Tuberculosis, drug resistance

The problem has reached the crisis stage, perhaps most acutely for tuberculosis. Drug-resistant Mycobacteria tuberculosis have emerged, especially, in patients being treated for HIV infection (see Box 21-C). Mechanisms of resistance often involve inactivation... 

Mutation Database tions associated with M. tuberculosis drug resistance (http //www.tbdreamdb.com/)... 

World Health Organization (2004) Anti-tuberculosis drug resistance in the world third global report. World Health Organization, Geneva... 

WHO Global Tuberculosis Programme, Geneva. Antituberculosis drug resistance in the world. The WHO/ lUATLD Global Project on Anti-tuberculosis Drug Resistance Surveillance, 1994-1997. 

Tuberculosis Drug Resistance through Decreased Drug Activation 383... 

Infectious patients present a difficult challenge when trying to protect health care workers. These patients must be isolated from the health care workers as well as from the other patients in the hospital. Special isolation rooms are used for this purpose. These rooms are generally used for isolation of infectious tuberculosis (TB) patients, but could be used for patients with other airborne-transmitted diseases. In the United States, there were 22 812 new cases of tuberculosis in 1993, equal to 8.7 per 100 000 population. This represents a 2.8% increase since 1985, following a 6-7% annual decline from 1981-1984.Several studies have documented higher than expected tuberculin skin test (TST) conversion rates in hospital personnel.The National Institute for Occupational Safety and Health " reports that multiple-drug-resistant (MDR) strains of TB have been reported in 40 states and have caused outbreaks in at least 21 hospitals, with 18-35% of exposed workers having documented TST conversions. 

Tuberculosis caused by drug-resistant organisms should be considered in patients who have no response to therapy and in patients who have been treated in the past... 

There has, unfortunately, been a global resurgenee of tuberculosis in recent years. Multiple drug-resistant M tuberculosis (MDRTB) strains have been isolated in which resistance has been aequired to many drugs used in the treatment of this disease. 

In recent years multi-drug resistance has increased among certain pathogens. These include aureus, enterococci andM. tuberculosis. Staphylococcus aureus... 

Isoniazid and rifampin are the two most important tuberculosis drugs organisms resistant to both these drugs [multidrug-resistant tuberculosis (MDR-TB)] are much more difficult to treat. 

Mahmoudi A, Iseman MD. Pitfalls in the care of patients with tuberculosis Common errors and their association with the acquisition of drug resistance. JAMA 1993 270 65-68. 

Gillespie SH Evolution of drug resistance in Mycobacterium tuberculosis Clinical and molecular perspective. Antimicrob Agents Chemother 2002 46 267-274. 

Fietta A, Cascina A, Meloni F, Morosini M, Casali L, Bono L, Minoli L, Marone P A 10-year survey of Mycobacterium tuberculosis isolates in Pavia and their drug resistance A comparison with other Italian reports. J Chemother 2002 14 33-40. 

Tuberculosis remains a major global public health problem. The World Health Organization estimates that there are 8 million new cases of tuberculosis and 3 million deaths directly attributable to tuberculosis each year [22], Drug resistance is a serious problem worldwide. In a study in New York City, 33% of patients with tuberculosis were infected by organisms resistant to at least one antituberculosis drug, and 19% were infected by organisms resistant... 

Frieden TR, Sterling T, Pablos-Mendez A, Kil-burn JO, Cauthen GM, Dooley SW The emergence of drug-resistant tuberculosis in New York City. N Engl J Med 1993 328 521-526. 

Primary resistance of M. tuberculosis Primary resistance of M. tuberculosis to pyrazinamide is uncommon. In cases with known or suspected drug resistance, perform in vitro susceptibility tests with recent cultures of M. tuberculosis against pyrazinamide and the usual primary drugs. 

Tuberculosis Treatment of tuberculosis in combination with other active agents. It is most commonly used in patients with multi-drug resistant tuberculosis (MDR-TB) or in situations when therapy with isoniazid and rifampin is not possible because of a combination of resistance and intolerance. 

Tuberculosis The standard regimen for the treatment of drug-susceptible tuberculosis has been 2 months of INH, rifampin, and pyrazinamide followed by 4 months of INH and rifampin (patients with concomitant infection with tuberculosis and HIV may require treatment for a longer period). When streptomycin is added to this regimen because of suspected or proven drug resistance, the recommended dosing for streptomycin is as follows ... 

Basu S, Andrews JR, Poolman EM, Gandhi NR, Shah NS, Moll A et al. Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals an epidemiological modelling study. Lancet 2007 370(9597) 1500-7. 

The emergence of microbial antibiotic drug resistance was speeded by the indiscriminate use of antibiotics in humans and livestock. Exposure to very low concentrations of antibiotic in meat or milk may have provided a path whereby human pathogens could eventually evolve high-level antibiotic drug resistance. Recently some strains of enterococcus and tuberculosis have developed resistance to all known antibiotic drugs. Inappropriate use of antibiotics is very common, and it accelerates the development of resistance in pathogens. 

Ethambutol is a water-soluble, heat-stable compound that acts by inhibition of arabinosyl transferase enzymes that are involved in cell wall biosynthesis. Nearly all strains of M tuberculosis and M. kansasii and most strains of Mycobacterium avium-intracellulare are sensitive to ethambutol. Drug resistance relates to point mutations in the gene (EmbB) that encodes the arabinosyl transferases that are involved in mycobacterial cell wall synthesis. 

Streptomycin is indicated as a fourth drug in combination with isoniazid, rifampin, and pyrazinamide in patients at high risk for drug resistance. It is also used in the treatment of streptomycin-susceptible MDR tuberculosis. 

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 ... 

Rifampin, usually 600 mg/d (10 mg/kg/d) orally, must be administered with isoniazid or other antituberculous drugs to patients with active tuberculosis to prevent emergence of drug-resistant mycobacteria. In some short-course therapies, 600 mg of rifampin are given twice weekly. Rifampin 600 mg daily or twice weekly for 6 months also is effective in combination with other agents in some atypical mycobacterial infections and in leprosy. Rifampin, 600 mg daily for 4 months as a single drug, is an alternative to isoniazid prophylaxis for patients with latent tuberculosis only, who are unable to take isoniazid or who have had exposure to a case of active tuberculosis caused by an isoniazid-resistant, rifampin-susceptible strain. 

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