Korean Journal of
Veterinary Service

The onset of sepsis triggers both pro-inflammatory and anti-inflammatory processes, and the balance between these processes is crucial for survival (Hotchkiss and Karl, 2003). An imbalance where pro-inflammatory responses dominate can lead to a cytokine storm and subsequent fatality, while an excessive anti-inflammatory response can result in nosocomial infections or reactivation of pathogens, leading to death.

A 5-year-old spayed female mixed-breed dog (weight, 29.8 kg), previously on 7 months of immunosuppressive therapy (prednisolone 0.5 mg/kg, per oral [PO], q12h [Solondo Tab., Yuhan, Seoul, Korea] and cyclosporine 8 mg/kg, PO, q24h [Cipol-N Soft Cap. 100 mg, Chong Kun Dang, Seoul, Korea]) for pemphigus foliaceus (Fig. 1), presented to our referral hospital with a history of dog bites on the right forelimb, chest, and flank 4 days prior (Fig. 2A). Physical examination revealed a rectal temperature of 38.6℃; heart rate of 130 beats per minute; panting; systolic blood pressure of 60 mmHg (Doppler method); and swelling, purulent discharge, warmth, pain, and lameness in the right forelimb (Fig. 2B). Laboratory investigations, including complete blood count (CBC) and serum chemistry, were performed using blood samples from the jugular vein. Neutropenia (neutrophil, 2,360 /μL; reference interval [RI] 2,950∼11,640 /μL) was found in the CBC. Elevation of C-reactive protein (CRP, 7.8 mg/dL; RI 0.1∼1 mg/dL), γ-glutamyl transferase (GGT, 223 U/L; RI 0∼11 U/L), and alkaline phosphatase (ALP, 2,970 U/L; RI 23∼212 U/L) were found in the serum chemistry (Table 1). There were no remarkable findings on radiography, and ultrasound examination of the right forelimb revealed a hypoechoic lesion suspected to be a purulent exudate located between the muscles (Fig. 2C). Suppurative neutrophilic infiltration with bacterial infection was detected by impression cytology of the pus on the right forelimb (Fig. 3). Pasteurella canis was isolated from pus cultures. Based on the results of these clinical examinations and laboratory findings, the dog was diagnosed with dog bite-induced sepsis with pemphigus.

Table 1 . Complete blood count (CBC) and serum chemistry results at initial visit.

CBC
RBC	8.86	5.65∼8.87 (1012/L)
HCT	46	37.3∼61.7 (%)
WBC	5.87	5.05∼16.76 (109/L)
WBC-NEU †	2.36	2.95∼11.64 (103/µL)
WBC-LYM †	1.49	1.05∼5.1 (103/µL)
WBC-MONO†	2	0.16∼1.12 (103/µL)
WBC-EOS†	0.02	0.06∼1.23 (103/µL)
WBC-BASO†	0	0∼0.1 (103/µL)
Platelet	229	148∼484 (109/L)
Serum chemistry
Glucose	127	74∼143 (mg/dL)
PHOS	5.8	2.5∼6.8 (mg/dL)
Calcium	9.1	7.9∼12 (mg/dL)
TP	7.3	5.2∼ 8.2 (g/dL)
ALB	3.1	2.3∼ 4 (g/dL)
GLB	4.2	2.5∼4.5 (g/dL)
ALT	167	10∼125 (U/L)
AST	59	0∼50 (U/L)
ALKP	2,970	23∼212 (U/L)
GGT	223	0∼11 (U/L)
Bilirubin-Total	0.6	0∼0.9 (mg/dL)
CHOL	261	110∼320 (mg/dL)
Creatinine	0.6	0.5∼1.8 (mg/dL)
BUN	6	7∼27 (mg/dL)
CRP	7.8	0.1∼1 (mg/dL)

ALB, albumin; ALKP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate aminotransferase; BASO, basophil; BUN, blood urea nitrogen; CHOL, cholesterol; CRP, C-reactive protein; GGT, γ-glutamyl transferase; GLB, globulin; HCT, haematocrit; LYM, lymphocyte; MONO, monocyte; NEU, neutrophil; PHOS, phosphate; RBC, red blood cell; TP, total protein; WBC, white blood cell..

Figure 1. Previous diagnosis (Pemphigus foliaceus) of the dog. (A) Lesions in nasal planum and footpad. (B) Histological features (multifocal neutrophilic and eosinophilic epidermitis with acantholytic cells) of the nasal planum.

Figure 2. (A) Dog-bite lesions of the chest, flank, and right forelimb of the dog. (B) Swelling and purulent discharge in the right forelimb. (C) Ultrasound features of hypoechoic lesion suspected to be purulent exudate in the right forelimb.

Figure 3. (A) Pus derived from the right forelimb. (B) Suppurative neutrophilic infiltration with bacterial infection.

