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The pharmacokinetics and safety of ceftriaxone were examined in 39 neonates who required antibiotics for clinically suspected sepsis. The drug was administered as a once daily dose of 50 mg/kg by the intravenous (IV) or intramuscular (IM) route. Ceftriaxone was assayed in 49 series of blood samples, 3 samples of cerebrospinal fluid (CSF) and 15 samples of urine by a microbiological technique. Blood was collected before, during and after treatment for biochemical analysis. Routine haematological investigations were also monitored. There was no significant difference between the maximum plasma concentrations following IV (153 +/- 39 mg/l) or IM (141 +/- 19 mg/l) administration (first dose). The mean elimination half-life, total body clearance, and volume of distribution following the first dose were 15.4 +/- 5.4 h, 0.28 +/- 0.12 ml/min per kg and 325 +/- 59 ml/kg respectively. Clearance increased with increasing postnatal age and body temperature (P less than 0.0002) and decreasing plasma creatinine concentration (P less than 0.005). Increasing plasma protein concentration was associated with a decrease in volume of distribution (P less than 0.001). There were no drug-associated changes in any of the biochemical or haematological parameters examined. Ceftriaxone is a safe and well tolerated antibiotic for use in the treatment of newborn sepsis and possibly meningitis. A once daily administration of 50 mg/kg by the IV and IM routes provides satisfactory plasma concentrations throughout the dosage interval whilst avoiding accumulation.

We report a prospective, non-blind, randomised, multicentre, parallel group, multinational investigation to compare ceftazidime to aminoglycoside based regimens as empirical treatment in 1316 cases of suspected sepsis in the newborn. In each of the 15 study centres either ceftazidime alone (CAZ) or ceftazidime + ampicillin (CAZ + AMP) was compared to an amino-glycoside/ampicillin combination (AG + AMP). In all cases treatment was based on "an intention to treat". Bacteria considered to be pathogenic were isolated from 176/1316 (13.4%) patients. The incidence of proven infection varied from 39% in a Yugoslav centre to 6% in a British centre; a further 489/1316 (37.1%) patients fulfilled the criteria for clinically suspected sepsis. A total of 210 bacterial isolates from 197 infection sites in 176 patients were considered to be clinically significant. The cure rate for evaluable patients with proven infection who were treated with CAZ + AMP (97%, 30/31) was significantly higher than that for the corresponding patients treated with AG + AMP (66%, 26/39), (P < 0.002). The difference in cure rate between CAZ monotherapy (79%, 34/43) and AG + AMP (86%, 32/37) was not significant. Treatment failed in 28/150 (18.7%) evaluable patients. There were significantly fewer failures (P < 0.001) with CAZ + AMP than with AG + AMP therapy. There were 55 staphylococcal infections. Treatment was successful in 16/19 evaluable patients treated with CAZ or CAZ + AMP and in 16/29 evaluable patients treated with AG + AMP. None of the study centres encountered problems with ceftazidime resistant bacteria. The cure rate for patients with only clinical and radiological evidence of sepsis was greater than 94% in all treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The peak and trough serum concentrations and total body clearance of chloramphenicol were determined by microbiological assay in a multicentre investigation of 90 babies. Chloramphenicol was administered by the intravenous, intramuscular or oral route and dosage ranged between 12 and 210 mg/kg/day. A wide variation in both serum levels and clearance amongst babies receiving the same dose was observed. Neonates (64) had significantly higher serum concentrations (P less than 0.001) and slower clearance (P less than 0.0001) than infants (26). Oral administration in neonates resulted in lower steady state serum levels (P less than 0.02) than those following intravenous administration. Term neonates cleared chloramphenicol more rapidly than their preterm contemporaries (P less than 0.005). Forty-one per cent of subjects had potentially toxic serum levels; subtherapeutic peak serum levels (less than 15 mg/l) were recorded in 39/90 babies. Concomitant penicillin therapy resulted in higher serum concentrations (P less than 0.05); phenobarbitone was not associated with increased clearance or lower steady state serum levels of chloramphenicol. Postnatal age and gestational age accounted for some of the variability in pharmacokinetic response to chloramphenicol. Although many babies receiving the recommended dose had serum levels within the accepted range (15-25 mg/l), others did not. Routine monitoring of chloramphenicol in every baby receiving this antibiotic is essential: the regimens of 18% babies in the present study were altered after assay.

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