Infective endocarditis (IE) is one of the serious infectious diseases in pediatrics. In recent years, the incidence of IE has been increasing, and the clinical characteristics of IE have also changed, making the diagnosis and management of IE face new challenges. After clinical practice, the sensitivity of the trial criteria for the diagnosis of IE is significantly higher than that of the previous diagnostic criteria. The clinical manifestations and course of IE vary depending on the pathogenic microorganisms, the patient’s age, the presence of underlying heart disease and complications, etc. Clinical management requires the participation of multidisciplinary (cardiology, surgery, infectious disease, microbiology and clinical pharmacology) professionals in order to further improve the diagnosis and treatment. In order to facilitate the clinical diagnosis and management of IE, we have developed “Recommendations for diagnosis, treatment and prevention of pediatric infective endocarditis” based on domestic clinical experience and expert consensus with reference to foreign guidelines for diagnosis and treatment of IE.
I. Diagnosis
(A) Diagnostic indicators
1.Susceptibility factors
More than 90% of IE patients have susceptibility factors, among which congenital heart disease is the most common (78%~89%). Among congenital heart diseases, ventricular septal defect, patent ductus arteriosus, aortic valve lesion and cyanotic congenital heart disease are common. The risk of IE is not increased if there is no residual shunt more than 6 months after surgery for ventricular septal defect and patent ductus arteriosus. In recent years, with the decreasing incidence of rheumatic fever, rheumatic heart disease is no longer a common underlying heart condition.
Cardiac catheterization, transcatheter interventions, and intravenous tubes are also susceptibility factors for IE. the pathogenic microorganisms of IEitis are mostly resident bacteria in the pharynx, gastrointestinal tract, and skin sites. tooth extraction, scaling, periodontal surgery, and tonsillectomy can lead to bacteremia.
Cases without underlying heart disease or other susceptibility factors account for about 5-10% of cases (2,8,9). Patients are mostly infected with Staphylococcus aureus and can involve the left heart valve.
2, Clinical presentation
Infective endocarditis is a multisystemic disease involving bacteraemia, inflammation and damage to the heart valves, immune response and embolism constitute its main clinical manifestations. The clinical manifestations and their severity are also closely related to the associated comorbidities and pathogenic microorganisms. The clinical manifestations of neonatal IE are atypical and difficult to distinguish from sepsis and other causes of cardiac insufficiency. Clinical manifestations such as osteomyelitis, meningitis, and pneumonia caused by infectious embolism are common, and respiratory distress, cardiac murmur, and hypotension may also be present. The morbidity and mortality rate of neonatal IE is high.
(1) Fever is the most common symptom, with body temperature between 38℃ and 39℃, irregular fever pattern or hypothermia. In a few cases, the body temperature may be normal.
(2) Cardiac insufficiency and heart murmur
Some cases present with cardiac insufficiency or aggravation of existing cardiac insufficiency. Patients with IE who have normal body temperature mostly have cardiac insufficiency. Regurgitation of valve damage may result in a corresponding heart murmur or a change in the nature and loudness of the existing murmur, but it is sometimes difficult to detect.
(3) Vascular Signs
Petechiae (bulbar conjunctiva, oral mucosa and skin of trunk and extremities) and Janeway spots (erythema or hemorrhagic petechial lesions without pressure on the palms and soles of the feet) are rare in pediatric cases. Embolism of major blood vessels (lung, brain, kidney, mesenteric and splenic arteries) is an important comorbidity of IE, and may present with ischemic and hemorrhagic symptoms (such as chest pain, hemiplegia, hematuria and abdominal pain) in related areas.
(4) Immune signs
Hemorrhage under the finger (toe) nail (dark red, linear), Osler’s nodule (red subcutaneous nodules on the metacarpal surfaces of fingers and toes), and Roth’s spot (oval hemorrhagic spot in the fundus with a pale center) are not unique to IE and are rare in pediatric cases. Immune complex glomerulonephritis is seen in some cases of IE, with hematuria and renal insufficiency.
