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The clinical effectiveness of cefaclor 500 mg three times daily in the treatment of acute infective exacerbations of chronic bronchitis has been investigated by a double-blind comparison with amoxycillin in the same dose in 30 in-patients and 50 out-patients. The two antibiotics were equally effective, in terms of resolution of presenting symptoms, sputum conversion and fall in 24 h sputum weight. Side effects were infrequent. Serum and sputum concentrations of antibiotics and 24 h urinary recovery were measured in 27 patients. Concentration of both cefaclor and amoxycillin was found to be significantly lower in mucoid sputum than in purulent sputum, in contrast to earlier reports in the case of amoxycillin. No clinical advantage was apparent for patients achieving higher sputum concentration of either antibiotic.

Penetration into the middle ear of four antibiotics commonly used in treatment of otitis media was studied by administering a single oral dose of amoxicillin, cefaclor, erythromycin-sulfisoxazole, or trimethoprim-sulfamethoxazole to 83 children with chronic serous otitis media. The antibiotic was given 15-240 min before the removal of middle ear fluid (MEF) by ventilation tubes inserted through the tympanic membrane. At the time MEF was obtained, a sample of blood was drawn from the patient, and concentrations of antibiotic in both specimens were assayed either microbiologically by a disk diffusion method or by high-pressure liquid chromatography. Amoxicillin had the highest ratio of mean peak concentration in MEF to minimal inhibitory concentration (MIC) for the three most common pathogens of otitis media (Streptococcus pneumoniae, ampicillin-sensitive Haemophilus influenzae, and Streptococcus pyogenes), whereas trimethoprim-sulfamethoxazole had the highest ratio of mean peak concentration in MEF to MIC for ampicillin-resistant Haemophilus influenzae.

In both Mueller-Hinton agar (MHA) and antibiotic medium no. 1 (AB1) cefaclor was more active than cephalothin or cephalexin against Enterobacteriaceae. Its activity was equivalent to cephalexin against S. aureus in MHA. Cefaclor was particularly active against P. mirabilis. The activity of this antibiotic was greated in AB1 than in MHA. The inoculum effect was pronounced for cefaclor when compared with cephalothin, but cefaclor retained greater activity even against the higher inoculum. In volunteers with normal renal function, cefaclor produced slightly lower blood levels than those reported for cephalexin. Absorption after eating was decreased and delayed. Despite severe renal failure, substantial urine levels of antibiotic were still achieved. In contrast to cephalexin, plasma half-life for cefaclor was only moderately prolonged by renal failure (two-to-threefold) and only minimally shortened by haemodialysis. Adequate concentrations of cefaclor in sputum, active against common respiratory pathogens, could not be consistently demonstrated after the oral administration of a 1 gram dose of cefaclor.

The toxicity of cefaclor, a new orally-administered cephalosporin, was evaluated in laboratory animals given single or multiple doses of the antibiotic. The acute toxicity data for cefaclor in mice, rats, dogs and monkeys were comparable to that previously reported for cephalexin. Rats were maintained on dietary mixtures of cefaclor which provided average daily doses of approximately 230 to 950 mg/kg for 28 days in subacute toxicity tests, and 160 to 675 mg/kg for 1 year in chronic toxicity tests. Treatment-related effects in the above studies were limited to soft stool excretion and caecal dilatation in the subacute test. Effects in dogs given daily oral doses of 50 to 200 mg/kg for 30 days were limited to a transient moderate fall in haemoglobin concentration in the two males at the highest dose. Soft stool excretion and occasional episodes of emesis were observed in dogs given cefaclor for 1 year at oral doses of 100 to 400 mg/kg/day. A reversible thrombocytopenia occurred in one animal at the highest dose. Analysis of various tissue fluids taken 2 hours after the last dose revealed that the concentration of cefaclor in the synovial fluid was approximatley one-half of that in serum. The results of these studies indicate that cefaclor has a low toxic potential in the species tested.

In a cross-over study, 10 healthy adult volunteers received 1 g cefaclor and 1 g cephalexin orally 1 hour after a standard breakfast. Serum levels of cefaclor rose somewhat faster and were higher than those of cephalexin in the first 60 minutes. At the end of the second hour the serum concentration of cephalexin was 50--100% higher. The area under the serum level curve averaged 45 hr-micrograms/ml for cefaclor and 60 hr-micrograms/ml for cephalexin. Calculated pharmacokinetic constants indicate that the absorption rate of cefaclor was nearly the same as that of cephalexin. The serum half-life of cefaclor was 1 hr. The urine recovery of cefaclor for 9 hours averaged 65%, whereas cephalexin resulted in a urine recovery of 85%. To evaluate sputum levels, 15 adult patients with bronchial carcinoma and secondary bronchitis or pneumonia were treated with 0.5 g of cefaclor orally 4 times daily. The mean individual sputum levels were 0.44 micrograms/ml (after the first dose) and 0.54 micrograms/ml (after repeated administration). In 10 other patients, after a single 1 g dose of cefaclor mean sputum levels after 1 hour and 3 hours doubled, whereas peak concentrations in sputum after 2 hours did not differ significantly. These results suggest that cefaclor will be useful in respiratory tract infections caused by sensitive bacteria.