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ecause the fluoroquinolones have such a wide spectrum of antimicrobial activity, they are used to treat many infections commonly seen in primary care, particu- larly those involving the respiratory and urologic sys- tems.1,2 Because they are generally well tolerated, fluoroquinolones have become one of the most popu- lar classes of antibiotics for outpatients.3This report, however, presents a rare but serious adverse reaction to ciprofloxacin.
Case report
A 69-year-old woman with a history of metastatic cer- vical cancer presented to the emergency room with a 24-hour histor y of anuria and fever. Her symptoms started after removal of a ureteric stent, which was originally inserted to relieve obstruction of her single functioning ureter. Other significant medical history included ischemic hear t disease and non–insulin- dependent diabetes mellitus. She had previously undergone total abdominal hysterectomy and bilat- eral salpingo-oophorectomy, nephrectomy, and a course of radiotherapy.
The patient had a fever and a decreased level of consciousness. Investigations revealed a white blood cell count of 18.0 109/L, a creatinine level of 330 µmol/L, and a potassium level of 6.6 mmol/L. The patient under went cystoscopy, and a stent was replaced. Following the procedure, she was placed on cefazolin, 1 g every 6 hours, and norfloxacin, 400 mg orally once a day. Results of blood and urine cultures revealed Pseudomonas sensitive to ciprofloxacin.
Norfloxacin was discontinued, and she was started on intravenous ciprofloxacin, 400 mg every 12 hours.
During the first infusion of ciprofloxacin, the patient became unresponsive, demonstrating decorti- cate posturing with rightward deviation of her gaze.
She had a positive Babinski sign on her left side, and she was unresponsive to confrontation of her right
visual field. Her vital signs were as follows: blood pressure, 170/70 mm Hg; heart rate, 105 beats/min;
respirator y rate, 14 breaths/min; and temperature, 37°C. An electrocardiogram revealed sinus tachycar- dia but was other wise normal. Investigations revealed her white blood cell count was 12.8 x 109/L;
hemoglobin level was 97 g/L, and platelet count was 251 x 109/L. Creatinine level was 271 µmol/L and blood urea nitrogen was 16.8 mmol/L; electrolytes and glucose levels were normal.
A provisional diagnosis of cerebrovascular acci- dent was made, and results of a computed tomogra- phy scan of her head were normal. Over the next 2 hours, her clinical presentation changed dramatically.
She developed facial tics consisting of grimacing and protruding her tongue, an automatism of her right hand, echolalia, and echopraxia. The possibility of an adverse reaction to ciprofloxacin was considered, and the drug was discontinued. She was treated with sup- portive therapy, and within several hours, her neuro- logic status returned to normal.
There were no residual ef fects, although she could not remember some of the events during the ciprofloxacin therapy. She continued to improve and was discharged 7 days after admission to hospital.
Discussion
The acuity and severity of the reaction to ciprofloxacin in this case prompted a literature review of central nervous system (CNS) reactions to this drug. A MEDLINE search was done for articles under the headings “Fluoroquinolones”/adverse effects. Only English articles were reviewed in which
“adverse effects” was a subheading and “nervous sys- tem” could be found. The search found 53 references.
The abstracts were reviewed to identify articles per- taining specifically either to ciprofloxacin or fluoro- quinolones as a class.
Adverse drug reactions to ciprofloxacin occur in about 5% to 10% of patients. They primarily affect the gastrointestinal, renal, and central nervous systems.4,5 Dizziness and headache are reported most commonly, and these abate quickly once the drug is terminated.2-6 Other CNS effects that have been reported include seizures, myoclonus, and hallucinations.4-7One case of Dr MacLeod practises family medicine in Halifax, NS.
This article has been peer reviewed.
Cet article a fait l’objet d’une évaluation externe.
Can Fam Physician 2001;47:553-555.
B
Case report:
Severe neurologic reaction to ciprofloxacin
Wayne MacLeod, MD, CCFP
CME
Severe neurologic reaction to ciprofloxacin
554 Canadian Family Physician•Le Médecin de famille canadien❖VOL 47: MARCH • MARS 2001
delirium has been reported in an AIDS patient treated with ciprofloxacin.8One case of psychosis temporally related to using ciprofloxacin and a single case of a Tourette’s-like syndrome in a patient receiving ciprofloxacin have been reported.3
As in this case, the Tourette’s-like reaction was seen in a patient with multiple medical problems, including compromised renal function.3The seizure- inducing effect of ciprofloxacin is thought to be due to inhibiting γ-aminobutyric acid (GABA) in the CNS.7,8 This inhibition is caused by binding to GABA receptor sites and is a dose-related effect.1 This effect might lower the seizure threshold in sus- ceptible individuals; fluoroquinolones should be used with caution for those with seizure disorders or risk factors for seizures.5Emergence of psychosis and of the Tourette’s-like manifestations suggests that fluoroquinolones might have some central dopaminergic action.3
Several points from the case need further discus- sion. In retrospect, the decision to start the patient on intravenous ciprofloxacin was a clinical error.
