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Gram-negative bacilli (GNB) are normal components of the human colonic microbiota and/or a number of environmental habitats and can colonize mucosal and skin surfaces, especially in pts in long-term-care facilities and hospital settings. GNB cause a wide variety of infections involving diverse anatomic sites in both healthy and compromised hosts; extraintestinal infections due to Escherichia coli and, to a lesser degree, Klebsiella species are most common. Isolation of GNB from any sterile site almost always implies infection, whereas isolation from nonsterile sites requires clinical correlation. Early appropriate antimicrobial therapy improves outcomes. Given worldwide increases in multidrug-resistant GNB (e.g., due to extended-spectrum β-lactamases [ESBLs] and AmpC β-lactamases), combination empirical antimicrobial therapy pending susceptibility results may be appropriate for critically ill pts.