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Background: The prevalence of glucose abnormalities has been reported to be greater in hospitalized patients receiving gatifloxacin than in patients receiving ceftriaxone., Objective: The purpose of the current study was to identify risk factors for hyperglycemia in hospitalized patients receiving gatifloxacin., Methods: This retrospective, nested case-controlled study was conducted in 69 patients and 69 controls in 2 nonteaching hospitals in Houston, Texas. Classification and regression tree (CART) analysis was conducted to identify break points in continuous variables. Univariate and multivariate logistic regression analyses were also performed., Results: A total of 138 patients (mean [SD] age, 68.3 [17.3] years; weight, 77.4 [21.1] kg; sex, women/ men, 69.6%/30.4%; race [Hispanic, 58.3%; white, 28.5%; black, 9.2%; other, 4.0%]) were identified. Patients who developed hyperglycemia (blood glucose level > 200 mg/dL) within 72 hours of gatifloxacin administration (cases) were matched 1:1 with patients who received gatifloxacin for > or = 5 days and did not experience hyperglycemia during treatment and for 3 days after the end of treatment (controls). In univariate analysis, cases were more likely than controls to have diabetes (89.9% vs 13.0%; P < 0.001), have a decreased mean (SD) creatinine clearance (CrCl) (53.8 [36.8] vs 69.2 [45.3] mL/min; P = 0.025), be located in the intensive care unit at the time of the event (20.3% vs 7.2%; P = 0.02), have received gatifloxacin doses higher than recommended based on renal function (> 200 mg/d when CrCl < 40 mL/min) (25/69 [36.2%] vs 9/69 [13.0%]), have leukocytosis (mean [SD] white blood cell [WBC] count, 15.5 [7.4] vs 12.8 [6.2] cells/mm3), and have received concomitant total parenteral nutrition (7/69 [10.1%] vs 0 [0%]; P = 0.02) and/or steroids (22/69 [31.9%] vs 8/69 [11.6%]; P = 0.008). CART analysis identified age > 65 years, albumin < 3.2 g/dL, WBC count > 14.5 cells/mm3, and CrCl < 40 mL/min to be more common in hyperglycemic patients. In logistic regression, diabetes (odds ratio [OR] = 233; 95% CI, 19-2784) and excessive dose for renal function (OR = 42; 95% CI, 2-770) were identified as independent predictors for hyperglycemia in patients receiving gatifloxacin. After controlling for diabetes, concomitant steroids (OR = 5.7; 95% CI, 1.5-21.1) and excessive dose for renal function (OR = 4.9; 95% CI, 1.2-20.4) were associated with hyperglycemia in patients receiving gatifloxacin., Conclusions: This retrospective, nested case-controlled study found that the risk of hyperglycemia increased in diabetic patients who received concomitant steroids or higher gatifloxacin doses than recommended by the manufacturer's prescribing information. The application of these data should be assessed for other fluoroquinolones used at higher doses.

The fluoroquinolones are an extremely popular class of antibacterials, owing to their broad spectrum of activity and the convenience of their intravenous and oral dosage formulations. Overall, the currently available fluoroquinolones have a good safety profile; however, certain fluoroquinolones within the class have been associated with severe and life-threatening adverse drug reactions. Dysglycaemic episodes (hyperglycaemia and hypoglycaemia) have been observed in patients taking multiple antibacterials, including the fluoroquinolones. Although gatifloxacin has been associated with dysglycaemias more frequently than other fluoroquinolones, dysglycaemic events have been reported with some of the other currently available fluoroquinolones as well. Hypoglycaemia appears to be related to insulin release and is an early-onset event. However, hyperglycaemia tends to present several days into therapy and the exact mechanism by which it is caused is still unclear. Recent studies point towards the important role of the adenosine triphosphate (ATP)-sensitive K+ channels in the pancreatic beta cell and the importance of anti-insulin hormones. Several retrospective studies have elucidated risk factors associated with fluoroquinolone exposure and subsequent dysglycaemic events. These studies suggest that dysglycaemia is a dose-related adverse effect involving the fluoroquinolone class; however, some drugs within the class appear to have a greater association. This may be related to the affinity of fluoroquinolones to the ATP-sensitive K+ channel or higher concentrations of drugs achieved in certain patients who are already at risk for hyperglycaemia and hypoglycaemia. Understanding these risk factors will allow the fluoroquinolones to be utilized in a way that minimizes the probability of associated dysglycaemic events.

