A Rare Case of Disseminated Group G Streptococcus Bacteremia Complicated by Multi-Systemic Infections: Infective Endocarditis, Endophthalmitis, and Meningitis

Introduction

Group G beta-hemolytic streptococci, including Streptococcus dysgalactiae subsp. equisimilis (SDSE), are normal inhabitants of the skin, oropharynx, and gastrointestinal and female genital tracts [1]. Recent epidemiological data indicate that the prevalence of GGS infections has been rising globally [2,3], particularly among older adults and individuals with underlying chronic illnesses [4]. Although typically associated with superficial infections such as pharyngitis and cellulitis, GGS has shown an increasing capacity to cause invasive disease, partly due to virulence factors shared with Streptococcus pyogenes (group A Streptococcus, GAS) [5,6]. These virulence factors include M proteins and streptolysins, which enable immune evasion and tissue invasion, leading to severe conditions such as streptococcal toxic shock syndrome (STSS), necrotizing fasciitis, meningitis, and infective endocarditis.

Notably, infective endocarditis occurs in approximately 4.9% to 8.2% of SDSE bacteremia cases, with a high mortality rate of 29% [7], suggesting a significant potential for invasive disease. Although GGS accounts for a variable proportion of invasive streptococcal infections, reports of severe outcomes such as meningitis and endogenous endophthalmitis are quite limited. A 2018 literature review identified only 16 cases of endogenous endophthalmitis associated with GGS [8], and a French multicenter study of 182 invasive GGS infections reported only 2 cases of meningitis [9]. Despite their rarity, these infections can be life-threatening, and there are few reports of multiple sites being affected concurrently. To our knowledge, this is the first reported case in which GGS simultaneously caused infective endocarditis, endogenous endophthalmitis, and meningitis, highlighting its potential to cause severe and disseminated infections.

Case Report

A 53-year-old Japanese man presented with fever, arthralgia, and limited mobility. His history was significant for a Bentall procedure (aortic root replaced with prosthetic SJM 25A valve and 28 mm Hemashield graft) for aortic regurgitation 28 years prior and a ventriculoperitoneal (VP) shunt placed 4 years earlier for traumatic hydrocephalus. He was followed by the cardiology department every 3 months for atrial tachycardia/atrial flutter. The patient was a former smoker with a 20 pack-year history from age 20 to 40. Two days prior to admission, he developed a fever of 39°C accompanied by chills, joint pain, and difficulty moving, which prompted emergency transport to our hospital.

Upon arrival, he had slightly impaired consciousness, with Japan Coma Scale (JCS) score of 1 and Glasgow Coma Scale (GCS) score of E4V5M6. His vital signs showed a body temperature of 38.9°C, blood pressure of 159/116 mmHg, heart rate of 138 bpm, respiratory rate of 28 breaths per minute, and SpO2 was 97% on room air. He exhibited conjunctival and palpebral congestion in the left eye, no jolt accentuation or nuchal stiffness, and had poor oral hygiene without any dental caries. No heart murmur was auscultated, and Janeway lesions, Osler’s nodes, and splinter hemorrhages were absent. Laboratory tests revealed elevated C-reactive protein (CRP) level of 19.63 mg/dL (normal range: <0.14), thrombocytopenia of 74 000/μL (normal range: 158 000–348 000), elevated liver enzymes and elevated total bilirubin of 5.4 mg/dL (normal range: 0.4*1.5), and a negative rheumatoid factor. Urinalysis showed microscopic hematuria and proteinuria. Brain CT revealed no cause of impaired consciousness, and contrast-enhanced CT of the chest and abdomen revealed no definite focus of infection.