3. Pathogenic examination
The most common pathogenic bacteria are Streptococcus gramineus (a-hemolytic) and Staphylococcus aureus, which account for about 80% or more of positive blood cultures, with Streptococcus gramineus accounting for more than 50% and Staphylococcus aureus showing an increasing trend (11). The number of Streptococcus mutans increased compared to the previous. Other still have b-hemolytic streptococci, Streptococcus pneumoniae, enterococci, HACEK group (Haemophilus, Actinobacillus, Human heart bacillus, Eckenobacter and Kingella bacillus), fungi, etc. Infective endocarditis caused by non-bacterial pathogens such as Burkholderia cepacia (Q fever pathogen), Baltonella cepacia, and Chlamydia cepacia has also been reported abroad. Neonatal IE is mainly caused by Staphylococcus aureus, coagulase-negative staphylococci, and group B streptococci.
The detection of pathogens and drug sensitivity testing are both important to help determine the diagnosis and select effective drugs.
(1) Blood cultures can be positive in more than 90% of patients with confirmed IE without antibiotics. Negative blood cultures may be associated with inappropriate culture techniques, infection with caustic bacteria or non-bacterial pathogens, and the use of antibiotics prior to blood culture. Therefore, it is important to standardize the operation of blood culture to improve the detection rate of pathogenic bacteria.
For patients to be diagnosed with IE, blood must be collected three times for blood culture within 1-2 hours before the administration of antibacterial drugs, each time at a different site. Since bacteraemia is continuous in IE, it is not necessary to choose to draw blood at high temperature. Blood should be collected by venipuncture after strict skin disinfection (do not collect blood at the indwelling catheter through the blood vessel). If antibiotics have been used for a short period of time, blood should be collected and sent for culture after at least 3 days of discontinuation if possible; if long-term antibiotic treatment has been given, the time of discontinuation should be longer. If the condition does not allow discontinuation, blood cultures can be taken half an hour before the next antibiotic, while using a blood culture bottle with added antimicrobial adsorbent.
Each blood culture should include aerobic and anaerobic cultures, with the addition of fungal cultures being considered based on the clinical situation. Children’s culture bottles must be used, and the ratio of culture medium to blood should be 10:1. The volume of blood collected should be 3-5 ml for children and 1-2 ml for infants. too little blood may reduce the chance of bacterial detection. Blood culture specimens should be sent to the laboratory as soon as possible (within 2 hours), with a note that the patient is clinically suspicious for IE.
Blood culture time varies depending on the strain and bacterial content. Positive results are seen in 18-24 hours for common organisms. Most IE blood cultures need to be cultured in a fully automated blood culture system for 6 days. If the result is negative, but the patient with high clinical suspicion of IE can be examined by other methods, such as considering fungal, anaerobic and other atypical pathogens infection need to improve the culture conditions; using serological methods (ELISA or immunofluorescence, etc.) or molecular biology techniques (PCR, etc.) to detect microbial antigens, antibodies, DNA fragments. When the blood culture is positive, the detected pathogens should be tested for drug sensitivity, and the minimum inhibitory concentration (MIC) of the drug should be determined when available, either by microdilution method or semi-quantitative E test method. Pathogenic microorganisms should be stored for at least 1 year.
(2) Culture and molecular biology of cardiac redundant or infected tissues The cardiac redundant or infected tissues obtained during surgery in patients with acute IE should also be examined by culture. Tissue culture is particularly useful for the detection of caustic bacteria. Small pieces of tissue should be spiked with a small amount of sterile saline to maintain a certain level of moisture, and the tissue should not be allowed to dehydrate and sent to the laboratory immediately. Molecular biology techniques can also be used to detect microorganisms within caustic or infected tissues to improve the detection rate of bacteria.
(3) Serologic methods Serologic tests are particularly important for diagnosing IE of infections such as Tritrichomonas burnetii (Q fever pathogen), Baltonella spp, Brucella, Legionella, and Chlamydia (immunodeficient individuals). Diagnosis can be made using indirect immunofluorescence or ELISA methods. Elevated antibody titers when combined with other clinical information can be helpful, such as a significant decrease in antibody titers within a few months after treatment can also be used as evidence for pathogenic diagnosis.
4.Echocardiography
The main echocardiographic signs of endocardial damage are: redundancy, intracardiac (perivalvular) abscesses, new partial dehiscence of prosthetic valves or intracardiac repair materials, and valve perforation. In pediatric IE cases, endocardial damage is seen on echocardiography in about 85% of cases, among which redundancy is the most common, valve perforation and postoperative patch dehiscence are rare, and intracardiac abscess and partial dehiscence of prosthetic valves are rare in pediatric IE cases.
