INFECTIVE ENDOCARDITIS

INFECTIVE ENDOCARDITIS

Infective endocarditis (IE) is defined as an infection of the endocardial surface of the heart, which may include one or more heart valves, the mural endocardium, or a septal defect. Its intracardiac effects include severe valvular insufficiency, which may lead to intractable congestive heart failure and myocardial abscesses. IE also produces a wide variety of systemic signs and symptoms through several mechanisms, including both sterile and infected emboli and various immunological phenomena.

IE currently can be described as infective endocarditis in the era of intravascular devices, as infection of intravascular lines has been determined to be the primary risk factor for Staphylococcus aureus bloodstream infections (BSIs). S aureus has become the primary pathogen of endocarditis.

IE generally occurs as a consequence of nonbacterial thrombotic endocarditis, which results from turbulence or trauma to the endothelial surface of the heart. A transient bacteremia then seeds the sterile platelet/fibrin thrombus, with IE as the end result. Pathologic effects due to infection can include local tissue destruction and embolic phenomena. In addition, secondary autoimmune effects, such as immune complex glomerulonephritis and vasculitis, can occur.

IE remains a diagnostic and therapeutic challenge. Its manifestations may be muted by the indiscriminate use of antimicrobial agents or by underlying conditions in frail and elderly individuals or immunosuppressed persons.

Effective therapy has become progressively more difficult to achieve because of the proliferation of implanted biomechanical devices and the rise in the number of resistant organisms. Antibiotic prophylaxis has probably had little effect in decreasing the incidence of IE.

Endocarditis has evolved into several variations, keeping it near the top of the list of diseases that must not be misdiagnosed or overlooked. Endocarditis can be broken down into the following categories:

·                     Native valve endocarditis (NVE), acute and subacute

·                     Prosthetic valve endocarditis (PVE), early and late

·                     Intravenous drug abuse (IVDA) endocarditis

Other terms commonly used to classify types of IE include pacemaker IE and nosocomial IE (NIE).

The classic clinical presentation and clinical course of IE has been characterized as either acute or subacute. Indiscriminate antibiotic usage and an increase in immunosuppressed patients have blurred the distinction between these 2 major types; however, the classification still has clinical merit.

Pathophysiology

IE develops most commonly on the mitral valve, closely followed in descending order of frequency by the aortic valve, the combined mitral and aortic valve, the tricuspid valve, and, rarely, the pulmonic valve. Mechanical prosthetic and bioprosthetic valves exhibit equal rates of infection.

All cases of IE develop from a commonly shared process, as follows:

1.                 Bacteremia (nosocomial or spontaneous) that delivers the organisms to the surface of the valve

2.                 Adherence of the organisms

3.                 Eventual invasion of the valvular leaflets

The microorganisms that most commonly produce endocarditis (ie, S aureus; Streptococcus viridans; group A, C, and G streptococci; enterococci) resist the bactericidal action of complement and possess fibronectin receptors for the surface of the fibrin-platelet thrombus. Among the many other characteristics of IE-producing bacteria demonstrated in vitro and in vivo, some features include the following:

·                     Increased adherence to aortic valve leaflet disks by enterococci, S viridans,and S aureus

·                     Mucoid-producing strains of S aureus

·                     Dextran-producing strains of S viridans

·                     S viridans and enterococci that possess FimA surface adhesin

·                     Platelet aggregation by S aureus and S viridans and resistance of S aureusto platelet microbicidal proteins

The pathogenesis of pacemaker IE is similar. Shortly after implantation, the development of a fibrin-platelet thrombus (similar to the nonbacterial thrombotic endocarditis described above) involves the generator box and conducting leads. After 1 week, the connective tissue proliferates, partially embedding the leads in the wall of the vein and endocardium. This layer may offer partial protection against infection during a bacteremia.

