STUDY ON USE OF LATAMOXEF IN NEONATES

Basic and clinical studies were carried out on latamoxef (LMOX) in relation to the use of this antibiotic in the treatment of infections in newborn infants.The results were as follows.<BR>1. The MICs of LMOX were determined for various clinical isolates of Gram-negative bacteria: 22 strains of E.coil, 18 strains of K.pneumoniae, 4 strains of K.oxytoca, 19 strains of P.mirabilis, 4 strains of P. vulgaris, 5 strains of P.morganii and 3 strains of C.freundii and 60 strains of H.influenzae.The MIC distributions against all of these strains for each species were 0.1, 0.2, 0.1, 0.2, 0.1, 0.1, 6.25 and 0.78μg/ml or less, respectively. The antibacterial activity of LMOX against all of these Gram-negative isolates was thus found to be excellent. For 38 strains of P.aeruginosa, the MIC distribution was from 6.25 to 200μg/ml;accordingly, although this antibiotic does show antibacterial activity against this microbe, it is not very potent. As Gram-positive bacteria, 28 clinical isolates of S.pyogenes and 34 strains of S.aureus were tested;their respective MIC distributions were 0.39-1.56μg/ml and 3.13-25μg/ml.Therefore, it is clear that the antibacterial activity of LMOX against these Gram-positive bacteria is not as good as against the above-mentioned Gramnegative species.<BR>2. LMOX was injected intravenously as a one-shot dose of 20μg/kg to 5 newborn infants (ranging in age from 0 to 13 days) and to 2 suckling infants (49 and 60 days of age), and then the concentration of the drug in the serum was monitored with time.The mean serum concentrations in the newborn group at various times were as follows: 38.5μg/ml at 0.5 hour, 31.6μg/ml at 1 hour, 26.9μg/ml at 2 hours, 17.8μg/ml at 4 hours and 15.5μg/ml at 6 hours. For the 2 suckling infants, the mean values at those same time points were 30.5, 23.9, 16.3, 7.4 and 4.0μg/ml.In addition the value for the mean serum half-life was 4.46 hours in the newborn infant group and 1.96 hours in the suckling infant group.The urinary recovery rate was 32.3% in the newborn infant group and 49.7% in the suckling infant group during 6 hours or 8 hours.<BR>Considering the extent of differences between the individuals, it can be said that there was very little variation in the peak serum concentrations (the value at 30 minutes after the dosing) recorded in the newborn infant group since their values were almost the same regardless of age. Similarly, there was no big difference seen between the 2 suckling infahts. However, the half-life of the drug in the serum decreased as the age of the subject increased, and it was surmised that the value at around 1 month of age was close to that for schoolchildren.<BR>In addition, as a separate experiment, approximately 20mg/kg and 10mg/kg of LMOX were administered to 2 newborn infants (15 and 26 days of age) by means of intravenous drip infusion over a period of 1 hour;the absorption and excretion of the drug were then investigated. It was found that the serum concentration of LMOX showed a clear dose response.<BR>3. LMOX was administered to 3 patients with acute bronchopneumonia (1 patient was excluded from the subsequent clinical efficacy evaluation), 2 cases of acute pyelonephritis and 1 case of purulent meningitis. The clinical efficacy of the treatment was analyzed. For all 5 of the patients, the clinical efficacy was evaluated as good or excellent.With regard to the bacteriological efficacy, the 2 strains of E. coil that had initially been isolated as the causative bacterium could no longer be detected after the LMOX therapy.No clinical side effects to the drug treatment were seen. In 1 of the patients, the laboratory tests revealed a slight elevation in the values for GOT and GPT, but these returned to normal thereafter.<BR>It was concluded that the above clinical results are indicative of the usefulness and safety of LMOX in the treatment of infections in newborn infants.