The primary treatment for mycobacterial infection is specific chemotherapy. The drugs for treatment of mycobacterial infection are discussed in Chapter 28. Two cases of tuberculosis are presented in Chapter 48.

Between one in 10⁶ and one in 10⁸ tubercle bacilli are spontaneous mutants resistant to first-line antituberculosis drugs. When the drugs are used singly, the resistant tubercle bacilli emerge rapidly and multiply. Therefore, treatment regimens use drugs in combination to yield cure rates of greater than 95%.

The two major drugs used to treat tuberculosis are INH and RMP. The other first-line drugs are pyrazinamide (PZA) and ethambutol (EMB). Second-line drugs are more toxic or less effective (or both), and they should be used in therapy only under extenuating circumstances (eg, treat ment failure and multiple drug resistance). Second-line drugs include kanamycin, capreomycin, ethionamide, cycloserine, ofloxacin, and ciprofloxacin.

A four-drug regimen of INH, RMP, PZA, and EMB is recommended for persons in the United States who have a slight to moderate risk for being infected with drug-resistant tubercle bacilli. The risk factors include recent emigration from Latin America or Asia, persons with HIV infections or who are at risk for HIV infection and live in an area with a low prevalence of multidrug-resistant tubercle bacilli, and per sons who were previously treated with a regimen that did not include RMP. These four drugs are continued for 2 months. If the isolate is susceptible to INH and RMP, PZA and EMB can be discontinued, and the remaining treatment with INH and RMP is continued to complete a 6-month course. In patients with cavitary disease or in whom the sputum culture results are still positive after 2 months of treatment, an additional 3 months of therapy (total course duration of 9 months) should be given to prevent relapse. In noncompliant patients, directly observed therapy is important.

Drug resistance in M. tuberculosis is a worldwide problem. Mechanisms explaining the resistance phenomenon for many, but not all, of the resistant strains have been defined. INH resistance has been associated with deletions or mutations in the catalase-peroxidase gene (katG); these isolates become catalase negative or have decreased catalase activity. INH resistance has also been associated with alterations in the inhA gene, which encodes an enzyme that functions in mycolic acid synthesis. Streptomycin resistance has been associated with mutations in genes encoding the ribosomal S12 protein and 16S rRNA, rpsL and rrs, respectively. RMP resistance has been associated with alterations in the B sub unit of RNA polymerase, the rpoB gene. Mutations in the DNA gyrase gene gyrA have been associated with resistance to fluoroquinolones. The possibility that drug resistance is present in a patient’s M. tuberculosis isolate must be taken into account when selecting therapy.

Multidrug-resistant M. tuberculosis (resistant to both INH and RMP) is a major problem in tuberculosis treatment and control. Such strains are prevalent in certain geographic areas and certain populations (eg, hospitals and prisons). There have been many outbreaks of tuberculosis with multidrug-resistant strains. They are particularly important in persons with HIV infections in resource-poor countries. Persons infected with multidrug-resistant organisms or who are at high risk for such infections, including exposure to another person with such an infection, should be treated according to susceptibility test results for the infecting strain. If susceptibility results are not available, the drugs should be selected according to the known pattern of susceptibility in the community and modified when the susceptibility test results are available. Therapy should include a minimum of three and preferably more than three drugs to which the organisms have demonstrated susceptibility.

Extensively drug-resistant (XDR) strains are now globally recognized. These are defined by the World Health Organization (WHO) as isolates of M. tuberculosis with resistance to INH and RMP; any fluoroquinolone; and at least one of three injectable second-line drugs such as amikacin, capreomycin, or kanamycin. The true prevalence of XDR tuberculosis is underestimated in resource-limited countries because of the lack of available diagnostic and susceptibility tests. Factors that have contributed to the global epidemic include ineffective tuberculosis treatment; lack of proper diagnostic testing; and most importantly, poor infection control practices. Persons infected with XDR tuberculosis have a poorer clinical outcome and are 64% more likely to die during treatment than persons infected with susceptible strains. In 2006, the WHO Global Task Force on XDR-TB issued multifaceted and comprehensive recommendations to address the XDR-TB epidemic (available at http://www.who.int/tb/ features_archive/global_taskforce_report/en/)

مواضيع ذات صلة

Pathogenesis and Spectrum of Disease of Streptococcus Pneumonia and Viridians Streptococci

Pathogenesis and Spectrum of Disease of Beta- Hemolytic Streptococci

Morphology and Identification of Mycobacterium Tuberculosis

Neisseria gonorrhea

Yersinia enterocolitica and Yersinia pseudotuberculosis

Yersinia pestis and Plague

Pseudomonas

Pathogenesis and Epidemiology of Salmonella

Francisella tularensis and Tularemia

Pseudomonas aeruginosa

Fermentation Media

Coagulase Test