Bacteremia (either spontaneous or due to an invasive procedure) infects the sterile fibrin-platelet vegetation described above. BSIs develop from various extracardiac types of infection, such as pneumonias or pyelonephritis, but most commonly from gingival disease. Of those with high-grade gingivitis, 10% have recurrent transient bacteremias (usually streptococcal species). Most cases of subacute disease are secondary to the bacteremias that develop from the activities of daily living (eg, brushing teeth, bowel movements).

The skin is quite resistant to S aureus infection due in great part to its production of antimicrobial peptides. Soong et al discovered that, in vitro, the secretion of alpha toxin by S aureus allows the organism to successfully penetrate the keratinocyte layer. This could explain the presence of staphylococcal bacteremia in the absence of any gross damage to the epithelial layer.

Bacteremia can result from various invasive procedures, ranging from oral surgery to sclerotherapy of esophageal varices to genitourinary surgeries to various abdominal operations. The potential for invasive procedures to produce a bacteremia varies greatly. Procedures, rates, and organisms are as follows:

·                     Endoscopy – Rate of 0-20%; coagulase-negative staphylococci (CoNS), streptococci, diphtheroids

·                     Colonoscopy – Rate of 0-20%; Escherichia coli, Bacteroides species

·                     Barium enema – Rate of 0-20%; enterococci, aerobic and anaerobic gram-negative rods

·                     Dental extractions – Rate of 40-100%; S viridans

·                     Transurethral resection of the prostate – Rate of 20-40%; coliforms, enterococci, S aureus

·                     Transesophageal echocardiography – Rate of 0-20%; S viridans, anaerobic organisms, streptococci

The incidence of nosocomial bacteremias, mostly associated with intravascular lines, has more than doubled in the last few years. Up to 90% of BSIs caused by these devices are secondary to the placement of various types of central venous catheters. Hickman and Broviac catheters are associated with the lowest rates, presumably because of their Dacron cuffs. Peripherally placed central venous catheters are associated with similar rates.

Intravascular catheters are infected from 1 of the following 4 sources:

·                     Infection of the insertion site

·                     Infection of the catheter

·                     Bacteremia arising from another site

·                     Contamination of the infused solution

Bacterial adherence to intravascular catheters depends on the response of the host to the presence of this foreign body, the properties of the organism itself, and the position of the catheter. Within a few days of insertion, a sleeve of fibrin and fibronectin is deposited on the catheter. S aureus adheres to the fibrin component.

S aureus also produces an infection of the endothelial cells (endotheliosis), which is important in producing the continuous bacteremia of S aureus BSIs. Endotheliosis may explain many cases of persistent methicillin-susceptible S aureus (MSSA) and methicillin-resistant S aureus (MRSA) catheter-related BSIs without an identifiable cause.

S aureus catheter-related BSIs occur even after an infected catheter is removed, apparently attributable to specific virulence factors of certain strains of S aureusthat invade the adjacent endothelial cells. At some point, the staphylococci re-enter the bloodstream, resulting in bacteremia.

Etiology

The different types of IE have varying causes and involve different pathogens.

The following are the main underlying causes of NVE:

·                     Rheumatic valvular disease (30% of NVE) – Primarily involves the mitral valve followed by the aortic valve

·                     Congenital heart disease (15% of NVE) – Underlying etiologies include a patent ductus arteriosus, ventricular septal defect, tetralogy of Fallot, or any native or surgical high-flow lesion.

·                     Mitral valve prolapse with an associated murmur (20% of NVE)

·                     Degenerative heart disease – Including calcific aortic stenosis due to a bicuspid valve, Marfan syndrome, or syphilitic disease

Approximately 70% of infections in NVE are caused by Streptococcus species, including S viridans, Streptococcus bovis, and enterococci. Staphylococcusspecies cause 25% of cases and generally demonstrate a more aggressive acute course (see the images below).

Early PVE, which presents shortly after surgery, has a different bacteriology and prognosis than late PVE, which presents in a subacute fashion similar to NVE.

