Infective endocarditis

Japanese: 感染性心内膜炎

Definition: Infective endocarditis is a systemic septic disease in which bacteria and fungi attach to and grow on valves and valve-supporting tissues, the endocardium of the heart in cases of ventricular septal defect, and the endocardium of large blood vessels, forming masses (vegetations, verruca), resulting in a variety of symptoms such as cardiac damage including valvular destruction, bacteremia, and vascular embolism. Diagnosis is not always easy, and this disease should be kept in mind when a patient presents with a fever of unknown origin, regardless of the presence or absence of a heart murmur. Diagnosis should be made based on clinical symptoms associated with sepsis, confirmation of pathogenic microorganisms (bacteria, fungi, etc.) in the blood, and abnormalities in the cardiac structure. Treatment requires the early administration of effective antibiotics in sufficient amounts for a sufficient period of time, management of various complications, and, if indicated, prompt cardiac surgery. It should be remembered that inappropriate judgment and treatment can lead to fatal outcomes.
Classification Based on the clinical course, endocarditis is classified into acute infective endocarditis (acute IE), which begins with a sudden high fever and progresses to valve destruction within a few days or weeks, and has a poor prognosis, and subacute endocarditis (subacute IE), which progresses gradually over a few weeks to months. Acute IE is often caused by Staphylococcus aureus, and can occur even if there is no abnormality in the cardiac tissue itself, including the valves. It progresses within a few days from valve destruction and embolism due to vegetations, and is a severe condition that relatively often leads to a fatal outcome. It is considered a medical emergency and requires prompt treatment. Subacute IE is often caused by viridans streptococci, enterococci, coagulase-negative staphylococci, and Gram-negative bacilli. It is common in patients with underlying diseases such as valvular heart disease, and it is not uncommon for patients to be mistaken for a cold, collagen disease, tuberculosis, or malignant disease when only a slight fever continues, and antibiotics are administered without much thought, or the patient is observed.
Regarding the affected valve, it is divided into native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE).
Causes and pathogenesisWhen turbulent and high-speed blood jets within the heart due to valvular regurgitation or other factors strike the inner surface of a valve or heart chamber, the lining of that area is damaged, causing platelet and fibrin deposits (nonbacterial thrombogenic endocarditis (NBTE), nonbacterial warts). If temporary bacteremia occurs due to dental, otorhinolaryngological, gynecological, or urological procedures under these conditions, bacteria will attach and grow on the platelet and fibrin deposits mentioned above. Furthermore, the deposition of fibrin, bacterial growth, and the migration and proliferation of surrounding cells all become intricately intertwined, forming large warts that result in endocarditis. (Figure 5-11-1)
The warts destroy the valve-supporting tissue, myocardial tissue, and conduction system around the warts, impairing valve function and causing complications such as circulatory failure and arrhythmia. Part of the wart may also detach and embolize into peripheral blood vessels, which may then form aneurysms in those peripheral blood vessels. Embolism and rupture of the aneurysm in the brain can have serious consequences. The causes of this disease are both the patient and the causative bacteria. Patient factors include ventricular septal defect, valve regurgitation, and stenosis, which cause abnormal high-speed jets in the cardiac chambers, and the presence of foreign or artificial objects such as artificial valves and pacemaker leads in the body. Although rare in Japan, it is known that in Europe and the United States, drug addicts who repeatedly administer drugs intravenously using contaminated syringes can develop right-sided endocarditis. In terms of causative bacteria, streptococci are generally present in the oral cavity, but tooth extraction can cause transient bacteremia, which can lead to endocarditis. Such transient bacteremia is frequently observed in daily life, and the incidence is unexpectedly high, ranging from a few percent to 40% after tooth brushing, 35% after tooth extraction when there is no gingivitis, 70-75% when there is gingivitis, 23% after infected tonsil massage, and 8-26% after urinary catheter insertion and removal. Gram-positive cocci such as epidermidis Staphylococcus aureus and coagulase-negative streptococcus (CNS), which are commonly present on the skin, are often the causative bacteria. Other causes include enterococci in the digestive tract, urinary and reproductive systems, Gram-negative rods, anaerobic bacteria, fungi (Candida, Actinomyces, etc.), chlamydia, and rickettsia in patients with malignant diseases, those receiving steroids or immunosuppressants, and those with long-term catheter placement. In Europe and the United States, HACEK group Gram-negative bacteria (Haemophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella, Kingella) account for 10-20% of cases, and are difficult to grow in culture media, causing blood cultures to appear negative (Table 5-11-1).
