Gatifloxacin and Dysglycemia in Older Adults
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《新英格兰医药杂志》
To the Editor: Park-Wyllie and colleagues (March 30 issue)1 advise avoiding the use of gatifloxacin because of the increased risk of dysglycemia, and they suggest using alternative antibiotics, including other fluoroquinolones, that confer little or no increased risk of dysglycemia. This suggestion must be questioned. Although it appears that the administration of moxifloxacin has no clinically relevant effect on blood glucose homeostasis,2 other fluoroquinolones may trigger dysglycemic events, especially in patients with diabetes who receive sulfonylureas.3 Clinicians should be aware of the possibility of dysglycemic events in patients receiving fluoroquinolones.
Karl P. Ittner, M.D., D.E.A.A.
University of Regensburg
D-93042 Regensburg, Germany
karl-peter.ittner@klinik.uni-regensburg.de
References
Park-Wyllie LY, Juurlink DN, Kopp A, et al. Outpatient gatifloxacin therapy and dysglycemia in older adults. N Engl J Med 2006;354:1352-1361.
Gavin JR III, Kubin R, Choudhri S, et al. Moxifloxacin and glucose homeostasis: a pooled-analysis of the evidence from clinical and postmarketing studies. Drug Saf 2004;27:671-686.
Mohr JF, McKinnon PS, Peymann PJ, Kenton I, Septimus E, Okhuysen PC. A retrospective, comparative evaluation of dysglycemias in hospitalized patients receiving gatifloxacin, levofloxacin, ciprofloxacin, or ceftriaxone. Pharmacotherapy 2005;25:1303-1309.
To the Editor: The article by Park-Wyllie et al. has an important implication for countries such as India, where gatifloxacin is widely used for the treatment of multidrug-resistant tuberculosis. Substantial data demonstrate the efficacy of gatifloxacin among patients with tuberculosis.1,2,3 In the study by Park-Wyllie et al., 30 of 366 case patients died from dysglycemia. We wonder whether patients who die while being treated with gatifloxacin for multidrug-resistant tuberculosis might be classified incorrectly and actually die from a severe reaction to the drug. In the light of the study by Park-Wyllie and others, the use of gatifloxacin in patients with multidrug-resistant tuberculosis should be reconsidered.
Vijay Yadav, M.D.
Kuldeep Deopujari, M.D.
Gandhi Medical College
Bhopal 462001, India
majorvkyadav@gmail.com
References
Sriram D, Aubry A, Yogeeswari P, Fisher LM. Gatifloxacin derivatives: synthesis, antimycobacterial activities, and inhibition of Mycobacterium tuberculosis DNA gyrase. Bioorg Med Chem Lett 2006;16:2982-2985.
Paramasivan CN, Sulochana S, Kubendiran G, Venkatesan P, Mitchison DA. Bactericidal action of gatifloxacin, rifampin, and isoniazid on logarithmic- and stationary-phase cultures of Mycobacterium tuberculosis. Antimicrob Agents Chemother 2005;49:627-631.
Sulochana S, Rahman F, Paramasivan CN. In vitro activity of fluoroquinolones against Mycobacterium tuberculosis. J Chemother 2005;17:169-173.
The authors reply: Ittner disputes our suggestion that clinicians should avoid gatifloxacin in favor of antibiotics that do not cause dysglycemia. He cites a retrospective hospital-chart review that grouped cases of hypoglycemia and hyperglycemia together for analytic purposes yet still had insufficient power to detect a difference in risk among the various fluoroquinolones.1 In contrast, our findings were derived from a population of more than 1 million people, including hundreds who were hospitalized for dysglycemia within days after starting treatment with a fluoroquinolone. Our analysis also incorporated many important determinants of glycemic control, including the use of sulfonylureas and insulin, and adds to a growing body of evidence indicating that gatifloxacin is uniquely associated with dysglycemia.2,3 We reiterate our suggestion that gatifloxacin be used with extreme caution, if at all, given the widespread availability of alternative antibiotics that do not influence blood glucose levels. In addition, we advise against the overinterpretation of the results of small studies, since such results are particularly prone to a type II error.
The data on mortality rates in our study should be interpreted with caution, because hospitalized patients may have died from infection (rather than from dysglycemia) and because we cannot ascertain the number of outpatient deaths related to dysglycemia. However, we agree with Yadav and Deopujari that the use of gatifloxacin for multidrug-resistant tuberculosis merits reconsideration. Although Bristol-Myers Squibb announced on May 1, 2006, that it would cease marketing its formulation of gatifloxacin (Tequin), other formulations remain available throughout the world, and glucose disturbances during treatment are more likely to have serious clinical consequences in areas where access to medical care is limited.
Laura Y. Park-Wyllie, Pharm.D.
Baiju R. Shah, M.D., Ph.D.
David N. Juurlink, M.D., Ph.D.
University of Toronto
Toronto, ON M4N 3M5, Canada
dnj@ices.on.ca
References
Mohr JF, McKinnon PS, Peymann PJ, Kenton I, Septimus E, Okhuysen PC. A retrospective, comparative evaluation of dysglycemias in hospitalized patients receiving gatifloxacin, levofloxacin, ciprofloxacin, or ceftriaxone. Pharmacotherapy 2005;25:1303-1309.
