Infectious Disease, Sepsis

Sick as a Dog: A Case of Overwhelming Post-splenectomy Infection

Although it is rare, it is important to recognize C. canimorsus sepsis, as it is associated with high mortality rate and the patient can deteriorate rapidly.

Case
A 57-year-old woman with a history of antiphospholipid syndrome, ITP, emphysema, and recurrent mesenteric vein thrombosis status-post bowel resections and splenectomy presented to the emergency department with fever, chills, and vomiting for 1 day. The patient reported multiple episodes of non-bilious non-bloody emesis over the prior 24 hours without abdominal pain. She had several loose stools, but no melena or hematochezia. She denied cough, shortness of breath, chest pain, sore throat, neck pain, or headache. Over the day prior to presentation, she had become increasingly weak and confused, prompting her partner to bring her in to the ED for evaluation. She reported no recent travel or sick contacts, no toxic ingestions or substance abuse, and multiple pets in her home.

Her triage vital signs were BP 123/100, HR 136, RR 24, temperature 97.5°F, and oxygen saturation 100% on room air. On physical exam she was ill-appearing. HEENT exam was unremarkable. Cardiovascular exam was significant for tachycardia with a regular rhythm. She was tachypneic but had an otherwise normal pulmonary exam. Abdominal exam was non-tender throughout, but did reveal multiple healed scars from prior surgeries. She was confused about the date but had no focal neurologic deficits and was answering questions. Her extremity exam showed no peripheral edema. Her skin was noted to be pale with delayed capillary refill of >3 seconds. Petechia and early purpura were noted on her back.

What is your working differential diagnosis? How would you treat this patient?

Workup
An initial point-of-care blood glucose demonstrated critical hypoglycemia to 25 mg/dL. iSTAT lactate was elevated at 10.8 mmol/L. Venous blood gas showed a pH 7.25, pCO2 31.7 mmHg, PO2 12 mmHg, HCO3 14 mmol/L, and Base Excess of -13. Laboratory studies returned with an abnormal CBC including WBC 3.1 K/uL, Hb 12.1 g/dL, platelets 28 K/uL, which also showed Howell-Jolly bodies and many intracellular bacteria. Chemistry resulted with a sodium of 138 mmol/L, potassium 6.4 mmol/L, chloride 98 mmol/L, CO2 10 mmol/L, urea nitrogen 56 mg/dL, creatinine 2.87 mg/dL, anion gap of 30, calcium of 9.8 mg/dL, bilirubin 0.6 mg/dL, AST 116 U/L, ALT 56 U/L, alk phos 66 U/L, albumin 4.0 g/dL, protein 7.0 g/dL. Prothrombin time was 25.4 seconds, INR 2.3, partial thromboplastin time 201.2 seconds, D-dimer was 7,695 ng/mL FEU, and fibrinogen 400mg/dL. Influenza PCR was negative.

With dextrose administration glucose improved to 236. Blood gas in the subsequent 2 hours worsened to 7.20/ CO2 35/O2 17, HCO3 13.9/ BE -14, with a mild improvement in lactate to 9.03 after volume resuscitation and antibiotics. Chest x-ray did not reveal a source of infection. CT of the abdomen did not show any acute cause of severe sepsis. Arterial vasculature was patent, portal vein and SMV showed chronic thrombus seen on imaging 10 years prior. Non-contrast CT of the head was unremarkable. The patient developed worsening respiratory distress and confusion, ultimately requiring intubation while still boarding in the emergency department.

Within 6 hours of arrival, aerobic blood cultures grew Capnocytophaga canimorsus.

Case Discussion

Background
The patient described in this case developed overwhelming post-splenectomy infection (OPSI) with septic shock and multi-organ failure due to Capnocytophaga canimorsus bacteremia. This gram-negative bacterium is commonly isolated from the oral microbiota of dogs and less commonly in cats.1 There are 7 species of Capnocytophaga, all of which can be found in the oral cavity of both humans and domestic animals. It is estimated that somewhere between 8% and 41% of canines have a colonized oropharynx.1,2 Capnocytophaga canimorsus infections in humans are most commonly associated with dog and cat bites, and to a lesser extent, scratches and licking.3 The first human infection was described in 1976, and there are very few documented cases each year.4,5

