No abstract

Erythromycin has been recommended for the treatment of staphylococcal and streptococcal infections in newborn infants even though few studies of its use in this age group have been reported. Fujii et al1 published serum levels for various doses of erythromycin in the full-term infant. No similar study has been reported for the premature infant. Reichelderfer et al2 noted no toxic reaction or accumulation of erythromycin in a study of 11 newborn infants of whom four were premature. He obtained serum levels on two of the prematures. Isenberg et al3 reported the recovery without toxic reactions of eight infected premature infants treated with erythromycin.Michael et al4,5 reported animal studies showing that chloramphenicol, penicillin, novobiocin, and tetracycline were more toxic for the newborn rat than the adult rat, while streptomycin was not. That the newborn infant may respond to drugs differently than the adult is amply demonstrated by reports

Infections are a significant cause of death in premature infants. Arey and Dent 1 reported, in 1953, a survey of 102 neonatal deaths of which 84 were premature. They listed infection as the major cause of death in 13 (15.4%) of the prematures. Six years later Branton,2 in a report of 176 consecutive newborn deaths, of which 136 were prematures, attributed death to infec-tion in 20 (14.7%) of the prematures. He reported gram-negative col i form bacilli in 5 of 6 positive blood cultures. Infection also plays a significant role in the mortality at the Premature Center of Los Angeles County Hospital, which cares for over 1,200 premature infants yearly. The main organisms cultured from infections have been gram-negative coliform bacilli, particularly E. coli and Klebsiella aerogenes group. Studies have indicated that these organisms are most consistently sensitive to chloramphenicol. The toxicity of chloramphenicol to premature infants in doses over 100 mg/kg is well documented.3-6 Reported studies have correlated this toxicity with high blood levels of chloramphenicol. Pro¬ phylaxis with chloramphenicol as well as other antibiotics has been discontinued at the Premature Center, since in a controlled study they did not lower the mortality rate.3 Chloramphenicol would still be useful for the treatment of infected prematures if a safe dosage schedule were established. This paper is a report of studies of bloodlevel responses to intramuscular and intra¬ venous chloramphenicol made to determine whether lower doses would give therapeutic blood levels without toxicity. MethodPremature infants of varying weights and ages were given microcrystalline or the succinate ester of chloramphenicol intra¬ muscularly and intravenously, according to planned dosage schedules. Blood levels of total nitro compounds were determined by analyzing capillary blood according to the method of Glazko.7 * This method meas¬ ures both active and inactive metabolites of chloramphenicol as total nitro compounds.Timed urine specimens were collected by plastic bag from some of the infants. These were analyzed for chloramphenicol content by microbiologie assay against Shigella sonnei,8 as well as by chemical determina¬ tion for total nitro compounds.*