1. Introduction

A 63-year-old man presented to the emergency department (ED) with fever (T 38°C), cough, fever and asthenia for a few days. His medical history was notable for coronary heart disease and Atrial Fibrillation which required implantable cardioverter defibrillator, chronic obstructive pulmonary disease, smoking habit, previous splenectomy for Immune thrombocytopenia (ITP), chronic myelomonocytic leukemia in treatment with hydroxycarbamide.

In the ED his vital signs quickly deteriorated revealing a drowsiness, tachycardia with 140 bpm, blood pressure of 50/30 mmHg, temperature of 37 °C and hypoxia (pO2 of 50 mmHg to blood gas analysis). Blood samples showed C-Reactive protein 14.57 mg/dL, white blood count (WBC) 28.440 10³/mm³ (93% neutrophils), procalcitonin (PCT) 151 ng/ml, creatinine 2.72 mg/dl, total bilirubin 1.9 mg/dl.

A total-body ultrasound (US) assessment was performed. Lung-US revealed bilateral basal consolidations and moderate pleural effusions. Abdominal US was negative for effusions of free fluids, whilst scans performed on left hypochondrium raised doubts on reliability since spleen was not clearly visible. Thus, a CT scan was required.

Non-contrast chest CT scan confirmed bilateral basal consolidations, CT scans of brain, abdomen and pelvis were negative for infective findings, abdominal CT scan confirmed splenectomy. Due to hypoxia and respiratory failure, after 3 hours of his arrival in the ED the patient was intubated and mechanically ventilated; then, he was transferred to intensive care for treatment of the septic shock.

Persistent hypotension required fluids and haemodynamic support with noradrenaline (peak dosage 0.8 mcg kg^-1 min^-1). Cultures were obtained in the ED and empiric antibiotic therapy with Piperacillin/Tazobactam was started aiming at infection control. As for source identification, common infectious etiologies (Cytomegalovirus, Mycoplasma pneumoniae, Epstein-Barr virus, Chlamydia pneumoniae, and Legionella pneumophila) were excluded. A SARS-CoV-2 test was repeated and confirmed to be negative. Bronchoalveolar lavage and urine cultures resulted negative. Meanwhile, after 11 hours of incubation, two aerobic blood cultures isolated a gram-negative rod. After 24-36 hours, small colonies grew in a chocolate agar under an enriched 5% CO2 environment. Using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) Vitek MS® (bioMérieux, Vila Nova de Gaia, Portugal), C. canimorsus was identified on blood culture on day 4. Further history taking revealed that the patient lived with his two dogs although no wound or scar was found after re-examination of skin.

During ICU stay, clinical conditions gradually improved, source control proved to be effective since C. canimorsus was sensitive to the empiric antibiotic therapy. Lung-US confirmed resolution of respiratory impairment. On day 7 patient was weaned from respiratory support, and discharge on the internal medicine ward was possible on day 15. Blood cultures repeated after 20 days from admission were negative, and patient was discharged alive from the hospital. After discharge from ICU, written informed consent and ethical approval were obtained for clinical case publication.

2. Discussion

Capnocytophaga canimorsus is a commensal bacterium in the oral flora of dogs and cats; the bacterium is a zoonotic agent and has been isolated from humans infected by dog or cat bites, scratches, licks or simply exposure to dogs or cats. Classified as a facultative anaerobic, it is a Gram-negative rod (1–4 mm long), fusiform or filamentous gliding bacteria closely related to Fusobacterium and Bacteroides species; it grows slowly on blood, incubated for at least 5 days, up to 14 days ^[1][2].C. canimorsus is able to avoid the immune system in the early stages of infection by means of down regulation of TLR4 and proinflammatory signaling cascade, likewise it is also resistant against phagocytosis and killing. Considered to be low virulent in healthy people, C. canimorsus could be seriously harmful in immunocompromised subjects such as patients with asplenia, long history of alcohol abuse, cirrhosis, immunosuppressive therapy, hemochromatosis, beta-talassemia major and cigarette smoking. Our patient presented some of these risk factors. Nevertheless, cases among immunocompetent persons have been described ^[3].

Initially patients may show local lesions related to animal bites, without significant signs of inflammation, or localized cellulitis, pain at the site of injury, lymphangitis and regional lymphadenopathy. The initial symptoms of septicemia are fever, chills, myalgia, vomiting, diarrhea, abdominal pain, dyspnea and mental confusion. A fulminant and severe course of the infection in immunocompromised persons are characterized by sepsis, meningitis, osteomyelitis, peritonitis, endocarditis, pneumonia, disseminated intravascular coagulation (DIC) and fulminant purpura; and they also been observed in healthy patients. The median time from exposure to sepsis is 3 days and 7 days for meningitis ^[4].

Due to unspecific presentation and slow growth on cultures, diagnosis and treatment of C canimorsus bacteremia are often challenging, unless the history of a dog bite is clear. Other studies have reported similar cases; however, in these cases, a dog bite was visible on presentation, unlike in the present case. Indeed, although specific bacteremia after an animal bite such as C. canimorsus or Pasteurella multocida could be suspected, the lack of any skin lesion as route of infection should not be employed as a rule-out criteria. Currently, MALDI-TOF MS method is the gold standard method to detect the bacteria in blood samples. Nevertheless, gram-stain exam under the microscope may reveal multiple gram-negative, extracellular, fusiform rods and several intracellular copies of the pathogen in neutrophils even before MALDI-TOF, thus leading to suspect the presence of C. canimorsus thanks to the observation toxic granulation in the cytoplasm of neutrophils in peripheral blood smear. Indeed, matching examination of peripheral blood smears with patient history and clinical examination might certainly assist diagnosis, and guide prompt empiric treatment in patients with septicaemia following close animal contact ^[5]. C. canimorsus is generally sensitive to penicillins, III generation cephalosporins, carbapenems, clindamycin, doxycycline, chloramphenicol, macrolides, rifampin and fluorochinolones; whilst it is considered to be resistant to aztreonam, trimethoprim, fosfomycin and aminoglycozides. Length of the treatment varies between reports, from 14 to 21 days. Literature presents a few cases of patients infected by C. canimorsus who died due to complications caused by the septic state, often due to misunderstood diagnosis or late treatment. According to the literature, mortality from C. canimorsus ranged from 10% to 30% ^[6] with mortality rate of severe sepsis being as high as 26%. Early culture samples collection, pertinent and timely administered antibiotic therapy and intensive support treatment, as in this case, decrease the risk of complications and increases the survival, especially in patients with coexisting risk factors or comorbidities ^[7].

3. Conclusions

C. canimorsus bacteremia is rare and difficult to diagnose, and lab cultures require time to provide useful findings. Although history taking in such cases is crucial, even more when considering that most patients have no signs of infection at the wound site, the key point is that the highest chance of survival is dependent on prompt culture samples collection and start of empiric antibiotic treatment, along with supportive treatment. Indeed, culture samples collection for type of infection identification and starting of empiric antibiotic treatment for source control are among the main bundles of the Surviving Sepsis Campaign recommendations and they are the essential points in ensuring patient survival especially in sepsis or septic shock of unknown origin or uncommon etiology such as in our case.