In total, 522 patients were registered with definite IE at the Karolinska University Hospital between 2008 and 2017, of these 165 (32%) had history of IDU. The clinical characteristics of the patients with IDU-IE and non-IDU-IE are presented in Table 1. About two thirds of the included patients with IDU-IE were male (110 patients, 67%), which was the same percentage as non-IDU-IE patients. Mean age among the patients with IDU-IE was 41.6 years, which was mean 22.7 years younger than patients with non-IDU-IE (P < 0.01). A majority of the patients with IDU-IE (101 patients, 61%) presented with vascular phenomena, which was more common than among patients with non-IDU-IE (Table 1). More specifically, spondylitis and pulmonary septic emboli were more common among IDU-IE compared with patients with non-IDU-IE (spondylitis n = 25, 15% vs n = 30, 9%; P = 0.02, pulmonary septic emboli n = 55, 33% vs n = 11, 3%; P < 0.01). Further, history of previous IE was more common among the patients with IDU-IE, while prosthetic heart valves, known valvular disease, cardiovascular implantable electronic device (CIED)-associated IE were more common among patients with non-IDU-IE (Table 1). The incidence of definite IE registered at the Karolinska University Hospital increased during the study period from 2.52 (2008) to 4.21 cases (2017) per 100,000 adult (18 years and older) inhabitants in Stockholm county (P < 0.01). Contrasting, there was an overall decrease in incidence of IDU-IE registered at the hospital between 2008 and 2017 (P < 0.01), however, an initial increase between 2008 and 2011 was seen from 0.58 to 1.34 cases per 100,000 adult inhabitants (P < 0.01, Fig 1), but from 2012 to 2017, there was a decrease in incidence from 1.14 to 0.89 cases per 100,000 adult inhabitants in Stockholm county (P < 0.01, Fig 1). Further, the rate of patients with IDU-IE were lower during the winter compared to the other seasons (P = 0.01, Fig 2).
Table 1. Characteristics of the patients with IDU-IE and non-IDU-IE admitted between 2008-2017
Clinical characteristics
|
IDU-IE (n=165 (%))
|
Non-IDU IE (n=357 (%))
|
P value
|
Women
|
55 (33)
|
119 (33)
|
1.00
|
Men
|
110 (67)
|
238 (67)
|
1.00
|
Age, mean (± SD); median (25th and 75th percentiles)
|
41.6 (11.9); 44 (31, 50)
|
64.3 (16.4); 67 (56, 76)
|
< 0.01
|
Predisposing factors
|
|
Bicuspid aortic valve
|
0 (0)
|
20 (6)
|
<0.01
|
Prosthetic valve
|
12 (7)
|
83 (23)
|
< 0.01
|
CIED
|
2 (1)
|
38 (11)
|
< 0.01
|
Rheumatic heart disease
|
0 (0)
|
2 (1)
|
1.00
|
Congenital heart disease
|
0 (0)
|
8 (2)
|
0.06
|
History of IE
|
49 (30)
|
34 (10)
|
< 0.01
|
Known valvular disease
|
3 (2)
|
78 (22)
|
< 0.01
|
Heart failure before or under IE treatment
|
19 (12)
|
45 (13)
|
0.72
|
Patients fulfilling Duke's major criteria
|
Blood culture positive for IE
|
144 (87)
|
304 (85)
|
0.78
|
Imaging positive for IE*
|
165 (100)
|
287 (80)
|
< 0.01
|
Patients fulfilling Duke's minor criteria
|
Fever
|
150 (91)
|
304 (85)
|
0.07
|
Vascular phenomena
|
101 (61)
|
120 (34)
|
< 0.01
|
New heart murmur
|
20 (12)
|
63 (18)
|
0.11
|
Immunological phenomenon
|
2 (1)
|
19 (5)
|
0.03
|
Other microbiological evidence
|
3 (2)
|
14 (4)
|
0.29
|
*In total, 101 (61%) of the IDU-IE patients underwent transthoracic echocardiography and 137 (83%) patients underwent transoesophageal echocardiography during hospital stay. Significant P values are marked in bold font. Abbreviations: CIED, cardiovascular implantable electronic device; IDU, injection drug use; IE, infective endocarditis; n, number of patients; SD, standard deviation.
Of the included patients with IDU-IE, 157 (95%) had positive blood cultures. One of the patients that had negative blood culture had positive polymerase chain reaction (PCR) from heart valve surgery (methicillin susceptible Staphylococcus aureus - MSSA) (Table 2 and Table 3). Aetiology of S. aureus was significantly more common among patients with IDU-IE compared with patients with non-IDU-IE (n = 121, 73% among patients with IDU-IE, P < 0.01). Of the patients with IDU-IE, 94%, compared with 80% of the patients with non-IDU-IE (P < 0.01), had findings consistent with IE during examination with echocardiography (ECHO), the most common manifestation was tricuspid valve vegetation (91 patients, 55%), followed by mitral valve vegetation (47 patients, 28%) and aortic valve vegetation (33 patients, 20%) (Table 4). A significantly higher prevalence of tricuspid and pulmonary valve vegetations was seen among the patients with IDU-IE compared with the non-IDU-IE patients who had higher prevalence of aortic- and mitral valve vegetations as well as abscess and CIED-associated IE (Table 4). Multiple valve vegetations were equally common among patients with IDU-IE (n = 27 (16%)) and non-IDU-IE (n = 46 (13%), P = 0.29).
