Antitubercular drugs, resistance

Parent strains of certain bacteria, e.g., antibiotic-resistant or antitubercular-drug-resistant strains, can be differentiated from nonresistant substrains. The spores of phytopathogenic fungi can be differentiated by means of their spectra. Viruses can also be differentiated. 

Rifampin is a first-line antitubercular drug used in the treatment of all forms of pulmonary and extrapul-monary tuberculosis. Rifampin is an alternative to isoniazid in the treatment of latent tuberculosis infection. Rifampin also may be combined with an antileprosy agent for the treatment of leprosy and to protect those in close contact with patients having H. influenza type b and N. meningitidis infection rifampin is also used in methicillin-resistant staphylococcal infections, such as osteomyelitis and prosthetic valve endocarditis. 

All mycobacteria produce (3-lactamase. In vitro, several (3-lactamase-resistant antibiotics or a combination of a (3-lactam with (3-lactamase inhibitors, such as clavulanic acid, are active against M tuberculosis and nontubercu-lous mycobacteria. However, the activity of (3-lactam agents against intracellular mycobacteria is generally poor. The (3-lactam agents may be useful in the treatment of MDR tuberculosis in combination with other antitubercular drugs but never as monotherapy. 

A 32-year-old Haitian man has acute-onset confusion and suicidal ideation. Two weeks ago he began combination therapy for multi-drug resistant pulmonary tuberculosis. He has a history of depression that required intermittent treatment in the past. Which of the following antitubercular agents is responsible for the patient s neurological symptoms ... 

When bacterial resistance to these primary agents exists or develops, treatment with the secondary antitubercular drugs has to be considered. The latter group comprises capreomycin, cycloser-... 

Table V-1 -4. Summary of the Actions, Resistance, and Adverse Effects of the Antitubercular Drugs...

Table V-l-4 summarizes the actions, resistance, and adverse effects of the antitubercular drugs.

Mechanism of Action. Based on both clinical experience and experimental demonstration it has been duly observed that the "drug" develops cross-resistance overwhelmingly in the tubercle bacilli specifically along with some other medicinal entities, such as vincomycin, dihydrostreptomycin and antitubercular drug substances. 

It is considered to be the drug of choice for the treatment of tuberculosis. It has also been employed as a prophylaetie for those who were constantly exposed to tubercular patients. It is invariably used in eombination with other antitubercular drugs to achieve better clinical response, to allow lower doses of other aetive agent(s), and above all to retard the emergence of resistant tubercle bacilli. 

Capreomycin resembles viomycin both chemically and pharmacologically. It is considered to be second-line antitubercular drug used in combination with other such agents. It is frequently used in place of streptomycin when either the patient is sensitive to it or the strain of M tuberculosis is resistant to it. 

Tuberculosis is a commimicable disease that is a detriment to the community therefore, the client is mandated to take the antitubercular medication and will be observed daily for the duration of the regimen, which may be 9-12 months. The risk of drug resistance is extremely high if the regimen is not strictly and continuously followed. This will result in multidrug-resistant TB in the community. 

Bueno, J., 2012. Antitubercular in vitro drug discovery tools for begin the search. In Cardona, P.-J. (Ed.), Understanding Tuberculosis — New Approaches to Fighting Against Drug Resistance. InTech, Rijeka, Croatia, pp. 147—169. Available from http //dx.doi.org/10.5772/2477. 

The prospects, including questions still unresolved, have recently been reviewed [435]. It is to be hoped that the usefulness of this effective, almost non-toxic addition to the antitubercular range of drugs will not be jeopardized by injudicious use of other rifamycins since cross-resistance exists between all known members of this group—at least so far as mycobacteria are concerned. 

Figure 25.3 Antitubercular agents small fragment-like molecules used as drugs (isoniazid, pyrazinamide, ethionamide, and ethambutoi) bedaquiline is recently approved for the treatment of multidrug-resistant TB PA824 and SQ109 are in clinical trial.

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