Early echocardiographic examination of clinically suspected IE cases to detect signs of membrane damage and to assess valve and cardiac function is important for diagnosis and observation of disease. Infective endocarditis cannot be ruled out without the presence of a superfluous organism. If the echocardiographic findings are negative and the clinical presentation is still cool for IE, a repeat echocardiogram is needed in 7 to 10 days. During the course of treatment, the echocardiogram needs to be repeated promptly if there is deterioration such as heart failure, change in heart murmur, etc., which is important for the decision of surgical management such as enlargement of superfluous organisms, valve perforation, and aggravation of regurgitation. Transesophageal echocardiography is superior to transthoracic echocardiography for the diagnosis of IE. However, the thinner chest wall and better sound transmission conditions in pediatric patients make the diagnosis of IE by transthoracic echocardiography clinically feasible.
5.General laboratory tests
Blood erythrocytes and hemoglobin decrease, which may be progressive. The total blood leukocyte count is increased, and the proportion of neutrophilic polynuclear leukocytes is elevated. The erythrocyte sedimentation rate is increased, serum C-reactive protein is increased, and proteinuria and microscopic hematuria are seen in some cases. The rheumatoid factor and circulating complexes are positive in about half of the cases, with a higher chance of positivity in those with longer disease duration.
(II) Diagnostic criteria
In 1994, Durack et al. proposed new criteria for the diagnosis of IE (Duke criteria), which first applied evidence of endocardial involvement by echocardiography and served as the basis for clinical confirmation of the diagnosis (12). An international multicenter controlled study demonstrated that the sensitivity and specificity of Duke’s criteria for the diagnosis of IE were higher than those of previous diagnostic criteria. However, in 18% to 24% of cases with pathologically or surgically confirmed infective endocarditis, the diagnosis was not confirmed by the Duke criteria (13). In addition, the chance of diagnosis of possible infective endocarditis by Duke’s criteria is overrepresented.
In order to improve the diagnostic sensitivity of the Duke criteria, Li et al. of Duke University proposed a revision of the Duke criteria in 2000. In 2000, the Cardiovascular Group of the Pediatrics Branch of the Chinese Medical Association and the Editorial Committee of the Chinese Journal of Pediatrics proposed diagnostic criteria for pediatric infective endocarditis (for trial).
The domestic Pediatric Infective Endocarditis Collaborative Research Group collected 216 pathologically confirmed or excluded cases of infective endocarditis and applied the Duke criteria and the trial criteria in a controlled study. The false-negative rate of the Duke criterion was 51.3%, and the false-negative rate of the trial criterion was 4.3%. Echocardiographic signs of endocardial involvement plus 2 secondary indicators as confirmatory criteria contributed significantly to the diagnostic sensitivity, while significant vascular signs as primary indicators had no effect on diagnostic sensitivity and specificity. Therefore, appropriate modifications of the trial criteria (Table 1) can be used as diagnostic criteria for pediatric infective endocarditis.
It should be emphasized that no diagnostic criteria can replace the clinical analysis judgment, and a comprehensive analysis with close combination of diagnostic criteria and clinical manifestations is needed to treat cases with different manifestations of IEitis. In the diagnosis of infants, neonatal IE fashion needs to be combined with the characteristics of clinical manifestations at different ages.
Table 1 Diagnostic criteria for pediatric infective endocarditis
I. Pathological indicators
(i) Superfluous organisms (including those that have formed emboli) or infected tissues of the heart found by culture or microscopic examination of microorganisms.
(b) Superfluous or cardiac infected tissue confirmed by pathological examination with active endocarditis.
II. Clinical indicators
(a) Main indicators
1. Positive blood culture;
2. 2 separate blood cultures with the same common microorganisms of infective endocarditis (Streptococcus straw green, Staphylococcus aureus, Enterococcus, etc.): or serologic evidence of microorganisms that are difficult to culture
3. Evidence of endocardial involvement (echocardiographic signs)
① (1) superfluous organisms attached to valves, valve devices, endocardium of the heart or great vessels, or implanted prosthetic materials.
