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Rakesh chandra chaurasia
Reviews Of Progress
Vol - 1, Issue - 29, Nov 13 2013
DRUG RESISTANCE TUBERCULOSIS - AN
Rakesh Chandra Chaurasia
Tuberculosis is one of the global public health concerns of morbidity and
mortality. India shares large number of cases. Concurrent occurrence of HIV infection makes the treatment very difficult.Emergence of antitubercular (ATT) resistance is alarming due to limited number of safe and effective pharmacological agents. Newer agents are comparatively less efficacious and more toxic. Multi drug resistance, extensively drug resistance, and now total drug resistance tuberculosis create problem with conventional pharma cotherapy.
Resistance, Pharmacotherapy, Mortality.
Tuberculosis (TB) 'the king of disease
' is mentioned In Indian text 'Ayurveda'. It is one of the
diseases resulting into worldwide morbidity and mortality. WHO declares TB as global emergency .For awareness among community towards this deadly disease '24th march'
is dedicated as 'World TB day'
. Till early four decades of 20th century, effective pharmacotherapy was not available .Treatment were consist of traditional measures such as rest, fresh air and nutritious diet. Sanatorium was places in hilly area specially serve affordable needy persons.
Anti tubercular's - at a glance
Streptomycin was credit as first antitubercular used since 1947. After 2 year para amino
salicylic acid (PAS) was introduced. Both of them have their own limitations in terms of toxicity. Introduction of Effective Isoniazid and Pyrazinamide were revolutionary steps in 1952. After the advent of ethambutol in 1961 domiciliary treatment was started. Short course therapy become possible after the additions of refimpicin in 1962.Now a day, agents indicated in other conditions are utilized as anti-tubercular's in special situations.
Antitubercular drugs are categorize as (i)Standard drugs – Iso Nicotinamide Hydrazide (H), Refampicin(R), Pyrazinamide( Z), Streptomycin (S) and Ethambutol (E) (ii)Reserve drugs - Flouroqinolones, Macrolide, Aminoglycosides, and Refamycins. Miscellaneous/newer drugs
Standard drugs are supposed to be first line drugs in the sense that those are highly efficacious, less
Reserve drugs are comparatively less efficacious and toxic therefore should be reserved for
special circumstances such as resistance.
DRUG RESISTANCE TUBERCULOSIS - AN ALARMING EMERGENCY
Problems with disease
Different subpopulations of bacilli in a lesions- Rapid grower, slow grower and persister
Shifting of bacilli from one subpopulation to other
Problems with pharmacotherapy
Atypical mycobacterium infection , resistant to available antitubercular
Poor patient compliance due to long therapy and drugs toxicity
Defaulter. Relapse or non responsiveness.
Resistance is simply 'non responsiveness' to pharmacological agents. Mutation is main reasons of
resistance among bacilli. In resistant strains there is reduce penetration of drug inside or there is over production of enzymes that are usually inhibited by drug. INH & R are dangerous in this context because these are only drugs recommended through out therapy (intensive as well as continuations phase) There combination is synergistic as well as preventing the resistance. Other first line agents are also prone to resistance.
Regarding to resistance, there are two well known entities – MDR & XDR. TDR is new entry.
MDR (multi drug resistance) TB
is resistance to commonly used first line drug i.e. Isoniazid and
refampicin with / without to other first line drugs. In other words, MDR TB means resistance with first line
drugs only. XDR (extensively drug resistance) TB
- In addition to MDR, mycobacterium are resistant to second line
fluoroquinolone and injectable aminoglycosides. Thus XDR TB shows resistance to first line as well as
second line drugs. TDR (total drug resistance) TB
here mycobacterium are resistance to virtually all the currently available
first as well as second line anti tubercular drugs.
Since the 1980 the prevalence of MDR-TB and XDR-TB has been increasing at an alarming rate.
Introduction of HIV also provides opportunity to bacilli thus making treatment more difficult. In the track
of resistance the new addition is TDR i.e. total drug resistance tuberculosis
.In TDR -TB the
mycobacterium are resistance to virtually all the currently available anti tubercular drugs. Mumbai has
been in world focus years back, after dozen of TDR –TB cases reported. Later scattered cases of TDR –TB
are reported from other part .Luckily, India is the third country to get this honor next to Italy (2006) and Iran
Effective anti tubercular's (first line) were developed half century back .Their constant exposer
from several decades also increases risk of resistance. MDR. XDR and TDR TB are different forms of resistance .Isoniazid and refampicin are safe, efficacious and resistance preventing thus used routinely through-out the course of treatment but their resistance will divert toward reserve option which are comparatively more toxic and less efficacious .Further their resistance may close all the doors of hope. A sophisticated way to assesses specific resistance is not widely available .On the other side, the disease may progresses toward fatal end till the other ways awaited.
George M Brenner, Craig W Stevens. Antimycobacterial Drugs , Pharmacology , Saunders publication , (Elsevier),3e,2010 ,4532
Satosker , Bhandarker ,Rage; Tuberculosis -Drug Resistances ;Pharmacology & Therapetics ; Papular Prakashan 2012 ; 21;751-752
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