Infective Endocarditis Medication

  • Author: John L Brusch, MD, FACP; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Nov 29, 2011
 

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.

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Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

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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.

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Oxacillin

 

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.

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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.

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Vancomycin (Vancocin, Lyphocin, Vancoled)

 

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.

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Gentamicin (Garamycin, Gentacidin)

 

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.

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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

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Ampicillin (Marcillin, Omnipen, Polycillin, Principen)

 

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.

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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.

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Cefazolin (Ancef, Kefzol, Zolicef)

 

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.

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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.

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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.

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Nafcillin (Nafcil, Unipen, Nallpen)

 

Nafcillin is used for staphylococcal IE caused by organisms susceptible to methicillin/oxacillin.

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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.[83]

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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.

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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.

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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.

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Doxycycline (Vibra-Tabs, 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.

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Sulfamethoxazole and Trimethoprim (Bactrim, Bactrim DS, Septra, Septra DS)

 

Trimethoprim and sulfamethoxazole inhibit bacterial growth by inhibiting the synthesis of dihydrofolic acid.

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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.

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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.

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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.

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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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Contributor Information and Disclosures
Author

John L Brusch, MD, FACP  Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Steven A Conrad, MD, PhD  Chief, Department of Emergency Medicine; Chief, Multidisciplinary Critical Care Service, Professor, Department of Emergency and Internal Medicine, Louisiana State University Health Sciences Center

Steven A Conrad, MD, PhD is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American College of Emergency Physicians, American College of Physicians, International Society for Heart and Lung Transplantation, Louisiana State Medical Society, Shock Society, Society for Academic Emergency Medicine, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Keith A Marill, MD  Faculty, Department of Emergency Medicine, Massachusetts General Hospital; Assistant Professor, Harvard Medical School

Keith A Marill, MD is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Medtronic Ownership interest None; Cambridge Heart, Inc. Ownership interest None; General Electric Ownership interest None

Specialty Editor Board

Jon Mark Hirshon, MD, MPH  Associate Professor, Department of Emergency Medicine, University of Maryland School of Medicine

Jon Mark Hirshon, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Public Health Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Thomas M Kerkering, MD  Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine

Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Barry E Brenner, MD, PhD, FACEP  Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

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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.
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.
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.
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.
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.
A young adult with a history of intravenous drug use diagnosed with right-sided staphylococcal endocarditis and multiple embolic pyogenic abscesses on chest radiograph.
Table 1. Clinical Features of Infective Endocarditis According to Causative Organism
Causative Organism(s) Clinical Features of IE
Staphylococcus aureus
  • Overall, S aureus infection is the most common cause of IE, including PVE, acute IE, and IVDA IE.
  • Approximately 35-60.5% of staphylococcal bacteremias are complicated by IE.
  • More than half the cases are not associated with underlying valvular disease.
  • The mortality rate of S aureus IE is 40-50%.
  • S aureus infection is the second most common cause of nosocomial BSIs, second only to CoNS infection.
  • The incidence of MRSA infections, both the hospital- and community-acquired varieties, has dramatically increased (50% of isolates). Sixty percent of individuals are intermittent carriers of MRSA or MSSA .
  • The primary risk factor for S aureus BSI is the presence of intravascular lines. Other risk factors include cancer, diabetes, corticosteroid use, IVDA, alcoholism, and renal failure.
  • The realization that approximately 50% of hospital- and community-acquired staphylococcal bacteremias arise from infected vascular catheters has led to the reclassification of staphylococcal BSIs. BSIs are acquired not only in the hospital but also in any type of health care facility (eg, nursing home, dialysis center).
  • Of S aureus bacteremia cases in the United States, 7.8% (200,000) per year are associated with intravascular catheters.
Streptococcus viridans
  • This organism accounts for approximately 50-60% of cases of subacute disease.
  • Most clinical signs and symptoms are mediated immunologically.
Streptococcus intermedius group
  • These infections may be acute or subacute.
  • S intermedius infection accounts for 15% of streptococcal IE cases.
  • S intermedius is unique among the streptococci; it can actively invade tissue and can cause abscesses.
Abiotrophia
  • Approximately 5% of subacute cases of IE are due to infection with Abiotrophia species.
  • They require metabolically active forms of vitamin B-6 for growth.
  • This type of IE is associated with large vegetations that lead to embolization and a high rate of posttreatment relapse.
Group D streptococci
  • Most cases are subacute.
  • The source is the gastrointestinal or genitourinary tract.
  • It is the third most common cause of IE.
  • They pose major resistance problems for antibiotics.
Nonenterococcal group D
  • The clinical course is subacute.
  • Infection often reflects underlying abnormalities of the large bowel (eg, ulcerative colitis, polyps, cancer).
  • The organisms are sensitive to penicillin.
Group B streptococci
  • Acute disease develops in pregnant patients and older patients with underlying diseases (eg, cancer, diabetes, alcoholism).
  • The mortality rate is 40%.
  • Complications include metastatic infection, arterial thrombi, and congestive heart failure.
  • It often requires valve replacement for cure.
Group A, C, and G streptococci
  • Acute disease resembles that of S aureus IE (30-70% mortality rate), with suppurative complications.
  • Group A organisms respond to penicillin alone.
  • Group C and G organisms require a combination of synergistic antibiotics (as with enterococci).
Coagulase-negative S aureus
  • This causes subacute disease.
  • It behaves similarly to S viridans infection.
  • It accounts for approximately 30% of PVE cases and less than 5% of NVE cases.[17]
Pseudomonas aeruginosa
  • This is usually acute, except when it involves the right side of the heart in IVDA IE.
  • Surgery is commonly required for cure.
HACEK (ie, Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae)
  • These organisms usually cause subacute disease.
  • They account for approximately 5% of IE cases.
  • They are the most common gram-negative organisms isolated from patients with IE.
  • Complications may include massive arterial emboli and congestive heart failure.
  • Cure requires ampicillin, gentamicin, and surgery.
Fungal
  • These usually cause subacute disease.
  • The most common organism of both fungal NVE and fungal PVE is Candida albicans.
  • Fungal IVDA IE is usually caused by Candida parapsilosis or Candida tropicalis.
  • Aspergillus species are observed in fungal PVE and NIE.
Bartonella
  • The most commonly involved species is Bartonella quintana.
  • IE typically develops in homeless males who have extremely substandard hygiene. Bartonella must be considered in cases of culture-negative endocarditis among homeless individuals.
Multiple pathogens (polymicrobial)
  • Pseudomonas and enterococci are the most common combination of organisms.
  • It is observed in cases of IVDA IE
  • The cardiac surgery mortality rate is twice that associated with single-agent IE.[18]
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