Treatment of infections caused by multidrug-resistant Gram-negative bacilli: a practical approach by the Italian (SIMIT) and French (SPILF) Societies of Infectious Diseases

Introduction: The emergence of multidrug-resistant Gram-negative bacilli, and the development of new antibiotics have complexified selection of optimal regimens. International guidelines are valuable tools, though limited by scarcity of high-quality randomized trials in many situations. Methods: A panel of experts from the French and Italian Societies of Infectious Diseases aimed to address unresolved issues in clinical practice based on their experience, updated literature review, and open discussions. Results: The panel reached a consensus for the following 'first-choices': i) cefepime for ventilator-acquired pneumonia due to AmpC β-lactamase-producing Enterobacterales; ii) The β-lactam/β-lactamase inhibitors combination most active in vitro, or cefiderocol combined with fosfomycin, and aerosolized colistin or aminoglycosides, for severe pneumonia due to Pseudomonas aeruginosa resistant to ceftolozane-tazobactam; iii) high-dose piperacillin-tazobactam (including loading dose and continuous infusion), for complicated urinary tract infections (cUTIs) caused by ESBL-producing Enterobacterales with piperacillin-tazobactam MIC ≤8 mg/L; iv) high-dose cefepime for cUTIs due to AmpC β-lactamase-producing Enterobacterales other than Enterobacter species if cefepime MIC ≤2 mg/L; v) ceftolozane-tazobactam or ceftazidime-avibactam plus metronidazole for intra-abdominal infections (IAIs) due to 3rd generation cephalosporin-resistant Enterobacterales; vi) ceftazidime-avibactam plus aztreonam plus metronidazole for IAIs due to metallo β-lactamase-producing Enterobacterales; vii) ampicillin-sulbactam plus colistin for bloodstream infections (BSIs) caused by carbapenem-resistant Acinetobacter baumannii (CRAB); viii) meropenem-vaborbactam for BSI caused by KPC-producing Enterobacterales; ix) ceftazidime-avibactam plus fosfomycin for neurological infections caused by carbapenem-resistant P. aeruginosa. Conclusions: These expert choices were based on the necessary balance between antimicrobial stewardship principles, and the need to provide optimal treatment for individual patients in each situation.