Anaphylactic reaction to ciprofloxacin in a toddler: successful desensitization.

Abstract

Previous studies have shown that ciprofloxacin is generally well-tolerated and is rarely associated with serious or life-threatening adverse reactions.1, 2 From a worldwide total of 9473 patients who received oral ciprofloxacin in clinical trials, only 0.6% had serious adverse effects associated with ciprofloxacin usage.3 Ciprofloxacin is possibly a releaser of histamine from mast cells; therefore differentiating whether a reaction is IgE-mediated or non-IgE-mediated is difficult.4 The overall incidence of anaphylactoid reactions has been estimated at 1.2 per 100 000 prescriptions.5 We describe a 29-month-old girl who developed a first-dose reaction to intravenous ciprofloxacin and who was subsequently successfully desensitized to the drug. Case report. A 29-month-old girl had polymicrobial gluteal abscesses and chronic osteomyelitis of the iliac bone for which she had received several antibiotics including vancomycin, gentamicin, clindamycin and nafcillin without any allergic complications. She developed profound neutropenia while receiving cefotaxime, which resolved after discontinuation of the drug. Because of poor clinical responses to the previous antimicrobial agents, ciprofloxacin (30 mg/kg/day in two divided doses) was added to vancomycin and gentamicin therapy. Within 15 min of the first infusion of ciprofloxacin she developed trembling, headache, tachycardia (heart rate,140/min), flushing, fever (102.3°F) and vomiting. The infusion was immediately stopped and symptoms resolved spontaneously within 1 h. Two days later she developed a generalized maculopapular rash. One week later an intradermal skin test with ciprofloxacin was performed. Prick skin test with 2 mg/ml ciprofloxacin was negative, but a 0.1-ml intradermal test with 0.004 mg/ml ciprofloxacin was positive with a wheal diameter of 9 mm and an erythema diameter of 15 mm. (The 0.004-mg/ml concentration has been shown to be a concentration that avoids a nonspecific skin test response.) The use of ciprofloxacin was considered necessary because the patient had failed to respond to other antimicrobial drugs. Based on the skin test result the reaction was thought to be IgE-mediated; therefore desensitization was performed. The desensitization protocol was started with 0.00001 mg, a 1000-log dilution of the dose causing positive skin test. The intravenous dose was increased first by 10-fold up to 0.01 mg and then by doubling doses up to a dose of 80 mg (Table 1). The doses were diluted in saline and given as continuous 15-min infusions each up to the last 3 doses of 20, 40 and 80 mg which were diluted consecutively in 10, 20 and 40 ml and given as 30-min infusions. There was no time interval between the doses. The vital signs were monitored before each dose. No rash, hypotension or wheezing developed during desensitization. The procedure took almost 6 h. The patient had received an equivalent of her first scheduled dose (160 mg twice daily) as the cumulative dose in the desensitization protocol. The patient subsequently received ciprofloxacin treatment twice daily without complications.TABLE 1: Desensitization regimen for ciprofloxacin Discussion. Ciprofloxacin and other fluoroquinolones are used in children on a risk-benefit basis. Possible uses have included febrile neutropenic episodes, urinary tract infections, chronic suppurative otitis media, exacerbation of cystic fibrosis, Mycobacterium tuberculosis infections, typhoid fever and chronic osteomyelitis as in our patient.6, 7 The tolerability of ciprofloxacin in children is suggested to be similar to that in adults.5 Because of concerns about the potential for fluoroquinolone-induced cartilage damage, data regarding ciprofloxacin use in children and its adverse effects is still limited.5 Our patient had a first-dose reaction with flushing, tachycardia and a delayed onset rash during administration of ciprofloxacin. More severe symptoms such as angioedema and hypotension and reactions such as fever and myalgias associated with ciprofloxacin usage have been reported.8 These reactions have been labeled as anaphylactoid because the majority of them have occurred with the first exposure to the drug and attempts to identify an IgE-based mechanism have been unsuccessful.8 There are occasional reports of anaphylaxis and desensitization in adults.4 Our patient's reaction was classified as anaphylactic because evidence of IgE-mediated sensitization was demonstrated by a positive skin test with a low dose of ciprofloxacin. There are three published cases of anaphylaxis in older children after oral administration of ciprofloxacin.5, 9 To our knowledge this is the first report of anaphylaxis in a young child after intravenous infusion and the first report of successful intravenous desensitization. Fluoroquinolones in children are often reserved for use as a last therapeutic option in most situations. Cross-reactivity among quinolones has been reported and precludes the substitution of one quinolone for another after an allergic reaction.10 We offer this desensitization protocol as a help in these situations; however, modifications in the dosages and rapidity of administration may be necessary and caution should be taken in each individual patient when applying this protocol. Guliz Erdem, M.D. Mary A. Staat, M.D., M.P.H. Beverly L. Connelly, M.D. Amal Assa'ad, M.D. Divisions of Infectious Diseases (GE, MAS, BLC) and Pulmonary Medicine, Allergy and Immunology (AA); Children's Hospital Medical Center; Cincinnati, OH