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Severe sepsis caused by Capnocytophaga canimorsus complicated by thrombotic microangiopathy in an immunocompetent patient

Case A 61‐year‐old man with an unremarkable medical history was admitted with fever 7 days after being bitten by his dog. On day 3, he showed altered mental status, and laboratory data showed progressive hemolytic anemia, thrombocytopenia, hyperbilirubinemia, renal dysfunction, coagulopathy, and schistocytosis. Severe sepsis complicated with thrombotic microangiopathy caused by Capnocytophaga canimorsus was suspected. Outcome Plasma exchange was applied to treat the thrombotic microangiopathy and resulted in platelet count increase and improved renal function, hyperbilirubinemia, and schistocytosis. Blood culture results confirmed the presence of C. canimorsus. The patient was discharged in good condition. Conclusion Capnocytophaga canimorsus is rare cause of severe sepsis, and should be suspected even in immunocompetent patients with dog‐bite history. Capnocytophaga canimorsus infection may be complicated by thrombotic microangiopathy, for which plasma exchange should be considered prior to definitive diagnosis of thrombotic microangiopathy.

C APNOCYTOPHAGA CANIMORSUS (C. canimorsus), a facultative anaerobic, gram-negative bacteria, is found in the normal oral flora of dogs. This bacterium, commonly transmitted by dog bites, can cause severe sepsis, especially in immunocompromised patients, and the overall mortality rate is reportedly approximately 30%. 1,2 Dogs are one of the world's most popular pets. Thus, health care providers should recognize this pathogen and disease.
Severe C. canimorsus sepsis can be complicated by thrombotic microangiopathy (TMA), which requires specific treatment such as plasma exchange (PE), plasma transfusion, and molecular-targeted drugs. 1,3,4 However, C. canimorsus is difficult to isolate and identify. 2 Therefore, the diagnosis of C. canimorsus infection and the associated TMA in patients with severe sepsis may be missed and appropriate treatment may be delayed. Here we present a case of severe sepsis caused by C. canimorsus complicated by TMA in an immunocompetent man who was bitten by a dog, and underwent PE based on presumptive diagnosis with effective improvement of his pathological status.

CASE
A 61-YEAR-OLD MAN with an unremarkable medical history was admitted to a nearby local hospital for a high fever that developed 7 days after being bitten by his dog. Capnocytophaga canimorsus sepsis was the clinically assumed diagnosis, despite no evidence of an immunocompromised history, and the patient received antibiotic therapy. For diagnostic confirmation, a blood sample was sent to the National Institute of Infectious Diseases for †These authors contributed equally to this work. polymerase chain reaction (PCR) testing. The day after admission, he developed renal dysfunction (serum creatinine, 4.96 mg/dL and anuria) and thrombocytopenia (14,000/lL). Therefore, he was transferred to our institution for intensive care. On admission, he had no consciousness disturbance, and normal vital signs (respiratory rate, 12/min; heart rate, 74 b.p.m.; blood pressure, 126/ 80 mmHg; and body temperature, 36.7°C). His left little finger had a black wound from the dog bite, without obvious local sign of infection. Laboratory data revealed leukocytosis (11,700/lL), thrombocytopenia (3,000/lL), a high level of lactate dehydrogenase (5673 U/L), acute kidney injury (serum creatinine level, 6.54 mg/dL, anuria), and coagulopathy (fibrin/fibrinogen degradation products, 56.6 lg/dL). The fibrinogen level was not decreased (296 mg/dL) ( Table 1). Schistocytes were also detected in the peripheral blood sample. The patient was diagnosed with severe sepsis and antibiotic therapy was started with meropenem and clindamycin. Continuous renal replacement therapy was applied for acute kidney injury with anuria, uncontrollable acidosis, and electrolyte abnormality. On day 3, he presented with altered mental status and hypoxic respiratory failure requiring mechanical ventilatory support. Further laboratory data showed progressive anemia, hyperbilirubinemia, a sustained high level of lactate dehydrogenase, and schistocytosis (Table 1). A clinical diagnosis of severe sepsis complicated with TMA was made based on these findings.
As the patient's condition deteriorated rapidly, we decided to initiate PE, despite the lack of a definite diagnosis from among several TMA disorders, including thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, atypical hemolytic-uremic syndrome, or other secondary TMA. We continued PE from days 3 to 6 based on the clinical improvement, which resulted in significant platelet count increase and improved renal function, hyperbilirubinemia, and schistocytosis (Fig. 1, Table 1). The blood culture on admission at the previous hospital showed Capnocytophaga species, and the PCR results also detected C. canimorsus. The antibiotic therapy was changed to ampicillin-sulbactam on day 10 and continued to day 14. A disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS13) activity on day 3 (without preceding plasma transfusion) was reported as 39% on day 12. Renal replacement therapy was discontinued on day 21. He was discharged in good condition on day 44. The patient was finally diagnosed with secondary TMA due to C. canimorsus infection. and to remove abnormal complement factor H and anticomplement factor H antibody. In addition, efficacy of PE was reported in adult Shiga toxin-mediated TMA with central nervous system symptoms. 10 Thus, in adult TMA cases with central nervous system symptoms, empiric PE might be recommended.
Our patient was diagnosed with TMA, and ADAMTS13 deficiency-and Shiga toxin-mediated TMA were ruled out. Disseminated intravascular coagulation often complicates severe sepsis, resulting in thrombocytopenia and coagulopathy; DIC may have contributed to the patient's pathophysiological condition, including thrombocytopenia and schistocytes. Significant hemolytic anemia is rarely observed in patients with DIC and fibrinogen levels are often decreased. In this case, the fibrinogen level remained within the normal range at all times (Table 1). Therefore, this patient would be diagnosed with possible secondary TMA due to C. canimorsus infection.

CONCLUSION
C APNOCYTOPHAGA CANIMORSUS is a rare cause of severe sepsis that can occur even in healthy people. Key to suspicion is dog-bite history. Capnocytophaga canimorsus infection may also be complicated by TMA, which is difficult to diagnose. Health care providers should consider applying PE when TMA is suspected in patients with severe symptoms, prior to definitive diagnosis.