#312 Infective Endocarditis

December 27, 2021 | By Beth Garbitelli

A Guide to High Valve-ue Care

Summary

Master endocarditis! Don’t feel thwarted by a positive set of blood cultures anymore. We’re joined by Dr. David Serota (@serotavirus) for a comprehensive discussion of the pathophysiology of infective endocarditis, frameworks for work-up and diagnosis, the TTE vs. TEE debate, indications for valve surgery, antibiotic tips,  harm reduction strategies, and more. 

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Credits

• Writer and Producer: Adam Barelski MD
• Show Notes: Beth Garbitelli; Adam Barelski MD
• Infographic: Adam Barelski MD
• Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP, Adam Barelski MD
• Reviewer: Meredith Trubitt, MD
• Executive Producer, Cover Art: Beth Garbitelli
• Showrunner: Matthew Watto MD, FACP
• Editor: Clair Morgan of nodderly.com
• Guest: David Serota MD

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Show Segments

• Intro, disclaimer, guest bio
• Guest one-liner, Picks of the Week*
• Case from Kashlak; Definitions
• What to do with positive blood cultures
• Initial workup for endocarditis 
• How to diagnose endocarditis
• When to get a TTE and a TEE
• Indications for valve surgery
• Antibiotic tips
• Oral vs IV antibiotics
• Treatment considerations for patients who inject drugs
• Take home points
• Outro

Infective Endocarditis Pearls

1. Fever is the most common presenting feature of endocarditis, present in up to 96% of patients with IE. 
2. Consider IE in “fever-plus” syndromes, such as: fever + stroke, heart failure, vision change, joint pain, low back pain, ischemic extremity.
3. Risk factors for IE include patient factors (prosthetic valves, cardiac devices, recent invasive procedure, injection drug use), organism factors on blood cultures (S. aureus, strep sp., enterococcus), and presentation factors (fever, new murmur, classic physical exam findings). 
4. The Duke criteria can be used to help “make a case” for endocarditis as a way to guide treatment.  
5. The utility of the TTE depends on pre-test probability, the quality of the study, and which side of the heart the lesion is on. Using strict criteria for a “normal” TTE increases the sensitivity to nearly 90%, but these criteria are infrequently met in clinical practice.
6. TEE should be obtained in anyone with a negative TTE in whom there is a high clinical suspicion of IE or who has a prosthetic valve/AICD. 
7. Treatment of IE involves (1) clearing blood cultures by using the right dose of the right antibiotic; (2) identifying metastatic infection and attempting source control; and (3) monitoring for surgical indications.
8. Indications for valve surgery include mechanical complications, “antibiotic failure” , and hard-to-treat organisms. Consider valve surgery when there is a potential for catastrophic embolization (large/mobile vegetations, ongoing emboli despite antibiotics). 
9. Vancomycin and ceftriaxone are good empiric choices if you are suspicious of IE, but once the diagnosis is made, antibiotics should be tailored to the organism using guideline recommendations.
10. Consult your friendly neighborhood ID specialist when you are considering IE and definitely when you are treating it! 

Endocarditis Show Notes

Definitions

Endocarditis is an infection of the endocardial structures of the heart, which includes the atria, ventricles, valves, papillary muscles, or congenital abnormalities. Infected cardiac thrombus is also classified as endocarditis. Valvular endocarditis is the most common. 

Pathophysiology of Endocarditis

Bacterial endocarditis is preceded by non-bacterial thrombotic endocarditis. Valvular insult and high pressures cause damage. This damaged tissue becomes a site of platelet and fibrin aggregation (Sullam 1985, Keynan 2013). Bacterial invasion then occurs via bloodstream inoculation through dental procedures, injection of drugs, GI malignancy, and other causes. Bacteria proliferate at the site of the platelet/fibrin aggregation. 

How it looks

Initial presentation usually includes fever, rigors, night sweats, weight loss, anorexia, while pathognomonic findings are often uncommon findings (Murdoch DR, et al.; 2009). Per Dr. Serota’s expert opinion, concern for endocarditis may be heightened when you see a “fever-plus” syndrome, i.e.: fever PLUS new stroke, severe back, joint pain, or new heart failure. 

Most common underlying etiology for bacterial endocarditis is valvopathy (such as bicuspid aortic valve, rheumatic heart disease), presence of a cardiac device, recent invasive procedures, or dental disease. People who inject drugs are at increased risk for developing endocarditis (Wurcel AG, et al.; 2016). According to a 2009 article reviewing the epidemiology of endocarditis in over 2500 patients around the globe, 10% of patients had injected drugs (Murdoch DR, et al.; 2009). Dr. Serota has also seen endocarditis in patients with ESRD.  Suspicion for endocarditis should be high if there is bacteremia without clear source, particularly with high risk organisms such as most gram-positive cocci and candida  (expert opinion). 

History and findings

Take a thorough prosthetic history, to assess for metal screws, plates, replacement joints. Dr. Serota suggests asking patients “Is there anything inside your body that you were not born with?” Ask about recent procedures, history of GI malignancy, recent colonoscopy. He also recommends culturally competent assessment of substance use.

