Tuberculosis resistance

It is chemically related to nicotinamide and thiosemicarbazone. It is bactericidal. It is effective against Mycobacterium tuberculosis resistant to INH and streptomycin. It is converted to pyrazinoic acid (active... 

In the treatment of tuberculosis, resistant strains of M. tuberculosis (multidrug-resistant tuberculosis, MDRTB) present a growing problem, so that new antituber-culotic agents are required which act according to a different mechanism to that of standard agents such as isoniazid, rifampicin, pyrazinamide, and ethambutol. The more modern fluoroquinolones are of particular interest, and in particular moxifloxacin, which has powerful in vitro and in vivo activity and, in contrast to sparfloxacin and clinafloxacin, is not photo toxic [191]. 

Pneumococci resistant to penicillins, certain cephalosporins, and macrolides are increasingly common. These organisms generally are susceptible to vancomycin, the new fluoroquinolones, and cefotaxime or ceftriaxone. M. tuberculosis resistant to one or more first-hue anti-tubercular agents (e.g., isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide) have increased in frequency as well. This has been... 

Isoniazid, the mainstay in virtually any regimen to treat M. tuberculosis, penetrates the CSF with or without meningeal inflammation and achieves concentrations of more than 30 times the MIC of M. tuberculosis (MICs of 0.05 to 0.2 mg/L)." Rifampin s penetration of CSF approximates only 20% of sernm concentrations in the presence of meningeal inflammation. M. tuberculosis typically is so exquisitely sensitive to rifampin, however, that the low penetration ratio is of little clinical significance. However, the incidence of M. tuberculosis resistance to rifampin has increased, necessitating empirical multiple-antibiotic regimens. 

Goble M, Iseman MD, Madsen LA, et al. Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin. N Engl J Med 1993 328 527-532. 

Ethambutol inhibits synthesis of one or more metabolites, causing impairment of cell metabolism, arrest of multiplication, and cell death. It is indicated in the treatment of tuberculosis, in combination with other agents in patients with Mycobacterium tuberculosis resistant to isoniazid or rifampin, or when there is intolerance to other antituberculous agents. 

John S. Blanchard received his BS in chemistry from Lake Forest College and obtained his Ph.D. from the laboratory of W. W. Cleland at the University of Wisconsin. After a 3-year NIH-sponsored postdoctoral fellowship, he was appointed assistant professor of biochemistry at the Albert Einstein College of Medicine in New York City in 1983. In 1998, he became the Dan Danciger Professor of Biochemistry. His early research interests focused on the determination of kinetic isotope effects exhibited by flavin-containing enzymes. His collaborative studies on the mechanism of action, and resistance, to isoniazid in Mycobacterium tuberculosis led to his current interests in antibiotic resistance. His present interests include the structure and function of essential biosynthetic enzymes in M. tuberculosis, resistance to aminoglycosides and fluoroquinolones, and proteome-wide identification of acetylated proteins. He is the author of over 140 research papers and 20 reviews and has been awarded seven United States patents. His work has been generously supported by the United States National Institutes of Health for the last 24 years. 

Mechanisms The mechanism of action of pyrazinamide is not known however, its bacteriostatic action appears to require metabolic conversion via pyrazinamidases (encoded by the pncA gene) present in M tuberculosis. Resistant mycobacteria lack these enzymes, and resistance develops rapidly if the drug is used alone. There is minimal cross-resistance with other antimycobacterial drugs. 

Ciprofloxacin and ofloxacin are often active against strains of M tuberculosis resistant to first-line agents. The fluoroquinolones should always be used in combination regimens with two or more other active agents. 

R = R = H) are intermediate, and gentamicin and tobramycin are most susceptible (66). Resistance to streptomycin is widespread, and its use is currently confined primarily to infections caused by Mycobacterium tuberculosis Yersiniapestis and Francisella tularensis. 

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. 

Although the advent of the antibiotics revolutionized the treatment of bacterial infections, tuberculosis has proven unusually resistant to chemotherapeutic attack. Although many antibiotics are effective to some extent in arresting the progress of... 

Of increasing concern is the development of mutant strains of tuberculosis that are resistant to many of the aiititubercular drug s currently in use. Bacterial resistance develops, sometimes rapidly, with the use of anti-tubercular drag s. Treatment is individualized and... 

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... 

The glucocorticoids are contraindicated in patients widi serious infections, such as tuberculosis and fungal and antibiotic-resistant infections. 

Mycobacterium tuberculosis is the causal organism of tuberculosis in humans. Allied strains cause infections in animals, e.g. bovine tuberculosis and tuberculosis in rodents. Due to the waxy nature of the cell wall this organism will resist desiccation and will survive in sputum. Tuberculosis has been largely eliminated by immunization and chemotherapy. 

Problems of recent years involving listeriosis, salmonellosis, giardiasis and Legionnaire s disease have received attention, as have the re-emergence of tuberculosis and the importance of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). 

Stiepton dn was isolated by Waksman in 1944, and its activity against M tuberculosis ensured its use as a primaiy ding in the treatment of tuberculosis. Unfortunately, its ototoxicity and the rapid development of resistance have tended to modify its usefulness, and although it still remains a front-hne dmg against tuberculosis it is usually used in combination with isoniazid and p(4)-aminosalicyhc acid (section 11.5). Streptomycin also shows activity against other types of bacteria,... 

Kanamycin (a complex of three antibiotics. A, B and C) is active in low concentrations against various Gram-positive (including penicillin-resistant staphylococci) and Gram-negative bacteria. It is a recognized second-line dmg in the treatment of tuberculosis. 

The three standard drugs used in the treatment of tuberculosis were streptomycin (considered above), -aminosalicylic acid (PAS) and isoniazid (isonicotinylhydrazide, INH synonym, isonicotinic acid hydrazine, INAH). The tubercle bacillus rapidly becomes resistant to streptomycin, and the role of PAS was mainly that of preventing this development of resistance. The current approach is to treat tuberculosis in two phases an initial phase where a combination of three dmgs is used to reduce the bacterial level as rapidly as possible, and a continuation phase in which a combination of... 

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... 

The advent of multidrug resistant strains of Mycobacterium tuberculosis (MDR-TB) has led to increased fears of untreatable infections by serious pathogens. Rifampicin, streptomycin and, occasionally, the quinolones are drugs used in the treatment of mycobacterial infections and resistance to those agents is as described previously. There... 

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