Minireview on Novel Anti-infectious Treatment Options and Optimized Drug Regimens for Sepsis

Abstract

Sepsis, a life-threatening organ dysfunction caused by a dysregulated response to infection is a major public health concern, as it is a leading cause of mortality and critical illness worldwide. Antibiotics are one of the cornerstones of the treatment of sepsis; administering appropriate antibiotics in a rapid fashion to obtain adequate drug concentrations at the site of the infection can improve survival of patients. Nevertheless, it is a challenge for clinicians to do so. Indeed, clinicians today are regularly confronted with infections due to very resistant pathogens, and standard dosage regimens of antibiotics often do not provide adequate antibiotic concentrations at the site of the infection. We provide a narrative minireview of different anti-infectious treatments currently available and suggestions on how to deliver optimized dosage regimens to septic patients. Particular emphasis will be made on newly available anti-infectious therapies.

Initial antimicrobial management of sepsis

“…A few new antibiotics can be used to treat severe infection due to resistant gram-positive and gram-negative bacteria [53,54]. Ceftolozane-tazobactam is active against multidrug-resistant (MDR) Pseudomonas aeruginosa.…”

“…For those with carbapenem-resistant Enterobacteriaceae, ceftazidime-avibactam, imipenemrelebactam, and meropenem-vaborbactam may be most effective. For organisms that produce metallo-beta-lactamases ceftazidime-avibactam and cefiderocol would be good options [53,54]. In the future, phage therapy may be a therapeutic option that needs study in sepsis [55].…”

Suboptimal drug exposure leads to selection of different subpopulations of ceftazidime-avibactam-resistant Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae in a critically ill patient

“…To date, data reporting the optimal dosing regimens for CAZ-AVI in critically ill patients are scarse (Hites et al 2021). Emerging clinical data suggest that more aggressive PK/PD target upto Css/MIC of 4-5 may not only improve clinical efficacy, but also suppress the emergence of resistance (Sumi et al 2019;Heffernan et al 2018;Tam et al 2017).…”