Practice recommendations
- Avoid giving gatifloxacin to patients.
- Consider selecting an antibiotic other than a fluoroquinolone for an elderly patient with diabetes mellitus (especially those taking sulfonylureas), hepatic insufficiency, or renal insufficiency (A).
- Discontinue fluoroquinolone therapy if a patient experiences symptoms of hypo- or hyperglycemia, or if blood glucose levels fall below 60 mg/dL or rise above 200 mg/dL (C).
When was the last time you checked a glucose level before prescribing a fluoroquinolone? Though most side effects of these drugs are mild and self-limited (nausea, anorexia, vomiting, abdominal pain, diarrhea, taste disturbance, dizziness, headache, and somnolence), dysglycemia—hypoor hyperglycemia—is another side effect that is potentially fatal.
From their inception, fluoroquinolones were known to upset glucose metabolism. However, recent publication of several case reports of gatifloxacin-associated dysglycemia, and Bristol-Myers Squibb’s announcement of a contraindication for gatifloxacin in diabetic patients, brought the matter of potentially severe dysglycemia to the forefront. Strength of recommendation taxonomy (SORT): A patient-centered approach to grading evidence in the medical literature,” in the February 2004 Journal of Family Practice. A retrospective chart review of more than 17,000 hospitalized patients receiving levofloxacin, gatifloxacin, or ceftriaxone, showed 101 patients with glucose concentrations >200 mg/dL or <50 mg/dL within 72 hours of receiving the drugs. Of these 101 patients, 92 experienced hyperglycemia. Most of these patients had underlying renal insufficiency. Eighty-nine percent had diabetes mellitus and 40% were taking oral hypoglycemics. Hyperglycemia rates were greater with levofloxacin and gatifloxacin than with ceftriaxone; no difference was found between levofloxacin and gatifloxacin.6
Finally, a second retrospective chart review of a VA population identified 64,076 prescriptions written for fluoroquinolones between 1998 and 2003. More than 10,000 glucose values were measured during treatment or within 7 days of treatment completion. Hyperglycemia occurred much more often than hypoglycemia—in 11.6% of 32,000 patients. The majority (59%) of hyperglycemic episodes occurred in diabetic patients, and it was not clear that fluoroquinolone use caused the hyperglycemia. In contrast to the data listed above, gatifloxacin had a lower rate of associated hyperglycemia than either levofloxacin or ciprofloxacin.23
Studies finding no hyperglycemic effect. The studies reviewed in the section on hypoglycemia found no clinically significant hyperglycemic effect of fluoroquinolones.
Take-home points
As with hypoglycemia, most cases of fluoroquinolone-associated hyperglycemia have occurred in patients with NIDDM and mild-to-moderate renal insufficiency. More definitive risk factors for hyperglycemia include decreased insulin secretion (eg, IDDM), decreased insulin sensitivity (eg, NIDDM), advanced age, high carbohydrate intake, acute infection, stress, and corticosteroid use.24 While an association with fluoroquinolone use appears to be multifactorial and dependent on these underlying host factors, strong evidence is lacking.11 As opposed to the timing of hypoglycemic events, review of several case reports revealed that fluoroquinolone-associated hyperglycemia has generally occurred later in treatment, usually after 4 days of therapy, and with higher doses.
Summary of practice recommendations
The following conclusions and recommendations can be made based on the studies reviewed.
First, because the rate of fluoroquinolone-associated dysglycemia is highest with gatifloxacin, and most patients who experience fluoroquinolone-associated dysglycemia have diabetes, gatifloxacin should be avoided in patients who have diabetes (SOR: A).
Second, it’s wise to not use any fluoroquinolone in elderly patients with diabetes mellitus (especially those taking sulfonylureas), hepatic insufficiency, and/or renal insufficiency (SOR: A). If a fluoroquinolone must be used in these patients, favor levofloxacin or moxifloxacin over gatifloxacin (SOR: B).
Third, discontinue fluoroquinolone therapy if a patient experiences symptoms of hypo- or hyperglycemia and/or blood glucose levels fall below 60 mg/dL or rise above 200 mg/dL (SOR: C). If symptomatic hypo- or hyperglycemia does occur, administer appropriate therapy, and if necessary, admit the patient to the hospital for appropriate treatment (SOR: C).
Acknowledgments
The author would like to thanks Barry Weiss, MD, and M. Moe Bell, MD, for their assistance in editing this manuscript, and Robert Marlow, MD, for his assistance in evidence ratings.
CORRESPONDENCE
Martin Catero, MD Heuser Family Medicine Center, 7301 East Second Street, Suite 210, Scottsdale, AZ 85251. E-mail: mcatero@shc.org