Epidemiology : The underlying diseases of this disease include valvular heart disease, congenital heart disease, hypertrophic obstructive cardiomyopathy, and foreign bodies such as pacemakers and artificial valves. In recent years, the number of elderly people is increasing, with men twice as often affected as women. The number of cases of rheumatic valvular disease, which was previously common, has decreased, and the number of cases of non-rheumatic valvular disease, which is thought to be caused by aging and degeneration, has increased. In the past, the most common causative bacteria was streptococcus, but recently the frequency of acute infective endocarditis caused by Staphylococcus aureus infection has increased. Cases caused by Gram-negative bacteria, fungi, and other rare bacteria have also increased. Recently, refractory endocarditis caused by multidrug-resistant Staphylococcus aureus and vancomycin-resistant enterococci have also become a problem. Infective endocarditis in the early stages after artificial valve surgery is often caused by Staphylococcus epidermidis, Staphylococcus aureus, and Gram-negative bacilli (Table 5-11-2).
PathologyThe mitral and aortic valves are frequently affected. The infected focus forms a wart surrounded by a thick mesh of platelets and fibrin, ranging in size from a few millimeters to several centimeters, and may cause functional valvular stenosis. As the infection progresses to the surrounding area, it can cause valve perforation/aneurysm formation, rupture of the chordae tendineae, papillary muscle disorders, valve annulus abscesses, Valsalva sinus aneurysms, ventricular septum and atrial septum abscesses, and myocarditis. In addition, embolism to the brain, spleen, kidneys, lungs, coronary arteries, etc., skin symptoms due to immunological abnormalities, and renal dysfunction may occur. Part of the wart may embolize to the brain or peripheral arteries, where it grows to form a micotic aneurysm, which may rupture and cause severe bleeding.
Clinical manifestations
1) Systemic symptoms due to infection:
Fever, fatigue, loss of appetite, weight loss, etc.
2) Cardiac symptoms due to progression of underlying heart disease or valvular disorders:
New heart murmurs due to valvular regurgitation or relative stenosis (heart murmurs are present in 85-90% of cases), cardiac enlargement, heart failure, and atrioventricular block due to valve annulus abscess.
3) Wart embolus symptoms:
Cerebral embolism, hematuria, abdominal pain/ileus, and right-sided endocarditis causes pulmonary embolism and pneumonia.
4) Immunological abnormalities:
Nephritis, arthritis, myocarditis, pericarditis, and vasculitis may occur. Rheumatoid factor, antinuclear antibodies, and ANCA may also be positive.
Acute endocarditis begins with a high fever, and within a few days, valve destruction progresses rapidly, so delay in diagnosis can be fatal. Skin and conjunctival findings can lead to suspicion of this disease. Small bleeding spots due to microemboli may be seen in the bulbar conjunctiva, oral mucosa, and fingertips. Signs such as sliver hemorrhages under the fingernails, Osler's nodes (tender reddish purple nodules on the fingers, palms, etc., caused by microemboli), Janeway rash (painless erythema on the fingers, palms, soles, etc.), and Roth spots on the fundus (hemorrhagic infarction with a white center surrounded by a red halo) are well-known for a long time, but are infrequent. Right-sided endocarditis may be accompanied by pulmonary embolism, hemoptysis, pleurisy, and pneumonia.
Test Results <br /> If a blood test detects the causative bacteria, the diagnosis is certain, so blood cultures are performed repeatedly. Venous blood is taken at least three to four times at different sites and times without administering antibiotics. There is no need to take arterial blood samples, and there is no need to wait for the patient to develop a fever. If the patient has already been administered antibiotics, discontinue the antibiotics if their condition is stable. If the blood culture is negative, it is assumed that the culture is being conducted during antibiotic treatment, or that the patient is a special type of bacteria that is difficult to grow in culture medium.
General examinations reveal nonspecific inflammatory findings, but nothing specific. A complete blood count may reveal mild anemia, leukocytosis (which may be normal), and elevated erythrocyte sedimentation rate and CRP, while serological tests may reveal elevated gamma globulin, positive rheumatoid factor, decreased complement levels, and immune complexes in the blood. Electrocardiograms, chest X-rays, CT scans, MRI, gallium scintigrams, and PET scans are used to determine the condition of any associated heart disease or heart failure, as well as complications such as peripheral embolism (Figure 5-11-2), and to differentiate from fever of unknown origin.
The most important imaging test is echocardiography, which is excellent at detecting valvular vegetations, but is often overlooked if the vegetations are small (Figure 5-11-3). Rather, it is also important to detect valvular dysfunction and changes in blood flow patterns, such as new regurgitation. Transesophageal echocardiography is extremely useful for detecting small vegetations and intracardiac abscesses, confirming the fine structure of native valves, and evaluating artificial valves and their surroundings. If infective endocarditis is suspected, transesophageal echocardiography should be performed even if no abnormalities are found on transthoracic echocardiography.
