New Antibiotics Against Multidrug-Resistant Gram-Negative Bacteria in Liver Transplantation: Clinical Perspectives, Toxicity, and PK/PD Properties

Abstract

Antimicrobial resistance is a growing global health problem, and it is especially relevant among liver transplant recipients where infections, particularly when caused by microorganisms with a difficult-to-treat profile, are a significant cause of morbidity and mortality. We provide here a complete dissection of the antibiotics active against multidrug-resistant Gram-negative bacteria approved over the last years, focusing on their activity spectrum, toxicity profile and PK/PD properties, including therapeutic drug monitoring, in the setting of liver transplantation. Specifically, the following drugs are presented: ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, cefiderocol, and eravacycline. Overall, studies on the safety and optimal employment of these drugs in liver transplant recipients are limited and especially needed. Nevertheless, these pharmaceuticals have undeniably enhanced therapeutic options for infected liver transplant recipients.

Keywords: BL/BLI; antimicrobial stewardship; liver transplantation; metallo-beta lactamases; multidrug-resistant microorganisms.

FIGURE 1

Comparison of propensity to new antibiotic use in common infectious conditions among LTR according to authors’ opinion (Personal view). Based on a hypothetical fully susceptible microorganism toward the antimicrobial considered. (0 = totally against use, 100 = totally in favour of use) (HAP/VAP: hospital-acquired pneumonia/ventilator-associated pneumonia, BSI: bloodstream infection; cIAI: complicated intraabdominal infection; cUTI, complicated urinary tract infection; SSI: surgical site infection; C/T: ceftolozane/tazobactam; CZA: ceftazidime/avibactam; MVB: meropenem/vaborbactam; I-R: imipenem/relebactam; FDC: cefiderocol; ERV: eravacycline).