This ESCMID guideline article provides key updates to manage Carbapenem-resistant Enterobacterales. The update focuses on the effectiveness of individual antibiotics and combination versus monotherapy.

Multi-drug-resistant Gram-negative bacteria (MDR-GNB) are a matter of global concern. Enterobacterales have developed resistance mechanisms to carbapenems, leaving very few antibiotic options. The ESCMID guidelines provide key recommendations for managing Carbapenem-resistant Enterobacterales (CRE).

Choosing the antibiotic of choice for CRE

In cases with severe infections due to CRE, meropenem-vaborbactam or ceftazidime-avibactam (if active in vitro) is suggested.

In cases with non-severe infections due to CRE, considering antibiotic stewardship, an old antibiotic can be considered. As a good clinical practice, these antibiotics should be chosen from among the in vitro active on an individual basis and according to the source of infection.

In cases with non-severe complicated UTIs (cUTI), aminoglycosides are conditionally recommended. The use of plazomicin is suggested over tigecycline.

Tigecycline is not recommended for bloodstream infections (BSI) and hospital-acquired pneumonia/ ventilator-associated pneumonia (HAP/VAP). The use of high-dose tigecycline is conditionally recommended in patients with pneumonia.

Due to a lack of evidence, imipenem-relebactam and fosfomycin monotherapies are not recommended for CRE.

Combination therapy in CRE: What can be used

Combination therapy is not recommended in cases with CRE infections susceptible to and treated with:

• Ceftazidime-avibactam
• Meropenem-vaborbactam
• Cefiderocol

A combination of aztreonam and ceftazidime-avibactam can be used in:

1. In patients with severe infections caused by CRE carrying metallo-β-lactamase (MBL) and/or
2. In patients resistant to new antibiotic monotherapies
3. Treatment with more than one drug active in vitro is conditionally recommended in
4. Cases with severe infections caused by CRE susceptible in vitro only to polymyxins, aminoglycosides, tigecycline or fosfomycin 

            Or

5. In the case of the non-availability of new β-lactamase inhibitors (BLBLI)

Considering antibiotic stewardship, the use of monotherapy (chosen from among the in vitro active old drugs) is suggested in patients with non-severe infections or among patients with low-risk infections. Monotherapy should be selected on an individual basis and according to the source of infection.

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