Diagnosis Diagnosis is based on identification of the causative bacteria by blood culture and demonstration of valvular dysfunction or valvular vegetations by echocardiography (Figure 5-11-4). An overview of the diagnostic criteria established by the Duke University group is shown below (Table 5-11-3).
To aid in diagnosis, it is necessary to confirm whether the patient has underlying heart disease or whether they have undergone any procedures within the past month that could cause bacteremia, such as dental, otorhinolaryngological, urinary, or gynecological procedures.
Differential diagnosis : In many cases, antibiotics are administered incompletely because of a cold or fever of unknown cause, and the fever subsides temporarily, but then recurs. There have also been cases where the condition has been mistaken for a collagen disease such as systemic lupus erythematosus, and steroids have been administered, resulting in death. It is also necessary to differentiate from tuberculosis, malignant tumors, rheumatic fever, thyroid dysfunction, drug allergies, etc.
ComplicationsSee Table 5-11-4 for complications .
Course and prognosis: With appropriate treatment, fever will subside quickly, but treatment is often difficult if empirical treatment is continued without identifying the causative bacteria. Although inflammatory signs may improve in response to antibiotic treatment and treatment may appear to be effective, patients may suddenly develop cerebral embolism or acute heart failure, so continued antibiotic administration over a long period of time and careful follow-up are important. Prognosis varies greatly depending on the causative bacteria; in cases of staphylococcal infection, the mortality rate is 20-40%, and in cases of MRSA in particular, the disease is resistant to treatment and the prognosis is poor. On the other hand, in cases of viridans streptococcus, the prognosis is good, with a recovery rate of 90-95%. Early cases after artificial valve surgery have a poor prognosis with a mortality rate of around 75%, but after two months of surgery the prognosis is the same as in cases of native valve surgery.
Treatment: Antibiotic therapy is performed in parallel with treatment for heart failure and other systemic symptoms. It is necessary to always keep in mind that surgery may be indicated, and to consult with a cardiac surgeon from the start of treatment.
1) Medical treatment with antibiotics:
Antibiotics must be bactericidal and administered over a long period while maintaining high blood concentrations. For details, refer to the respective guidelines, but in the case of streptococci and enterococci, in addition to administering penicillin G, aminobenzylpenicillin or vancomycin for 4 to 6 weeks, the aminoglycoside antibiotic gentamicin should also be administered. In the case of methicillin-susceptible staphylococci, gentamicin should be added to cefazolin or vancomycin. In the case of methicillin-resistant bacteria, a combination of vancomycin and an aminoglycoside drug should be considered, as well as the use of teicoplanin or arbekacin, which can be used to treat resistant bacteria.
In the case of fungi, most cases are Candida genus, and amphotericin B, which has high antifungal activity, is selected. Flucytosine, micafungin, and voriconazole are also used. However, it is often difficult to manage, and surgery is often required.
The effectiveness of treatment is assessed comprehensively based on factors such as fever reduction, improvement of inflammatory signs such as CRP and erythrocyte sedimentation rate, improvement in overall condition, and the condition of the warts on echocardiogram.
2) Indications for surgery:
Surgery should be considered when medical treatment is unable to control heart failure, infection, or embolism. However, in cases where there is associated cerebral hemorrhage due to cerebral embolism, micotic aneurysm, or other conditions, there is a high risk of developing or worsening cerebral hemorrhage due to the administration of heparin when the patient is attached to a cardiopulmonary bypass during cardiac surgery, and there are cases in which cardiac surgery must be postponed. In the case of artificial valves, early surgical intervention is said to result in a better prognosis, so it must not be delayed (Table 5-11-5).
Prevention: In cases where there is a high risk of endocarditis, preventive antibiotic treatment is performed during procedures involving transient bacteremia, such as tooth extraction, dental procedures involving gingival bleeding, and surgical operations. For example, 2 g of amoxicillin is administered orally (1 hour before the procedure), or 2 g of amoxicillin is administered intravenously or intramuscularly 30 minutes before the procedure. In cases with a penicillin allergy, clindamycin, cephalexin, clarithromycin, and azithromycin are used. When performing dental procedures, the risk of developing the disease can be reduced by thoroughly disinfecting the oral cavity before the procedure. In high-risk cases such as congenital heart disease or valvular disease, it is important to educate patients and their families about endocarditis prevention methods and provide information to doctors in each medical department (Table 5-11-6). [Imai Yasushi]

