Is Community-Acquired SAB complicated SAB? Probably

It seems I can never get around talking about staphylococcus aureus. I believe it was Paul Sax who mentioned that an infectious disease fellowship is essentially a staphylococcus fellowship, since you see all different types of complications. Many institutions have implemented automatic infectious disease consultation for anyone with staphylococcus aureus bacteremia (SAB), as it has been proven to lead to better overall outcomes. While in training, one of the topics hammered to me was the concept of uncomplicated vs complicated SAB. What is considered complicated SAB? Per the IDSA guidelines (1):

1. Follow up blood cultures at 24-72hrs after initial cultures result negative
2. Defervescence within 72hrs after antibiotic therapy
3. Echo without endocarditis
4. No evidence of metastatic infection
5. No indwelling intravascular catheter/prosthetic devices such as valves, arthroplasties, dialysis caths, etc

It seems pretty cut and dry, doesn’t it? I did find, however, many of my attendings treating folks who came in with community-acquired SAB being treated for 4 weeks. Recall, uncomplicated SAB gets 2 weeks, and complicated gets 4 to 6 weeks of antibiotics depending on the complication. Why is this?

As it so happens, community acquisition is associated with higher rates of infective endocarditis! Several retrospective studies have evaluated this and it seems to pan out. One of the earlier studies on the topic I was able to find compared 30 episodes  with nosocomial endocarditis and 148 episodes of community acquired endocarditis (2).  While patients in the nosocomial group tended to be significantly older (53% aged >60 vs 39% in the community acquired group), they also had higher rates of mortality (40 vs 18%, p=0.02), perhaps from their significant number of comorbidities. The higher numbers of community-acquired IE suggests community acquisition may play a role, however this was not the primary outcome of the study. Subsequently, Fowler and colleagues evaluated a prospective cohort of 724 patients with SAB, of which 310 of those had complicated SAB (3). The goal was to identify those at risk of complicated SAB. Patients who had community acquisition, a prosthetic device, ongoing fever for 72 hours, and positive follow-up blood cultures were at higher risk of complicated SAB and served as an indicator of existing complications:

A reduced model of 4 variables, which included exam consistent with embolic phenomena, positive follow up blood cultures, ongoing fever at 72 hours, and community acquisition found that the lack of all variables yielded a predicted complication rate of 16%, going up with each variable:

This was subsequently confirmed in a multicenter, retrospective cohort of 505 patients with SAB which found that, numerically, patients with community acquired SAB had higher rates of infective endocarditis, though mortality was higher in the bacteremia group (4):

One notably thing was the factors that were evaluated in a multivariate logistic regression model for risk of endocarditis. Amongst these were native valve disease (OR 4.5, 95% CI 2-9.9), prosthetic valve presence (OR 10.5, 95% CI 2.5-43.7), persistent bacteremia (OR 7.4, 95% CI 3.3-16.6), IV drug use (OR 3.2, 95% CI 1.2-8.6), history of prior IE (OR 10, 95% CI 2-50), and community acquisition (OR 2.9, 95% CI 1.4-4.9).

A multicenter study that sought to use a multivariate model to identify low-risk patients with SAB and did not need a TEE found that community acquisition of bacteremia was associated with high risk of IE (5):

A large, prospective Danish cohort of over 13,000 patients with SAB  (6) found that rates of IE were significantly higher in the community acquired cohort when compared to the hospital acquired cohort (12.1% vs 6.6%, respectively):

Moreover, after adjustment, community SAB was associated with higher odds of IE (OR 2.12, 95% CI 1.87-2.41). Interestingly, those patients under the age of 40 with community-acquired SAB had the highest odds of IE compared to health-care associated SAB (OR 5.58, 95% CI 3.06-10.17):

In a prospective, multicenter study of 244 patients with SAB which attempted to clarify the value of echocardiogram in unselected SAB patients found 2 interesting risk factors for the development of IE (7): unknown source of SAB (38% for SAB with IE vs 16% SAB without IE) and community acquisition (57% vs 34%).  Further data has confirmed these findings. Joseph et al (8) performed a retrospective study of 306 patients with SAB who underwent echocardiogram, and univariate analysis found that the strongest risk factors for IE were prosthetic heart valve, a cardiac device, or community acquisition:

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A French prospective study of 2008 patients with SAB found that IE was more frequent in patients with community acquired SAB regardless of predisposing heart disease or IV drug use (9):

Even nosocomial bacteremia did not have as high rates of IE as the other cohorts.

