New perspectives in the antibiotic treatment of mechanically ventilated patients with infections from Gram-negatives.

Karvouniaris, Marios; Pontikis, Konstantinos; Nitsotolis, Thomas; Poulakou, Garyphallia

INTRODUCTION Ventilator-associated pneumonia (VAP) is a common and potentially fatal complication of mechanical ventilation that is often caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB). Despite the repurposing of older treatments and the novel antimicrobials, many resistance mechanisms cannot be confronted, and novel therapies are needed. AREAS COVERED We searched the literature for keywords regarding the treatment of GNB infections in mechanically ventilated patients. This narrative review presents new data on antibiotics and non-antibiotic approaches focusing on Phase 3 trials against clinically significant GNB that cause VAP. EXPERT OPINION Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam stand out as new options for infections by Klebsiella pneumoniae carbapenemase-producing bacteria, whereas ceftolozane-tazobactam adds therapeutic flexibility in Pseudomonas aeruginosa infections with multiple resistance mechanisms. Ceftazidime-avibactam and ceftolozane-tazobactam have a literature base about VAP. Aztreonam-avibactam holds promise for the treatment of infections by metallo-β-lactamase (MBL)-producing organisms. Recently approved cefiderocol possesses an extended antibacterial spectrum, including, among others, KPC- and MBL-producers. However, recently published data have toned down optimism about treating VAP caused by carbapenem-resistant Acinetobacter baumannii. For the latter, eravacycline may provide additional hope, pending pertinent data. Non-antibiotic treatments currently being considered as adjunct therapeutic approaches are welcome. Nevertheless, they will hopefully substitute current antimicrobials in the future.