Treatment of infective endocarditis

Treatment of infective endocarditis consists of a long course of antimicrobial therapy. Surgery may be necessary for complications that disrupt the biomechanics of the valve apparatus or resistant microorganisms. As a rule, antibiotics are administered intravenously. Since the duration of therapy is 2-8 weeks, intravenous injections are often performed on an outpatient basis.

Any sources of bacteremia should be aggressively addressed, including surgical excision of necrotic tissue, drainage of abscesses, and removal of foreign material and infected devices. Intravenous catheters (especially central venous) should be replaced. If endocarditis develops in a patient with a newly inserted central venous catheter, it should be removed. Organisms present on catheters and other devices are unlikely to respond to antimicrobial therapy, leading to treatment failure or relapse. If continuous infusions are used instead of intermittent bolus administration, the interval between infusions should not be too long.

Antibacterial treatment regimens for infective endocarditis

The drugs and doses depend on the microorganism and its resistance to antimicrobial therapy. Initial treatment before identifying the microorganism is carried out with a broad-spectrum antibiotic to cover all probable pathogens. Typically, patients with native valves who do not inject intravenous drugs receive ampicillin 500 mg/h continuously intravenously plus nafcillin 2 g intravenously every 4 hours plus gentamicin 1 mg/kg intravenously every 8 hours. Patients with prosthetic valves receive vancomycin 15 mg/kg intravenously every 12 hours plus gentamicin 1 mg/kg every 8 hours plus rifampin 300 mg orally every 8 hours. Intravenous drug injectors receive nafcillin 2 g intravenously every 4 hours. In all regimens, patients with penicillin allergy require substitution with vancomycin 15 mg/kg intravenously every 12 hours. Intravenous drug injectors are often non-adherent, continue taking drugs, and tend to rapidly leave the hospital. Such patients may be treated with short courses of intravenous or (less preferably) oral medications. For right-sided endocarditis caused by methicillin-sensitive Staphylococcus aureus, nafcillin 2 g intravenously every 4 hours plus gentamicin 1 mg/kg intravenously every 8 hours for 2 weeks is effective, as is oral ciprofloxacin 750 mg twice daily plus oral rifampin 300 mg twice daily. Left-sided endocarditis does not respond to 2-week courses of treatment.

