Stimulation of innate immunity by susceptible and multidrug-resistant Pseudomonas aeruginosa: an in vitro and in vivo study

Abstract

SUMMARYIn attempt to investigate the stimulatory effect of Pseudomonas aeruginosa on innate immunity and to correlate it to its level of resistance to antimicrobials, 20 isolates were applied; 8 isolates were susceptible and 12 multidrug-resistant. Genetic diversity was defined by PFGE. Human monocytes of two healthy volunteers were in vitro stimulated by the isolates for the production of pro-inflammatory (TNF-a , IL-1 b , IL-6, IL-8 and IL-12) and anti-inflammatory cytokines (IL-10), of malondialdehyde and of procalcitonin. Cytokines were estimated by EIA, malondialdehyde by the thiobarbiturate assay and procalcitonin by an immunochemiluminometric assay. Survival of 48 Wistar rats was recorded after induction of sepsis by the intraperitoneal injection of three susceptible and three multidrug-resistant isolates. To test whether comparative effect of the latter isolates on survival correlates with any difference of monocyte-mediated release of pro-inflammatory mediators, monocytes of two rats were in vitro stimulated for the production of TNF-a and of malondialdehyde. In vitro stimulation of human monocytes by the susceptible isolates elicited elevated production of malondiadeheyde, of IL-1 b and of IL-6 compared to stimulation by multidrug-resistant isolates. Similar differences were found for TNF-a and IL-8, but they were not statistically significant. Production of IL-10 and IL-12 was not detected after stimulation with any isolate. Levels of procalcitonin were similar after induction with either susceptible or multidrug-resistant isolates. Mean survival of animals was 7·56, 21·80 and 55·20 h, respectively, after challenge by the susceptible isolates and 28·89, 61·8 and more than 120 h, respectively, after challenge by the multidrug-resistant isolates. Differences of survival were accompanied by greater rodent monocyte-release of TNF-a and malondialdehyde after stimulation by the susceptible isolates compared to multidrug-resistant ones. It is concluded that considerable differences are encountered on the stimulation of human monocytes by susceptible and resistant isolates of Pseudomonas aeruginosa . These results correlate with in vivo evidence and might influence decision on therapeutics.

Prospective Multicenter Study of the Impact of Carbapenem Resistance on Mortality in Pseudomonas aeruginosa Bloodstream Infections

“…These findings may be consistent with in vitro ev- idence showing that resistance genes or mutations can alter the fitness of microorganisms (4), making them less virulent and reducing their capacity to generate deleterious host inflammatory responses (22). Nevertheless, the complex interplay between resistance mechanisms, cost-compensatory mutations, fitness, and virulence in the clinical setting has yet to be fully elucidated (1).…”

Interactions of Klebsiella pneumoniae with the Innate Immune System Vary in Relation to Clone and Resistance Phenotype

“…Several attempts to correlate resistance and individual isolate characteristics to virulence and immune system stimulation have been made in the past. Giamarellos-Bourboulis et al (15) demonstrated that significant differences are encountered in host-pathogen interactions between MDR and susceptible Pseudomonas aeruginosa isolates; susceptible isolates induced a greater release of proinflammatory cytokines accompanied by increased mortality in rodents. The opposite was found when the study design was repeated with E. coli species.…”

Pandrug-resistant isolate of Klebsiella pneumoniae causes less damage than drug-susceptible isolates in a rabbit model

“…No analgesics were used, as the operation was brief. A 2 cm-long midline incision was made on the neck to expose the right inner jugular vein [8,9]. An 18G catheter was inserted and 1 × 10 8 colony forming units (cfu) per kg of the prepared K. pneumoniae isolate was injected, in a volume of 2.0 mL.…”

“…Some studies have concluded that patients infected with bacteria susceptible to drug treatment had a better outcome than did patients infected with multidrug-resistant bacteria [6,7]. Other studies by Giamarellos-Bourboulis and Bristianou showed that rabbits infected with drug susceptible strains of E. coli had worse outcomes than those infected with multidrug-resistant strains, and cytokine release patterns were di erent [8][9][10]. Glauser suggested that multidrug-resistant isolates might interfere with the mechanism leading to sepsis, resulting in lower pathogenicity [11].…”