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Omadacycline drug susceptibility testing for non-tuberculous mycobacteria using oxyrase to overcome challenges with drug degradation.
Boorgula, Gunavanthi D; Gumbo, Tawanda; Singh, Sanjay; McShane, Pamela J; Philley, Julie V; Srivastava, Shashikant.
Afiliação
  • Boorgula GD; Department of Medicine, University of Texas at Tyler School of Medicine, Tyler, TX, USA.
  • Gumbo T; 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.
  • Singh S; Department of Medicine, University of Texas at Tyler School of Medicine, Tyler, TX, USA.
  • McShane PJ; Department of Medicine, Section of Pulmonary and Critical Care, University of Texas at Tyler School of Medicine, Tyler, TX, USA.
  • Philley JV; Department of Medicine, Section of Pulmonary and Critical Care, University of Texas at Tyler School of Medicine, Tyler, TX, USA.
  • Srivastava S; 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.
Tuberculosis (Edinb) ; 147: 102519, 2024 Jul.
Article em En | MEDLINE | ID: mdl-38754247
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tetraciclinas / Testes de Sensibilidade Microbiana / Mycobacterium abscessus / Antituberculosos Limite: Humans Idioma: En Revista: Tuberculosis (Edinb) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tetraciclinas / Testes de Sensibilidade Microbiana / Mycobacterium abscessus / Antituberculosos Limite: Humans Idioma: En Revista: Tuberculosis (Edinb) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos