Gentamicin: pharmacologic observations in newborns and infants.

time. These began by determining the infecting pathogens against which the drug offered advantages over drugs currently used in therapy. The first step was to evaluate the susceptibility to gentamicin of various clinical isolates from patients in this age group. These isolates were maintained, either lyophilized or frozen in skim milk. After the results of these preliminary pilot studies had been evaluated by the staff of the Pediatric Pharmacology Unit, 9 organisms were selected for study. Subsequently, over 3,000 disk-susceptibility tests were performed on these organisms; the results are shown in table 1. All, or almost all, strains of Proteus, Escherichia coli, Pseudomonas aeruginosa, Alcaligenes faecalis, and Hemophilus influenzae were susceptible; also, more than 957o of KlebsiellaEnterobacter and Hafnia were susceptible. Penicillin-resistant coagulase-positive staphylococci were the least susceptible by the disk method; 73^o of them were inhibited by the 10-zxg disk. Several of these organisms?notably P. aeruginosa, Proteus, etc.?cause particularly difficult therapeutic problems in children. The results of disk-susceptibility tests of isolates of 4 of these organisms to gentamicin, chloramphenicol, kanamycin, and neomycin are compared in table 2. The proportions of strains susceptible to the polymyxins, colistin, and polymyxin B, were similar to those of neomycin, and, since no significant difference can be demonstrated, neomycin was chosen as an example. Of strains resistant to chloramphenicol, 987o were susceptible to gentamicin; of those resistant to kanamycin and neomycin, more than 94^o were susceptible to gentamicin; of those susceptible to gentamicin, 34^o were resistant to chloramphenicol, 25 ^o to kanamycin, and 117o to neomycin. Among the strains of P. aeruginosa that were susceptible to gentamicin, 887o were resistant to chloramphenicol, 79^o to kanamycin, and 117o to neomycin. Of the isolates of P. aeruginosa that were resistant to chloramphenicol, 987o were susceptible to gentamicin; of those resistant to kanamycin and neomycin, more than 94^o were susceptible to gentamicin. Representative results of 2-fold tube-dilution tests for susceptibility of 378 strains of several organisms are shown in table 3 as the percentage susceptible to concentrations up to 100 ^ig/mWliliter of gentamicin. The large majority of strains of Klebsiella-Enterobacter, P. aeruginosa, E. coli, and penicillin-resistant staphylococci were susceptible to 1.6-3.1 ^g/milliliter, and 30^0-4090 of those of Proteus species, which were the most resistant of the organisms we have tested by the tube-dilution method, were susceptible to these concentrations. All strains, including those of the resistant Proteus species, were susceptible to 100 times this concentration. Figure 1 shows the mean serum levels, with 95^o confidence limits, observed with doses of 0.4 mg/kilogram given parenterally every 8 hr in subjects ranging in age from 3 months to 16 years, with a median age of 3 years. Table 4 gives data concerning these means. These values were obtained during the third day of therapy after the seventh dose had been administered.