from Dog Saliva Exposure Causing Severe Sepsis in a Healthy Adult: A Case Report

Introduction

Capnocytophaga canimorsus is a gram-negative bacterium found in the oral cavity of up to 74% of dogs and 57% of cats [1]. While it is a commensal bacterium that is part of the normal oral flora of these animals, in rare cases, it can cause illness in humans. The annual human infection rate is approximately 0.5 to 0.7 cases per million individuals [2]. C. canimorsus is transmitted to humans through bites, scratches, licks, or close contact with infected animals. The bacterium can also be transmitted when an animal’s saliva comes into contact with open wounds or mucus membranes [3]. The infection rate of C. canimorsus from dog bites is reported to be 3% to 18% [4]. Common clinical manifestations of C. canimorsus infection include localized wound infections, characterized by blistering, erythema, swelling, purulent drainage, or pain at the wound site. Systemic symptoms can include fever, chills, diaphoresis, generalized myalgia, and arthralgia. Gastrointestinal symptoms, such as abdominal pain, nausea, vomiting, and diarrhea, can also occur, along with neurological signs, including headache, confusion, and altered mentation [3].

In some cases, C. canimorsus infections in humans can rapidly progress to sepsis, due to its ability to evade the immune system’s initial defense mechanisms [5,6]. Studies have shown that macrophages infected with a strain of C. canimorsus isolated from a septicemic patient do not promote the release of proinflammatory cytokines [7]. Furthermore, C. canimorsus has been found to be enveloped by a polysaccharide capsule, contributing to increased resistance for phagocytosis [5,8,9]. Diagnosis is typically confirmed via blood culture, although the organism’s slow growth can make identification through automated blood culture systems challenging. More reliable diagnostic methods include polymerase chain reaction (PCR), 16S ribosomal ribonucleic acid (rRNA) gene amplification, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) [10].

Infections caused by C. canimorsus are more commonly seen in individuals with immunodeficiency, including those with hematologic malignancies, asplenia, and cirrhosis [11,12]. Complications can range from mild to severe, including localized cellulitis, sepsis, meningitis, thrombocytopenic purpura, disseminated intravascular coagulation (DIC), acute endocarditis, and gangrene [3,12,13]. Furthermore, multiorgan failure can occur due to septic shock with acute renal failure and/or respiratory failure [13]. Treatment options include parenteral antibiotic treatment and oral antibiotic treatment, generally for 2 to 3 weeks [14]. Despite these interventions, the fatality rate remains high, occurring in 24% to 30% of cases [15].

Previous reports have documented septic shock and multi-system organ failure in immunocompromised patients following C. canimorsus infection. Risk factors for bacteremia due to C. canimorsus include a history of splenectomy, excessive alcohol use, cirrhosis, cancer, chronic lung disease, immunodeficiency, and diabetes [10–12]. However, such occurrences are rare in otherwise healthy patients. Here, we present the case of an initial presentation of weakness, joint pain, myalgia, and altered mentation in the setting of C. canimorsus septicemia, complicated by DIC, acute renal failure, and shock liver. Despite the rarity of C. canimorsus in immunocompetent individuals, this case report highlights the importance of recognizing C. canimorsus in patients with potential exposure to dog saliva and subsequent sepsis.

Case Report

A 63-year-old man with no significant medical history presented to the Emergency Department with symptoms of weakness, confusion, neck pain, joint pain, low back pain, and pain in the proximal thighs. He was accompanied by his wife, and they reported that symptoms had started 2 days prior. Despite a prior visit to the Emergency Department and discharge with medications for muscular spasm, his condition worsened significantly within the following 12 h. Notably, his weakness progressed to the point where he was unable to lift his legs, walk, or stand without assistance. During this time, he denied experiencing increased weakness in his upper extremities. Furthermore, he denied fever, headaches, visual changes, chest pain, shortness of breath, gastrointestinal symptoms, urinary symptoms, and sensory changes.

