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Background . Although gatifloxacin is no longer available, other fluoroquinolones may significantly interfere with glucose homeostasis. The objective of the present study was to compare the risk of severe hypo- and hyperglycemia in a cohort of patients treated with gatifloxacin, levofloxacin, ciprofloxacin, or azithromycin.


Methods . This was a retrospective inception cohort study of outpatients with a new prescription for gatifloxacin, levofloxacin, ciprofloxacin, or azithromycin from 1 October 2000 through 30 September 2005 in the Veterans Affairs health care system. For patients who received one of these antibiotics, we identified outcomes of hospitalization with a primary diagnosis of hypo- or hyperglycemia. Multivariable logistic regression was used to determine the odds of hypo- and hyperglycemia with the individual fluoroquinolones versus azithromycin.


Results . The crude incidence rates for severe hypo- and hyperglycemia among those who received gatifloxacin, levofloxacin, ciprofloxacin, and azithromycin were 0.35 and 0.45, 0.19 and 0.18, 0.10 and 0.12, and 0.07 and 0.10 cases per 1000 patients, respectively. Among patients with diabetes, the odds ratios for hypoglycemia compared with azithromycin were 4.3 (95% confidence interval [CI], 2.7–6.6) for gatifloxacin, 2.1 (95% CI, 1.4–3.3) for levofloxacin, and 1.1 (95% CI, 0.6–2.0) for ciprofloxacin. The odds ratios for hyperglycemia were 4.5 (95% CI, 3.0–6.9) for gatifloxacin, 1.8 (95% CI, 1.2–2.7) for levofloxacin, and 1.0 (95% CI, 0.6–1.8) for ciprofloxacin.


Conclusions . The odds of severe hypo- and hyperglycemia were significantly greater with gatifloxacin and levofloxacin, but not ciprofloxacin, than with azithromycin. Thus, the risk of a clinically relevant dysglycemic event appears to vary among the fluoroquinolones.

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The fluoroquinolone antibiotics are widely used because they are generally well tolerated and have a broad spectrum of activity. However, gatifloxacin—which had been used in the treatment of a variety of infections, including those involving the skin and the respiratory and genitourinary tracts [ 1 , 2 ]—was withdrawn from the market because of concerns about severe glucose disturbances. Although hypoglycemia and hyperglycemia were reported only rarely during clinical trials with gatifloxacin, severe dysglycemic events, typically in elderly patients and in patients with diabetes, were reported during the postmarketing period [ 3 ] and published in the medical literature [ 4–21 ].

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