Chapter 149

The gram-negative enteric bacilli are common causes of a wide variety of infections involving diverse anatomic sites in both healthy and compromised hosts. Some members of this group have become increasingly resistant to antimicrobial treatment, and new infectious syndromes have emerged. Therefore, a thorough knowledge of clinical presentations and appropriate therapeutic choices is necessary for optimal outcomes.

### Epidemiology

Escherichia coli, Klebsiella, Proteus, Enterobacter, Serratia, Citrobacter, Morganella, Providencia, and Edwardsiella are components of the normal animal and human colonic flora and/or of the flora of a variety of environmental habitats, including long-term-care facilities (LTCFs) and hospitals. As a result, except for certain pathotypes of intestinal pathogenic E. coli, these genera are global pathogens. In healthy humans, E. coli is the predominant species of gram-negative bacilli (GNB) in the colonic flora. GNB (primarily E. coli, Klebsiella, and Proteus) only transiently colonize the oropharynx and skin of healthy individuals. In contrast, in LTCF and hospital settings, a variety of GNB emerge as the dominant flora of both mucosal and skin surfaces, particularly in association with antimicrobial use, severe illness, and extended length of stay. This colonization may lead to subsequent infection; for example, oropharyngeal colonization may lead to pneumonia. In general, among adults, the incidence of infection due to these agents increases with age. Thus, as the mean age of the population increases, so will the number of these infections.

### Structure and Function

GNB possess an extracytoplasmic outer membrane, a feature shared generally among gram-negative bacteria. This outer membrane consists of a lipid bilayer with associated proteins, lipoproteins, and polysaccharides [capsule, lipopolysaccharide (LPS)]. The outer membrane interfaces with the bacterial environment, including the human host. A variety of components of the outer membrane are critical determinants in pathogenesis and antimicrobial resistance.

### Pathogenesis

Multiple bacterial virulence factors are required for the pathogenesis of infections caused by GNB. Possession of specialized virulence genes defines pathogens and enables them to infect the host efficiently. Hosts and their cognate pathogens have been co-adapting throughout evolutionary history, and it has been speculated that infection is just one point on the spectrum of evolved relationships between microbes and hosts. At one end of this spectrum is a commensal/symbiotic interaction (e.g., mitochondria—formerly bacteria—within eukaryotic cells); at the other end is a lethal outcome, producing a dead-end relationship (e.g., Ebola virus). During the host-pathogen “chess match” over time, various and redundant strategies have emerged in both the pathogens and their hosts that enable these partners to maintain their coexistence (Table 149-1).

Table 149-1 Interactions of Extraintestinal Pathogenic E. Coli with the Human Host: A Paradigm for Extracellular, Extraintestinal Gram-Negative Bacterial Pathogens

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