Pulmonic Valve Endocarditis and Septic Pulmonary Embolism Caused by Staphylococcus haemolyticus: A Case Study

Introduction

Infective endocarditis is a condition related to the inflammation and microbial colonization of the cardiac valve endocardium. Most cases of infective endocarditis are associated with left heart valvulopathies, with right-sided infective endocarditis implicated in approximately 5 to 10% of all reported cases [1,2]. Of the aforementioned right heart infective endocarditis cases, the tricuspid valve is predominantly impacted (~90% of cases) with isolated involvement of the pulmonic valve being exceedingly rare [1,2]. Without early detection and treatment, numerous extracardiac manifestations can develop, often resulting in death. The diagnosis of infective endocarditis consists of a combination of laboratory testing and clinical manifestations known as the Duke criteria [3].

The majority of infective endocarditis cases are caused by Gram-positive Streptococcus, Staphylococcus, and Enterococcus species; Staphylococcus aureus causes about 30% of the cases of infective endocarditis worldwide [3,4]. Less commonly, Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella (HACEK), as well as Bartonella, Coxiella, and fungi can lead to infective endocarditis [3,5]. Staphylococcus haemolyticus is a coagulase-negative Staphylococcus, and an unusual causative pathogen of infective endocarditis that is associated with prosthetic valves and indwelling medical devices [6].

As previously noted, infective endocarditis of the pulmonic valve is a very uncommon pathology comprising less than 2% of all cases of infective endocarditis [2,7]. The majority of cases of pulmonic valve endocarditis occur in those with congenital heart disease and those who are intravenous (IV) drug users [7,8]. The presentation of pulmonic valve endocarditis in adults is rare, and even less likely in individuals without risk factors such as indwelling catheters, implanted devices, or a history of IV drug use. Pulmonic valve endocarditis only accounts for 1.5–2% of the total number of cases of infective endocarditis; however, septic pulmonary emboli are seen in around 50% of these cases [7]. The diagnosis requires blood cultures and echocardiography for early characterization, and IV antibiotics remain the mainstay of treatment, similar to other types of infective endocarditis. Pulmonary valve replacement is rarely utilized as management, but it has been associated with favorable long-term outcomes [9].

Case Report

A 31-year-old man with no past medical history presented with bilateral lower extremity and facial swelling for several days. A review of systems was positive for shortness of breath on exertion and subjective fevers, chills, and night sweats that had persisted over the previous 3 months. Upon presentation, the patient was afebrile, tachycardic, and saturating at 97–99% O2 on room air. Physical examination revealed tachycardia with regular rhythm, hepatomegaly, and bilateral axillary lymphadenopathy; his lungs were clear to auscultation. Initial laboratory testing was notable for a low hemoglobin level of 4.9 g/dL despite no evidence of active bleeding, leukocytosis at 19.41 cells/mm3, creatinine of 1.85 mg/dL, and an elevated n-terminal pro brain natriuretic peptide of 9633 pg/mL (Table 1). Given the tachycardia and laboratory abnormalities, there was a high index of suspicion of a possible pulmonary embolism. As such, computed tomography (CT) of the chest, abdomen, and pelvis was performed and revealed a right lower lobe segmental pulmonary embolism with evidence of right heart strain, ground-glass opacifications in the right lower lobe of the lung, and cardiomegaly with evidence of a large pericardial effusion along with multi-station lymphadenopathy. He was started on empiric antibiotic coverage with ceftriaxone and azithromycin for suspected pneumonia, with opacifications in the right lower lobe of the lung. These antibiotics were chosen for their broad coverage of common community-acquired pathogens including Streptococcus pneumoniae as well as atypical organisms such as Mycoplasma pneumoniae.

Additionally, following his diagnosis of the pulmonary embolism, further investigation was warranted for the significant anemia he presented with on admission. Given his anemia along with the presence of lymphadenopathy, a lymph node biopsy was performed to evaluate for malignancy, but was unsuccessful due to the small size of his lymph nodes. Additional laboratory testing, including lactate dehydrogenase and haptoglobin, returned results within normal limits, indicating that there was no evidence of hemolysis either. Flow cytometry also did not identify any abnormal monoclonal cell populations. As such, with no active signs of bleeding, and with an appropriate increase in his hemoglobin following blood transfusions, his hemoglobin eventually stabilized between 7–10 g/dL through the remainder of his hospital course.

