Echo? Who, what, when, how? Role of echo modality in Staph aureus bacteremia.

I absolutely love this song. I tried to learn how to play it on guitar, but I think you may need 7 strings for it, at least when I checked back in the day. This week we are adding to last week’s topic and talking about when and what type of echo to get. There is vast literature here, but we will focus on a fairly common organism that ID folks (should) get consulted: staphylococcus aureus.

Some people will recommend to have anyone who has complicated bacteremia to get a TEE. I know Dr. Mark Crislip, of Puscast fame, does not advocate for an echo for the sake of diagnosis but rather to look for complications such as perivalvular abscess, however this is something I have always struggled with. Does anyone with SAB require an echo? Which modality is useful, TTE or TEE? Do you jump right to TEE or do you need a TTE prior to TEE? The IDSA guidelines recommend TEE over TTE when it comes to MRSA bacteremia (1), however TEE is more invasive, requires some degree of sedation, and is susceptible to some complications. The superiority of TEE was evaluated in a  retrospective study of 215 episodes of SAB (2). TEE was found to be more sensitive overall when compared to TTE (86% vs 21%), a relationship that held true regardless of the risk factor present. Furthermore, multivariate analysis found that a prior history of IE, unknown source of bacteremia, and underlying heart disease known to predispose to endocarditis were associated with IE:

Risk Factors

Several retrospective cohort studies have identified risk factors for IE in SAB cases. In a cohort of 98 cases of SAB (3), the authors noted that only the presence  of a cardiac device was associated with IE, though the numbers were overall small to draw any meaningful conclusions in other terms such as prolonged fever or hemodialysis requirement as a risk factor:

A larger cohort study of 688 patients (4) performed univariate analysis and found that prosthetic heart valve, a cardiac device, or community acquisition were associated with evidence of IE, while line-related SAB and hospital acquisition were associated with a lower likelihood of IE:

Interesting, the degree of valvular regurgitation was also associated with risk of IE, with moderate-severe regurgitation associated with an OR of 28:

Further, in a post-hoc analysis of 2 studies that attempted to evaluate patients with low-risk nosocomial SAB found that patients that met one of the following risk factors were at a higher risk of IE: prolonged bacteremia, presence of permanent intracardiac device, hemodialysis dependency, spinal infection, and non-vertebral OM (5). Those who met greater than one criteria had a higher risk of IE:

A meta-analysis of 30 studies found that embolic events (positive likelihood ratio 12.7, 95% CI 9.2-17.7), pacemaker (PLR 9.7, 95% CI 3.7-21.2), history of prior IE (PLR 8.2, 95% CI 3.1-22), prosthetic valve (PLR 5.7, 95% CI 3.2-9.5), and IV drug use (PLR 5.2, 95% CI 3.8-6.9) were predictors of subsequent IE (6). As you can see, those with complicated bacteremia (i.e not meeting uncomplicated criteria, which are: catheter associated infection and removal of the catheter, negative result of follow-up blood culture, defervescence within 72 h, normal findings on transesophageal echocardiogram, no prosthetic material in the joints or intravascular space, and no symptoms suggestive of metastatic infection) tend to be more likely to have IE.

Scoring Systems

The above data suggests that TEE would be advisable for anyone with complicated SAB, however several investigators have attempted to develop scoring systems to facilitate decision making. One study employed multivariate analysis to develop and internally validate a scoring system using a bootstrap method (7). 678 patients with SAB were included, of which 71% underwent a TEE within 12 weeks of diagnosis. Risk factors for IE at day 1 included presence of an ICD (OR 4.58, 95% Ci 2.03-10.35) or PPM (OR 7.94, 95% CI 4.08-15.44), and community onset of SAB (OR 5.01, 95% CI 2.22-11.31). At day 5, prolonged bacteremia of at least 72hrs (OR 5.23, 95% CI 2.85-9.61) was also associated with risk of IE:

Using this tool, the authors applied the scores at day 1 and day 5, with higher scores representing higher risk:

They propose an algorithm where day 1 score of >4 lead to TEE as well as a day 5 score of >2, as shown below:

Another score, the VIRSTA score, was developed from a prospective cohort study using the bootstrap mode (8). A total of 2091 patients were enrolled, with 221 patients (11%) having define IE. presence of emboli (cerebral or peripheral), meningitis, presence of intracardiac device, IVDU, persistent bacteremia, and pre-existing native valve disease were associated with IE. others included CRP >190 or community acquired acquisition:

Cut-off with the greatest NPV was 2, with a NPV of 98.9:

Similarly, in another study of 833 SAB cases, a score was developed to identify patients who have low-risk SAB and can forego TEE (9). IVDU, indeterminate or positive TTE, high-risk cardiac condition, and community acquisition were the risk factors associated with IE:

The risk of IE increased significantly in those who had more than 2 criteria:

Several patterns emerge with the above studies. First, the presence of a cardiac device such as a pacemaker or ICD seems to be a risk factor, as well as persistent bacteremia. IV drug abuse is also a significant risk factor. One surprising risk factor is community acquisition, which I think may be due to the uncertainty of the duration of bacteremia prior to presentation. I think a general “gestalt” as to what makes up a complicated SAB case may be better than trying to remember these scores. For simplicity, if you do not know when the SAB started and if there is any place where it may stick, get a TEE.

So, can a TTE still be used in SAB?

Given the above, does TTE have a role in SAB? Perhaps in certain situations. One retrospective study evaluated the utility of echo in uncomplicated catheter-related SAB (10). 95 patients were included in the cohort, with those who underwent echocardiography being less likely to be neutropenic and having higher comorbidity scores. Using a primary outcome of IE rate, relapse, SAB-related death, all-cause death, and treatment failure within 90 days of blood culture, there was no difference in outcome between those who underwent an echo and those who didn’t:

Further, another small retrospective study (11) evaluated paired TTE/TEE and found that a normal TTE had a sufficient NPV for IE, provided the study was adequate with visualization of all heart valves.

This was confirmed in another study, where the performance of a TTE was assessed using a stricter definition for vegetation in comparison to a TEE (12):

While the specificity decreased when compared to a standard approach to TTE, the negative predictive value was significantly increased:

Conclusion

I think anyone with complicated bacteremia (read: those with an ICD/PPM, IV drug users, community acquisition) may warrant a TEE, as the complications of IE can be devastating. Outside of that, those with uncomplicated, nosocomial bacteremia may do ok with a TTE. Whether other imaging modalities (such as CT, MRI, PET) may be of help for diagnosis is a question that remains to be answered, but I think it may be where we go next to forego the nuisance of TEE.

References:

1. Catherine Liu, Arnold Bayer, Sara E. Cosgrove, Robert S. Daum, Scott K. Fridkin, Rachel J. Gorwitz, Sheldon L. Kaplan, Adolf W. Karchmer, Donald P. Levine, Barbara E. Murray, Michael J. Rybak, David A. Talan, Henry F. Chambers, Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children, Clinical Infectious Diseases, Volume 52, Issue 3, 1 February 2011, Pages e18–e55, https://doi.org/10.1093/cid/ciq146
2. Sekar P, Johnson JR, Thurn JR, Drekonja DM, Morrison VA, Chandrashekhar Y, Adabag S, Kuskowski MA, Filice GA. Comparative Sensitivity of Transthoracic and Transesophageal Echocardiography in Diagnosis of Infective Endocarditis Among Veterans With Staphylococcus aureus Bacteremia. Open Forum Infect Dis. 2017 Feb 22;4(2):ofx035. doi: 10.1093/ofid/ofx035. PMID: 28470017; PMCID: PMC5407216.
3. Holden E, Bashir A, Das I, Morton H, Steadman CD, Nightingale P, Steeds RP, David MD. Staphylococcus aureus bacteraemia in a UK tertiary referral centre: a ‘transoesophageal echocardiogram for all’ policy. J Antimicrob Chemother. 2014 Jul;69(7):1960-5. doi: 10.1093/jac/dku082. Epub 2014 Mar 27. PMID: 24677159.
4. Joseph JP, Meddows TR, Webster DP, Newton JD, Myerson SG, Prendergast B, Scarborough M, Herring N. Prioritizing echocardiography in Staphylococcus aureus bacteraemia. J Antimicrob Chemother. 2013 Feb;68(2):444-9. doi: 10.1093/jac/dks408. Epub 2012 Oct 30. PMID: 23111851.
5. Kaasch AJ, Fowler VG Jr, Rieg S, Peyerl-Hoffmann G, Birkholz H, Hellmich M, Kern WV, Seifert H. Use of a simple criteria set for guiding echocardiography in nosocomial Staphylococcus aureus bacteremia. Clin Infect Dis. 2011 Jul 1;53(1):1-9. doi: 10.1093/cid/cir320. PMID: 21653295; PMCID: PMC3149212.
6. Bai AD, Agarwal A, Steinberg M, Showler A, Burry L, Tomlinson GA, Bell CM, Morris AM. Clinical predictors and clinical prediction rules to estimate initial patient risk for infective endocarditis in Staphylococcus aureus bacteraemia: a systematic review and meta-analysis. Clin Microbiol Infect. 2017 Dec;23(12):900-906. doi: 10.1016/j.cmi.2017.04.025. Epub 2017 May 6. PMID: 28487168.
7. Palraj BR, Baddour LM, Hess EP, Steckelberg JM, Wilson WR, Lahr BD, Sohail MR. Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT): Scoring System to Guide Use of Echocardiography in the Management of Staphylococcus aureus Bacteremia. Clin Infect Dis. 2015 Jul 1;61(1):18-28. doi: 10.1093/cid/civ235. Epub 2015 Mar 25. PMID: 25810284; PMCID: PMC4542912.
8. Tubiana S, Duval X, Alla F, Selton-Suty C, Tattevin P, Delahaye F, Piroth L, Chirouze C, Lavigne JP, Erpelding ML, Hoen B, Vandenesch F, Iung B, Le Moing V; VIRSTA/AEPEI Study Group. The VIRSTA score, a prediction score to estimate risk of infective endocarditis and determine priority for echocardiography in patients with Staphylococcus aureus bacteremia. J Infect. 2016 May;72(5):544-53. doi: 10.1016/j.jinf.2016.02.003. Epub 2016 Feb 22. PMID: 26916042.
9. Showler A, Burry L, Bai AD, Steinberg M, Ricciuto DR, Fernandes T, Chiu A, Raybardhan S, Science M, Fernando E, Bell CM, Morris AM. Use of Transthoracic Echocardiography in the Management of Low-Risk Staphylococcus aureus Bacteremia: Results From a Retrospective Multicenter Cohort Study. JACC Cardiovasc Imaging. 2015 Aug;8(8):924-31. doi: 10.1016/j.jcmg.2015.02.027. Epub 2015 Jul 15. PMID: 26189120.
10. Mun SJ, Kim SH, Huh K, Cho SY, Kang CI, Chung DR, Peck KR. Role of echocardiography in uncomplicated Staphylococcus aureus catheter-related bloodstream infections. Medicine (Baltimore). 2021 May 7;100(18):e25679. doi: 10.1097/MD.0000000000025679. PMID: 33950948; PMCID: PMC8104220.
11. McDermott BP, Cunha BA, Choi D, Cohen J, Hage J. Transthoracic echocardiography (TTE): sufficiently sensitive screening test for native valve infective endocarditis (IE). Heart Lung. 2011 Jul-Aug;40(4):358-60. doi: 10.1016/j.hrtlng.2010.07.007. Epub 2011 Apr 11. PMID: 21481468.
12. Sivak JA, Vora AN, Navar AM, Schulte PJ, Crowley AL, Kisslo J, Corey GR, Liao L, Wang A, Velazquez EJ, Samad Z. An Approach to Improve the Negative Predictive Value and Clinical Utility of Transthoracic Echocardiography in Suspected Native Valve Infective Endocarditis. J Am Soc Echocardiogr. 2016 Apr;29(4):315-22. doi: 10.1016/j.echo.2015.12.009. Epub 2016 Feb 3. PMID: 26850679; PMCID: PMC6052444.