We report a fatal case of WFS due to bacteremia with C. canimorsus in a 61-year-old asplenic female.
The patient was bitten on the third finger of the right hand by her own dog, and developed cephalgia, nausea and diarrhea on the same day. She was admitted to the nearest hospital (Fig. 1) and covered with piperacillin/tazobactam (4 g/0.5 g tid) and gentamicin (320 mg qd).
The history of the patient revealed a systemic Lupus erythematodes (without immunosuppressive therapy), arterial hypertension, mitral valve regurgitation, angiodysplasia of the colon with recurrent hemorrhages, polyarthrosis and fibromyalgia. The patient had been splenectomised in the 1980s for an unknown reason.
Within 24 h, a massive platelet drop and an INR elevation in the sense of disseminated intravascular coagulopathy (DIC) occurred. Similarly, purpura developed, especially in the face and upper trunk. Because of the purpura, WFS was suspected and antibiotic therapy was changed to ceftriaxone and ampicillin after obtaining microbiological samples.
Blood cultures (BD, Heidelberg) turned positive 16.5 h after incubation in an automated blood culture system (Bactec, BD, Heidelberg) and revealed Gram-negative rods by Gram staining. Cultures remained negative despite three repeated attempts every second day on Columbia blood agar and Chocolate agar (incubation at 37 °C with 5% CO2; both agars from Oxoid, Wesel, Germany), Schaedler agar (anaerobic incubation at 37 °C; Oxoid, Wesel, Germany) and MacConkey agar (aerobic incubation at 37 °C; Oxoid, Wesel, Germany). Additionally, at admission to the hospital, the patient was tested positive for SARS-CoV-2 on a rapid antigen diagnostic test (Ag-RDT), which was not verified by SARS-CoV-2 nucleic acid amplification.
Subsequently, a progressive decrease in vigilance occurred, whereupon the patient was transferred to the intensive care unit of the University Hospital Münster, a tertiary care hospital.
On arrival, she was in septic shock with ubiquitous purpura fulminans. She had a massive cytokine release syndrome (IL-6: 140,000 ng/mL), procalcitonin of 138 ng/mL, type A lactic acidosis, and severe DIC. The patient received extensive therapy, including mechanical ventilation, antibiotic coverage with meropenem (2 g qid as prolonged infusion), clindamycin (900 mg tid) and ampicillin (3 g qid), systemic corticosteroids (methylprednisolone 500 mg tid, 250 mg bid, 250 mg qd, 125 mg qd), vasopressor therapy, continuous renal replacement therapy (with additional Seraph® 100 Microbind® Affinity Blood Filter, ExThera Medical). Patients with acquired protein C deficiency may develop purpura fulminans. Therefore, during plasmapheresis in total around 40 units of Fresh Frozen Plasma had been administered as a source of protein C. Septic cardiomyopathy was managed by implantation of a veno-arterial extracorporeal membrane oxygenation (vaECMO).
While the patient initially stabilized clinically, her condition worsened quickly 5 days after admission. In the course of the disease, the patient developed dry perioral and acral necroses on the right and left hand and a paralytic ileus (Fig. 2). She finally died 10 days after the dog bite due to refractory septic shock with WFS.
Blood cultures collected on the day the patient died were positive for Candida albicans, which was interpreted as a mycetal superinfection most likely due to transmigration of Candida due to the paralytic ileus.
The autopsy showed bilateral hemorrhagic necrosis of the adrenal cortex (Fig. 3), septic embolism to heart, kidneys, and liver with mycetal superinfection. Consequently, the patient was diagnosed with WFS. A minor, superficial skin defect in the area of the right middle finger after the dog bite classified as grade I using the Rueff classification of animal bites was considered as the port of entry for the pathogen [17].
Post-mortem, blood culture bottles obtained at the referring hospital were sent to our microbiology laboratory for detailed analysis. We confirmed long, thin, Gram-negative rods after Gram staining (Fig. 4). Within 48 h, small, greyish, sharply defined colonies were visible on BBL Columbia blood agar with 5% sheep blood (BD, Heidelberg, Germany) after incubation at 37 °C under 5% CO2. Identification based on MALDI-TOF (Bruker, Bremen, Germany) revealed C. canimorsus. Antibiotic susceptibility testing was performed using Epsilometric tests (Etest®, biomérieux, France) in accordance to the European Committee on Antimicrobial Susceptibility Testing (EUCAST; version 10.0) and minimal inhibitory concentrations (MIC) were interpreted using non-species related clinical breakpoints. As there was no growth on standard agar plates for antibiotic susceptibility testing (Mueller Hinton agar or Mueller Hinton agar with horse blood), BBL Columbia blood agar with 5% sheep blood was used. The isolate was susceptible to penicillin (MIC: 0.047 mg/L), ceftriaxone (MIC: 0.19 mg/L) and meropenem (MIC: 0.004 mg/L).
In order to confirm that the unsuccessful culture in the referring laboratory was due to different manufacturers of Columbia blood agar, we compared the growth of C. capnocytophaga on Columbia blood agar using our standard media and the standard media from the referring laboratory. Varying results (weaker respectively absent growth on agar plates from Oxoid) were confirmed (Fig. 5). We were unable to identify the reason for the discrepant growth on agar plates from different manufacturers. The classical formula of both agar plates showed the same composition of ingredients.