What is the recommended treatment for New Delhi metallo-beta-lactamase (NDM) producing Escherichia coli (E. coli) infections?

Treatment of NDM-Producing Escherichia coli Infections

For infections caused by New Delhi metallo-β-lactamase (NDM) producing Escherichia coli, the combination of ceftazidime-avibactam plus aztreonam is strongly recommended as first-line therapy due to its superior clinical outcomes and mortality benefit.

First-line Treatment Options

• Ceftazidime-avibactam plus aztreonam is the preferred regimen for NDM-producing E. coli infections, showing significantly lower 30-day mortality (19.2% vs 44%) compared to other treatment options 1
• This combination demonstrates synergistic activity against metallo-β-lactamase (MBL) producing organisms, as aztreonam is not hydrolyzed by MBLs while avibactam protects aztreonam from other co-produced β-lactamases 1
• For severe infections caused by CRE carrying metallo-β-lactamases like NDM, European guidelines strongly support this combination therapy approach 1

Alternative Treatment Options

• Cefiderocol is conditionally recommended as an alternative option for NDM-producing E. coli infections when the organism is susceptible 1

  • Clinical cure was achieved in 75% of patients with MBL-producing CRE treated with cefiderocol compared to only 29% with best available therapy 1
  • However, recent reports have identified emerging resistance to cefiderocol in some NDM-producing isolates 2

• Fosfomycin may be considered as an alternative therapy:

  • Recent studies show 98% of NDM-producing E. coli isolates remain susceptible to fosfomycin 3
  • Can be used in combination with other active agents for synergistic effect 4

• Combination therapy with multiple active agents should be considered for severe infections:

  • Rifampin-meropenem-colistin combination has demonstrated synergistic and bactericidal effects against NDM-producing organisms in vitro 4
  • Tigecycline has shown relatively high in vitro activity (86.5% susceptible) against NDM-producing Enterobacterales 5

Treatment Considerations

• Susceptibility testing is essential as resistance patterns can vary significantly among NDM-producing isolates 1, 5
• For non-severe infections in stable patients, monotherapy with an active agent may be considered based on susceptibility testing 1
• Treatment options are extremely limited - a CDC study found that no FDA-approved antibiotic exceeded 90% susceptibility against NDM-producing Enterobacterales in the US 5

Special Considerations

• Monitor for emerging resistance during therapy, as NDM-producing organisms can rapidly develop additional resistance mechanisms 2
• Be aware of potential resistance to ceftazidime-avibactam plus aztreonam in isolates with additional resistance mechanisms like PBP3 modifications 2
• Treatment duration should be determined based on infection site, severity, and clinical response 1

Common Pitfalls to Avoid

• Avoid monotherapy with carbapenems even if the isolate appears susceptible in vitro, as treatment failure rates are high 1
• Do not rely on fluoroquinolones or trimethoprim-sulfamethoxazole without confirmed susceptibility, as resistance is common 1
• Be cautious with polymyxins (colistin) as monotherapy, as resistance is emerging and clinical outcomes are generally poor 1, 6
• Recognize that NDM-producing E. coli often harbor multiple resistance mechanisms, potentially limiting the efficacy of standard combination approaches 2