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274
Episodes (%)
Staphylococcus aureus
Coagulase-negative
staphylococci
Viridans streptococci
Enterococci
Other streptococci
Pseudomonas aeruginosa
Other gram-negative
aerobes
Other organisms
Candida spp
Polymicrobial
Negative blood culture
endocarditis
1138 (74)
44 (3)
94
21
37
12
11
(6)
(1.5)
(2)
(<1)
(<1)
4
18
44
106
(<1)
(1.5)
(3)
(7)
275
Cases (%)
Right-sided endocarditis
Tricuspid valve
Pulmonic valve
Tricuspid and pulmonic valves
Unknown
Left-sided endocarditis
Aortic valve
Mitral valve
Aortic and mitral valves
Mural/Coarctation of aorta
Unknown
Mixed (right and left) endocarditis
1199
1045
14
8
132
254
103
98
27
3
24
76
(79)
(68)
(1)
(<1)
(9)
(16)
(7)
(6)
(1.5)
(<1)
(1.5)
(5)
276
277
Fig. 1. Chest radiograph of a female IV heroin addict with S. aureus tricuspid endocarditis
showing bilateral inltrates secondary to septic pulmonary embolizations.
meninges, brain, joints, bones, spleen, or other sites. These may confuse the
diagnostic process, and when present they are associated with a worse prognosis [2,46,12,14,15,24,42]. Sometimes disseminated intravascular coagulation (DIC) may develop. The associated petechial and purpuric skin lesions
may lead to a misdiagnosis of meningococcemia if the patient has signs of
meningitis [15].
Diagnostic criteria
Diagnosis of IE is made according to the clinical, microbiological, and
echocardiographical criteria described by Durack et al. [45]. It is also important to take into account that the clinical hallmark of right-sided endocarditis is the presence of radiological pulmonary inltrates, and that in IVDAs
one must discard peripheral septic thrombophlebitis [2,4,6,12,14,15,24,
42,46]. If the patient has HIV infection, it is important not to confuse
right-sided IE with a community-acquired pneumonia or P. carinii pneumonia. Bidimensional echocardiography and blood cultures are the most eective diagnostic tools for diagnosing IE in IVDAs [2,4,6,12,14,15,24,42].
Transthoracic echocardiography (TTE) remains useful for detecting vegetations and identifying the aected valve (see Fig. 2) [4648]. In right-sided
endocarditis, TTE detects tricuspid vegetations with a reported sensitivity
as high as 80% [42,46,4951], a sensitivity similar to that of transesophageal
echocardiography (TEE) [52]. Blood cultures are positive in 80% to 100% of
cases [6,12,14,15,24,40,42].
278
Fig. 2. Transthoracic echocardiography of a male IV heroin addict with S. aureus right side
endocarditis showing a large tricuspid valve vegetation (arrowhead). Top: during diastolic
period; bottom: during systolic period. VD right ventricle; AD right atrium. (Courtesy of
M. Azqueta, MD, Barcelona, Spain).
Prognosis
In the past two decades endocarditis has become one of the most prevalent causes of death in patients with drug addiction. In several recent studies,
mortality ranged between 5% and 30% [26,1215,24,42]. Mortality depends
on the side of the heart involved and the etiological agent [2,4,6,1215]
(Table 3). The prognosis of right-sided staphylococcal endocarditis is usually good (mortality <5%, with surgery <2%) [26,1215,24,42]. Patients with
tricuspid valve vegetations >2 cm in size [50] and with ARDS [53] have high
mortality (P < 0.05). The prognosis of left-sided IE, particularly when the
aortic valve is involved, is notably worse (mortality 20% to 30%, with
surgery 15% to 25%) [19,37,39,48,54,6264,80,93,98]. IE caused by gramnegative bacilli or fungi has the worst prognosis. Heart failure and systemic embolization (especially to the CNS) are the main causes of mortality
[26,1215,24,42].
279
Table 3
Surgery and mortality of 1106 episodes of methicillin-susceptible Staphylococcus aureus
(MSSA) endocarditis in Spanish IV drug abusers (197793) according to the side of the heart
involved [13]
Surgery
Mortality
a
Right-sided IE
N 950
Left-sided IEa
N 156
OR (95% CI)
P value
1%
5%
15%
28%
18 (843)
7 (411)
<0.001
<0.001
55 episodes of mixed (right + left) MSSA endocarditis were included in this group.
Antibiotic treatment
The authors will focus on the antibiotic treatment of right-sided endocarditis because it is especially important in IVDAs. The duration of therapy
for right-sided infections can be shortened in some cases. Favorable factors
are that the density of bacteria in right-sided vegetations is smaller than on
the left side [24,5456], and prognosis of right-sided endocarditis is very
good [26,1215,24,42].
