While fluoroquinolones (FQs) have been successful in helping cure multidrug-resistant tuberculosis (MDR TB), studies in mice have suggested that if used as first-line agents they might reduce the duration of therapy required to cure drug-sensitive TB. The results of phase II trials with FQs as first-line agents have been mixed, but in at least three studies where moxifloxacin substituted for ethambutol, there was an increase in the early percentage of sputa that converted to negative for bacilli. Phase III trials are in progress to test the effectiveness of 4-month FQ-containing regimens, but there is concern that the widespread use of FQs for other infections could engender a high prevalence of FQ-resistant TB. However, several studies suggest that despite wide FQ use, the prevalence of FQ-resistant TB is low, and the majority of the resistance is low-level. The principal risk for resistance may be when FQs are used to treat nonspecific respiratory symptoms that are in fact TB, so curtailing this use of FQs could reduce the development of resistance and also the delays in TB diagnosis and treatment that have been documented when an FQ is given in this setting. While the future of FQs as first-line therapy will likely depend upon the results of the ongoing phase III trials, if they are to be effectively employed in high-TB-burden regions their use for community-acquired pneumonias should be restricted, the prevalence of FQ-resistant TB should be monitored, and the cost of the treatment should be comparable to that of current standard drug regimens.There are two main problems with tuberculosis (TB) chemotherapy, and the fluoroquinolones (FQs) may be able to help with both. First, although the total duration of treatment has been reduced from 18 to 24 months to 6 months by the systematic use of rifampin (RIF) and pyrazinamide, such a 6-month duration is still very long for patients and burdensome for health services in numerous countries where TB is highly endemic and can lead to the second problem, the development of strains resistant to the drugs. The success of the fluoroquinolone antibiotics in treating strains that are resistant to the standard first-line drugs has led to the suggestion that if used as first-line therapy they may be able shorten the duration of treatment. However, excitement over this possibility is tempered by the fear that their widespread community use for other infections will engender a high prevalence of FQ-resistant TB strains in the population.
FQs: HIGH HOPES BUT ALSO HIGH RATES OF RESISTANCEThe quinolones are synthetic molecules that got their start when nalidixic acid was discovered in 1962 (47) and then introduced into clinical use in 1967 for the treatment of Gramnegative urinary tract infections (26). The addition of a fluorine atom significantly increased their antibacterial activity, and by adding various side groups literally thousands of different fluoroquinolones were synthesized. Although the increased broad-spectrum activity of ciprofloxacin (CIP) created the expectation ...