Current profile of infective endocarditis in intravenous drug users: The prognostic relevance of the valves involved

Current profile of infective endocarditis in intravenous drug users: The prognostic relevance of the valves involved

International Journal of Cardiology 187 (2015) 472–474 Contents lists available at ScienceDirect International Journal of Cardiology journal homepag...

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International Journal of Cardiology 187 (2015) 472–474

Contents lists available at ScienceDirect

International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard

Letter to the Editor

Current profile of infective endocarditis in intravenous drug users: The prognostic relevance of the valves involved Carlos Ortiz-Bautista a,⁎, Javier López a, Pablo Elpidio García-Granja a, Teresa Sevilla a, Isidre Vilacosta b, Cristina Sarriá c, Carmen Olmos b, Carlos Ferrera b, Carmen Sáez c, Itziar Gómez a, José Alberto San Román a a b c

Instituto de Ciencias del Corazón (ICICOR), Hospital Clínico Universitario, Valladolid, Spain Hospital Clínico Universitario San Carlos, Madrid, Spain Servicio de Medicina Interna-Infecciosas, Instituto de Investigación del Hospital La Princesa, Madrid, Spain

a r t i c l e

i n f o

Article history: Received 2 March 2015 Accepted 25 March 2015 Available online 27 March 2015 Keywords: Infective endocarditis Intravenous drug use Right-sided infective endocarditis

To the Editor, Intravenous drug use is a well-known predisposing condition for infectious diseases [1], such as infective endocarditis (IE). In fact, this condition represents a minor diagnostic criterion for IE. Although incidence of IE in intravenous drug users (IDUs) has decreased during the last decades [2], it is still responsible for 5% to 10% of deaths in IDUs [3]. Even though IDUs have been classically related to right-sided IE (RSIE), left-sided IE (LSIE) has been reported with similar frequency [4]. Nonetheless, the profile and outcome of LSIE in IDUs are not well known and the few reported data about this topic are outdated. The aim of this work is to describe and compare the clinical profile and outcome of RSIE and LSIE in a consecutive IDU population. Among 1234 episodes of IE consecutively diagnosed from 1995 to 2014 in three tertiary centres with cardiac surgery facilities, 66 were in IDUs (5%). Of them, 40 were RSIE (61%) and 26 LSIE (39%). There were 3 episodes with concomitant left and right side involvement that we have considered them as LSIE for analysis purposes. Most episodes (91%) affected a native valve. An analysis of 85 epidemiological, clinical, microbiological, echocardiographic and outcome variables has been performed. Continuous variables are presented as mean ± standard deviation and categorical variables as absolute values and percentages. ⁎ Corresponding author at: Instituto de Ciencias del Corazón (ICICOR), Hospital Clínico Universitario de Valladolid., C/Ramón y Cajal 3, 47003 Valladolid, Spain. E-mail address: [email protected] (C. Ortiz-Bautista).

http://dx.doi.org/10.1016/j.ijcard.2015.03.368 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.

The normal distribution of the quantitative variables was verified with the Kolmogorov–Smirnov test. All data were analysed with the version 15.0 Statistical Package for Social Sciences (SPSS Inc., Chicago, Illinois). Differences were considered statistically significant if p-value was b0.05. Results are shown in Table 1 and Fig. 1. Mean age (± SD) was 35 ± 8 years, 86% were males and 88% community-acquired. Comorbidities were common (64%), being HIVpositive (61%) and chronic anaemia (22%) the most frequently associated. The only epidemiological difference between RSIE and LSIE was that HIV-positive serology was significantly higher in RSIE (73% vs. 42%, p = 0.01). Patients with LSIE developed heart failure (28% vs. 50%, p = 0.06) and renal failure (25% vs. 54%, p = 0.02) during hospital admission more frequently than RSIE. Systemic embolism occurred in 35% of LSIE and pulmonary embolism in 70% of RSIE. Staphylococcus aureus (53%) and Streptococcus viridans (12%) were the main causative microorganisms, being S. aureus significantly more frequent in RSIE (68% vs. 31%, p = 0.003) and S. viridans in LSIE (3% vs. 27%, p = 0.005). Among episodes caused by S. aureus only 3 (9%) were caused by methicillin-resistant strains. Considering TOE as gold standard, TTE sensitivity was 84% (95% IC: 69%–98%), specificity 100% (95% CI: 75%–100%), positive predictive value 100% and negative predictive value 29%. Vegetation size was similar in both groups. Tricuspid valve was the most frequently valve affected in patients with RSIE (88%), and the aortic (62%) in LSIE, followed by the mitral valve (50%). Multivalvular episodes (8% vs. 39%, p = 0.002) and periannular complications (3% vs. 27%, p = 0.005) were significantly more frequent in LSIE, and there was a non-significant trend towards more significant valve regurgitation (55% vs. 77%, p = 0.07) in LSIE. Persistent bacteraemia was similar in both groups (25% vs. 31%, p = 0.99). Need for cardiac surgery (8% vs. 50%, p b 0.001) and in-hospital mortality (15% vs. 39%, p = 0.03) was significantly higher in LSIE. RSIE represents 5% to 10% of all IE episodes in adults [5]. IDUs have been classically related to RSIE with an incidence ranging from 0.7 to 13/1000 years [6]. Nevertheless, in the last decades, IE episodes in IDUs have decreased, being nowadays responsible for one third of all RSIE [2] and 2% to 5% of all IE episodes [3]. Our study confirms this data and also some relevant differences between RSIE and LSIE. Consistent with other studies, our series of IE in IDUs is formed mainly by HIV-seropositive young males (male:female ratio 6:1), with frequent previous IE episodes and mainly community-acquired [3,4,7,8].