Table 2. Aetiology obtained from blood- and valve culture among patients with IDU-IE.
Blood culture results* (n (%))
|
144 (87)
|
Staphylococcus aureus (MSSA)
|
110 (67)
|
Enterococcus faecalis
|
14 (8)
|
Viridans group streptococci
|
9 (5)
|
S. aureus (MRSA)
|
3 (2)
|
Bacillus cereus
|
3 (2)
|
CoNS
|
2 (1)
|
Group A streptococci
|
1 (1)
|
Group G streptococci
|
1 (1)
|
Klebsiella spp
|
1 (1)
|
Unspecified funghi**
|
1 (1)
|
Polymicrobial blood cultures
|
13 (8)
|
MSSA and E. faecalis
|
4 (2)
|
E. faecalis and unspecified funghi
|
1 (1)
|
MSSA and aerobic gramnegative stave
|
1 (1)
|
MSSA and candida
|
1 (1)
|
MSSA and group G streptococci
|
1 (1)
|
MSSA and MRSA
|
1 (1)
|
MSSA and unspecified funghi
|
1 (1)
|
MSSA and viridans group streptococci
|
1 (1)
|
Viridans group streptococci and CoNS
|
1 (1)
|
Blood culture negative
|
8 (5)
|
Bacteria in valve culture from cardiac surgery
|
9 (5)
|
Staphylococcus aureus (MSSA)
|
5 (3)
|
Unspecified funghi
|
2 (1)
|
CoNS
|
1 (1)
|
Enterococcus faecalis
|
1 (1)
|
* Single bacteria in blood culture. ** None had Candida albicans. All patients with positive valve culture had positive blood culture. Of all patients with positive valve culture, one had bacteria that differed between blood culture (MSSA) and valve culture (unspecified funghi). Among the patients with non-IDU-IE, 12 patients (3%) had more than one bacterium in blood cultures. Abbreviations: CoNS, coagulase negative staphylococci; E, enterococcus; IDU, injection drug use; IE, infective endocarditis; MRSA, methicillin resistant Staphylococcus aureus; MSSA, methicillin susceptible Staphylococcus aureus; n, number of patients; PCR, polymerase chain reaction; S, staphylococcus; spp, species.
Table 3. Aetiology obtained from valve PCR among patients with IDU-IE.
Bacteria in valve PCR from cardiac surgery (n (%))
|
19 (12)
|
Staphylococcus aureus (MSSA)
|
15 (9)
|
CoNS
|
2 (1)
|
Enterococcus faecalis
|
2 (1)
|
One patient had positive valve PCR (MSSA) and negative blood culture, all other patients with positive valve PCR had positive blood cultures. Among the patients with positive valve PCR had positive blood cultures, the bacteria found in blood culture were the same as those found in valve PCR. Abbreviations: CoNS, coagulase negative staphylococci; IDU, injection drug use; IE, infective endocarditis; MSSA, methicillin susceptible Staphylococcus aureus; n, number of patients; PCR, polymerase chain reaction.
Table 4. Manifestations detected by ECHO among patients with IDU-IE
All manifestations
|
IDU-IE
(n=165 (100%))
|
Non-IDU-IE
(n=287 (80%))
|
P value
|
Aortic valve vegetation
|
33 (20)
|
171 (48)
|
< 0.01
|
Mitral valve vegetation
|
47 (28)
|
162 (45)
|
< 0.01
|
Tricuspid valve vegetation
|
91 (55)
|
23 (6)
|
< 0.01
|
Pulmonary valve vegetation
|
7 (4)
|
2 (1)
|
< 0.01
|
CIED-associated IE
|
1 (1)
|
25 (7)
|
< 0.01
|
Abscess
|
4 (2)
|
27 (8)
|
0.03
|
Multiple valve vegetations
|
Aortic and mitral valve vegetation
|
11 (7)
|
31 (9)
|
0.43
|
Aortic and tricuspid valve vegetation
|
5 (3)
|
3 (1)
|
|
Aortic and pulmonary valve vegetation
|
1 (1)
|
0 (0)
|
|
Mitral and tricuspid valve vegetation
|
5 (3)
|
5 (1)
|
|
Mitral and pulmonary valve vegetation
|
1 (1)
|
0 (0)
|
|
Tricuspid and pulmonary valve vegetation
|
4 (2)
|
1 (0)
|
|
CIED and tricuspid valve vegetation
|
0 (0)
|
6 (2)
|
|
Among the patients listed with, for instance, aortic valve vegetation, some patients had vegetations also on other valves and thus were listed also under the topic “multiple valve vegetations”. Significant P values are marked in bold font. Abbreviations: CIED, cardiovascular implantable electronic device; ECHO, echocardiography; IDU, injection drug use, IE, infective endocarditis.