Antibiotic therapy for left-sided endocarditis in IVDAs is essentially the
same as in the general population with native or prosthetic valve endocarditis.
Empiric therapy
The choice of empiric therapy at admission depends primarily on the suspected microorganism, side of the heart involved, and type of drug injected,
as summarized in Table 4 [26,1215,24,42]. Because S. aureus is the most
common microorganism on both sides of the heart, it must always be
covered [26,1215,24,42]. In this case the treatment will include antistaphylococcal antibiotics (nafcillin, cloxacillin, or vancomycin, depending
on the methicillin-resistant S. aureus [MRSA] prevalence [8,9,30] in the geographical area aected). If IVDAs are addicted to pentazocine [7,10] an antipseudomonas antibiotic therapy should be added to the previous treatment;
if IVDAs use brown heroin dissolved with lemon juice [11,39], candidemia
should be considered and an antifungal treatment (e.g., uconazole) may
be added. On the other hand, in IVDAs with underlying valvulopathy or
left-sided involvement, antibiotics eective against streptococcus and enterococcus must be included [26,1215,24,42] until blood culture results
become available.
Once the causative agent has been isolated, therapy must be adjusted to
its antibiotic susceptibility pattern [5761].
Therapy of methicillin-susceptible S. aureus endocarditis
The standard therapy for methicillin-susceptible S. aureus (MSSA) endocarditis on the native valve is a 4 to 6 week course of nafcillin or cloxacillin
(8 g/day to 12 g/day) [2,4,6,1215,5759,61]. An aminoglycoside (usually
gentamicin) can be given during the rst 3 to 5 days of therapy to reduce the
duration of fever, leukocytosis, and bacteremia [6,12,15,57,59,61]. If the
280
Table 4
Empiric antimicrobial therapy for infective endocarditis in IV drug abusers
Side of the heart involved
Right/mixed
Common: S. aureusa
Less common:
P. aeruginosab,
estreptococci, Candidac,
other bacteria
Penicillinase-resistant
penicillind plus gentamicin
Left
Common: S. aureusa,
estreptococci, enterococci
Less common:
P. aeruginosab,
other GNR,
Candidac, other bacteria
Ampicillin plus
penicillinase-resistant
penicillind plus
gentamicin
a
If methicillin-resistant S. aureus (MRSA) predominates in a given country, vancomycin
replaces penicillinase-resistant penicillin.
b
If IVDA uses pentazocine, add an anti-pseudomonas agent to the previous regimens to
cover P. aeruginosa infection.
c
If IVDA uses brown heroin dissolved with lemon juice, add an antifungal agent to the
previous regimens to cover C. albicans infection.
d
Nafcillin or cloxacillin.
281
Table 5
Recommended antibiotic regimens for methicillin-susceptible S. aureus endocarditis in IVDAs
Type of endocarditis
Non-complicated right-sided IEa
Non-complicated left-sided IE
Prosthetic valve IE
Recommended antibiotics
(dosage, route, and duration)
Nafcillin or cloxacillinb 2 g/4h IV for 2
weeks + gentamicin 1 mg/kg/8h IV/IM rst
5 days, or Ciprooxacin 750 mg/12h
po + rifampin 300 mg/12h po for 4 weeks
Nafcillin or cloxacillinb 2 g/4h IV for 4
weeks + gentamicin 1 mg/kg/8h IV/IM rst
5 days
Nafcillin or cloxacillinb 2 g/4h IV for 6
weeks + gentamicin 1 mg/kg/8h IV/IM rst
5 days
Nafcillin or cloxacillinb 2 g/4h IV + rifampin
300 mg/8h po for 6 weeks + gentamicin
1 mg/kg/8h IV/IM for 2 weeks
a
The short-course treatment is only recommended for uncomplicated cases (see text for the
exclusion criteria).
b
If the patient is allergic to penicillin the eligible antibiotic treatment will be a
cephalosporin (cefazolin 2 g/8h IV) for patients without anaphylactic reactions and vancomycin
(1 g/12h IV) or teicoplanin (610 mg/kg/12h for 9 doses and thereafter 610 mg/kg/24h IV or
IM) for patients with anaphylactic reactions.
c
It is recommended to prolong therapy until 6 weeks for complicated cases: left heart
failure, renal failure, local or systemic septic metastases, vegetation size >2 cm in diameter, and
prosthetic valve endocarditis.