Empiric ceftriaxone 2 g every 24 hours was initiated for presumed bacteremia. On hospital day 2, his consciousness declined to JCS score of 10, with a GCS score of E3V4M6. He was transferred to the intensive care unit, where he was intubated. Cerebrospinal fluid analysis revealed a cloudy, xanthochromic appearance with pleocytosis (white blood cells 408/μL, 93.8% neutrophils), elevated protein level of 197 mg/dL (normal range: 10–50), and decreased glucose level of 31 mg/dL (normal range: 45–70, serum glucose 159 mg/dL). CSF culture yielded no bacteria. He also developed ophthalmoplegia with pain on eye movement. An ophthalmologic consultation was promptly performed. Evaluation revealed bilateral endogenous endophthalmitis. Intraocular vancomycin was initiated on the same day. Blood cultures obtained upon admission yielded 2/2 sets of GGS. Mass spectrometry failed to identify the species. Antimicrobial susceptibility testing indicated susceptibility to penicillin G, ampicillin, cefotaxime, vancomycin, clindamycin, and levofloxacin. The antibiotic was de-escalated to ampicillin 2 g every 4 hours. On hospital day 4, the blood cultures became negative. Inflammatory markers showed a trend toward improvement, and on hospital day 7, the level of consciousness returned to normal and he was extubated. On hospital day 12, vitrectomy and removal of bacterial clumps were performed, followed by intravitreal vancomycin and ceftazidime and topical therapy. On hospital day 8 and day 24, he had elevated inflammatory markers and fever. Suspecting central line-associated bloodstream infection and pneumonia, antimicrobial therapy was escalated to cefepime and vancomycin. After confirming that blood cultures were negative after 1 week of incubation, the antibiotics were de-escalated to ampicillin. Repeated transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) showed no vegetations; however, gallium scintigraphy performed on hospital day 33 revealed uptake around the aortic valve annulus (Figure 1), suggesting prosthetic valve endocarditis. Contrast-enhanced MRI conducted on hospital day 36 was negative for any brain abscess, arterial emboli, or intracranial hemorrhage. Upon discharge, there were no neurological abnormalities. No severe valvular regurgitation was observed, and left ventricular function was preserved. The left eye progressed to blindness (Figure 2), whereas the right eye improved from counting fingers at 50 cm to a corrected visual acuity of 1.0. The patient completed 8 weeks of intravenous antibiotic therapy following negative blood cultures on hospital day 4 and was discharged on hospital day 66.

Discussion

This case illustrates the potential for GGS to cause aggressive, multisystem invasive infections. Skin and soft tissue are the predominant portals of entry in GGS infection, with cellulitis being the most common clinical manifestation of SDSE bacteremia, accounting for up to 68% of cases in some cohorts [10]. Given our patient’s history of a heart condition, despite the absence of edema on presentation, it is conceivable that conditions such as venous congestion or subclinical edema could have created a susceptible environment for infection. Such circulatory disturbances may have led to localized stasis or minor skin breakdown, thereby facilitating bacterial entry. Additionally, disruption of barriers in the oropharyngeal cavity, gastrointestinal tract, or genital tract could also have contributed to the infection. Among these, the patient’s poor oral hygiene suggests that the oral cavity may have served as the source of infection in this case. However, since there was no evident dental caries or other oral pathology, a dental consultation was not pursued. Nonetheless, primary bacteremia without an identifiable focus occurs in 13% to 37% of SDSE cases [10–12], and the definitive source of infection in our patient remains unconfirmed.

The diagnosis of infective endocarditis (IE) in this patient was particularly challenging. The modified Duke criteria are reported to detect approximately 80% of all IE cases and less than 60% of prosthetic valve endocarditis cases [13]. Applying these criteria, this case was classified as “probable” IE, as it fulfilled 1 major criterion (GGS isolated from 2 different blood cultures) and 3 minor criteria (fever >38°C, presence of a prosthetic valve as a predisposing heart condition, and metastatic infection). Regarding imaging modalities, prosthetic valves are more challenging to visualize with echocardiography compared to native valves. In response, the International Society for Cardiovascular Infectious Diseases (ISCVID) proposed in 2023 an update to the criteria, advocating for the inclusion of cardiac computed tomography (CCT) and 18F-FDG PET/CT as major criteria [14]. Echocardiography and CCT are complementary tools in the evaluation of suspected IE, improving diagnostic accuracy. Performing CCT on this patient may have contributed to enhanced diagnostic confidence. In this case, gallium scintigraphy was utilized as an adjunctive diagnostic tool. Historically, gallium scintigraphy has been limited by high radiation doses, lengthy procedure times, and lower spatial resolution, leading to its gradual replacement by FDG PET/CT. While FDG PET/CT is considered the best imaging modality for IE diagnosis and is included in current diagnostic criteria, practical constraints such as cost and the ability to perform the procedure during hospitalization may limit its use. As such, gallium scintigraphy may serve as a useful alternative in selected cases, providing valuable supplementary information when PET imaging is not feasible.

