Omadacycline drug susceptibility testing for non-tuberculous mycobacteria using oxyrase to overcome challenges with drug degradation

Gunavanthi D Boorgula; Tawanda Gumbo; Sanjay Singh; Pamela J McShane; Julie V Philley; Shashikant Srivastava

doi:10.1016/j.tube.2024.102519

Omadacycline drug susceptibility testing for non-tuberculous mycobacteria using oxyrase to overcome challenges with drug degradation

Tuberculosis (Edinb). 2024 May 13:147:102519. doi: 10.1016/j.tube.2024.102519. Online ahead of print.

Authors

Gunavanthi D Boorgula¹, Tawanda Gumbo², Sanjay Singh¹, Pamela J McShane³, Julie V Philley³, Shashikant Srivastava⁴

Affiliations

¹ Department of Medicine, University of Texas at Tyler School of Medicine, Tyler, TX, USA.
² Mathematical Modeling and AI Department, Praedicare Inc., Dallas, TX, USA; Hollow Fiber System & Experimental Therapeutics Laboratories, Wet Lab Systems, Praedicare Inc., Dallas, TX, USA. Electronic address: rozvi1@praedicareinc.com.
³ Department of Medicine, Section of Pulmonary and Critical Care, University of Texas at Tyler School of Medicine, Tyler, TX, USA.
⁴ Department of Medicine, University of Texas at Tyler School of Medicine, Tyler, TX, USA; Department of Cellular and Molecular Biology, University of Texas Health Science Centre at Tyler, Tyler, TX, USA. Electronic address: Shashi.kant@uthct.edu.

PMID: 38754247
DOI: 10.1016/j.tube.2024.102519

Abstract

Background: Drug susceptibility testing (DST) protocol of omadacycline against non-tuberculous mycobacteria has not yet been established. We developed a method to accurately determine MIC omadacycline MIC against Mycobacterium abscessus (Mab), Mycobacterium avium-complex (MAC), and Mycobacterium kansasii (Mkn).

Methods: First, we identified the oxyrase concentration not affecting Mab, MAC, and Mkn growth followed by omadacycline MIC experiments with and without oxyrase using reference and clinical strains.

Results: Oxyrase 0.5 % (v/v) stabilized omadacycline in the culture medium. The median omadacycline MIC was 1 mg/L for Mab and 8 mg/L for Mkn. For MAC, the median omadacycline MIC was 2 mg/L for M. avium, 256 mg/L for M. intracellulare, and 4 mg/L for M. chimaera (p < 0.0001). Wilcoxon matched-pairs signed rank test revealed statistically lower MICs with oxyrase for all MAC subspecies (p < 0.0001), all Mab subspecies (p < 0.0001), and Mkn (p = 0.0002). The decrease in MICs with oxyrase was 17/18 of Mab, 14/19 of Mkn, 8/8 of M. avium, 4/5 M. chimera, but only 11/18 of M. intracellulare (p < 0.013).

Conclusion: Use of 0.5 % oxyrase could be a potential solution to reliable and reproducible omadacycline MIC of Mab. However, oxyrase demonstrated a variable effect in reducing MICs against MAC and Mkn.

Keywords: Minimum inhibitory concentration; Mycobacterium abscessus; Mycobacterium avium-complex; Mycobacterium kansasii; Oxyrase.