GRAM-POSITIVE SEPSIS: Mechanisms and Differences from Gram-Negative Sepsis

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In modern intensive care settings, gram-positive bacteria account for up to 50% of severe sepsis or septic shock cases, yet the pathogenesis of gram-positive shock is poorly understood.36, 45 This contrasts with the well-researched field of gram-negative sepsis, where the role of bacterial endotoxin is known to be central to development of septic shock. In this article, we attempt to review the mechanisms by which a range of clinically important gram-positive bacteria cause septic shock (Table 1) and, where appropriate, highlight contrasts and similarities with gram-negative pathogenesis.

Clinical differentiation of gram-positive and gram-negative sepsis is often attempted but seldom successful. There are situations, however, where it is possible to predict the type of infecting organism. Septic shock may be related to a focal infection, such as necrotizing fasciitis, which is known to be associated with a particular bacterial species, in this case Streptococcus pyogenes. Similarly, there may be clues from pathognomonic rashes, for example, streptococcal and staphylococcal toxic shock syndromes and meningococcemia. Finally, particular groups of patients may be particularly susceptible to septic shock caused by certain types of bacteria; urology patients with septic shock are likely to have gram-negative infection, and asplenic patients are more likely to suffer pneumococcal shock. Predicting the bacterial causes of septic shock may present an academic challenge, but in practice, broad-spectrum antibiotics will be used empirically until the laboratory isolates a causative pathogen.

The broad mechanisms by which both gram-positive and gram-negative organisms cause shock involve bacterial factors (cell wall, soluble/secreted products) and host factors (susceptibility, primary (immune) response, secondary (tissue) response). There are, however, many contrasts in the ways in which bacteria apply these mechanisms, and this will affect the success of any novel empiric therapeutic approaches to sepsis.

Section snippets

BACTERIAL FACTORS

Gram-positive infections often arise from infected foci at, or just under, the body surface (e.g., skin infections, wound infections, muscle). Infection is often associated with an influx of host neutrophils, and the bacteria have an array of tools that allow, first, invasion of the outer host layers and, second, evasion of neutrophil-mediated phagocytosis. The processes of invasion and killing of phagocytes contribute to the inflammatory cascade leading to septic shock. In contrast,

Host Susceptibility Factors

Certain patient groups are more likely to sustain infection owing to particular groups of pathogens. Patients with surgical or traumatic wounds distant from the abdomen are more likely to develop wound infections and septic shock from gram-positive bacteria. In addition, certain groups of patients respond to infection in a distinct fashion. One example is the “alpha strep shock syndrome,” characteristically seen in neutropenic patients who have undergone bone marrow transplantation and who

SUMMARY

This article has reviewed the mechanisms by which gram-positive bacteria lead to septic shock, with regard to bacterial structure and toxicology and the host responses elicited both in animal models and in the clinical setting. Gram-positive organisms are better suited to invade host tissues and elicit, in general, a brisker phagocytic response than gram-negative organisms. The lack of endotoxin in the outer cell wall is compensated for by the presence of exposed peptidoglycan and a range of

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      In general, Gram positive and Gram negative bacteria are able to start the infection and promote the evolution for a more complicate case, as the sepsis. However, the fact that gram-positive bacteria are better suited to invade tissues than Gram-negative bacteria is known (Minasyan, 2017; Sriskandan and Cohen, 1999). The reason is based in the fact that the lack of endotoxin in the outer cell wall is compensated for by the presence of exposed peptidoglycan and a range of other toxic secreted products.

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    Address reprint requests to Shiranee Sriskandan, MD, PhD, Dept of Infectious Diseases, Imperial College School of Medicine, at Hammersmith Hospital, Du Cane Road, London W12 ONN, UK

    This work was supported by the Medical Research Council (U.K.) through a Career Development Award to Shiranee Sriskandan

    *

    Department of Infectious Diseases, Imperial College School of Medicine at Hammersmith Hospital, London, United Kingdom

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