Infection associated with aortic valve prostheses is particularly associated with local abscess and fistula formation, and valvular dehiscence. This may lead to shock, heart failure, heart block, shunting of blood to the right atrium, pericardial tamponade, and peripheral emboli to the central nervous system and elsewhere.

Early PVE may be caused by a variety of pathogens, including S aureus and S epidermidis. These nosocomially acquired organisms are often methicillin-resistant (eg, MRSA). Late disease is most commonly caused by streptococci. Overall, CoNS are the most frequent cause of PVE (30%).

S aureus causes 17% of early PVE and 12% of late PVE. Corynebacterium,nonenterococcal streptococci, fungi (eg, C albicans, Candida stellatoidea, Aspergillus species), Legionella, and the HACEK (ie, Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) organisms cause the remaining cases.

Fungal endocarditis is found in intravenous drug users and intensive care unit patients who receive broad-spectrum antibiotics. Blood cultures are ofteegative, and diagnosis frequently is made after microscopic examination of large emboli.

History

In patients with infective endocarditis (IE), the present illness history is highly variable. Symptoms commonly are vague, emphasizing constitutional complaints, or complaints may focus on primary cardiac effects or secondary embolic phenomena. Fever and chills are the most common symptoms; anorexia, weight loss, malaise, headache, myalgias, night sweats, shortness of breath, cough, or joint pains are common complaints as well.

Primary cardiac disease may present with signs of congestive heart failure due to valvular insufficiency. Secondary phenomena could include focal neurologic complaints due to an embolic stroke or back pain associated with vertebral osteomyelitis. As many as 20% of cases present with focal neurologic complaints and stroke syndromes.

Dyspnea, cough, and chest pain are common complaints of intravenous drug users. This is likely related to the predominance of tricuspid valve endocarditis in this group and secondary embolic showering of the pulmonary vasculature.

A key concern is the distinction between subacute and acute IE. The diagnosis of subacute IE is suggested by a history of an indolent process characterized by fever, fatigue, anorexia, back pain, and weight loss. Less common developments include a cerebrovascular accident or congestive heart failure.

The patient should be questioned about invasive procedures and recreational drug use that may be causing the bacteremia. Most subacute disease caused by S viridans infection is related to dental disease. Most cases are not caused by dental procedures but by transient bacteremias secondary to gingivitis. In 85% of patients, symptoms of endocarditis appear within 2 weeks of dental or other procedures.

The interval between the onset of disease and diagnosis averages approximately 6 weeks. The fact that less than 50% of patients have previously diagnosed underlying valvular disease significantly limits the effectiveness of antibiotic prophylaxis.

Acute IE is a much more aggressive disease. The patient notices an acute onset of high-grade fevers and chills and a rapid onset of congestive heart failure. Again, a history of antecedent procedures or illicit drug use must be investigated.

The distinction between these 2 polar types of IE has become less clear. Intermittent use of antibiotics aimed at treating misdiagnosed endocarditis can suppress bacterial growth within the valvular thrombus, giving rise to the state of muted IE. This is often the case iosocomial infective endocarditis (NIE; also referred to as healthcare-associated IE [HCIE]), which commonly manifests with elements of a sepsis syndrome (ie, hypotension, metabolic acidosis fever, leukocytosis, and multiple organ failure).

The source of the bacteremia may be an infection in another organ (eg, pneumonia, pyelonephritis) or in a central venous catheter. Most often, these patients are in the intensive care unit. Approximately 45% of cases of NIE/HCIE occur in patients with prosthetic valves. Muted IE due to S aureus infection may resemble IE that results from S viridans infection.

The symptoms of early subacute native valve endocarditis (NVE) are usually subtle and nonspecific. They include low-grade fever (absent in 3-15% of patients), anorexia, weight loss, influenzalike syndromes, polymyalgia-like syndromes, pleuritic pain, syndromes similar to rheumatic fever (eg, fever, dulled sensorium as in typhoid, headaches), and abdominal symptoms (eg, right upper quadrant pain, vomiting, postprandial distress, appendicitis-like symptoms).