Fever is your most helpful physical exam findings, 96% of folks with endocarditis have fever at the beginning of hospitalization (Murdoch DR, et al.; 2009). Lack of known source for bacteremia is very concerning for underlying endocarditis in Dr. Serota’s expert opinion.  New or worsening murmur is seen in more than half of patients with endocarditis. Osler nodes, Janeway lesions, are seen in at most 5% of endocarditis patients (Murdoch DR, et al.; 2009).  Dr. Serota recommends looking at conjunctiva, fingernails, hands, feet, and percussing the spine. 

Work-up and Management

Start antibiotics if you have not already when blood cultures result positive. Gram positive cocci should be broadly covered with vancomycin, with close follow-up on rapid species identification.  Classic teaching is to collect 3 sets of blood cultures (2 sets on the first draw and 1 set drawn 1 hour later. A ‘set’ of blood involves one blood draw from the arm with filling of anaerobic and aerobic bottles; usually, a phlebotomist will stick in both arms and take four bottles total (2 sets). A hallmark of endocarditis is high-grade, persistent positive blood cultures even in the setting of proper antibiotic therapy, so the use of antibiotics after initial 2 sets of blood cultures is not a major concern, per Dr. Serota’s expert opinion. 

Order echocardiography! Usual practice is to start with a transthoracic echo. If a TTE is negative, consider three factors:

1) Established pre-test probability of endocarditis (based on presentation, history, vitals)

2) Quality of TTE (not all are created equal)

3) Suspected side of lesion (people who inject drugs most commonly have right-sided endocarditis and the TTE is better at evaluating right-sided lesions) 

Dr. Serota recommends TEE if a patient has community-acquired Staph aureus bacteremia even with negative TTE, due to high prevalence of endocarditis with this organism. Patients with a prosthetic valve or cardiac device will generally need a TEE as the imaging modality of choice, since this has improved sensitivity compared to TTE for detecting endocarditis in patients with prosthetic valves (Otto CM, et al.; 2020). 

Dr. Serota also recommends a non-contrast CT of the chest in patients who inject drugs, as this sometimes reveals septic emboli that would not be apparent on an x-ray as well as splenomegaly.

Urine protein and microscopy is important as there can be an increase in glomerulonephritis with endocarditis (Murdoch DR, et al.; 2009). Rheumatoid factor may also be useful as it is frequently positive in indolent presentation. It can be an immunologic finding in the Modified Duke Criteria (Li JS, et al.; 2000).  

Some providers obtain brain imaging as some studies indicate that up to 70-80% of patients with endocarditis will have an abnormal finding on brain MRI (Champey J, et al.; 2016), but there is debate on how this changes management if the patient is asymptomatic. Due to embolic risk, providers should have a low threshold for head imaging in patients with endocarditis. Some CNS complications of endocarditis might require antibiotics with better ability to penetrate the blood brain barrier.

Bugs and Drugs

75% of the organisms that cause endocarditis are gram positive cocci (Murdoch DR, et al.; 2009). In people who inject drugs, Staph aureus is the most common organism. In patients with no underlying valve disease, Staph aureus and oral strep are most common. In patients with prosthetic valve endocarditis, you see more enterococci and coagulase negative Staph. 

When to consult ID? Staph aureus bacteremia, positive blood cultures of unknown source, and new diagnosis of endocarditis are all times when Dr. Serota recommends consulting Infectious Disease formally. 

Modified Duke Criteria

Provides a way to “make the case” for endocarditis (Li JS, et al.; 2000).

Major Criteria:

-Major blood culture criteria

-Vegetation on echo (echo evidence of endocardial involvement)

Minor Criteria

-Predisposing heart condition or injection drug use

-Fever

-Vascular phenomena (metastatic site of infection, septic emboli, mycotic aneurysm, Janeway lesions)

-Immunologic phenomena (RF, glomerulonephritis, Osler notes, Roth spots)

-Minor blood culture criteria or serological criteria (e.g. bartonella)

Definitive diagnosis: 2 Major, 1 Major and 3 Minor, or 5 minor. 

Dx of “possible endocarditis” if you have less than those combinations 

Treatment

Three components of treatment:  

1) Sterilize blood cultures 

2) Look for complications of endocarditis, including metastatic sites/cardiac complications 

3) Assess for need for surgical intervention

Dr. Serota recommends 2 sets of blood cultures daily for the first 3-4 days of treatment. If persistently positive at approximately day 4, it is Dr. Serota’s opinion to spread out culture sets to every 48-72hrs. Once you get the first negative set,  some recommend 2 days of negative cultures, but some providers with improving clinical status may be okay with one negative set. 

