Review of Ceftazidime-Avibactam, Meropenem-Vaborbactam, and Imipenem/Cilastatin-Relebactam to Target Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales

Abstract

Objective: To provide a review of 3 novel antimicrobial agents—ceftazidime-avibactam, meropenem-vaborbactam, and imipenem/cilastatin-relebactam—regarding treatment of Klebsiella pneumoniae carbapenemase-producing Enterobacterales (KPC). Data Sources: A literature search of PubMed and OVID (MEDLINE) was performed up to March 2020 using the following search terms: Vabomere, meropenem-vaborbactam, vaborbactam, RPX7009, Klebsiella pneumoniae carbapenemase, KPC, carbapenem-resistant Enterobacteriaceae, CRE, relebactam, imipenem-relebactam, MK-7655, ceftazidime-avibactam. Abstracts from conferences, article bibliographies, and product information were also reviewed. Study Selection and Data Extraction: Articles were first screened by English language, then title, then abstract, and finally by review of the full article. Fifty-five clinical and preclinical studies were included. Data Synthesis: These 3 novel β-lactam/β-lactamase inhibitor combinations have shown considerable improvement in safety and efficacy as compared with traditional polymyxin-based combination therapy for the treatment of KPC infections. While meropenem-vaborbactam has not shown improved activity against Pseudomonas aeruginosa, it has shown decreased rates of resistance to KPC versus ceftazidime-avibactam. Conclusions: With increasing incidence of KPC infections on a global scale, pharmacists should be aware of the notable similarities and differences between these 3 agents, and the current data supporting their use. Pharmacists may want to consider meropenem-vaborbactam over ceftazidime-avibactam for KPC infections due to decreased likelihood of resistance.

Cost-Effectiveness of Imipenem/Cilastatin/Relebactam Compared with Colistin in Treatment of Gram-Negative Infections Caused by Carbapenem-Non-Susceptible Organisms

“…choosing these new agents. For instance, IMI/REL along with ceftazidime/avibactam and meropenem/vaborbactam are effective against the resistant mechanisms of ESBL, AmpC, and KPC [33,34]; and ceftazidime/ avibactam and IMI/REL both have good activity against multidrug resistant P. aeruginosa [34,35].…”

Carbapenem-Resistant Gram-Negative Fermenting and Non-Fermenting Rods Isolated from Hospital Patients in Poland—What Are They Susceptible to?

“…However, new combinations of antibiotics in conjunction with β-lactamase inhibitors e.g., meropenem with vaborbactam or imipenem with relebactam, offer hope in treating resistant strains [ 42 , 43 , 44 , 45 , 46 , 47 ]. Additionally, some new agents are developed to cope with such infections [ 48 , 49 , 50 ].…”

“…Since the publication of this report, the European Medicines Agency (EMA) has approved several new broad-spectrum antibiotics. Two of them are new combinations of carbapenems with non-β-lactam inhibitors of β-lactamases (also active against carbapenemases), belonging to two new groups of inhibitors: diazabicyclooctane (relebactam, associated with imipenem) and boron (vaborbactam, associated with meropenem) [ 47 ]. The third new drug is a siderophore cephalosporin (cefiderocol) with an innovative mechanism of penetration into the bacterial cell [ 48 ].…”

Evolution of bla KPC Under the Pressure of Carbapenems and Ceftazidime/Avibactam in a Patient With Persistent Bacteremia Caused by Klebsiella pneumoniae

“… 4 Recently, it has been reported that three novel β-lactam (BL)/BLI combinations would be effective for the treatment of KPC-producing Enterobacterales ; ceftazidime-avibactam (CAZ/AVI), meropenem-vaborbactam, and imipenem/cilastatin-relebactam. 5 Not surprisingly, the emergence of CAZ/AVI resistance has been reported since the introduction of CAZ/AVI and 2–8% of K. pneumoniae harboring KPC (KPC-KP) in the United States (US) and Europe are currently CAZ/AVI-resistant. 6 7 8 9 10 CAZ/AVI resistant KPC strains were mainly identified in the US, Italy and Greece, countries where prevalence of KPC-producing K. pneumoniae is high.…”