Pneumococcal Endocarditis, Sepsis, and Meningitis in an Immunocompromised Patient: A Case Study

Introduction

Streptococcus pneumoniae is a rare cause of infective endocarditis (IE) accounting for a small percentage of cases, compared with other streptococcal species. A large observational study conducted in Denmark, including 2598 patients with pneumococcal bacteremia found that the prevalence of IE in patients with pneumococcal bacteremia was approximately 1.2% [1]. Concurrence of endocarditis and meningitis because of invasive pneumococcal disease is even rarer. Risk factors associated with an increased likelihood of developing pneumococcal IE include immunosuppression, alcoholic liver disease, underlying heart disease, and splenectomy or asplenia [2].

Pneumococcal IE commonly presents clinically with fever and a new heart murmur [2]. Notably, concurrent pneumococcal meningitis has been reported in up to 40.5% of affected patients, highlighting the aggressive nature of invasive pneumococcal infections [2]. In patients with pneumococcal IE, the aortic valve is most commonly affected [2]. Despite the low prevalence of invasive pneumococcal infections in the general population, immunocompromised patients are at risk for invasive infection, including pneumococcal IE. In fact, studies have shown that people living with HIV are at a heightened risk for invasive pneumococcal diseases, including bacteremia, meningitis, and IE [3]. Pneumococcal IE is characterized by a highly progressive course, often resulting in extensive valvular damage and necessitating surgical intervention. Among streptococcal species causing IE, S. pneumoniae has been associated with the highest rate of heart valve surgery required, likely due to its aggressive nature [4].

In this report, we present a rare case of concurrent pneumococcal sepsis, meningitis, and native mitral valve endocarditis in a patient with untreated HIV infection. This case underscores the importance of considering IE in immunocompromised patients presenting with invasive pneumococcal disease and highlights the critical role of early diagnosis and surgical management in improving patient outcomes.

Case Report

A 37-year-old man with HIV infection not on antiretroviral treatment presented with progressively worsening fever, confusion, back pain, and headache for a few weeks. He was found in an obtunded state, with a III/VI holosystolic murmur in the left lower sternal border. No other pertinent positive clinical findings were present on physical examination. The patient’s vital signs on presentation were as follows: blood pressure of 122/80 mmHg, heart rate of 103 beats per min, respiratory rate of 34 breaths per min, temperature of 38.2°C. Notable past medical history included a previous hospitalization, with severe pneumococcal sepsis and meningitis requiring intensive care unit level of care and intubation for airway protection 1 year prior to this presentation, housing insecurity, and limited access to healthcare. The patient had never received pneumococcal vaccination. Of note, the patient had initially received a diagnosis of HIV 16 months prior to his presentation to the Emergency Department and had never been on antiretroviral treatment. Initial differential diagnosis included central nervous system (CNS) infections (bacterial meningitis, viral meningitis or meningitis/encephalitis related to opportunistic pathogens), IE with embolic phenomena involving the CNS, CNS malignancies, acute metabolic derangements, toxic ingestion, and acute substance withdrawal.

Initial laboratory workup was remarkable for leukocytosis, with 27 600 white blood cells (WBCs)/µL (reference range 4.5–11.0×103/µL) with neutrophilia, HIV viral load of 102 000 copies/mL (undetectable <20 copies/mL) and CD4+ count of 220 cells/mm3 (normal 500–1500 cells/mm3), and hemoglobin A1c of 6%. Non-contrast head computed tomography (CT) was unrevealing, and brain magnetic resonance imaging (MRI) revealed leptomeningeal enhancement within the superior bilateral frontal and parietal lobes (Figure 1). Cerebrospinal fluid studies were notable for the presence of 100 nucleated cells, with neutrophilia (85%), low glucose (<10 mg/dL), and elevated protein (>200 mg/dL). Bacterial cultures in the blood and cerebrospinal fluid grew S. pneumonia, with resistance to penicillin (Table 1). Given the presence of a suspected new murmur in an immunocompromised patient with unclear duration of bacteremia, transthoracic echocardiography was performed to screen for infective endocarditis, revealing large (largest measuring 2.3×1.3 cm), mobile, echogenic, and multilobular masses present on the anterior and posterior leaflets of the mitral valve, associated with mild mitral valve regurgitation (Figure 2). At this point, pneumococcal sepsis, meningitis, and IE were diagnosed.

