Medication Summary
Antibiotics are the mainstay of treatment for infective endocarditis (IE). Goals to maximize treatment success are early diagnosis, accurate microorganism identification, reliable susceptibility testing, prolonged intravenous (IV) administration of bactericidal antimicrobial agents, proper monitoring of potentially toxic antimicrobial regimens, and aggressive surgical management of correctable mechanical complications.
Antibiotics
Class Summary
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Penicillin G (Pfizerpen)
Penicillin G is used for IE caused by S viridans or S bovis with a penicillin G minimum inhibitory concentration (MIC) of 0.1 mcg/mL or less.
Oxacillin (Bactocil in Dextrose)
Oxacillin is a bactericidal antibiotic that inhibits cell wall synthesis. It is used to treat infections caused by penicillinase-producing staphylococci. It is used to initiate therapy when MSSA infection is present.
Ceftriaxone (Rocephin)
Ceftriaxone is given as once-daily treatment of S viridans or HACEK (ie, H aphrophilus, A actinomycetemcomitans, C hominis, E corrodens, K kingae) IE. It is a third-generation cephalosporin with broad-spectrum gram-negative activity. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to one or more penicillin-binding proteins.
Vancomycin
Vancomycin is the drug of choice for patients who are allergic to penicillin who have streptococcal or enterococcal endocarditis, those with methicillin-resistant S aureus (MRSA) IE, and those with other beta-lactam–resistant gram-positive IE infections.
It is important to achieve adequate trough levels of 15-20 mcg/mL. If theMIC of the isolate is 2 mcg/mL or greater, vancomycin should not be administered.
The duration of treatment is 4 weeks in penicillin-susceptible streptococcal IE and 4-6 weeks for staphylococcal infections, prosthetic valve infections, or enterococcal IE.
Gentamicin
Gentamicin is an aminoglycoside used in combination therapy to attain bactericidal activity against enterococci and resistant streptococcal species, to shorten treatment of penicillin-susceptible streptococcal IE, and for prosthetic staphylococcal IE.
The duration of treatment is 2 weeks for penicillin-susceptible streptococcal IE and 4-6 weeks for penicillin-resistant streptococci and enterococci.
Streptomycin
Streptomycin is an aminoglycoside antibiotic that has bacteriocidal activity and acts by inhibiting protein synthesis. It may be used for the treatment of streptococcal or enterococcal endocarditis
Ampicillin
Ampicillin is used for treatment of enterococcal IE, IE caused by HACEK organisms, or as a penicillin G substitute for penicillin-susceptible organisms.
For enterococcal endocarditis, duration of treatment is 4-6 weeks in combination with gentamicin.
Ampicillin and sulbactam (Unasyn)
Ampicillin and sulbactam is a drug combination consisting of a beta-lactamase inhibitor with ampicillin. It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms.
Cefazolin
Cefazolin is a first-generation cephalosporin that is used for staphylococcal endocarditis susceptible to methicillin/oxacillin. It may be substituted for penicillin G or ampicillin for penicillin-susceptible streptococcal endocarditis. It is used if the patient develops a mild rash to penicillins but no anaphylaxis or severe immediate hypersensitivity reactions.
Ceftazidime (Fortaz, Tazicef)
Ceftazidime is a third-generation cephalosporin with broad-spectrum, gram-negative activity, including against pseudomonas. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to one or more penicillin-binding proteins, which, in turn, inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell wall synthesis, thus inhibiting cell wall biosynthesis. The condition of the patient, severity of the infection, and susceptibility of the microorganism should determine the proper dose and route of administration.
Cefepime (Maxipime)
Cefepime is a fourth-generation cephalosporin with gram-negative coverage comparable to ceftazidime, but it has better gram-positive coverage (comparable to ceftriaxone). Cefepime is a zwitter ion and rapidly penetrates gram-negative cells.
Nafcillin (Nallpen in Dextrose)
Nafcillin is used for staphylococcal IE caused by organisms susceptible to methicillin/oxacillin.
Linezolid (Zyvox)
Linezolid prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. It is bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. It is used as an alternative in patients allergic to vancomycin and for treatment of vancomycin-resistant enterococci (VRE).
The FDA warns against the concurrent use of linezolid with serotonergic psychiatric drugs, unless indicated for life-threatening or urgent conditions. Linezolid may increase serotonin CNS levels as a result of MAO-A inhibition, increasing the risk of serotonin syndrome.
Daptomycin (Cubicin)
Daptomycin is a cyclic lipopeptide antibiotic that is used for Staphylococcus aureus bacteremia, including those with right-sided infective endocarditis caused by MSSA or MRSA. There is a risk of developing eosinophilic pneumonia with daptomycin use. Immediate discontinuation of daptomycin is recommended if eosinophilic pneumonia is suspected.
Rifampin (Rifadin)
Rifampin is used synergistically in the treatment of staphylococcal infections associated with a foreign body, such as a prosthetic heart valve.
Rifampin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. Cross-resistance has been shown only with other rifamycins.
Ciprofloxacin (Cipro, Cipro XR)
Ciprofloxacin is a fluoroquinolone antibiotic that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad-spectrum activity against gram-positive and gram-negative aerobic organisms. It has no activity against anaerobes.
