The article “Gatifloxacin should be avoided in patients with diabetes”, published in the April 2006 issue of the Canadian Medical Association Journal (CMAJ, 2006, 174:1089-1090), has generated a lot of interest in the world of medicine. The authors, Dr. David Juurlink, suggested that gatifloxacin should be avoided in patients with diabetes by conducting a large, two-year case-control study of the antibiotic gatifloxacin (Tequin), manufactured by Bristol-Myers Squibb Co.
The drug was marketed in 1999 and is sold worldwide without any mention in the product insert that it should be used with caution in patients with diabetes. The U.S. Food and Drug Administration (FDA) has also announced that Schweppes will place a black box warning on the label of gatifloxacin, and Canadian health care providers have recommended that gatifloxacin not be given to patients with diabetes.
Gatifloxacin is a commonly used third-generation broad-spectrum quinolone antibacterial agent that is resistant to Gram-negative and Gram-positive aerobic and anaerobic bacteria and atypical bacteria, and is ultimately excreted via the kidneys through biotransformation. It can be used for the treatment of socially acquired pneumonia, acute exacerbation of chronic bronchitis, sinusitis and other respiratory tract infections and urinary tract infections.
This latest case-control study demonstrates the effect of the drug on blood glucose levels and quantifies the risk of gatifloxacin compared to other antibiotics. The study data were obtained from patients aged 65 years or older in Ontario, Canada, who had received oral quinolones, or second-generation cephalosporins or macrolides in the previous month and were admitted to hospital with hyperglycemia or hypoglycemia. The study included diabetic and non-diabetic patients, 778 of whom developed hypoglycemia and 470 of whom developed hyperglycemia.
Macrolides have similar indications to this drug, but do not cause abnormalities in glucose metabolism. And abnormal glucose metabolism can be caused by infection or self-induced factors during hospitalization, the study set up patients taking macrolides as a control group. Patients with impaired glucose metabolism in each case were matched according to their age, gender, presence or absence of diabetes, and negative impact on the onset of antimicrobial action to obtain the five test groups in Table 1.
Table 1 Relationship between abnormal glucose metabolism and recent antimicrobial use
Adjusted dominance ratio* (95% confidence interval)
Hospital survey related to abnormal glucose metabolism
Medication use
Hypoglycemia
Hyperglycemia
Diabetic patients
Gatifloxacin
4.2 (2.8C6.3)
23.6 (12.4C44.6)
Levofloxacin
1.5 (1.2C2.0)
1.6 (1.0C2.5)
Moxifloxacin
0.8 (0.5C1.3)
1.7 (0.8C3.9)
Ciprofloxacin
0.9 (0.7C1.1)
1.3 (0.9C1.8)
Cephalosporin
0.8 (0.6C1.1)
1.0 (0.6C1.7)
Macrolide (reference group)
1.0
1.0
Non-diabetic patients
Gatifloxacin
9.0 (1.3-63.4)
12.8 (5.9C27.8)
Levofloxacin
2.1 (0.7-6.0)
1.0 (0.5C1.8)
Moxifloxacin
1.7 (0.2-11.8)
1.6 (0.7C3.9)
Ciprofloxacin
1.2 (0.5-2.9)
0.9 (0.6C1.6)
Cephalosporin
2.3 (0.8-6.7)
1.5 (0.8C2.7)
Macrolide (reference group)
1.0
1.0
*For liver and kidney disease, alcohol abuse, hospital confirmed association with impaired glucose metabolism in the past 2 years, visits to endocrinologist, internist, family doctor in the past 1 year, administration of insulin or oral hypoglycemic agents in the past 180 days, and other drugs that can affect glucose regulation, common inhibitors or inducers of cytochrome p450 isoenzyme 2c9, social status, and the same disease in the past 1 year number of medications taken, adjustment for the above factors.
It was seen that: the risk was increased in both diabetic and non-diabetic groups with gatifloxacin The incidence of hypoglycemia was four times higher after gatifloxacin use relative to macrolides than in the control group. Of the 778 patients with hypoglycemia, 336 were admitted to hospital and 30 of them (8.1%) died before discharge. The median time from initiation of gatifloxacin to hospital admission was 6 days. On the other hand, in patients with hyperglycemia, the risk was 17 times higher with gatifloxacin than with macrolides.
About half of the 470 patients who presented as hyperglycemic were admitted to hospital and 39 of them (16.5%) died in hospital. The median time from initiation of gatifloxacin to hospital admission was 5 days. Levofloxacin also slightly increased the risk of hypoglycemia, but no hyperglycemia occurred.
In additional analysis, the highest frequency of abnormal glucose regulation within 30 days of antibiotic use was found with gatifloxacin (1.1%), followed by ciprofloxacin (0.3%), levofloxacin (0.3%), both moxifloxacin and second-generation cephalosporins (0.2%), and the lowest with macrolides (0.1%). According to Dr. Zulink, these frequencies may be underestimated because surveys of hospitals or emergency departments include only patients with confirmed hypoglycemia or hyperglycemia. The mechanism is unclear, and gatifloxacin may cause hypoglycemia by promoting insulin release and hyperglycemia by vacuolating pancreatic B cells to lower insulin levels.
The use of gatifloxacin can clearly lead to life-threatening abnormalities in blood glucose regulation in patients who are elderly (>75 years of age), diabetic, have low renal function, and have recently taken glucose-lowering drugs.
There are about 35 million diabetic patients in China and the trend is increasing, but there are no large-scale clinical case-control studies on gatifloxacin and other quinolone antimicrobials and glucose regulation abnormalities in China. This study suggests that gatifloxacin should not be used in diabetic patients, and levofloxacin should be used with caution, and other drugs with less effect on glucose regulation should be chosen for diabetic patients. Remember to inform patients of the signs and symptoms of hypoglycemia and hyperglycemia when prescribing gatifloxacin, and consider monitoring the patient’s blood glucose levels for at least the first week of administration.