Older Folks and Hypoglycemia: Another Cautionary Tale Regarding Antibiotics

It should come as no surprise that physicians have repeatedly (and correctly) been accused of overprescribing antibiotics. The blame is not necessarily one-sided; patients often demand antibiotics to treat even the common cold, despite a total lack of efficacy. 

So, why should we be concerned about excessive antibiotic use?

The additional costs and prohibitive risks include a spectrum of mild-to-severe allergic reactions (some fatal), the growing specter of Clostridium difficile, and pharmacological alterations in warfarin metabolism that cause bleeding, as well as a host of other untoward effects, such as increasing resistance. And this month’s Top Paper¹ adds another caveat to the growing list of complications consequent to antibiotic overuse.

Sulfonylureas 

This Top Paper¹ specifically identifies a vulnerable group at increased risk from antibiotics use—elder individuals with diabetes who are prescribed sulfonylureas. Sulfonylureas have been known to have the potential to precipitate severe hypoglycemia. In the at-risk geriatric demographic, sulfonylureas may lead to stroke, dementia, cognitive decline, and sometimes, death. 

Through an empiric observation, researchers from this month’s Top Paper¹ have reviewed population-based data from the United States and Canada and documented that both glyburide and glipizide have been associated with increased hospitalizations in patients who simultaneously take antibiotics. Note: Medicare Part D drug data allows an accurate record of concurrent antibiotic and sulfonylurea prescribing, which allowed the authors to determine the prevalence of hypoglycemia as a consequence of combined sulfonylurea and antibiotic therapy. 

The Research

 For this 2006 to 2009 analysis, the target demographic was patients age 66 or older who were taking glipizide or glyburide, and were prescribed 1 of 7 antibiotic agents thought to be associated with an increased risk of hypoglycemia.¹ The outcome was measured as any hospitalization or emergency department visit due to hypoglycemia. 

Researchers noted that the list of problematic antibiotics was a virtual “Who’s Who” of primary care favorites, including clarithromycin (odds ratio [OR] for hypoglycemia, 3.96), levofloxacin (OR, 2.60), sulfamethoxazole-trimethoprim (OR, 2.56), metronidazole (OR, 2.11), and ciprofloxacin (OR, 1.62). This panel of “offenders” was compared to 9 other antibiotics that did not increase the risk of hypoglycemia when prescribed with glyburide and glipizide. 

Keep in mind that antibiotics, such as clarithromycin, already put older persons at risk from alterations in the QTc interval. In this case, simultaneous prescribing of clarithromycin and a sulfonylurea was harmful in 1 out of 77 prescriptions.¹ 

The most vulnerable patients within this age group tended to be older individuals, women more than men, individuals of black or Hispanic ancestry, persons with higher comorbidity scores, and individuals known to have experienced prior hypoglycemia reactions. 

The study noted that in 2009, 28.3% of patients who were prescribed a sulfonylurea also filled a prescription for 1 of 5 of the aforementioned “risky” antimicrobials—accounting for 13.2% of all hypoglycemic events in all patients taking sulfonylureas.¹ 

The Top Paper¹ concluded with a mind-boggling reality: Hospitalizations for hypoglycemia are presently more common than for hyperglycemia. Primary care practitioners should note that a critical contingent to this statistic is that as a result, the current mortality rates for hypoglycemia also exceed those of hyperglycemia. When will we ever learn? ■

Gregory W. Rutecki, MD, is a physician at the National Consult Service at the Cleveland Clinic. He is also a member of the editorial board of Consultant. He has no relevant financial relationships to disclose.

Reference:

1.Parekh TM, Raji M, Lin Y-L, et al. Hypoglycemia after antimicrobial drug prescription for older patients using sulfonylureas. JAMA Intern Med. 2014;174(10):1605-1612.American College of Physicians. Ann Intern Med. 2014;161:429-440.