During hospitalization, immunosuppressants were discontinued, and a combination of two broad-spectrum antibacterial drugs (cefotaxime 30 mg/kg, intravenous [IV], q8h [Pharmgen cefotaxime sodium inj. 1 g, Pharmgen Science, Seoul, Korea] and enrofloxacin 10 mg/kg, IV, q24h [Baytril 50 inj., Yuhan]) was administered. Additionally, the dog received fluid (Plasma Solution-A Inj., HK inno.N Corp., Cheongju, Korea; bolus or continuous rate infusion [CRI]) for hypotension, analgesic treatment (remifentanil 6 μg/kg/hr, lidocaine 3 mg/kg/hr, and ketamine 0.6 mg/kg/hr, CRI), and gastrointestinal medications (esomeprazole 1 mg/kg, IV, q24h [Nexium inj., AstraZeneca, Cambridge, UK] and metoclopramide hydrochloride 0.3 mg/kg, subcutaneous, q12h [Meckool inj., Jeil jeyak, Daegu, Korea]). However, CRP and neutropenia did not stabilize after treatment with these broad-spectrum antibacterial drugs for 2 days (Fig. 4). Therefore, we decided to change the antibacterial drugs, and on day 2, the dog received meropenem (12 mg/kg, IV, q8h [Meropen inj. 0.5 g, Yuhan]) and metronidazole (7.5 mg/kg, IV, q 12h [Trizele inj., JW Pharmaceutical, Gyeonggi, Korea]) for antibacterial treatment. Subsequently, the CRP levels, neutropenia, and injuries markedly improved (Fig. 4). The dog was discharged from the hospital on day 5. On the day of discharge, meropenem and metronidazole for antibacterial treatment, and oxycodone (0.3 mg/kg, PO, q 12h [Ocodone Tab. 5 mg, Hana Pharm, Seoul, Korea]) for analgesia were prescribed . The dog was rechecked on day 21. The CRP level was within the normal reference range, and the clinical signs were completely resolved. However, pemphigus foliaceus relapsed in the dog, and the dog is currently undergoing re-administration of immunosuppressive medications (prednisolone 1 mg/kg, PO, SID and cyclosporine 8 mg/kg, PO, SID).

Figure 4. Monitoring of (A) CRP and (B) neutrophil count of the dog during hospitalization CRP, C-reactive protein.

Millions of animal injuries occur annually (Lauer et al, 1982; Weiss et al, 1998). Among these, 90% involve injuries caused by dogs and cats, and 3∼18% of dog bites result in infections (Talan et al, 1999). Aerobic bacteria commonly isolated from dog bites include Pasteurella spp, Streptococcus spp, Staphylococcus spp, and Neisseria spp, whereas anaerobic bacteria comprise Fusobacterium spp, Bacteroides spp, Porphyromonas spp, Prevotella spp, and Capnocytophaga spp (Oehler et al, 2009). Microbial examination via needle aspiration of the patient’s right forelimb revealed Pasteurella canis. Pasteurella canis, commonly found in the normal flora of animal skin, oral cavity, and gastrointestinal mucosa, manifests pathogenicity through opportunistic infections or trauma. In humans, it is the most frequently isolated bacterium from dog bite injuries (Talan et al, 1999).

Several studies on the autopsies of patients who died from sepsis revealed significantly suppressed cytokine production in splenocytes (Meakins et al, 1977; Hotchkiss and Karl, 2003). Given this immunosuppressive state in patients with sepsis, there is a current argument to focus not only on appropriate antibiotic therapy and supportive care, but also on enhancing the host’s immunity (Meisel et al, 2009; Hall et al, 2011). Therefore, immunosuppressive therapy the dog was receiving for pemphigus was discontinued.

When there is a recurrence or persistent hypotension due to septic shock, the delay in initiating effective antibiotic treatment significantly increases the risk of death (Kumar et al, 2006a; Kumar et al, 2006b). According to a study by Kumar et al., if effective antibiotic therapy begins within one hour of confirming hypotension, the survival rate markedly improves (Kumar et al, 2006a). However, for each subsequent delay, the average survival rate decreases by 7.6% (Kumar et al, 2006a). This emphasizes the critical importance of early and effective antibiotic interventions (Garnacho-Montero et al, 2003; Larché et al, 2003). Based on this evidence, in this patient, the combination of cefotaxime and enrofloxacin did not improve persistent hypotension and worsening neutropenia. Therefore, treatment was changed to a combination of meropenem and metronidazole (Roberts et al, 2009). Subsequently, the CRP levels, neutropenia, and injury significantly improved.

To the best of our knowledge, this is the first case report of successful management of dog bite-induced sepsis in a dog undergoing long-term immunosuppressive therapy.

This study was supported by the National Research Foundation (NRF) of Korea grant funded by the Korea government (MSIT) (RS-2023-00252033).

The dog described in this report was a client-owned patient presented for care at the veterinary medical teaching hospital of Jeju National University. Informed owner consent was received for any possible research use of all diagnostic samples acquired from the dog.

No potential conflict of interest relevant to this article was reported.