Simultaneously, while his anemia was undergoing investigation, weighing the risks versus the benefits given his pulmonary embolism, the patient was started on intravenous heparin and admitted to the intensive care unit (ICU) for management of his intermediate-to-high-risk pulmonary embolism (Figure 1). Transthoracic echocardiography (TTE) was initially chosen to evaluate for a cardiac source of the pulmonary embolism as well as to assess for right heart strain, which revealed a 9-mm pulmonic valve vegetation (Figure 2). However, limitations in determining vegetation size later necessitated transesophageal echocardiography (TEE) for more accurate assessment.

With the patient reporting subjective fevers at home prior to presentation, he also continued to be febrile after hospitalization, prompting an infectious workup. Two sets of blood cultures were obtained on admission, and after 2 days of incubation, both grew Staphylococcus haemolyticus, establishing persistent bacteremia. In accordance with the modified Duke criteria, the patient met 2 major criteria (persistent bacteremia and vegetation confirmed by echocardiography), fulfilling a definitive diagnosis of infective endocarditis [3]. He was then started on intravenous vancomycin as treatment, for its coverage of gram-positive organisms, in particular, methicillin-resistant Staphylococcus aureus. His hospital course following his diagnosis of infective endocarditis and bacteremia was then complicated by worsening dyspnea and eventual acute hypoxic respiratory failure requiring supplemental oxygen via nasal cannula in the setting of a right-sided pleural effusion. He underwent a diagnostic and therapeutic thoracentesis, reporting some improvement in his dyspnea thereafter. The resulting pleural fluid culture was negative, but fluid testing revealed an exudative nature of the effusion. His hospitalization was further complicated by recurring fevers for which he was then started on cefepime in addition to vancomycin, selected for its role in the broad-spectrum empiric coverage of gram-negative organisms, in addition to vancomycin’s coverage of gram-positive organisms. However, after 3 days of dual therapy with cefepime and vancomycin, his fevers resolved and repeat infectious workup was negative, after which cefepime was discontinued.

During the patient’s inpatient admission, upon further inquiry, the patient denied a history of indwelling catheters, implanted devices, or prior IV drug use. His urine drug screen was negative for illicit substances. Additionally, further autoimmune workup revealed a positive rheumatoid factor. The following workup was negative: human immunodeficiency virus (HIV), hepatitis B and C, Epstein Barr virus (EBV) panel, anti-double stranded DNA antibody, anti-cyclic citrullinated peptide antibody, anti-neutrophil cytoplasmic autoantibody, immunoglobulin G4, Quantiferon Gold, urine streptococcal antigen, Q fever antigen, Coxsackie antibody, and complement C3 levels.

Once the patient’s fevers had abated, to complete the workup of the vegetation seen on TTE, a TEE was then performed, showing an 18-mm vegetation on the pulmonic valve associated with a flail leaflet, with an otherwise preserved ejection fraction (Figure 3). On hospital day 18, the patient underwent cardiothoracic surgery for pulmonary valve replacement using a bioprosthetic valve, pericardial patch augmentation of the pulmonary artery, and primary closure of his patent foramen ovale (PFO). The decision for valve replacement was made based on treatment guidelines, as his vegetation was greater than 10 mm, to reduce the risk of further embolic events, along with the presence of valve dysfunction likely resulting in his persistent dyspnea. Intraoperative wound cultures and surgical pathology were obtained; however, both returned negative, along with negative repeat blood cultures, likely owing to the fact that the patient had already been on IV antibiotics since presentation on hospital day 1. Following surgery, he reported resolution of his shortness of breath and reported feeling significantly less fatigued compared with his condition on admission. Eleven days later, on hospital day 29, he was discharged on apixaban as anticoagulation therapy for the pulmonary embolism along with intravenous vancomycin for a duration of 6 weeks from the date of surgical valve replacement. On discharge, he was also instructed to follow up at regular intervals with cardiology and cardiothoracic surgery, along with a follow-up TTE in 3 months’ time to evaluate for right ventricular remodeling. At subsequent follow-up visits, he was noted to have completed the course of vancomycin and reported feeling well without any additional complications.

When reviewing the patient’s entire hospital course from the day of admission to the diagnosis of infective endocarditis, numerous differential diagnoses were considered. Initially, given the tachycardia and dyspnea on presentation, pulmonary embolism was important to consider on the differential, and given the positive imaging findings, he was appropriately started on anticoagulation. As the patient had also reported subjective fevers, chills, and night sweats, along with evidence of lymphadenopathy, a broad differential of infectious etiologies was also considered. Among these, tuberculosis, HIV, hepatitis, EBV, Coxsackie infection, and Coxiella infection causing Q fever were all considered. However, as stated above, all specific workup and testing for these infectious etiologies returned negative. Autoimmune pathologies were also considered as part of the differential diagnosis, but apart from a positive rheumatoid factor, the more specific anti-cyclic citrullinated peptide antibody assays returned negative, and the remainder of autoimmune testing also returned negative, helping to rule out an autoimmune etiology. Overall, given the presence of bacteremia, with equivocal findings of vegetation on echocardiography, per Duke criteria, the diagnosis of infective endocarditis was firmly established, with the CT imaging findings further confirming the presence of septic pulmonary emboli.

