Introduction

Multidrug resistance tuberculosis (MDR-TB), an emerging global health crisis, is caused by mycobacterium tuberculosis that is resistant to isoniazid and rifampicin, the two most effective first line antitubercular drugs. MDR-TB involve young population including women of reproductive age group [1]. India and China account for 50% of the total estimated burden of multidrug resistance tuberculosis worldwide [2]. The incidence of multidrug resistance tuberculosis in India is 1.3% in new cases and 1217% in retreatment cases [3,4,5]. Management issues raised by pregnant patient with MDR-TB are full of controversies and lack of experience [6-8]. Pregnancy per se is not a contraindication for MDR-TB treatment, but has less favorable prognosis. All females of reproductive age group with MDR-TB should be strongly motivated for effective contraception.

Case Report

26-year-old multigravida at 15 weeks gestation presented to emergency OPD with complaints of cough with purulent sputum, abdominal distension and bilateral lower limb swelling for 3 weeks. She had conceived spontaneously and ultrasonography done at 14 weeks revealed live fetus with corresponding gestation and significant maternal ascites.

In her past history, she was diagnosed to have pulmonary tuberculosis 10 year ago during her first conception and received antitubercular treatment for six months. She was cured and her subsequent two pregnancies at an interval of 3 years were uneventful. She had reactivation of pulmonary tuberculosis 1 year back, again started on drug therapy but stopped of her own and reported with cough, dyspnea, lower limb swelling and progressive abdominal distension.

General physical examination revealed pallor, tachypnea (RR=26/min), right cervical lymphadenopathy, decreased breath sounds on right side, free fluid in abdomen, pedal edema. Blood investigations revealed anemia (Hb=7.5gm %), deranged renal function tests (urea/creatinine =146/4.6), hypoproteinemia and hypoalbuminemia (3.1/1.1) and normal liver function tests (0.18/24/12/348).Chest X-ray showed right lung collapse, sputum smear examination and culture revealed infection with mycobacterium tuberculosis and ultrasonography confirmed ascites along with renal parenchymal disease. Diagnosis of multidrug resistance disseminated tuberculosis (defaulter) was established after sputum examination confirmed mycobacterium tubercular strain resistant to rifampicin and isoniazid. Patient clinical profile mandated us to start second line drugs and injectable immediately. Decision for therapeutic abortion was taken after full agreement with patient and relatives. Her pregnancy was successfully terminated with oral mifepristone 200 mg followed insertion of 400 microgram misoprostol vaginally. Supportive treatment along with chemotherapy (according to susceptibility) i.e., Levofloxacin, Ethionamide, Pyrazinamide, Ethambutol and Cycloserine along with injectable kanamycin and she was discharged after one week in stable condition with advice to continue the drugs and next follow up.

Discussion

Treatment of gestational multidrug resistance tuberculosis is more complex, controversial and challenging, nonetheless poorly or untreated patients can have adverse consequences on mother and baby. Lack of consensus and limited experience still persist with regard to the treatment of MDR-TB during pregnancy despite existing guidelines [5,9]. The influence of multidrug resistance tuberculosis on maternal health is very important especially in developing countries where this is underestimated. Non-adherence to the standard therapy, malnutrition, religious concepts, access to medical care and illiteracy are the factors that contribute to the acquisition of drug resistance in low resource settings as in our case. Successful management of such patients depends on appropriate individualized therapy considering the relative risk versus benefit for baby and mother. According to fewer guidelines second line drugs are usually deferred till second trimester due to the fear of teratogenicity, however in conditions like co-infection with retrovirus, advanced disease and respiratory failure treatment is recommended immediately irrespective of gestation with informed discussion. In situations where treatment is mandatory before 20 weeks of gestation, patient should be given option to undergo therapeutic abortion in order to avoid potential risks to baby and mother. If patient denies for Medical Termination of Pregnancy (MTP) high risk of disease dissemination along with vertical transmission should be explained and modified regimen in which less efficacious Paraminosalicylic Acid (PAS) is substituted for kanamycin can be considered [10,11].The treatment in our case was challenging and more complicated as patient had disseminated disease along with renal involvement. It was obligated to start her on aggressive treatment along with injectable in order to prevent dire consequences. Her worsening general conditions and chest x-ray was another hallmark of resistance. Luckily, she agreed upon termination of pregnancy and expelled abortus after first dose of misoprostol. No dose modification was done for mifepristone in index case as she was having adequate urine output despite deranged renal function tests [12].

So, to conclude, multidrug resistance tuberculosis during pregnancy poses therapeutic challenge due to more controversies than evidence and successful outcome of these patients depend on appropriate, well timed and individualized treatment. We do advocate therapeutic abortion in critically ill patient in order to prevent grievous consequences.

1. Aziz MA, Wright A, Laszlo A, De Muynck A, Portaels F, et al (2006) Epidemiology of anti-tuberculosis drug resistance the Global Project on Anti-Tuberculosis Drug Resistance Surveillance an updated analysis. Lancet 368: 2142-2154.
2. Giridhar MK, et al. (2014) Sch J App Med Sci 2:269-273.
3. Mahadev B, Kumar P, Agarwal SP, Chauhan LS, Srikantaramu N (2005) Surveillance of drug resistance to anti-tuberculosis drugs in districts of Hoogli in West Bengal and Mayurbhanj in Orissa. Indian J Tuberc 52: 5-10.
4. Paramasivan CN, Venkataraman P, Chandrasekaran V, Bhat S, Narayanan PR (2002) Surveillance of           drug resistance in tuberculosis in two districts of South India. Int J Tuberc Lung Dis 6: 479-484.
5. Central TB Division (2009) Directorate General of Health Services Ministry of Health & Family Welfare. DOTS-Plus Guidelines Feb 2009NirmanBhavan New Delhi: Revised National Tuberculosis Control Programme: 39-54.
6. Shin S, Guerra D, Rich M, Seung KJ, Mukherjee J, et al. (2003) Treatment of multidrug resistant tuberculosis during Pregnancy a report of 7 cases. Clinical Infectious Diseases 36: 996-1003.
7. Palacios E, Dallman R, Muñoz M, Hurtado R, Chalco K, et al. (2009) Drug-resistant tuberculosis and pregnancy treatment outcomes of 38 cases in Lima Peru. Clin Infect Dis 48: 1413-1419.
8. Schaefer G, Zervoudakis IA, Fuchs FF, David S(1975)Pregnancy and pulmonary tuberculosis. Obstet Gynecol 46:706-715.
9. World Health Organization (2003) Treatment of tuberculosis guidelines for national programmes:1-113.
10. Drobac PC, del Castillo H, Sweetland A, Anca G, Joseph JK, et al. (2005) Treatment of multidrug-resistant tuberculosis during pregnancy long-term follow-up of 6 children with intrauterine exposure to second-line agents. Clin Infect Dis 40:1689-1692.
11. Guidelines on Programmatic Management of Drug Resistant TB (PMDT) in India (2012) Central TB    Division Directorate General of Health Services Ministry of HealthMay 2012: 1-133.
12. Hamadeh MA, GlassrothJ (1992) Tuberculosis and Pregnancy. Chest 101:1114-1120.