Levofloxacin-Induced Hypoglycemia in a
Nondiabetic Patient
SUSAN WANG, DO; ALI A. RIZVI, MD
ABSTRACT: The fluoroquinolones can cause severe hy-
poglycemia in older individuals with diabetes who are
taking oral hypoglycemic agents. We describe a patient
without diabetes who had new-onset hypoglycemia
when given oral levaquin for pneumonia that developed
after cardiac bypass surgery. The condition manifested
with profound neurologic disturbances and required
intravenous dextrose and parenteral glucagon for treat-
ment. No other cause could be identified, and the
problem remitted a few days after administration of the
antibiotic was stopped. Laboratory evaluation showed
relatively inappropriate insulin elevation at the time of
H ypoglycemia as a side effect of prescription med-
ications is usually encountered during the use of
oral hypoglycemic agents and insulin. The fluoro-
quinolones have become widely available since their
introduction in the market and are generally regarded
as safe and effective antimicrobial agents. They are
used on a broad scale for therapy in both the inpatient
and the ambulatory setting. Perturbation of glucose
metabolism has been described with all members of
this class. Worsening of glucose tolerance and hyper-
glycemia can occur, while hypoglycemia related to flu-
oroquinolone use is also being recognized. The latter is
mentioned in the package inserts for moxifloxacin and
levofloxacin and described in case reports. It has been
described almost exclusively in older patients with
diabetes being concurrently treated with oral hypogly-
cemic agents. We report a case of severe hypoglycemia
in a hospitalized nondiabetic patient who was not
taking any glucose-lowering medication and in whom
this life-threatening adverse effect was related in a
temporal fashion to the administration of oral levo-
floxacin for the treatment of pneumonia.
From the Department of Medicine, University of South Carolina
School of Medicine, Columbia, South Carolina
Submitted October 19, 2005; accepted in revised form January
28, 2006.
Correspondence: Ali A. Rizvi, MD, Department of Medicine, Uni-
versity of South Carolina School of Medicine, Two Medical Park,
Suite 502, Columbia, SC 29203 (E-mail: arizvi@gw.mp.sc.edu).
334
the hypoglycemic episodes, consistent with pancreatic
beta-cell stimulation. The report highlights glucose-low-
ering as an adverse effect of the fluoroquinolone class of
antibiotics in persons without diabetes or taking hypo-
glycemic medication. Although levaquin is useful as
broad-spectrum therapy in a variety of situations, clini-
cians should be cognizant of the occurrence of poten-
tially serious or even fatal hypoglycemia with its use.
KEY INDEXING TERMS: Hypoglycemia; Levaquin;
Fluoroquinolones. [Am J Med Sci 2006;331(6):334–
335.]
Case Report
A 65-year-old woman with a history of congestive heart failure,
hypertension, hypothyroidism, and coronary artery disease underwent
coronary bypass surgery complicated by pneumonia in the postopera-
tive period. She was started on a 10-day course of levofloxacin 500 mg
daily 3 days prior to discharge to a physical rehabilitation facility. Other
medications included aspirin, atenolol, furosemide, warfarin, and levo-
thyroxine. During physical rehabilitation, the patient manifested re-
current episodes of hypoglycemia. These episodes were noted 2 weeks
after the cardiac surgery and 3 days after initiating antibiotic therapy.
The patient had no history of hypoglycemia or diabetes and had a
hemoglobin A1c of 5.6% with a blood glucose level of 96 mg/dL at the
time of hospital admission. She denied tobacco or alcohol use. Review of
her medications revealed no evidence of inadvertent administration of
hypoglycemic agents or insulin. Serum chemistry studies showed a
creatinine level of 0.9 mg/dL, blood urea nitrogen level of 20 mg/dL, and
no abnormalities of liver function. Oral food intake, although subopti-
mal at first, continued to improve gradually. On day 5 of antibiotic
treatment, the patient became poorly responsive and was found to have
blood glucose level of 45 mg/dL. The patient had further episodes of
hypoglycemia in the ensuing days that required dextrose and glucagon
administration. She continued to have hypoglycemia even after leva-
floxacin was discontinued, with a blood glucose level of 38 mg/dL 4 days
after her last antibiotic dose. The hypoglycemic episodes stopped spon-
taneously 6 days after completion of levofloxacin therapy.
