Capnocytophaga canimorsus-associated sepsis presenting as acute abdomen: do we need to think outside the box?

Abstract

Capnocytophaga canimorsus is a commensal bacterium commonly found in the oral cavity of dogs and cats. Although this organism rarely causes infection, prompt diagnosis is crucial for survival of these patients. Several unusual clinical presentations of this infection have been reported in the published medical literature. The present report represents the first case of C. canimorsus-related sepsis presenting with symptoms of acute abdomen in a patient with no known history of immunodeficiency. Prompt aggressive care and appropriate antibiotic therapy resulted in a successful clinical outcome with no long-term morbidity. This paper illustrates that clinicians should include this infectious aetiology among the differentials of patients presenting with acute abdomen, regardless of their immune status. Additionally, this paper outlines our current understanding of the epidemiology of and risk factors for C. canimorsus-associated sepsis, the pathophysiology of this disorder, and currently available approaches to diagnosis and management.

Background

Capnocytophaga canimorsus is a dog oral cavity commensal and causative organism of severe sepsis in human beings. The incidence of this infection is approximately 0.5–0.7 cases per million individuals per year.¹ The prevalence is relatively higher among immunocompromised patients, especially with splenectomy and alcoholism. However, canine exposure is a key variable to consider as about 60% of the patients demonstrate a history of dog bite while others confirm having scratches from dogs or occasionally cats, or even a benign exposure to dogs without bites or scratches.² C. canimorsus infection may have a constellation of clinical presentations such as soft-tissue infection, meningitis, fever of unknown origin or fulminant sepsis. In most cases, diagnosis can be established using blood cultures. However, requirements of special media enrichments, temperature control and slow growth (mean: 6 days) make it a diagnostic challenge even in the laboratory. Due to these factors, morbidity and case fatality rates associated with C. canimorsus infection are high (~30%).^{3 4} Prognosis is particularly dismal in patients with initial presentation related to septic shock, with mortality rates reaching up to 60%.⁴

To the best of our knowledge, approximately 500 cases of C. canimorsus infection have been reported in the medical literature as of October 2018.² However, only two patients who both had a history of splenectomy, presented with predominant clinical features of acute abdomen.^{5 6} Due to this extremely rare association, such patients may undergo unnecessary laboratory investigations and even invasive surgical procedures like exploratory laparotomy. It is further notable that a delay in the administration of appropriate antibiotics may occur, which can potentially lead to a poor clinical outcome, especially in patients presenting to the emergency clinical settings.⁶ We describe here a case of a patient with no prior evidence of immunodeficiency who presented with features of acute abdomen secondary to C. canimorsus-related sepsis, following a minor dog bite. Furthermore, we review the pertinent medical literature for this rare but serious clinical presentation of C. canimorsus-associated sepsis.

Case presentation

A 41-year-old Filipino man presented to the emergency department with fever, abdominal pain, headache and dizziness for 1 day. The fever was associated with rigors and chills. Abdominal pain was localised in the epigastric region, colicky in character, non-radiating with no positional change and was not alleviated by intravenous paracetamol. The patient had nausea but no vomiting. His bowel habits were regular. He also reported a diffuse headache and dizziness on standing since morning. He had no history of immunodeficiency disorders and he was not under therapy with any medications. On further questioning, he reported a stray dog bite on his left arm 2 days ago for which he did not seek any medical care.

On physical examination, the patient was in acute distress with severe colicky abdominal pain that only partially responded to intravenous fentanyl. Vital sign examination showed blood pressure 82/49 mm Hg, heart rate 122 beats per minute, respiratory rate 26 breaths per minute, temperature 38.4°C and oxygen saturation of 95% on room air. Chest auscultation revealed bilateral vesicular breath sounds with good air entry. Abdominal examination was significant for rigidity, guarding and severe tenderness in the epigastric and right upper quadrants. Bowel sounds were audible. There were no scar marks over abdomen. His left forearm showed two bite marks with each of the depth 2–3 mm on both dorsal and ventral surfaces with mild swelling and surrounding erythema. There was no active discharge from the wound.

