An overview of drugs for the treatment of Mycobacterium kansasii pulmonary disease

Shashikant Srivastava; Jotam G Pasipanodya; Scott K Heysell; Gunavanthi D Boorgula; Tawanda Gumbo; Pamela J McShane; Julie V Philley

doi:10.1016/j.jgar.2021.12.010

An overview of drugs for the treatment of Mycobacterium kansasii pulmonary disease

J Glob Antimicrob Resist. 2022 Mar:28:71-77. doi: 10.1016/j.jgar.2021.12.010. Epub 2021 Dec 18.

Authors

Shashikant Srivastava¹, Jotam G Pasipanodya², Scott K Heysell³, Gunavanthi D Boorgula⁴, Tawanda Gumbo², Pamela J McShane⁵, Julie V Philley⁵

Affiliations

¹ Department of Pulmonary Immunology, University of Texas at Tyler, Tyler, Texas, USA; Department of Immunology, UT Southwestern Medical Center, Dallas, Texas, USA; Department of Pharmacy Practice, Texas Tech University Health Science Center, Dallas, Texas, USA. Electronic address: Shashi.kant@uthct.edu.
² Quantitative Preclinical & Clinical Sciences Department, Praedicare Inc., Dallas, Texas, USA.
³ Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA.
⁴ Department of Pulmonary Immunology, University of Texas at Tyler, Tyler, Texas, USA.
⁵ Section of Pulmonary and Critical Care, University of Texas at Tyler, Tyler, Texas, USA.

Abstract

Objectives: The aim of this study was to determine and compare the efficacy of drugs to treat Mycobacterium kansasii (Mkn) pulmonary disease by performing minimum inhibitory concentration (MIC) determination and time-kill studies.

Methods: We determined the MICs to 13 drugs against the Mkn standard laboratory strain ATCC 12478 and 20 clinical isolates and performed time-kill studies with 18 drugs from different classes using the standard laboratory strain of Mkn. The β-lactam antibiotics were tested with or without the combination of the β-lactamase inhibitor avibactam. An inhibitory sigmoid E_max model was used to describe the relationship between drug concentrations and bacterial burden.

Results: Among the 13 tested drugs in the MIC experiments, the lowest MIC was recorded for bedaquiline. Among the 18 drugs used in the time-kill studies, maximum kill with cefdinir, tebipenem, clarithromycin, azithromycin, moxifloxacin, levofloxacin, tedizolid, bedaquiline, pretomanid and telacebac was greater than that for some of the drugs (isoniazid, rifampicin and ethambutol) used in standard combination therapy.

Conclusion: We report preclinical data on the efficacy and potency of drugs that can potentially be repurposed to create a safe, effective and likely shorter-duration regimen for the treatment of Mkn pulmonary disease.

Keywords: Efficacy; Mycobacterium kansasii; Nontuberculous mycobacteria; Repurposed drugs.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Humans
Lung Diseases* / drug therapy
Lung Diseases* / microbiology
Microbial Sensitivity Tests
Moxifloxacin / pharmacology
Mycobacterium kansasii*

Substances

Anti-Bacterial Agents
Moxifloxacin

Abstract

Publication types

MeSH terms

Substances

Grants and funding