Gram-positive and Gram-negative Sepsis: Two Disease Entities?
Sepsis and its sequelae are the leading causes of death among critically ill patients in non-coronary intensive care units (ICUs). Paradoxically, despite a fall in the mortality rate, the incidence of sepsis has increased, with about 750,000 cases annuall
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Gram-positive and Gram-negative Sepsis: Two Disease Entities? S. Leaver, A. Burke Gaffney, and T.W. Evans
Introduction Sepsis and its sequelae are the leading causes of death among critically ill patients in non-coronary intensive care units (ICUs). Paradoxically, despite a fall in the mortality rate, the incidence of sepsis has increased, with about 750,000 cases annually resulting in about 215,000 deaths a year [1, 2]. This is, in part, a consequence of increased provision of intensive care facilities in the UK and elsewhere [3]. Many factors contribute to the increasing incidence of sepsis and its sequelae including improved chemotherapy for malignancies leading to greater numbers of immunosuppressed patients; more organ transplantations and cardiac surgery; and also the increased use of internal devices such as prostheses, chest drains and endotracheal tubes [3]. Moreover, 40 – 60 % of patients with severe sepsis develop acute lung injury (ALI) or its extreme manifestation, acute respiratory distress syndrome (ARDS), which is associated with a particularly high mortality [4, 5]. In addition, there has been a change in the etiology of sepsis in recent years. Thus, although bacteria still cause the majority of cases of sepsis an increasing proportion is due to Gram-positive rather than Gram-negative sepsis [6]. Indeed, a study from the USA performed in the year 2000 showed that Gram-positive bacteria accounted for 52.1 % of hospital admissions with sepsis, compared to 37.6 % for Gram-negative organisms [1]. Moreover, whereas mortality related to Gram-negative organisms has decreased that due to Gram-positive infections remains the same and the overall mortality resulting from Gram-positive septicemia is higher than that from Gram-negative bacteria [7]. Of particular concern is the increasing emergence of multi-resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), which may have contributed to this [8] with around 50 % of nosocomial S. Aureus isolates being methicillin-resistant strains. Infection with MRSA is associated with increases in ICU length of stay, post operative complications, treatment costs, and mortality [8]. Despite these emerging differences between Gram-negative and Gram-positive sepsis, current clinical dogma dictates that both should be managed with similar therapeutic protocols. However, evidence suggests that the mechanisms contributing to the clinical manifestations of Gram-positive and Gram-negative sepsis differ and that they, therefore, might represent distinct disease entities. We suggest that a better understanding of these differences could provide a new target to develop more specific therapeutic strategies for sepsis. In this chapter we discuss differences reported between Gram-positive and Gram-negative disease in stimuli, signaling pathways, cytokine release, clinical trial outcomes, clinical presentation, genetic predisposition, and therapeutic implications.
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S. Leaver, A. Burke Gaffney, and T.W. Evans
Bacterial Components and the Origins of Se
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