Health care–associated infections from invasive medical devices in the intensive care unit (ICU) are a major threat to patient safety. Most published studies of ICU-acquired infections have come from industrialized western countries. In a Centers for Disease Control and Prevention (CDC) National Nosocomial Infections Surveillance (NNIS) System report, the U.S. pooled mean rates of central venous catheter (CVC)–related bloodstream infections, ventilator-associated pneumonia, and catheter-associated urinary tract infections were 4.0 per 1000 CVC days, 5.4 per 1000 mechanical ventilator days, and 3.9 per Foley catheter days, respectively. To ascertain the incidence of device-associated infections in the ICUs of developing countries. Multicenter, prospective cohort surveillance of device-associated infection by using the CDC NNIS System definitions. 55 ICUs of 46 hospitals in Argentina, Brazil, Colombia, India, Mexico, Morocco, Peru, and Turkey that are members of the International Nosocomial Infection Control Consortium (INICC). Rates of device-associated infection per 100 patients and per 1000 device days. During 2002–2005, 21 069 patients who were hospitalized in ICUs for an aggregate 137 740 days acquired 3095 device-associated infections for an overall rate of 14.7% or 22.5 infections per 1000 ICU days. Ventilator-associated pneumonia posed the greatest risk (41% of all device-associated infections or 24.1 cases [range, 10.0 to 52.7 cases] per 1000 ventilator days), followed by CVC-related bloodstream infections (30% of all device-associated infections or 12.5 cases [range, 7.8 to 18.5 cases] per 1000 catheter days) and catheter-associated urinary tract infections (29% of all device-associated infections or 8.9 cases [range, 1.7 to 12.8 cases] per 1000 catheter days). Notably, 84% of Staphylococcus aureus infections were caused by methicillin-resistant strains, 51% of Enterobacteriaceae isolates were resistant to ceftriaxone, and 59% of Pseudomonas aeruginosa isolates were resistant to fluoroquinolones. The crude mortality rate for patients with device-associated infections ranged from 35.2% (for CVC-associated bloodstream infection) to 44.9% (for ventilator-associated pneumonia). These initial data are not adequate to represent any entire country, and likely variations in the efficiency of surveillance and institutional resources may have affected the rates that were detected. Device-associated infections in the ICUs of these developing countries pose greater threats to patient safety than in U.S. ICUs. Active infection control programs that perform surveillance of infection and implement guidelines for prevention can improve patient safety and must become a priority in every country. *For a list of members of the International Nosocomial Infection Control Consortium, see the Appendix.

Sepsis remains a major cause of morbidity and mortality worldwide, with increased burden in low- and middle-resource settings. The role of the inflammatory response in the pathogenesis of the syndrome has supported the modern concept of sepsis. Nevertheless, a definition of sepsis and the criteria for its recognition is a continuous process, which reflects the growing knowledge of its mechanisms and the success and failure of diagnostic and therapeutic interventions. Here we review the evolving concepts of sepsis, from the “systemic inflammatory response syndrome triggered by infection” (Sepsis-1) to “a severe, potentially fatal, organic dysfunction caused by an inadequate or dysregulated host response to infection” (Sepsis-3). We focused in the pathophysiology behind the concept and the criteria for recognition and diagnosis of sepsis. A major challenge in evaluating the host response in sepsis is to characterize what is protective and what is harmful, and we discuss that, at least in part, the apparent dysregulated host response may be an effort to adapt to a hostile environment. The new criteria for recognition and diagnosis of sepsis were derived from robust databases, restricted, however, to developed countries. Since then, the criteria have been supported in different clinical settings and in different economic and epidemiological contexts, but still raise discussion regarding their use for the identification versus the prognostication of the septic patient. Clinicians should not be restricted to definition criteria when evaluating patients with infection and should wisely use the broad array of information obtained by rigorous clinical observation.

Since the definition of systemic inflammatory response syndrome/sepsis was originally proposed, a large amount of new information has been generated showing a much more complex scenario of inflammatory and counterinflammatory responses during sepsis. Moreover, some fundamental mechanisms of sensing and destroying invading microorganisms have been uncovered, which include the discovery of TLR4 as the lipopolysaccharide (LPS) gene, implications of innate immune cells as drivers of the adaptive response to infection, and the modulation of multiple accessory molecules that stimulate or inhibit monocyte/macrophage and lymphocyte interactions. The complexity of the infection/injury-induced immune response could be better appreciated with the application of genomics and proteomics studies, and LPS was a useful tool in many of these studies. In this review, we discuss aspects of bacterial recognition and induced cellular activation during sepsis. Because of the relevance of endotoxin (LPS) research in the field, we focus on LPS and host interactions as a clue to understand microorganisms sensing and cell signaling, then we discuss how this response is modulated in septic patients.

Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiologic alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently, the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without overinterpretation. Hopefully, a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.