(2) valve perforation, new partial dehiscence of the prosthetic valve or defective patch.
(3) Intracardiac abscess
(2) Secondary indicators
1.Infection-prone conditions
(a) underlying cardiac disease, cardiac surgery, cardiac catheterization, transcatheter interventions, and central venous intubation
2, longer-term fever ≥38℃ with blood.
3. aggravation of existing cardiac murmur, appearance of new cardiac murmur, or cardiac insufficiency.
4. vascular signs important arterial embolism, infected aneurysm, petechiae, splenomegaly, intracranial hemorrhage, conjunctival hemorrhage, Janeway’s spot’
5. immunological signs glomerulonephritis, Osler’s node, Roth’s spot, positive rheumatoid factor5, microbiological evidence positive blood culture, but not meeting the requirements in the main criteria
III. Diagnostic basis
(a) Infective endocarditis can be diagnosed with any one of ①-⑤: ① 2 major clinical indicators; ② 1 major clinical indicator and 3 minor clinical indicators; ③ evidence of endocardial involvement and 2 minor clinical indicators; ④ 5 minor clinical indicators; ⑤ 1 pathological indicator.
(b) The diagnosis of infective endocarditis can be ruled out when there is a clear alternative diagnosis explaining the manifestation of endocarditis; the manifestation of endocarditis is eliminated by antibiotic treatment ≤ 4 days; there is no pathological evidence of infective endocarditis after antibiotic treatment ≤ 4 days of surgery or autopsy
(c) clinical examination of infective endocarditis, but does not have the basis for a definitive diagnosis should still be treated, based on clinical observation and further examination results to confirm or exclude the diagnosis of infective endocarditis.
II. Treatment
(A) Antibiotic therapy
1.Treatment principles
Early diagnosis and timely and reasonable application of antibacterial drug therapy is the key to improve the therapeutic effect of IE. The choice of antibacterial drugs is best based on the detection of pathogenic microorganisms and their drug sensitivity test results to antibacterial drugs. If the blood culture is negative, the appropriate antimicrobial drug should be selected according to the clinical characteristics and analysis of the possible pathogenic microorganisms. The antimicrobial drugs with large penetration should be selected, and sufficient dose and long course of treatment are needed to achieve the purpose of cure. It is advisable to use intravenous administration to ensure that the effective blood concentration is reached quickly. Combined application of drugs with synergistic antibacterial effects can increase the efficacy. After the treatment regimen is established, close observation of clinical manifestations and follow-up blood cultures and inflammatory markers are needed to evaluate the therapeutic effect.
The combination of aminoglycoside antibacterial drugs and β-lactam antibacterial drugs often results in synergistic effects and is an effective drug for the treatment of endocarditis. Due to the serious toxic side effects of aminoglycoside antimicrobial drugs, caution is needed when using them in pediatric cases. According to the national pharmacopoeia, they can be used with caution in children older than 6 years of age when other antibacterial drug treatments are ineffective. A careful family history of neurogenic deafness needs to be asked and informed family consent obtained before application. Nephrotoxicity of aminoglycoside antibacterial drugs is dose-related and blood levels need to be monitored during use, e.g., gentamicin, which requires peak concentrations of 4-8 μg/ml and trough concentrations at 2 weeks), and has not been approved by the US FDA for IE therapy.
Table 2. antimicrobial drug regimen for streptococcal endocarditis Dosage and administration Course of treatment (weeks)# Remarks
Streptococci highly sensitive to penicillin (MIC ≤ 0.1 μg/ml) Penicillin 200,000 U/kg・d q4~6h IV 4
Amoxicillin 300mg/ kg・d q4～6h IV 4
or Ceftriaxone* 100mg/kg・d qd IV 4
Vancomycin 30～40mg/kg・d q8h IV (for >1 h) 4
For relative resistance of Streptococcus to penicillin (MIC>0.1μg/ml, ≤0.5μg/ml) in those who are intolerant to penicillin or ceftriaxone
Penicillin 300~400,000U/kg・d q4~6h IV 4
Amoxicillin 300mg/ kg・d q4～6h IV 4
Ceftriaxone 100mg/kg・d qd IV 4
Gentamicin 3mg/kg?d q8h IV 2
Streptococci resistant to penicillin (MIC>0.5μg/ml) for 2 weeks of initial treatment
Streptococcus nutrient variant penicillin 400,000 U/kg・d q4-6h IV 4 to 6
Amoxicillin 300mg/ kg・d q4～6h IV 4～6
Ceftriaxone 100mg/kg・d qd IV 4～6
Gentamicin 3mg/kg・d q8h IV 4
Vancomycin 30-40mg/kg/d q8h IV 4～6 for 4 weeks of initial treatment
For penicillin or plus gentamicin 3mg/kg・d q8h IV 4
Ceftriaxone intolerant; MIC of ceftriaxone >2μg/ml.
