Methicillin-resistant Staphylococcus aureus-induced Sepsis: Role of Nitric Oxide

Abstract

Sepsis is the 10th leading cause of death with an incidence of 750,000 cases per year in the United States and mortality rates up to 70 %, depending on severity [1]–[3]. Despite the outstanding achievements in treating sepsis in the past two decades, the morbidity and mortality still remain high. Fluid resuscitation, antibiotic therapy, and vasopressor agents are the basic treatment approach for sepsis. However, the increasing resistance of microorganisms to antibiotics and severe hypotension refractory even to aggressive fluid replacement and vasopressors complicates the course of therapy. Underestimation of the heterogeneity of the clinical symptoms/syndromes underlying the variations in the pathology, particularly the nature of the infectious agents and the diverse host responses to the different stimuli, may also diminish, at least in part, the effectiveness of the therapeutic interventions. Until 1980, Gram-negative microorganisms predominantly caused sepsis and accordingly extensive research has been dedicated to exploring the pathophysiology of and therapeutic approaches to Gram-negative sepsis-related multiple organ dysfunction, specifically Pseudomonas aeruginosa-induced septic changes. However, bacterial epidemiology evolves constantly and since 1990 sepsis due to Gram-positive cocci has increased in frequency and in antimicrobial resistance becoming a large causative factor for sepsis [3]. Staphylococcus aureus bacteremia, especially those species resistant to methicillin (MRSA), has become a major source of morbidity and mortality [4]–[6]. Despite the alarming trend of increased incidence of MRSA-related sepsis, the pathophysiological aspects of MRSA-induced sepsis or septic shock are neither well-described nor widely discussed.