. The mean volumes of distribution were 5,540 and 4,760 ml after intravenous and intramuscular doses, respectively. Mean plasma clearance was 242 and 257 ml/min per m2 after intravenous and intramuscular doses, respectively. Therapy was discontinued in one patient because of neutropenia, which resolved after cefoxitin was stopped. Eosinophilia and transiently elevated liver function tests occurred in eight and six patients, respectively. These data indicate that cefoxitin may be an effective treatment for infections due to susceptible bacteria in the dosage tested, but its use may be limited because of the occurrence of meningitis during therapy in some patients.Cefoxitin is a new semisynthetic ,8-lactam cephamycin antibiotic with a wide in vitro spectrum of antibacterial activity which includes many common pathogens in infants and children such as Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae (1,3,12). It is also active in vitro against strains of H. influenzae that produce a fi-lactamase (

Penetration of cefoxitin into cerebrospinal fluid of infants and children with bacterial meningitis

“…The dosage used in this study of 75 mg of cefoxitin per kg every 6 hours was larger than those previously reported (2,8). However, the half-lives and volumes of distribution were comparable with those previously reported (2) for a smaller dosage (37.5 mg/kg) every 6 hours.…”

“…Cefoxitin is a semisynthetic cefamycin, active in vitro against common meningeal pathogens such as Neisseria meningitidis, Streptococcus pneumoniae, and ampicillin-susceptible and -resistant strains of Haemophilus influenzae type b (1,2,6,8,14,17). The results of clinical trials in adults (6,12,13) and children (2,8) have shown that this drug is safe and effective against infections with S. pneumoniae and H. influenzae b outside the central nervous system.…”

“…The results of clinical trials in adults (6,12,13) and children (2,8) have shown that this drug is safe and effective against infections with S. pneumoniae and H. influenzae b outside the central nervous system. Thus, cefoxitin has the potential for single-drug therapy for infants and children with suspected bacterial meningitis provided it effectively penetrates into the cerebrospinal fluid (CSF).…”

Pharmacokinetics of β-Lactam Antibiotics

“…However, the apparent serum half-life is shorter in children 2-11 years of age than in adults and approaches 3 h in premature infants and neonates (WARREN et al 1979;Roos et al 1979;MARGET et al 1979;WILKINSON et al 1979;FELDMAN et al 1980;OLEGARD et al 1979). BUCHANAN et al (1980) noted no large differences in the disposition of cefoxitin in children during kwashiorkor and after the disease was cured.…”

Cefoxitin: A Neglected Intravenous Betalactam with Interesting Perspectives

“…1980 Feldman et al [57] Prospective cohort study 32 children Cellulitis, abscess, arthritis, bacteremia 89% 1996 Stiglmayer et al [52] Randomized controlled trial 76 Pelvic inflammatory disease 79%…”