Dissociation between results of in vitro and in vivo antibiotic susceptibility tests for some strains of Pseudomonas aeruginosa

Abstract

The relative efficacy in vivo of the polymyxin and aminoglycoside antibiotics in experimental Pseudomonas infection has apparently never been established. This study was designed to determine such efficacy in experimental infection of mice. Eleven strains of Pseudomonas aeruginosa were selected for the study, representing six of the seven recognized immunotypes. All strains were susceptible to colistin, gentamicin, and tobramycin in vitro, and all were virulent for mice. None was lethal because of preformed toxins. Infections were established in mice by intraperitoneal (i.p.) injection of 100 ID(50) of bacteria (infectious doses that would kill 50% of the mice). Graduated doses of antibiotics or saline were given subcutaneously 1 h later. Infections by three strains of P. aeruginosa were cured by low doses of all three antibiotics. Infections by two strains were relatively resistant in vivo to all three antibiotics. Infections by seven strains were relatively resistant in vivo to colistimethate. For most strains, colistimethate was less effective in vivo than gentamicin or tobramycin. To determine the influence of the size of the bacterial inoculum upon the results of chemotherapy, groups of mice were infected with serial dilutions of bacterial suspensions and treated with antibiotics. The antibiotics were more effective when a lighter bacterial inoculum was used. However, colistimethate at 30 mg/kg failed to cure some infections established with an inoculum of only 10 ID(50). To examine the possibility that death despite apparently adequate chemotherapy might be due to bacterial lysis and delayed release of toxins, numbers of viable bacteria in the peritoneal cavity of treated animals were determined by colony count. Antibiotic failure by colistimethate was associated with a steady rise in the number of i.p. bacteria. The findings support the conclusion that i.p. infections in mice with some strains of P. aeruginosa that are fully susceptible in vitro are relatively resistant to chemotherapy in vivo. The dissociation between in vitro and in vivo results was greatest for colistimethate.