What is the treatment of choice for Enterobacter cloacae complex (E. cloacae) bacteremia?

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DS

Dainyal Siddiqui, MD

Internal Medicine

MJ

Manuel Jimenez, MD

Cardiology

FP

Franz Pierre-Louis, MD

Infectious Disease

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Last updated: May 9, 2025 • View editorial policy

From the Guidelines

The treatment of choice for Enterobacter cloacae complex bacteremia is a carbapenem, specifically meropenem or imipenem, as targeted therapy for patients with bloodstream infections (BSI) and severe infection due to third-generation cephalosporin-resistant Enterobacterales (3GCephRE) 1.

Key Considerations

  • For patients with BSI due to 3GCephRE without septic shock, ertapenem may be used as an alternative to imipenem or meropenem 1.
  • The use of carbapenems is recommended due to the high risk of inducible resistance to third-generation cephalosporins, such as cefepime, in Enterobacter species 1.
  • Source control through removal of infected devices or drainage of abscesses is crucial for successful treatment.

Antibiotic Therapy

  • Meropenem (1 gram IV every 8 hours) or imipenem-cilastatin (500 mg IV every 6 hours) are recommended for 10-14 days, depending on source control and clinical response 1.
  • For patients with severe infections or sepsis, initial empiric therapy may include combination treatment with an aminoglycoside, such as amikacin, until susceptibility results are available 1.

Important Notes

  • Cephamycins, such as cefoxitin, and cefepime are not recommended for 3GCephRE infections due to limited evidence and potential for inducible resistance 1.
  • Tigecycline is not recommended for infections caused by 3GCephRE due to limited efficacy 1.
  • New beta-lactam/beta-lactamase inhibitors (BLBLI) are reserved for extensively resistant bacteria and should be avoided for infections caused by 3GCephRE, unless necessary, due to antibiotic stewardship considerations 1.

From the FDA Drug Label

Table 16. Clinical Cure Rates at TOC by Baseline Pathogen from the Phase 3 cIAI Trial, mMITT Population Aerobic Gram-negative group or pathogenAVYCAZ plus metronidazolea n/N (%)Meropenemb n/N (%) Enterobacteriaceae272/334 (81.4)305/353 (86.4) Escherichia coli218/271 (80.4)248/285 (87.0) Klebsiella pneumoniae40/51 (78.4)37/49 (75. 5) Klebsiella oxytoca14/18 (77.8)12/15 (80.0) Enterobacter cloacae11/13 (84.6)16/19 (84.2) Citrobacter freundii complex14/18 (77.8)9/12 (75.0) Proteus mirabilis5/8 (62.5)7/9 (77.8) Pseudomonas aeruginosa30/35 (85.7)34/36 (94.4)

The treatment of choice for Enterobacter cloacae complex bacteremia is not explicitly stated in the provided drug labels. However, based on the clinical cure rates presented in Table 16, AVYCAZ (ceftazidime and avibactam) plus metronidazole and meropenem appear to have similar efficacy against Enterobacter cloacae, with clinical cure rates of 84.6% and 84.2%, respectively 2.

From the Research

Treatment Options for Enterobacter cloacae Complex Bacteremia

The treatment of choice for Enterobacter cloacae complex bacteremia is a topic of ongoing research and debate. Several studies have investigated the effectiveness of different antibiotics in treating this condition.

Carbapenems as a Treatment Option

  • Carbapenems are considered a treatment of choice for bacteremia caused by potential AmpC-producing bacteria, including Enterobacter spp. 3
  • A study found that carbapenem treatment was not advantageous to alternative antibiotics, including third-generation cephalosporins, among patients with Enterobacter spp. bacteremia 3
  • However, another study suggested that carbapenem therapy may provide therapeutic benefits for ESBL-producing E. cloacae that cause bacteremia 4

Cefepime as a Treatment Option

  • Cefepime is one of the therapeutic alternatives for cefepime-susceptible E. cloacae bacteremia, but it is inefficient for cases of cefepime-SDD E. cloacae bacteremia compared with carbapenem therapy 5
  • A study found that cefepime represents a safe therapeutic option and an alternative to carbapenems to treat BSIs due to Ecl when the prevalence of ESBL-producers is low 6

Other Treatment Options

  • A study evaluated the effect of increasing meropenem MIC on the killing activity of meropenem in combination with amikacin or polymyxin B against MBL- and KPC-producing Enterobacter cloacae, and found that bactericidal activity and synergy were maintained for 48 hours in isolates exposed to meropenem and amikacin 7
  • Another study found that patients with BSIs due to Ecl showed a favourable treatment outcome with cefepime, carbapenems, ceftriaxone, piperacillin/tazobactam, and ciprofloxacin 6

Key Findings

  • The choice of antibiotic for treating Enterobacter cloacae complex bacteremia depends on various factors, including the susceptibility of the isolate and the presence of ESBL or AmpC enzymes 3, 5, 4, 6
  • Carbapenems and cefepime are potential treatment options, but their effectiveness may vary depending on the specific circumstances of the infection 3, 5, 4, 6

References

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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