Dosage, pros and author's perspective of the new antibiotics currently approved for the treatment of pneumonia due to Gram-negative pathogens

Antimicrobial activityMoraxella catarrhalis, Haemophilus influenza, non-ESBL-, non-AmpC- and noncarbapenemases-producing Enterobacterales; Pseudomonas aeruginosaESBL-producing Enterobacterales; MDR P. aeruginosaESBL-, KPC-, AmpC- and OXA-48-producing Enterobacterales; MDR P. aeruginosaESBL- and CRE (class A, B, and D enzymes)-producing Enterobacterales; MDR P. aeruginosa, S. maltophilia and A. baumanniiESBL-, KPC- and AmpC-producing Enterobacterales; non-MDR P. aeruginosa; non-MDR A. baumanniiESBL- and KPC-producing Enterobacterales; MDR P. aeruginosa
Approved dosage for the treatment of pneumonia2 h i.v. infusion 500 mg every 8 h2 g of ceftolozane and 1 g of tazobactam every 8 h by i.v. infusion over 1 h2 g of ceftazidime and 0.5 g of avibactam every 8 h by i.v. infusion over 2 h2 g every 8 h by i.v. infusion over 3 h2 g of meropenem and 2 g of vaborbactam every 8 h by i.v. infusion over 3 h500 mg of imipenem and 250 mg of relebactam by i.v. infusion every 6 h over 30 min
ProsApproved for CAP and HAP, but not for VAPBest β-lactam with activity against P. aeruginosa
Carbapenem-sparing agent
Lower mortality observed in patients with ventilated HAP
Good clinical experience for treatment of KPC infection
Carbapenem-sparing agent
Good activity OXA-48-producing Enterobacterales
Can be combined with aztreonam for the treatment of MBL-producing Enterobacterales
Wide spectrum of activity
Unique drug with activity against MBL-producing Enterobacterales
Potent activity against KPC
Low-propensity for developing in vivo resistance
Potent activity against KPC
Potent activity against MDR P. aeruginosa
Authors’ perspectiveCeftobiprole could be a viable single therapeutic option for the treatment of CAP and HAP caused by Gram-negatives, especially when concomitant MRSA is suspected.We believe that ceftolozane-tazobactam represents the first option as a backbone for the treatment of MDR P. aeruginosa as well as a carbapenem-sparing regimen for the treatment of pneumonia in clinical settings with a high rate of ESBL-producing strains.Ceftazidime–avibactam currently represents one of the drugs of choice for the treatment of CRE infections. When treating patients with MDR Gram-negative bacteria pneumonia, ceftazidime-avibactam can be used in association with a second drug such as gentamycin, fosfomycin or colistin (or, in the future, with plazomycin). Moreover, it may have a role as a potential alternative to carbapenems in patients with nosocomial pneumonia with high rates (>20–25%) of infections caused by ESBL-producing or OXA-48-producing Gram-negative bacteria.We believe that cefiderocol represents an interesting choice for empirical and definitive treatment of HAP and VAP when a carbapenem-resistant Gram-negative bacteria, including CRE, MDR P. aeruginosa, and MDR A. baumannii is suspected or confirmed. Whether or not it should be used as part of a combination treatment is still an unresolved issue.In our opinion, meropenem-vaborbactam should be considered the first treatment option for CRE pneumonia, especially in consideration of its lower mortality rates, as recently documented in the TANGO II trial.Imipenem-relebactam could offer an important new treatment option as part of an empirical or targeted therapy for HAP or VAP due to MDR Gram-negative bacteria. We believe that further studies coming from real-life experiences are needed.

A.: Acinetobacter; CAP: community-acquired pneumonia; CRE: carbapenem-resistant Enterobacterales; ESBL: extended-spectrum β-lactamases; HAP: hospital-acquired pneumonia; KPC: Klebsiella pneumoniae carbapenemases; MBL: metallo-β-lactamases; MDR: multidrug resistant; MRSA: methicillin-resistant Staphylococcus aureus; OXA: OXA-β-lactamases; S.: Stenotrophomonas; VAP: ventilator-associated pneumonia.