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Vancomycin and Red Man Syndrome Vancomycin can cause two types of hypersensitivity reaction – the red man syndrome and anaphylaxis. 'Red man Syndrome' is thought to be an infusion-related reaction consisting of pruritus, an erythematous rash involving the face, neck and upper torso. Patients commonly complain of the sensations of burning and itching. Agitation, dizziness, headaches, chills, fever and perioral paresthesia are also described.

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The incidence of red man syndrome varies between 3.7% and 47% in infected patients []. The 'Red Man Syndrome' seen in association with intravenous vancomycin administration is not a true allergic reaction. It appears to be due to vancomycin-induced histamine release without involvement of preformed antibodies []. In animal models, vancomycin provokes histamine release from rat peritoneal mast cells []. There is evidence of reduced side effects associated with vancomycin when antihistamines are given with therapy. In a prospective, randomized, double-blind, placebo-controlled study in 30 patients who required vancomycin chemoprophylaxis before elective arthroplasty, oral pre-treatment with either a histamine H1 receptor antagonist (diphenhydramine 1 mg/kg) or a histamine H2 receptor antagonist (cimetidine 4 mg/kg) significantly reduced the histamine-related adverse effects of rapid vancomycin infusion []. Hypothesized mechanism of reaction It is generally understood that systemic bioavailability of orally administered vancomycin is negligible [].

In one study, after 7 doses of oral vancomycin 250 mg every 8 hours in healthy volunteers, no vancomycin concentrations were detected in serum (sensitivity limit 0.64 micrograms/ml) or urine []. However, the presence of an inflammatory bowel process can result in increased absorption of oral vancomycin []. In patients with pseudomembranous colitis and severe renal failure, several studies have revealed that orally administered vancomycin may occasionally reach therapeutic concentrations in serum and even pose a risk of systemic toxicity [,].

In one of these case reports an anephric girl with C. Difficile pseudomembranous colitis received oral vancomycin 250 mg every 6 hours.

She developed unexplained fever and encephalopathy. Sustained serum vancomycin concentrations of 34 micrograms/ml were recorded, with Cerebrospinal fluid (CSF) concentrations of 4.3 microgram/ml.

Discontinuation of the drug, along with haemodialysis caused the serum concentration to fall to 24 microgram/ml with resolution of the symptoms []. Case presentation The patient, an 82 year old Caucasian woman, was admitted to hospital with confusion. She had a number of active medical problems, including atrial fibrillation, ischaemic heart disease, chronic kidney disease, hypertension and osteoarthritis. Six years prior to admission she had undergone a right hemicolectomy for Dukes B colorectal carcinoma. During admission she was diagnosed as having a urinary tract infection (UTI).

Prior to admission her general practitioner had treated the patient with a 3 day course of trimethoprim 200 mg bd. On admission to hospital, urine culture was positive for Escherichia. Coli and she was prescribed a 5 day course of oral co-amoxiclav 625 mg tds. Four days following completion of this course of antibiotics, she developed diarrhoea, which was positive for Clostridium difficile toxin. Metronidazole 400 mg tds was prescribed immediately. The patient's diarrhoea worsened, she was opening her bowels 7 times daily with a Bristol Stool classification Type 7 stool.

After five days of oral metronidazole therapy, oral vancomycin 250 mg qds was started. Four days after oral vancomycin therapy was instigated, the patient developed a widespread pruritic, confluent, erythematous rash over her chest, back, neck and thighs. She also complained of a severe headache.

Dermatology review was requested and the opinion was that the rash appeared to be like that seen in 'Red Man Syndrome'. It was confirmed with nursing staff that no drug errors had been made and no vancomycin had been administered intravenously in error. Vancomycin therapy was stopped immediately and regular antihistamines were prescribed. The rash then cleared and did not return. Rechallenge with oral vancomycin was not initiated. No other drug therapy was altered during this time, and no other potential allergens could be indentified. On admission the patient had Chronic Kidney Disease (CKD) stage 2.