Severe local vancomycin induced skin necrosis

Vancomycin is a glycopeptide antibiotic with activity against gram-positive bacteria, used in the treatment of endocarditis, as an alternative to penicillin in the case of allergy and is the drug of choice for the treatment of infections due to methicillin-resistant staphylococci (MRSA). With the increase of MRSA infections, the use of vancomycin is on the rise. Vancomycin use is estimated at 3.5/100 admissions in the Netherlands [1].

Vancomycin has been documented to cause a variety of adverse reactions that can be roughly divided into two groups. The first is related to an acute release of histamine and is also called vancomycin pseudo-allergic reaction [2]. A well-known example is the Red Men Syndrome (RMS) with an incidence 1–10%. Clinical signs are erythematous or maculopapular rash on face, upper body and extremities, in some cases accompanied by hypotension [3, 4]. The causative mechanism is related to a direct release of histamine by vancomycin or coproducts. This reaction is not IgE mediated. RMS is often associated with the speed of the infusion. Antihistamines, epinephrine and corticosteroids can reduce this reaction. Desensitization is an option for these pseudo-allergic reactions like RMS, IgA dermatosis and Stevens–Johnson syndrome if no other therapy is available [5, 6]. The second group of adverse reactions is related to a hypersensitivity reaction caused by IgE mediated histamine release and can occur in up to 5% of patients [6, 7]. The third group of adverse reactions consists of a heterogeneous mix which include ototoxicity, nephrotoxicity, drug-induced fever, neurological, haematological, gastrointestinal and various dermatological reactions [8]. The mechanism of these reactions is not clear but some may be due to impurities in the vancomycin.

We would like to describe a new adverse effect of vancomycin.

A 63 year old woman was admitted to the ICU after an emergency laparotomy for an anastomotic leakage after hemicolectomy. Peritoneal cultures became positive for Enterococcus faecium for which intravenous vancomycin therapy was started, using an IV line in the dorsum of the left foot due to difficulty in obtaining peripheral venous access. After 48 h, a progressive skin lesion was noted in the regional vascular bed of the IV line and the left leg was swollen and red (Figure 1). An ischaemic lesion developed after 72 h. The line was tested for patency, working appropriately and not running subcutaneously. No other drugs were given over the IV line and a 0.9% saline drip was running. After discontinuation of the vancomycin and removal of the IV line the lesions regressed and recovered gradually over several weeks. Four weeks later vancomycin administered through a subclavian central venous catheter did not cause any adverse effects.

Figure 1.

Left foot with ischaemic lesions after vancomycin infusion in the flow area of the vein. Double arrow venous access point

Phlebitis can occur in up to 3–13% in patients with a peripheral venous line. Vancomycin is an irritating drug most likely because of its low pH (2.8–4.5), which has a direct irritant effect on the vascular wall [9]. Therefore, the most likely cause of the skin necrosis was a leakageof the i.v. line or capillary leakage, with drug extravasation causing necrosis. An allergic or generalized reaction did not occur after rechallenge of vancomycin. This adds to the likelihood of a local irritant aetiology. In addition, although drug-induced bullous dermatosis and more generalized toxic epidermal necrolysis have been related to vancomycin use, local nonbullous vancomycin-induced skin necrosis as encountered in our patient has not been reported before [10, 11].

If vancomycin is administered via a peripheral line, regular checks for phlebitis and skin necrosis are advised.