Ciprofloxacin

Observational studies

Antimicrobial prophylaxis to prevent inhalational anthrax has been recommended for people potentially exposed to Bacillus anthracis as a result of recent bioterrorist attacks. Of 3428 people taking ciprofloxacin, 666 (19%) reported severe nausea, vomiting, diarrhea, or abdominal pain; 484 (14%) reported fainting, light-headedness, or dizziness; 250 (7%) reported heartburn or acid reflux; and 216 (6%) reported rashes, hives, or an itchy skin. Of those taking ciprofloxacin, 287 (8%) stopped taking it, 116 (3%) because of adverse events, 27 (1%) because of fear of possible adverse events, and 28 (1%) because they “did not think it was needed” [ ].

The imaging of inflammation/infection with 99mTm-labeled ciprofloxacin in 96 patients had a sensitivity of 81% and specificity of 87%. The positive and negative predictive values were 90% and 75% respectively. No adverse reactions were reported [ ].

In a post-marketing surveillance study in 3859 hospitalized patients with urinary tract infections, 136 (3.5%) had 181 adverse events; 106 of them (2.8%) had 138 adverse events that were possibly or probably related to ciprofloxacin [ ]. The most frequent adverse events that were considered drug-related were diarrhea (1.7%), rash (0.3%), nausea (0.2%), allergic reactions (0.2%), pruritus (0.2%), vomiting (0.1%), and abnormal tests of liver function (0.1%). There were severe adverse events in 26 patients (0.7%).

Comparative studies

In a multicenter, double-blind study of 234 patients with acute bacterial exacerbations of chronic bronchitis, ciprofloxacin (500 mg bd) was associated with a trend toward a longer infection-free interval and a significantly higher bacteriological eradication rate compared with clarithromycin (500 mg bd) after 14 days [ ].

In a double-blind study, ciprofloxacin (500 mg bd) was associated with an infection-free interval and clinical response that were similar to those achieved with cefuroxime axetil (500 mg bd), but the bacteriological eradication rate associated with ciprofloxacin was significantly higher [ ].

Cardiovascular

Ciprofloxacin causes prolongation of the QT interval [ , ].

The risk of ciprofloxacin-associated torsade de pointes [ ] appears to be low, but caution is still warranted when it is given in the presence of pre-existing QT prolongation.

• A 70-year-old woman who was taking azathioprine, olanzapine, and valsartan developed marked QT interval prolongation after the intravenous administration of ciprofloxacin 800 mg/day. Ciprofloxacin was immediately replaced by a third-generation cephalosporin, and during the next few days the QT interval gradually returned to normal [ ].

• Torsade de pointes and QT interval prolongation occurred when intravenous ciprofloxacin was given to a 22-year-old healthy man with pneumonia [ ].

• Cardiac arrest temporally related to ciprofloxacin occurred in two women (aged 44 and 67 years) when they developed marked QT _c interval prolongation (590 and 680 ms) within 24 hours of ciprofloxacin administration, with recurrent syncope and documented torsade de pointes requiring defibrillation [ ]. The QTc interval normalized after withdrawal of ciprofloxacin.

• A 76-year-old man with acute on chronic renal insufficiency, developed torsade de pointes in combination with hypocalcemia, triggered by hemodialysis [ ]. The QT interval prolongation was corrected by treating the hypocalcemia.

Respiratory

Ciprofloxacin can cause interstitial pneumonitis with acute respiratory failure.

• A 68-year-old woman developed severe respiratory failure 6 days after taking ciprofloxacin. C-reactive protein rose she had an intermittent high fever, dyspnea, and severe hypoxemia [ ]. Bronchoalveolar lavage was consistent with hypersensitivity pneumonitis. Her symptoms rapidly improved with systemic glucocorticoid therapy.

Nervous system

Headache was recorded in 8% of patients taking ciprofloxacin [ ].

Ciprofloxacin can cause confusion and general seizures [ , ] and can exacerbate the risk of seizures in epilepsy.

• A 65-year-old woman on peritoneal dialysis had recurrent generalized tonic-clonic seizures while taking Ciproxin ear drops (ciprofloxacin 2 mg, hydrocortisone 10 mg) for otitis media. She had a seizure-free period of 9 months after she stopped using the eardrops, despite tapering of the dose of sodium valproate [ ].

Ciprofloxacin might have prolonged a seizure associated with electroconvulsive therapy in a patient with a urinary tract infection [ ].

• A 43-year old woman developed a subacute confusional state and involuntary movements after being given ciprofloxacin, cephalexin, and co-amoxiclav after an insect bite [ ]. The antibiotics were withdrawn. She later had two generalized tonic–clonic seizures.

