Novel Antibiotics for Gram-Negative Nosocomial Pneumonia

Abstract

Nosocomial pneumonia, including hospital-acquired pneumonia and ventilator-associated pneumonia, is the leading cause of death related to hospital-acquired infections among critically ill patients. A growing proportion of these cases are attributed to multi-drug-resistant (MDR-) Gram-negative bacteria (GNB). MDR-GNB pneumonia often leads to delayed appropriate treatment, prolonged hospital stays, and increased morbidity and mortality. This issue is compounded by the increased toxicity profiles of the conventional antibiotics required to treat MDR-GNB infections. In recent years, several novel antibiotics have been licensed for the treatment of GNB nosocomial pneumonia. These novel antibiotics are promising therapeutic options for treatment of nosocomial pneumonia by MDR pathogens with certain mechanisms of resistance. Still, antibiotic resistance remains an evolving global crisis, and resistance to novel antibiotics has started emerging, making their judicious use crucial to prolong their shelf-life. This article presents an up-to-date review of these novel antibiotics and their current role in the antimicrobial armamentarium. We critically present data for the pharmacokinetics/pharmacodynamics, the in vitro spectrum of antimicrobial activity and resistance, and in vivo data for their clinical and microbiological efficacy in trials. Where possible, available data are summarized specifically in patients with nosocomial pneumonia, as this cohort may exhibit 'critical illness' physiology that affects drug efficacy.

Keywords: cefiderocol; ceftazidime–avibactam; ceftolazone–tazobactam; hospital-acquired pneumonia (HAP); imipenem–relebactam; meropenem–vaborbactam; multi-drug resistant (MDR); nosocomial pneumonia; sulbactam–durlobactam; ventilator-associated pneumonia (VAP).

Figure 1

Physiological causes of differences in pharmacokinetic and pharmacodynamic parameters of antibiotics between normal alveoli and critical illness/pneumonia alveoli.