Interactions of Klebsiella pneumoniae with the innate immune system vary in relation to clone and resistance phenotype.

Apart from inadequate antimicrobial treatment, specific virulence factors contribute to the high attributable mortality of infections caused by multidrug-resistant (MDR) Klebsiella pneumoniae. We explored the roles of MDR and clones as virulence determinants of K. pneumoniae and their interaction with innate immunity. Twenty isolates were studied and characterized by resistance phenotype and multilocus sequence type (MLST). Human peripheral blood mononuclear cells (PBMCs) were stimulated for the production of proinflammatory cytokines by live and heat-killed isolates and plasmid DNA; modulation by cellular pathway inhibitors was explored. Survival of 30 mice was recorded after intraperitoneal challenge with susceptible and K. pneumoniae carbapenemase (KPC)-producing isolates. Splenocytes of mice were stimulated for the production of pro- and anti-inflammatory cytokines. Isolates were divided into different patterns of production of tumor necrosis factor alpha (TNF-α) and interleukin-1ß (IL-1ß) poststimulation in relation to both the MLST clone and resistance phenotype. The sequence type 383 (ST383) clone producing Verona integron-encoded metallo-ß-lactamase (VIM) stimulated high production of both TNF-α and IL-1ß. Clone ST17 producing KPC elicited low TNF-α production; this was reversed by Toll-like receptor 9 (TLR9) antagonists, indicating an effect of plasmid DNA. This isolate was linked with early death of mice compared to high-TNF-α-producing isolates. We conclude that KPC-producing isolates seem to be highly virulent in a low-TNF-α-release environment, suggesting an immunoparalysis induction mechanism. KPC plasmids may directly contribute to the immune system stimulation.

Can procalcitonin monitoring reduce the length of antibiotic treatment in bloodstream infections?

Antibiotic overconsumption and subsequent bacterial multidrug resistance are associated with increased mortality, length of hospitalisation and healthcare costs. Discontinuation of antibiotic treatment in severe infections, such as bloodstream infections (BSIs), is a demanding clinical decision. In this review, we aim to investigate the usefulness of procalcitonin (PCT) monitoring in guiding appropriate treatment duration in BSIs and its impact on clinical outcomes. Data from clinical studies conducted after 2005 that included patients with BSIs indicate that change of PCT is an early indicator for prognosis in terms of survival and, overall, support the usefulness of a PCT-guided clinical algorithm in reducing the duration of antibiotic treatment without compromising survival. Furthermore, the presented data indicate that PCT assessment is helpful in the diagnosis of infective endocarditis. In conclusion, monitoring of PCT together with evaluation of the clinical situation is a valuable tool in reducing the length of antimicrobial treatment in BSIs.