When appropriate therapy is delayed for weeks or months, additional clinical features, embolic or immunological in origin, develop.

Signs and symptoms secondary to emboli include acute meningitis with sterile spinal fluid, hemiplegia in the distribution of the middle cerebral artery, regional infarcts that cause painless hematuria, infarction of the kidney or spleen, unilateral blindness caused by occlusion of a retinal artery, and myocardial infarction arising from embolization of a coronary artery.

The emboli of right-sided IE commonly produce pulmonary infarcts. The rate of embolization is related to the organism, the size of the vegetation and its rate of growth or resolution, and its location.

The vegetations of S aureus, Haemophilus influenzae, H parainfluenzae, and the fungi are much more likely to embolize than those of S viridans. Those larger than 10 mm in diameter and mobile or prolapsing have a high rate of embolization. A vegetation that grows during therapy is associated with a significant increase in the risk of embolization but with the persistence of bacteremia.

Clinically separating the importance of the absolute size and the rate of change in the size of the vegetation from the causative organism is difficult. The vegetations of the mitral valve are much more likely to embolize than those in any other location. The risk of embolization markedly decreases after 1 week of appropriate antibiotic therapy.

The deposition of circulating immune complexes in the kidney may produce interstitial nephritis or proliferative glomerulonephritis, with renal failure progressing to the point of uremia at the time of the patient’s presentation. Similarly, various musculoskeletal symptoms (44% of patients) arise from immunologically mediated synovitis.

Osler nodes and Roth spots arise from immune-mediated vasculitis. Patients may experience palpitations, ie, the symptoms of an immune-mediated myocarditis.

The origin of lumbosacral back pain in patients with subacute IE (15%) is unclear but probably results from the deposition of immune complexes in the disk space. However, antibiotic therapy rapidly abolishes these symptoms. In 50% of patients with cerebral emboli, this event is the first manifestation of IE and is associated with a 2- to 4-times higher mortality rate. Stroke in younger people should always raise the possibility of underlying IE.

Rarely observed today, the bacteria-free state of IE is one in which patients have multiple negative blood culture results in the presence of severe congestive heart failure, renal failure, multiple sterile emboli, massive splenomegaly, severe anemia, brown facial pigmentation, bilateral thigh pain, and massive leg edema. These patients are usually afebrile. This process appears to indicate prolonged and unchecked stimulation of the immune system.

The clinical symptoms of acute IE result from either embolic or intracardiac suppurative complications. The onset of illness is abrupt, with rapidly progressive destruction of the infected valve (see the images below). The valvular leaflets are quickly destroyed by bacteria that multiply rapidly within the ever-growing friable vegetations. Complications develop within a week. These include the dyspnea and fatigue of severe congestive heart failure and a wide spectrum of neuropsychiatric complications resulting from CNS involvement.

Patients with right-sided intravenous drug abuse (IVDA) IE (53% of cases) frequently present with pleuropulmonary (pneumonia and/or empyema) manifestations. Symptoms due to metastatic infection develop early in a disease course caused by S aureus. Right-sided disease is associated with a low rate of congestive heart failure and valvular perforation.

Infection with P aeruginosa has a high rate of neurological involvement, with 2 distinctive features: (1) mycotic aneurysms with a higher-than-average rate of rupture and (2) panophthalmitis (10% of patients). The course of infection with P aeruginosa is much slower than that of S aureus.

The course of left-sided IVDA IE is similar to that of non-IVDA disease.

Approximately 5-8% of febrile individuals who abuse intravenous drugs have underlying IE. Many users of illicit drugs may lose their fever within a few hours of hospitalization. This phenomenon, termed cotton wool fever, is probably caused by the presence of adulterants contained within the injected drugs.

Clinical features of prosthetic valve endocarditis (PVE) closely resemble those of NVE. Early PVE is defined as infection occurring within 60 days of valve implantation; late PVE occurs after this period. For valvular infection with coagulase-negative staphylococci (CoNS), this division should be extended to 12 months.