It appears that community acquisition of SAB is such a strong predictor for IE that several scores have utilized it to see who is at low risk and thus, a TEE would be able to be deferred. A cohort of 637 patients from the POSITIVE, PREDICT, and VIRSTA cohorts, which aimed to predict patients who were at low risk of IE in whom TEE could be deferred, takes a look at the three different scores performance (10). In looking at the diagnostic accuracy, both the PREDICT at day 5 and VIRSTA had the highest sensitivity and negative predictive value, suggesting its good at ruling out IE:

One interesting thing is that both of these scores, compared to the POSITIVE scoring system, uses community-acquisition of SAB as a risk factor:

Indeed, when looking at the PREDICT cohort independently (11), which included 678 patients with SAB, multivariate analysis found that community-acquisition was associated with greater odds of IE at day 1 (OR 5.01, 95% CI 2.2-11.31) and day 5 (OR 3.83, 95% CI 1.64-8.96). While the odds were lower than other risk factors such as ICD at day 5, the odds were higher for community acquired SAB on day 1:

Why is this a risk factor though? I suspect that many people from the community may actually be bacteremic for a lot longer than we give them credit for. This is all my own conjecture, but on the inpatient side, anyone who fevers gets a culture, so we know time 0 from the onset of their bacteremia. In the community, we have no such luxury. As a result, they may have metastatic foci we cannot be able to account for. It would be reasonable to treat these community-acquired SAB as complicated SAB, meaning a minimum of 4 weeks of IV antibiotics. Which ones? That’s for another post. 

References:

1. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF; Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/cid/ciq146. Epub 2011 Jan 4. Erratum in: Clin Infect Dis. 2011 Aug 1;53(3):319. PMID: 21208910.
2. Chen SC, Dwyer DE, Sorrell TC. A comparison of hospital and community-acquired infective endocarditis. Am J Cardiol. 1992 Dec 1;70(18):1449-52. doi: 10.1016/0002-9149(92)90298-d. Erratum in: Am J Cardiol 1993 Mar 1;71(7):630. PMID: 1442617.
3. Fowler VG Jr, Olsen MK, Corey GR, Woods CW, Cabell CH, Reller LB, Cheng AC, Dudley T, Oddone EZ. Clinical identifiers of complicated Staphylococcus aureus bacteremia. Arch Intern Med. 2003 Sep 22;163(17):2066-72. doi: 10.1001/archinte.163.17.2066. PMID: 14504120.
4. Chang FY, MacDonald BB, Peacock JE Jr, Musher DM, Triplett P, Mylotte JM, O’Donnell A, Wagener MM, Yu VL. A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance. Medicine (Baltimore). 2003 Sep;82(5):322-32. doi: 10.1097/01.md.0000091185.93122.40. PMID: 14530781.
5. 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.
6. Østergaard L, Voldstedlund M, Bruun NE, Bundgaard H, Iversen K, Køber N, Dahl A, Chamat-Hedemand S, Petersen JK, Jensen AD, Christensen JJ, Rosenvinge FS, Jarløv JO, Moser C, Andersen CØ, Coia J, Marmolin ES, Søgaard KK, Lemming L, Køber L, Fosbøl EL. Prevalence and Mortality of Infective Endocarditis in Community-Acquired and Healthcare-Associated Staphylococcus aureus Bacteremia: A Danish Nationwide Registry-Based Cohort Study. Open Forum Infect Dis. 2022 Dec 16;9(12):ofac647. doi: 10.1093/ofid/ofac647. PMID: 36540385; PMCID: PMC9757695.
7. Rasmussen RV, Høst U, Arpi M, Hassager C, Johansen HK, Korup E, Schønheyder HC, Berning J, Gill S, Rosenvinge FS, Fowler VG Jr, Møller JE, Skov RL, Larsen CT, Hansen TF, Mard S, Smit J, Andersen PS, Bruun NE. Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography. Eur J Echocardiogr. 2011 Jun;12(6):414-20. doi: 10.1093/ejechocard/jer023. PMID: 21685200; PMCID: PMC3117467.
8. 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.
9. Le Moing V, Alla F, Doco-Lecompte T, Delahaye F, Piroth L, Chirouze C, Tattevin P, Lavigne JP, Erpelding ML, Hoen B, Vandenesch F, Duval X; VIRSTA study group. Staphylococcus aureus Bloodstream Infection and Endocarditis–A Prospective Cohort Study. PLoS One. 2015 May 28;10(5):e0127385. doi: 10.1371/journal.pone.0127385. PMID: 26020939; PMCID: PMC4447452.
10. van der Vaart TW, Prins JM, Soetekouw R, van Twillert G, Veenstra J, Herpers BL, Rozemeijer W, Jansen RR, Bonten MJM, van der Meer JTM. Prediction Rules for Ruling Out Endocarditis in Patients With Staphylococcus aureus Bacteremia. Clin Infect Dis. 2022 Apr 28;74(8):1442-1449. doi: 10.1093/cid/ciab632. PMID: 34272564; PMCID: PMC9049276.
11. 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.