Multiple drug-resistant tuberculosis

Drug resistance of bacteria is a great issue in modern medicine. In general, it means that a strain is resistant to the drugs which are given and, therefore, the treatment won’t be successful and a disease won’t be cured. It is suggested that all the cases of drug resistance are related to poor medical practice and poor adherence to therapy, which in turn leads to the development of drug resistance. As long as the humanity has been dealing with tuberculosis for centuries and lots of drugs were invented many decades ago and since that time were widely used for the treatment of tuberculosis Mycobacteria adapted to many of these medications and became drug resistant.

Stethoscope and pharmaceuticals on a blackboard - TuberculosisIn 2011 more than 600000 cases of multiple drug-resistant tuberculosis to isoniazid and rifampin were reported with the highest prevalence of MDR-TB in China, India and the Russian Federation. 30 countries including Angola, Azerbaijan, Bangladesh, Belarus, China, DPR Korea, DR Congo, Ethiopia, India, Indonesia, Kazakhstan, Kenya, Kyrgyzstan, Mozambique, Myanmar, Nigeria, Pakistan, Papua New Guinea, Peru, Philippines, Republic of Moldova, Russian Federation, Somalia, South Africa, Tajikistan, Thailand, Ukraine, Uzbekistan, Viet Nam,  Zimbabwe have the highest burden of drug-resistant TB.

  • tuberculosis strains resistant to at least isoniazide and rifampin (the most potent drugs available for TB treatment) are known as multiple drug-resistant (MDR-TB).
  • Strains resistant to isoniazide, rifampin, a fluoroquinolone, and an aminoglycoside are referred to as extensively drug-resistant (XDR-TB) which were detected in approximately 120 countries.
  • Lately cases of totally/extremely drug-resistant TB have been reported (XXDR-TB or TDR-TB) in India, Iran and Italy. This strain is not susceptible to a wide range of antibiotics – even more than XDR-TB, making it extremely difficult to treat.

Drug susceptibility tests are used to identify whether the strain is susceptible to drugs or not and verify which of the medications may effectively eliminate bacteria.

Primary and secondary drug-resistant TB

  • Primary drug resistance means that the resistance was present before the start of the treatment – a person caught a drug-resistant M. tuberculosis strain – whether this strain was drug-resistant mutant (had resistance naturally) or a person got these bacteria from another ill person who wasn’t treated properly;
  • Secondary drug resistance indicates the development of drug-resistance after antituberculosis treatment due to poor adherence to therapy (a person fails to take drugs properly) or the inadequate regimen with wrong doses of drugs (for example, monotherapy – with a single drug);

Natural drug resistance

Natural resistance of Mycobacteria is provided by the multi-layer cell envelopes which prevent the antibiotics from entering into the bacteria and active multidrug efflux pumps which actively pump molecules of the medicines out of the bacterial cells. Mycobacteria also produce various proteins able to inactive the drugs or modify their activity.

Acquired drug resistance           

Acquired drug resistance is related to the spontaneous mutations of the bacterial genes which help bacteria to survive the antibiotic attack.

Factors related to increased risk of acquiring MDR M.tuberculosis

  • Being in contact with a person who 1) has known drug-resistant tuberculosis or 2) has active tuberculosis despite prior treatment (treatment failure or relapse) or 3) has positive sputum smears after combination therapy for 2 months;
  • Being in contact with individuals with active tuberculosis who have visited the areas with high prevalence of drug resistance;
  • Travelling in the areas of high prevalence of drug resistance;

Prevention of drug resistance

  • Rapid diagnosis and prescription of appropriate treatment regimen, avoidance of monotherapy which is associated wih increased risk of developing drug resistance;
  • High adherence to therapy, if needed – directly observed therapy meaning that a healthcare worker must observe how a person consumes drugs;
  • Treatment completion – interrupted therapy leads to drug resistance;

Treatment

Multiple drug-resistant TB requires treatment with second-line antituberculosis drugs which are both more toxic and more expnsive than first-line medications.

For tuberculosis caused by the strains resistant to isoniazid and rifampin, combinations of a fluoroquinolone, ethambutol, pyrazinamide, and streptomycin (or alternatively amikacin or kanamycin) must be given for 18–24 months and for at least 9 months after the Mycobacteria are no longer detected in the sputum ve. In case of resistance to all of the first-line medications a combination of four second-line drugs for 24 months is recommended.

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