Ciprofloxacin can cause propriospinal myoclonus by inhibiting gamma-aminobutyric acid metabolism [ ].

Ciprofloxacin can cause facial dyskinesia [ , ].

Two cases of generalized painful dysesthesia associated with ciprofloxacin have been reported [ ].

An 84-year-old woman was given ciprofloxacin 500 mg bd for a wound infection but took it four times a day by mistake. After 3 days she developed slurring of speech and a palatal tremor. Ciprofloxacin was withdrawn and valproate was started. The symptoms resolved within 2 days [ ].

Sensory systems

Psychiatric

The administration of ciprofloxacin has been associated with psychosis [ , ] and hypoactive delirium [ , ].

• A 27-year-old woman developed an acute psychotic reaction following the use of ciprofloxacin eye-drops (one drop hourly to each eye) [ ].

• A 28-year-old white man with a history of primary sclerosing cholangitis and controlled ulcerative colitis developed signs of suppurative cholangitis and was treated with intravenous metronidazole 500 mg bd, intravenous cefazolin 1 g 8-hourly, intravenous ciprofloxacin 400 mg bd, Gravol 25–50 mg 4-hourly, ursodeoxycholic acid 1500 mg bd, and folate 1 mg/day [ ]. On day 1, sulfasalazine 300 mg tds was added and increased on the next day to 1000 mg tds. He improved quickly. On day 5, all medications were discontinued, except ciprofloxacin 500 mg bd. The next day, he became agitated and violent. He was highly irritable, expansive, and grandiose, wanting to publish a book and run a religious mission. He was given piperacillin + tazobactam 4.5 g qds, thiamine 100 mg, and aciclovir 600 mg 8-hourly. Ciprofloxacin was withdrawn, and he was given intramuscular haloperidol 5 mg every 4–6 hours as required and sublingual lorazepam 1 mg 8-hourly. He was then given olanzapine 5 mg bd, the dose of haloperidol was reduced to 2.5 mg 2-hourly (maximum 10 mg/day), and all other medications were withdrawn. On the next day, he had increased delusional thought content and expansive mood. By day 15, he was alert and oriented, with no delusions or persisting hostility, and with insight into his previous mental disturbance.

• A 45-year-old man without previous mental disorders developed an acute delusional parasitosis after taking ciprofloxacin. He had a complete sustained remission within a few days after withdrawal of ciprofloxacin, without the use of any other medication [ ].

• Psychosis occurred in a 32-year-old woman who was taking ciprofloxacin for multidrug resistant tuberculosis; the symptoms resolved within 48 hours after the ciprofloxacin was withdrawn [ ].

Hematologic

Ciprofloxacin has been associated with hemolysis in combination with a severe skin reaction in a young adult [ ].

Fatal ciprofloxacin-associated thrombotic thrombocytopenic purpura [ ] and thrombocytopenia [ ] have been reported.

Treatment with ciprofloxacin and piperacillin/tazobactam was associated with thrombocytosis in a 50-year-old man [ ].

In two patients with cystic fibrosis the INR and activated partial thromboplastin time rose after ciprofloxacin treatment and returned to normal after withdrawal [ ].

• In a 29-year-old woman the INR rose from 1.0 to 3.4 within 2 days of treatment with intravenous ciprofloxacin 400 mg bd. The activated partial thromboplastin time (aPTT) rose from 22 seconds while she was receiving subcutaneous enoxaparin to 41 seconds. Ciprofloxacin was changed to ceftazidime and both values returned to baseline within 24 hours.

• In an 18-year-old woman with a high serum creatinine and normal liver function, the INR was 2.6 and the aPTT 45 seconds after she had taken oral ciprofloxacin 1 g bd and rifampicin 300 mg bd for 5 days; the INR returned to baseline 1 week later and the serum creatinine 3 weeks later.

Gastrointestinal

In a randomized, double-blind comparison of prulifloxacin 600 mg/day and ciprofloxacin 500 mg bd in 235 patients with acute exacerbations of chronic bronchitis, the most common treatment-related adverse event was gastric pain of mild or moderate intensity, reported in 8.5% of the patients taking prulifloxacin and 6.8% of those taking ciprofloxacin [ ].

Ciprofloxacin has been associated with diarrhea due to Clostridium difficile [ ]. In 27 patients the only significant risk factor for nosocomial C. difficile -associated diarrhea was the use of ciprofloxacin [ ].

Liver

Ciprofloxacin causes a mild reversible rise in liver enzymes in 2–3% of patients. Acute hepatitis is rare, but has been reported in a 32-year-old man [ ].