Note: * Ceftriaxone# should be given for 6 weeks for prosthetic valve or prosthetic material placement.
(2) Staphylococcal endocarditis
Staphylococcal endocarditis accounts for 20-30% of all IEs, and the proportion is gradually increasing. It includes Staphylococcus aureus and coagulase-negative staphylococci (Staphylococcus epidermidis and other species). After the application of penicillin, penicillin-resistant Staphylococcus aureus soon appeared, and later methicillin-resistant Staphylococcus aureus (MRSA) appeared. 90% or more of Staphylococcus aureus can produce penicillinase and are resistant to β-lactam anti-chaplains. Vancomycin-resistant strains have also been reported in recent years, but are rare.
The recommended regimen and dose are shown in Table 3. based on blood culture results, staphylococci sensitive to benzocillin are preferred to benzocillin (or cefazolin) plus gentamicin (or rifampin), and if intolerant to β-lactam antibacterial drugs, vancomycin plus gentamicin (or rifampin) is preferred. For staphylococci resistant to benzocillin, use vancomycin plus gentamicin (or rifampicin).
In patients with IE after cardiac surgery, application of prosthetic materials or prosthetic valves, staphylococci are sensitive to benzocillin: benzocillin (or cefazolin) plus gentamicin plus rifampin is preferred; if staphylococci are resistant to benzocillin, vancomycin plus gentamicin plus rifampin is preferred.
Table 3. antimicrobial regimen for staphylococcal endocarditis Dosage and administration Course of treatment (weeks) Remarks
Staphylococci sensitive to benzocillin Benzocillin 200 mg/kg・d q4~6h IV 6
Cefazolin 100 mg/kg・d q6～8h IV 6
With or without gentamicin 3 mg/kg・d q8h IV 3～5 days
(at initial treatment) or rifampicin 20 mg/kg・d q8h PO 6
Vancomycin 30～40mg/kg・d q8h IV 6
Staphylococci intolerant to β-lactam antibiotics resistant to benzocillin Vancomycin 30-40mg/kg・d q8h IV 6
Add gentamicin 3mg/kg・d q8h IV 3-5 days (at initial treatment)
Rifampin 20mg/kg・d q8h PO 6
Application of artificial material or prosthetic valve sensitive to benzocillin Benzocillin 200 mg/kg・d q4-6h IV 6
Cefazolin 100 mg/kg・d q6～8h IV 6
Plus rifampicin 20 mg/kg・d q8h PO 6
Add gentamicin 3 mg/kg・d q8h IV 3～5 days
(At initial treatment) Benzoxicillin-resistant vancomycin 40 mg/kg?d q8h IV ≥6
Plus rifampicin 20 mg/kg・d q8h PO ≥6
Plus gentamicin 3 mg/kg・d q8h IV 2 (at initial treatment)
(3) Enterococcal endocarditis
Enterococcal endocarditis is less common in pediatric patients. Enterococcus faecalis (E. faecalis), Enterococcus faecium (E. faecium) and Enterococcus persistentus (E. durans) are three types of enterococci that can cause IE, among which Enterococcus faecalis is the most common. There are more multidrug-resistant strains, and E. faecium is still mostly sensitive to ampicillin, and resistant strains to glycopeptide antimicrobials are gradually increasing, and about 10%-35% are highly resistant to aminoglycoside antimicrobials (in 2008, the resistance rate of E. faecium to gentamicin in Shanghai was 52%, and 66% for E. faecium). The recommended dosing regimen is shown in Table 4.
Table 4. antimicrobial drug regimen for enterococcal endocarditis Drug regimen Dose and usage Course (weeks) Remarks Sensitivity to penicillin, ampicillin, and aminoglycoside antimicrobials.
