Enterobacter cloacae is a Gram-negative bacterium that commonly causes serious infections, particularly within healthcare settings. It is part of the Enterobacteriaceae family and is recognized as a significant opportunistic pathogen, often complicating the recovery of hospitalized patients. While it is a natural component of the human gut flora, it becomes problematic when it invades sterile body sites, often via medical devices. Treating E. cloacae infections is challenging due to its inherent and acquired mechanisms of antibiotic resistance.
Characteristics and Common Infection Sites
Enterobacter cloacae is a rod-shaped, facultatively anaerobic bacterium that is motile and can ferment lactose. This characteristic is often used for initial laboratory identification. It is an opportunistic pathogen, typically causing disease only in individuals with weakened immune systems or compromised natural barriers. The bacterium is often grouped into the Enterobacter cloacae complex (ECC), which includes closely related species with similar clinical significance and resistance patterns.
The organism thrives in environmental niches like soil, water, and sewage, but its presence in hospital environments is the greatest concern. Patients with prolonged hospital stays, especially in intensive care units, are most susceptible. Underlying conditions like cancer, diabetes, or severe trauma also increase risk. The presence of medical devices such as central venous catheters, urinary catheters, and mechanical ventilators significantly increases the risk of infection.
E. cloacae causes a wide range of healthcare-associated infections. Common sites include the urinary tract, often leading to complicated urinary tract infections in catheterized patients. It is also a frequent cause of bloodstream infections, ventilator-associated pneumonia, and surgical site infections. Less commonly, the bacterium can cause osteomyelitis, endocarditis, and meningitis, particularly in newborns or post-neurosurgical patients.
Confirming the Infection
The definitive diagnosis of an E. cloacae infection relies on isolating and identifying the bacterium from a clinical sample taken from the suspected site. This process begins with obtaining appropriate samples, such as blood cultures, urine, sputum, or tissue swabs, which are then placed on growth media. A Gram stain provides a rapid, preliminary identification of Gram-negative rods, which helps guide the initial selection of broad-spectrum antibiotics.
Once the organism is cultured, Antimicrobial Susceptibility Testing (AST) is mandatory for this pathogen. AST determines which specific antibiotics are effective against the isolated strain by measuring its growth response to various drugs. This testing is necessary because standard treatment protocols cannot be reliably used due to the high likelihood of resistance.
AST results are reported as susceptible, intermediate, or resistant, dictating the final, targeted treatment plan. For E. cloacae, AST is important to detect resistance mechanisms like AmpC beta-lactamase or carbapenemases. Rapid molecular tests are increasingly used to quickly identify specific resistance genes, such as those for carbapenemase production, which reduces the time needed to initiate appropriate therapy.
Standard Antimicrobial Treatment Approaches
For susceptible strains of E. cloacae, treatment typically involves carbapenems, such as meropenem or imipenem. These drugs are considered the most reliable beta-lactams for serious Enterobacter infections because they are structurally stable against many beta-lactamase enzymes. Carbapenems are often the preferred choice for empirical therapy—treatment started before AST results are finalized—in severe suspected infections.
Another effective option for susceptible strains is the fourth-generation cephalosporin, cefepime, which is stable against AmpC beta-lactamases. However, the use of third-generation cephalosporins, such as ceftriaxone, is discouraged for serious E. cloacae infections. The bacterium can quickly develop resistance to these drugs during treatment due to the induction and overproduction of its chromosomal AmpC enzyme, leading to clinical failure.
Fluoroquinolones or aminoglycosides may be considered if the strain is confirmed susceptible, particularly for less severe infections like an uncomplicated urinary tract infection. The removal or replacement of any infected medical device is also a fundamental part of the strategy. Foreign materials like catheters or central lines can act as a persistent source of infection and must be addressed for a definitive cure.
Managing Drug-Resistant Strains
The management of drug-resistant E. cloacae strains is challenging due to the pathogen’s capacity for both intrinsic and acquired resistance. A major intrinsic mechanism is the production of AmpC beta-lactamase, an enzyme encoded on the chromosome that inactivates many common beta-lactam antibiotics. While carbapenems are resistant to AmpC, the enzyme’s expression can be induced by certain antibiotics, causing resistance to emerge during therapy with drugs like third-generation cephalosporins.
A greater concern is the acquisition of carbapenem resistance, which renders first-line agents ineffective. This resistance is often mediated by plasmid-encoded carbapenemases, such as Klebsiella pneumoniae Carbapenemase (KPC), which break down carbapenems. The presence of these genes drastically limits treatment options and necessitates the use of specialized agents.
For these multidrug-resistant (MDR) strains, treatment relies on newer beta-lactam/beta-lactamase inhibitor combinations designed to overcome resistance mechanisms like KPC. Ceftazidime-avibactam is frequently recommended as a first-line treatment for KPC-producing strains. Meropenem-vaborbactam and imipenem-cilastatin-relebactam offer effective alternatives, pairing an antibiotic with an inhibitor that protects the drug from the destructive enzyme.
Specialized drugs are reserved for highly resistant strains, including those that produce metallo-beta-lactamases (MBLs), which are not inhibited by the aforementioned combinations. Complex cases may involve the combination of ceftazidime-avibactam with aztreonam, or the use of the siderophore cephalosporin cefiderocol. Older, more toxic antibiotics like polymyxins (colistin) or tigecycline may also be employed, often in combination, though their use is limited by potential side effects.