282
Table 6
Published studies with nafcillin or cloxacillin plus an aminoglycoside for 2 weeks for right-sided
methicillin-sensitive S. aureus endocarditis in IV drug abusers (IVDAs) [42,7075]
Author (year)
Tx
Chambers (1988)
Espinosa (1993)
Torres-Tortosa (1994)
Miro (1994)
Fortun (1995)
Ribera (1997)
Fortun (2001)
Naf+Tob
Clo+Gen
Clo+Amk
Clo+Gen
Clo+Gen
Clo+Gen
Clo+Gen
Total
N
50
12
72
20
8
36
11
209
Cures
47
12
67
19
7
31
11
194 (93%)
Failures/relapses
Deaths
0/3
0/0
4/0
0/1
1/0
2/1
0/0
0
0
1
0
0
2
0
7/5 12 (6%)
3 (1%)
Tx Antibiotic therapy; Naf nafcillin (IV 1.5 g/4h); Tob tobramycin (IV 1 mg/kg/8h);
Clo cloxacillin (IV 2 g/4h); Gen gentamicin (IV 1 mg/kg/8h); Amk amikacin (7.5 mg/kg/
12h).
283
284
of persistent or recurrent P. aeruginosa bacteremia despite optimal antimicrobial therapy for at least 7 days (see Surgical therapy section). The
therapy of choice is administration of ceftazidime, meropenem/imipenem,
piperacillin, or ciprooxacin plus high doses of an aminoglysoside (e.g., tobramycin or amikacin) for at least 6 weeks. Therapy for fungal endocarditis
should also be started according to the general recommendations [12,15] prior
to valve replacement (see Surgical therapy section).
Therapy of negative blood culture endocarditis
In these cases, initial antibiotic therapy should be given during the recommended period of time if there is a good clinical response (see Table 4). In
other clinical situations the approach will be the same as in the non-addict
population, taking into account that HIV-infected IVDAs can have a wide
dierential diagnosis because of AIDSrelated diseases.
Surgical therapy
The authors will discuss only the surgery of right-sided endocarditis with
tricuspid valve involvement. The indications for surgery and the technical
options for left-sided involvement are the same as in the general population
with native or prosthetic valve endocarditis [87,88]. Furthermore, two special
issues are usually taken into account before considering surgery in this population: the likelihood of continuing IV drug abuse with continuing risk of
reinfection, overdose, and other complications, and the issue of HIV infection (see Inuence of HIV-1 infection in endocarditis in IVDAs section).
This explains why the surgical approach is usually more conservative in IV
drug abusers; they have a higher incidence of recurrent IE compared to the
general population with IE [2,4,6,12,14,15], most often due to continued use
of IV drugs. Indeed, this type of surgery also requires special considerations
for IVDAs to avoid the development of prosthetic valve endocarditis if there
is continued use of IV drugs. Despite this, IV drug abuse by itself must not be
a contraindication for surgery. Several studies have shown that cardiac surgery improves the outlook for early and late survival of IVDAs with IE in
whom surgery is indicated. Mathew et al. [55] studied a cohort of 80 IVDAs
who underwent several types of operations for IE. The probability of survival
at 3 and 5 years was 74% and 70%, respectively, and these gures are comparable to the general population who underwent surgery for IE. Arbulu et al.
[89] found a survival rate of 64% at 22 years in a cohort of 54 IVDAs who
underwent surgery for right-sided IE.
Indications for right-sided surgery
There are two main indications for surgery in this type of endocarditis:
(1) endocarditis caused by microorganisms dicult to eradicate, such as fungal
etiology or persistent or recurrent bacteremia despite optimal antimicrobial
therapy for more than 7 days (e.g., S. aureus or P. aeruginosa endocarditis)
285
[12,87,88], and (2) patients with tricuspid valve vegetations >2 cm with
dilated right ventricle (TTE) and recurrent pulmonary emboli or right heart
failure [49,50,53].
Technical options for right-sided involvement
In tricuspid valve endocarditis the surgical approach is very conservative.
Most surgeons opt to avoid the implantation of foreign material. The
options are: (1) total or partial valve resection without valve replacement
(tricuspid valvulectomy). This procedure helps prevent recurrent endocarditis if patients continue IV drug use [15,89,90]. This simple operation
described by Arbulu et al. almost 30 years ago [91,92] is usually indicated
as a life-saving maneuver. Long-term follow-up showed, however, that
10% to 15% of cases may require late implantation of a valve prosthesis
as a consequence of right-sided heart failure due to chronic massive tricuspid regurgitation [89,93,94]. (2) Vegetectomy or tricuspid valve repair [90].
