In vitro antimicrobial activities of ceftizoxime and its therapeutic effect on respiratory tract infections

On a new semisynthetic derivities of. cephalosporin, cftizoxime (CZX), an in vitro study was conducted to compare its antimicrobial activities with those of other antibiotics which had been in clinical use. Its clinical efficacy was also evaluated in patients with respiratory tract infections, and in 3 of them serum levels of the drug concentration were estimated and followed until 2 hours after the end of drip infusion of 2 grams of the drug. One hundred and eighty four patient strains of gram-positive and -negative microorganisms were used for determination of inhibitory concentrations (MICs) of ceftizoxime, and the MICs determined were compared with those of cefazolin, sulbenicillin, dibekacin and amikacin. Against 20 patient strains of Staphylococcus aureus the peak among MIC distribution was found at 1.56 μg/ml and this value was twice as much that of cefazolin, but one fifth of that of sulbenicillin. Of 42 strains of Escherichia coli tested, the growth of 35 strains was inhibited at 0.39 μg/ml or less of ceftizoxime and the peak among MICs distribution was found at 0.025 μg/ml or less, and ceftizoxime was shown to be the most active agent against E. coli among the drugs tested. Furthermore, it was known that almost all of CEZ-resistant strains of E. coli were susceptible to 0.39 μg/ml or less of ceftizoxime. Of 49 strains of Klebsiella pneumoniae tested, 42 strains were inhibited at 0.20 μg/ml or less of ceftizoxime and the peak value among distribution of MICs was 0.025 μg/ml and against Klebsiella pneumoniae the agent was most active as compared with any other drugs employed for comparison. About a half of the strains of Klebsiella pneumoniae which had been shown to be refractory to CEZ was found susceptible to 0.1 μg/ml or less of ceftizoxime. Against patient strains of β-lactamase producing Enterobacter cloacae, ceftizoxime was demonstrated to be still active and the growth of 6 out of 7 patient strains was inhibited at 0.2 μg/ml or less of the agent. Antimicrobial activity of ceftizoxime against Enterobacter cloacae was most potent as compared with those of the other drugs examined. In contrast to the results above mentioned, ceftizoxime was found to be not so active against patient strains of Pseudomonas aeruginosa. The peak among MICs distribution was found between 25 and 50 μg/ml, and this value was 4 or more times less than that of sulbenicillin, but was 4 or 5 times as much as that of dibekacin or amikacin.Against 8 strains of Acinetobacter calcoaceticus, a species of glucose non-fermentative gram negative bacilli, the pattern of MICs distribution of ceftizoxime was similar to that obtained against Pseudomonas aeruginosa. In 3 patients with no abnormalities in renal function tests, serum concentrations of ceftizoxime were determined at the end of 2 hour drip infusion of 2 g of the drug and serum levels were followed through 2 hours thereafter. The mean serum concentration was 139.7 μg/ml at the end of infusion, and was 110.3 μg/m\ and 71.0 μg/ml at 30 minutes and 2 hours thereafter respectively.Twenty patients with respiratory tract infections were treated with ceftizoxime. Pour patients were omitted from evaluation of efficacy of the drug because in 2 of them the underlying disease, lung cancer, was in so far advanced state that evaluation might be inadequately made and in other 2 patients diagnosis was made as pulmonary tuberculosis during the treatment. Sixteen patients on whom evaluation was made consisted of 6 patients with pneumonia, 4 with lung abscess, 1 with emphysema, 2 with diffuse panbronchiolitis, and 3 with secondary pulmonary infection to lung cancer. The drug was given by intravenous drip infusion with daily dose of 4 g in 14 patients or of 2 g in the remaining 2 patients. The days of the treatment ranged from 7 to 58 with average of 21.1. The therapeutic effect was excellent in 6 patients and good in other 7 patients, and cure rate was 81.3 per cent. In contrast to high cure rate in patients with pneumonia, lung abscess or acute exacerbation of diffuse panbronchiolitis, the therapeutic effect was poor on secondary infections in patients with emphysema or with underlying disease such as lung cancer. Before or at the beginning of the treatment, the following pathogenic organisms were cultured from the sputum of the patients; i.e. Staphylococcus aureus, Escherichia coli, Citrobacter freundii and Pseudomonas maltophilia from each one patient, and Streptococcus pneumoniae and Haemophilus influenzae from each 2 patients, and Klebsiella pneumoniae from 5 patients, and in other 3 patients nonpotential pathogen alone. By the treatment with ceftizoxime in 12 patients, the organisms were eradicated from the sputum (in 3 of the patients emerged super infection) and in a patient a marked decrease in viable cell counts was noted. Clinical tolerance and safety of ceftizoxime were examined in all of the 20 patients treated with the drug. In 3 patients, fever of 38. to 40.C was noted at 10th to 14th days of the treatment. In two of them fever was associated with elevation of serum levels of GOT and/or GPT. In other 3 patients modest elevation of s- GOT and s-GPT were noted and in the other one slight elevation of s-GPT alone was observed. Minor eosinophilia was noted in a patient but number of eosinophile returned to normal range soon after the withdrawal of the drug, and in this patient a very slight elevation of s-GPT was also detected.