IgE-Mediated Hypersensitivity in Two Pediatric Patients After Intraoperative Bacitracin Irrigation


 Background: Bacitracin is a common topical antibiotic that is also used for tissue irrigation in the operative setting. While bacitracin is generally well tolerated, Twelve reports of anaphylaxis to intraoperative applications have been published, all in adults.Case presentation: Here, we present the first reported cases of intraoperative Immunoglobulin E-mediated hypersensitivity to bacitracin irrigation in the pediatric population. Both cases were corroborated by allergy testing. Case 1 is a 10 year old male who had surgery to remove an infected tissue expander placed in setting of trauma from motor vehicle accident. Case 2 is a 6 year old female with history of spina bifida who underwent vesicostomy recreation.Conclusions: Bacitracin should be considered a potential occult allergen in the perioperative setting in both adult and pediatric populations.


Background
The incidence of perioperative anaphylaxis is poorly de ned, however it is likely in the range of 1 in 10,000 to 1 in 20,000 procedures. 1 Neuromuscular blocking agents, latex, and antibiotics are the most frequently identi ed etiologies, though approximately 30-40% of cases have no identi ed trigger. [1][2][3] In these scenarios with no clear culprit, other perioperative exposures must be considered.
Bacitracin, a cyclic polypeptide antibiotic, is frequently administered both intraoperatively via wound irrigation as well topically over-the-counter. 4 Bacitracin was rst identi ed in 1943 from Bacillus subtilis culture obtained from the wound of a patient named Tracy-hence the name bacitracin. 5 Due to systemic toxicity, bacitracin is predominantly used in topical preparations either alone or in combination with other antibiotics such as neomycin and polymyxin. While bacitracin is generally well tolerated, reports of anaphylaxis to both topical and intraoperative applications have been published. Twelve cases of intraoperative bacitracin IgE-mediated hypersensitivity have been reported in the medical literature (Table   1). Reactions thus far have been limited to the adult population in a variety of operative settings. 6-9 Of the 12 published cases, 6 reported results of allergy testing (Table 1). IgE mediated reactions to topical bacitracin have also been reported, including in one pediatric patient. 10 We have seen two cases of IgE-mediated bacitracin hypersensitivity corroborated by allergy testing in pediatric patients.

Case Presentation
Case 1 A 10-year-old male underwent abdominal surgery for removal of an infected tissue expander placed in preparation for repair of a large fascial defect as a result of a motor vehicle accident. Sevo urane, midazolam, propofol, rocuronium, fentanyl, and cefazolin were given at induction. Dissection to the tissue expander in the right ank was performed and the pocket was irrigated with bacitracin (200,000 units in 500 mL lactated ringers). This procedure was repeated for the left ank. Acetaminophen, hydromorphone, and phenylephrine were also given. The reaction was noted 150 minutes into the case-2 hours following bacitracin irrigation-as the team was preparing to extubate. The drapes were removed revealing full body urticaria without hemodynamic instability, respiratory symptoms, or gastrointestinal symptoms. Diphenhydramine and cetirizine were administered. Serologic testing obtained 10 minutes after the urticaria were noted showed an elevated plasma histamine at 14 nmol/L (normal 0-8 nmol/L) and normal tryptase at 7.5 mcg/L (normal < 11 mcg/L). The patient was admitted for monitoring and had no further allergic symptoms. Table 2 contains details of allergy testing. Skin prick testing was positive to bacitracin 500 units/ml resulting in a 5 mm wheal and 34 mm are. Negative skin prick testing was noted to cefazolin 20 mg/mL, chlorhexidine 4%, cisatricurium 2 mg/mL, fentanyl 50 mcg/mL, midazolam 5 mg/mL, propofol 10 mg/mL, rocuronium 10 mg/mL, sugammadex 100 mg/mL, and mixture of rocuronium 10 mg/mL and sugammadex 100 mg/mL. Intradermal testing was negative to cefazolin 2 mg/mL, cisatricurium 0.02 mg/ml, fentanyl 5 mcg/mL, midazolam 0.5 mg/mL, propofol 1 mg/mL, rocuronium 0.05 mg/mL, sugammadex 1 mg/mL, and mixture of rocuronium 0.2 mg/mL and sugammadex 2 mg/mL.

Case 2
A 6-year-old female with a medical history of spina bi da with multiple sequelae and egg allergy underwent vesicostomy recreation. Lidocaine, propofol, fentanyl, morphine, cisatracurium, midazolam, sevo urane, and nitrous oxide were given at induction. Cystoscopy was performed followed by ureteral reimplantation with subsequent laparotomy for vesicostomy recreation. Bacitracin irrigation (50 units/mL in normal saline) occurred at 165 minutes. At 255 minutes, shortly after the patient received both cefoxitin and metronidazole, the patient became hypotensive and tachycardic without rash, change in airway pressure, or gastrointestinal symptoms. Hypotension and tachycardia were refractory to both crystalloid uid resuscitation and ephedrine but improved after epinephrine. The case was aborted before vesicostomy revision, and the patient was admitted to the Pediatric Intensive Care Unit on an epinephrine continuous infusion. Serum histamine and tryptase obtained 2.5 hours after the reaction were both normal (< 8.0 nmol/L and 3.9 mcg/L respectively). The patient was weaned from epinephrine infusion and extubated later that day with no further reaction. Notably, testing was negative to cefoxitin (100 mg/mL skin prick test, 10 mg/mL intradermal), and the patient had subsequently tolerated metronidazole without reaction. Bacitracin gave a negative reaction to skin prick test, but intradermal testing to 50 units/ml bacitracin was positive with a 10 mm wheal and 25 mm are. Testing was negative to cisatriciurim (2 mg/mL skin prick test, 0.2 mg/mL intradermal). Additional testing to lidocaine, propofol, midazolam, and fentanyl were deferred as the patient had subsequently tolerated these medications. Table 2 contains details of allergy testing.
Both patients had bacitracin labeled as an allergy and have since undergone subsequent procedures with general anesthesia without further reactions.

Discussion And Conclusions
We believe these are the rst reported cases of intraoperative IgE-mediated bacitracin hypersensitivity in the pediatric population. While contact dermatitis reactions to bacitracin are well recognized 17 , IgE-mediated allergic reactions to this antibiotic are rare. It can affect pediatric patients and should be considered as a potential occult allergen. This is especially true in the operative setting as irrigants are not administered by anesthesia teams and therefore may not be reported in the anesthesia documentation. In each case, the bacitracin reaction occurred with the rst intraoperative exposure to the medication. However, both patients had previously received topical bacitracin prior to their surgeries and may have become sensitized via this exposure. Patients who have had an allergic reaction to bacitracin may be at risk for subsequent reactions to topical preparations including products intended for use in the eyes, nose, ears and skin 6 . Patients should be instructed to read labels of topical antibiotic products and to avoid using products containing bacitracin. Over-the-counter, bacitracin is combined with polymyxin B (brand name: Double antibiotic, Polysporin), polymyxin B and neomycin (Triple antibiotic, Neosporin), polymyxin B, neomycin, and pramoxine (Neosporin + Pain Relief, Tri Biozene), and polymyxin B, neomycin, and hydrocortisone (Corticosporin). In ophthalmic formulation by prescription, bacitracin is combined with polymyxin B (brand name: AK Poly-Bac, Polycin), polymyxin B and neomycin (Neo-Polycin), and polymyxin B, neomycin, and hydrocortisone (Neo-Polycin HC) 18 . These formulations are summarized in Table 3. There are no reports of bacitracin cross-reactivity to other antibiotics, so use of alternative antibiotics should be feasible for patients with history of allergy to bacitracin.