Table 5-11-1
Causing bacteria of infective endocarditis in native valves ">

Table 5-11-1

Table 5-11-2
Background of infective endocarditis in native valves ">

Table 5-11-2

Table 5-11-3
Duke University Infective Endocarditis Diagnostic Criteria

Table 5-11-3

Table 5-11-4
Complications of infective endocarditis

Table 5-11-4

Table 5-11-5
Indications for surgery for infective endocarditis ">

Table 5-11-5

Table 5-11-6
Procedures for which antibiotic prophylaxis against infective endocarditis is recommended ">

Table 5-11-6

Figure 5-11-1
Mechanism of infective endocarditis ">

Figure 5-11-1

Figure 5-11-4
Flowchart for the diagnosis of infective endocarditis

Figure 5-11-4

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

定義
　感染性心内膜炎は弁や弁の支持組織，心室中隔欠損症などの心内膜，大血管内膜に細菌，真菌などが付着・繁殖し塊（疣贅，疣腫；vegetation，verruca）となり，弁破壊を含めた心障害，菌血症，血管塞栓など多彩な所見を呈する全身性敗血症性疾患である．診断は必ずしも容易ではなく，不明熱をみたら心雑音の有無に関係なく必ず本疾患を念頭におくべきである．敗血症に伴う臨床症状，血液中の病原微生物（細菌，真菌など）の確認，心内構造の異常について診断する．治療は有効な抗菌薬の早期かつ十分な量を十分な期間投与，種々の合併症の管理，さらに適応があれば時期を逸することなく心臓外科手術を行うことが重要であり，不適切な判断・治療が致死的転帰に結びつくことを銘記すべきである．
分類
　臨床経過からは突然の高熱で発症し，数日ないし数週間で弁破壊が短期間に進む予後不良の急性感染性心内膜炎（acute IE）と，数週から数カ月かけて徐々に施行する亜急性心内膜炎（subacute IE）に分類される．acute IEは黄色ブドウ球菌が起炎菌のことが多く，弁を含めた心臓組織自体に異常がなくても罹患し，弁破壊と疣贅による塞栓などから数日以内に進行し，致死的な転帰をたどることが比較的多い重篤な病態である．内科的緊急症と考え，迅速な対応が望まれる．　subacute IEでは緑色連鎖球菌，腸球菌，コアグラーゼ陰性ブドウ球菌，Gram陰性桿菌などによることが多い．心臓弁膜症など基礎疾患がある症例に多く，微熱が続く程度でかぜ，膠原病，結核や悪性疾患と誤られ，漫然と抗菌薬投与がなされたり，経過観察されていることが少なくない．
　罹患弁に関しては自然弁心内膜炎（native valve endocarditis：NVE）と人工弁心内膜炎（prosthetic valve endocarditis：PVE）に分けられる．
原因・病因