Congestive heart failure occurs earlier and is more severe in persons with PVE. The patient may present with symptoms of myocarditis or pericarditis. The rate of embolic stroke is high in the first 3 days of PVE.

NIE commonly manifests with elements of a sepsis syndrome (ie, hypotension, metabolic acidosis fever, leukocytosis, and multiple organ failure). The source of bacteremia may develop from an infection in another organ (eg, pneumonia, pyelonephritis) or from a central venous catheter. Most often, these patients are in the intensive care unit.

Approximately 45% of cases of NIE/HCIE occur in patients with prosthetic valves.

Physical Examination

Fever, possibly low-grade and intermittent, is present in 90% of patients.

The AHA (endorsed by the Infectious Diseases Society of America [IDSA]) 2010 guideline update on cardiovascular implantable electronic device (CIED) infections and their management recommends that patients with CIED who develop unexplained fever or bloodstream infection should seek evaluation for CIED infection by cardiologists or infectious disease specialists.

Heart murmurs are heard in approximately 85% of patients. Change in the characteristics of a previously noted murmur occurs in 10% of these patients and increases the likelihood of secondary congestive heart failure.

One or more classic signs of IE are found in as many as 50% of patients. They include the following:

·                     Petechiae – Common but nonspecific finding (see the image below)

·                     Subungual (splinter) hemorrhages – Dark red linear lesions in the nailbeds

·                     Osler nodes – Tender subcutaneous nodules usually found on the distal pads of the digits

·                     Janeway lesions – Nontender maculae on the palms and soles

·                     Roth spots – Retinal hemorrhages with small, clear centers; rare and observed in only 5% of patients.

Signs of neurologic disease occur in as many as 40% of patients. Embolic stroke with focal neurologic deficits is the most common etiology. Other etiologies include intracerebral hemorrhage and multiple microabscesses.

Signs of systemic septic emboli are due to left heart disease and are more commonly associated with mitral valve vegetations. Multiple embolic pulmonary infections or infarctions are due to right heart disease.

Signs of congestive heart failure, such as distended neck veins, frequently are due to acute left-sided valvular insufficiency.

Splenomegaly may be present.

Other signs include the following:

·                     Stiff neck

·                     Delirium

·                     Paralysis, hemiparesis, aphasia

·                     Conjunctival hemorrhage

·                     Pallor

·                     Gallops

·                     Rales

·                     Cardiac arrhythmia

·                     Pericardial rub

·                     Pleural friction rub

Approximately 3-15% of patients with subacute IE (primarily elderly and chronically ill individuals) have normal or subnormal temperatures. The vast majority of patients have detectable heart murmurs. The presence of a murmur is so common (99% of cases) that its absence should cause clinicians to reconsider the diagnosis of IE. The major exception is right-sided IE, in which only one third of patients have a detectable murmur.

Because many of these murmurs are hemodynamically insignificant and have been present for years, their role in the patient’s illness may be underestimated. The saying “a changing murmur is extremely helpful in diagnosing subacute IE” is a myth. Only 15% do so early in the course of infection.

The peripheral lesions of subacute IE are observed in only approximately 20% of patients, compared with 85% in the preantibiotic era. Currently, the most common of these is petechiae. They may occur on the palpebral conjunctivae, the dorsa of the hands and feet, the anterior chest and abdominal walls, the oral mucosa, and the soft palate.

Subungual hemorrhages (ie, splinter hemorrhages) are linear and red. They are usually caused by workplace trauma to the hands and feet rather than by valvular infection. Hemorrhages that do not extend for the entire length of the nail are more likely the result of infection rather than trauma.

Osler nodes are smallish tender nodules that range from red to purple and are located primarily in the pulp spaces of the terminal phalanges of the fingers and toes, soles of the feet, and the thenar and hypothenar eminences of the hands. Their appearance is often preceded by neuropathic pain. They last from hours to several days. They remain tender for a maximum of 2 days. The underlying mechanism is probably the circulating immunocomplexes of subacute IE. They have been described in various noninfectious vasculitides.

