How Should We Treat HAP/VAP Caused by Carbapenemase-Producing Enterobacteriaceae?

Abstract

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) represent a common problem in hospital setting worldwide. Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are an emergent problem due to the lack of therapeutic options available, leading to significant increases in morbidity and mortality. CRE have frequently been reported both in HAP/VAP, but limited data regarding the optimal treatment strategy in this setting are available. This review focuses on the current epidemiology of CRE, with a specific focus on HAP/VAP. Moreover, we will suggest a possible strategy for the empiric and targeted treatment of HAP and VAP in which the involvement of CRE is suspected or is confirmed.

Activity of Meropenem-Vaborbactam against Bacterial Isolates Causing Pneumonia in Patients in U.S. Hospitals during 2014 to 2018

“…The findings of this study, where meropenem-vaborbactam, aminoglycosides, carbapenems, and tigecycline were the only agents displaying susceptibility rates Ͼ90% against 4,790 Enterobacterales isolates, reinforce the challenges to improve care for patients with HAP/VAP, for which delayed and inadequate treatments have been associated with increased rates of morbidity and mortality (25,26). Similar results were observed when these agents were tested against a worldwide collection of Enterobacterales recovered from different infection sources (12).…”

“…The emergence and widespread geography of CRE isolates have added considerable challenges to treating severe infections, and mortality rates are as high as 40% to 50% (27)(28)(29). Therapeutic options to treat CRE HAP/VAP infections are limited, and traditionally, agents from either the polymyxin or aminoglycoside classes have been recommended in combined therapy, usually with carbapenem-containing regimens (1,26,30,31). However, studies have shown that colistin, tigecycline, and gentamicin have poor lung penetration, whereas carbapenems have good distribution in lungs, achieving clinically relevant concentrations (26,32).…”

“…Therapeutic options to treat CRE HAP/VAP infections are limited, and traditionally, agents from either the polymyxin or aminoglycoside classes have been recommended in combined therapy, usually with carbapenem-containing regimens (1,26,30,31). However, studies have shown that colistin, tigecycline, and gentamicin have poor lung penetration, whereas carbapenems have good distribution in lungs, achieving clinically relevant concentrations (26,32). In fact, herein, only meropenem-vaborbactam (98.5%) and tigecycline (96.9%) displayed Ͼ90% susceptibility rates against CRE isolates causing PHP.…”

Molecular Characterization of Baseline Enterobacterales and Pseudomonas aeruginosa Isolates from a Phase 3 Nosocomial Pneumonia (ASPECT-NP) Clinical Trial

“…Staphylococcus aureus is the leading cause of nosocomial pneumonia, followed by Pseudomonas aeruginosa and Klebsiella/Enterobacter species. The occurrence of multidrug-resistant Gram-negative organisms in nosocomial pneumonia differs according to the hospital and geographic region (5, 7), but P. aeruginosa isolates are intrinsically resistant to multiple antimicrobial agents, and Klebsiella and Enterobacter species have been shown to have increasing rates of resistance to several antimicrobial agents; therefore, the therapeutic options for treating nosocomial pneumonia caused by Gram-negative organisms are limited (8,9).…”

Ceftazidime–Avibactam-Based Versus Tigecycline-Based Regimen for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae-Induced Pneumonia in Critically Ill Patients

“…CAZ-AVI, a promising option for the treatment of carbapenem-resistant Gram-negative bacteria, has been approved by the US Food and Drug Administration (FDA) and European Medicines Agency for the treatment of HAP/ VAP owing to its attractive bactericidal broadspectrum activity, linear pharmacokinetics with a moderate degree of lung penetration, and low risk of serious adverse events [35]. Previous studies have shown the efficacy of CAZ-AVI in the treatment of CRE infection, including CRKP, with low mortality and recurrence rates even following monotherapy [14,20,[36][37][38][39][40].…”