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Semin Respir Crit Care Med 2017; 38(03): 346-358
DOI: 10.1055/s-0037-1602715
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

New Strategies Targeting Virulence Factors of Staphylococcus aureus and Pseudomonas aeruginosa

Bruno François
1   Intensive Care Unit/CIC-1435, University Hospital of Limoges, Limoges, France
,
Charles-Edouard Luyt
2   Medical Intensive Care Unit, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique–Hôpitaux de Paris, Paris, France, and Sorbonne Universités, UPMC Université Paris 06, INSERM, UMRS_1166-ICAN Institute of Cardiometabolism and Nutrition, Paris, France
,
C. Kendall Stover
3   Research and Development, Research Infectious Disease, MedImmune, Gaithersburg, Maryland
,
Jeffery O. Brubaker
4   Scientific Publications, Medical Communications, MedImmune, Gaithersburg, Maryland
,
Jean Chastre
5   Service de Réanimation Médicale, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75651 Paris Cedex 13, France
,
Hasan S. Jafri
6   Clinical Development, Infectious Disease and Vaccines, MedImmune, Gaithersburg, Maryland
› Author Affiliations
Further Information

Publication History

Publication Date:
04 June 2017 (online)

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Abstract

Morbidity, mortality, and economic burden of nosocomial pneumonia caused by Staphylococcus aureus and Pseudomonas aeruginosa remain high in mechanically ventilated and hospitalized patients despite the use of empirical antibiotic therapy or antibiotics against specific classes of pathogens and procedures to reduce nosocomial infections in hospital settings. Newer agents that neutralize or inhibit specific S. aureus or P. aeruginosa virulence factors may eliminate or reduce the risk for developing pneumonia before or during mechanical ventilation and may improve patient outcomes through mechanisms that differ from those of antibiotics. In this article, we review the types, mechanisms of action, potential advantages, and stage of development of antivirulence agents (AVAs) that hold promise as alternative preventive or interventional therapies against S. aureus– and P. aeruginosa–associated nosocomial pneumonias. We also present and discuss challenges to the effective utilization of AVAs separately from or in addition to antibiotics and the design of clinical trials and meaningful study end points.

Keywords

antivirulence agents - Staphylococcus aureus - Pseudomonas aeruginosa - nosocomial pneumonia - ventilator-associated pneumonia
 

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