Enterobacter cloacae Complex: Clinical Impact and Emerging Antibiotic Resistance

Maria Lina Mezzatesta; Floriana Gona; Stefania Stefani


Future Microbiol. 2012;7(7):887-902. 

In This Article

Abstract and Introduction


Species of the Enterobacter cloacae complex are widely encountered in nature, but they can act as pathogens. The biochemical and molecular studies on E. cloacae have shown genomic heterogeneity, comprising six species: Enterobacter cloacae, Enterobacter asburiae, Enterobacter hormaechei, Enterobacter kobei, Enterobacter ludwigii and Enterobacter nimipressuralis, E. cloacae and E. hormaechei are the most frequently isolated in human clinical specimens. Phenotypic identification of all species belonging to this taxon is usually difficult and not always reliable; therefore, molecular methods are often used. Although the E. cloacae complex strains are among the most common Enterobacter spp. causing nosocomial bloodstream infections in the last decade, little is known about their virulence-associated properties. By contrast, much has been published on the antibiotic-resistance features of these microorganisms. In fact, they are capable of overproducing AmpC β-lactamases by derepression of a chromosomal gene or by the acquisition of a transferable ampC gene on plasmids conferring the antibiotic resistance. Many other resistance determinants that are able to render ineffective almost all antibiotic families have been recently acquired. Most studies on antimicrobial susceptibility are focused on E. cloacae, E. hormaechei and E. asburiae; these studies reported small variations between the species, and the only significant differences had no discriminating features.


Bacteria of the Enterobacter genus are facultative anaerobic Gram-negative strains belonging to the family of Enterobacteriaceae and widely found in nature. These microorganisms are saprophytic in the environment, as they are found in soil and sewage, and are also part of the commensal enteric flora of the human GI tract.

Over recent decades, the Enterobacter spp. have taken on clinical significance and have emerged as nosocomial pathogens from intensive care patients.[1] The National Nosocomial Infections Surveillance System reported data on nosocomial bacteremia from 1976 to 1989 in the USA, and the National Healthcare Safety Network (2008) reported that Enterobacter spp. account for approximately 5% of nosocomial bacteremia cases; these data have not varied.[1–3] Another multicenter study focused on 24,179 cases of nosocomial bloodstream infections between 1995 and 2002, showing Enterobacter spp. to be among the ten most commonly isolated nosocomial pathogens with a greater incidence in intensive care unit wards.[4]

Currently, six species have been assigned to the Enterobacter cloacae complex, including E. cloacae, Enterobacter asburiae, Enterobacter hormaechei, Enterobacter kobei, Enterobacter ludwigii and Enterobacter nimipressuralis. Its most important representative, E. cloacae, has emerged as a troublesome pathogen for healthcare institutions globally. E. cloacae accounts for up to 5% of hospital-acquired sepsis, 5% of nosocomial pneumonias, 4% of nosocomial urinary tract infections and 10% of postsurgical peritonitis cases.[5,6] Their clinical significance, especially over the last 15 years, has been reported in many publications, demonstrating their remarkable ability to upregulate or acquire resistance determinants and making them some of the most worrying microorganisms of the current antibiotic era. The last review of Enterobacter spp. was written in 1997 by Sanders and Sanders,[1] and since then, there have been many changes in the taxonomy of this genus in which the species of the E. cloacae complex, due to common characteristics, have emerged as nosocomial pathogens. Moreover, there have also been many developments in clinical diagnostic methods and in nosocomial surveillance of these species that today use new molecular methods.

For these reasons, we propose, with this first review of the E. cloacae complex, to describe the advances, and also provide a comprehensive appraisal, of the relevant microbiological identification methods, as well as their clinical impact. We also report emerging antibiotic-resistance trends of the six species belonging to this complex.