Clubbing of fingers and toes was found almost universally, but it is now observed in less than 10% of patients. It primarily occurs in those patients who have an extended course of untreated IE.

The arthritis associated with subacute IE is asymmetrical and is limited to 1-3 joints. Clinically, it resembles the joint changes found in patients with rheumatoid arthritis, Reiter syndrome, or Lyme disease. The fluid is usually sterile.

Splenomegaly is observed more commonly in patients with long-standing subacute disease. It may persist long after successful therapy.

Roth spots are retinal hemorrhages with pale centers. The Litten sign represents cotton-wool exudates.

In approximately one third of patients with acute IE, murmurs are absent. The most common type is an aortic regurgitation murmur. Because of the suddenness of onset, the left ventricle does not have a chance to dilate. In this situation, the classic finding of increased pulse pressure in significant valvular insufficiency is absent.

Fever is always present, and it usually is high.

Janeway lesions are irregular erythematosus and painless macules (1-4 mm in diameter). They most often are located on the thenar and hypothenar eminences of the hands and feet. They usually represent an infectious vasculitis of acute IE resulting from S aureus infection.

Acute septic monoarticular arthritis in patients with acute IE most often is caused by S aureus infection.

Purulent meningitis may be observed in patients with acute IE, compared with the aseptic type observed in patients with subacute disease. Other neurological findings are similar to those observed in patients with subacute disease.

Complications

The following are potential complications of IE:

·                     Myocardial infarction, pericarditis, cardiac arrhythmia

·                     Cardiac valvular insufficiency

·                     Congestive heart failure

·                     Sinus of Valsalva aneurysm

·                     Aortic root or myocardial abscesses

·                     Arterial emboli, infarcts, mycotic aneurysms

·                     Arthritis, myositis

·                     Glomerulonephritis, acute renal failure

·                     Stroke syndromes

·                     Mesenteric or splenic abscess or infarct

Congestive heart failure due to aortic valve insufficiency is the most common intracardiac complication of subacute endocarditis. It develops after months of untreated disease but may occur a full year following microbiological cure.

The complication of arterial embolization is second in frequency to congestive heart failure for both subacute and acute IE. The frequency of this complication has decreased, from 80% in the preantibiotic era to 15-35% today. The emboli are usually sterile because of the minimally invasive nature of the causative organisms (eg, S viridans).

The persons most at risk are younger (20-40 y), have mitral or aortic valve (native or prosthetic) involvement, and are infected with certain organisms such asCandida or Aspergillus species, S aureus, Haemophilus parainfluenzae, group B streptococci, and nutritionally variant streptococci.

The prevalence of embolization appears to be the same for both types of disease. The most common areas of deposition include the coronary arteries, kidneys, brain, and spleen. Infarction at the site of embolization is common; abscess formation is not. Cerebral emboli occur in 33% of patients. The middle cerebral artery is involved most often.

Other neurological embolic damage includes cranial nerve palsies, cerebritis, and mycotic aneurysms caused by weakening of the vessel walls and produced by embolization to the vasa vasorum. Mycotic aneurysms may occur in the abdominal aorta and the splenic, coronary, and pulmonary arteries.

In acute IE, the frequency of aneurysms and other suppurative intracardiac complications is high. In addition to valvular insufficiency, other intracardiac complications of acute IE include (1) aortocardiac and other fistulas, (2) aneurysms of the sinus of Valsalva, (3) intraventricular abscesses, (4) ring abscesses, (5) myocardial abscesses, (6) mycotic aneurysms, (7) septic coronary arterial emboli, and (8) pericarditis.

In patients with acute disease, especially disease caused by S aureus infection,emboli almost inevitably lead to abscesses in the areas where they are deposited. Multiple abscesses can occur in almost every organ, including the kidneys, heart, and brain. Mycotic aneurysms may occur in almost any artery. Paradoxically, they are less common in patients with acute IE.

