Correspondence

Gatifloxacin and Dysglycemia in Older Adults

N Engl J Med 2006; 354:2725-2726June 22, 2006

Article

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

3 References

1. 1

   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
   Full Text | Web of Science | Medline

2. 2

   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
   CrossRef | Web of Science | Medline

3. 3

   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
   CrossRef | Web of Science | Medline

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.1-3 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

3 References

1. 1

   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
   CrossRef | Web of Science | Medline

2. 2

   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
   CrossRef | Web of Science | Medline

3. 3

   Sulochana S, Rahman F, Paramasivan CN. In vitro activity of fluoroquinolones against Mycobacterium tuberculosis. J Chemother 2005;17:169-173
   Web of Science | Medline

Author/Editor Response

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

3 References

1. 1

   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
   CrossRef | Web of Science | Medline

2. 2

   Frothingham R. Glucose homeostasis abnormalities associated with use of gatifloxacin. Clin Infect Dis 2005;41:1269-1276
   CrossRef | Web of Science | Medline

3. 3

   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
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Ann M. Ginsberg. (2010) Tuberculosis drug development: Progress, challenges, and the road ahead. Tuberculosis 90:3, 162-167
   CrossRef

2. 2

   John F. Mohr, Patti J. Peymann, Eric Troxell, Thomas P. Lodise, Luis Ostrosky-Zeichner. (2008) Risk factors for hyperglycemia in hospitalized adults receiving gatifloxacin: A retrospective, nested case-controlled analysis. Clinical Therapeutics 30:1, 152-157
   CrossRef

3. 3

   (2006) Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 15:12, i-xii
   CrossRef