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Levofloxacin-induced Hypoglycemia: A Rare but Life-threatening Side Effect of a Widely Used Antibiotic

2009; Elsevier BV; Volume: 122; Issue: 3 Linguagem: Inglês

10.1016/j.amjmed.2008.10.003

1555-7162

Theodoros Kelesidis, Elvia Canseco,

Blood disorders and treatments

Levofloxacin is one of the most commonly prescribed antimicrobial agents. However, hypoglycemia due to levofloxacin is a rarely reported complication and, to our knowledge, only 7 cases have been published. We report the eighth case of an uncommon but potentially fatal side effect of levofloxacin. A 65-year-old woman with type 2 diabetes on glipizide, chronic obstructive pulmonary disease, chronic kidney disease, and cirrhosis presented with a 2-day history of cough, worsening dyspnea, and acute renal failure with an estimated creatinine clearance of 25.1 mL/min. Her management and treatment strategies included the use of diuretics, corticosteroids (60 mg of intravenous methylprednisone daily), and levofloxacin (250 mg intravenously once daily). The last dose of glipizide was given 8 hours before the first dose of levofloxacin. The following day the patient experienced multiple episodes of hypoglycemia (capillary glycemia <50 mg/dL) that were treated with repeated doses of intravenous 50% dextrose. In the next 72 hours, due to persistent hypoglycemia, the patient received 2 doses of glucagon (1 mg), multiple infusions of 50% dextrose, and dextrose-containing fluids (10% dextrose infusion). On the fourth day, levofloxacin was discontinued and the patient continued to receive the D10 intravenous infusion. After 2 days, the patient's glycemic values gradually returned to her baseline. Serum insulin levels sent during an episode of hypoglycemia revealed unsuppressed values (77 μIU/mL), suggesting hyperinsulinemic hypoglycemia. Several articles have associated the administration of fluoroquinolones, especially gatifloxacin, with alterations in glucose metabolism.1Singh N. Jacob J.J. Levofloxacin and hypoglycemia.Clin Infect Dis. 2008; 46: 1127Crossref PubMed Scopus (11) Google Scholar However, contrary to other quinolones, there are no randomized controlled trials assessing the incidence of hypoglycemia with levofloxacin. Levofloxacin has been previously reported to cause hypoglycemia in 7 patients.1Singh N. Jacob J.J. Levofloxacin and hypoglycemia.Clin Infect Dis. 2008; 46: 1127Crossref PubMed Scopus (11) Google Scholar, 2Friedrich L.V. Dougherty R. Fatal hypoglycemia associated with levofloxacin.Pharmacotherapy. 2004; 24: 1807-1812Crossref PubMed Scopus (61) Google Scholar, 3Kanbay M. Aydogan T. Bozalan R. et al.A rare but serious side effect of levofloxacin: hypoglycemia in a geriatric patient.Diabetes Care. 2006; 29: 1716-1717Crossref PubMed Scopus (13) Google Scholar, 4Lawrence K.R. Adra M. Keir C. Hypoglycemia-induced anoxic brain injury possibly associated with levofloxacin.J Infect. 2006; 52: e177-e180Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 5Wang S. Rizvi A.A. Levofloxacin-induced hypoglycemia in a nondiabetic patient.Am J Med Sci. 2006; 331: 334-335Crossref PubMed Scopus (20) Google Scholar, 6Gibert A.E. Porta F.S. Hypoglycemia and levofloxacin: a case report.Clin Infect Dis. 2008; 46: 1126-1127Crossref PubMed Scopus (11) Google Scholar, 7Vallurupalli S. Huesmann G. Gregory J. Jakoby M.G. Levofloxacin-associated hypoglycaemia complicated by pontine myelinolysis and quadriplegia.Diabet Med. 2008; 25: 856-859Crossref PubMed Scopus (23) Google Scholar In 4 of these instances, delays in recognizing the etiology of the hypoglycemia led to unfortunate consequences.1Singh N. Jacob J.J. Levofloxacin and hypoglycemia.Clin Infect Dis. 2008; 46: 1127Crossref PubMed Scopus (11) Google Scholar, 2Friedrich L.V. Dougherty R. Fatal hypoglycemia associated with levofloxacin.Pharmacotherapy. 2004; 24: 1807-1812Crossref PubMed Scopus (61) Google Scholar, 4Lawrence K.R. Adra M. Keir C. Hypoglycemia-induced anoxic brain injury possibly associated with levofloxacin.J Infect. 2006; 52: e177-e180Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 7Vallurupalli S. Huesmann G. Gregory J. Jakoby M.G. Levofloxacin-associated hypoglycaemia complicated by pontine myelinolysis and quadriplegia.Diabet Med. 2008; 25: 856-859Crossref PubMed Scopus (23) Google Scholar The persistent and severe hypoglycemia over 6 days, the lack of response to a dextrose infusion despite the fact that the patient was on steroids, and the elevated serum insulin levels despite low blood sugar values imply a different mechanism for hypoglycemia other than a combination of risk factors such as renal failure, hepatic dysfunction, and therapy with glucose-lowering medications. Application of the Naranjo adverse drug reaction probability scale to this case determined that the hypoglycemia was possibly due to levofloxacin. The inappropriately uninhibited levels of insulin in our case were consistent with an effect of levofloxacin on beta-cell function and data from animal studies that have demonstrated that fluoroquinolones directly stimulate insulin secretion from pancreatic B-cells.3Kanbay M. Aydogan T. Bozalan R. et al.A rare but serious side effect of levofloxacin: hypoglycemia in a geriatric patient.Diabetes Care. 2006; 29: 1716-1717Crossref PubMed Scopus (13) Google Scholar Despite the frequent use of levofloxacin, awareness about the potential hypoglycemic effect is poor. In a recent survey, 80.4% of physicians were unaware that levofloxacin could cause hypoglycemia.1Singh N. Jacob J.J. Levofloxacin and hypoglycemia.Clin Infect Dis. 2008; 46: 1127Crossref PubMed Scopus (11) Google Scholar We describe the eighth case of hypoglycemia associated with levofloxacin. Interestingly, the diabetic patient in our case had severe and persistent hypoglycemia despite the fact that she also was receiving a high dose of corticosteroids for treatment of bronchitis. To the best of our knowledge, this is the first published case of such severe and persistent hypoglycemia caused by levofloxacin in a diabetic patient being treated with a combination of high dose of corticosteroids and continuous infusion of intravenous dextrose. In conclusion, hypoglycemia associated with the use of levofloxacin is an uncommon occurrence but can be very persistent and severe and often responds only to discontinuation of levofloxacin. Increased awareness can prevent significant mortality and morbidity associated with this rare but life-threatening side effect of this widely used antibiotic.