Penicillin 400,000 U/kg・d q4~6h IV 6
or ampicillin 300mg/kg・d q4~6h IV 6
or Amoxicillin 300mg/kg・d q4~6h IV 6
Add gentamicin 3mg/kg・d q8h IV 4
Intolerant to β-lactam antibiotics.
Vancomycin 30~40mg/kg・d q8h IV 6
Add gentamicin 3mg/kg・d q8h IV 4
Vancomycin resistant to β-lactam antibiotics 30-40mg/kg・d q8h IV 6
or ampicillin/sulbactam 300mg/kg・d q6h IV 6
Add gentamicin 3mg/kg・d q8h IV 4
Linezolid resistant to β-lactam antibiotics, aminoglycoside antibiotics and glycopeptide antibiotics 30mg/kg・d q8h IV 6
(4) HACEK bacillary endocarditis
HACEK is a group of Gram-negative bacilli, including: Haemophilus haemolytica, Actinobacillus actinomycetemcomitans, Bacillus cardiacus, Acinetobacter spp. and Aureus spp. This group of bacteria grows slowly in the usual culture medium. It accounts for about 5-10% of the pathogenic bacteria of infective endocarditis. This group of bacteria used to be sensitive to ampicillin, but now many strains are resistant to it because of β-lactamase production. β-lactamase-producing HACEK strains are sensitive to ceftriaxone (or other third-generation cephalosporins). The recommended dosing regimen is shown in Table 4.
(5) Pseudomonas aeruginosa endocarditis
Most commonly seen in IE caused by intravenous cannulation, a large proportion of which involves normal valves and is prone to embolism, with neurological complications in about 50% of patients, rapid progression and high mortality rate. The recommended drug regimen is shown in Table 4.
(6) Fungal endocarditis
Fungal endocarditis accounts for 2% of all IEs, with Candida spp. infections being more common, Aspergillus infections being rare, and plural fungal infections with Staphylococcus spp. or Streptococcus spp. may also occur. Fungal endocarditis has a high mortality rate and a high recurrence rate. Amphotericin B is commonly used as the first-line agent for Candida spp. infections, and oral daflucan (fluconazole) is still required for long-term treatment after clinical symptoms improve. The recommended dosing regimen is shown in Table 4.
Table 5. antimicrobial drug regimens for Mycobacterium HACEK, Pseudomonas aeruginosa, and fungal endocarditis dosing regimen and duration of therapy (weeks) Remarks
Ceftriaxone 100mg/kg・d qd IV4
or ampicillin / sulbactam 300mg/kg・d q4~6h IV4
Pseudomonas aeruginosa tobramycin 8mg/kg・d qd, IV≥6
Add piperacillin 200 mg/kg・d q4～6d IV≥6
or ceftazidime 150 ~ 200 mg/kg・d q8d IV≥6
Candida amphotericin B lipid-containing complex 3-5mg/kg・d q6h IV≥6～8
Surgical treatment is often required.
With or without 5-fluorocytosine 100mg/kg・d q6h p.o≥6～8
or amphotericin B conventional preparation 0.6-1mg/kg・d IV≥6～8
With or without 5-fluorocytosine 100mg/kg・d q6h p.o≥6～8
Trichothecene voriconazole day 1: 6mg/kg q12h
IV day 2: 4mg/kg q12h IV≥6～8 (FDA not approved for this indication, little clinical data)
Amphotericin B liposome 3-5mg/kg・d IV, ≥6～8 often requires surgery.
or Amphotericin B lipid-containing complex (ABLC), 5mg/kg・d IV ≥6 (7)
Blood cultures are negative for endocarditis in up to 20% of patients with IE who meet diagnostic criteria. However, about 5% remained negative after exhaustive testing. The reasons for negative blood cultures are related to the fact that the pathogenic microorganisms are bacteria or non-bacterial pathogenic microorganisms that require high nutritional requirements (Bernadette Rickettsia, Baltonella, Ehrlichia, etc.); the fact that antibiotics have been used before the blood culture and inappropriate techniques for pathogenic microorganism detection.
