Beta-lactam antibiotics in combination with novel β-lactamase inhibitors – an alternative therapy for infections caused by multidrug-resistant bacteria

Małgorzata Brauncajs, Filip Bielec, Anna Macieja, Dorota Pastuszak-Lewandoska


Introduction: New combinations of old β-lactam drugs with novel β-lactamase inhibitors, approved in recent years by the US Food and Drug Administration and the European Medicines Agency, are a promising alternative for the treatment of infections caused by multidrug-resistant strains. Due to limited availability and increasing resistance to antibacterial drugs, they should be used with caution, especially in patients with limited treatment options. It should be noted that both diazobicycloctane and boron inhibitors are inactive against metallo-β-lactamase (MBL) producing strains.
The aim of this study was to evaluate the in vitro susceptibility of carbapenemase-producing Gram-negative bacilli to meropenem/vaborbactam, imipenem/relebactam and ceftazidime/avibactam in clinical samples from hospitalized patients.
Materials and methods: The analysis included 102 clinical strains of carbapenemase-producing Enterobacterales and nonfermenters from hospital centers in Łódź, Poland. A minimum inhibitory concentration test strip method was used to determine antimicrobial susceptibility.
Results: Seventy-one percent of Escherichia coli, 40% of Klebsiella pneumoniae, and 67% of Pseudomonas aeruginosa were resistant to meropenem/vaborbactam, 57%, 66%, and 60% to imipenem/relebactam, and 71%, 74%, and 60% to ceftazidime/avibactam, respectively. Considering carbapenemase resistance mechanisms, the highest efficacy was observed in Klebsiella pneumoniae carbapenemases (KPC) strains for each drug combination tested.
Conclusions: The results of our study confirm the conclusions of the studies evaluating the susceptibility of Gram-negative, fermenting, and non-fermenting bacilli to ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam and indicate that there are reasonable grounds for using these antibiotics in the treatment of patients hospitalized with serious infections. However, limitations in their use against MBL-producing strains are highlighted.


antimicrobials; meropenem/vaborbactam; imipenem/ relebactam; ceftazidime/avibactam; multi-drug resistance; antimicrobial susceptibility testing; epidemiology

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