Outpatient gatifloxacin therapy and dysglycemia in older adults.

BACKGROUND Gatifloxacin has been associated with both hypoglycemia and hyperglycemia. We examined dysglycemia-related health outcomes associated with various antibiotics in a population of approximately 1.4 million Ontario, Canada, residents 66 years of age or older. METHODS We conducted two population-based, nested case-control studies. In the first, case patients were persons treated in the hospital for hypoglycemia after outpatient treatment with a macrolide, a second-generation cephalosporin, or a respiratory fluoroquinolone (gatifloxacin, levofloxacin, moxifloxacin, or ciprofloxacin). In the second, case patients were persons who received hospital care for hyperglycemia. For each case patient, we identified up to five controls matched according to age, sex, the presence or absence of diabetes, and the timing of antibiotic therapy. RESULTS Between April 2002 and March 2004, we identified 788 patients treated for hypoglycemia within 30 days after antibiotic therapy. As compared with macrolide antibiotics, gatifloxacin was associated with an increased risk of hypoglycemia (adjusted odds ratio, 4.3; 95 percent confidence interval, 2.9 to 6.3). Levofloxacin was also associated with a slightly increased risk (adjusted odds ratio, 1.5; 95 percent confidence interval, 1.2 to 2.0), but no such risk was seen with moxifloxacin, ciprofloxacin, or cephalosporins. We then identified 470 patients treated for hyperglycemia within 30 days after antibiotic therapy. As compared with macrolides, gatifloxacin was associated with a considerably increased risk of hyperglycemia (adjusted odds ratio, 16.7; 95 percent confidence interval, 10.4 to 26.8), but no risk was noted with the other antibiotics. Risks were similar in the two studies regardless of the presence or absence of diabetes. CONCLUSIONS As compared with the use of other broad-spectrum oral antibiotics, including other fluoroquinolones, the use of gatifloxacin among outpatients is associated with an increased risk of in-hospital treatment for both hypoglycemia and hyperglycemia.

[1]  A. Peiris,et al.  Drug-Induced Disorders of Glucose Tolerance , 1993, Annals of Internal Medicine.

[2]  A. Laupacis,et al.  Use of statins and the subsequent development of deep vein thrombosis. , 2001, Archives of internal medicine.

[3]  Edwin Lee,et al.  Effects of pioglitazone versus rosiglitazone on lipoprotein subclasses. , 2004, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[4]  G. Wilding,et al.  Association of poor glycemic control with prolonged hospital stay in patients with diabetes admitted with exacerbation of congestive heart failure. , 2004, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[5]  Michel Leblanc,et al.  Severe and Resistant Hypoglycemia Associated with Concomitant Gatifloxacin and Glyburide Therapy , 2004, Pharmacotherapy.

[6]  S. E. Baker,et al.  Possible Gatifloxacin-Induced Hypoglycemia , 2002, The Annals of pharmacotherapy.

[7]  S. Knowles,et al.  Analysis of Spontaneous Reports of Hypoglycemia and Hyperglycemia Associated with Marketed Systemic Fluoroquinolones Made to the Canadian Adverse Drug Reaction Monitoring Program , 2004 .

[8]  P. Ball.  New antibiotics for community-acquired lower respiratory tract infections: improved activity at a cost? , 2000, International journal of antimicrobial agents.

[9]  Amy R. Donaldson,et al.  Possible Gatifloxacin-Induced Hyperglycemia , 2004, The Annals of pharmacotherapy.

[10]  A. Laupacis,et al.  Drug-drug interactions among elderly patients hospitalized for drug toxicity. , 2003, JAMA.

[11]  P. Austin,et al.  Factoring Socioeconomic Status Into Cardiac Performance Profiling for Hospitals: Does it Matter? , 2002, Medical care.

[12]  R. Frothingham.  Quinolone Safety and Efficacy More Important than Potency , 2004, Emerging infectious diseases.

[13]  F. LaCreta,et al.  Effect of Multiple‐Dose Gatifloxacin or Ciprofloxacin on Glucose Homeostasis and Insulin Production in Patients with Noninsulin‐Dependent Diabetes Mellitus Maintained with Diet and Exercise , 2000, Pharmacotherapy.

