From the Guidelines
Enterobacter cloacae infections should be treated with carbapenems, such as meropenem (1g IV every 8 hours) or imipenem (500mg IV every 6 hours), as the first-line therapy, especially for severe infections, as recommended by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines 1.
Treatment Options
- For patients with bloodstream infections (BSI) and severe infection due to third-generation cephalosporin-resistant Enterobacterales (3GCephRE), carbapenem therapy, such as meropenem or imipenem, is strongly recommended 1.
- For less severe infections, alternatives like piperacillin-tazobactam, amoxicillin/clavulanic acid, or quinolones may be considered, with the choice of antibiotic depending on the susceptibility pattern of the isolate and the site of infection 1.
- For complicated urinary tract infections (cUTI), aminoglycosides or IV fosfomycin may be conditionally recommended, especially when the infection is not severe and the patient does not have septic shock 1.
Duration of Treatment
- The duration of treatment should be individualized based on the site of infection, severity, and clinical response, but typically ranges from 7 to 14 days 1.
Important Considerations
- Susceptibility testing is crucial to guide definitive therapy and ensure appropriate coverage, as Enterobacter cloacae can produce AmpC beta-lactamases that may lead to resistance during treatment 1.
- Source control, such as drainage of abscesses or removal of infected devices, is essential in the management of Enterobacter cloacae infections 1.
- Clinical monitoring is vital to detect any potential development of resistance during therapy with initially effective antibiotics 1.
From the FDA Drug Label
AVYCAZ (ceftazidime and avibactam) in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections (cIAI) in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa.
Treatment of Enterobacter cloacae infections can be achieved with AVYCAZ (ceftazidime and avibactam) in combination with metronidazole, for complicated intra-abdominal infections (cIAI), and also for complicated urinary tract infections (cUTI) and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) 2.
- Key points:
- AVYCAZ is indicated for the treatment of cIAI, cUTI, and HABP/VABP caused by Enterobacter cloacae.
- The recommended dosage of AVYCAZ is 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered every 8 hours by intravenous (IV) infusion over 2 hours in patients 18 years of age and older with CrCl greater than 50 mL/min.
- For treatment of cIAI, metronidazole should be given concurrently.
- Clinical cure rates for Enterobacter cloacae were 11/13 (84.6%) in the AVYCAZ plus metronidazole group and 16/19 (84.2%) in the meropenem group 2.
From the Research
Treatment Options for Enterobacter cloacae
- Cefepime has been shown to be effective in treating Enterobacter cloacae infections, including those caused by carbapenem-hydrolyzing beta-lactamase-producing strains 3.
- Ceftazidime/avibactam and meropenem/vaborbactam are newer agents that have been approved for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections, including those caused by Enterobacter cloacae 4, 5, 6.
- Cefiderocol, a novel siderophore cephalosporin, has also been shown to be effective against Enterobacter cloacae, but its use may be limited by the development of resistance 7, 5.
- Other treatment options, such as amikacin, polymyxins, tigecycline, and fosfomycin, may be effective against some Enterobacter cloacae strains, but their use is often limited by adverse effects or the need for combination therapy 4.
Mechanisms of Resistance
- Enterobacter cloacae can develop resistance to carbapenems and other beta-lactam antibiotics through the production of carbapenem-hydrolyzing beta-lactamases, such as the NmcA enzyme 3.
- The development of resistance to ceftazidime/avibactam and meropenem/vaborbactam can occur through the selection of resistant mutants or the transfer of resistance genes 6.
- The AmpC β-lactamase can also contribute to resistance to ceftazidime/avibactam and cefiderocol in Enterobacter cloacae 7.
Diagnosis and Treatment Considerations
- Accurate and rapid diagnosis of Enterobacter cloacae infections, including the determination of antimicrobial resistance mechanisms, is crucial for effective treatment 4.
- The choice of treatment agent should be based on the results of antimicrobial susceptibility testing and the mechanism of resistance present in the infecting strain 6.
- Antibiotic stewardship programs should be implemented to ensure the appropriate use of these agents and to minimize the development of resistance 5, 6.