Significantly less of the IDU-IE patients was treated with surgery; 27 (16%), compared with 121 (34%) among the non-IDU-IE patients (P < 0.01). The rate of patients with IDU-IE treated with surgery did not change significantly during the study period (P = 0.06). The most common single valve surgery performed in the IDU-IE group were biological aortic valve replacement (n = 6) followed by biological tricuspid valve replacement (n = 5), and one removal of tricuspid valve vegetation. Eight surgical procedures included more than one prosthetic or mechanical valve replacement of which 5 cases included tricuspid valve replacement. Among the patients with IDU-IE treated with surgery, none were re-operated during hospital stay nor during follow-up (up to 6 months). One patient with IDU-IE caused by E faecalis, that was not treated with surgery during hospital stay was operated during follow-up due to prosthetic (mechanical) mitral valve dehiscence, that was inserted 14 years prior to the IE diagnosis. Among the patients with IDU-IE treated with surgery, one died during hospital stay but none died during follow-up after discharge from hospital. In-hospital mortality was equal among the patients treated with surgery and the patients not treated with surgery, both in the IDU-IE group (1 (4%) of the 27 patients treated with surgery died during hospital stay and 6 (5%) of the 132 patients not treated with surgery died during hospital stay, P = 1.00) and in the non-IDU-IE group (12 (10%) of the 121 patients treated with surgery died during hospital stay and 15 (6%) of the 236 patients not treated with surgery died during hospital stay, P = 0.23).
In-hospital mortality, defined as death during hospital stay, was equally common among patients with IDU-IE (n = 7 (4%)), and those with non-IDU-IE (non-IDU-IE n = 27 (8%), P < 0.15). However, among patients with S. aureus aetiology, in-hospital mortality was higher among patients with non-IDU-IE compared with the patients with IDU-IE (n = 18 (15%) and n = 5 (4%), respectively, P = 0.01). In the IDU-IE group, 80 (70%) of the patients with S. aureus aetiology had right-sided IE, and 35 (30%) had left sided IE. In the non-IDU-IE group, 20 (18%) of the patients with S. aureus aetiology had right-sided IE, and 95 (83%) had left sided IE. Hence, of the patients with S. aureus aetiology, right sided IE was more common in the IDU-IE group (OR 10.74; P < 0.01). In the IDU-IE group, 3 (4%) of the patients with S. aureus aetiology and right-sided IE died during hospital stay, which was equal to the in-hospital mortality among the left-sided IE (n = 2 (6%); OR 0.64; P = 0.64). In the non-IDU-IE group, 2 (10%) of the patients with S. aureus aetiology and right-sided IE died during hospital stay, which was equal to the in-hospital mortality among the left-sided IE (n = 14 (15%); OR 0.63; P = 0.73).
The duration of hospital stay was equally long among patients with non-IDU-IE (median 32, mean 40.8 days, SD 148.9) compared with patients with IDU-IE (median 32, mean days 35.5, SD 15.9, P = 0.65 for comparison of the mean and P = 1.00 for comparison of the median). Patients with left-sided IDU-IE caused by S aureus had significantly longer antibiotic treatment durations compared to patients with S aureus and right-sided IDU-IE (mean 35.88 days versus 30.04 days, P < 0.01, Table 5).
Table 5. Antibiotic treatment duration among patients with IDU-IE, comparing left- and right-sided IE.
|
Both left- and right-sided IDU-IE
|
Left-sided IDU-IE
|
Right-sided IDU-IE
|
P value
|
All patients with IDU-IE
|
32.42
(30.30, 34.54)
|
34.53
(30.87, 38.18)
|
30.80
(27.74, 33.86)
|
0.12
|
Staphylococcus aureus aetiology
|
32.14
(29.56, 34.72)
|
35.88
(30.79, 40.97)
|
30.04
(26.49, 33.59)
|
<0.01
|
Non-Staphylococcus aureus aetiology
|
30.27
(29.03, 37.51) a
|
32.68
(27.90, 37.46)
|
34.57
(28.19, 40.96)
|
0.634
|
All values are presented in mean days (95% confidence intervals). P values between the comparisons of left- and right-sided IDU-IE, significant P values are marked in bold font. a No difference in treatment duration mean among S. aureus positive patients and non S. aureus patients (P = 0.63). Abbreviations: IDU, injection drug use; IE, infective endocarditis; S, staphylococcus.