New targets for new therapeutic approaches

Abstract

Because of its resistance profiles, Pseudomonas aeruginosa remains probably one of the challenging bacteria responsible for ventilator-associated pneumonia in the ICU. Nevertheless, a much better understanding of its mechanism of virulence, such as the type 3 secretion system that can also impact on resistance, gives some opportunities for management improvement. The most promising approach is probably the production of monoclonal antibodies that enable not only more targeted treatments but also development of some early preemptive approaches at the time of colonization through real-time diagnosis.

New Strategies Targeting Virulence Factors of Staphylococcus aureus and Pseudomonas aeruginosa

“…40,46,56 Bacteria secrete QS molecules during replication to levels that activate the expression of certain genes, such as the agr gene expression pathway in S. aureus [57][58][59] and lasR and or rhlR genes expression and rhamnolipid production by P. aeruginosa. 60 Examples of QS molecules include the N-acyl homoserine lactones (AHLs) used by gram-negative species, derivatives of the sugar-like molecule dihydroxypentanedione used by both gram-negative and gram-positive bacteria, auto-inducing oligopeptides used by gram-positive bacteria, and quinolone signaling molecules found in Pseudomonas spp. 56 QS inhibitors include AHL-degrading enzymes such as AHL lactonases and acylases, naturally occurring halogenated furanones and several AHL analogues, 40,56,61 and the antibiotic azithromy-cin, which has preferential inhibitory effects on transcription of lasR and rhlR codons and reduces rhamnolipid-dependent VAP in patients at high risk for P. aeruginosa nosocomial pneumonia.…”

Rebuttal From Dr Kollef

“…6 Similarly, the development of monoclonal antibodies targeting virulence factors in MDR GNB, such as the type 3 secretion mechanism in P aeruginosa, hold promise for future nonantibiotic therapy for VAP. 7 In summary, aerosolized antibiotics for the treatment of VAP are likely to be a valuable addition to our therapeutic armamentarium, especially for the treatment of infections attributed to MDR GNB. However, the use and delivery of aerosolized antibiotics should be guided by indications supported by appropriately designed clinical trials and should only be used to treat salvageable patients with true infections given the variability of documented practices.…”