Guidelines for the treatment of multidrug-resistant gram-negative bacilli were published in December 2021 by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in Clinical Microbiology and Infection, with the endorsement of the European Society of Intensive Care Medicine (ESICM).
Third-Generation Cephalosporin–Resistant Enterobacterales (3GCephRE)
For bloodstream infection (BSI) and severe infection due to 3GCephRE, a carbapenem (imipenem or meropenem) is recommended. For BSI without septic shock, ertapenem may be used instead. Stepdown targeted therapy is good clinical practice after carbapenems once patients are stabilized.
For low-risk nonsevere infection, piperacillin-tazobactam, amoxicillin-clavulanate, or a quinolone is suggested. Trimethoprim-sulfamethoxazole may be considered for nonsevere complicated urinary tract infection (cUTI). For cUTI without septic shock, aminoglycosides are conditionally recommended, and IV fosfomycin is strongly recommended.
Tigecycline, cephamycins, and cefipime are not recommended. Newer beta-lactams with beta-lactamase inhibitors (BLBLIs) should not be used.
Carbapenem-Resistant Enterobacterales (CRE)
For severe infection due to CRE, meropenem-vaborbactam or ceftazidime-avibactam is suggested if active in vitro. For severe infection due to CRE carrying metallo-beta lactamases and/or resistant to all other antibiotics, cefiderocol is conditionally recommended.
For nonsevere infections, an older antibiotic with in-vitro activity should be considered. For cUTI, aminoglycosides are suggested over tigecycline.
Tigecycline should not be used for BSI and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP); if necessary for pneumonia, high-dose tigecycline may be used.
For infection susceptible to and treated with ceftazidime-avibactam, meropenem-vaborbactam, or cefiderocol, combination therapy is not recommended.
For severe infection due to CRE carrying metallo-beta lactamases and/or resistant to new antibiotic monotherapies, aztreonam plus ceftazidime-avibactam is suggested. For severe infection due to CRE susceptible in vitro only to polymyxins, aminoglycosides, tigecycline, or fosfomycin, or if new BLBLIs are unavailable, combination therapy with drugs active in vitro is suggested.
Carbapenem-based combination therapy should be avoided unless the minimum inhibitory concentration (MIC) for meropenem is ≤8 mg/L.
For nonsevere or low-risk infection, monotherapy with an older drug that is active in vitro is good clinical practice.
Carbapenem-Resistant Pseudomonas aeruginosa (CRPA)
For severe infection due to CRPA, ceftolozane-tazobactam is suggested if active in vitro.
For nonsevere or low-risk infection, use of old antibiotics with in-vitro activity is good clinical practice.
In treating severe infection with polymyxins, aminoglycosides, or fosfomycin, use of two drugs active in vitro is suggested.
For nonsevere or low-risk infection, monotherapy with a drug that is active in vitro is good clinical practice.
Carbapenem-Resistant Acinetobacter baumanni (CRAB)
For CRAB susceptible to sulbactam and HAP/VAP, ampicillin-sulbactam is suggested. For CRAB resistant to sulbactam, a polymyxin or high-dose tigecycline can be used if active in vitro.
Cefiderocol, polymyxin-meropenem combination therapy, and polymyxin-rifampin combination therapy are not recommended.
For severe and high-risk infection, combination therapy using two of the available drugs with in-vitro activity (polymyxin, aminoglycoside, tigecycline, sulbactam combinations) is suggested.
When meropenem MIC <8 mg/L, carbapenem combination therapy is good clinical practice.
For more information, please go to Enterobacter Infections, Urinary Tract Infection (UTI) and Cystitis (Bladder Infection) in Females, Urinary Tract Infection in Males, Pseudomonas aeruginosa Infections, and Acinetobacter.