Does empirical treatment of community-acquired pneumonia with fluoroquinolones delay tuberculosis treatment and result in fluoroquinolone resistance in Mycobacterium tuberculosis? Controversies and solutions

Current guidelines for treating community-acquired pneumonia recommend the use of fluoroquinolones for high-risk patients. Previous studies have reported controversial results as to whether fluoroquinolones are associated with delayed diagnosis and treatment of pulmonary tuberculosis (TB) and the development of fluoroquinolone-resistant Mycobacterium tuberculosis. We performed a systematic review and meta-analysis to clarify these issues. The following databases were searched through September 30, 2010: PubMed, EMBASE, CINAHL, Cochrane Library, Web of Science, BIOSIS Previews, and the ACP Journal Club. We considered studies that addressed the issues of delay in diagnosis and treatment of TB and the development of resistance. Nine eligible studies (four for delays and five for resistance issues) were included in the meta-analysis from the 770 articles originally identified in the database search. The mean duration of delayed diagnosis and treatment of pulmonary TB in the fluoroquinolone prescription group was 19.03 days, significantly longer than that in the non-fluoroquinolone group (95% confidence interval (CI) 10.87 to 27.18, p<0.001). The pooled odds ratio of developing a fluoroquinolone-resistant M. tuberculosis strain was 2.70 (95% CI 1.30 to 5.60, p=0.008). No significant heterogeneity was found among studies in the meta-analysis. Empirical fluoroquinolone prescriptions for pneumonia are associated with longer delays in diagnosis and treatment of pulmonary TB and a higher risk of developing fluoroquinolone-resistant M. tuberculosis. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

There has not been a comprehensive multi-center study investigating the microbial profile of community acquired pneumonia (CAP) in Taiwan. A prospective study of adult CAP patients requiring hospitalization between December 2001 and April 2002 was carried out in 13 hospitals in Taiwan. Etiology was determined based on laboratory data from blood and sputum cultures plus serology from paired serum and urine antigen detection tests. Etiology was assigned to 99 (58.9%) of the 168 patients having the most complete data for etiology determination, with mixed infection in 21 (12.5%) patients. More than half (51.8%) of the patients were>60 years and 63.7% of the patients were males. The most common etiologic agent was Streptococcus pneumoniae (40, 23.8%), the majority (60%, 24 cases) of which was detected by positive urine antigen test. Other common agents included Mycoplasma pneumoniae (24, 14.3%), Chlamydia pneumoniae (12, 7.1%), Influenza A virus (11, 6.5%), Klebsiella pneumoniae (8, 4.8%) and Haemophilus influenzae (8, 4.8%). The prevalence of S. pneumoniae and M. pneumoniae was highest in patients>60 years (25/87, 28.7%), and<44 years (12/59, 19%), respectively; while K. pneumoniae comprised a larger proportion (4/22, 18%) in the 45-59 years group. S. pneumoniae was the most common etiology agent in adult patients hospitalized due to CAP in Taiwan and the spectrum of other major pathogens was similar to studies conducted elsewhere in the world. Empiric treatment recommendations developed in other parts of the world may be appropriately adapted for local use after taking into account local resistance profiles. Our data also support the recommendation that urine antigen test be added as an adjunct to adult CAP etiology diagnosis protocol.

A study was conducted to evaluate the effect of the empirical use of fluoroquinolones on the timing of antituberculous treatment and the outcome of patients with tuberculosis in an endemic area. All patients with culture confirmed tuberculosis aged > or =14 years diagnosed between July 2002 and December 2003 were included and their medical records were reviewed. Seventy nine (14.4%) of the 548 tuberculosis patients identified received a fluoroquinolone (FQ group), 218 received a non-fluoroquinolone antibiotic (AB group), and 251 received no antibiotics before antituberculous treatment. Fifty two (65.8%) experienced clinical improvement after fluoroquinolone use. In the FQ group the median interval from the initial visit to starting antituberculous treatment was longer than in the AB group and in those who received no antibiotics (41 v 16 v 7 days), and the prognosis was worse (hazard ratio 6.88 (95% CI 1.84 to 25.72)). More patients in the FQ and AB groups were aged >65 years (53.2% and 61.0% v 31.5%), had underlying disease (53.2% and 46.8% v 34.3%), and were hypoalbuminaemic (67.2% and 64.9% v 35.1%). Of the nine mycobacterial isolates obtained after fluoroquinolone use from nine patients whose initial isolates were susceptible to ofloxacin, one (11.1%) was resistant to ofloxacin (after fluoroquinolone use for 7 days). Independent factors for a poor prognosis included empirical fluoroquinolone use, age >65, underlying disease, hypoalbuminaemia, and lack of early antituberculous treatment. 14.4% of our patients with tuberculosis received a fluoroquinolone before the diagnosis. With a 34 day delay in antituberculous treatment and more frequent coexistence of underlying disease and hypoalbuminaemia, empirical fluoroquinolone treatment was associated with a poor outcome. Mycobacterium tuberculosis isolates could obtain ofloxacin resistance within 1 week.