　弁逆流などにより心臓内の乱流・高速の血流ジェットが弁，心腔内面に当たると，その部位の内膜が傷害を受け血小板，フィブリンなどの沈着が生じる（非細菌性血栓性心内膜炎（nonbacterial thrombogenic endocarditis：NBTE），非細菌性疣贅）．その状態において歯科処置，耳鼻咽喉科的処置，婦人科的処置，泌尿器科的処置などが原因で一過性に菌血症が生じると，先述の血小板・フィブリンなどの沈着物に菌が着床し増殖する．さらにフィブリンなどの沈着，菌増殖，周辺細胞の遊走・増殖などが複雑に絡み合って大きな疣贅となり心内膜炎となる．（図5-11-1）
　疣贅の周囲の弁支持組織，心筋組織，刺激伝導系などを破壊し弁機能が損なわれたり，循環不全，不整脈などの合併症が生じ得る．また疣贅の一部がはがれて末梢血管に塞栓することがあり，塞栓した疣贅がその末梢血管で動脈瘤（micotic aneurysm）を形成することがある．特に脳内での塞栓，瘤破裂は重大な転帰を招く．　本症の誘因は患者・起炎菌側の両者があり，患者側の因子として，心室中隔欠損，弁逆流・狭窄などで心腔内に異常な高速ジェットを伴う場合や，人工弁，ペースメーカリードなどの異物・人工物が体内に存在する場合があげられる．またわが国には少ないが，欧米では麻薬中毒患者が汚染された注射器を使って静脈内投与を繰り返すために，右心系の心内膜炎をきたすことが知られている．起炎菌からいえば，一般的に連鎖球菌は口腔内に常在しているが，抜歯を行うと一過性に菌血症を生じ心内膜炎の契機となる．このような一過性の菌血症は日常生活の中で頻回に認められており，歯磨きで数％～40％，抜歯では歯肉炎がない場合では35％，歯肉炎を伴うと70～75％，感染扁桃マッサージでは23％，尿道カテーテル挿入・抜去では8～26％などと予想外に高い．また皮膚常在の表皮・黄色ブドウ球菌やコアグラーゼ陰性ブドウ球菌（coagulase-negative streptococcus：CNS）などのGram陽性球菌が起因菌となることも多い．そのほか消化管，泌尿・生殖系の腸球菌（enterococcus），悪性疾患・ステロイドや免疫抑制薬投与例，長期カテーテル留置例ではGram陰性桿菌，嫌気性菌，真菌（カンジダ，アクチノミセスなど），クラミジア，リケッチアなどが原因となることもある．欧米ではHACEK群Gram陰性菌（Haemophilus，Actinobacillus actinomycetemcomitans，Cardiobacterium hominis，Eikenella，Kingella）が1～2割と多く，培地での発育が困難で血液培養がみかけ上陰性となる（表5-11-1）．
疫学
　本症の背景疾患としては心臓弁膜症，先天性心疾患，肥大型閉塞性心筋症，ペースメーカ・人工弁などの体内異物などがあげられる．近年，高齢者で増加しており，男性が女性の約2倍の頻度で罹患し，従来多かったリウマチ性弁膜症が減少し，加齢・変性によるとされる非リウマチ性弁膜症の合併が増加している．また起炎菌は以前は連鎖球菌が多かったが，最近は黄色ブドウ球菌感染による急性感染性心内膜炎の頻度が増加している．またGram陰性菌，真菌，そのほかのまれな菌による症例も増加している．最近は多剤耐性黄色ブドウ球菌，バンコマイシン抵抗性腸球菌など難治性心内膜炎も問題となっている．なお人工弁の術後早期の感染性心内膜炎においては表皮ブドウ球菌，黄色ブドウ球菌，Gram陰性桿菌などが多い（表5-11-2）．
病理
　僧帽弁や大動脈弁の罹患頻度が高い．感染巣は血小板とフィブリンからなる厚い網目に囲まれた疣贅を形成し数mmから大きいものでは数cmに達し，機能的な弁狭窄を生じる場合もある．感染が周辺に進展することにより，弁穿孔・瘤形成，腱索断裂，乳頭筋障害，弁輪部膿瘍，Valsalva洞瘤，心室中隔，心房中隔膿瘍，心筋炎をきたす．また脳，脾，腎，肺，冠動脈などへの塞栓症や免疫学的異常による皮膚症状，腎機能障害を合併することもある．疣贅の一部が脳や末梢動脈へ塞栓，そこで増殖し感染性動脈瘤（micotic aneurysm）を形成し，破裂，大出血をきたすことがある．
