Authors: Mayesha Sharaf, Arman Manjikian, Rakahn Haddadin, Michael Ghobrial, Victoria Diaz, Li-chien Chen
Categories: Case Report, Streptococcus equi, Bacteremia, Cellulitis, Horse, Equine
Source: IDCases
Authors: Mayesha Sharaf, Arman Manjikian, Rakahn Haddadin, Michael Ghobrial, Victoria Diaz, Li-chien Chen
Streptococcus equi species is known to cause diseases in horses and other animals. This species, however, is a rare human pathogen and transmission usually occurs via direct interaction with horses or other domestic animal or unpasteurized dairy consumption. Reports of S. equi infections in human are relatively rare in the United States compared to the higher incidences in Europe. However, more and more cases of S. equi have been reported in the US as equine activities are gaining popularity. Whereas Streptococcus equi can involve any organ system, cellulitis caused by Streptococcus equi is hardly ever reported. As skin and soft tissue infection by Streptococcus equi is so rare and can pose fatal outcomes, it is imperative to keep this rare pathogen as a microbiologic differential of skin and soft tissue infection. We present a case of Streptococcus equi cellulitis and bacteremia in a patient with horse exposure*.* Considering how popular equine sports are becoming, Streptococcus equi infections are probably more widespread than we realize.
Streptococcus equi is a group C beta-hemolytic streptococcus. Subspecies includes equi, ruminatorum and zooepidemicus, all of which use various animals as their hosts and cause both serious and opportunistic infections [1]. Streptococcus equi subspecies equi is known to cause ‘Strangles’ in horses, which is a highly contagious respiratory infection characterized by fever, nasal discharge, and lymphadenopathy with lymph node abscessation. Streptococcus zooepidemicus causes opportunistic infections in horses. However, human infection with Streptococcus equi species is considered rare. S. equi is usually transmitted to human via contact with infected animals and consumption of unpasteurized dairy. Among the three subspecies*, Streptococcus equi* subspecies equi and zooepidemicus are more commonly associated with human infections including foodborne disease, meningitis, septicemia, arthritis, pneumonia, glomerulonephritis, and streptococcal toxic shock syndrome [2].
While there are case reports on Streptococcus equi foodborne disease, meningitis, septicemia, arthritis, pneumonia, glomerulonephritis, and streptococcal toxic shock syndrome in human; cellulitis or other skin and soft tissue infection is very rarely reported. There are only four cases of S. equi induced cellulitis reported worldwide [3], [4], [5], [6]. One of which was a patient in Poland who presented with multiple, oval and confluent, erythematous, scaly and crusted plaques over face, neck and chin after being exposed to a horse having nasal discharge and lymphadenopathy. Culture of skin swab yielded Group C Streptococcus [3]. Another case was described in United Kingdom where a patient developed wound infection, and later, meningitis after being trampled by a horse [4].
Although, Streptococcus equi infections had been frequently reported in Europe and other continents, it is rarely encounted in the United States. Only two cases of horse to human transmission of Streptococcus equi subsp. equi have been reported in the United States [5], [7], only one of them being a skin and soft tissue infection, where the patient developed facial erythema and tender lymphadenopathy following horse exposure, however, the route of transmission was not identified [5]. Also, to the author’s best knowledge, only one case of Streptococcus equi subsp. zooepidemicus bacteremia have been reported in the United States; however, the source of bacteremia was not identified [8]. We are presenting a case of horse to human transmission of Streptococcus equi causing cellulitis and bacteremia in the United States. Our patient most likely had direct inoculation of S. equi via a laceration injury. Although the subspecies of S. equi was not identified in our patient, the rarity of horse to human transmission of Streptococcus equi infections in United States makes our case unique and noteworthy.
A 73-year-old male with medical history significant of hypertension, well-controlled type 2 diabetes, bilateral knee arthroplasty (right and left knee 7 and 6 years ago respectively) presented to the emergency department with 9 days of right leg pain and redness with right knee swelling. He started to endorse high-grade fever and chills 2 days after the initial symptom onset as well. His home medications included one antihypertensive drug and one oral hypoglycemic agent and no recent changes were made in his medications. He denied any recreational or intravenous substance use. He reported working in a horse stall for the past month and unintentionally cutting himself in his right leg while working in the horse stall prior to the symptom onset.
On admission, he described constant severe pain in his right leg, worsening with walking and interfering with his activities of daily living. His vital signs on admission included a blood pressure of 155/76 mmHg, a heart rate of 93 beats/min, a respiratory rate of 18 breaths/min and an oral temperature 37.6-degree celsius. A complete physical examination was significant for dry mucous membrane, a cardiac murmur, and bright red erythema and confluent rash of the entire right lower leg spreading up to the right knee (Fig. 1). The right knee was warm and swollen with limited range of motion due to pain. The laboratory results showed a white blood cell count of 15.8 × 10*3/uL, C-reactive protein 25.3 mg/dL, erythrocyte sedimentation rate 93 mm/Hr, creatinine 1.67 mg/dL, and lactic acid 3.1 mmol/L. Empiric broad spectrum antibiotics were started.Fig. 1Right leg on presentation showing bright red erythema and confluent rash spreading up to right knee.