[14]  R. Pasmantier,et al.  Severe hyperglycemia during gatifloxacin therapy in patients without diabetes. , 2004, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[15]  E. Badley,et al.  Socioeconomic Misclassification in Ontario’s Health Care Registry , 2003, Canadian journal of public health = Revue canadienne de sante publique.

[16]  Jingyang Fan,et al.  Gatifloxacin therapy associated with hypoglycemia. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  Douglas G Altman,et al.  Interaction revisited: the difference between two estimates , 2003, BMJ : British Medical Journal.

[18]  Paul Grootendorst,et al.  Coding accuracy of administrative drug claims in the Ontario Drug Benefit database. , 2003, The Canadian journal of clinical pharmacology = Journal canadien de pharmacologie clinique.

[19]  M. Toublanc,et al.  Pentamidine-induced dysglycaemia: experimental models in the rat. , 1993, Diabete & metabolisme.

[20]  S. Seino,et al.  Effects of fluoroquinolones on insulin secretion and beta-cell ATP-sensitive K+ channels. , 2004, European journal of pharmacology.

[21]  Gatifloxacin-induced hyperglycemia. , 2004, Annals of internal medicine.

[22]  B. Cunha,et al.  Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemic agents. , 2002, The American journal of medicine.

[23]  Socioeconomic status, service patterns, and perceptions of care among survivors of acute myocardial infarction in Canada. , 2004, JAMA.

[24]  M Maclure,et al.  Performance of comorbidity scores to control for confounding in epidemiologic studies using claims data. , 2001, American journal of epidemiology.

[25]  M. Cahalan,et al.  Gatifloxacin as a possible cause of serious postoperative hypoglycemia. , 2005, Anesthesia and Analgesia.

[26]  J. Avorn,et al.  Improved comorbidity adjustment for predicting mortality in Medicare populations. , 2003, Health services research.

[27]  J. Aldag,et al.  Hypoglycemia in Inpatients After Gatifloxacin or Levofloxacin Therapy: Nested Case‐Control Study , 2005, Pharmacotherapy.

[28]  D. Cooper,et al.  Amiodarone and the thyroid. , 2005, The American journal of medicine.

[29]  W. Biggs.  Hypoglycemia and hyperglycemia associated with gatifloxacin use in elderly patients. , 2003, The Journal of the American Board of Family Practice.

[30]  P. Austin,et al.  Postmenopausal estrogen replacement therapy and increased rates of cholecystectomy and appendectomy. , 2000, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[31]  A. Skene,et al.  Antibiotic treatment of Chlamydia pneumoniae after acute coronary syndrome. , 2005, The New England journal of medicine.

[32]  B. Cirincione,et al.  Gatifloxacin and the elderly: pharmacokinetic-pharmacodynamic rationale for a potential age-related dose reduction. , 2003, The Journal of antimicrobial chemotherapy.

[33]  P. Austin,et al.  Effects of socioeconomic status on access to invasive cardiac procedures and on mortality after acute myocardial infarction. , 1999, The New England journal of medicine.

[34]  A. Laupacis,et al.  Rates of Hyperkalemia after Publication of the Randomized Aldactone Evaluation Study , 2004 .

[35]  M Maclure,et al.  Use of comorbidity scores for control of confounding in studies using administrative databases. , 2000, International journal of epidemiology.

[36]  R. Stafford,et al.  Fluoroquinolone prescribing in the United States: 1995 to 2002. , 2005, The American journal of medicine.

[37]  E. Septimus,et al.  A Retrospective, Comparative Evaluation of Dysglycemias in Hospitalized Patients Receiving Gatifloxacin, Levofloxacin, Ciprofloxacin, or Ceftriaxone , 2005, Pharmacotherapy.

[38]  A. Laupacis,et al.  Cyclo-oxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study , 2004, The Lancet.

[39]  J. Chan,et al.  Drug-Induced Disorders of Glucose Metabolism , 1996, Drug safety.

[40]  J. Avorn,et al.  Consistency of performance ranking of comorbidity adjustment scores in canadian and U.S. utilization data , 2004, Journal of General Internal Medicine.

[41]  F. LaCreta,et al.  A Dose‐Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous Gatifloxacin in Healthy Adult Men , 2000, Pharmacotherapy.

[42]  E. Rubinstein.  History of Quinolones and Their Side Effects , 2001, Chemotherapy.

[43]  R. Frothingham.  Glucose homeostasis abnormalities associated with use of gatifloxacin. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.