Evaluation of Norfloxacin in the Pediatric Field: Pediatric Study Group for Norfloxacin

Norfloxacin (NFLX, AM-715), a new quinolone antibiotic agent, was evaluated clinically and bacteriologically for its efficacy and safety in pediatrics by a study group organized with pediatricians from all over the country. A summary of the results of the evaluation is as follows. 1. Incidence of NFLX-resistant strains (MIC over 12.5 μg/ml) isolated from children with various infections was 1.6% (8/512). One resistant strain was observed among 45 isolates of Staphylococcus aureus, and none among 30 isolates of Pseudomonas aeruginosa. 2. After single oral administration of 1.5~2.9, 3.0~4.8 and 5.1~6.1 mg/kg NFLX in tablet form at fasting, mean peak values of serum concentration of 0.37, 0.56, 0.92 μg/ml, T 1/2 of 2.5, 2.6, 2.6 hours and urinary recovery rates in 8 hours at 25.3, 25.3, 27.1% were observed, respectively. 3. Clinical effects were studied chiefly in intestinal and urinary tract infections. Among 317 patients from whom pathogens had been isolated, responses to the treatment were excellent in 187, good in 79, fair in 9, poor in 7, and unknown in 35 cases. The overall efficacy rate was 94.3% (266/282) and the efficacy rate for excellent responses was 70.3% (187/266). Among all the 406 patients treated, including those with undetermined pathogens, responses were excellent in 233, good in 106, fair in 11, poor in 11, and unknown in 45 cases. The overall efficacy rate was 93.9% (339/361). 4. Clinical effects of NFLX classified by diseases with identified pathogens were 81.8% (9/11) for acute pneumonia, 80.8% (21/26) for other respiratory infections, 95.8% (23/24) for bacillary dysentery, 98.6% (70/71) for Campylobacter enteritis, 100% (24/24) for Salmonella enteritis, 100% (6/6) for other acute enteritis and 98.1% (104/106) for urinary tract infections. Including other infections as high as 94.3% (266/282) of efficacy rate was obtained in total. There was no significant difference in NFLX efficacies between unidentified and identified pathogens. Thus, the total clinical efficacy rate was 93.9% (339/361). 5. The total eradication rate of 325 pathogens evaluable was 84.3%,with identical eradication rates for Gram-positive cocci (GPC) (43/51) and for Gram-negative rods (GNR) (231/274). 6. The optimal daily dose of NFLX seemed to be in a range between 6.0 and 12.0 mg/kg, and the optimal duration of treatment to be 7 days for children over 5 years old. 7. The clinical efficacy in treating P. aeruginosa infections in 12 patients was 100% (11/11) and the eradication rate was 83.3% (10/12). 8. In 59 non-responsive cases to other antimicrobials (treated over 3 days), efficacy rate was 88.9% with 58.3% of the excellent responder rate. Particularly in 13 cases treated with penicillin of cephems the overall efficacy rate was 90.9%, and the eradication rate was 93.6%. Except 1 strain of Streptococcus pneumoniae in 10 strains of GPC and 2 strains of P. aeruginosa in 37 strains of GNR, all bacteria were eradicated. 9. Adverse reactions were found in 6 (1.5%) cases of 406 patients. The reactions were all mild and could continue the administration of the drug. The joint injuries were not found in all cases nevertheless our careful observation to the joint. Laboratory examinations revealed transient and mild eosinophillia in 8 cases of 309 patients studied. And no changed was observed in serum Cathepsin D, ASPRO-GP, Al-P, urinary mucopolysiaccharide titers and electrophoretic isozyme patterns of Al-P which suggest arthropathy, during the course of NFLX therapy.