A 3-view X-Ray of the right knee showed periosteal reaction along proximal fibular diaphysis with cortical lucency (Fig. 2). These findings prompted a right lower extremity MRI which showed no evidence of osteomyelitis or abscess but a small knee joint effusion (Fig. 3). Our patient’s knee pain and swelling started to improve with broad spectrum antibiotics. Blood culture drawn on the day of admission returned positive for Streptococcus equi in biofire blood culture polymerase chain reaction. However, routine susceptibilities or further speciation was not performed. A transthoracic echocardiogram to rule out infective endocarditis showed normal left ventricular function and no valvular abnormalities or vegetations. Right lower extremity wound culture yielded no organisms. A right lower extremity CT scan without contrast to rule out septic arthritis showed no evidence of periprosthetic bone abnormality (Fig. 4). A whole-body white blood cell scintigraphy showed no abnormal focal white blood cell accumulation.Fig. 2X-Ray of right knee showing periosteal reaction along proximal fibular diaphysis with cortical lucency (blue block arrow). Right knee joint arthroplasty is evident as well.Fig. 3MRI of right knee showing total knee arthroplasty with small knee joint effusion within the expected volume (green block arrow), without any evidence of osteomyelitis or abscess.Fig. 4CT scan of right lower extremity without contrast showing no periprosthetic bony abnormalities.
Antibiotic was deescalated to intravenous Ceftriaxone (2000 mg every 24 h). His knee pain and range of motion improved with intravenous antibiotics. Repeat blood culture 48 h later showed clearance of bacteremia. His bacteremia was thought to be secondary to Streptococcus equi skin and soft tissue infection. Although, right knee arthrocentesis was not performed as our patient only had a small knee effusion, given the presence of a hardware, clinical suspicion for prosthetic joint infection was still of concern. Therefore, shared decision was made to treat our patient empirically for septic arthritis and six weeks of antibiotic treatment was initiated followed by suppressive therapy with oral Cephalexin for 6–12 months.
Cellulitis is a fairly common bacterial skin infection physicians encounter. It presents as a warm, tender, erythematous, and poorly demarcated area with associated edema [9]. Cellulitis and other skin and soft tissue infections can be a source of bacteremia like in our patient. Bacteremia from cellulitis and other skin and soft tissue infections can potentially lead to severe dissemination and infectious involvement of other organs making the microbiologic identification imperative. Most frequently encountered pathogens for cellulitis and other skin and soft tissue infections are group A streptococci followed by Staphylococcus aureus [9]. However, certain environmental and occupational exposure could increase the risk of infection by rare pathogens and, as in our case, Streptococcus equi was the microbiologic agent driving our patient’s cellulitis and eventually bacteremia.
All the three subspecies of Streptococcus equi are zoonotic agents, and rarely reported as human pathogens [10]. Streptococcus equi subspecies equi is known for causing the equine infection ‘Strangles’. S. equi subsp. zooepidemicus is an opportunistic pathogen in horses. It can cause outbreaks of hemorrhagic pneumonia in dogs as well. S. equi subsp. ruminatorum was described to cause mastitis in domestic sheep and goats. It can also result in severe infections in spotted hyenas and zebras. It is noteworthy that the host animal for S. equi subsp. zooepidemicus may appear healthy or asymptomatic as it is an opportunistic pathogen. On the other hand, strangles caused by S. equi subsp. equi is one of the most common infectious diseases in horses worldwide. The bacteria gain entry to the upper respiratory tract via inhalation or ingestion and colonizes regional lymph nodes. Bacterial replication and neutrophil influx contribute to the lymphadenopathy and lymph node abscessation that characterize clinical disease. Hematogenous and lymphatic spread of bacteria beyond the upper respiratory tract may also occur, resulting in abscess formation throughout the body (metastatic strangles) [14]. Strangles in horses became a reportable disease in the United States in 2017.
