New β-Lactamase Inhibitors Nacubactam and Zidebactam Improve the In Vitro Activity of β-Lactam Antibiotics against Mycobacterium abscessus Complex Clinical Isolates

Abstract

The new diazabicyclooctane-based β-lactamase inhibitors avibactam and relebactam improve the in vitro activity of β-lactam antibiotics against bacteria of the Mycobacterium abscessus complex (MABC). Here, we evaluated the in vitro activities of two newer diazabicyclooctane-based β-lactamase inhibitors in clinical development, nacubactam and zidebactam, with β-lactams against clinical isolates of MABC. Both inhibitors lowered the MICs of their partner β-lactams, meropenem (8-fold) and cefepime (2-fold), respectively, and those of other β-lactams, similar to prior results with avibactam and relebactam.

<p>Antimicrobial Susceptibility of <em>Mycobacterium abscessus</em> Complex Clinical Isolates from a Chinese Tertiary Hospital</p>

“…Although knowledge regarding the efficacy of β-lactams and β-lactamase inhibitors in MABC remains limited, several studies have used the available data to develop synergistic treatment regimens for treating MABC infections. 22,43 In this study, we evaluated the in vitro susceptibility of the 129 MABC isolates to IPM in the presence of CAZ and/or AVI. The MIC 50 and MIC 90 values of IPM after the addition of CAZ plus AVI, compared to the values after the addition of AVI only, decreased 4-fold to 4 and 8μg/mL, respectively.…”

Rifabutin Is Inactivated by Mycobacterium abscessus Arr

“…The RRR of about 250.000 (log 2 =18) clearly shows that RBT is a substrate of Arr which in turn suggests that the potency of RBT against M. abscessus might be improved by either Arr-inhibitors or by RBT modification. Regimens co-applying drugs in conjunction with inhibitors of drug-modifying enzymes have been developed to restore antibiotic activity and are widely used in clinics (24)(25)(26). Similarly, Arr-inhibitors might be beneficial to establish a rifamycin-based treatment for M. abscessus infections.…”

Inhibiting Mycobacterium abscessus Cell Wall Synthesis: Using a Novel Diazabicyclooctane β-Lactamase Inhibitor To Augment β-Lactam Action

“…Diazabicyclooctanes (DBOs) are a recently developed class of β-lactamase inhibitors that may provide an opportunity to address the challenges of Bla Mab and Ldts and expand the use of β-lactams in the treatment of Mab . Avibactam, nacubactam, and zidebactam restore susceptibility to β-lactams and inhibit growth of Mab in vitro ( 16 – 20 ). The DBO avibactam is a potent inhibitor of Bla Mab ( 21 ).…”