Experimental sepsis using Pseudomonas aeruginosa: the significance of multi-drug resistance

Abstract

In order to clarify whether susceptible and multidrug-resistant Pseudomonas aeruginosa differ in the mechanism of induction of sepsis, three different isolates were used; one susceptible (isolate A) and two (isolates B and C) multidrug-resistant. Isolate B had moderately elevated MICs of antipseudomonal antimicrobials and isolate C highly elevated MICs. Each isolate was infused by a catheter inserted into the right jugular vein of six rabbits. Survival was recorded; blood was sampled at regular time intervals for estimation of bacterial blood counts, malondialdehyde (MDA) and tumour necrosis factor-alpha (TNFα). Quantitative cultures of various organs were performed after death or sacrifice. Mean survival after challenge by isolates A, B and C was 0.73, 2.58 and 11.00 days, respectively ( P of comparisons A versus B, 0.0048; A versus C, 0.0012; B versus C, 0.0005). The number of viable organisms in the blood after challenge using isolates A and B was greater than the viable counts of C. Serum MDA was lower after challenge with B and C compared with A. Serum TNFα levels were higher after challenge by isolate A compared with isolate C. The bacterial loads of the liver, lower right lung lobe, spleen and mesenteric lymph nodes were greater after challenge by isolate A than the other isolates. It is concluded that infection by multidrug-resistant P. aeruginosa is accompanied by increased survival compared with infection by susceptible isolates; that finding might be explained by the different mechanisms leading to sepsis. Further studies must be done to clarify the significance of these observations for therapeutics.