The in-vitro activity of clarithromycin and its main metabolite 14-hydroxy clarithromycin against Haemophilus influenzae was evaluated by determining minimum inhibitory and minimum bactericidal concentrations. The 14-hydroxy metabolite was more active than the parent compound against H. influenzae. The activity of the parent compound/metabolite combination was evaluated against 20 strains of H. influenzae by the chequerboard technique. The combination was synergistic against seven isolates in terms of fractional bactericidal concentration index and against five isolates in terms of fractional inhibitory concentration index; the combination demonstrated additive activity against the remaining strains. Serum bactericidal activity against H. influenzae was measured in sera from six healthy volunteers who had received 250 mg clarithromycin by mouth. The area under the serum bactericidal activity curve correlated with the area under the curves for clarithromycin and 14-hydroxy clarithromycin, and with the in-vitro susceptibility of the strains tested. Serum bactericidal activity was detected at 30 min after dosing and lasted for 5-6 h.

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The in vitro susceptibility of recent clinical isolates of Haemophilus equigenitalis to various antimicrobial agents was determined by the disk diffusion test and the World Health Organization-International Collaborative Study agar dilution procedure. Ampicillin and tetracycline were the most active drugs. All strains were susceptible to beta-lactam antibiotics, chloramphenicol, trimethoprim-sulfamethoxazole, nalidixic acid, nitrofurantoin (Furadantin), and bacitracin. All but two strains were resistant to streptomycin, whereas all strains were susceptible to the other aminocycitol antibiotics. All strains were resistant to clindamycin, lincomycin, and metronidazole.In 1977, an episode of acute endometritis was observed in mares on a stud farm in Newmarket, U.K. (8). The illness had been noted in 1976 in Ireland (5), and the disease appeared to be sexually transmitted. Next, the disease was seen in others countries, France (6), Australia (2), the United States (10), and Germany (3).The agent responsible for contagious equine metritis has been isolated from cervical swabs and from the external genitalia of stallions. The organism is a fastidious gram-negative, microaerophilic, nonfermentative coccobacillus, very unreactive in biochemical tests; only oxidase, catalase, and phosphatase tests are positive (11). Some stimulation of growth by factor X (hemin) has been observed, but total dependence on either X or V factors has not been demonstrated. The sickness has been reproduced experimentally in pony mares (7). In 1978, Taylor et al. (11) proposed that the causative organism of contagious equine metritis be considered a new species of Haemophilus named Haemophilus equigenitalis.Antimicrobial susceptibility of this organism has been reported for only a limited number of clinical isolates (3,8,11 C02. After isolation, they were stored at -80°C in brain heart infusion broth containing 15% glycerol.Disk diffusion method. Disk diffusion susceptibility tests were performed by the International Collaborative Study method (1) on Mueller-Hinton agar supplemented with 1% Fildes enrichment (Difco) and using commercial disks distributed by Institut Pasteur (Paris, France). The antibiotics tested were penicillin, ampicillin, carbenicillin, cephalothin, streptomycin, kanamycin, gentamicin, tobramycin, amikacin, neomycin, chloramphenicol, tetracycline, erythromycin, clindamycin, lincomycin, colistin, sulfamethoxazole, co-trimoxazole, trimethoprim, nalidixic acid, oxolinic acid, nitrofurantoin (Furadantin), fusidic acid, metronidazole, and bacitracin. Plates were inoculated with a 10-fold dilution of a fresh culture in brain heart infusion broth supplemented with 1% Fildes enrichment with incubation for 72 h under 10% C02.