The perils of prescribing fluoroquinolones
These broad-spectrum antibiotics—notable for combatting pathogens resistant to other drugs—have a small but noteworthy potential for adverse effects. This review and patient handout highlight signs and symptoms to watch for.
Monitor older adults taking FQs. Because the risk of psychiatric adverse events is greatest in older individuals, especially those with known atherosclerotic disease or epilepsy, FQ therapy should be used cautiously—and with close monitoring—in this patient population. Symptoms such as weakness, confusion, tremor, loss of appetite, and depression are often incorrectly attributed simply to age, and thus go unreported as potential adverse effects of FQs.29 The exact mechanism by which FQs may induce seizures is unknown, but it may be related to excitatory effects at GABA receptors in the hippocampus.30
FQs may affect glucose levels
FQs have been reported to have varying effects on glucose metabolism, and have been implicated in both hypo- and hyperglycemia. FQ-related hypoglycemia has been thought to occur as a result of an increase in insulin secretion through a sulfonylurea-like action on pancreatic beta cells,31 via drug-drug interactions in patients with renal impairment,32 or via cytochrome P450 interactions.33 The mechanism of action relating to hyperglycemia is less well understood.
One retrospective cohort study in outpatients at a Veterans Administration facility sought to identify outcomes of hospitalization with a primary diagnosis of either hypo- or hyperglycemia in patients with a new prescription for either an FQ or azithromycin.34 In patients with diabetes, the OR for FQ-associated hypoglycemia (compared with azithromycin) was 2.1 for levofloxacin (95% CI, 1.4-3.3) and 1.1 for ciprofloxacin (95% CI, 0.6-2.0). The ORs for hyperglycemia were 1.8 for levofloxacin (95%, CI 1.2-2.7) and 1.0 for ciprofloxacin (95% CI, 0.6-1.8).
A retrospective chart review of more than 17,000 hospitalized patients who were receiving either an FQ or ceftriaxone revealed that 101 patients had either high (>200 mg/dL) or low (<50 mg/dL) glucose levels within 72 hours of receiving the antibiotic.35 Nearly 89% of those studied had diabetes and 40% had prescriptions for oral hypoglycemic agents. While most of these patients had underlying renal insufficiency, rates of hyperglycemia were greater with levofloxacin than with ceftriaxone. (In this study and the VA study, gatifloxacin had greater effects on glucose levels than the non-FQ antibiotics they were compared with; as noted earlier, however, gatifloxacin was removed from the US market in 2006.)
Diplopia is the most common ophthalmologic effect
A database review found 171 case reports of diplopia associated with FQs; ciprofloxacin was the most commonly implicated FQ, with 75 cases. The median time between medication initiation and the development of diplopia was 9.6 days. Most FQ-associated diplopia is completely reversible upon cessation of drug therapy, as evidenced by 53 published reports in which that was the case.36
Adverse effects of intraocular FQs. Ocular keratitis, corneal infiltrates and precipitates, and delayed corneal epithelial healing have been linked to the administration of intraocular FQs.36-38 In addition, retinal detachment has been found to occur in 3.3% of patients being treated with intraocular FQs, compared with 0.6% of controls (adjusted rate ratio=4.50; number needed to harm= 2500).39
CASE Suspecting CDAD and Achilles tendinitis secondary to ciprofloxacin, you stop the medication. Ms. Z’s urine culture is positive for Klebsiella pneumoniae, which is also sensitive to nitrofurantoin, so a 7-day course is prescribed. And, because a stool test for C difficile is positive, you prescribe a 7-day course of metronidazole, as well. Within 4 weeks of stopping the ciprofloxacin, the Achilles tendinitis had completely resolved.
CORRESPONDENCE
Joel J. Heidelbaugh, MD, Ypsilanti Health Center, 200 Arnet Suite 200, Ypsilanti, MI 48198; jheidel@umich.edu
