Meropenem/Vaborbactam Plus Aztreonam as a Possible Treatment Strategy for Bloodstream Infections Caused by Ceftazidime/Avibactam-Resistant Klebsiella pneumoniae: A Retrospective Case Series and Literature Review

Abstract

Objectives: The aim of this study was to describe our experience of a combination treatment including meropenem/vaborbactam (M/V) plus aztreonam (ATM) for bloodstream infections (BSIs) due to ceftazidime/avibactam-resistant Klebsiella pneumoniae (CAZ/AVI-R-Kp), for which gene typing was not available at the time the blood culture (BC) results were obtained. Methods: Between 20 July and 22 August 2021, in our hospital laboratory, the molecular test for carbapenemase gene typing was not available. All Gram-negative bloodstream infections were recorded, and characteristics of patients were analysed. Among them, three patients had positive BCs for CAZ/AVI-R-Kp, and the empirical therapy was switched to M/V plus ATM pending phenotypic testing of sensitivity to M/V. Therapy was subsequently targeted on the basis of the results of this test. Results: KPC and NDM represent the most prevalent carbapenemases in our polyclinic. Three patients with CAZ/AVI-R-Kp sepsis were treated with M/V plus ATM not knowing the carbapenemase gene. Two had an NDM-Kp infection for which, upon obtaining the result of sensitivity to M/V, combination therapy was maintained. The third had KPC-Kp infection for which ATM was discontinued, after the acquisition of an antibiogram reporting full sensitivity to M/V (MIC = 0.25 mg/L). One patient with NDM-Kp infection died due to complications of the underlying disease for which he was hospitalised. Conclusions: Meropenem/vaborbactam plus ATM and subsequent de-escalation could represent a possible therapeutic strategy in severe CAZ/AVI-R-Kp infections when carbapenemase gene typing is not rapidly available.

Novel Antimicrobial Agents for Gram-Negative Pathogens

“…Alternatively, when we have evidence for a CRE infection, but we do not know the resistance phenotype, we can initially treat with a novel beta-lactam/beta-lactamase inhibitor plus aztreonam. When the susceptibility test results become available, we can de-escalate treatment accordingly [ 171 ].…”

Efficacy and Safety of Colistin versus Tigecycline for Multi-Drug-Resistant and Extensively Drug-Resistant Gram-Negative Pathogens—A Meta-Analysis

“…Newer drugs such as ceftazidime/avibactam have shown good clinical outcomes and better survival outcomes when compared with colistin-based combinations for CRE infections [ 5 , 36 ]. Additionally, meropenem/vaborbactam, which has recently been demonstrated to be a potential therapeutic strategy against ceftazidime/avibactam-resistant Klebsiella pneumoniae when combined with ATM [ 37 ], showed better clinical cure rates compared to colistin- or tigecycline-based combinations in treating patients with CRE infections [ 38 ].…”

What to Do with the New Antibiotics?

“…A retrospective study showed similar efficacy between MEV and CZA for the treatment of KPC-producing Enterobacterales -related infections [ 49 ]. Meropenem/vaborbactam may be effective against KPC-producing Enterobacterales resistant to CZA [ 50 , 51 , 52 ].…”