Frothingham R. Glucose homeostasis abnormalities associated with use of gatifloxacin. Clin Infect Dis 2005;41:1269-1276.
Graumlich JF, Habis S, Avelino RR, et al. Hypoglycemia in inpatients after gatifloxacin or levofloxacin therapy: nested case-control study. Pharmacotherapy 2005;25:1296-1302.
Karl P. Ittner, M.D., D.E.A.A.
University of Regensburg
D-93042 Regensburg, Germany
karl-peter.ittner@klinik.uni-regensburg.de
References
Park-Wyllie LY, Juurlink DN, Kopp A, et al. Outpatient gatifloxacin therapy and dysglycemia in older adults. N Engl J Med 2006;354:1352-1361.
Gavin JR III, Kubin R, Choudhri S, et al. Moxifloxacin and glucose homeostasis: a pooled-analysis of the evidence from clinical and postmarketing studies. Drug Saf 2004;27:671-686.
Mohr JF, McKinnon PS, Peymann PJ, Kenton I, Septimus E, Okhuysen PC. A retrospective, comparative evaluation of dysglycemias in hospitalized patients receiving gatifloxacin, levofloxacin, ciprofloxacin, or ceftriaxone. Pharmacotherapy 2005;25:1303-1309.
To the Editor: The article by Park-Wyllie et al. has an important implication for countries such as India, where gatifloxacin is widely used for the treatment of multidrug-resistant tuberculosis. Substantial data demonstrate the efficacy of gatifloxacin among patients with tuberculosis.1,2,3 In the study by Park-Wyllie et al., 30 of 366 case patients died from dysglycemia. We wonder whether patients who die while being treated with gatifloxacin for multidrug-resistant tuberculosis might be classified incorrectly and actually die from a severe reaction to the drug. In the light of the study by Park-Wyllie and others, the use of gatifloxacin in patients with multidrug-resistant tuberculosis should be reconsidered.
Vijay Yadav, M.D.
Kuldeep Deopujari, M.D.
Gandhi Medical College
Bhopal 462001, India
majorvkyadav@gmail.com
References
Sriram D, Aubry A, Yogeeswari P, Fisher LM. Gatifloxacin derivatives: synthesis, antimycobacterial activities, and inhibition of Mycobacterium tuberculosis DNA gyrase. Bioorg Med Chem Lett 2006;16:2982-2985.
Paramasivan CN, Sulochana S, Kubendiran G, Venkatesan P, Mitchison DA. Bactericidal action of gatifloxacin, rifampin, and isoniazid on logarithmic- and stationary-phase cultures of Mycobacterium tuberculosis. Antimicrob Agents Chemother 2005;49:627-631.
Sulochana S, Rahman F, Paramasivan CN. In vitro activity of fluoroquinolones against Mycobacterium tuberculosis. J Chemother 2005;17:169-173.
The authors reply: Ittner disputes our suggestion that clinicians should avoid gatifloxacin in favor of antibiotics that do not cause dysglycemia. He cites a retrospective hospital-chart review that grouped cases of hypoglycemia and hyperglycemia together for analytic purposes yet still had insufficient power to detect a difference in risk among the various fluoroquinolones.1 In contrast, our findings were derived from a population of more than 1 million people, including hundreds who were hospitalized for dysglycemia within days after starting treatment with a fluoroquinolone. Our analysis also incorporated many important determinants of glycemic control, including the use of sulfonylureas and insulin, and adds to a growing body of evidence indicating that gatifloxacin is uniquely associated with dysglycemia.2,3 We reiterate our suggestion that gatifloxacin be used with extreme caution, if at all, given the widespread availability of alternative antibiotics that do not influence blood glucose levels. In addition, we advise against the overinterpretation of the results of small studies, since such results are particularly prone to a type II error.
The data on mortality rates in our study should be interpreted with caution, because hospitalized patients may have died from infection (rather than from dysglycemia) and because we cannot ascertain the number of outpatient deaths related to dysglycemia. However, we agree with Yadav and Deopujari that the use of gatifloxacin for multidrug-resistant tuberculosis merits reconsideration. Although Bristol-Myers Squibb announced on May 1, 2006, that it would cease marketing its formulation of gatifloxacin (Tequin), other formulations remain available throughout the world, and glucose disturbances during treatment are more likely to have serious clinical consequences in areas where access to medical care is limited.
Laura Y. Park-Wyllie, Pharm.D.
Baiju R. Shah, M.D., Ph.D.
David N. Juurlink, M.D., Ph.D.
University of Toronto
Toronto, ON M4N 3M5, Canada
dnj@ices.on.ca
References
Mohr JF, McKinnon PS, Peymann PJ, Kenton I, Septimus E, Okhuysen PC. A retrospective, comparative evaluation of dysglycemias in hospitalized patients receiving gatifloxacin, levofloxacin, ciprofloxacin, or ceftriaxone. Pharmacotherapy 2005;25:1303-1309.
Frothingham R. Glucose homeostasis abnormalities associated with use of gatifloxacin. Clin Infect Dis 2005;41:1269-1276.
Graumlich JF, Habis S, Avelino RR, et al. Hypoglycemia in inpatients after gatifloxacin or levofloxacin therapy: nested case-control study. Pharmacotherapy 2005;25:1296-1302.