Antibiotic regimens for endocarditis

Microorganism	Medicine / Adult Doses	Medicine / Doses for adults allergic to penidillin drugs
Penicillin-susceptible streptococci (penicillin G MIC < 0.1 μg/ml), including most S. viridans	Benzylpenicillin (penicillin G sodium salt sterile) 12-18 million units per day intravenously continuously or 2-3 million units every 4 hours for 4 weeks, or for 2 weeks if the patient simultaneously receives gentamicin 1 mg/kg* intravenously (up to 80 mg) every 8 hours	Ceftriaxone 2 g once a day intravenously for 4 weeks, or the same for 2 weeks if the patient simultaneously receives gentamicin 1 mg/kg* intravenously (up to 80 mg) every 8 hours. The drugs are administered through a central venous catheter (can be administered on an outpatient basis). The patient should not have anaphylaxis to penicillin drugs. Vancomycin 15 mg/kg intravenously every 12 hours for 4 weeks
Streptococci relatively resistant to penicillin (MIC penicillin G > 0.1 μg/ml), including enterococci and some other strains of streptococci	Gentamicin 1 mg/kg* IV every 8 hours plus benzylpenicillin (penicillin G sodium salt sterile) 18-30 million units per day IV or ampicillin 12 g/day IV continuously or 2 g every 4 hours for 4-6 weeks ++	Desensitization to penicillins. Vancomycin 15 mg/kg IV (up to 1 g) every 12 hours plus gentamicin 1 mg/kg* IV every 8 hours for 4-6 weeks
Pneumococci or group A streptococci	Benzylpenicillin (penicillin G sodium salt sterile) 12-18 million IU per day intravenously continuously for 4 weeks if microorganisms are susceptible to penicillins. Vancomycin 15 mg/kg IV every 12 hours for 4 weeks for pneumococci with penicillin G MIC > 2 mcg/ml	Ceftriaxone 2 g once a day intravenously for 4 weeks through a central venous catheter (can be used on an outpatient basis), if there is no history of anaphylaxis to penicillins. Vancomycin 15 mg/kg IV every 12 hours for 4 weeks
Staphylococcus aureus strains resistant to oxacillin and nafcillin	Vancomycin 15 mg/kg IV every 12 hours - only this antibiotic, if the native valve is affected, gentamicin 1 mg/kg* IV every 8 hours for 2 weeks, rifampicin orally 300 mg every 8 hours if the prosthetic valve is involved for 6-8 weeks are added to it
Microorganisms of the NACEK group	Ceftriaxone 2 g once a day intravenously for 4 weeks. Ampicillin 12 g/day IV continuously or 2 g every 4 hours plus gentamicin 1 mg/kg* IV every 8 hours for 4 weeks	Ceftriaxone 2 g once daily intravenously for 4 weeks or for 2 weeks if the patient simultaneously receives gentamicin 1 mg/kg* intravenously (up to 80 mg) every 8 hours. The patient should not have a history of anaphylaxis to penicillin
Bacteria of the intestinal group	B-Lactam antibiotics if susceptibility is proven (eg, ceftriaxone 2 g IV q12-24 h or ceftazidime 2 g IV q8 h) plus an aminoglycoside (eg, gentamicin 2 mg/kg* IV q8 h) for 4-6 weeks
Pseudomonas aeruginosa	Ceftazidime 2 g IV q8h or cefepime 2 g IV q8h or imipenem 500 mg IV q6h plus tobramycin 2.5 mg/kg q8h for 6-8 weeks; amikacin 5 mg/kg q12h replaces tobramycin if bacteria are sensitive	Ceftazidime 2 g IV q8h or cefepime 2 g IV q8h plus tobramycin 2.5 mg/kg q8h for 6-8 weeks; amikacin 5 mg/kg q12h replaces tobramycin if bacteria are sensitive only to kamikacin
Penicillin-resistant strains of Staphylococcus aureus	For patients with damage to left-sided native valves: oxacillin or nafcillin 2 g intravenously every 4 hours for 4-6 weeks. For patients with damage to right-sided native valves: oxacillin or nafcillin 2 g IV every 4 hours for 2-4 weeks plus gentamicin 1 mg/kg* IV every 8 hours for 2 weeks For patients with a prosthetic valve: oxacillin or nafcillin 2 g IV every 4 hours for 6-8 weeks plus gentamicin 1 mg/kg* IV every 8 hours for 2 weeks plus rifampin orally 300 mg every 8 hours for 6-8 weeks	Cefazolin 2 g IV q8h for 4-6 weeks if staph is susceptible to oxacillin or nafcillin and no history of anaphylaxis to penicillins. Cefazolin 2 g IV q8h for 2-4 weeks plus gentamicin 1 mg/kg* IV q8h for 2 weeks Cefazolin 2 g IV every 8 hours for 4-6 weeks plus gentamicin 1 mg/kg* IV every 8 hours for 2 weeks plus rifampicin orally 300 mg every 8 hours for 6-8 weeks. Vancomycin 15 mg/kg IV every 12 hours - only this antibiotic, if the native valve is affected, gentamicin 1 mg/kg* IV every 8 hours for 2 weeks, rifampicin orally 300 mg every 8 hours if the prosthetic valve is involved for 4-6 weeks are added to it

* Calculate the ideal, not the actual body weight if the patient is obese. When prescribing vancomycin, its concentration in the blood serum should be monitored if the dose exceeds 2 g in 24 hours. ⁺⁺ If enterococcal endocarditis lasts more than 3 months and causes large vegetations or vegetations on prosthetic valves, treatment should be carried out for more than 6 weeks. Some clinicians add gentamicin 1 mg/kg IV every 8 hours for 3-5 days in patients with a native valve.

Cardiac surgery for valve pathology

Surgical treatment (debridement, valve repair, or replacement) is often indicated for abscess, persistent infection despite antimicrobial therapy (persistently positive blood cultures or recurrent emboli), or severe valvular regurgitation.

Timing of surgical intervention requires clinical judgment. If heart failure caused by a potentially correctable lesion worsens (especially when caused by Staphylococcus aureus, Gram-negative bacteria, or fungi), surgical treatment may be required immediately after a 24- to 72-hour course of antimicrobial therapy. In patients with prosthetic valves, surgical treatment may be required in the following situations:

• TTE demonstrates valve clefting or presence of perivalvular abscess;
• valve dysfunction causes heart failure;
• repeated embolisms were detected;
• The infection is caused by antibiotic-resistant microorganisms.

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Response to treatment for infective endocarditis

After initial therapy, patients with penicillin-susceptible streptococcal endocarditis usually feel better and their fever resolves within 3 to 7 days. Fever may persist for reasons other than infection (eg, drug allergy, phlebitis, embolic infarction). Patients with staphylococcal endocarditis usually respond more slowly to treatment.

Recurrence occurs within 4 weeks in most cases. Sometimes repeated antibiotic therapy is effective; in other cases, surgical treatment of infective endocarditis is necessary. In patients without prosthetic valves, recurrence of endocarditis after 6 weeks is usually the result of a new infection rather than a relapse. Even after successful antimicrobial therapy, sterile emboli and valve rupture may occur for up to 1 year.

Prevention of infective endocarditis

Antimicrobial prophylaxis is recommended for patients at high and moderate risk of infective endocarditis prior to procedures associated with bacteremia and subsequent infective endocarditis. In most cases, a single dose given shortly before the procedure is effective.