Upon evaluation, his vital signs revealed a respiratory rate of 30 breaths per min and blood pressure of 100/45 mm Hg. He had no fever, and his oxygen concentration was normal. Electrocardiography revealed normal sinus rhythm, with a rate of 87 beats per min, and no acute ischemic changes. Laboratory findings revealed significant abnormalities, including elevated levels of blood urea nitrogen at 52 mg/dL and serum creatinine at 4.42 mg/dL, indicating impaired renal function. Liver function tests revealed significantly elevated levels of aspartate transaminase >6000 U/L and alanine transaminase at 3928 U/L, consistent with liver damage. Additional findings included white blood cell count of 8.4 K/μL, with 55% bands, lactate level of 5.5 mmol/L, and platelet count of 31 K/μL, confirming the diagnosis of severe sepsis. Additionally, the DIC profile revealed a prothrombin time of 21.9 s, D-dimer greater than 4000 μg/mL, and fibrinogen of 99 mg/dL (Table 1).

Imaging studies revealed left lower lobe pneumonia, persistent bilateral nephrograms, concerning for acute tubular necrosis without hydronephrosis or perinephric fluid collection, and mild hepatomegaly (Figure 1). Neurology consultation led to a diagnosis of inflammatory and immune myopathies, for which the patient was initiated on intravenous immunoglobulin and methylprednisolone, leading to symptomatic improvement. Additional imaging, including magnetic resonance imaging of the brain and spine and a pan computed tomography scan, was recommended to rule out malignancy.

The patient was admitted to the Intensive Care Unit (ICU) for the treatment of septic shock, thrombocytopenia, renal dysfunction, and liver failure. He received aggressive resuscitation with intravenous fluids and vasopressors. Broad-spectrum antibiotics were also initiated empirically for septic shock. The antibiotic course included ampicillin and acyclovir on day 1, vancomycin day 2 to day 4, meropenem day 2 to day 8, doxycycline day 2 to day 8, and micafungin day 3 to day 7.

Additionally, an autoimmune workup, including tests for anti-nuclear antibody, anti-smooth muscle antibody, and ganglioside antibodies (GQ1b IgG and IgM, GD1b IgG and IgM), was done and yielded negative results. C-reactive protein level was elevated at 22.5 mg/dL, and ADAMTS13 activity was reduced to 30%. However, blood cultures returned positive for gram-negative rods (Figure 2), later identified as C. canimorsus, using MALDI-TOF, which identifies slow-growing bacteria. A wound on his right shin, which had been licked by his dog was identified as the source of infection (Figure 3). Notably, we were unaware whether the patient’s dog was tested for the presence of C. canimorsus in the saliva.

The broad-spectrum antibiotic regimen for septic shock, although nonspecific, effectively covered the bacterial infection and was discontinued on day 8. The Infectious Disease Department was consulted and subsequently started the patient on intravenous ampicillin/sulbactam on day 9, continuing until day 15, one day before discharge. The targeted antibiotic for C. canimorsus is ampicillin/sulbactam; however, considering that meropenem is broad-spectrum, the total duration of antibiotic therapy was 2 weeks. Leukocytosis peaked on day 2 at 35.2 K/μL but steadily improved over the hospital course to within the reference range prior to discharge. The Infectious Disease Department continued to monitor his progress, with repeat blood cultures yielding negative results.

Nephrology consultation was sought due to acute kidney injury, which necessitated continuous renal replacement therapy, and the patient was later transitioned to hemodialysis.

The Nephrology Department continued to monitor the patient throughout the hospital course. Additionally, the patient received a diagnosis of DIC and shock liver, for which he received platelet transfusions, N-acetylcysteine infusion, and cryoprecipitate, resulting in clinical and laboratory improvement. Thrombocytopenia improved, with full resolution prior to discharge.

The patient demonstrated significant clinical improvement throughout the hospital course. His blood pressure readings stabilized to the 120s to 150s systolic and 70s to 90s diastolic. Confusion resolved on day 5. Fatigue and weakness improved throughout the hospital course, and he was able to ambulate on day 11. Physical therapy interventions resulted in significant functional improvement, as evidenced by an Activity Measure for Post-Acute Care score of 23 of 24.

He underwent vascular surgery consultation for the exchange of his temporary hemodialysis catheter to a tunneled catheter. Upon discharge on day 16, the patient continued outpatient hemodialysis 3 times per week. He was advised to follow up with nephrology and primary care physicians within 1 to 2 weeks. Approximately 1 month after discharge, the patient continued to require hemodialysis 3 times per week. He still reported residual generalized weakness and fatigue, although significantly improved from before.

