1. Empirical Treatment of Community-Acquired Pneumonia and the Development of Fluoroquinolone-Resistant Tuberculosis Clinical Infectious Diseases 2009; 48:1354–60 동서신의학병원 감염내과 R2 최재호

2. BACKGROUND Fluoroquinolones (FLQs) broad spectrum relative abscence of hepatotoxicity no cross-resistance between FLQs and other anti TB drugs

3. BACKGROUND Fluoroquinolones (FLQs) are emerging as important drugs for the treatment of multidrug-resistant tuberculosis (TB) New FLQs, particularly the 8-methoxy FLQs moxifloxacin and gatifloxacin, also promise to shorten the duration TB patient may mistakenly receive a diagnosis of CAP  may produce a favorable short –term reponse cause : FLQs have good activity against M.tuberculosis

4. BACKGROUND 1.delayed diagnosis of pul.TB 2.increase in severity, mortality, and transmission 3.increase in the risk of development of FLQ-resistant TB

5. METHOD Drug benefit plan age, >14yrs Cx-proven pul.TB in Alberta(all population group) and Saskatchewan(Status indians) July 1996 ~ December 2003 whether and when type of FLQ duration during the 6mns – TB Dx outpatient

6. METHOD TB who had received an FLQ vs TB who had not received an FLQ age, sex, population group, disease type (new active vs. relapse), cavitation on chest radiograph, first-line anti-TB drug resistance multiple (2) prescriptions were compared with those who had received a single prescription

7. METHOD To evaluate the association between FLQ-resistant pulmonary TB and prior FLQ use, performed a case-control study. case group : pulmonary TB and a history of FLQ use control group : random from a pool of patients who had not received FLQ treatment and was matched by age (5 years), sex, population group, and province of residence.

8. METHOD SPSS,version 13.0 isolates of M.tuberculosis susceptibility to ciprofloxacin, ofloxacin, and levofloxacin Drug resistance- MIC > 2.0 ug/mL for ciprofloxacin and ofloxacin MIC > 1ug/mL for levofloxacin detection of mutations responsible for resistance

9. RESULTS 731 –Dx of Cx positive pul.TB 563 (Alberta,all population group) + 168(Saskatchewan, Status Indian) 428 (58.5%) were covered by a drug benefit plan Alberta,age > 64yrs status indian > canadian-not indian, forein-born

10. RESULTS total 103 prescriptions: 16(15.5%) norfloxacin 70(68.0%) ciprofloxacin, 3(2.9%) ofloxacin 13(12.6%) levofloxacin, 1(1.0%) moxifloxacin 54: single 20: multiple

11. RESULTS-drug susceptibility test FLQ-R PTB - 15.0% vs 0.0%; OR,11.4 ; P=0.4 Total duration of FLQ Tx single : 7 days [range, 1–14]; multiple : 16 days [range, 8–43 days] P <.001 >64 yrs 2 : newly active 1 : relapse FLQ exposure did not affect the smear status

12. FLQ-resistant isolates were from patients who had received multiple ciprofloxacin treatments

13. Median time from the last FLQ prescription to the date of Dx : 42days Single prescription, n=54 Multiple prescription, n=20 White circles : the prescription closest to the Dx for patients with FLQ-s TB, circles with an “x” : the prescription closest to the diagnosis for patients with FLQ-r TB, black circles : earlier FLQ prescriptions in patients who had received multiple FLQ prescriptions.

14. CONCLUSION Outpatient FLQ use, ostensibly for community-acquired pneumonia, is not uncommon among patients with pulmonary TB, especially older patients. Single FLQ prescriptions were not associated with FLQ resistant M. tuberculosis, whereas multiple FLQ prescriptions were associated with FLQ resistance.