Table 3.

New antibiotics for DTR-GNB currently approved with dosing, pros and cons.

Drug Name	Dosing for Patients with Normal Kidney Function	Comments
Ceftolozane-tazobactam	1.5 (ceftolozane 1 g + tazobactam 0.5 g) IV q 8 h iv for UTI and IAI 3 g (ceftolozane 2 g + tazobactam 1 g) IV q 8 h for NP	PROS: rapid tissue distribution (including lung); safe; limited activity also against S.maltophilia CONS: no activity against most anaerobes, staphylococci and enterococci; variably susceptibility of AmpC producers, two dosages, lower success in patients with CRRT
Ceftazidime-avibactam	2/0.5 g IV q 8 h	PROS: rapid tissue distribution (including lung); safe; approved for empiric and targeted therapy of DTR GNB; combination treatment with aztreonam against MBL CONS: no activity against most anaerobes staphylococci and enterococci; lower success in patients with CRRT; resistance
Imipenem-relebactam	1.25 g (imipenem 500/cilastatin 500/relebactam 250 mg) IV q 6 h	PROS: possible activity in strains resistant to both ceftolozane/tazobactam and ceftazidime/avibactam CONS: risk of neurotoxicity
Meropenem-vaborbactam	2/2 g IV q 8 h	PROS: promising efficacy in the setting of pneumonia and/or other severe KPC -CRE infections; resistance selection overall lower than ceftazidime/avibactam CONS: not active against Amber class B or D carbapenemases
Cefiderocol	2 g IV q 8 h (2 g IV q 6 h if CrCl > 120 mL/min)	PROS: novel siderophore cephalosporin; promising for the treatment of DTR A. baumannii no activity also against S. maltophilia CONS: not activity against gram positives and anaerobes
Plazomicin	15 mg/kg IV q 24 h	PROS: once daily dose; carbapenem or β-lactam/β-lactamase inhibitor sparing alternative for UTI CONS: no activity against anaerobes, A. baumannii, S. maltophilia,; lower risk for aminoglycosides associated toxicity
Eravacycline	1 mg/kg IV/oral q 12 h	PROS: oral formulation, activity also against gram positive (including MRSA, VRE) bacteria, anaerobes, S. maltophilia CONS: suboptimal urinary pharmacokinetics; limited data in pneumonia and BSI; no activity against P. aeruginosa

BSI, blood stream infections; CRE; carbapenem resistant Enterobacteriales; CRRT, continuous renal replacement therapy; DRT, difficult to treat resistance; GNB, Gram negative bacteria; IAI, intrabdominal infections; KPC, Klebsiella pneumoniae carbapenemase producers; MBL, metallobetalactamase; MRSA, methicillin-resistant Staphylococcus aureus; NP, nosocomial pneumonia; UTI, urinary tract infections; VRE, vancomycin-resistant Enterococcus.