Enterobacter

  • TRANSMISSION ROUTE: Variable

Definition

Enterobacter are gram-negative, aerobic, motile bacteria found in soil, water, and the human intestinal tract. Enterobacter is an opportunistic pathogen responsible for various infections.

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Natural Habitat and Features

Enterobacter is a rod-shaped, gram-negative bacteria in the family Enterobacteriaceae, which also includes the genera Klebsiella, Escherichia, Citrobacter, and Serratia. Enterobacter infections exhibit symptoms similar to those of other gram-negative bacteria.

Not all Enterobacter species cause diseases in humans. Among the most common pathogenic species are E. aerogenes and E. cloacae. Various species can be found in water, plants, plant materials, insects, and dairy products, as well as in human and nonhuman animal feces. E. cloacae has been used in the biological control of plant diseases and insects on mulberry leaves.

Enterobacter species are rod-shaped bacteria that can be identified by large lactose-fermenting colonies of gram-negative rods that are either raised or mucoid. Because of lactose fermentation, these mucoid colonies appear pink to purple. Enterobacter strains are mainly fimbriated and slime-forming.

Species of Enterobacter can be differentiated by their ability to ferment particular sugars and by their possession of arginine dihydrolase, lysine, and ornithine decarboxylase. E. aerogenes and E. cloacae can be differentiated by testing for lysine decarboxylase and arginine dihydrolase. Most Enterobacter species grow well at 86 degrees to 98.6 degrees Fahrenheit (30 degrees to 37 degrees Celsius), using eosin methylene blue (EMB) agar. MacConkey agar, when used, will give a red stain to the growing colonies.

Pathogenicity and Clinical Significance

Gram-negative pathogens possess endotoxins, giving them pathogenic properties. The most common pathogenic Enterobacter species are E. cloacae and E. aerogenes. These types of bacteria can cause opportunistic infections in immunocompromised persons. Enterobacter rarely becomes problematic in a healthy person. The urinary and respiratory tracts are the most common sites of infection.

The acquisition of Enterobacter infections can be from either endogenous or exogenous sources. Most nosocomial (hospital-acquired) Enterobacter infections cannot be traced to a single common exogenous source. Endogenous sources of nosocomial Enterobacter infections typically arise from a previously colonized site, such as the skin, gastrointestinal tract, or urinary tract. A person can be colonized with more than one Enterobacter species at any given time.

Nosocomial acquisition of Enterobacter is more common than community-acquired Enterobacter. These infections are acquired from prolonged hospitalization, especially in intensive care units, often as a result of poor handwashing technique, invasive procedures, mechanical ventilation (which can cause ventilator-associated pneumonia), hyperalimentation with dextrose, indwelling catheters (such as intravenous catheters), or prior use of antimicrobial agents.

Incubation times for Enterobacter are variable. Symptoms can appear as early as two hours to three weeks after infection, with the majority occurring between two hours and two days.

Enterobacter bacteria associated with skin and soft-tissue infections, burn and surgical-wound infections, intra-abdominal infections, endocarditis, septic arthritis, osteomyelitis, meningitis, and bloodstream infections further complicate an already ubiquitous pathogen. Morbidity and mortality rates with Enterobacter are significant. The severity of the underlying disease is the most critical factor in determining the risk of mortality in a person with an Enterobacter infection. Additional factors include other aspects of treatment and the microorganism’s virulence and resistance. E. cloacae has the highest mortality rate of all Enterobacter infections.

Drug Susceptibility

Pharmacotherapy's goals in treating Enterobacter infection are to reduce morbidity, eradicate infection, and prevent complications. Prior antimicrobial agent use is the most frequently cited risk factor for developing Enterobacter resistance. Initial drugs of choice include aminoglycosides, carbapenems, fluoroquinolones, and fourth-generation cephalosporins. Susceptibility testing is essential because some Enterobacter infections are resistant to the initial drugs of choice, making choosing appropriate antimicrobial agents more complicated.

Carbapenems (imipenem and meropenem) are often the most effective drugs of choice against E. cloacae, E. aerogenes, and other Enterobacter species. First- and second-generation cephalosporins are virtually ineffective against Enterobacter. Third-generation cephalosporins show good in vitro activity but increase the risk of developing drug resistance. The combination antibiotic piperacillin/tazobactam has been shown to lower thirty-day mortality rates.

Enterobacter species contain subpopulations of organisms that produce low levels of beta-lactamase. Once exposed to broad-spectrum cephalosporins, the subpopulation of these beta-lactamase-producing organisms will predominate. Thus, an Enterobacter infection that initially appears sensitive to cephalosporins may eventually become resistant during therapy.

Antimicrobial drug resistance occurs when an inactivating enzyme is produced, the drug’s target is altered, and the drug's ability to enter and accumulate in the cell is altered. Resistance can be detected as soon as twenty-four hours after initiation and up to two to three weeks into therapy.

Bacterial resistance to antibiotics continues to be a significant threat. Multiple Enterobacter strains are already resistant to many antibiotics. Infectious disease specialists are instrumental in determining appropriate antibiotic treatment. Handwashing remains the single most helpful tactic in preventing the spread of Enterobacter infections.

Twenty-first century discoveries continue to provide increased insight into Enterobacter infections. Clinical samples have identified Enterobacter xiangfangensis as the most common strain in many countries, and Enterobacter bugandensis was discovered by scientists on the International Space Station (ISS). The strains found on the ISS are unique from those on Earth. They have different genetic makeup, functions, and the ability to survive in a drastically different environment. Antibiotic resistance remains an essential health issue as Enterobacter strains become resistant to even last-resort antibiotics. Finally, new detection techniques have made it easier and faster to identify Enterobacter infections.

Bibliography

Doijad, Swapnil P., et al. "Resolving Colistin Resistance and Heteroresistance in Enterobacter Species." Nature Communications, vol. 14, no. 1, 2023, pp. 1-16, doi.org/10.1038/s41467-022-35717-0. Accessed 2 Oct. 2024.

Forsythe, Stephen J., Sharon L. Abbott, and Johann Pitout. "Klebsiella, Enterobacter, Citrobacter, Cronobacter, Serratia, Plesiomonas, and Other Enterobacteriaceae." Manual of Clinical Microbiology. Edited by James H. Jorgensen, et al. 11th ed., Vol. 1. Washington: ASM, 2015. 714–37.

Ghazawi, Akela, et al. "Genomic Study of High-Risk Clones of Enterobacter Hormaechei Collected from Tertiary Hospitals in the United Arab Emirates." Antibiotics, vol. 13, no. 7, 2024, p. 592, doi.org/10.3390/antibiotics13070592. Accessed 2 Oct. 2024.

Sanders, C. C. "Enterobacter Spp.: Pathogens Poised to Flourish at the Turn of the Century." Clinical Microbiology Reviews, vol. 10, no. 2, 1997, pp. 220-241, doi.org/10.1128/cmr.10.2.220. Accessed 2 Oct. 2024.

Tortora, Gerard J., Berdell R. Funke, and Christine L. Case. Microbiology: An Introduction. 12th ed., San Francisco: Benjamin, 2016.