COPD: grepafloxacin was not clearly better than ciprofloxacin.

Clinical bottom line (level 1b-)

  1. Patients with acute bacterial exacerbations of chronic bronchitis who were given grepafloxacin 400 mg or 600 mg, had no clear difference in treatment success immediately after treatment than those given ciprofloxacin.
  2. Patients given grepafloxacin 400 mg or 600 mg had no clear difference in treatment success at 28 days than those given ciprofloxacin.
  3. Patients given grepafloxacin 400 mg were more likely to have taste perversion than those given ciprofloxacin (NNH = 11 at years) .
  4. Patients given grepafloxacin 600 mg are more likely to have nausea (NNH = 11 at years) , and taste perversion (NNH = 7 at years) than those given ciprofloxacin.
Chodosh et al: Antimicrobial Agents and Chemotherapy 1998; 42 (1): 114-120
Expires November 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 33 centres, USA

624 patients (aged range 18 to 82 years; mean 48, 54% female) acute exacerbation of chronic bronchitis (chronic or recurrent productive cough present on most days for a minimum of 3 months in a year and for >2 successive years)

Excluded if
  • <18 and >80 years old
  • history of allergy to quinolone derivatives
  • pregnant or breast-feeding
  • respiratory tract disease or infection that required paternal antimicrobial therapy or systemic high-dose steroids
  • active bronchiectasis, pneumonia or cystic fibrosis
  • chest x-ray signs of pneumonia, abscesses, tumour or active tuberculosis
  • hepatic disease or severe renal impairment
  • history of seizures
  • gastrointestinal disease that could affect drug absorption
  • treatment quinolone or an oral nonquinolone antibiotic within the preceding 3 days or a long-acting parenteral antibiotic within the previous 4 weeks unless it was administered for <24 hours or the patient received no more than one dose or unless the infecting organism was demonstrated to be resistant to the prior antibiotic and the patient was considered to be a treatment failure
  • received treatment with another investigational drug within the preceding 4 weeks
  • pretreatment plasma theophylline level of >20 µ g/ml
  • terminally ill or immunocompromised
  • taking probenecid, warfarin, fluconazole or diflunisal


    • Control Group: (n = 213, 213 analysed): ciprofloxacin 500 mg twice daily for 10 days
    Experimental Group: (n = 207, 207 analysed): grepafloxacin 400 mg once daily for 10 days
    Experimental Group: (n = 204, 204 analysed): grepafloxacin 600 mg once daily for 10 days

    99% followed for 28 days
    Outcome notes:
    • treatment success : Cure (disappearance of signs and symptoms of acute infection) and improvement (reduction in severity and /or number of signs and symptoms of the acute infection).
    • treatment success : Persistent resolution (as good as or better than that at end of treatment) or mild relapse (not quite as good as at the end of treatment)

    The evidence

    grepafloxacin 400 mg vs ciprofloxacin
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    treatment success 15 days 146
    (91.3%)    		 139
    (92.1%)    		 9%
    (-90% to 57%)    		 0.80%
    (-5.34% to 6.95%)    		 125
    (NNT = 14 to infinity;
    NNH = 19 to infinity)
    treatment success 28 days 123
    (79.9%)    		 124
    (86.7%)    		 34%
    (-11% to 61%)    		 6.84%
    (-1.59% to 15.27%)    		 15
    (NNT = 63 to infinity;
    NNH = 7 to infinity)
    nausea 28 days 27
    (12.7%)    		 30
    (14.5%)    		 -14%
    (-85% to 29%)    		 -1.82%
    (-8.37% to 4.74%)    		 -55
    (NNT = 12 to infinity;
    NNH = 21 to infinity)
    taste perversion 28 days 8
    (3.76%)    		 26
    (12.6%)    		 -234%
    (-622% to -55%)    		 -8.80%
    (-14.0% to -3.62%)    		 -11
    (-28 to -7)

    grepafloxacin 600 mg vs ciprofloxacin
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    treatment success 15 days 146
    (91.3%)    		 137
    (87.8%)    		 -39%
    (-168% to 28%)    		 -3.43%
    (-10.2% to 3.32%)    		 -29
    (NNT = 10 to infinity;
    NNH = 30 to infinity)
    treatment success 28 days 123
    (79.9%)    		 122
    (80.8%)    		 5%
    (-50% to 39%)    		 0.92%
    (-8.00% to 9.85%)    		 108
    (NNT = 13 to infinity;
    NNH = 10 to infinity)
    nausea 28 days 27
    (12.7%)    		 45
    (22.1%)    		 -74%
    (-169% to -12%)    		 -9.38%
    (-16.6% to -2.15%)    		 -11
    (-47 to -6)
    taste perversion 28 days 27
    (12.7%)    		 54
    (26.5%)    		 -109%
    (-218% to -37%)    		 -13.8%
    (-21.3% to -6.27%)    		 -7
    (-16 to -5)

  • 151 patients in the grepafloxacin 400 mg group, 156 in the 600 mg group and 160 in the ciprofloxacin group were available for clinical efficacy evaluation after treatment.
  • 143 patients in the ciprofloxacin 400 mg group, 151 in the 600 mg group and 154 ciprofloxacin group were available for the clinical efficacy evaluation after follow-up.

    • Comments

    1. The study is too small to show any clear difference in successful treatment between the two groups.

    Citation

    1. Chodosh S, Laksminarayan S, Swarz H, et al: Efficacy and safety of a 10-day course of 400 or 600 milligrams of grepafloxacin once daily for treatment of acute bacterial exacerbations of chronic bronchitis: comparison with a 10-day course of 500 milligrams of ciprofloxacin twice daily. Antimicrobial Agents and Chemotherapy 1998; 42 (1): 114-120
    Search Terms: chronic bronchitis and therapy in Medline
    Contributor: Clare Wotton and Musab Hayatli, November 1999
    Reviewer: Gerard Ryan

    Clinical Question.
    Patient chronic bronchitis
    Intervention or Exposure grepafloxacin
    Comparison ciprofloxacin
    Outcome efficacy and safety