Investigations

Laboratory studies revealed leucocytosis (24.4×10⁹/L), haemoglobin (125 g/L), thrombocytopenia (52×10⁹/L), with deranged coagulation profile (prothrombin time, 18.3  s; activated partial thromboplastin time, 54 s; international normalized ratio, 1.8), suggestive of disseminated intravascular coagulation. The results of arterial blood gas analysis (pH, 7.35; pCO₂, 37 mm Hg; HCO_³, 18 mmol/L; pO₂, 60 mm Hg and lactate 7.1 mmol/L) revealed lactic acidosis. Urinalysis was significant for proteinuria and haematuria with no leucocytes or nitrite. Liver function testing showed slight rise in aspartate aminotransferase to 51 IU/L along with drop in serum albumin to 2.09 g/dL. Serum amylase, lipase, sodium and potassium were within normal limits. Chest and abdominal radiographs were inconclusive for abnormalities. Abdominal ultrasonography revealed moderate amount of free intraperitoneal fluid. Due to the likely infectious aetiology of patient’s presentation, blood specimens were sent for culture.

Treatment

Empirical antibiotic therapy (cefuroxime, metronidazole) was initiated. Rabies and tetanus vaccination along with rabies immunoglobulins were administered. Despite intravenous fluid boluses, antibiotics, and adequate analgesia, patient’s clinical milieu did not improve. The clinical features were strongly suggestive of sepsis likely originating from the abdominal source. Contrast-enhanced CT abdomen was unremarkable for pneumoperitoneum or visceral perforation. Based on the abdominal imaging results, surgical intervention was deferred. The patient was shifted to intensive care unit for close monitoring and conservative management. Therein, blood microscopy revealed intracellular Gram-negative rods (figure 1). Intravenous antibiotics were changed to piperacillin-tazobactam for suspected polymicrobial bacteraemia from dog’s oral cavity commensals while waiting for culture sensitivity reports. Blood cultures confirmed the growth of C. canimorsus (figure 2). He responded adequately to fluid resuscitation and intravenous antibiotics. Therefore, no inotropic support was required during the hospital course.

Figure 1.

Photomicrograph showing pathological examination of the blood specimen. Gram-negative rods with spindle-shaped ends were identified (Gram staining; 100×).

Figure 2.

Colonies of Capnocytophaga on sheep blood agar after 7 days of incubation in a microaerophilic atmosphere.

Outcome and follow-up

On day 3 of admission, the patient became haemodynamically stable. After 8 days of inpatient treatment, he was discharged from the hospital on oral triple antibiotic regimen (amoxicillin-clavulanic acid, clarithromycin and ciprofloxacin). The therapy was completed in 7 days along with rabies immunisation course. At the 1-week follow-up, the patient did not report recurrence of his symptoms. He continues to do well to date.

Discussion

Capnocytophaga is a group of Gram-negative, facultative anaerobic, non-spore forming motile rods with spindle-shaped ends. These bacteria are found in the normal oral flora of 22%–74% healthy dogs. Nine different species have been identified so far and all are commonly found in canine flora.⁷ However, C. canimorsus is responsible for most of Capnocytophaga infections after dog bites and may cause severe sepsis in human beings. It was first isolated by Bobo and Newton in 1976 at the Centers for Disease Control and Prevention, Atlanta, Georgia, USA from the spinal fluid and blood of a patient who experienced dog bite. Subsequently, this organism was given a distinct name in 1989. The transmission to humans is predominantly by carnivore bites and scratches, but benign animal contact may also cause the disease.^{8 9}

C. canimorsus has an incubation period of 1–8 days. The disease spectrum ranges from being self-limited skin infection to fulminant sepsis, multiorgan failure and death.¹⁰ Major risk factors for severe infection include hyposplenism, alcohol-induced liver disease and immunosuppressive disorders.¹¹ It is also an interesting observation that in approximately 40% of patients, as in the present case, no clear risk factors are identified. C. canimorsus evades the immune system of the host by inhibiting activation cascade of macrophages and prevent phagocytosis by polymorphonuclear leucocytes. Furthermore, the polysaccharide capsule also prevents complement-mediated phagocytosis. These mechanisms help the bacterium in evading the local inflammatory response to the infection that leads to an early dissemination in blood. Systemic inflammatory response to bacteraemia causes vasodilation culminating in septic shock, whereas concurrent endothelial injury leads to disseminated intravascular coagulation.¹²

The diagnosis of C. canimorsus is frequently established based on the blood culture. However, it is relatively difficult to grow in laboratory due to its fastidious culture media, specific environment and slow growth requiring up to 14 days before turning fully positive on the plate. Therefore, it is of utmost importance to alert the microbiology laboratory early if Capnocytophaga infection is suspected. Meanwhile, microscopic examination of the peripheral smear may expedite the identification of the organism in some cases.¹³ Newer data suggest that matrix-assisted laser desorption ionisation time of flight spectrometry or 16S PCR can also enhance the time sensitivity for pathogen detection in cases of C. canimorsus septicaemia.¹⁴

