What is the recommended treatment for Enterobacter cloacae bacteremia in an adult without β‑lactam allergy?

Treatment of Enterobacter cloacae Bacteremia

For Enterobacter cloacae bacteremia in adults without β-lactam allergy, use a carbapenem (meropenem or imipenem) as first-line therapy, or cefepime as a carbapenem-sparing alternative when adequate source control is achieved. 1, 2

Primary Treatment Recommendations

First-Line: Carbapenems

• Carbapenems (meropenem, imipenem, or doripenem) are the preferred agents for E. cloacae bacteremia, particularly for severe infections or when source control is inadequate 1, 3
• Carbapenems provide reliable activity against AmpC β-lactamase-producing organisms and avoid the risk of inducible resistance that occurs with third-generation cephalosporins 1, 4
• For ESBL-producing E. cloacae bacteremia, carbapenem therapy significantly reduces breakthrough bacteremia (9.6% vs 58.0% with non-carbapenem β-lactams, P<0.001) 3

Carbapenem-Sparing Alternative: Cefepime

• Cefepime is a reasonable alternative to carbapenems when adequate source control is achieved 1, 2
• Cefepime showed no difference in 30-day mortality (OR 0.63,95% CI 0.23-2.11) or length of hospital stay compared to meropenem in propensity-matched patients with AmpC-producing organisms 2
• Cefepime is stable against AmpC β-lactamases and is effective against AmpC-producing organisms when ESBL is absent 1, 4
• Cefepime must be combined with metronidazole for empiric therapy as it lacks anti-anaerobic activity 1

Antibiotics to AVOID

Third-Generation Cephalosporins

• Do NOT use third-generation cephalosporins (ceftriaxone, cefotaxime, ceftazidime) for E. cloacae bacteremia 1, 4, 5
• Third-generation cephalosporins are poor inducers but excellent substrates for AmpC β-lactamases, leading to treatment failures through selection of stably derepressed mutants 4, 5
• E. cloacae has inducible chromosomal AmpC that can be triggered during therapy, resulting in breakthrough bacteremia 1, 5

Piperacillin-Tazobactam

• Piperacillin-tazobactam use for E. cloacae bacteremia remains controversial 1, 6
• While one study showed no significant difference in outcomes between piperacillin-tazobactam and cefepime/meropenem for AmpC-producing Enterobacteriaceae bloodstream infections 6, guidelines note its use is controversial for ESBL infections and should be reserved for stable patients only 1
• Given the uncertainty, piperacillin-tazobactam should not be considered first-line for E. cloacae bacteremia

Treatment Duration and Monitoring

• Standard duration is 7-14 days for uncomplicated bacteremia 1
• Duration should be extended beyond 7-14 days based on clinical response, presence of metastatic foci, or inadequate source control 1
• Obtain follow-up blood cultures within 72 hours to document clearance of bacteremia 3

Source Control Considerations

• Remove infected intravascular catheters in all cases of E. cloacae catheter-related bloodstream infection 1
• For intra-abdominal sources, urgent surgical source control is essential in critically ill patients with sepsis/septic shock 1
• Adequate source control is particularly important when using cefepime instead of carbapenems 2

Special Populations

Critically Ill or Septic Patients

• Use carbapenems as first-line therapy in critically ill patients, those with septic shock, or when source control is inadequate 1, 3
• Empiric therapy should be initiated immediately while awaiting culture results 1

Patients with ESBL-Producing E. cloacae

• Carbapenems are mandatory for ESBL-producing E. cloacae bacteremia 1, 3
• Do not use cefepime or piperacillin-tazobactam for ESBL producers, even if in vitro susceptibility suggests otherwise 1, 3

Key Clinical Pitfalls

• Never assume susceptibility to third-generation cephalosporins means they are safe to use—E. cloacae may appear susceptible in vitro but develop resistance during therapy through AmpC induction 4, 5
• Do not rely on fluoroquinolones (ciprofloxacin, levofloxacin) as first-line therapy due to widespread resistance, though ciprofloxacin has FDA approval for E. cloacae urinary tract infections 1, 7
• Aminoglycosides should not be used as monotherapy but may be considered in combination with β-lactams for suspected multidrug-resistant infections 1