Study Objectives: To compare rates of hypoglycemia and hyperglycemia among elderly hospitalized patients with normal blood glucose concentrations at baseline who were receiving either gatifloxacin or levofloxacin, and to determine if appropriateness of their doses, according to their package inserts, was associated with hypoglycemia or hyperglycemia., Design: Retrospective cohort study., Setting: Integrated Veterans Administration (VA) health care system., Patients: Nine hundred thirty-seven elderly (>or= 65 yrs) patients with documented blood glucose levels of 65-140 mg/dl before receiving a fluoroquinolone., Measurements and Main Results: Between January 2003 and April 2004, 405 patients receiving levofloxacin met study criteria. In April 2004, gatifloxacin was substituted for levofloxacin on the formulary of this VA system. Thus, between April 2004 and December 2004, 532 patients received gatifloxacin. All blood glucose concentrations during hospitalization that were measured during fluoroquinolone therapy or within 72 hours of completion of therapy were reviewed. Demographic characteristics, comorbidities, insulin and oral hypoglycemic therapies, disease severity, blood glucose levels, and outcomes were recorded and compared between groups. The two groups were similar at baseline for all characteristics examined except previous hospitalization. In the logistic regression, gatifloxacin was independently associated with both hypoglycemia (adjusted odds ratio [AOR] 2.5, 95% confidence interval [CI] 1.2-5.7, p=0.04) and hyperglycemia (AOR 2.4, 95% CI 1.5-3.6, p<0.001). Improper dosage adjustment based on renal function was not associated with higher rates of hypoglycemia and hyperglycemia for either drug. Of the 532 patients receiving gatifloxacin, 465 (87.4%) received appropriate doses, yet gatifloxacin was associated with higher rates of hypoglycemia and hyperglycemia compared with patients receiving levofloxacin., Conclusions: Higher rates of both hypoglycemia and hyperglycemia were noted among elderly hospitalized patients who received gatifloxacin compared with those receiving levofloxacin, irrespective of dosing.

Study Objectives: To compare rates of blood glucose abnormalities in hospitalized patients receiving fluoroquinolones or ceftriaxone, and to describe the characteristics of patients who develop blood glucose abnormalities while receiving these agents., Design: Retrospective chart review., Setting: Two community-based hospitals in the Houston, Texas, region., Patients: Seventeen thousand one hundred eight patients who received fluoroquinolones or ceftriaxone; of those, 101 received levofloxacin, gatifloxacin, or ceftriaxone and also had serum glucose concentrations above 200 or below 50 mg/dl within 72 hours of receiving the drug., Measurements and Main Results: Baseline demographics of patients with glucose abnormalities while receiving gatifloxacin, levofloxacin, or ceftriaxone were similar. Mean +/- SD patient age, weight, and estimated creatinine clearance were 67 +/- 17 years, 79 +/- 21 kg, and 52 +/- 32 ml/minute, respectively. Dysglycemia rates relative to treatment were as follows: gatifloxacin 76 (1.01%) of 7540 patients, levofloxacin 11 (0.93%) of 1179, ceftriaxone 14 (0.18%) of 7844, ciprofloxacin 0 (0%) of 545, and any fluoroquinolone 87 (0.94%) of 9264. Dysglycemia was more likely to occur in patients receiving any fluoroquinolone than in those receiving ceftriaxone (relative risk [RR] 3.32, 95% confidence interval (CI) 2.31-4.78, p < 0.05). The rate of dysglycemia did not differ with gatifloxacin and levofloxacin (RR 1.07, 95% CI 0.62-1.86, p = 0.8). Of the 101 patients with dysglycemias, hypoglycemia occurred in nine (9%) and hyperglycemia in 92 (91%). In a multivariate analysis of patients receiving fluoroquinolones, only concomitant sulfonylurea therapy was identified as an independent risk factor for development of hypoglycemia compared with patients who experienced hyperglycemia., Conclusion: In the 17,108 patients receiving a fluoroquinolone or ceftriaxone, the rate of dysglycemia was greater in those receiving levofloxacin or gatifloxacin than in those receiving ceftriaxone. However, no difference was noted in the rate of glucose abnormalities with levofloxacin versus gatifloxacin. Clinicians should be aware of dysglycemic events that may occur in patients receiving fluoroquinolones, especially in those with diabetes mellitus or those receiving sulfonylureas.