Fluoroquinolone Exposure Prior To Tuberculosis Diagnosis Is Associated With An Increased Risk Of Death

Abstract

SUMMARYSETTING-Fluoroquinolone (FQ) exposure before tuberculosis (TB) diagnosis is common, but its effect on outcomes, including mortality, is unclear. DESIGN-Among TB patients reported to the Tennessee Department of Health from 2007 to2009, we assessed FQ exposure within 6 months before TB diagnosis. The primary outcome was the combined endpoint of death at the time of TB diagnosis and during anti-tuberculosis treatment.RESULTS-Among 609 TB cases, 214 (35%) received FQs within 6 months before TB diagnosis. A total of 71 (12%) persons died; 10 (2%) were dead at TB diagnosis and 61 (10%) died during anti-tuberculosis treatment. In multivariable logistic regression analysis, factors independently associated with death were older age (OR 1.05 per year, 95%CI 1.04-1.07), human immunodeficiency virus infection (OR 8.08,, US birth (OR 3.03, 95%CI 1.03-9.09), and any FQ exposure before TB diagnosis (OR 1.82,. Persons with FQ exposure before TB diagnosis were more likely to have culture-and smear-positive disease than unexposed persons.CONCLUSIONS-Among this patient population, FQ exposure before TB diagnosis was associated with an increased risk of death. These findings underscore the need for cautious use of FQs in persons with possible TB.Keywords drug-susceptible TB; drug resistance; mortality Despite a Decrease in worldwide incidence since 2002, tuberculosis (TB) continues to be a major cause of mortality worldwide; it is estimated that 1.45 million persons died from TB in 2010. The use of FQs prior to TB diagnosis has been associated with an increased risk of FQ resistance [10][11][12] and delays in diagnosis and treatment of pulmonary TB. [13][14][15][16][17] One retrospective study in a TB-endemic area found that FQ exposure before TB diagnosis was associated with increased mortality. 14 We sought to clarify the association between FQ exposure before TB diagnosis and mortality in an area of low TB incidence using a prospective cohort with both in-and out-patient FQ exposure data. METHODSWe performed a prospective cohort study among patients with newly diagnosed TB reported to the Tennessee Department of Health (DoH) from January 2007 to December 2009. Patients from the cohort were included if they had an assessment for possible FQ exposure starting 6 months before TB diagnosis from at least one of four sources. An FQ exposure assessment survey was completed by Tennessee DoH staff who questioned TB patients regarding receipt of FQs. An in-home questionnaire recorded data from face-to-face interviews of patients with culture-positive TB conducted by research study staff regarding patient recall of FQ prescriptions. Research study staff reviewed clinic and hospital records to assess details of FQ prescriptions among culture-positive patients who gave consent and for any culture-positive patients who were dead at diagnosis, died during treatment or died after completion of anti-tuberculosis treatment. For each of the four sources of FQ exposure data, the names of specific FQs prescribed during the 6 months preceding...

JAID/JSC Guidelines for the Treatment of Respiratory Infectious Diseases: The Japanese Association for Infectious Diseases/Japanese Society of Chemotherapy – The JAID/JSC Guide to Clinical Management of Infectious Disease/Guideline-preparing Committee Respiratory Infectious Disease WG

“…In elderly patients or those with underlying lung diseases such as COPD/old pulmonary tuberculosis, the use of respiratory quinolones should be considered positively from the perspective of the effects on penicillin-resistant Pneumococcus and tissue transfer [11,14,15] (BII). However, many new quinolones also have antimicrobial activities against Mycobacterium tuberculosis; therefore, the presence or absence of active tuberculosis must be strictly checked before administration [16] (AII).…”

Review of Nucleic Acid Amplification Tests and Clinical Prediction Rules for Diagnosis of Tuberculosis in Acute Care Facilities

“…The substantial proportion of deaths that occur prior to treatment highlights the importance of timely diagnosis. Analyses of county and statewide TB surveillance data have identified several risk factors associated with death among TB patients 28 – 34 that may be important to consider among hospitalized patients. Receipt of fluoroquinolones in the 6 months prior to TB diagnosis, 28 HIV infection, 28 – 32 , 34 excessive alcohol use, 30 , 33 and age 65 years and older 33 , 34 have all been identified as risk factors associated with death among patients with TB.…”

“…Analyses of county and statewide TB surveillance data have identified several risk factors associated with death among TB patients 28 – 34 that may be important to consider among hospitalized patients. Receipt of fluoroquinolones in the 6 months prior to TB diagnosis, 28 HIV infection, 28 – 32 , 34 excessive alcohol use, 30 , 33 and age 65 years and older 33 , 34 have all been identified as risk factors associated with death among patients with TB. Although the proportion of TB deaths that are preventable is unknown, interventions that could result in earlier TB diagnosis among patients hospitalized with risk factors and symptoms consistent with TB or death with TB may decrease the proportion of patients who die.…”

A comparison of interview methods to ascertain fluoroquinolone exposure before tuberculosis diagnosis

“…In a study of culture-confirmed TB patients in Tennessee, we previously found that 7/54 (13%) patients with >10 days of fluoroquinolone exposure had fluoroquinolone-resistant TB [3]. Fluoroquinolone exposure before TB diagnosis has also been associated with delays in the diagnosis and initiation of appropriate treatment for TB [5], and an increased risk of death at the time of TB diagnosis or during TB treatment [6]. Since fluoroquinolones may be used in patients who do not tolerate first-line anti-TB medications and are under investigation for inclusion in first-line drug-susceptible TB treatment regimens, preserving fluoroquinolone susceptibility and optimizing conditions for successful treatment are essential [7, 8].…”