Site of entry and surgical timing in infective endocarditis

Introduction Infective endocarditis affects native cardiac structures (valves, atrial, and ventricular endocardium) or surgically implanted devices (valve prosthesis, endocardial electrodes). The first description of this condition belongs to Jean Francois Fernel, a French doctor, in 1554.1 More than 300 years later, in 1885, Sir William Osler further defined the condition. The key pathogenic element to define infective endocarditis is the demonstration of the infectious organism, isolation and antibiotic susceptibility test of which directs the specific antimicrobial treatment, its duration, and the prognosis of the condition. Infective endocarditis has an occurrence of three to nine cases per 100 000 people per year in the Western countries and a male-to-female ratio of 2 : 1.2 The highest prevalence is found in patients with valve prosthesis and intracardiac devices, in patients with uncorrected cyanotic congenital heart conditions, or with previous endocarditis. Notwithstanding the improvement of current treatment, infective endocarditis has a recurrence rate between 5 and 10%3 and still carries a high mortality rate.4 Hence, the rationale for the search and the cure of the site of entry of endocarditis is also important in the prevention of the recurrence of the disease.5 Site of entry for infective endocarditis A multicenter study suggested that a previous episode of endocarditis was an important independent risk factor for its recurrence.6 There are sparse data in literature investigating the site of entry for endocarditis, and the present European Guidelines7 do not offer methodological advice as far as their search or treatment. This important aspect has been well outlined in a recent prospective study8 in which the possible sites of entry and the responsible microorganisms were systematically investigated and identified. All patients admitted to the hospital between 2005 and 2011 were investigated by dentists, ear nose & throat (ENT) specialists, gastroenterologists, and urologists for men and gynecologists for women. Dermatologic conditions were assessed by dermatologists. Diagnostic radiology was used to search for possible dental, cerebral, or thoracoabdominal infections. For every single patient, the site of entry of the disease was assessed (Table 1) according to the results of clinical exam and the diagnostic imaging, paying particular attention to the natural habitat of the identified pathogens. When microorganisms with likely gastrointestinal origin were identified in patients older than 50 years of age, at high risk, with a history, or family history of a gastrointestinal tumor, colonoscopy was performed. The sites of infection were addressed with specific medical treatment. The site of entry was identified in 74% of the patients with infective endocarditis entering this study; in 40%, the site of entry was identified in skin lesion mainly related to medical intervention or with drug abuse; in 29% of the cases, dental or oral infections were responsible, and 23% of the patients had intestinal polyposis. Less often genital-urinary sites or other ENT sites were responsible.Table 1: Potential entry sites for infective endocarditisThe current study demonstrates that the search for the site of entry in infective endocarditis is clinically feasible in the vast majority of the cases, starting from accurate assessment of the oral cavity, leaving advance imaging or colonoscopy only to specific situations. Prophylaxis and search for entry site In the last few years, prophylaxis of infective endocarditis has been the center of intense debate and discussion. At variance from the past,9 the latest European Guidelines7 recommend antibiotic prophylaxis only in high-risk patients undergoing a dental procedure likely to cause significant bacteremia. Oral cavity has a very high bacterial colonization rate, with the highest concentration at the level of the dental plaque, periodontal pocket, at the base of the tongue, and on the palate mucosa. Hence, careful attention to daily dental hygiene is paid to control low-grade bacteremias.10 The development of infective endocarditis is related to the degree of the bacteremia, the virulence of the bacteria involved, and the patient's immunological status. Both congenital and acquired valve problems, particularly in the left site cavities, in which higher velocity of flow is present, are more prone to endothelial damage, thus facilitating bacterial colonization.11 The latter could be because of low-virulence bacteria (Streptococcus viridans) colonizing endothelial lesions of patients with preexisting congenital abnormalities, or high-virulence bacteria (Staphylococcus aureus) affecting normal endothelium. European Guidelines7 outline patients at higher risk for infective endocarditis, including patients with valvular prosthesis, intracardiac devices, and patients with complex congenital abnormalities. These patients require not only antibiotic prophylaxis but also careful search for possible infections that should be quickly addressed and treated.12 In addition to these situations, considering that antibiotics could have significant side effects which number could be similar in frequency to the number of episodes of infective endocarditis prevented, large-scale use of antibiotic prophylaxis is not recommended. The risks of antibiotic treatment include various degrees of allergic reactions up to anaphylactic shock, the unabated growth of Clostridium difficile, the development of antibiotic resistant strains of bacteria, antibiotic toxicity, and arrhythmias. Due to the potential significant risk connected with endocarditis, it is important to provide prophylaxis at least for the group of patients for whom the prognosis would be dismal should they develop the condition. Delahaye et al.8 reported that 18% of the cutaneous site of entry was in relation to vascular access and recommended compulsory hygienic practice and disinfection before any kind of cutaneous punctures, so as to prevent locoregional contamination and allow, at most, negligible bacteremia. Particular attention should