What is the recommended treatment for a patient with a urine culture positive for E. coli (Escherichia coli) showing resistance to carbapenems (Carbapenem-Resistant Enterobacteriaceae)?

Treatment of Carbapenem-Resistant E. coli Urinary Tract Infection

For carbapenem-resistant E. coli UTI, use ceftazidime-avibactam 2.5 g IV every 8 hours as first-line therapy, with meropenem-vaborbactam or imipenem-cilastatin-relebactam as alternative options. 1, 2, 3

Treatment Algorithm Based on UTI Severity

For Complicated UTI (Symptomatic Cystitis with Systemic Features)

Primary Options:

• Ceftazidime-avibactam 2.5 g IV every 8 hours for 5-7 days 1, 3
• Meropenem-vaborbactam 4 g IV every 8 hours for 5-7 days 1, 2
• Imipenem-cilastatin-relebactam 1.25 g IV every 6 hours for 5-7 days 1, 2

Alternative Options if Above Are Unavailable:

• Aminoglycosides as monotherapy for UTI only: Gentamicin 5-7 mg/kg IV once daily OR Amikacin 15 mg/kg IV once daily for 5-7 days 1, 4
• Plazomicin 15 mg/kg IV every 12 hours for 5-7 days 1, 3

The newer beta-lactam/beta-lactamase inhibitor combinations (ceftazidime-avibactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam) are superior to aminoglycosides for complicated UTI because they achieve better tissue penetration and have lower nephrotoxicity risk, though aminoglycosides remain effective for simple UTI when given as single daily dosing. 1, 3

For Bloodstream Infection or Pyelonephritis (Parenchymal Infection)

Primary Options:

• Ceftazidime-avibactam 2.5 g IV every 8 hours for 7-14 days 1
• Meropenem-vaborbactam 4 g IV every 8 hours for 7-14 days 1
• Imipenem-cilastatin-relebactam 1.25 g IV every 6 hours for 7-14 days 1

Combination Therapy for Critically Ill Patients:

• Colistin 5 mg CBA/kg IV loading dose, then 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours PLUS Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours for 7-14 days 1
• Colistin (same dosing) PLUS Meropenem 1 g IV every 8 hours by extended 3-hour infusion for 7-14 days 1

The combination therapy with polymyxins is reserved for critically ill or hemodynamically unstable patients, as monotherapy with newer agents is preferred when the organism is susceptible. 1

Critical Resistance Mechanism Considerations

Carbapenemase Type Matters:

• KPC-producing strains: Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-cilastatin-relebactam are all highly effective 1, 5
• Metallo-beta-lactamase (NDM, VIM) producers: Ceftazidime-avibactam and other beta-lactam combinations will NOT work; use polymyxin-based combinations or aztreonam-based regimens 1, 6
• OXA-48 producers: Variable susceptibility to newer agents; susceptibility testing is essential 1, 7

If the specific carbapenemase mechanism is unknown, empiric therapy should cover the most likely local resistance patterns, but definitive therapy MUST be guided by susceptibility testing results. 1

Common Pitfalls and How to Avoid Them

Do NOT use carbapenems for carbapenem-resistant organisms - this seems obvious but bears emphasis; even "intermediate" susceptibility should prompt alternative therapy. 1

Avoid aminoglycoside monotherapy for anything beyond simple UTI - while gentamicin and amikacin retain activity against many carbapenem-resistant E. coli strains, they should only be used as monotherapy for uncomplicated UTI, not for pyelonephritis or bloodstream infections. 1, 4

Do NOT treat asymptomatic bacteriuria - even with carbapenem-resistant organisms, treatment of asymptomatic bacteriuria is not indicated and only promotes further resistance. 1, 8

Verify susceptibility to tigecycline before using it - tigecycline achieves poor urinary concentrations and should NOT be used for UTI, only for intra-abdominal infections when other options are unavailable. 1

Ensure adequate source control - for complicated UTI with obstruction, abscess, or foreign body (catheter), antimicrobial therapy alone will fail without drainage or removal. 1

Infection Control Measures

All patients with carbapenem-resistant E. coli must be placed on contact precautions immediately to prevent nosocomial transmission. 1

Conduct surveillance cultures of epidemiologically linked patients (same unit, same healthcare workers) when a case is identified to detect unrecognized carriers. 1

Alert infection control and epidemiology staff immediately when carbapenem resistance is detected in E. coli to trigger outbreak investigation protocols. 1