MDR-TB

Mehak Goyal

MDR-TB results from either infection with organisms, which are already drugresistant or may develop in the course of a patient's treatment. TB resistant to at least two of first-line anti-tubercular drugs example Isoniazid and Rifampicin with or without resistance to one or more other drugs. The global problem is especially in HIV infected individuals patients. They are obligate aerobe, acid-fast bacilli and grow slowly. The cell wall is composed of mycolic acid, Wax D, phosphatides and it is resistant to acids and alkalis. Another is a in a gene for catalase-peroxidase an enzyme required to activate INH within the bacterium. Drug resistance is more common in people who have spent time with someone with drug-resistant TB disease, do not take their medicine regularly, do not take all of their prescribed medicine and develop TB disease again, after having taken TB medicine in the past come from areas where drug-resistant TB is common (Russia, former USSR, Southeast Asia, Latin America, Haiti, Dominican Republic, and the Philippines) Tuberculosis transmission is through respiratory aerosols. The initial site of infection is the lung. The cord factor is serpentine like growth. For the lab diagnosis acid fast staining, Auramine stain, Lowenstein Jensen agar (8 weeks) can be performed. The clinical course presents with fever, fatigue, night sweats, and weight loss. The Pulmonary manifestations are cough and hemoptysis, scrofula - cervical adenitis (unilateral), tuberculosis meningitis and osteomyelitis. Gastrointestinal effects include abdominal pain and diarrhea; renal system is affected and causes sterile pyuria, dysuria, hematuria, flank pain, and Miliary tuberculosis

Treatment consists of multidrug therapy with duration of 6-9 months. In the Pulmonary disease Isoniazid, Rifampin and pyrazinamide can be given. If the patient is asymptomatic: Isoniazid (6-9 months). These are the first line and second line drugs.

Directly observed treatment, short course, and DOTS means administering potent anti-mycobacterial regimens in an intermittent manner to a patient with tuberculosis under direct supervision. Despite the short course, tuberculosis remains the leading infectious cause of death in India. DOTS is a five-point program that can ensure effective TB control:

Political and administrative that can ensure effective TB control Diagnosis of sputum microscopy in patients attending health facilities Good drugs fro short course therapy Directly observed treatment that should be assessable, acceptable and accountable. Systematic monitoring accountability.

Multidrug resistant TB: It is the worldwide growing health concern, possible resistance to all the first line drugs. Extensive therapy required and it is expensive, toxic and higher mortality rates. Improper drug combinations, poor patient management, and non-compliant patient and poor national program cause it. Strains resistant to at least two drugs (Isoniazid and Rifampin) with or without resistance to other line drugs. Possibility of resistance to all-major anti-TB drugs as well. Single Isoniazid or Rifampicin resistance is not MDR- TB Expensive

 Genetic factors Treatment could be toxic to patients Lack o good laboratory facilities to monitor drug susceptibility Extensively drug resistant TB (XDR TB) Strains resistant to first line (INH and rifampin) and second line drugs

Fluoroquinolones and at least one of three injectable second line drugs: amikacin, kanamycin and capreomycin. Suspect: Drug resistant areas, sputum positive after three months Serious in immunocompromised and elderly Resistance develops due to spontaneous mutations. 1. Isoniazid, there is a deletion or mutation in the catalase peroxidase gene (KatG), alterations in the inhA gene, mutation in the mycolic acid synthesis. 2. Streptomycin, mutations in genes encoding ribosomal s12 proteins (rspL) and 16S rRNA (rrs) Mechanism of resistance 1. Rifampin: Alterations in the b subunit of RNA polymerase (rpoB), reduced cell wall permeability 2. Fluoroquinolones: Mutations in the DNA gyrase gene (gyrA) 3. Pyrazinamide: Mutations in the PncA gene encoding pyrazinamidase For diagnosis PCR to detect mutations, DNA sequencing, Microarrays, and Drug susceptibility tests. Microscopic-observation drug-susceptibility (MODS) assay is used for rapid diagnosis of multidrug resistance TB: Tests for both Rifampicin and INH resistance.

MODS KIT: Detects the presence of viable Mycobacterium tuberculosis and Performs susceptibility testing simultaneously and within the same procedure. Detects resistance to both isoniazid and rifampicin Uses liquid culture for accelerated growth. Utilizes the TB cording phenomenon for identification, which is easily viewed with an inverted microscope. Detects susceptible, mono-resistant, and multi-drug resistant (MDR) TB usually within a 5 to 10 day incubation period rug TREATMENT HIV

-Manage HIV and TB - Drug Interactions - Rifabutin instead of Rifampin Children -Susceptibility testing -Source unknown +increased risk Standard four line first line regimen until source known -Long term use of fluoroquinolones not approved Pregnant Women -Consult experts because most second line drugs are toxic to fetus -Pyrazinamide should not be used Prevention: Better housing and nutrition, prompt identification and treatment, PPD skin test, BCG vaccine, DOT, Patient compliance.

Management: Treatment should be in a specialized center with standard laboratory facilities Never add a single drug to a failing regimen Be careful about cross resistance If possible, give all the drugs in a single daily dose Avoid intermittent therapy Therapy should be in monitor for at least 3-4 months or until sputum conversion Surgical treatment should be considered as a adjunct to chemotherapy, wherever applicable as results of chemotherapy are very unpredictable All measures should be taken to persuade and encourage patients not to stop treatment despite all its discomfort as it is the last treatment that stands between the patient and death

Work cited Davis, Bernard D.. Microbiology. 4th ed. Philadelphia: Lippincott, 1990. Print. Prescott, Lansing M., John P. Harley, and Donald A. Klein. Microbiology. 6th ed. Dubuque, IA: McGraw-Hill Higher Education, 2005. Print. Tortora, Gerard J., and Berdell R. Funke. Microbiology: an introduction. 10th ed. Boston: Pearson, 2013. Print. "TB MODS Kit for TB Identification - Tuberculosis Detection." Microbiology Culture Media and Laboratory Supplies - by Hardy Diagnostics. N.p., n.d. Web. 8 May 2013. <http://hardydiagnostics.com/tbmodskit.h "Directly Observed Therapy (DOT) for the Treatment of Tuberculosis - Minnesota Dept. of Health." Minnesota Department of Health. N.p., n.d. Web. 8 May 2013. <http://www.health.state.mn.us/divs/idepc/diseases/tb/dot.html>. "MDR-TB." WHO. N.p., n.d. <http://www.who.int/tb/challenges/mdr/en Web. 8 May 2013.