Treatment approach for extensively Drug-Resistant Tuberculosis (XDR-TB)

Dr. S. Sivaram Kannan¹, D. Suryaprabha²,*

¹Senior Consultant Internal Medicine & Diabetology, Department of Internal Medicine & Diabetology, Kauvery Hospital, Chennai

²Assistant Manager – Clinical Research, Kauvery Hospital, Trichy

Correspondence: suryaprabha@kauveryhospital.com

Background

India has the highest estimated burden of tuberculosis infection globally, with nearly 35-40 crores Indian population having the infection, of which 26 lakhs people are estimated to develop tuberculosis (TB) disease annually. This demographic may change after the ongoing national TB prevalence survey data becomes available.

Extensively drug-resistant (XDR) tuberculosis is defined as disease caused by Mycobacterium tuberculosis with resistance to at least isoniazid and rifampicin, any fluoroquinolone, and at least one of three injectable second-line drugs (amikacin, capreomycin, or kanamycin).

Clinical manifestations, although variable in different settings and among different strains, have in general shown that XDR tuberculosis is associated with greater morbidity and mortality than non-XDR tuberculosis. The treatment of XDR tuberculosis should include agents to which the organism is susceptible, and should continue for a minimum of 18-24 months [1].

Case Presentation

A 31-year-old male was apparently normal till three months back. He developed a loss of weight and appetite. He underwent a check-up. Chest X-ray showed nodular opacities in the left upper zone. However, he did not take treatment.

He developed low-grade intermittent fever, with cough and expectoration one month later. Sputum AFB, sputum C/S and sputum Gene Xpert were done and revealed rifampicin resistant – TB pneumonia. The patient was advised ATT but did not take medication. Symptoms worsened and he was brought to Kauvery Hospital for further management.

No history of contact with a person with TB was available.

On Examination

Patient conscious, oriented, afebrile,

Dehydration (+), tachycardia (+), tachypnea (+)

PR – 124/min, BP – 160/100 mmHg, SpO2 – 80% in room air, 95% with 15L O2/min, CBG – 199 mg/dl

RS – BAE (+), B/L coarse crepitations, CVS – S1 S2 (+), P/A – Soft, BS (+), CNS – NFND

Course in the Hospital

The patient was brought with tachypneic, and the oxygen requirement was high. Arterial blood gas studies revealed hypoxemia with type II respiratory failure. He was started on non-invasive ventilation, which he did not tolerate. After informed consent, he was electively intubated.

CT chest was done which showed consolidation with air bronchograms, with surrounding ground glass opacities involving the right posterior segment of the upper lobe, a lateral segment of the right middle lobe, an apicoposterior segment and lingular segment of the left upper lobe and bilateral superior-basal & posterior-basal segments of lower lobes, thick-walled cavities in the apico-posterior segment of left upper lobe and centrilobular nodules in the tree- in- bud pattern involving bilateral lung fields. Features were suggestive of active infection with endobronchial spread.

Covid, H1N1 and RT-PCR were negative. HIV I & II, Hepatitis B, anti-HCV IgM, and anti-HBC were non-reactive. HBV DNA quantitative was not detected. Liver enzymes were elevated.

Sputum AFB was positive. Blood, C-line and ET culture and sensitivity turned out to be negative.

He was started on antitubercular therapy with Linezolid, Levofloxacin, Clofazimine, cycloserine, amikacin, ethambutol, ethionamide and pyrazinamide. His liver function was serially monitored. Keeping possible worsening of liver function in mind, pyrazinamide and ethionamide was stopped.

The patient improved with ventilator support. Serial ABG and CXR were done. After a trial of spontaneous breathing, the patient was extubated and started on high-flow oxygen support. The patient’s oxygen requirement and tachypnea gradually decreased and he was weaned off high-flow oxygen. Patient’s oxygen saturation and respiratory rate were held with venturi mask support.

Diagnosis

Hains MTB’s first and second drug resistance profiles showed resistance to Rifampicin, Isoniazid, fluoroquinolones, amikacin, capreomycin, kanamycin, viomycin. The patient was found to have XDR TB.

The patient was clinically stable. He was discharged with venturi mask oxygen support and referred, as per the Director of Health Policy, to the Government General Hospital, Department of Respiratory Medicine.

He was advised with the following medications – Linezolid 600 mg injection, Clofazimine 100 mg tablet, Cycloserine 750 mg tablet, Moxifloxacin 400 mg tablet, Ethambutol 1000 mg tablet.

Discussion Drug Regimen [2]

Fig. 1. Treatment algorithm for Rifampicin resistant tuberculosis (MDR/RR-TB).

Dosage of shorter oral Bedaquiline-containing MDR/RR-TB regimen drugs is 9-11 months

High dose H (Hh ), Ethambutol (E), Pyrazinamide (Z), Levofloxacin (Lfx), Bedaquiline (Bdq), Clofazimine (Cfz), Ethionamide (Eto), Pyridoxine (Pdx)

Total duration of longer oral M/XDR-TB regimen is 18-20 months.

Levofloxacin (Lfx), Moxifloxacin (Mfx), High dose Mfx (Mfxh), Bedaquiline (Bdq), Clofazimine (Cfz), Cycloserine (Cs), Linezolid (Lzd), Delamanid (Dlm), Amikacin (Am), Pyrazinamide (Z), Ethionamide (Eto), Na – PAS (60% weight/vol), Ethambutol (E), Imipenem-Cilastatin (Imp-Cln), Meropenems (Mpm), Amoxicillin-Clavulanate (Amx-Clv) (to be given with carbapenems only), Pyridoxine (Pdx)

Contact tracing

Contact tracing must be done during the initial home visit or virtual interaction through tele/video calls by health workers with family/close contacts for enumeration, counselling, screening and encouraging eligible HHC for TPT initiation at HWC or HF. Enumeration and contact tracing/investigation of the target population needs to be proactively undertaken by the health-care workers at every HF (HWC, primary health centre [PHC]/ community health centre [CHC], private clinic, ICTC/ART centres and institutions providing care to the specific risk groups considered eligible for TPT) using the Prevent TB India app for information management and monitoring of the TPT care cascade.

Pre-treatment assessment and TPT initiation

Personal history. Elicit information relevant for TPT initiation and continuation, such as

Allergy or known hypersensitivity to TB drugs (isoniazid, rifampicin, rifabutin or rifapentine).
HIV status and ART regimen.
Pregnancy status or birth control method used.
Assess the presence of co-morbidities such as malnutrition, diabetes, liver disease and record medications being taken.

Abbreviations: FL LPA, first line-line probe assay; SL-LPA, second-line-line probe assay; LC DST, liquid culture Drug susceptibility testing; Z, Pyrazinamide; FQ, Fluoroquinolone; MDR-TB, Multi-drug resistant TB; RR-TB, Rifampicin resistant tuberculosis; PTE, pre-treatment evaluation.

References