Fluoroquinolones tuberculosis

Most of the fluoroquinolones antibiotics (see Chapter 44) have activity against M. tuberculosis and M. avium-intracellulare. Ciprofloxacin, ofloxacin, and levofloxacin inhibit 90% of the strains of susceptible tubercula bacilli at concentrations of less than 2 xg/mL. Levofloxacin is preferred because it is the active L-optical isomer of ofloxacin and is approved for once-daily use. The... 

Moxifloxacin Oral, TV "respiratory" fluoroquinolone once-daily dosing improved activity versus anaerobes and Mycobacterium tuberculosis hepatic clearance results in lower urinary levels so use in urinary tract infections is not recommended... 

Sulochana S, Rahman F, Paramasivan CN In vitro activity of fluoroquinolones against Mycobacterium tuberculosis. J Chemother 2005 17 169. [PMID 15920901]... 

Anand R, Somasundaram S, Doble M, Paramasivan C (2011) Docking studies on novel analogues of 8 methoxy fluoroquinolones against GyrA mutants of Mycobacterium tuberculosis. BMC Struct Biol 11 47... 

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]. 

Moxifloxacin s MIC90 value of 1 mg L"1 means that it has the same in vitro activity against M. tuberculosis as levofloxacin, and is more effective than ofloxacin (MIC90 = 2 mg L"1) and ciprofloxacin (MIC90 = 4 mg IT1) [192-194]. A combination of moxifloxacin and isoniazid proved to be more effective in vivo than the individual compounds [195,196], whereas a combination with ethambutol was less effective [196]. Based on the mutant prevention concentration (MPC), which is a parameter for the selection of resistant pathogens during antibiotic treatment, moxifloxacin was found to be the most effective fluoroquinolone against M. tuberculosis [197]. 

Rodriguez JC, et al. In vitro activity of four fluoroquinolones against Mycobacterium tuberculosis. Int. J. Antimicrob. Agents, 2001, 17, 229-231. 

Rodriguez JC, et al. Mutant prevention concentration comparison of fluoroquinolones and linezolid with Mycobacterium tuberculosis. J. Antimicrob. Chemother., 2004, 53, 441-444. 

Multidrug-resistant tuberculosis generally results from inadequate therapy or lack of compliance with therapy. A strain of mycobacteria is called resistant when it is insensitive to one of the first-line drugs. It is called multiresistant when it is insensitive to both isoniazid and rifampicin. In this case other antituberculosis drugs may also be ineffective (35). In practice, at least two second-line antituberculosis drugs, selected on the basis of individual drug susceptibility, are given in combination with a fluoroquinolone (36). 

Berning SE. The role of fluoroquinolones in tuberculosis today. Drugs 2001 61(1) 9-18. 

Fluoroquinolones as anti-bacterial compounds and their use in the therapy of tuberculosis 02MI46. 

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... 

Infections caused by Mycobacterium tuberculosis are treated with combination therapy. The primary drugs used are isoriazid, rifampin, ethambutol, and pyrazinamide. Highly resistant organisms may require the use of additional agents. Backup drugs include aminoglycoside, fluoroquinolones, capreomycin, and cycloserine. 

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. 

Intracellular pathogens e.g., Salmonella, Brucella, Toxoplasma, Listeria, and M. Tuberculosis) are protected from the action of antibiotics that penetrate into cells poorly. Certain antibiotics e.g., fluoroquinolones, isoniazid, trimethoprim-sulfamethoxazole, and rifampin) penetrate cells well and can achieve intracellular concentrations that inhibit or kill pathogens residing within cells. 

The fluoroquinolones are highly active against M. tuberculosis and are important drugs for multidrug-resistant tuberculosis (Table 47-1). Agents such as gatifloxacin (TEQUIN) and moxifloxadn (avelox) are most active and least likely to select for quinolone resistance. Mycobacterial resistance to one fluoroquinolone imparts cross-resistance for the entire class. 

Patients with inactive tuberculosis who have not received adequate therapy should be considered for 1 year of isoniazid treatment. HIV-infected intravenous drug abusers with a positive PPD test have 8% chance per year of developing active tuberculosis. Isoniazid prophylaxis in HIV-infected persons appears to be as effective as in non-immunocompromised persons. The CDC recommends that isoniazid prophylaxis be continued for 12 months. Persons infected with HIV who are exposed to multidrug-resistant tuberculosis should receive prophylaxis with rifampin and pyrazinamide (with close monitoring for hepatic toxicity) or high-dose ethambutol and pyrazinamide, with or without a fluoroquinolone. 

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. 

Fluoroquinolones are used to treat bacterial infections. These drugs are prescribed for the treatment of bone and joint, skin, ear, urinary tract infections, inflammation of the prostate and serious diseases such as bronchitis, pneumonia, tuberculosis, sexually transmitted diseases (STDs), and infections affecting people with AIDS. ... 

Multidrug-resistant tuberculosis (MDR-TB) no longer can be cured by the leading TB antibiotics isoniazid (2) and rifampicin (3). Extensively drug-resistant TB (XDR-TB) is a form of TB caused by organisms that are resistant to isoniazid (2) and rifampicin (3), as well as fluoroquinolones such as ciprofloxacin (7), and ofloxacin (8) and any of the second-line anti-TB injectable drugs such as amikacin, kanamycin, or capreomycin. 

Bryskier, A. Lowther, J. Fluoroquinolones and Tuberculosis A Review In Antimicrobial... 

---