Both S. equi subsp. equi and zooepidemicus reported in humans were following close contact with horses and resulted in severe disseminated infections in both immunocompromised and immunocompetent patients [11], [12]. A literature review conducted on cases of meningitis caused by group C Streptococcus showed 31% of the reported cases arose from equine exposure and 19% from ingestion of dairy products [13]. Nature of horse exposure varies widely, direct personal contact being the most common. However, infection can also transmit through close contact with a person who had direct contact with horses and horse bites [11]. S. equi subsp*. ruminatorum* has been isolated from an HIV infected patient [2]. Immunodeficiency increases the risk of S. equi subsp. ruminatorum transmission to humans. Unpasteurized dairy consumption caused outbreaks of S. equi subspecies equi and zooepidemicus as well [11], [15]. However, irrespective of their routes of transmission and other associations, both S. equi subsp. equi and ruminatorum are very rare causes of human infections while subsp. zooepidemicus is a more common disease-causing pathogen in humans. Table 1 indicates equine and human associations of different S. equi subspecies.Table 1Different S. equi subspecies with their corresponding associations.S. equi subspeciesAssociation in animalsAssociation in humanReferencesS. equi subspecies equi- Strangles in horses- Bloodstream infection- CNS infection (meningitis, subdural empyema)- Endocarditis- Infected aortic aneurysm with psoas abscess- Pneumonia- Septic arthritis7, 10, 11, 12, 14S. equi subspecies zooepidemicus- Opportunistic infections in horses- Hemorrhagic pneumonia in dogs- Bloodstream infection- Cellulitis with subcutaneous abscesses- CNS infection (meningitis)- Endocarditis- Pharyngitis- Septic arthritis- Toxic shock-like syndrome- Uveitis3, 4, 8, 15, 16S. equi subspecies ruminatorum- Mastitis in domestic sheep and goats- Severe infections in spotted hyenas and zebras- CNS infection (meningitis)- Endocarditis- Pneumonia with bilateral pulmonary infiltrate2, 6
Infections caused by S. equi species in humans include outbreaks of foodborne illness, meningitis, septicemia, septic arthritis, pneumonia, glomerulonephritis, and streptococcal toxic shock syndrome [9], [16], [17], [18], [19]. However, cellulitis caused by any of the S. equi species is uncommon. Cellulitis is a clinical diagnosis; however, gram stain and blood cultures are necessary if a patient has signs of systemic infection similar to our patient. S. equi is a gram-positive coccus that appear in pairs or chains on gram stains. Blood or other bloody fluid culture yields growth of catalase-negative, beta-hemolytic, gram-positive cocci. Colonies on blood agar are often mucoid, honey colored, and surrounded by a wide zone of beta hemolysis [20], [21]. Displayed mucoid colonies indicate the expression of a hyaluronic acid capsule, a well-known virulence factor in other pathogenic Streptococcus strains [12]. Diagnosis of Equidae infection is usually made by cultures of nasopharyngeal swab or wash [14].
In our case, the subspecies of S. equi was not identified. However, the rarity of human infection from S. equi subspecies as a whole rendered our case notable. Although routine sensitivity was not reported from the microbiology lab, our patient responded well to third generation Cephalosporin. From the literature review, beta-lactam antibiotics have been used to treat all three subspecies of Streptococcus equi infection along with symptomatic management [13].
Two horse-to-human transmissions of S. equi subsp equi have been reported in the United States until 2023 [5], [6]. One was a skin and soft tissue infection; however, the route of transmission was not specified [5]. The other case demonstrated a patient suffering from pneumonia. Among the worldwide reported cases of Streptococcus equi subsp equi and zooepidemicus, only two cases constituted skin and soft tissue infection by the pathogen [3], [4]. To our knowledge, only 2 cases of human infection by S. equi subsp. ruminatorum have been reported worldwide so far [2], [6], and only one case reported probable contamination via the skin, a mode of transmission that has not been described previously for this specific subspecies [6]. Our patient likely had cellulitis and bacteremia via direct inoculation through skin contamination which has been shown to be a clear route of transmission [11]. Although it was unknown if any of the horses in the stable were infected and therefore, direct causal link between our patient’s horse exposure and presenting illness cannot be established. However, due to the rarity S. equi bacteremia in human without zoonotic exposure, we suspect our patient’s septic state was most likely linked to contact with horses. Had it gone untreated, it could have become fatal. Hence, our case discusses the importance of keeping a broad microbiologic differential of skin and soft tissue infection. Clinicians should routinely ask about equine exposure in cellulitis and consider zoonotic streptococci when gram-positive cocci are isolated, especially in areas where farming and ranching are prevalent, as proper identification of the causative organism in skin and soft tissue infection is essential to guide the treatment and prevent further life-threatening complications. Fig. 5 delineates a timeline graph summarizing the events, admission and, treatment course of our case.Fig. 5Timeline graph summarizing events.
Rakahn Haddadin: Resources. Michael Ghobrial: Resources. Victoria Diaz: Project administration. Chen Li-Chien: Writing – review & editing, Supervision, Conceptualization. Mayesha Sharaf: Writing – original draft, Validation. Arman Manjikian: Methodology.
Informed written consent was obtained from the patient for the publication of this case report and any accompanying images.
The authors declare that they have no known competing financial or personal interests that could have influenced the work reported in this paper.