Approach Considerations

The major goals of therapy for infective endocarditis (IE) are to eradicate the infectious agent from the thrombus and to address the complications of valvular infection. The latter includes both the intracardiac and extracardiac consequences of IE. Some of the effects of IE require surgical intervention. Emergent care should focus on making the correct diagnosis and stabilizing the patient with acute disease and cardiovascular instability. General measures include the following:

·                     Treatment of congestive heart failure

·                     Oxygen

·                     Hemodialysis (may be required in patients with renal failure)

In most cases, the etiologic microbial agent is not known while the patient is in the ED. Three sets of blood cultures should be drawn over a few hours, and then empiric antibiotic therapy tailored to the patient’s history and circumstances may be administered (see Antibiotic Therapy, below).

No special diets are recommended for patients with endocarditis; however, if the patient has congestive heart failure, administer a sodium-restricted diet. Activity limitations are determined by the severity of the illness, complications (eg, stroke), and the presence of significant congestive heart failure.

Mild congestive heart failure resulting from valvular insufficiency or myocarditis may be managed with standard medical therapy. Often, this is progressive, and despite achieving a microbiological cure, it requires valvular surgery.

Antibiotic Therapy

Antibiotics remain the mainstay of treatment for IE.

In the setting of acute IE, institute antibiotic therapy as soon as possible to minimize valvular damage. Three to 5 sets of blood cultures are obtained within 60-90 minutes, followed by the infusion of the appropriate antibiotic regimen. By necessity, the initial antibiotic choice is empiric in nature, determined by clinical history and physical examination findings.

Empiric antibiotic therapy is chosen based on the most likely infecting organisms. Native valve endocarditis (NVE) has often been treated with penicillin G and gentamicin for synergistic coverage of streptococci. Patients with a history of intravenous (IV) drug use have been treated with nafcillin and gentamicin to cover for methicillin-sensitive staphylococci. The emergence of methicillin-resistant S aureus (MRSA) and penicillin-resistant streptococci has led to a change in empiric treatment with liberal substitution of vancomycin in lieu of a penicillin antibiotic.

Prosthetic valve endocarditis (PVE) may be caused by MRSA or coagulase-negative staphylococci (CoNS); thus, vancomycin and gentamicin may be used for treatment, despite the risk of renal insufficiency. Rifampin is necessary in treating individuals with infection of prosthetic valves or other foreign bodies because it can penetrate the biofilm of most of the pathogens that infect these devices. However, it should be administered with vancomycin or gentamicin. These latter 2 agents serve to prevent the development of resistance to the rifampin.

Substitution of linezolid for vancomycin should be considered in patients with unstable renal function because of the difficulty of achieving therapeutic trough levels in this situation.

Linezolid or daptomycin are options for patients with intolerance to vancomycin or resistant organisms. Organisms with a minimum inhibitory concentration (MIC) to vancomycin of equal to or greater than 2 mcg/mL should be treated with alternative agents. Appropriate regimens should be devised in consultation with a specialist in infectious disease.

In the case of subacute IE, treatment may be safely delayed until culture and sensitivity results are available. Waiting does not increase the risk of complications in this form of the disease.

Eradicating bacteria from the fibrin-platelet thrombus is extremely difficult because (1) the high concentration of organisms present within the vegetation (ie, 10-100 billion bacteria per gram of tissue), (2) their position deep within the thrombus, (3) their location in both a reduced metabolic and reproductive state, and (4) the interference of fibrin and white cells with antibiotic action. For all of these reasons, bactericidal antibiotics are considered necessary for cure of valvular infection.

IV administration is preferred because more reliable therapeutic levels are achieved with this route. Orally administered antibiotics have been used as suppressive therapy for incurable valvular infections (ie, inoperable PVE).

Treat all patients in a hospital or skilled nursing facility to allow adequate monitoring of the development of complications and the response to antibiotic therapy.