Discussion

From this case report, we learn that C. canimorsus infection, although rare, can cause severe and life-threatening complications, even in immunocompetent individuals. This highlights the importance of considering C. canimorsus in the differential diagnosis of sepsis, particularly in patients with a history of exposure to dog saliva, as prompt recognition and treatment are crucial for favorable outcomes. This is a rare case of gram-negative sepsis due to C. canimorsus, which was complicated by multisystem organ failure, including acute renal failure/acute tubular necrosis, liver failure, and DIC. Septic shock has been reported in only 13% of C. canimorsus cases [16]. In a previous retrospective study involving patients with C. canimorsus bacteremia who were admitted to an ICU, organ dysfunction was commonly observed, with coagulopathy affecting 94% of cases, and acute kidney injury occurring in 69% of patients [17]. Renal replacement therapy emerged as the primary treatment modality for acute kidney injury in this context [18]. Notably, a similar prior case of septic shock with acute liver failure, acute tubular necrosis requiring renal replacement therapy, and DIC occurred in a 38-year-old male patient; however, the patient did have a history notable for excessive alcohol use [19]. In the case of our patient, he did not possess any known lifestyle risk factors.

Furthermore, individuals with splenectomies comprise 60% of C. canimorsus infections [10]. Notably, our patient did not have a history of asplenia, immunodeficiency, or cirrhosis. In addition, while immunocompromised patients are known to be at higher risk for C. canimorsus complications, it is noteworthy that up to 40% of infection cases occur in individuals without underlying immunocompromised states, such as in the case of our patient [15,20]. In a previous observational study and systemic review of all cases of C. canimorsus, a total of 128 cases were identified in immunocompetent patients from 2002 to 2019. This study concluded that C. canimorsus infection is frequently complicated by sepsis in immunocompetent individuals; 74.2% of cases were male patients [21]. Furthermore, male patients over the age of 50 (median age of 58) years seem to be at greater risk than the general population [16,21]. As a man in his 60s, our patient did possess these risk factors. On the other hand, it was found that a fatal outcome can be prevented, despite risk factors, by early wound cleansing, initial antibiotic treatment with penicillin beta-lactamase inhibitor combinations, and surgical excision of the infection site [21].

The typical incubation period of C. canimorsus is approximately 1 to 8 days [11]. Diagnosis primarily relies on blood culture, although it can be challenging to detect. Due to its fastidious culture media and slow growth in culture media, which takes 2 to 7 days on average, it can require up to 14 days to turn positive [16,22]. Early recognition is important for prompt initiation of antibiotic therapy. The recommended duration of antibiotic therapy is approximately 14 to 21 days [14]. First-line treatment for C. capnocytophaga bacteremia in immunocompetent patients includes parenteral broad-spectrum antibiotics, including beta-lactams, beta-lactam/beta-lactamase inhibitors, and/or imipenem/cilastatin [23]. As many strains of C. canimorsus are susceptible to all antibiotics, treatment with broad-spectrum antibiotics has been successful in most cases [24]. Our patient had initial treatment with empiric broad-spectrum antibiotics, which included 7 days of carbapenem. Subsequently, targeted antibiotic therapy (ampicillin/sulbactam) was administered for 7 days, totaling 2 weeks of antibiotic therapy. He demonstrated significant functional improvement on this antibiotic regimen. Notably, septic shock due to C. canimorsus does not seem to require treatments that are not included in current septic shock guidelines [18].

This case report highlights the complexities involved in diagnosing C. canimorsus infections and emphasizes the importance of early recognition. It reveals the severe and potentially life-threatening nature of C. canimorsus infection, even in otherwise healthy individuals. Moreover, this case exemplifies how C. canimorsus can progress rapidly into septic shock with multiorgan failure, which can be irreversible. As in the case of our patient, appropriate treatment of septic shock can prevent further detriment of C. canimorsus septicemia.

Conclusions

Our patient presented with systemic symptoms and was later found to have septic shock with end-stage organ failure due to C. canimorsus. This is a rare response in immunocompetent patients. Prompt initiation of empirical broad-spectrum antibiotics prior to identification of the source of infection proved to be beneficial, resulting in clinical and symptomatic improvement. In septic patients with potential dog exposure, C. canimorsus should be considered as a potential causative pathogen.