Evaluation revealed a fasting glucose level of 75 mg/dL correspond-
ing with an insulin level of 11.4 mU/L (normal, 3–25) and a slightly
elevated C-peptide level of 3.4 ng/mL (normal, 0.8–3.1 ng/mL). During
a hypoglycemic episode, when the fingerstick value was 44 mg/dL,
laboratory test samples drawn soon after treatment with fruit juice
revealed serum glucose level of 85 mg/dL, insulin level of 53.3 mU/L,
and C-peptide level of 6.5 ng/mL. The serum and urine sulfonylurea
screens were negative. Since discharge, nurse visits at home have not
revealed any recurrence of symptoms or laboratory findings indicative
of either hypoglycemia or impaired glucose tolerance.
June 2006 Volume 331 Number 6

Discussion
Fluoroquinolones are commonly used antibiotics for
treatment of both community-acquired and nosoco-
mial infections. These agents have a broad spectrum of
antibacterial activity and are widely used for the treat-
ment of respiratory tract infections, acute sinusitis,
urinary tract infections, and certain sexually transmit-
ted diseases. Both hyperglycemia and hypoglycemia
have been associated with fluoroquinolone therapy.
Hypoglycemia occurred in premarketing trials and
was reported by the manufacturers as a side-effect of
moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxa-
cin. Some earlier members of this class were with-
drawn from the market due to serious adverse occur-
rences.1 Temafloxacin was withdrawn specifically for
causing serious adverse reactions such as hypoglyce-
mia in elderly patients. Hypoglycemia has been ob-
served predominantly in patients with diabetes melli-
tus taking oral antidiabetic agents and has been
reported with both intravenous and oral routes of
administration. In a phase IV study of levofloxacin,
hypoglycemia occurred in only two out of 1701 patients
(0.1%).2 More significantly, clinical reports have come
to light recently, after several years of post-marketing
experience with these agents. These cases have usu-
ally involved elderly patients with diabetes receiving
concomitant antidiabetic medications, notably sulfo-
nylureas.3–5 In a study of 48 patients with diabetes
treated with diet and exercise only, gatifloxacin was
found to lower blood glucose level by an average of 20
mg/dL by the mechanism of beta cell stimulation and
increased secretion of insulin.6 A case of fatal hypogly-
cemia was reported in an elderly hospitalized man
with diabetes treated with glyburide who received
intravenous levofloxacin for aspiration pneumonia.7
Our patient did not have diabetes and was not
receiving insulin or oral hypoglycemic agents. She
had no prior history of hypoglycemia, the temporal
course of hypoglycemic episodes coincided with leva-
quin administration, and the condition resolved
within a week of stopping the medication. Hypogly-
cemia was severe (i.e., leading to profound neuro-
logic manifestations and requiring active emergency
intervention) and persistent. The inappropriately
uninhibited levels of insulin and C-peptide were
consistent with an effect on beta-cell function and
augmented insulin release that is thought to under-
lie quinolone action in these situations.
The cause of hypoglycemia in fluoroquinolones is not
well understood. The most probable mechanism seems to
be stimulation of insulin secretion by inhibition of the
pancreatic-beta-cell ATP-sensitive potassium chan-
nels.8,9 Quinolones have been reported to increase insu-
lin release from rat pancreatic islets.9 In addition,
other factors that increase the propensity to severe
hypoglycemia (like sulfonylurea therapy, concomitant
illness, and old age) seem to contribute to its occur-
rence. Although structural variations in the newer
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Wang and Rizvi
synthetic members of this class give them better phar-
macokinetic profiles and improved gram-positive and
anaerobic coverage, potential safety issues still re-
main. Our description of the occurrence of hypoglyce-
mia in a patient with no known history of diabetes or
use of other glucose-lowering agents has not been
clearly documented in the literature before. It points to
the possibility that older age alone may be a predis-
posing factor, and poor oral intake, lack of gluconeoge-
netic capacity secondary to concomitant illness, and
suboptimal counter-regulatory hormone responses to
hypoglycemia may assume importance in certain pa-
tients. It is even possible that stimulation of insulin
secretion by levofloxacin can potentially induce hypo-
glycemia de novo, even in patients without apparent
risk factors. Indeed, this action is likely more common
than recognized in everyday clinical setting, although
it is probably asymptomatic or minimally symptomatic
in the vast majority of patients who receive the medi-
cation.
Conclusion
This case emphasizes the occurrence of profound
hypoglycemia secondary to levofloxacin use, an ad-
verse reaction that has been described with almost
all members of the quinolone family of antibiotics. In
contrast with most of the previous reports, however,
our study illustrates that even patients without a
history of diabetes, hypoglycemic agent use, or other
traditional risk factors can manifest this life-threat-
ening side-effect. Given the frequency of fluoroquin-
olone use in both the hospital and ambulatory set-
ting, clinicians should be aware of this hazard.
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