Clinical Presentation
A patient with a remote splenectomy may not recognize initial symptoms of infection, and may be unaware of how quickly infections can become fulminant. In addition, they may not associate a canine bite or other common exposures with symptoms of infection, so a careful history is essential in all ill-appearing splenectomy patients. In the case of C. canimorsus infection, symptom onset typically occurs within 5 days of bite, and hospitalization occurs on average at 7 days after exposure.1,6 The infection may present in a variety of ways, from localized skin and soft tissue infection to systemic symptoms of septicemia.1 In those who develop sepsis, the most common symptoms are fever (78%), chills (46%), vomiting (31%), diarrhea (26%), abdominal pain (26%), dyspnea (23%), confusion (23%) and headache (18%).7

Sepsis due to C. canimorsus can be devastating, with mortality rates estimated to be 30%.5 It is essential that bacteremia is considered early and antibiotics that treat C. canimorsus are administered promptly. The rapid progression of disease suggests that the organism may be able to evade the immune system.1 While it is possible for severe sepsis to occur in immunocompetent individuals, in 33% of cases there is a history of splenectomy, which is also associated with a higher risk of death.1,8,9 Besides splenectomy, other risk factors for severe disease include immunosuppression and alcohol abuse.5

In the case of this patient, fever, vomiting, and confusion were the primary symptoms, although she was afebrile upon presentation. She had three SIRS criteria and a qSOFA score of 2, which initiated workup and treatment for sepsis. Her confusion, tachypnea, purpura, and extremely high lactic acid were all ominous signs of a life-threatening infection. On review of the patient’s chart, she had a remote history of splenectomy which predisposed her to infection with encapsulated bacteria, intraerythrocytic parasites, and gram-negative bacteremia such as C. canimorsus.10 While there was no specific history of animal bite, her exposure to pets may have put her at risk for this infection.

ED Management
The first step in ED management is consideration of life-threatening infection and atypical pathogens in a patient with a history of splenectomy who presents with sepsis or septic shock.1 C. canimorsus is one of the pathogens which may be considered in such patients, and the emergency physician should take a careful history, asking the patient about any exposure to animals or recent bite wounds.

The spleen is responsible for phagocytosis of bacteria and production of antibodies. Asplenic patients are at risk for serious infection from not only encapsulated bacteria, but also other pathogens like C. canimorsus.10 Patients may develop OPSI which is characterized by initial vague symptoms (fever, malaise, headache, vomiting, diarrhea) followed by septic shock with disseminated intravascular coagulation and mortality of 50 to 80%, even with appropriate antibiotics. Mortality can be reduced if patients seek medical care and are treated immediately, which is why early recognition in the ED is essential.11

The ED work-up should include a complete blood count, chemistry, lactate, and blood cultures. Peripheral blood smear examination may demonstrate extracellular and phagocytosed bacilli.12 Blood cultures often confirm the diagnosis of C. canimorsus (88% of cases).13 However, because blood cultures may not become positive during the ED stay, it is essential for the EM physician to have a high index of suspicion for bacteremia in a patient presenting with sepsis. If there is a concern for meningitis, a lumbar puncture should be performed to obtain cerebrospinal fluid (CSF). The cerebrospinal fluid culture may take an extended period of time to become positive (median of 5 days, with a range of 1-19) so it is important to continue culture growth beyond five days.14 Antibiotics should be given based on clinical concern and the physician should not wait for a clear source of infection to be identified in laboratory workup, cultures or CSF.

The patient should be given a broad-spectrum antibiotic that covers C. canimorsus while awaiting susceptibility testing. For the initial treatment of severe infections, empiric antibiotics should include a carbapenem or a beta-lactam beta-lactamase combination such as piperacillin-tazobactam, though the bacterium may end up being susceptible to a variety of other antimicrobials such as penicillin G, linezolid, chloramphenicol, third generation cephalosporins, fluoroquinolones, erythromycin, doxycycline, and metronidazole.1,15 It is unlikely that a diagnosis will be confirmed during the ED stay, and thus for severe infections broad-spectrum antibiotics should be administered while the differential remains open. Non-severe infections may instead by treated with oral amoxicillin-clavulanate or clindamycin. For confirmed cases, duration of treatment ranges from 14-21 days.6

Finally, in order to prevent life-threatening infection from C. canimorsus and other bacteria, prophylactic antibiotics (usually amoxicillin-clavulanate) should be given to asplenic individuals who have been bitten by a dog, even in the absence of infectious symptoms.1,5 Currently there is not clear utility on the testing of canines, since it does not guarantee that particular dog will stay infection-free. Furthermore, isolation from canine saliva or bite wounds is challenging.1

Case Conclusion
Patient was admitted to the MICU for septic shock due to Capnocytophaga canimorsus bacteremia. Her course was complicated by anuric renal failure with severe metabolic acidosis requiring initiation of CRRT. Hemodynamics continued to worsen, and within hours the patient progressed to PEA arrests and ultimately passed away despite maximal support.