There is increasing evidence that ciprofloxacin can cause severe liver damage, and 14 cases have been reported.

• A 22-year-old man took ciprofloxacin 500 mg/day and developed acute liver failure 14 days later [ ]. Liver biopsy showed extensive hepatocellular necrosis. His symptoms resolved after glucocorticoid therapy.

• Severe liver injury was associated with ciprofloxacin 500 mg bd in a 79-year-old woman with a Gram negative infection; she developed a metabolic acidosis 48 hours after the first dose and her symptoms resolved after withdrawal [ ].

Three cases of ciprofloxacin-induced liver damage have been reported.

• A 65-year-old man with an ischemic cardiomyopathy developed acute cholestatic jaundice with liver failure and acute renal failure requiring hemodialysis after taking ciprofloxacin 500 mg bd for 6 days for cellulitis [ ]. A liver biopsy was consistent with drug-induced liver damage. After withdrawal of ciprofloxacin his renal function improved and the liver tests normalized within 5 months.

• A 26-year-old man developed jaundice, weakness, and anorexia preceded by a rash after taking ciprofloxacin for 5 days for diarrhea; the liver enzymes gradually normalized over 6 months [ ].

• A 39-year-old woman with a diverticular abscess was given oral ciprofloxacin 500 mg bd and metronidazole 500 mg bd for 14 days and developed nausea, icterus, and raised liver enzymes [ ]. A liver biopsy showed infiltration of the portal tracts by a mixed inflammatory infiltrate with prominent eosinophils. She was given tapering doses of prednisone and the liver enzymes normalized over 3 months.

Pancreas

A report has suggested that ciprofloxacin can cause pancreatitis [ ].

Urinary tract

Ciprofloxacin can cause acute interstitial nephritis, as in the case of an 81-year-old man with diabetic nephropathy [ ].

• A 77-year-old man developed interstitial nephritis after taking ciprofloxacin for an infected knee-prosthesis; withdrawal led to recovery of renal function [ ].

Acute renal failure secondary to ciprofloxacin crystal nephropathy has been reported.

• A 90-year-old woman had surgery for a perforated duodenal ulcer and was given ciprofloxacin 750 mg bd for a respiratory infection [ ]. After 8 days her serum creatinine rose to 140 μmol/l (1.6 mg/dl) and she developed oliguria. The fractional sodium excretion was 2%, the urine pH was 6.5, and the urine sediment showed granular casts, epithelial cells, and needle-shaped birefringent crystals in round conglomerates. There was no eosinophilia and no urinary leukocytes. Intravenous fluids had no effect on urine output. Ciprofloxacin was withdrawn and the oliguria resolved over the next day. The serum creatinine peaked at 336 μmol/l (3.8 mg/dl) and returned to baseline within 10 days.

• A 58-year-old woman developed acute renal insufficiency after taking ciprofloxacin 1 g without any other identifiable risk factor [ ]. Renal biopsy showed no evidence of interstitial nephritis, but there were tubular lesions and deposits of a brown-yellowish substance, which was identified as ciprofloxacin salt. The outcome was favorable.

Two cases of acute renal insufficiency due to necrotizing vasculitis associated with ciprofloxacin were reported in elderly patients [ ]. In two patients who underwent high-dose chemotherapy with autologous stem cell rescue, acute renal insufficiency developed while they were taking prophylactic ciprofloxacin; withdrawal resulted in prompt reversal of renal insufficiency [ ]. Ciprofloxacin-induced acute renal insufficiency has been reported in cancer patients undergoing high-dose chemotherapy and autologous stem cell rescue [ ]. A case report has suggested that ciprofloxacin overdose can lead to acute renal insufficiency characterized by acute tubular necrosis with distal nephron apoptosis [ ].

• An 18-year-old woman with cystic fibrosis had pronounced impairment of renal function after taking oral ciprofloxacin 750 mg tds (30 mg/kg/day) for 3 weeks; withdrawal led to normalization of renal function within 10 days [ ].

Hemolytic-uremic syndrome has been attributed to ciprofloxacin [ ].

• A 53-year-old white man was given chemotherapy for acute lymphoblastic leukemia and after 4 weeks recovered his blood cell count but developed a fever and was given oral ciprofloxacin 500 mg bd. After four doses he developed the typical features of hemolytic-uremic syndrome with microangiopathic hemolytic anemia. The ciprofloxacin was withdrawn, and he received five sessions of plasma exchange. He recovered completely.

Bilateral hydronephrosis and acute renal insufficiency due to urinary tract stones predominantly composed of ciprofloxacin has been reported [ ].