This surgical approach should be used in all cases if possible. (3) Tricuspid
valve replacement with a biological or mechanical prosthesis. If this option
is deemed necessary, anticoagulation is recommended when mechanical
prosthesis are implanted. Fatal complications have been described in noncompliant IVDAs [89,94], and if IV drug abuse persists patients can develop
prosthetic endocarditis; in this case the prognosis is very poor [89,94]. Finally, (4) tricuspid valve replacement with a mitral homograft. This is a new
approach that has been performed successfully in some cases to avoid the
use of any synthetic material by transplanting a cryopreserved mitral homograft into the tricuspid position [95]. It was described by Pomar and Mestres
in 1993 [95]. Technically it is not a complex operation and provides valvular
competence in the acute phase, avoiding the appearance of late clinical right
heart failure [56,96,97]. Furthermore, if IV drug abuse persists, recurrent
endocarditis on the homograft can be managed conservatively without
operation [56,96,97]. A tricuspid homograft could also be used; however, tricuspid valves are seldom harvested as the tricuspid valve usually has fragile
tissues.
In the very unusual case of pulmonary valve endocarditis, the surgical
approach also has the same considerations. Pulmonary valvulectomy or the
replacement of the pulmonary valve with a pulmonary homograft are
the best surgical options [88].
286
Incidence
Several epidemiological studies [20,104,105] have shown that HIV infection is associated with a several-fold increased risk of endocarditis in
IVDAs. Mano et al. [104] have shown that compared to HIV-negative
IVDAs, HIV-infected IVDAs with CD4 cell counts 350 cells/lL had an
OR of 2.31 (0.61 to 8.8) for developing IE, whereas those with a CD4 cell
count <350 cells/lL had an OR of 8.31 (1.2 to 56) for developing IE. However, the risk in HIV-infected patients who do not abuse drugs is not
increased (see Infective endocarditis in HIV-infected patients not related
to IV drug abuse section). HTLV-II infection has no inuence on the risk
of IE [106].
Clinical characteristics and etiology
HIV infection does not alter the febrile response of IVDA patients with
IE [107]. HIV-infected patients have lower WBC counts [99101] a higher
ratio of right-sided endocarditis and S. aureus infections than HIV-negative
IVDA patients [99,100].
Antibiotic therapy
Response to antibiotic therapy is similar among HIV-infected or nonHIV-infected IVDAs [74,80]. It is not known, however, if right-sided MSSA
endocarditis can be treated successfully with short-course therapy in HIVinfected IVDAs. Ribera et al. [74] and Fortun et al. [73] showed that
cure rates for asymptomatic HIV-infected IVDAs were the same as for
HIV-negative IVDAs (90% and 100%, respectively). In both studies, HIVinfected IVDAs had a mean/median CD4 cell count of 300/lL [73,74].
Although these data are very promising, the reality is that there is not
enough information about the ecacy of this short-course regimen in AIDS
or severely immunosupressed patients (CD4 cell counts <200/lL), the subgroups of HIV-infected patients with the highest mortality rates [98100].
It seems prudent, therefore, to treat these patients with the more active antibiotic regimens for 4 weeks.
Surgery
Cardiac surgery in HIV-infected IVDAs with IE does not worsen neither
the endocarditis nor the HIV infection prognosis [102,103].
Prognosis
Overall mortality between HIV-infected or non-HIV-infected IVDAs
with IE is similar [98100]. In HIV-infected IVDAs with endocarditis, however, several studies have demonstrated that the AIDS stage and severe
287
288
Table 7
Characteristics of 22 episodes of infective endocarditis in HIV-1 infected patients not related to
active or former IV drug abuse (19801999) [25,108,112123]
Variables
Sex
Male
Female
HIV risk factor
Homosexuality
Heterosexuality
Blood product recipient
Unknown (no-IVDA)
HIV stage
A
C
no data
CD4/lL
<200
200
No data
Etiological agent
Enterococcus faecalis
Viridans group streptococci
Staphylococci
Streptococcus pneumoniae
Salmonella spp
Fungi
Other
Acquisition
Community
Nosocomial
No data
Type of valve
Native
Prosthetic
No data
Valve involved
Mitral
Aortic
Aortic and mitral
Tricuspid
No data
Surgery
Yes
No
No data
Mortality
Yes
No
No data
Number
of cases (%)
21 (95)
1 (5)
10
6
3
3
(45)
(27)
(14)
(14)
8 (36)
13 (59)
1 (5)
12 (55)
4 (18)
6 (27)
4
2
2
2
5
4
3
(18)
(9)
(9)
(9)
(23)
(18)
(14)
13 (59)
4 (18)
5 (23)
19 (86)
2 (9)
1 (5)
9
6
4
1
2
(41)
(27)
(18)
(5)
(9)
4 (18)
16 (73)
2 (9)
4 (18)
16 (73)
2 (9)
289
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