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Table 1 Epidemiological, clinical, echocardiographic and outcome differences between groups. IE: infective endocarditis. Right-sided IE N = 40 (61%)

Left-sided IE N = 26 (39%)

Total N = 66

p value

Epidemiological characteristics Sex (male), n (%) Age, mean ± SD Community acquired, n (%) Previous endocarditis, n (%) Predisposing factors Unknown, n (%) Local infection, n (%) HIV, n (%) Chronic anaemia, n (%) Chronic renal failure, n (%) Diabetes mellitus, n (%)

35 (88) 35 ± 7 36 (90) 11 (28)

22 (85) 35 ± 9 22 (85) 3 (12)

57 (86) 35 ± 8 58 (88) 14 (21)

0.73 0.73 0.70 0.12

7 (18) 4 (10) 29 (73) 11 (28) 0 (0) 1 (3)

11 (42) 1 (4) 10 (42) 3 (13) 2 (8) 0 (0)

18 (27) 5 (8) 39 (61) 14 (22) 2 (3) 1 (2)

0.03 0.64 0.01 0.15 0.15 0.99

Clinical characteristics Symptoms onset b 15 days, n (%) Fever, n (%) Pulmonary embolism, n (%) Heart failure, n (%) Renal failure, n (%) Systemic embolism, n (%) Septic shock, n (%)

27 (68) 37 (95) 28 (70) 11 (28) 10 (25) 0 (0) 5 (13)

17 (65) 20 (83) 0 (0) 13 (50) 14 (54) 9 (35) 3 (13)

44 (67) 57 (91) 28 (42) 24 (36) 24 (36) 9 (14) 8 (13)

0.86 0.19 b0.001 0.06 0.02 b0.001 0.99

Echocardiographic characteristics Vegetation size (higher diameter), mean ± SD Tricuspid valve, n (%) Pulmonary valve, n (%) Eustachian valve, n (%) Tricuspid prosthesis, n (%) Aortic valve, n (%) Mitral valve, n (%) Aortic prosthesis, n (%) Mitral prosthesis, n (%) Multivalvular, n (%) Periannular complications, n (%) Pseudoaneurysm, n (%) Abscess, n (%) Moderate or severe valve regurgitation, n (%)

16 ± 8 35 (88) 4 (10) 1 (3) 2 (5) 0 (0) 0 (0) 0 (0) 0 (0) 3 (8) 1 (3) 1 (3) 1 (3) 22 (55)

18 ± 10 3 (12) 0 (0) 0 (0) 0 (0) 16 (62) 13 (50) 3 (12) 1 (4) 10 (39) 7 (27) 5 (19) 4 (15) 20 (77)

17 ± 9 38 (58) 4 (6) 1 (2) 2 (3) 16 (24) 13 (20) 3 (5) 1 (2) 13 (20) 8 (12) 6 (9) 5 (8) 42 (64)

0.67 b0.001 0.15 0.99 0.52 b0.001 b0.001 0.06 0.39 0.002 0.005 0.03 0.07 0.07

Outcomes Positive blood cultures at 48–72 h, n (%) Cardiac surgery, n (%) In-hospital mortality, n (%)

5 (25) 3 (8) 6 (15)

4 (31) 13 (50) 10 (39)

9 (27) 16 (24) 16 (24)

0.99 b0.001 0.03

Data in bold and italic indicate that the results are statistically significant.

HIV-seropositive is the main comorbidity in IDUs and, as previously reported [8], it is significantly more frequent in patients with RSIE. IE in HIV-seropositive occurs almost exclusively in IDUs and is a risk factor for in-hospital mortality in patients with severe immunosuppression (CD4 b 200/mm3) [8]. HIV-related immunosuppression was also

reported as a risk factor for developing IE, as female sex, alcohol intake and increasing injection drug frequency [9]. Repeated IE episodes in IDUs are frequent (28% in our series), with previously reported rates ranging from 5.6% to 22% [3,4,7]. This fact can be explained by the continuation of drug abuse in many of these patients.