be given to the prolonged use of central venous catheters which are associated with high risk of contamination and potential endocarditis.13 The diagnostic work up to identify possible site of entry of endocarditis should be guided by the characteristics of the isolated pathogen: when S. aureus is responsible, careful examination should be extended to the skin; when Streptococcus is present, then careful inspection of the oral cavity and the pharynx is important; and when enterococcus or Streptococcus bovis are the infective pathogens, colonoscopy should be considered.14 Surgical timing in infective endocarditis European Guidelines7 clearly outline the indication for surgery in infective endocarditis. Heart failure is a frequent and ominous complication of infective endocarditis varying in severity from mild to cardiogenic shock. When there are no absolute surgical contraindications or severe comorbidity, heart failure caused by mitral and/or aortic insufficiency or intracardiac fistulas are indications for emergent surgical intervention; on the other hand, when heart failure is secondary to left ventricular outflow tract obstruction caused by large vegetation, causing hemodynamic instability, the surgical treatment is urgent.15 With surgery, the major decrease in mortality is obtained for patients with moderate-to-severe heart failure. Patients who developed acute mitral and/or aortic insufficiency with echocardiographic evidence of increase in filling pressure, with or without pulmonary hypertension, must have urgent surgical intervention to correct the valvular defect. The uncontrolled infections are another severe complication of endocarditis and represent the second most common indication for early surgical intervention. Often, these infections are caused by more virulent or multiresistant microorganisms, such that the sole medical treatment is not able to eradicate the infection. These infections, persisting despite aggressive antibiotic therapy, and without extracardiac sites of infection (splenic, renal, and vertebral abscesses), are associated with increased vegetation sizes, paravalvular extension of the process with abscesses, pseudoaneurysms, and/or fistulas. The guidelines suggest that surgery should be considered also when there is persistent fever with positive blood cultures while on optimal antibiotic treatment for over a week. Prevention of systemic embolization is the third most common indication for urgent surgery aimed at valvular repair or replacement. When large free-floating vegetations (>10 mm) are present with concomitant embolic events in patients on optimal antibiotic treatment, or in presence of severe mix valvular problems (stenosis/insufficiency), urgent surgery is recommended.16 Early surgical intervention is still controversial for patients with a single large vegetation. When neurological complications are a consequence of septic embolic events, surgery should be considered despite the increased operative risk. In this situation, the necessary intraoperative anticoagulation could determine or aggravate intracerebral hemorrhage, and the hypotension connected with cardiopulmonary bypass could worsen cerebral ischemia and neurologic consequences. The two main goals of surgery in the treatment of endocarditis are the complete removal of all infected tissues and the anatomical reconstruction utilizing, whenever possible, reparative techniques. When valvular prosthesis is necessary, the prognosis is not affected whether a mechanical or biological prosthesis is used. Accordingly, a delay in surgical treatment could be associated with a dramatic increase in the intraoperative mortality as a consequence of progressive worsening of heart failure or the progression of the infection causing further complications such as abscesses, fistula, systemic embolization, and more severe valvular destruction. Surgical treatment should rarely be planned electively after an adequate antibiotic course during a careful clinical and imaging control. Early surgical intervention has a lower in-hospital and long-term mortality as compared with elective interventions.17 Notwithstanding the clear indications for surgery, its optimal timing rests on a difficult and complex clinical decision process. The definition of early surgical intervention according to International Guidelines is still uncertain. European Guidelines7 define emergency surgery when undertaken during the first 24 h, urgent in a few days, and elective when a patient is taken to surgery after 1 or 2 weeks of antibiotic treatment. On the other hand, American Guidelines9 give early surgery a wider time spectrum, which includes the first hospitalization during which the first cycle of antibiotics has been completed. The decision for surgery and its timing should be individualized and the result of a team approach among cardiologists, heart surgeons, and infectious diseases specialists, aiming at the more effective and specific treatment so as to improve the prognosis of this condition. Conclusion There are few data in the literature addressing the not rare physiopathologic causes of recurrence of infective endocarditis. Recent studies suggest that the potential site of entry should be systematically identified, analyzed, and treated. It could be interesting in the future to know whether the elimination of the site of entry could indeed favorably affect the prognosis of these patients in the long term. Patients with complicated infective endocarditis should be offered early surgical intervention even though the exact timing of the procedure is still debated. There are few randomized studies available, and the guidelines apparently encourage an aggressive approach toward this dreadful condition with early surgical intervention. Heart failure, uncontrolled infections, and prevention of systemic embolization are the three main certain indications for surgery. Once the decision to operate is taken, the operation should be undertaken without delays, failure of which could only lead to deterioration of the patient's conditions and worsen his outcome. Acknowledgements Conflicts of interest There are no conflicts of interest.