Infective Endocarditis: A Case Series

Introduction

Infective endocarditis (IE) is an infection of the endocardial surface of the heart. It most commonly involves heart valves but may also involve other endocardial sites in the heart. Congenital anomalies such as ventricular septal defect, bicuspid aortic valve (BAV), patent ductus arteriosus, and coarctation of the aorta predispose for the development of IE. The incidence of IE worldwide is approximately 3 to 10 per 100,000 people annually.¹, ², ³, ⁴ The incidence of IE remains high in spite of better diagnostic facilities, newer antibiotics, and early surgical intervention.⁵ In India, rheumatic heart disease (RHD) is the most common underlying cardiac condition for developing IE, whereas in the developed countries, congenital heart disease is the predominant underlying pathology.⁶, ⁷, ⁸ A recent study in the Indian population revealed that approximately 76% patients with IE were less than 40 years old, with a mean age of 27.6 (±12) years).⁷ In comparison to adults, IE is less common in children; however, its incidence is on the rise. IE is classified on the basis of location, presence or absence of intracardiac device or prosthetic valve, and mode of acquisition (community-acquired, nosocomial, or intravenous [IV] drug related). Patients with a prosthetic valve or prosthetic material used for cardiac repair have a high incidence of IE. Prosthetic valve IE can be classified early (<1 year) or late (>1 year) after valve replacement of surgery. The most common causative organism for prosthetic valve endocarditis (PVE) is Staphylococcus followed by Streptococcus species.⁹

IE is associated with high mortality. Twenty percent of patients die during the hospital stay, and the mortality may reach 25 to 30% six months postinfection.¹⁰, ¹¹, ¹², ¹³ Early mortality is similar between native valve endocarditis (NVE) and PVE and between mitral and aortic valve endocarditis. The mortality is highest (50%) in patients developing infections due to gram-negative bacilli or fungus.¹¹, ¹⁴, ¹⁵, ¹⁶, ¹⁷

Diagnosis of IE requires clinical finding, microbiological analysis, and imaging. The clinical features are often nonspecific and may include fever, chills, fatigue, or weight loss. Fever is the most common clinical manifestation present in approximately 95 to 100% of patients (both in NVE and PVE). The diagnosis of IE is concluded on the basis of the modified Duke criteria (Table 1). The presence of two major, one major and three minor, or five minor clinical criteria is diagnostic of IE.

Laboratory investigations show an increase in the levels of inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) and normocytic normochromic anemia. Urine analysis often reveals microscopic hematuria and occasionally RBC cast or pus cells. The electrocardiogram is essentially normal with infrequent finding of new conduction abnormalities suggestive of paravalvular or myocardial extension of infection. Positive blood cultures are obtained in approximately 60 to 80% in developed countries as compared with developing countries like India, where only 40 to 60% are positive.¹⁸, ¹⁹ Echocardiography has become a standard modality for diagnosis of IE. Transesophageal echocardiography has greater sensitivity and specificity than transthoracic echocardiography (TTE) for diagnosing valvular vegetations and abscesses.

We hereby report six patients treated for IE in the Department of Cardio-Thoracic and Vascular Surgery between June 2019 and January 2020.

Case Report

Discussion

IE causes significant morbidity and mortality in patients with cardiovascular diseases or postcardiac surgery patients. The risk factors for mortality are development of heart failure, intracardiac abscess, embolism, large mobile vegetation, hemodynamic instability, altered mental status, immunocompromised state, and advanced age.¹², ¹⁶, ¹⁷, ²⁰, ²¹ The two challenges when managing a patient with IE are diagnosing the causative organism and deciding when to operate. The laboratory diagnosis of IE is dependent on markers of inflammation and blood cultures. Echocardiography is an important investigation to document vegetation and abscesses, evaluate regurgitant lesions, quantify the heart failure, and serially follow the functional status of heart.

Out of our six patients reported, only one (16.7%) died (Table 2). The cause for death was late presentation and lack of coverage for Burkholderia in the prescribed empirical antibiotic therapy. The inherent resistance of Burkholderia to aminoglycosides and first- and second-generation cephalosporins is well documented. The recommended antibiotics are trimethoprim–sulfamethoxazole, ceftazidime, and meropenem. One of our patients with culture-negative endocarditis responded to doxycycline and did not require any surgery. Five out of six patients who underwent surgery had vegetations more than 10 mm in size, and one patient had an aortic valve abscess (caused by Staphylococcus haemolyticus). A high index of suspicion for fungus and atypical bacteria as causative organisms should be maintained for patients not responding to empirical antibiotic therapy within a week. The upgradation or change of antibiotics should be considered once culture reports are received. Five of our patients were alive and well 3 months postdischarge and were not followed any further.

