The present study was undertaken to evaluate efficacy, safety and patient acceptability of three antibiotic regimens for the treatment of acute brucellosis. Six different centres were involved: three in France, one in Greece and two in Spain. The regimens were: oral rifampicin 900 mg/day plus oral doxycycline 200 mg/day for 45 days (A), oral doxycycline 200 mg/day for 45 days plus im streptomycin 1 g/day for 21 days (regimen B) [corrected] and the WHO regimen (C) combining oral tetracycline 2 g/day for 21 days plus im streptomycin, 1 g/day, for 14 days. Regimens A and B were randomly allocated in all centres, while regimen C was allocated only in two centres. All patients were suffering from acute brucellosis clinically and biologically proven. 143 patients were allocated for treatment and analysed. Their mean age was 41 years (range 13-70), 49 were female and 94 male, and their mean weight was 64 kg (range 35-98). Among these patients, 14% had localized disease (nine orchitis, eight osteo-articular involvement and one pleural effusion), but there was no statistical difference between the three regimens in regard to this localized disease. Forty-five per cent of the patients had positive blood cultures. The cure rate with regimen A was 95%, 96% with regimen B and 59% with regimen C. Thus regimen A presented the same efficacy rate as regimen B, but regimen C cannot be regarded as the treatment of choice for acute brucellosis.

Cefoxitin, a semisynthetic cephamycin, has been compared with the widely used parenteral cephalosporin, cephalothin, in terms of antibacterial activity, human pharmacokinetics, and toxicity. For both compounds, minimal inhibitory concentrations were within the therapeutic range against the 156 gram-positive cocci tested (except group D streptococci), but cephalothin was 8 to 20 times more active. Regarding the 313 gram-negative organisms tested, both antibiotics were of approximately equal activity against cephalothin-susceptible strains, but cefoxitin was outstandingly superior against Providencia spp. and indoleproducing Proteus spp., and markedly better against Serratia marcescens and Bacteroides fragilis. Against these organisms, cefoxitin but not cephalothin would be expected to be therapeutically valuable. Antibiotic activity levels in the serum and urine of 18 human volunteers after parenteral administration were higher and more prolonged in the case of cefoxitin, which had an average terminal serum half-life of about 45 min and a urinary recovery of about 90%. Cefoxitin was entirely nontoxic and, given intramuscularly, slightly less painful then cephalothin. These preliminary results suggest that cephamycins may prove to be a significant chemotherapeutic advance.

SummaryThe activity of cefoxitin was compared with that of cephalothin against 229 bacterial strains. Cefoxitin was more active against most Gram-negative strains, notably against indoleproducfng Proteus spp., which are usually resistant to the cephalosporins. Cefoxitin was not susceptible to any significant extent to degradation by f-lactamases produced by Gram-negative organisms. Aga-nst Gram-positive organisms, however, cefoxitin was considerably less active than cephalothin, but minimum inhibitory concentrations for Staphylococcus aureus were well within therapeutically attainable blood leve's.Pharmacokinetic studies in 18 volunteers showed a higher and longer sustained antibiotic activity in serum and urine after injections of cefoxitin than after equal doses of cephalothin. Urinary recovery of cefoxitin activity was also much higher than that of cephalothin. No evidence of toxicity due to cefoxitin was found. Cefoxitin was slightly less painful after intramuscular injection than cephalothin.

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Forty-five patients with acute or recurrent pyelonephritis (32), lower respiratory infection (7) or various other serious infections (6), were treated with ceftazidime. Most infections were severe, often in the presence of aggravating factors, and had failed to respond to previous antibiotic therapy. Infecting organisms were Escherichia coli (23), other Enterobacteriaceae (5), Pseudomonas aeruginosa (11), mixed flora including Ps. aeruginosa (3) and Staphylococcus albus (1). The organisms were often multiresistant. Dosage ranged from 1 to 6 g daily im or iv. All patients were clinically cured, except two who only improved. In 35 patients the organisms were eradicated, in two partially eradicated, and in six persisted or recurred. Most bacteriological failures were observed in patients infected with Ps. aeruginosa. Tolerance of the drug was excellent. A transient leucopenia was observed in one patient and transient high SGOT and LDH in another. After an intramuscular dose of 1 g im serum levels were 33 mg/l at 2 h, 137 mg/l at 6 h and 85 mg/l at 12 h. The average half-life was 2.6 h. Urinary levels were high and 79-92% of the dose was recovered from the urine after 12 h. After 3 days therapy with 1 and 2 g im 12-hourly, bone levels exceeded 10 and 15 mg/l, respectively. Ceftazidime was a safe and effective drug for the treatment of infection. A dose of 0.5 g 12-hourly is sufficient for urinary infections, but higher doses are needed in other infections, especially when due to Ps. aeruginosa.