What antibiotic is recommended for treating Enterobacter (E.) cloacae in urine, given resistance to quinolones and intermediate sensitivity to cefepime (Cefepime) and amikacin (Amikacin)?

Treatment of Enterobacter cloacae Urinary Tract Infection with Quinolone Resistance and Intermediate Sensitivity to Cefepime and Amikacin

Given quinolone resistance and intermediate sensitivity to both cefepime and amikacin, a carbapenem (meropenem or imipenem) is the most appropriate choice for treating this Enterobacter cloacae urinary tract infection. 1

Rationale for Carbapenem Selection

Why Not Cefepime or Amikacin

• Cefepime with intermediate sensitivity is unreliable for Enterobacter cloacae. The ESCMID guidelines specifically suggest against using cefepime for third-generation cephalosporin-resistant Enterobacterales (conditional recommendation against use, very low certainty of evidence), and intermediate sensitivity falls into this concerning category 1

• Intermediate susceptibility represents a gray zone where clinical failure rates increase significantly. For cefepime specifically, studies show higher mortality when MICs are elevated within the susceptible range, even when technically "susceptible" 1

• Amikacin with intermediate sensitivity for urinary tract infections is problematic. While aminoglycosides can be considered for uncomplicated UTIs when fully susceptible 1, intermediate sensitivity substantially increases failure risk, and aminoglycosides have unclear prostate penetration with conflicting efficacy results 1

• Enterobacter cloacae is notorious for developing resistance during therapy with third-generation cephalosporins due to AmpC beta-lactamase induction, and fourth-generation cephalosporins like cefepime remain vulnerable when resistance mechanisms are present 1

Carbapenem as First-Line Choice

• For severe or complicated urinary tract infections with resistant Enterobacter species, carbapenems (meropenem or imipenem) represent the gold standard. 1

• ESCMID guidelines provide strong recommendation (moderate certainty of evidence) for carbapenems in bloodstream infections and severe infections due to third-generation cephalosporin-resistant Enterobacterales 1

• Ertapenem may be considered as an alternative if the patient does not have septic shock, as it provides adequate coverage for ESBL-producing Enterobacterales while being more narrow-spectrum than meropenem/imipenem 1

• Carbapenems are specifically effective against E. cloacae and E. aerogenes, the most clinically relevant Enterobacter species 1

Alternative Considerations

If Carbapenem Must Be Avoided

• Piperacillin-tazobactam could be considered ONLY if: 1

  • The infection is non-severe (no sepsis/septic shock)
  • Susceptibility testing confirms full susceptibility
  • Close clinical monitoring is available for treatment failure

• Fosfomycin (intravenous) is strongly recommended by ESCMID for complicated UTIs caused by resistant Enterobacterales (strong recommendation, high certainty of evidence) 1

• Trimethoprim-sulfamethoxazole may be considered if susceptibility is confirmed and the infection is non-severe 1

Combination Therapy Option

• Cefepime plus amikacin combination shows synergy against Enterobacter cloacae in both in vitro and in vivo studies, with significant bacterial count reduction compared to either agent alone 2

• However, this combination should only be attempted if carbapenems are contraindicated and both agents show at least intermediate susceptibility, as synergy may overcome intermediate resistance 2

• The combination requires close monitoring for nephrotoxicity given dual aminoglycoside exposure 1

Critical Pitfalls to Avoid

• Do not use quinolones given documented resistance—this is a treatment failure waiting to happen 1

• Avoid relying on intermediate susceptibility results as if they were fully susceptible—intermediate means unpredictable clinical outcomes 1

• Do not use third-generation cephalosporins (ceftriaxone, cefotaxime) for Enterobacter infections due to high likelihood of resistance development during therapy 1

• Monitor renal function closely if aminoglycosides must be used, especially in combination with other nephrotoxic agents 1

Practical Treatment Algorithm

1. First choice: Meropenem 1g IV every 8 hours or Imipenem 500mg IV every 6 hours 1

2. Alternative if non-severe and carbapenem-sparing needed: Ertapenem 1g IV daily 1

3. If carbapenems contraindicated and susceptibility confirmed: IV fosfomycin 1

4. Last resort with close monitoring: Cefepime + amikacin combination (only if intermediate susceptibility to both) 2

5. Reassess at 48-72 hours with repeat cultures and adjust based on clinical response and definitive susceptibility results 1