Patients presenting with an advanced stage of C. canimorsus septicaemia are more likely to have preceding minor dog bite injuries rather than more severe bites. The findings in our patient were in line with these observations. Due to presumably a minor dog bite, most patients do not seek any medical care. C. canimorsus septicaemia may also manifest as acute abdomen. This clinical presentation can frequently be deceptive as it may lead to incorrect diagnostic approach and management due to major suspicion of surgical intra-abdominal pathologies such as perforated viscus, acute appendicitis, acute cholecystitis, biliary or renal colic. According to our literature search, only two case reports of C. canimorsus sepsis have been documented where patients presented with features of acute abdomen. The data on C. canimorsus-related acute abdomen in terms of patient characteristics, epidemiology, clinical features, comorbid conditions, diagnostic modalities and management are summarised (table 1).

Table 1.

Literature review of dog-bite-related sepsis secondary to Capnocytophaga canrnimorsus infection presenting acute abdomen

Authors	Sawmiller et al 5	Deprés-Brummer et al 6	The present report
Publication year	1998	2001	2019
Country	USA	The Netherlands	Qatar
Age (years)/gender	37/F	46/M	41/M
Clinical presentation	Severe upper abdominal pain, vomiting, fever with chills	Fever, generalised body aches, abdominal pain, hypotension	High-grade fever, severe abdominal pain, hypotension
Immunodeficiency	Splenectomy, 11 years ago	Splenectomy, 19 years ago	No history of immunodeficiency
Dog-bite features	Small, single erythematous bite wound on right thumb	Multiple bite wounds on left hand. Largest one 2 cm with surrounding blackish discoloration	Two bite marks over left forearm with mild swelling and erythema around wounds
qSOFA score at presentation	1/3	2/3	2/3
Radiologic findings	CXR: bilateral pulmonary infiltrates. CT: moderate amount of free Intraperitoneal fluid	CT: minimal free intraperitoneal fluid	USG: mural thickening of pylorus and proximal duodenum, hepatomegaly, moderate free fluid in gallbladder fossa
Blood cultures and sensitivity	CC grew on day 12 of admission. No sensitivity reported	CC grew on day 5 of admission. Sensitive to penicillin, amoxicillin, and ofloxacin. Resistant to tobramycin	CC grew on day 7 of admission. Organism failed to propagate for sensitivity report
Initial antibiotics	Penicillin G, mezlocillin sodium, gentamicin sulfate and ciprofloxacin hydrochloride	Cefazolin, ofloxacin and metronidazole	Cefuroxime, metronidazole and piperacillin–tazobactam
Antibiotics after organism detection	No	Amoxicillin-clavulanic acid	Amoxicillin-clavulanic acid, clarithromycin, ciprofloxacin
Inotropic support	Yes	Yes	No
Ventilatory support	Yes	Yes	No
Laparotomy	No	Laparotomy ruled out acute intra-abdominal pathologies. Diffuse hepatomegaly and clear intraperitoneal fluid were noted	No
Patient outcome	Uneventful recovery and discharged from the hospital after 15 days	Died on day 40 due to refractory shock and respiratory failure	Uneventful recovery and discharged from the hospital after 8 days

CC, Capnocytophaga canimorsus; CXR, chest X-ray; qSOFA, quick sepsis-related organ failure assessment; USG, ultrasonography.

The recommended treatment algorithms for dog bite wounds comprise high pressure irrigation, surgical exploration and debridement of the wound in the emergency department under local anaesthesia.¹⁵ Although universal antibiotic prophylaxis after dog bites is not recommended due to the lack of the evidence, it may reduce the rate of wound infections, especially for hand bites. Most experts recommend early use of amoxicillin-clavulanic acid for 3–5 days in cases with fresh, deep bite wounds to vital body parts. C. canimorsus is usually susceptible to penicillin antibiotics. However, patients with severe infection should be treated empirically with beta-lactamase inhibitor combination until the availability of susceptibility report as beta-lactamase production has been reported in few strains of this organism.^{16 17}

Learning points.

• Capnocytophaga canimorsus is a rare but serious cause of acute abdomen in patients with history of canine exposure, irrespective of their immune status. A thorough clinical history allows clinicians to suspect the potential C. canimorsus infection and treat empirically before the culture results or any serious clinical sequel of the infection.

• Physicians should maintain a high index of clinical suspicion for C. canimorsus bacteraemia, especially in patients presenting with consistent clinical features in a few days after dog bite.

• The present report illustrates that antibiotic prophylaxis is warranted in patients with dog bite injury to prevent the clinical progression to fulminant sepsis.