The selection of antimicrobial drugs is more difficult in patients with negative blood cultures. In this case, a comprehensive analysis is needed to determine the possible pathogenic microorganisms according to the epidemiological and clinical characteristics of endocarditis. For those who have used antimicrobial drugs after the onset of the disease, are in the acute phase, and have no history of cardiac surgery, antimicrobial drugs targeting Staphylococcus aureus need to be selected (Table 2); for those who are clinically subacute, the selection of antimicrobial drugs needs to consider both Staphylococcus aureus, Streptococcus spp. and Enterococcus spp. and HACEK bacilli (Tables 1 to 4); for patients with prosthetic valves or application of prosthetic materials, who develop within 1 year after cardiac surgery Treatment needs to target benzocillin-resistant Staphylococcus spp. (Table 2); within 2 months after cardiac surgery, aerobic Gram-negative bacilli need to be considered (Table 4); onset after 1 year of cardiac surgery, with benzocillin-sensitive Staphylococcus spp., Streptococcus spp., and Enterococcus spp. being more common. Among the nonbacterial pathogens, Bartonella is the most common, accounting for about 3% of all IEs, and the recommended drug regimen is shown in Table 5.
Table 5. Antimicrobial regimens for Bartonella endocarditis Dosage and administration Duration of therapy (weeks) Remarks
Ceftriaxone 100mg/kg・d qd IV 6
Add gentamicin 3mg/kg/d q8h IV 2
or Rifampicin 20 mg/kg・d q12h PO 2
With or without doxycycline** 2 to 4 mg/kg・d q12h PO 6
Note** doxycycline
(ii) Surgical treatment
In recent years, surgical treatment has been actively used in the treatment of acute IE, which is the reason for the significant reduction in the death rate of acute IE, especially staphylococcal endocarditis. Domestic data also prove that the clinical regression of cases in the antimicrobial drug plus surgical treatment group is significantly better than that in the antimicrobial drug treatment group alone. Indications for surgical treatment include
(1) Damage to the mitral or aortic valve with severe regurgitation leading to heart failure.
(2) persistent fever, positive blood cultures, or enlarged intracardiac bullae despite more than 1 week of appropriate antimicrobial therapy
(3) Heart valve perforation, rupture, perivalvular abscess or fistula formation, presenting with localized destructive infection or spread of infection.
(4) Large or risk of dislodgment of the flab, especially if located on the left heart valve, or more than 1 embolic event within 2 weeks of antimicrobial therapy.
(5) Endocarditis caused by fungal or antimicrobial-resistant pathogens, etc. Surgical procedures include debridement of superfluous organisms, management of infected tissue or artificial material implants, repair or replacement of heart valves, correction of underlying congenital heart disease or residual defects or obstruction after congenital heart surgery.
It has been reported that about 25-30% of patients with IE require surgical treatment. If surgical treatment is indicated, surgery should be performed as early as possible. Clinical experience has demonstrated that patient prognosis is related to early surgery and has little to do with the timing and intensity of preoperative antibiotic application. Waiting for heart failure before surgery increases the mortality rate of surgery. The timing of postoperative antibiotics is based on the results of the culture of the superfluous or infected tissue obtained. If the culture is negative, the duration of postoperative application of antibiotics should be added to the duration of preoperative medication for a complete course of treatment or at least 2 weeks, and if the culture is positive, the treatment should be restarted for 4-6 weeks after surgery, and the type of antibiotics should be adjusted with reference to the degree of bacterial sensitivity to drugs.
(iii) Supportive treatment
Systemic supportive therapy is also important, including rest, nutrition and blood transfusion. In case of cardiac insufficiency, anti-cardiac failure treatment should be provided according to the condition.
(D) Disease course observation and follow-up
Most patients with IE can be cured after appropriate antibacterial drugs or surgical treatment.
The indicators of effective antimicrobial drug treatment are: the body temperature gradually decreases and becomes normal 3-5 days after the drug is administered; the blood culture turns negative and the non-specific inflammatory index turns normal. If fever persists even after more than 1 week of antimicrobial therapy, ineffective treatment or the presence of comorbidities (such as abscess) should be considered. Re-emergence of fever after normalization of body temperature, especially at 3-4 weeks of treatment, may be caused by drug (b-lactam antibiotics) allergy.
Endpoints of treatment: attainment of the course of antimicrobial therapy; negative blood cultures; normalization of non-specific inflammatory markers.