Our unit receives two types of IE patients: NVE and PVE patients. NVE patients are referred from cardiology and are already on antibiotic therapy. Usually, we do not alter these antibiotics unless they develop renal failure, hemodynamic instability, fever, or sepsis. Our first-line antibiotics for NVE are ceftriaxone and gentamicin. Vancomycin is added in patients who do not respond within 72 hours. In patients with renal compromise, meropenem is used instead of vancomycin. Then antibiotics may be altered based on blood culture reports. Serum galactomannan and (1,3)-β-D-glucan are used to rule out fungal endocarditis. In patients with persistent fever for 7 days and raised fungal biomarkers, antifungal agents are added (caspofungin for Candida, voriconazole for Aspergillus, and liposomal amphotericin B for persistently high serum galactomannan levels in spite of antifungal therapy). The antifungal therapy is administered for at least 6 weeks. In patients with persistent fever for 7 days and normal serum levels of (1,3)-β-D-glucan and galactomannan, doxycycline is added to cover atypical bacteria. In patients responding to doxycycline, the duration of therapy is 6 months. In patients with PVE, the first-line antibiotics are vancomycin, gentamicin, and rifampicin. In select patients of PVE, it is recommended to continue antifungals lifelong. Rest of the protocol is similar to NVE.

Approximately 80 to 90% of IE cases are caused by Staphylococcus, Streptococcus, and Enterococcus spp. Staphylococcus aureus is the most frequently isolated microorganism (30%) associated with IE in developed countries.¹⁰, ²² Coagulase-negative staphylococcus is a common cause of hospital-acquired NVE. Streptococcus viridians is the most common cause for IE in India.²³ Enterococci are the third most common cause of IE, with approximately 10% of total cases.¹⁰, ²² Enterococcus faecalis is the most common species causing both NVE and PVE in elderly or chronically ill patients. Gram-negative bacilli account for approximately 5% of IE cases.²⁴ Approximately 3% patients are infected by HACEK bacteria (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella corrodens, Kingella), which are often found as colonizers in the oropharynx.²⁵ Gram-negative bacteria (e.g., Acinetobacter spp, Pseudomonas aeruginosa), Mycoplasma spp, Legionella spp, and Tropheryma whipplei are rare causes of IE.²⁶ Fungal endocarditis caused either by Candida or Aspergillus is rare but associated with high mortality. Fungal infections occur in immunocompromised patients or after cardiac surgery, mostly on prosthetic valves.²⁷

The management of IE requires multidisciplinary approach with inputs from cardiologists, cardiothoracic surgeons, intensivists, and infectious disease specialists. Antibiotic therapy should be started on the empirical basis soon after obtaining blood cultures, but a clinician can wait for culture results if the patient is clinically stable. Majority of the patients respond to antibiotic therapy. In such patients, there is a dilemma of whether to replace the infected valve or not. Following are the indications for surgery in NVE and PVE.²⁸, ²⁹, ³⁰

Indications for Surgery in Native and Prosthetic Valve Endocarditis

1. Patients who develop heart failure due to valve dysfunction require surgery irrespective of antibiotic course status.

2. Patients with IE caused by S. aureus, fungal, or other highly resistant microorganisms of the left-sided valves require surgery irrespective of antibiotic course status.

3. Patients with IE who develop heart block, aortic root abscess, or other destructive lesions require surgery irrespective of antibiotic course status.

4. Patients with persistent bacteremia or fever of more than 5 to 7 days even after initiation of appropriate antimicrobial therapy require surgery irrespective of antibiotic course status.

5. Patients with PVE and relapsing infection (recurrence of bacteremia after a complete course of antibiotics and subsequently negative blood cultures) without any other identifiable source of infection may require surgery.

6. Patients with IE who present with recurrent emboli and persistent vegetations despite appropriate antibiotic therapy may require surgery irrespective of antibiotic course status.

7. Patients with NVE or PVE with mobile vegetations more than 10 mm in size and evidence of embolic phenomena despite appropriate antimicrobial treatment may require urgent or emergency surgery.

8. Patients with IE of the right-sided valves with large vegetations and persistent infection (bacteremia or fever more than 5–7 days after starting antibiotics) or with evidence of septic pulmonary embolism may require surgery.

Conclusion

Both PVE and NVE can be treated successfully with antimicrobial agents and surgery (when indicated). A high index of suspicion is required to diagnose IE caused by fungus and atypical bacteria.