Discussion

This case highlights a rare presentation of infective endocarditis involving the pulmonic valve in a patient with no predisposing risk factors [10]. An important aspect to note is that while our patient did have a PFO, this cardiac abnormality by itself does not predispose patients to infective endocarditis unless it is accompanied by other congenital heart defects or prosthetic heart valves, neither of which were present in our patient. This case also emphasizes the clinical importance of obtaining a TEE for evaluation of infective endocarditis, especially for confirmatory diagnosis and to establish the size of a vegetation. The TTE underestimated the size significantly in this instance, which ultimately impacted the overall management of this patient.

In our patient, the diagnosis of infective endocarditis was confirmed through utilization of the modified Duke criteria, in conjunction with his blood cultures and further negative workup for other etiologies including other autoimmune and infectious workup. During his admission, 2 sets of blood cultures that were obtained on admission returned positive for Staphylococcus haemolyticus, establishing persistent bacteremia. Imaging with a TTE and thereafter with a TEE, confirmed the presence of valve vegetation. In accordance with the modified Duke criteria, the patient met 2 major criteria, establishing the definitive diagnosis of infective endocarditis [3]. Additionally, the presence of a pulmonary embolism as identified on CT imaging in the setting of his diagnosed infective endocarditis and bacteremia was consistent with the diagnosis of septic pulmonary embolism.

Generally, the treatment of infective endocarditis involves intravenous antibiotics such as nafcillin for methicillin-susceptible strains and vancomycin or daptomycin for methicillin-resistant strains of Staphylococcus or more serious clinical presentations, as in our patient. The typical duration of antimicrobial therapy for native-valve infective endocarditis is 4 to 6 weeks, depending on the severity and complications of the infection, but the duration may be extended due to complications or involvement of prosthetic heart valves [11]. Additionally, while valve replacement is not always indicated, studies have shown that surgical treatment improves long-term outcomes. Per the American College of Cardiology/American Heart Association guidelines, vegetations ≥ 10 mm are associated with a higher risk of embolic events and complications [12]. The American Association for Thoracic Surgery guidelines recommend urgent or even emergency surgery in patients with left-sided native-valve endocarditis or prosthetic valve endocarditis, who exhibit mobile vegetations greater than 10 mm in length with clinical evidence of embolic phenomena despite appropriate antibiotic therapy [13]. Our patient’s vegetation was almost 20 mm and associated with a flail leaflet as well as a septic pulmonary embolism, thus qualifying for surgery per guidelines. Additionally, his clinical symptoms of persistent dyspnea as a result of his pulmonic regurgitation, secondary to the vegetation, was another factor deeming surgery necessary in addition to antibiotics. In this patient, with native pulmonic valve infective endocarditis secondary to S. haemolyticus, the combination of IV vancomycin and source control via pulmonic valve replacement per the aforementioned guidelines facilitated a positive outcome without any further complications.

After conducting a thorough literature review of similar cases, it is evident that the presentation of pulmonic valve endocarditis in our patient, in the absence of risk factors, highlights the uniqueness of this case. The majority of cases reviewed mention important predisposing factors for pulmonic valve endocarditis and its sequelae, whereas our case lacked any identifiable predisposing risk factors [14,15]. For all forms of endocarditis, management with IV antibiotics remains the mainstay of treatment, and the decision for surgical valve repair varies based on guidelines and patients’ clinical presentations. A similar case in 2017 by Seraj et al highlighted the importance of antibiotic therapy and surgical valve repair in the management of pulmonic valve endocarditis, in accordance with management decisions in our case [16]. Another case in 2024 by Iturriagagoitia et al involved similar management through antibiotics and surgical repair, while also emphasizing the importance of echocardiography as the key diagnostic modality [14].

Of note, the literature review for this case presentation was assisted by the help of artificial intelligence, specifically OpenEvidence.

Conclusions

This case highlights the importance of considering infective endocarditis in patients without obvious risk factors. Infective endocarditis may manifest with a variety of symptoms, often masquerading as other diagnoses, and it is important to utilize the Duke criteria to formally diagnose infective endocarditis. Correctly identifying infective endocarditis in an atypical presentation can allow for rapid administration of appropriate antibiotics and surgical management, if warranted, thus leading to improved patient outcomes.