Psychosomatics 44:85-86, February 2003
© 2003 The Academy of Psychosomatic Medicine

Letter

Delirium Associated With Gatifloxacin
C. Loraine Sumner, B.A., and Richard L. Elliott, M.D., Ph.D., F.A.P.A., Macon, Ga.
TO THE EDITOR: Gatifloxacin, a broad-spectrum 8-methoxyfluoroquinolone antibiotic, has CNS toxicity, occurring in 0.1%–3.0% of patients.1 There are previous reports in the English literature of delirium associated with other fluoroquinolones, but we know of no reports of delirium associated with gatifloxacin.

Case Report

Mr. A was a 69-year-old white man with a history of depression, non-insulin-dependent diabetes mellitus, hypertension, benign prostatic hyperplasia, hypothyroidism, and atherosclerotic disease. He was admitted to the hospital for an L3-L4 laminectomy/fusion. Upon admission, Mr. A was alert and oriented. The results of all preoperative laboratory data were normal, with the exception of a low BUN/creatinine ratio (11.3), a low RBC count (3.92x106/mm3), and a low hemoglobin/hematocrit ratio (12.6/36.1). His surgery proceeded without complications, and he was placed on a morphine patient-controlled analgesia pump. This was discontinued within 24 hours of the surgery.

On postoperative day 1, Mr. A's temperature reached 101.2°F. He also developed a cough that was productive of rust-colored sputum. A chest X-ray on postoperative day 2 revealed areas of subsegmental atelectasis versus bibasilar infiltrates. A sputum culture contained few gram-positive cocci, few gram-positive rods, rare gram-negative rods, and many WBCs. The results of laboratory tests were normal, except for a decreased serum sodium level (130 meq/liter), a decreased serum potassium level (3.0 meq/liter), and an elevated glucose level (203 mg/ dl). Mr. A's WBC count at this time was 9.89x103/mm3.

Intravenous gatifloxacin (400 mg/ 200 ml) was ordered that evening, with the first dose given the next morning, on postoperative day 3. Laboratory data on this day revealed continued low serum sodium (134 meq/liter), potassium (3.3 meq/liter), and chloride (95 meq/liter) levels, and an elevated glucose level (134 mg/dl), a low BUN/creatinine ratio (8.9), and a low serum calcium level (8.4 meq/liter). Mr. A was now afebrile. A chest X-ray showed better lung aeration. However, Mr. A's wife and nurses noticed that he had become confused and disoriented. That night, several hours after gatifloxacin had been started, Mr. A had numerous hallucinations of people in his hospital room, and he slept very little.

The next day, postoperative day 4, Mr. A's confusion worsened, and his hallucinations became more violent in nature. He believed that men were coming into his room carrying guns and gas, attempting to kill him. He told the nurses that he did not feel safe in his room and that security guards could not protect him. He stated that the only way to survive was to hold his breath while the men sprayed him with some sort of foul-smelling gas. He also had vivid hallucinations of involvement in car crashes. Mr. A was placed in restraints at this point.

The results of a computerized tomography scan without contrast were normal on postoperative day 5. A urinalysis revealed that Mr. A had developed a urinary tract infection, so treatment with gatifloxacin was continued. He was also receiving haloperidol, 2 mg/day i.v., and risperidone, 0.5 mg/ day orally at bedtime, for treatment of agitation. Again, he slept very little. For the next 2 days, Mr. A's condition remained unchanged. On postoperative day 7, his WBC count was elevated, at 15.3x103/mm3. The next day, Mr. A's wife and nurses reported that his hallucinations and confusion seemed to worsen after each dose of gatifloxacin. Gatifloxacin was discontinued because of concerns that the antibiotic was causing Mr. A's delirium and hallucinations.

A psychiatric evaluation at that time revealed him to be alert and oriented, with no further hallucinations. His speech was normal in rate and flow, and his concentration and recall were intact. Mr. A slept well that night. The next day he reported no further hallucinations. He did well thereafter and was discharged to go home on postoperative day 10.

Discussion

Delirium and hallucinations associated with the fluoroquinolones have been reported, particularly with levofloxacin and ciprofloxacin.2 The proposed mechanism involved in the development of such side effects seems to be related to the quinolones' ability to inhibit the binding of -aminobutyric acid (GABA) to the GABA receptors, leading to CNS excitation.3

Other diagnoses contributing to mental status changes and hallucinations could not be completely ruled out in this case, especially the presence of a urinary tract infection. However, the patient had never experienced any problems with the other medications he had received in the past. Furthermore, his hallucinations seemed to occur more intensely after each dose of gatifloxacin, suggesting a close relationship between the antibiotic and hallucinations in this patient. This aspect is similar to the reports of hallucinations and delirium with other fluoroquinolones. Thus, the temporal relationship between the patient's gatifloxacin use and the onset and resolution of his hallucinations is strongly suggestive of a causal relationship between gatifloxacin and the onset of delirium with violent hallucinations.

REFERENCES


Bristol-Myers Squibb Company: Tequin (gatifloxacin). www.tequin.com

Farrington J, Stoudemire A, Tierney J: The role of ciprofloxacin in a patient with delirium due to multiple etiologies. Gen Hosp Psychiatry 1995; 17:47-53[CrossRef][Medline]

Segev S, Rehavi M, Rubinstein E: Quinolones, theophylline, and diclofenac interactions with the gamma-aminobutyric acid receptor. Antimicrob Agents Chemother 1998; 32:1624-1626