[Pharmacokinetic and clinical studies with meropenem in the pediatric field. Pediatric Study Group of Meropenem].
Pharmacokinetic and clinical evaluations in pediatrics were made on meropenem (SM-7338, MEPM), a new parenteral dehydropeptidase-1 stable carbapenem used without any inhibitors, at 33 medical institutions. The results are summarized as follows. 1. Pharmacokinetic studies. MEPM at a dose of 10, 20, or 40 mg/kg was administered to 53 children by 30-minute drip infusion. Peak plasma concentrations (Cmax's) and plasma half-lives (T1/2's) of these doses were 28.5, 47.2 and 130.0 micrograms/ml, and 0.80, 0.93 and 0.94 hours, respectively. A clear dose response was observed in Cmax's and T1/2 values were quite similar to those observed in adults. In the first 6 hours after administration, 54.4 to 68.1% of the administered drug was recovered in urine. The cerebrospinal fluid (CSF) levels of MEPM in patients with purulent meningitis were 0.13 microgram/ml at a dose of 6 mg/kg, and 0.64 to 4.22 micrograms/ml at a dose of 29 to 44 mg/kg within day 4 of onset. The penetration rate of MEPM showed an intermediate value among those for other cephalosporin antibiotics. 2. Clinical study. Clinical efficacies of MEPM were evaluated in 389 cases. The most common doses used were 10 to 20 mg/kg/once, 2 to 3 times a day. The maximum dose was 173 mg/kg/day q.i.d. MEPM gave "excellent" or "good" responses in 242 (97.6%) out of 248 cases in which causative organisms were documented and in 134 (95.0%) out of 141 cases in which causative organisms were not identified. Clinical efficacy rates were 100% in 11 patients with purulent meningitis, 85.7% in 7 with septicemia, 98.8% in 173 with pneumonia, and 100% in 65 with UTI. Bacteriologically, 260 strains (96.7%) out of 269 strains were eradicated by MEPM treatment. Eradication rates were 89.2% for Staphylococcus aureus (37 strains) and 100% for Streptococcus pneumoniae (35 strains). The overall eradication rate for Gram-positive bacteria was 94.6%. Among Gram-negative bacteria, 98.3% out of 172 strains were eradicated. The eradication rate of Haemophilus influenzae (73 strains) was 98.6% and Pseudomonas aeruginosa (11 strains) was 90.9%, and all of Branhamella catarrhalis (15 strains), Escherichia coli (42 strains), and Klebsiella pneumoniae (6 strains) were eradicated. Out of 84 cases for which previous antibiotic therapies of 3 days or longer were not successful, MEPM gave "excellent" or "good" responses in 77 cases (91.7%) and excellent bacteriological responses (95.7%).(ABSTRACT TRUNCATED AT 400 WORDS)
Fujii
R
R
Department of Pediatrics, School of Medicine, Teikyo University.
Yoshioka
H
H
Fujita
K
K
Maruyama
S
S
Sakata
H
H
Inyaku
F
F
Chiba
S
S
Tsutsumi
H
H
Wagatsuma
Y
Y
Fukushima
N
N
D001424:Bacterial Infections / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004927:Escherichia coli Infections / Q000188:drug therapy; D005260:Female; D006192:Haemophilus Infections / Q000188:drug therapy; D006193:Haemophilus influenzae; D006801:Humans; D007223:Infant; D007710:Klebsiella Infections / Q000188:drug therapy; D007711:Klebsiella pneumoniae; D008297:Male; D000077731:Meropenem; D001936:Moraxella catarrhalis; D016870:Neisseriaceae Infections / Q000188:drug therapy; D011552:Pseudomonas Infections / Q000188:drug therapy; D013203:Staphylococcal Infections / Q000188:drug therapy; D013290:Streptococcal Infections / Q000188:drug therapy; D013845:Thienamycins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D013845:Thienamycins; D000077731:Meropenem