title: 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 (TNFalpha). 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 TNFalpha 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.
authors.affiliation: 4th Department of Internal Medicine, Medical School, University of Athens, Attikon University General Hospital, Athens 124 64, Greece. giamarel@internet.gr
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.forename: Vassilios
authors.initials: V
authors.lastname: Koussoulas
authors.forename: Charalambos
authors.initials: C
authors.lastname: Panagou
authors.forename: Theodoros
authors.initials: T
authors.lastname: Adamis
authors.forename: Fotini
authors.initials: F
authors.lastname: Baziaka
authors.forename: Ioannis
authors.initials: I
authors.lastname: Skiadas
authors.forename: Despina
authors.initials: D
authors.lastname: Perrea
authors.forename: Amalia
authors.initials: A
authors.lastname: Dionyssiou-Asteriou
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D018432:Drug Resistance, Multiple; D006801:Humans; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008198:Lymph Nodes / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D011817:Rabbits; D018805:Sepsis / Q000188:drug therapy*; D013154:Spleen / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents