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 ID50 of bacteria (infectious doses that would kill 50% of the mice).

Involvement of the outer membrane in gentamicin and streptomycin uptake and killing in Pseudomonas aeruginosa

“…1 and 2). Our previous data (21) (23) have demonstrated that polymyxin has a higher affinity for Salmonella typhimurium lipopolysaccharide than does Mg2+, whereas others have demonstrated that moderately high levels of Mg2e are necessary to inhibit polymyxin activity (6). In the case of aminoglycosides, antagonism by Mg2e occurs at quite low Mg2e levels, and this competition tends to mask the protective effects of protein Hi when the protein is iriduced by growth in low Mg2".…”

“…The discrepancy between in vitro and in vivo susceptibility is a major problem in aminoglycoside therapy (6,8). The well-documented antagonism of aminoglycosides by divalent cations (18,25) is one probable cause, and development of adaptive (nonmutational) resistance in vivo may also play a part.…”

Activity of Gentamicin, Tobramycin, Polymyxin B, and Colistimethate in Mouse Protection Tests with Pseudomonas aeruginosa

“…MATERIALS AND METHODS The methods were generally those previously described (3). Important changes will be noted.…”

Experimental Keratitis Due to Pseudomonas aeruginosa: Model for Evaluation of Antimicrobial Drugs

“…Colistimethate was relatively ineffective in the treatment of experimental keratitis by one strain of Pseudomonas. In an earlier study in mice, colistimethate was significantly less effective than tobramycin or gentamicin (2). In a more recent study (3), colistimethate was distinctly inferior in the mouse protection tests with four strains of P. aeruginosa when compared to polymyxin B sulfate.…”

“…Immediate chemotherapy avoids a second dose of general anesthetic and is analogous to the usual method for the mouse protection test (2). In the future, we plan to evaluate the effects of delayed chemotherapy.…”