臨床症状
1）感染による全身症状：
発熱，倦怠感，食欲不振，体重減少など．
2）基礎心疾患・弁障害の進行による心症状：
弁逆流・相対的狭窄などによる心雑音の新出（85～90％で心雑音を認める），心拡大，心不全，弁輪部膿瘍による房室ブロックなど．
3）疣贅の塞栓症状：
脳塞栓，血尿，腹痛・イレウス，右心系心内膜炎では肺塞栓，肺炎など．
4）免疫学的異常：
腎炎，関節炎，心筋炎，心膜炎，血管炎をきたすこともある．またリウマチ因子，抗核抗体，ANCAなどが陽性になることがある．
　急性心内膜炎では高熱で発症し，数日以内の経過で急速に弁破壊が進行し診断の遅れが致命的となりえる．皮膚，結膜所見は本症を疑う契機となる．眼球結膜，口腔粘膜，指尖部などには微小塞栓による小出血点をみることがある．指の爪下線状出血，Osler結節（指，掌などの赤紫色の圧痛のある結節で疣贅による微小塞栓症），Janeway疹（痛みを伴わない指，手掌，足底などの紅斑），眼底Roth斑（中心が白色で周囲が赤色暈に囲まれる出血性梗塞）などは古くから有名な徴候であるが，頻度は低い．右心系心内膜炎では肺塞栓や喀血，胸膜炎，肺炎などが認められる．
検査成績
血液検査で起炎菌が検出されれば診断が確実となるため，血液培養を繰り返し行う．抗菌薬を投与せず採血部位・時間を変えて静脈採血を3～4回以上実施する．動脈採血の必要性はなく，また発熱するタイミングを待つ必要はない．すでに抗菌薬を投与されている場合は患者の状態が安定していれば抗菌薬を中止する．血液培養陰性の場合，抗菌薬治療中の培養であったり，培地での発育が困難な特殊な菌を想定する．
　一般検査では非特異的な炎症所見を認めるが，特異的なものはない．血算では軽度貧血，白血球増加（正常のこともある），赤沈・CRP亢進，血清学的検査ではガンマグロブリン増加，リウマチ因子陽性，補体価低下，血中免疫複合体を認めることがある．心電図，胸部X線，CT，MRI，ガリウムシンチグラム，PET検査などにより合併する心疾患・心不全の状態の把握，末梢塞栓症などの合併症の把握（図5-11-2），また不明熱の鑑別が実施される．
　画像検査で最も重要なのは心エコー検査で，弁の疣贅の検出にすぐれているものの，疣贅が小さいと見逃されることも少なくない（図5-11-3）．むしろ新出の逆流など弁機能不全や血流パターンの変化を拾い出すことも重要である．小さな疣贅や心内膿瘍の検出，自己弁の微細な構造確認，人工弁およびその周囲の評価などにおいては経食道エコーがきわめてすぐれており，感染性心内膜炎を疑う場合には経胸壁心エコーで異常がなくとも経食道エコーを実施すべきである．
診断
　診断は血液培養による起因菌の証明と心エコーによる弁機能不全や弁の疣贅の証明にある（図5-11-4）．Duke大学グループによる診断基準の概要を示す（表5-11-3）．
　診断の補助としては基礎心疾患の有無や1カ月程度以内に歯科，耳鼻咽喉科，秘尿器・婦人科系処置など菌血症をきたすような処置を受けていないかを確認する必要がある．
鑑別診断
　感冒，原因不明の発熱ということで中途半端な抗菌薬投与が行われ，一時的に解熱しても発熱が再発しているという場合が多い．また全身性エリテマトーデスなどの膠原病と間違われ，ステロイドを投与され死亡した症例もある．結核，悪性腫瘍，リウマチ熱，甲状腺機能障害，薬物アレルギーなどとの鑑別も必要である．
合併症
　合併症は表5-11-4を参照．
