Chest Infections |

A Case of Phenotypically Occult MDR-TB - What Is the Optimal Therapeutic Regimen? FREE TO VIEW

Julia Pritchard, MD; Julie Jarand, MD; Dina Fisher, MD
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University of Calgary - Division of Respiratory Medicine, Calgary, AB, Canada

Chest. 2015;148(4_MeetingAbstracts):106A. doi:10.1378/chest.2277707
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SESSION TITLE: Chest Infections II: Student Resident Case Report Posters

SESSION TYPE: Student/Resident Case Report Poster

PRESENTED ON: Tuesday, October 27, 2015 at 01:30 PM - 02:30 PM

INTRODUCTION: The rate of multiply drug resistant Mycobacterium tuberculosis (MDR-TB) is increasing; but with new rapid screening time to effective therapy can be decreased. Early detection and appropriate treatment is essential as MDR-TB is associated with longer therapy duration, higher failure rates, increased morbidity from antibiotic side effects and overall mortality(1). Conventional drug susceptibility testing (DST), conveys phenotypic susceptibility whilst new molecular techniques detect genes involved in drug resistance (ex. rpoB and rifampin resistance). However, discordant genotype and phenotype susceptibility results are described.

CASE PRESENTATION: A 41-year-old previously healthy Korean woman presents with chronic productive cough, and dyspnea. Pulmonary tuberculosis was confirmed following sputum analysis and culture. The patient was started standard quadruple therapy using isoniazid (INH), rifampin (RMP) ethambutol (EMB) and pyrazinamide (PZA). Conventional DST reported sensitivity to RMP and EMB and resistance to INH and PZA. Discordantly, molecular testing reported resistance to RMP and EMB. Given discrepant susceptibility results EMB was continued, however RMP, INH and PZA were replaced with rifabutin, levofloxacin, linezolid and cycloserine as the strain was both genotypically and phenotypically sensitive. Unfortunately the patient developed severe drug rash with levofloxacin and rifabutin. She has continued therapy with EMB, linezolid and cycloserine and is currently smear and culture negative.

DISCUSSION: MDR-TB by definition requires resistance to both RMP and INH. Phenotypically occult MDR-TB refers to strains that are INH resistant with RMP sensitivity by conventional DST whilst containing rpoB mutations. Studies suggest a link between harboring rpoB mutations with treatment failure with rifampicin based regimens but increased adverse drug reactions with second line therapies(2,3). We designed a treatment strategy based on the patient’s specific rpoB mutation and DST while navigating adverse drug reactions.

CONCLUSIONS: Phenotypically occult MDR-TB will be an emerging dilemma as access to rapid susceptibility testing becomes increasingly available. In our case the patient was successfully treated using modified therapeutic regimen for MDR-TB. Further research is required to determine the optimal treatment regimes that achieve cure without increased drug toxicity.

Reference #1: (1) Long R, Avendano M, Kunimoto D. Drug-Resistant Tuberculosis. In: Menzies D, editor. Canadian Tuberculosis Standards. 7th Edition ed.: Canadian Thoracic Society;2014.p.185-218.

Reference #2: (2) Ho J, Jelfs P, Sintchencko V. Phenotypically occult multidrug-resistant Mycobacterium tuberculosis: dilemmas in diagnosis and treatment. J Antimicrob Chemother 2013 Dec;68(12):2915-2920.

Reference #3: (3) Pang Y, Ruan YZ, Zhao J, Chen C, Xu CH, Su W, et al. Diagnostic dilemma: treatment outcomes of tuberculosis patients with inconsistent rifampicin susceptibility. Int J Tuberc Lung Dis 2014 Mar;18(3):357-362.

DISCLOSURE: The following authors have nothing to disclose: Julia Pritchard, Julie Jarand, Dina Fisher

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