What treatment options are available for Enterobacter (E.) cloacae infections that are resistant to meropenem but sensitive to imipenem (Imipenem/Cilastatin)?

Enterobacter cloacae Resistant to Meropenem but Sensitive to Imipenem

Use imipenem/cilastatin as your primary treatment option for this unusual resistance pattern, as the organism demonstrates documented susceptibility and imipenem maintains activity against this specific isolate. 1

Understanding This Resistance Pattern

This resistance pattern is uncommon but clinically significant:

• Meropenem resistance with imipenem susceptibility suggests a specific carbapenemase mechanism or porin mutation that differentially affects these carbapenems 2
• E. cloacae can produce various β-lactamases including AmpC cephalosporinases and carbapenemases (KPC, MBL, NmcA) that may show differential activity against carbapenems 3
• The NmcA carbapenem-hydrolyzing β-lactamase specifically can cause higher MICs for imipenem than meropenem in some strains, though your pattern shows the reverse 3

Treatment Recommendations by Infection Site

Bloodstream Infections

• Imipenem/cilastatin 500 mg IV every 6 hours (for susceptible organisms) or 1000 mg IV every 6-8 hours (for organisms with intermediate susceptibility) 1
• Treatment duration: 7-14 days 4
• Adjust dosing based on creatinine clearance 1

Complicated Urinary Tract Infections

• Imipenem/cilastatin 500 mg IV every 6 hours 1
• Treatment duration: 5-7 days 4
• Consider aminoglycosides (gentamicin 5-7 mg/kg/day or amikacin 15 mg/kg/day) as alternatives if imipenem unavailable 4

Complicated Intra-Abdominal Infections

• Imipenem/cilastatin 500-1000 mg IV every 6-8 hours 1
• Treatment duration: 5-7 days 4
• Imipenem provides adequate anaerobic coverage without additional metronidazole 4, 2

Hospital-Acquired/Ventilator-Associated Pneumonia

• Imipenem/cilastatin 1000 mg IV every 6-8 hours 1
• Treatment duration: 10-14 days 4
• Infuse doses >500 mg over 40-60 minutes 1

Dosing Considerations

Standard Dosing (CrCl ≥90 mL/min)

• 500 mg IV every 6 hours for susceptible organisms 1
• 1000 mg IV every 6-8 hours for organisms with intermediate susceptibility or severe infections 1
• Infuse doses ≤500 mg over 20-30 minutes; doses >500 mg over 40-60 minutes 1

Renal Impairment Adjustments

• CrCl 60-89 mL/min: 400 mg every 6 hours or 500 mg every 6 hours 1
• CrCl 30-59 mL/min: 300 mg every 6 hours or 500 mg every 8 hours 1
• CrCl 15-29 mL/min: 200 mg every 6 hours or 500 mg every 12 hours (increased seizure risk) 1
• CrCl <15 mL/min: Do not use unless hemodialysis within 48 hours 1

Combination Therapy Considerations

Consider adding colistin or amikacin for severe infections or critically ill patients:

• Imipenem + colistin shows synergistic activity against multidrug-resistant E. cloacae in vitro and in vivo models 5, 6
• Colistin dosing: 5 mg CBA/kg IV loading dose, then 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours 4
• Imipenem + amikacin maintains bactericidal activity even with elevated carbapenem MICs 7
• Combination therapy particularly important for critically ill or immunocompromised patients 4

Critical Warnings and Monitoring

Seizure Risk

• Increased seizure risk in patients with CNS disorders, renal impairment (especially CrCl <30 mL/min), or concurrent valproic acid use 1
• Monitor closely in hemodialysis patients; use only when benefit outweighs risk 1
• If patient on valproic acid/sodium valproate, consider alternative anticonvulsant as imipenem reduces valproic acid levels 1

Hypersensitivity

• Screen for β-lactam allergies before initiation 1
• Cross-reactivity possible with penicillin allergies 1

Infusion-Related Adverse Effects

• Nausea/vomiting may occur; slow infusion rate if develops 1
• Monitor for Clostridioides difficile infection 1

Alternative Agents (If Imipenem Unavailable)

While guidelines focus on carbapenem-resistant Enterobacterales (CRE), your isolate is carbapenem-susceptible (to imipenem):

• Fourth-generation cephalosporins (cefepime) may be effective if ESBL-negative 4, 3
• Newer β-lactam/β-lactamase inhibitor combinations (ceftazidime/avibactam, imipenem/relebactam) are options for CRE but unnecessary here given imipenem susceptibility 4
• Avoid third-generation cephalosporins due to high resistance rates in E. cloacae 4

Key Clinical Pitfalls

• Do not assume all carbapenems are equivalent: This case demonstrates differential susceptibility requiring susceptibility-guided therapy 2, 3
• Verify susceptibility testing: Confirm imipenem MIC and ensure meropenem resistance is reproducible
• Avoid carbapenem monotherapy for high-inoculum infections: Consider combination therapy for severe sepsis or pneumonia 5, 6, 7
• Monitor renal function closely: Adjust doses promptly with changing creatinine clearance 1
• Do not use imipenem in patients with CrCl <15 mL/min unless hemodialysis planned within 48 hours 1