経過・予後
　適切な治療を受ければ早期に解熱するが，起炎菌不明のまま経験的な治療を続けるだけでは治療は困難なことが多い．なお抗菌薬治療に反応し炎症所見が軽快して一見，治療が奏効したようにみえても突然脳塞栓をきたしたり，急性心不全をきたすことがあり，長期間の抗菌薬投与継続と慎重な経過観察が重要である．予後は起炎菌により大きく異なり，ブドウ球菌性の場合，死亡率は20～40％に達し，特にMRSAでは治療抵抗性であり予後不良である．一方，緑色連鎖球菌性では予後良好で90～95％治癒するとされる．人工弁術後の早期例は死亡率が75％程度で予後不良であるが，術後2カ月を経過すれば自然弁例と予後は同等である．
治療
　抗菌薬治療と合併する心不全・全身所見などの治療を並行して行う．外科手術適応となる可能性を常に念頭におき，治療開始時から心臓外科医へのコンサルテーションが必要である．
1）抗菌薬による内科治療：
抗菌薬は殺菌性のものを血中濃度を高く保ち，長期間投与することが必要である．詳細は各ガイドラインを参照されたいが，連鎖球菌・腸球菌の場合，ペニシリンG，アミノベンジルペニシリンまたはバンコマイシンを4～6週間投与することに加えて，アミノグリコシド系抗菌薬ゲンタマイシンを追加投与する．メチシリン感受性ブドウ球菌の場合，セファゾリンまたはバンコマイシンにゲンタマイシンを追加投与する．メチシリン耐性の場合には，バンコマイシン，アミノグリコシド系薬併用，また耐性菌に対応できるテイコプラニンやアルベカシンを考慮する．
　真菌の場合は大半がカンジダ属であるが，抗真菌活性の高いアムホテリシンBを選択する．そのほかフルシトシン，ミカファンギン，ボリコナゾールも使用する．しかし，管理困難なことが多く外科手術となることが多い．
　治療効果の判定は解熱，CRP，赤沈などの炎症所見の軽快，全身状態の改善，心エコーにおける疣贅の状態などから総合的に判断する．
2）外科手術の適応：
内科治療で心不全や感染，塞栓がコントロールできない場合には外科手術を考慮する．しかし，脳塞栓，micotic aneurysmなどの関連した脳出血がある場合などは，心臓手術時の人工心肺装着時のヘパリン投与などで脳出血発症・悪化のリスクが高く，心臓手術を延期せざるを得ない状況も存在する．人工弁の場合，早期手術介入の方が予後良好とされており，時期を逸してはならない（表5-11-5）．
予防
　心内膜炎の危険性が高い症例では抜歯，歯肉出血を伴う歯科的処置，外科手術など一過性の菌血症を伴う処置に際し，抗菌薬による予防処置を行う．投与例として経口アモキシシリン2 g内服（処置1時間前），あるいはアモキシシリン2 g処置30分前に静注または筋注などが実施される．ペニシリンアレルギーのある症例ではクリンダマイシン，セファレキシン，クラリスロマイシン，アジスロマイシンなどが用いられる．歯科処置の場合には口腔内消毒を十分に行ってから処置をすると発症リスクが軽減する．また先天性心疾患や弁膜症などのハイリスク例では必ず心内膜炎予防法について患者・家族を教育すること，各診療科医師へ情報提供しておくことが重要である（表5-11-6）．［今井　靖］

表5-11-1
自己弁における感染性心内膜炎の起因菌">

表5-11-1

表5-11-2
native valve における感染性心内膜炎の背景疾患">

表5-11-2

表5-11-3
Duke 大学・感染性心内膜炎診断基準">

表5-11-3

表5-11-4
感染性心内膜炎の合併症">

表5-11-4

表5-11-5
感染性心内膜炎に対する外科手術の適応">

表5-11-5

表5-11-6
抗菌薬投与による感染性心内膜炎予防が推奨される手技">

表5-11-6