Fatal Case of Toxic Epidermal Necrolysis Caused by Cefozopran and Associated with Psoriasis

Abstract

Cefozopran is a fourth-generation cephem antibiotics and has a broad spectrum of antibacterial activity, inhibiting most of the gram-negative and gram-positive organisms and is used as an antibiotic agent for the empirical treatment of bacterial infections in febrile neutropenia patients (1). There have been several case reports of mild cutaneous side effects, such as exanthema, due to cefozopran, however, no severe drug eruption by cefozopran has been documented in English literature. Herein, we report the first case of toxic epidermal necrolysis (TEN) caused by cefozopran.CasE REpoRT a 71-year-old woman was referred to our department for evaluation of a generalised eruption. she had been treated for psoriasis with narrowband ultraviolet B light intermittently for 10 years. Because of pyelonephritis and septicaemia, she received cefozopran, which gradually improved her general condition. However, 7 days after intravenous administration of 1 mg cephozopran twice daily, she developed a widespread skin eruption accompanied with a high fever, 39°C. she had no medication other than cefozopran and no history of allergy to any medicine. on physical examination, erosions and scaly crusts spread widely on the chest (Fig. 1), back, and extremities involving more than 70% of body surface area. The oral mucosa was also affected and Nikolsky sign was positive. Laboratory examination revealed C-reactive protein 14.53 mg/dl (normal < 0.2 mg/dl), fasting serum glucose 469 mg/dl (normal 126 mg/dl), blood urea nitrogen (BUN) 39 mg/dl (normal 8-22 mg/dl). Her SCORTEN score was 4 points (age > 40 years, serum BUN > 27 mg/dl, blistering body surface > 10%, serum glucose > 250 mg/dl). We performed lymphocyte stimulation test with cefozopran as described previously (2, 3). 3 H-thymidine incorporation was significantly increased by the addition of 1.6×10 -7 M cefozopran (corresponding to C max for intravenous dosing) to the peripheral lymphocyte culture with a stimulation index of 4.2 (Fig. 2). Three normal volunteers showed negative results. Histological evaluation was difficult for this patient because of the detached epidermis in skin biopsy specimen. The patient did not give consent to another biopsy, and direct immunofluorescence could not be performed. We diagnosed her eruption as TEN caused by cefozopran. Although Fig. 1. Erosive and ulcerative lesions on the chest 7 days after starting cefozopran.Fig. 2. The patient's peripheral blood mononuclear cells (2×10 5 /well) taken at the initial visit and were cultured for 72 h in a 96-well plate with cefozopran at 3 different concentrations.

Acute Generalized Exanthematous Pustulosis Caused by Faropenem: A Possible Pathogenetic Role for Interleukin-23

“…To our knowledge, this is the first report of drug eruption, specifically AGEP, caused by faropenem. AGEP is caused by a variety of medicines and has been reported as exemplified by antibiotics (5,7). In our patient, the apparently positive LST with faropenem confirmed the causative drug.…”

“…1B). A lymphocyte stimulation test (LST) was performed, as described previously (5)(6)(7). 3 H-thymidine incorporation was significantly increased by the addition of 6.7×10 -6 M faropenem (corresponding to C max ) to the peripheral lymphocyte culture, with a stimulation index of 1.8 (Fig.…”

Photodistributed Stevens–Johnson syndrome and toxic epidermal necrolysis: a systematic review and proposal for a new diagnostic classification

“…This case was excluded due to limited case information (only description was in a figure legend), and no causal drug or timeline of sun exposure was provided. Two studies reported patients with past histories of psoriasis who regularly received treatments of ultraviolet-B light and experienced fatal cases of TEN, one after seven days on cefozopran and the other 16 days after starting etretinate [ 131 , 132 ]. These cases did not meet inclusion criteria because the studies did not report whether the patient received ultraviolet-B light therapy after starting the causal drug.…”

Diagnostic Tools and Biomarkers for Severe Drug Eruptions

“…The pathogenesis of drug eruption is classified into allergic and non-allergic reactions [ 13 ]. In an allergic reaction, the majority of drug eruption is mediated by type IV delayed hypersensitivity reaction, and the importance of this mechanism is proven by commonly used patch testing and lymphocyte stimulation test for the diagnosis [ 14 , 15 , 16 , 17 ]. On the basis of the pathogenesis, type IV delayed hypersensitivity reaction consists of two phases, namely, sensitization and elicitation ( Figure 1 ) [ 9 , 18 ].…”