The response of Streptococcus pyogenes to amoxicillin or amoxicillin-clavulanic acid (Augmentin; Beecham Group) therapy of a mixed streptococcal-staphylococcal infection was studied in a surgical wound in mice. A superficial wound was produced on the backs of anesthetized mice, and a suture infected with S. pyogenes, Staphylococcus aureus, or a mixed inoculum of both organisms was inserted. Oral therapy was started 4 h after infection and continued for 3 days. Both amoxicillin and amoxicillin-clavulanic acid were effective in eliminating the streptococci from the pure wound infection. In contrast, amoxicillin failed to eliminate the streptococci from a mixed infection in which a ,-lactamase-producing strain of S. aureus was also present, wound counts reaching 107 streptococci per wound by 80 h, whereas amoxicillin-clavulanic acid reduced the count to <33 streptococci per wound by 24 h. Numbers of S. aureus were also reduced by amoxicillin-clavulanic acid therapy, controlling the infection, whereas amoxicillin was ineffective. Also of significance was the fact that successful therapy was achieved with blood and tissue concentrations of amoxicillin and clavulanic acid of the same order as those measured in humans. These results show that amoxicillin therapy failed to eliminate S.pyogenes from a wound infection in the presence of a P-lactamase-producing strain of S. aureus and suggest the potential of amoxicillin-clavulanic acid in the treatment of mixed bacterial skin infections involving P3-lactamase-producing organisms.

The efficacy of topically-applied mupirocin was evaluated against an experimental surgical staphylococcal wound infection in the guinea-pig. A suture impregnated with Staphylococcus aureus was inserted into a superficial wound, and topical therapy with mupirocin ointment was started 24 h after infection. In non-treated wounds, the bacterial counts increased to greater than 10(6) organisms/wound in the majority of animals at 24 h, remaining at this level for up to seven days. Therapy with placebo ointment (polyethylene glycol base) was ineffective, whereas twice daily application of mupirocin ointment resulted in elimination of the staphylococci. Mupirocin was as effective as topically-applied fusidic acid cream in reducing the bacterial counts of infected wounds.

The therapeutic effects produced by formulations of amoxicillin plus clavulanic acid (BRL 25000A and BRL 25000G) were compared with those of amoxicillin and clavulanic acid separately against a variety of infections produced by amoxicillinsusceptible and P-lactamase-producing (amoxicillin-resistant) bacteria. The infection models studied included intraperitoneal infections, a mouse pneumonia, experimental pyelonephritis, and local lesions caused by Staphylococcus aureus and Bacteroides fragilis. The distribution of amoxicillin and clavulanic acid in infected animals after the administration of amoxicillin-clavulanic acid was evaluated by measurement of the concentrations of the substances present in specimens collected at the sites of infection. The results showed that both amoxicillin and clavulanic acid were well distributed in the animal body after the administration of amoxicillin-clavulanic acid formulations, being present in significant concentrations at various sites of infection, e.g., peritoneal washings, pleural fluid, pus, and infected tissue homogenates. In a number of cases, the amoxicillin concentrations measured after the administration of BRL 25000 were higher than those found after treatment with amoxicillin alone, presumably as a result of inhibition of bacterial 3-lactamases by clavulanic acid at the site of infection. The ability of clavulanic acid to protect amoxicillin in vivo was confirmed by the efficacy of amoxicillin-clavulanic acid formulations in the treatment of the infections studied, most of which were refractory to therapy with amoxicillin.

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(15). Experimental animal models have been of significant value in studying the pathogenesis of chlamydial infection, particularly the immunopathological sequelae of untreated asymptomatic infection in females-salpingitis, ectopic pregnancy, and tubal infertility. Nonhuman primate models resemble the human disease most closely (19), but these animals are costly and in restricted supply. Guinea pigs, rabbits, and cats have also been used (11,20,21 on fertility. The mouse pneumonitis biovar of C. trachomatis, MoPn, is genetically and antigenically distinct from human biovars (32) but has the advantage that it is a natural mouse pathogen, particularly of the respiratory tract. To our knowledge, the use of this strain in experimental genital tract chemotherapy has been restricted to two studies involving intrabursal inoculation of mice to induce hydrosalpinx and infertility (5, 26) and a third in which C. trachomatis MoPn was introduced intravaginally to progesterone-treated mice. In the last study, therapy experiments were terminated after 12 days and long-term sequelae were not described (3).We report here, for the first time, the development of an upper genital tract infection in progesterone-treated outbred mice caused by intravaginal inoculation with C. trachomatis MoPn, in which salpingitis, hydrosalpinx formation, and loss of fertility were observed. We have used the model to assess the effects of minocycline, doxycycline, amoxicillin-clavulanic acid, and azithromycin on chlamydial shedding and preservation of fertility. MATERUILS AND METHODS Organism