Treatment involves lengthy antibiotics partially because of the pathophysiology of endocarditis, which involves some dormancy of the bacteria on the valve. Treatment of left-sided Staph aureus endocarditis requires treatment for 6 weeks. Strep species are typically treated for 4 weeks (in some circumstances, 2 weeks may be acceptable). Enterococci are treated for 4-6 weeks depending on the regimen (sometimes longer if a prosthetic valve is involved). Ultimately, we are parsing between 4 -6 weeks. Duration has not been robustly studied, per Dr. Serota. Dr. Serota tries to avoid aminoglycoside for treatment in patients with native valves. If patient cultures indicate a streptococcus with higher MIC for penicillin, Dr. Serota will turn to ceftriaxone. Enterococcus is treated with ampicillin and ceftriaxone or an aminoglycoside. Prosthetic valves sometimes require aminoglycoside. Rifampin is used as a theoretically biofilm dissolver for staph infection of prosthetic valves as well. Overall, treatment regimens should be determined by reviewing guidelines (Baddour LM, et al.; 2016) and consulting with an ID specialist per Dr. Serota. 

It is Dr. Serota’s experience that if someone develops fever early on during their endocarditis treatment, it is most likely due to a complication of endocarditis. So it is important to keep this in mind when considering broadening antibiotics in the face of fever, when this may potentially lead to a change to less optimal endocarditis treatment. For example, in a patient with MSSA endocarditis on oxacillin/nafcillin with fever, broadening antibiotics to vancomycin+cefepime would be changing to suboptimal MSSA endocarditis treatment. 

Who needs surgery?

There are 4 main buckets of patients who may need surgery: 

1) Mechanical complication that antibiotics cannot fix (valve with hole in it, heart failure, abscess or paravalvular extension, new heart block/involvement of the conduction system)

2) Organisms that are not killed by antibiotics well (fungi, prosthetic valve endocarditis with a biofilm, multi-drug resistant organisms, mycobacterium, weird bugs)

3) “Antibiotic failure”: persistent positive blood cultures or progressive disease despite appropriate antibiotic therapy

4) Potential for catastrophic embolic complications (large mobile vegetation, ongoing emboli)

(Source: Otto CM, et al.; 2020)

Who can switch to oral antibiotics?

Dr. Serota discussed his take-aways from the POET trial: 

– POET showed that in a highly selected group of stable patients with left-sided endocarditis who had already received a median of 17 days IV antibiotics, those randomized to combination oral therapy and followed very closely had non-inferior outcomes to those who continued on IV therapy.

– Dr. Serota feels more comfortable finishing treatment courses off with oral antibiotics, especially when the benefit of oral far outweighs the perceived benefit of completed IV antibiotics. 

– The oral regimens are often a bit complicated, and oral therapy requires no less follow up (probably more follow up!)

Dr. Serota recommends two recent articles by Dr. Brad Spellberg, et al. on considering oral step-down therapy: Oral Is the New IV and Evaluation of a Paradigm Shift From Intravenous Antibiotics to Oral Step-Down Therapy for the Treatment of Infective Endocarditis. 

Treatment considerations for patients who inject drugs

Dr. Serota recommends listeners check out Curbsiders episode #299 with Dr. Melissa Weimer. From an infection standpoint, he finds that patients who inject drugs often have more advanced disease because they come in later in their presentation. He recommends a very thorough exam for metastatic sites. Patients who inject drugs often have excellent kidney function in Dr. Serota’s experience, so it can be difficult to obtain a therapeutic vancomycin trough level. If this is the case, consider other agents if able (expert opinion). In determining the best antibiotic course, involve the patient in the plan! Consult with ID about appropriate oral options for those who choose self-directed discharge before completing a full course of antibiotics. He recommends an integrated care model for patients who inject drugs who develop endocarditis.

Culture-negative endocarditis

Consider getting additional cultures in case of culture-negative endocarditis (expert opinion). Dr. Serota recommends that listeners check out Episode #26 of the Febrile podcast on culture-negative endocarditis. HACEK organisms are fastidious, but NOT culture negative as they grow on culture mediums today (Tattevin P, et al.; 2015). 

Links*

1. The Narcotic Drug Problem by Ernest Bishop (book)
2. Puscast (podcast)
3. Fantastic Planet by Failure (album) – Paul’s off-air Pick of the Week

Learned League (online trivia league) – Adam’s off-air Pick of the Week

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on our Amazon.com links and buy something we earn a (very) small commission, yet you don’t pay any extra.

Goal

Listeners will develop an approach to the evaluation and management of infective endocarditis.

Learning objectives

After listening to this episode listeners will…  

1. Develop an illness script for infectious endocarditis, including risk factors that predispose patients to developing endocarditis and classic physical exam findings.
2. List elements of the modified Duke criteria in the evaluation of endocarditis.
3. Determine when to perform a TTE and TEE in the evaluation of patients for endocarditis. 
4. Recognize the complications of endocarditis and when to refer patients for surgery. 
5. Develop an approach for treatment of endocarditis with antibiotics. 
6. Explain management considerations for patients with endocarditis who inject drugs.

Disclosures

Dr Serota reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Barelski AM, Serota DP, Williams PN, Watto MF. “Infective Endocarditis – A Guide to High Valve-ue Care”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list December 27, 2021.