The patient was initially treated empirically for bacterial meningitis with intravenous (i.v.) vancomycin, ceftriaxone, ampicillin, and dexamethasone, according to the standard of care, followed by targeted treatment with ceftriaxone, according to bacterial culture species identification and susceptibility studies. The Cardiothoracic Service was consulted for further management of the sizeable mitral valve vegetations. Due to the size of the vegetations posing a risk for septic embolization, a shared decision was made between the patient and the treatment team for surgical repair/replacement of the mitral valve. The patient underwent coronary CT angiography for preoperative evaluation, which revealed vegetations attached to both leaflets of the mitral valve (Figure 3). Initial intraoperative transesophageal echocardiography (TEE) imaging revealed mitral valve leaflet thickening with multiple mobile masses, with the largest measuring at least 1.2×1.6 cm attached to the anterior and posterior mitral valve leaflets and associated with multiple eccentric jets (Video 1A). Operative exposure of the mitral valve revealed sizable vegetations attached to both leaflets of the mitral valve leading to perforation and destruction of significant portions of the valve leaflets. Given the extent of destruction of the valve leaflets, valve replacement was decided. A bioprosthetic valve was selected due to concerns regarding the patient’s adherence to medical treatment and inadequate access to healthcare. The final intraoperative TEE (post-valve deployment) revealed appropriate positioning of the valve, without significant leak or regurgitation (Video 1B). Histopathologic examination of the native mitral valve specimen was consistent with acute suppurative destructive endocarditis. Of note, the intraoperative bacterial cultures were negative. Following the results of species identification and the susceptibility studies, and given that the intraoperative cultures of the affected valve tissue were negative, the patient was treated with i.v. ceftriaxone 2 g every 24 h, for a total duration of 4 weeks, starting from the day of initial blood culture clearance. The above recommendations were outlined by the Infectious Disease Service in accordance with guidance from the Infectious Disease Society of America for the management of pneumococcal endocarditis [5]. The patient was started on bictegravir/emtricitabine/tenofovir alafenamide for the management of his HIV infection on the day of discharge from the hospital, with recommendations to follow-up with the HIV clinic. The patient was discharged in good clinical condition 1 week after the cardiac surgery.

Discussion

Our patient presented with a unique combination of pneumococcal sepsis, meningitis, and infective endocarditis affecting the mitral valve. IE diagnosis follows the updated modified Duke criteria [6]. Given that S. pneumoniae is not typically associated with IE, the decision for echocardiographic screening for IE in patients with pneumococcal sepsis should be individualized [1,4]. A study of 6393 patients with streptococcal bloodstream infections suggested that patients with pneumococcal bacteremia should be screened with echocardiography if they have 3 or more positive blood cultures and an additional risk factor (native valve disease, previous endocarditis, prosthetic valve, cardiac device) [4]. Patients not meeting these criteria should be screened with echocardiography, based on high clinical suspicion for endocarditis, such as persistent or recurrent bacteremia, metastatic infectious disease, or acute heart failure. In our case, the decision for echocardiographic screening for IE was based on the following factors: immunocompromised status of the patient (untreated HIV), suspected prolonged bacteremia (patient had been symptomatic for a few weeks prior to his presentation), and presence of a presumed new murmur.

Pneumococcal endocarditis can progress rapidly with minimal systemic symptoms and cause extensive thrombotic vegetations that lead to destruction of the affected valve with high mortality rates (20%) [2]. Of note, IE caused by S. pneumoniae has been associated with the highest rates of surgical valve intervention among all streptococcal species, according to Chamat-Hedemand et al [1]. Major contributing factors to mortality in S. pneumoniae IE are acute heart failure and cardiogenic shock related to acute valve destruction (occurs in more than 50% of patients with pneumococcal IE) [6]. Therefore, surgical management of IE is required in more than half of patients presenting with pneumococcal IE, to prevent detrimental outcomes [2,6]. The following criteria for surgical management of patients with native valve pneumococcal IE have been suggested: (i) acute heart failure related to severe valvular dysfunction causing hemodynamic instability; (ii) uncontrolled infection evidenced by persistent bacteremia or fever despite appropriate antibiotic therapy; (iii) development of perivalvular complications such as abscess, fistula, conduction system abnormalities, pseudoaneurysm formation, valve dehiscence or valve leaflet perforation, and rupture of chordae tendineae or papillary muscles; and (iv) presence of large vegetations (>10 mm), increasing risk for septic embolization [2,4,6,7]. Our patient exhibited large vegetations exceeding 10 mm on the mitral valve, causing valvular dysfunction and posing a high risk for embolic events. Early surgical intervention was crucial to prevent potential embolic events and further deterioration. The decision to replace the mitral valve was based on extensive leaflet destruction that precluded repair.

Antimicrobial resistance is an emerging concern in pneumococcal infections. Our patient’s isolate was resistant to penicillin, aligning with global trends of increasing pneumococcal resistance [8]. This resistance highlights the necessity of performing susceptibility testing to guide appropriate antibiotic selection. Accordingly, our patient was treated with i.v. ceftriaxone, based on the susceptibility profile of the isolate. Combining timely surgical intervention with targeted antimicrobial therapy was essential for successful management and contributed to a favorable outcome.

Pneumococcal vaccination is particularly important in high-risk populations, like patients with HIV [9]. Unfortunately, our patient had not received pneumococcal vaccination, which could have altered the natural history of his disease. This underscores the need for improved vaccination strategies and better access to healthcare services for vulnerable populations.

Conclusions

IE related to pneumococcal bacteremia is a rare but potentially detrimental complication. Diagnosis of pneumococcal IE requires high clinical suspicion. Timely involvement of a multidisciplinary team for early operative management of IE can prevent detrimental outcomes.