Indications for surgical valve replacement in infective endocarditis include acute heart failure due to valvular dysfunction, uncontrolled infection with persistent bacteremia, and large vegetations (>10 mm) [15]. In the present case, vegetations were not detected on echocardiography, there was no evidence of advanced valvular destruction, and the patient’s hemodynamics remained stable; thus, surgical intervention was not undertaken.

Endophthalmitis is classified into 2 types based on the route of infection: exogenous and endogenous. Exogenous endophthalmitis occurs when microorganisms are introduced into the eye following ocular surgery, penetrating trauma, or the presence of retained foreign bodies. In contrast, endogenous bacterial endophthalmitis is a rare condition, accounting for 2% to 8% of all cases of endophthalmitis [16]. The most frequent gram-positive microorganisms that cause endogenous endophthalmitis are Staphylococcus and Streptococcus species, while Pseudomonas aeruginosa is the most common gram-negative organism. Approximately half of GGS-associated endophthalmitis cases are complicated by concurrent infective endocarditis. When GGS endophthalmitis develops, visual improvement is only observed in 31.3% of cases [8], and the visual prognosis is reportedly poor. Furthermore, 25% of bacterial endophthalmitis cases are initially misdiagnosed as uveitis, fungal endophthalmitis, orbital cellulitis, or conjunctivitis [16]. In patients with prosthetic valves or other risk factors for infective endocarditis, as in the present case, clinicians should maintain a high index of suspicion for hematogenous dissemination to the eye and other organs. Prompt ophthalmologic assessment is crucial when ocular symptoms arise. Standard treatment for endogenous endophthalmitis includes vitrectomy and intravitreal antibiotics, typically vancomycin for gram-positive organisms and ceftazidime for gram-negative organisms. Early intervention, particularly within 24 hours of diagnosis, is associated with improved visual outcomes [17], as demonstrated in this case.

The increase in invasive infections caused by GGS is an emerging public health concern that warrants further attention. It is important for healthcare professionals to recognize these infections as emerging invasive diseases, and to actively investigate multisite involvement even when only subtle clinical symptoms are present. Chronic diseases such as diabetes mellitus, cardiovascular diseases, malignancy, obesity, immunosuppression, and chronic skin conditions are major risk factors for recurrent SDSE infections [4]. From an infection prevention standpoint, emphasis should be placed on managing underlying comorbidities and ensuring meticulous skin and wound care, along with a growing expectation for future vaccine development.

Conclusions

This case highlights a rare presentation of GGS infection manifesting concurrently as infective endocarditis, endogenous endophthalmitis, and bacterial meningitis. Although the exact entry route remains unconfirmed, clinical findings suggested possible portals such as the skin and oral cavity. Recent updates to diagnostic criteria, including advanced imaging modalities like cardiac CT and FDG PET/CT, may further enhance diagnostic accuracy in similar cases. Early recognition and prompt ophthalmologic intervention proved crucial in achieving visual recovery despite the generally poor prognosis associated with GGS endophthalmitis. This case underscores the importance of clinical vigilance, timely diagnosis, and multidisciplinary management in severe invasive GGS infections. Moreover, it highlights the need for further research into a broader understanding of the epidemiology, effective diagnostic strategies, and preventive measures to better manage and curtail the increasing incidence of invasive GGS infections.