Increasing Outpatient Fluoroquinolone Exposure Before Tuberculosis Diagnosis and Impact on Culture-Negative Disease

Abstract

Background: Fluoroquinolones are widely used to treat routine bacterial infections, but they are also potential firstline antituberculosis agents. Empirical fluoroquinolone therapy can delay the diagnosis of tuberculosis and cause resistance in Mycobacterium tuberculosis. Rates of fluoroquinolone exposure before tuberculosis diagnosis and the impact of fluoroquinolones on culture-negative tuberculosis have not been previously reported. Methods: All newly diagnosed tuberculosis cases reported to the Tennessee Department of Health between January 1, 2000, and December 31, 2004, were crossmatched with the TennCare (Medicaid) pharmacy database to assess for outpatient fluoroquinolone use in the 12 months before tuberculosis diagnosis. Results: Of 1562 tuberculosis cases reported, 1055 occurred in TennCare participants; of these 1055 TennCare patients, 507 were enrolled in TennCare more than 300 days during the year before tuberculosis diagnosis. Of the 507 patients, 119 (23%) received a fluoroquinolone before tuberculosis diagnosis. The proportion of fluoroquinolone-exposed patients increased from 9% in 2000 to 41% in 2004 (2 test for trend P Ͻ.001). In multivariate logistic regression analysis, factors associated with fluoroquinolone exposure were older age (odds ratio [OR], 1.03 per year; 95% confidence interval [CI], 1.02-1.04) and year of diagnosis (OR,1.64 per 1-year increase; 95% CI, 1.39-1.93); human immunodeficiency virus infection tended to be associated with increased exposure (OR,1.94; 95% CI, 0.97-3.90). After controlling for age, sex, race, site of disease, human immunodeficiency virus, and year of diagnosis, prior fluoroquinolone exposure was not associated with culture-negative tuberculosis (OR,0.81; 95% CI, 0.41-1.60). Conclusions: Fluoroquinolone use before tuberculosis diagnosis increased significantly during the study period. However, fluoroquinolone exposure was not associated with an increased risk of culture-negative tuberculosis.

DNA Gyrase Inhibition Assays Are Necessary To Demonstrate Fluoroquinolone Resistance Secondary to gyrB Mutations in Mycobacterium tuberculosis

“…XDR-TB, which represents 4 to 19% of MDR-TB cases (6,7,8,25,38), is difficult to treat, and the death rate can be as high as 50%, i.e., close to the historical rate of death observed in untreated TB (7,17,18,22). Alarmingly, XDR-TB is likely to increase in the future due to the poor management of MDR-TB patients and the increasing use of fluoroquinolones for empirical treatment of a large range of nonmycobacterial infections, such as urinary and respiratory tract infections, diarrhea, and typhoid fever, which are common infections in high-tuberculosis-incidence areas (16). Analysis of drug susceptibility of Mycobacterium tuberculosis strains is essential for the following reasons: (i) to guide the clinical management of cases and ensure rapid and adequate chemotherapy of tuberculosis and (ii) to determine the need for institutional isolation of patients and so prevent the spread of XDR-TB strains.…”

High Proportion of Fluoroquinolone-Resistant Mycobacterium tuberculosis Isolates with Novel Gyrase Polymorphisms and a gyrA Region Associated with Fluoroquinolone Susceptibility

“…Many such patients likely received extensive prior treatment, including fluoroquinolones. In contrast, our patient population was comprised of newly diagnosed fluoroquinolonemonoresistant tuberculosis patients in whom the proportion with fluoroquinolone exposure was high-but presumably with shorter treatment courses for presumptive nontuberculous bacterial infections rather than known chronic tuberculosis (10,11). Our patient population more closely reflects the population in whom fluoroquinolones might be used in the future as a first-line short-course antituberculosis therapy (9,26).…”

Extensively Drug‐Resistant Tuberculosis and HIV/AIDS

“…This may exert some selection pressure for resistant organisms even before TB treatment has been initiated [59,60]. A recent report from the United States found that the proportion of TB patients exposed to fluoroquinolone within the year prior to TB diagnosis increased from 9% in 2000 to 41% in 2004 [61]. In the same study, HIV status emerged as the strongest predictor of fluoroquinolone exposure prior to TB diagnosis, along with older age and calendar year.…”