Doxycycline (Adoxa, Doryx, Monodox, Vibramycin)
Doxycycline is a broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. It is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations. It inhibits protein synthesis and, thus, bacterial growth by binding to the 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Sulfamethoxazole and Trimethoprim (Bactrim, Bactrim DS, Septra DS, Sulfatrim)
Trimethoprim and sulfamethoxazole inhibit bacterial growth by inhibiting the synthesis of dihydrofolic acid.
Quinupristin and dalfopristin (Synercid)
Quinupristin and dalfopristin belong to the macrolide/lincosamide/streptogramin group of antibiotics. The combination inhibits protein synthesis and is usually bacteriostatic. This drug combination is effective against Enterococcus faecium, but not Enterococcus faecalis strains. It is an option for the treatment of vancomycin-resistant E faecium infections.
Ticarcillin-clavulanate (Timentin)
Ticarcillin-clavulanate inhibits the biosynthesis of cell wall mucopeptide and is effective during the stage of active growth. The drug combination includes an antipseudomonal penicillin plus a beta-lactamase inhibitor that provides coverage against most gram-positive, most gram-negative, and most anaerobic organisms.
Chloramphenicol
Chloramphenicol binds to the 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. It is effective against gram-negative and gram-positive bacteria.
Piperacillin and Tazobactam sodium (Zosyn)
combination includes an antipseudomonal penicillin plus beta-lactamase inhibitor. It inhibits biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication.
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Acute bacterial endocarditis caused by Staphylococcus aureus with perforation of the aortic valve and aortic valve vegetations. Courtesy of Janet Jones, MD, Laboratory Service, Wichita Veterans Administration Medical Center.
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Acute bacterial endocarditis caused by Staphylococcus aureus with aortic valve ring abscess extending into myocardium. Courtesy of Janet Jones, MD, Laboratory Service, Wichita Veterans Administration Medical Center.
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A middle-aged man with a history of intravenous drug use who presented with severe myalgias and a petechial rash. He was diagnosed with right-sided staphylococcal endocarditis.
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This is a magnified portion of a parasternal long axis view from a transthoracic echocardiogram. There is a small curvilinear vegetation on the mitral valve as indicated. The patient presented with a headache and fever, and CT scan of the brain revealed an occipital hemorrhage. The patient had a history of intravenous drug use and multiple blood cultures grew Staphylococcus aureus.
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A young adult with a history of intravenous drug use, endocarditis involving the tricuspid valve with Staphylococcus aureus, and multiple septic pulmonary emboli. Pulmonary lesions on chest radiograph are most prominent in the right upper lobe with both solid and cavitary appearance.
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Mitral valve: endocarditis with valve destruction and vegetation. Note the posterior leaflet of the mitral valve, with an irregular vegetation on the atrial surface, resulting in valve destruction at the commissure between the anterior leaflet and the posterior leaflet.
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Aortic valve: healed endocarditis. Note the gaping hole with the fibrous rim, and a small strand at the free edge. The hole is at the line of closure. The affected valve is the left cusp. Note the right noncoronary cusp (immediate to the left in this image) demonstrates a small, multichanneled fenestration at the commissure, immediately adjacent to similar fenestrations in the left coronary cusp. These are physiologic lesions occurring with age and are unrelated to endocarditis.
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Aortic valve: bicuspid, with infectious endocarditis. In this excised valve, note the bulky vegetations on the ventricular surfaces, with distortion of the valve surfaces.
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Mitral valve: postrheumatic, with infectious endocarditis. A defect is seen in the scarred valve, with focal surface hemorrhage. The patient also underwent aortic valve replacement, as there was contiguous infection.
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The surface of the valves, in most cases, demonstrates areas of acute neutrophilic inflammation with admixed fibrin and platelets. Degenerated bacterial colonies are seen at the left. Also, areas of microcalcification may mimic bacterial deposits.
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Infectious endocarditis, subacute phase. Hemorrhage and prominent granulation tissue with neovascularity is apparent throughout. This aortic valve showed fibrin exudate on the ventricular surface (below), with more prominent organization and granulation on the aortic surface (above).
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Infectious endocarditis, surface of valve leaflet with fibrin; higher magnification of previous image. A chronic infiltrate is seen, just under the denuded thrombosed surface, with primarily macrophages and focal macrophage giant cells.
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Bioprosthetic valve with endocarditis. Note the large bacterial colony (staphylococci by culture) in the absence of significant inflammation; the xenograft tissue is not viable, and nuclear detail is not apparent.
Tables
| Causative Organism(s) | Clinical Features of IE |
| Staphylococcus aureus |
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| Streptococcus viridans |
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| Streptococcus intermedius group |
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| Abiotrophia |
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| Group D streptococci |
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| Nonenterococcal group D |
|
| Group B streptococci |
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| Group A, C, and G streptococci |
|
| Coagulase-negative S aureus |
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| Pseudomonas aeruginosa |
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| HACEK (ie, Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) |
|
| Fungal |
|
| Bartonella |
|
| Multiple pathogens (polymicrobial) |
|