Fig. 1. Microbiological differences. LSIE: left-sided infective endocarditis, NS: not significant, RSIE: right-sided infective endocarditis.

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S. aureus is the leading aetiology in IDUs [5], being responsible for 40% to 74% of IE episodes [3,4,7–10]. Several risk factors for S. aureus infections in IDUs have been reported, such as nasal colonization, contaminated drugs use, drug-use paraphernalia and drug-use environment [1]. In spite of the spread risk of antibiotic-resistant strains [1], frequency of methicillin-resistant strains in our series is low compared with other RSIE groups, such as cardiac device carriers [2], reflecting that infections in IDUs are mostly community-acquired. Unlike non-IDU patients, S. aureus seems not to be related with IE in-hospital mortality in IDUs [3,8], which may be associated with more benign course of RSIE where this microbe is predominant. Accordingly with previous reports [8], S. aureus involve right-sided valves significantly more frequent, whereas S. viridans, the second aetiology in LSIE, is anecdotic in RSIE. However, the incidence of S. viridans as a causative microorganism in LSIE is significantly higher than in RSIE, resembling the microbiological profile of non-IDU LSIE. Overall in-hospital mortality in our series is higher than previously reported (9% to 18%) [3,4,7,8,10]. This can be explained by higher heart failure, renal failure and pulmonary embolism rates during hospitalization in our series compared with previously reported [4,8]. As expected [7,8,10], in-hospital mortality is higher in LSIE. Of note, patients in this group have more periannular complications, multivalvular episodes, renal failure and systemic embolism rates. They require cardiac surgery significantly more frequently than RSIE group. In conclusion, almost 40% of IE episodes in IDUs are left-sided and S. aureus is the main causative microorganism. There are significant differences between RSIE and LSIE in IDUs influencing in-hospital prognosis. LSIE episodes have a poor prognosis, with in-hospital mortality two-fold higher than patients with RSIE and similar to that in non-IDUs with LSIE.

Conflicts of interest The authors report no relationships that could be construed as a conflict of interest. References [1] S. Bassetti, M. Battegay, Staphylococcus aureus infections in injection drug users: risk factors and prevention strategies, Infection 32 (2004) 163–169. [2] C. Ortiz, J. López, H. García, T. Sevilla, A. Revilla, I. Vilacosta, C. Sarriá, C. Olmos, C. Ferrera, P.E. García, C. Sáez, I. Gómez, J.A. San Román, Clinical classification and prognosis of isolated right-sided infective endocarditis, Medicine 27 (2014) 137–140. [3] A. Weymann, T. Borst, A.-F. Popov, A. Sabashnikov, C. Bowles, B. Schmack, G. Veres, N. Chaimow, A. Rüdiger Simon, M. Karck, G. Szabo, Surgical treatment of infective endocarditis in active intravenous drug users: a justified procedure? J. Cardiothorac. Surg. 9 (2014) 58. [4] J. Mathew, T. Addai, A. Anand, A. Morrobel, P. Maheshwari, S. Freels, Clinical features, site of involvement, and outcome of infective endocarditis in intravenous drug users, Arch. Intern. Med. 155 (1995) 1641–1648. [5] C. Sousa, C. Botelho, D. Rodrigues, J. Azeredo, R. Oliveira, Infective endocarditis in intravenous drug abusers: an update, Eur. J. Clin. Microbiol. Infect. Dis. 31 (2012) 2905–2910. [6] A. Axelsson, H. Søholm, M. Dalsgaard, J. Helweg-Larsen, N. Ihlemann, H. Bundgaard, L. Køber, K. Iversen, Echocardiographic findings suggestive of infective endocarditis in asymptomatic Danish injection drug users attending urban injection facilities, Am. J. Cardiol. 114 (2014) 100–104. [7] A. Thalme, K. Westling, I. Julander, In-hospital and long-term mortality in infective endocarditis in injecting drug users compared to non-drug users: a retrospective study of 192 episodes, Scand. J. Infect. Dis. 39 (2007) 197–204. [8] S. Cicalini, G. Forcina, F.G. De Rosa, Infective endocarditis in patients with human immunodeficiency virus infection, J. Infect. 42 (2001) 267–271. [9] L.E. Wilson, D.L. Thomas, J. Astemborski, T.L. Freedman, D. Vlahov, Prospective study of infective endocarditis among injection drug users, J. Infect. Dis. 185 (2002) 1761–1766. [10] F.G. De Rosa, S. Cicalini, F. Canta, S. Audagnotto, E. Cecchi, G. Di Perri, Infective endocarditis in intravenous drug users from Italy: the increasing importance in HIV-infected patients, Infection 35 (2007) 154–160.