Neither the oral nor the intravenous fluoroquinolone doses prescribed took into account the patient’s diminished renal function. Many of the adverse drug reactions described have been associated with reduced renal function.2Elderly patients are espe- cially at risk of excessive dr ug accumulation, because decreased plasma volume contributes to increased drug concentrations.2
Fur thermore, ciprofloxacin has such good bioavailability that intravenous administration is rarely necessar y.1 Finally, not enough time had elapsed between discontinuing the norfloxacin and starting the ciprofloxacin to allow for sufficient fluo- roquinolone clearance given her renal failure. A toxic level of fluoroquinolone could thus have resulted, causing the neurologic side effects.
Neurologic adverse effects with ciprofloxacin have been described with concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), theophylline, and caffeine.6-8Seizures have been reported in patients taking both ciprofloxacin and theophylline.
Ciprofloxacin might inter fere with theophylline metabolism, resulting in higher levels of the drug.7 The epileptogenic potential of ciprofloxacin is enhanced by concomitant use of NSAIDs. All NSAIDs, except acetylsalicylic acid, enhance the inhibition of GABA-receptor binding that has been attributed to the fluoroquinolone group.6 Renal disease induced by NSAIDs might conversely result in impaired clearance of ciprofloxacin and, thus, higher plasma levels.
Conclusion
Because of their wide spectrum of activity, fluoro- quinolones are used to treat a variety of infections that could otherwise be treated with older antibiotics.
Physicians are advised to use the older antibiotics when possible and to reser ve fluoroquinolones for more serious or complicated infections. In addition, their use warrants caution in some patient groups.
The elderly, patients being treated with NSAIDs or theophylline, and patients with underlying seizure disorders need to be monitored carefully. Doses of fluoroquinolones should be adjusted for patients with renal failure. Finally, physicians are reminded to allow adequate time to elapse when switching between medications in the same class to avoid excessive drug accumulation.
Competing interests None declared.
Correspondence to: Dr Wayne MacLeod, 117 Kearney Lake Rd, Halifax, NS B3M 4N9
References
1. LeBel M. Ciprofloxacin: chemistry, mechanism of action, resistance, antimicrobial spectrum, pharmacokinetics, clinical trials, and adverse reactions.
Pharmacotherapy 1988;8(1):3-33.
2. Gantz NM. Quinolones: their use in geriatric infections. Geriatrics 1988;43(Jan):41-7.
3. Thomas RJ, Reagan DR. Association of a Tourette-like syndrome with ofloxacin.
Ann Pharmacother1996;30:138-41.
Editor’s key points
• This case report illustrates an acute neurologic complication of ciprofloxacin used for an elderly patient with renal function impairment.
• Exercise caution using ciprofloxacin for the elder- ly, patients taking NSAIDs or theophylline, and those with impaired renal function or seizures.
• Reserve ciprofloxacin for more serious, compli- cated infections, particularly Pseudomonas.
Points de repère du rédacteur
• Ce rapport de cas met en évidence une complication neurologique aiguë causée par la ciprofloxacine chez un patient âgé souffrant d’une déficience de l’activité fonctionnelle rénale.
• Il faut user de pr udence dans le recours à la ciprofloxacine chez les personnes âgées, les patients qui prennent des AINS ou de la théo- phylline, ceux qui présentent une déficience de l’activité fonctionnelle rénale ou de l’épilepsie.
• Il vaut mieux réserver le recours à la ciprofloxacine aux cas d’infections plus sérieuses et complexes, en particulier celles aux Pseudomonas.
4. Reeves RR. Ciprofloxacin-induced psychosis. Ann Pharmacother1992;26:930-1.
5. Walton GD, Hon JK, Malphur TG. Ofloxacin-induced seizure. Ann Pharmacother 1997;31:1475-7.
6. Rollof J, Vinge E. Neurologic adverse effects during con- comitant treatment with ciprofloxacin, NSAIDS, and chloroquine: possible drug interaction. Ann Pharmacother 1993;27:1058-9.
7. Semel JD, Allen N. Seizures in patients simultaneously receiving theophylline and imipenem or ciprofloxacin or metronidazole. South Med J 1991;84(4):465-8.
8. Schwartz MT, Calvert JF. Potential neurologic toxicity related to ciprofloxacin. DICP 1990;24:138-40.
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