TAKE-HOME POINTS

  • All post-splenectomy patients who present with fever or other signs of sepsis should be treated with broad-spectrum antibiotics while work-up is pending, as infections may become rapidly fulminate (overwhelming post-splenectomy infection).
  • Although it is rare, it is important to recognize C. canimorsus sepsis, as it is associated with high mortality rate and the patient can deteriorate rapidly.
  • C. canimorsus bacteremia results from bites, scratches, and licking by dogs and cats among patients at risk, such as those with splenectomy, history of alcohol abuse, or immunosuppression.
  • Gram negative rods may be seen in the blood smear for patients with C. canimorsus bacteremia.
  • For severe cases, preferred antibiotics to treat C. canimorsus include carbapenems or a beta-lactam beta lactamase combination.

References

  1. Gaastra W, Lipman LJA. Capnocytophaga canimorsus. Veterinary Microbiology. 2010;140(3):339-346.
  2. Bailie WE, Stowe EC, Schmitt AM. Aerobic bacterial flora of oral and nasal fluids of canines with reference to bacteria associated with bites. J Clin Microbiol. 1978;7(2):223-231.
  3. Lion C, Escande F, Burdin JC. Capnocytophaga canimorsus infections in human: Review of the literature and cases report Eur. J. Epidemiol.1996; 12, 521-533
  4. Bobo RA, Newton EJ. A previously undescribed gram-negative bacillus causing septicemia and meningitis. Am J Clin Pathol. 1976;65(4):564-569.
  5. Macrea MM, McNamee M, Martin TJ. Acute Onset of Fever, Chills, and Lethargy in a 36-Year-Old Woman. Chest. 2008;133(6):1505-1507.
  6. LeMoal G, Landron, C, Grollier, G, Robert, R, Burucoa, C. Meningitis due to Capnocytophaga canimorsis after receipt of a dog bite: case report and review of the literature. Clin. Infect. Dis. 2003; 36, e42–e46.
  7. Pers C, Gahrn-Hansen, B, Frederiksen, W, 1996. Capnocytophaga canimorsus septicemia in Denmark 1982–1995: review of 39 cases. Clin. Infect. Dis. 1996; 23, 71–75.
  8. Singer, D.B., 1973. Post-splenectomy sepsis. In: Rosenberg, H.S., Bolande, R.P. (Eds.), Perspectives in Pediatric Pathology, vol. I. Year Book Medical Publishers, Chicago, IL, pp. 549–563.
  9. Deprés-Brummer, P, Buijs J, van Engelenburg KCA, Oosten, HR.Capnocytophaga canimorsus sepsis presenting as an acute abdomen in an aplenic patient. Neth. J. Med. 2001. 59, 213–217.
  10. Brigden ML. Detection, education and management of the asplenic or hyposplenic patient. Am Fam Physician. 2001;63(3):499-506, 508.
  11. Lortan JE. Management of asplenic patients. Br J Haematol 1993;84:566-9.
  12. Taquin H, Roussel C, Roudière L, et al. Fatal infection caused by Capnocytophaga canimorsus. The Lancet Infectious Diseases. 2017;17(2):236.
  13. Janda MJ, Graves MH, Lindquist D, Probert WS. Diagnosing Capnocytophaga canimorsus infections. Emerg. Infect. Dis. 2006;12, 340–342.
  14. van Samker A, Brouwer MC, Schultsz C, van der Ender A, van de Beek, D. Capnocytophaga canimorsus Meningitis: Three Cases and a Review of the Literature. Zoonoses and Public Health. 2016; 63, 442-448.
  15. Gougeon AJ, Sixou JL, Tamanai-Shacoori Z, Bonnaure-Mallet M. Antimicrobial treatment of Capnocytophaga infections. International Journal of Antimicrobial Agents. 2007, 29, 367-373.

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