Chest Infections |

INH Resistance on Effective Antituberculous Therapy. When Do We Need Molecular Testing? FREE TO VIEW

Ahmed Abuzaid, MBChB; Cezarina Mindru, MD
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Department of Veterans Affairs and Baylor College of Medicine, Houston, TX

Chest. 2014;146(4_MeetingAbstracts):173A. doi:10.1378/chest.1988744
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SESSION TITLE: Infectious Disease Student/Resident Case Report Posters II

SESSION TYPE: Medical Student/Resident Case Report

PRESENTED ON: Tuesday, October 28, 2014 at 01:30 PM - 02:30 PM

INTRODUCTION: There is 7% prevalence of INH resistant MTB strains in US population, mostly in immigrant population. We rarely question the efficacy of the 4 anti-tuberculous regimen for the treatment of pansensitive strains.

CASE PRESENTATION: A 53 years old white homeless male was admitted with dyspnea of few days duration, associated with subjective fever. He had yellowish bloody sputum for the past two years. He travelled by bus over the past two months prior to admission, during which time he noticed progressive leg swelling. Imaging revealed bilateral upper lobes pulmonary cavitations, pulmonary embolism ( as in chest CT image) and DVT of the extremities. The interferon immunoassay test and HIV serology were negative. High amount of AFB in the sputum were identified as M. tuberculosis. The conventional four drug antituberculous therapy was initiated then narrowed down to INH and RIF after 2 months, when the initial isolate came back pansensitive. Surprisingly, 10 weeks later, a repeated culture of the sputum showed the MTB to be resistant to INH despite therapeutic blood levels of INH and rifampin. CDC confirmed INH resistance but the molecular testing did not detect any of the mutations associated with INH resistance. Further sensitivity testing showed sensitivity to all other drugs, including second line drugs. On PZA, ETB, levafloxacin, rifampin, patient had negative sputum cultures.

DISCUSSION: The development of INH resistance on effective therapy is rare. We describe the possible mechanisms of resistance leading to this event. Resistance to INH in Mycobacterium tuberculosis is mediated by at least two genes, katG and inhA (see drug pathway figure). Mutations in other genes are considered compensatory mutations that may be a marker for INH resistance but do not appear to confer INH resistance. Host factors (malnutrition, low CD4 count, immunocompromised status) may be more important than pathogen related factors in determining clinical manifestations of disease and clinical outcomes. Compared to current drug sensitivity testing method, that are reporting isolates as either drug susceptible or drug resistant, rapid molecular methods may provide information concerning both the level of resistance and cross-resistance to other anti-TB drugs.

CONCLUSIONS: The development of resistance on effective therapy, as it was the case in our patient, is rare. Our case raises questions regarding the appropriate use of molecular techniques to detect and identify mycobacterial resistance mechanisms and the clinical impact of lack of detectable genetic mutations.

Reference #1: World Health Organization (2010) Multidrug and extensively drug-resistant TB (M/XDR-TB)- 2010 Global Report on Surveillance and Response. Geneva, Switzerland: World Health Organization Press

Reference #2: •Dantes R, et al. (2012) Impact of Isoniazid Resistance-Conferring Mutations on the Clinical Presentation of Isoniazid Monoresistant Tuberculosis. PLoS ONE 7(5): e37956

DISCLOSURE: The following authors have nothing to disclose: Ahmed Abuzaid, Cezarina Mindru

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