Influence of clavulanic acid on the activity of amoxicillin against an experimental Streptococcus pneumoniae-Staphylococcus aureus mixed respiratory infection

Abstract

An experimental respiratory infection caused by Streptococcus pneumoniae was established in weanling rats by intrabronchial instillation. Treatment of this infection with amoxicillin rapidly eliminated the pneumococci from the lung tissue. A ,B-lactamase-producing strain of Staphylococcus aureus, when inoculated in a similar manner, did not persist adequately in the lungs long enough to permit a reasonable assessment of the therapy, but staphylococcal survival was extended in the lungs of rats infected 24 h previously with S. pneumoniae. Amoxicillin therapy was relatively ineffective against the pneumococci in this polymicrobial infection and had no effect on the growth of S. aureus. In contrast, amoxicillin-clavulanic acid eliminated the pneumococci from the lung tissue and brought about a reduction in the numbers of staphylococci. The data illustrate the utility of this model for the study of polymicrobial lung infections and demonstrate the role of amoxicillin-clavulanic acid in the treatment of polymicrobial infections involving ,B-lactamase-producing bacteria.Streptococcus pneumoniae remains the most common pathogen in community-acquired bacterial pneumonia. The antibiotics most frequently prescribed by general practitioners for this infection are ampicillin and amoxicillin (23). However, coinfection or superinfection of pneumococcal pneumonia has been recognized since the 1930s (10), and recent reports have described polymicrobial pyogenic pneumonia with S. pneumoniae and Staphylococcus aureus (8,11,20). In the majority of the cases reported, initial penicillin therapy directed against S. pneumoniae failed because of the presence of P-lactamase-producing staphylococci, which now account for more than 90% of community-acquired strains of S. aureus (9). The failure of penicillin therapy to eradicate penicillin-susceptible pathogens in the presence of ,B-lactamase-producing bacteria has been reported for a number of clinical situations (4,14,16).The objective of this study was to develop an experimental model of mixed respiratory infection caused by a penicillinsusceptible strain of S. pneumoniae and a P-lactamaseproducing strain of S. aureus, in order to study the role of the P-lactamase inhibitor clavulanic acid in such a situation.Clavulanic acid is a potent inhibitor of a wide range of bacterial P-lactamases, including those produced by S. aureus (18,19), and has been reported to protect amoxicillin from inactivation by the f-lactamase activities of mixed bacterial cultures which are refractory to this penicillin in vitro and in vivo (2,5,22 Organisms. S. aureus MB9, a P-lactamase-producing strain, and S. pneumoniae 1629, a penicillin-susceptible strain, were used. S. aureus was maintained on nutrient agar slants, and a broth culture was grown overnight for each experiment in double-strength veal infusion broth (Difco Laboratories, Detroit, Mich.). S. pneumoniae was grown overnight in Todd-Hewitt broth (Oxoid Ltd., London, England), and the culture was stored in aliquots at -70°C. One aliquot was used for...

Effects of antibiotics on protected specimen brush sampling in ventilator-associated pneumonia

“…These results corroborate the data of GARRAD and A9COURT [12] who demonstrated the persistence of P. aeruginosa in respiratory secretions several days after adequate treatment, suggesting that the behaviour of this organism may be different from other species. Similar results were obtained by SMITH et al [26] studying an animal model of polymicrobial pneumonia caused by S. aureus and S. pneumoniae. Although amoxycillin-clavulanate was effective against these micro-organisms, SMITH et al [26] observed that the number of colonies of S. aureus cultured from the pulmonary tissue decreased more slowly than in the case of the pneumococcus.…”

“…Similar results were obtained by SMITH et al [26] studying an animal model of polymicrobial pneumonia caused by S. aureus and S. pneumoniae. Although amoxycillin-clavulanate was effective against these micro-organisms, SMITH et al [26] observed that the number of colonies of S. aureus cultured from the pulmonary tissue decreased more slowly than in the case of the pneumococcus. The causes and the clinical implications of the persistence of the organisms hours or even days after the introduction of an empirically appropriate antibiotic are not known.…”

Comparative efficacies of ciprofloxacin, amoxicillin, amoxicillin-clavulanic acid, and cefaclor against experimental Streptococcus pneumoniae respiratory infections in mice

“…The results of these studies concur with those of others (19), who demonstrated the superior activity of amoxicillin vis-A-vis the variable efficacy of the quinolones in experimental models of pneumonia. Although the presence of the 13-lactamase inhibitor played no part in the efficacy of amoxicillin-clavulanic acid against the pneumococcal experimental infections reported here, studies in a rat model of pneumococcal pneumonia (24) have demonstrated the lack of efficacy of amoxicillin when P-lactamase-producing organisms were present, and the protection of amoxicillin by clavulanic acid resulted in the successful therapy of the mixed infection.…”

Bactericidal effects of ticarcillin-clavulanic acid against Legionella pneumophila pneumonia in immunocompromised weanling rats

“…Groups of five treated and five nontreated rats were sacrificed daily from days 0 to 7, and blood samples were taken from the posterior venae cavae. For each rat, the trachea was exposed and the lungs were lavaged twice with 10 (14) and has since been used for the production of L. pneumophila pneumonia in this species (13).…”