Antibiotics for Pseudomonas aeruginosa Sepsis: Inadequate Proof of Efficacy

Rats made neutropenic with cyclophosphamide were infected intraperitoneally with Pseudomonas aeruginosa . The challenge organism was killed synergistically in vitro by the combination of gentamicin and carbenicillin. Untreated neutropenic rats infected with 3 × 10 6 Pseudomonas died between days 2 and 7, and the overall mortality was 70%. Groups of infected neutropenic rats were treated intramuscularly with 1.5 or 6 mg of gentamicin per kg per dose, 100 or 400 mg of carbenicillin per kg per dose, or 1.5 mg of gentamicin and 100 mg of carbenicillin per kg per dose. Treatment was begun at 2 h postinfection and was continued every 8 h for about 72 h. Cultures of blood and peritoneal washings were performed in control and treated rats at 1, 4, 24, 48, and 72 h postinfection. Gentamicin at either dose level was ineffective in preventing death, but mortality was significantly reduced by high-dose carbenicillin and low-dose combination therapy. In addition, the latter regimens sterilized the peritoneal fluid and blood. Carbenicillin and gentamicin showed in vivo synergy in the treatment of neutropenic Pseudomonas -infected rats.

mentioning

confidence: 99%

Synergistic Activity of Carbenicillin and Gentamicin in Experimental Pseudomonas Bacteremia in Neutropenic Rats

Scott¹,

Robson

1976

“…susceptibility of Pseudomonas aeruginosa to antibiotics in vitro, there are few on chemotherapy of experimental infections (5). Polymyxin B and colistimethate, the two forms of polymyxin available for parenteral use in humans, have rarely been directly compared in mouse protection tests on P. aeruginosa.…”

mentioning

confidence: 99%

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

Davis

1975

Mouse protection tests were carried out with four antibiotics and six strains of Pseudomonas aeruginosa . All strains were susceptible to all four antibiotics by an in vitro test. A heavier bacterial inoculum increased the mean effective dose of gentamicin and tobramycin, but not polymyxin B. Second and third doses of gentamicin in the mouse protection test made little change in the mean effective dose. In the mouse protection tests, tobramycin was the most active antibiotic if the results were analyzed in terms of the therapeutic index or ratio of toxicity to efficacy. Colistimethate was poorly inactive in vivo. Polymyxin B was most active on an absolute basis but also was the most toxic. One strain of Pseudomonas was classified as resistant to gentamicin in vivo although it was susceptible in vitro. Strains of Pseudomonas that were uniformly susceptible to antibiotics in vitro were not uniformly susceptible in the mouse protection test to low doses of antibiotic.

“…The relative efficacy of the polymyxin and aminoglycoside antibiotics has apparently never been rigorously established in the treatment of Pseudomonas aeruginosa infections in vivo (16). Results of chemotherapy of human infections with P. aeruginosa have been poor, but patients with such infections usually have serious underlying diseases (10,19,32).…”

mentioning

confidence: 99%

Dissociation Between Results of In Vitro and In Vivo Antibiotic Susceptibility Tests for Some Strains of Pseudomonas aeruginosa

Davis

1974

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).