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Infective Endocarditis at a Tertiary Care Centre in Lebanon: Predominance of Streptococcal Infection
Journal of Infection (2002) 45: 152±159 doi:10.1053/jinf.2002.1041, available online at http://www.idealibrary.com on
Infective Endocarditis at a Tertiary Care Centre in Lebanon: Predominance of Streptococcal Infection Z. A. Kanafani, T. H. Mahfouz and S. S. Kanj* Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Centre, PO Box 113-6044, Hamra 110 32090, Beirut, Lebanon Objectives: Infective endocarditis (IE) remains a disease associated with high morbidity and mortality. Many epidemiological studies have been reported worldwide; however, data from the Middle East is scarce. Most studies have recently shown a trend towards increasing incidence of Staphylococcus aureus endocarditis and decreasing prevalence of rheumatic heart disease as a predisposing condition. Methods: We conducted a retrospective review of all recorded cases of IE in adult patients admitted between 1986 and 2001 to the American University of Beirut-Medical Centre. Results: The total number of cases was 91. The mean age was 48 years. Fifty-nine percent of patients had a predisposing cardiac condition, rheumatic heart disease being the most common (33%). Blood cultures were positive in 77.5% of the cases: the most commonly isolated organisms were Streptococcus spp. (51%; of which 57% were viridans streptococci.) and Staphylococcus spp. (36%; of which 72% were S. aureus and 28% were coagulase-negative staphylococci). Transoesophageal echocardiography was performed in 36 patients (40%), of which 32 (89%) showed positive findings. When applying the revised Duke criteria, 82% of the patients were classified as definite and 16.5% as possible endocarditis. Surgery was performed in 32% of cases mostly for valvular regurgitation, followed by heart failure. The complication rate was 69% with congestive heart failure, drug-related toxicities, new valvular regurgitation and systemic embolisation being the most common. The in-hospital mortality rate was 18%. Conclusions: Unlike data reported from the United States and northern Europe, this study confirms that in Lebanon, a developing country, we continue to have a predominance of streptococci as aetiologic agents in IE, and rheumatic heart disease as the most common underlying heart condition. Application of the revised Duke criteria was useful in confirming the diagnosis of IE. # 2002 The British Infection Society. Published by Elsevier Science Ltd. All rights reserved.
Introduction Infective endocarditis (IE) remains a relatively rare disease worldwide. An estimated 10,000±15,000 new cases of infective endocarditis (IE) are diagnosed each year in the United States [1]. However, the precise incidence of IE is difficult to ascertain because case definitions have varied over time, between authors, and among different medical centres. In a review of 10 large surveys, IE was responsible for 1 case per 1000 hospital admissions (range 0.16±5.4) [2]. Nevertheless, it is still associated with high morbidity and mortality rates and the incidence of predisposing conditions has varied over time and between different areas. A wealth of medical literature * Please address all correspondence to: Souha S. Kanj, Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Centre, PO Box 113-6044, Hamra 110 32090, Beirut, Lebanon. Tel.: 961-1-350000 ext 5353; Fax: 961-1-370814. E-mail address: [email protected]. (S. S. Kanj). 0163±4453/02/$35.00
has been devoted to the study of this condition. However, data from Lebanon and the surrounding region is scarce and the epidemiology of IE in this part of the world remains largely unknown. In fact, the only available epidemiological data from Lebanon has addressed the paediatric age group [3]; the authors have shown the importance of rheumatic heart disease as risk factor for IE, and reported an equal share for viridans streptococci and S. aureus as etiologic agents. Herein, we report the first study from Lebanon investigating IE in adult patients.
Materials and Methods Patients older than 13 years admitted to the American University of Beirut-Medical Centre (AUB-MC) between January 1, 1986 and April 30, 2001 with the discharge diagnosis of IE were included in the analysis. AUB-MC is one of two tertiary care referral centres in Beirut; it serves a large proportion of the population of Beirut and
# 2002 The British Infection Society. Published by Elsevier Science Ltd. All rights reserved.
Infective Endocarditis at a Tertiary Care Centre the surrounding regions. Patients were treated by a cardiologist and/or an Infectious Disease specialist. Relevant clinical and laboratory data, as well as echocardiographic findings were recorded from the patients' medical records.
Statistical methods Data were collected and entered into a database using Microsoft1 Access 2000. Statistical analysis was conducted using SPSS 10.0 for Windows and Microsoft1 Excel 2000. When applicable, phi coefficient, Cramer's V, contingency coefficient and chi-square test were performed. Odds ratios were calculated from two-by-two contingency tables and the respective 95% confidence intervals were obtained.
Definitions In this study, we used the revised Duke criteria for the diagnosis of infective endocarditis to validate our results (Tables I and II).
Table I. Definition of infective endocarditis according to the modified Duke criteria.y Definite infective endocarditis Pathologic criteria (1) Microorganisms demonstrated by culture or histologic examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen; or (2) Pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis Clinical criteria* (1) 2 major criteria; or (2) 1 major criterion and 3 minor criteria; or (3) 5 minor criteria Possible infective endocarditis (1) 1 major criterion and 1 minor criterion; or (2) 3 minor criteria Rejected (1) Firm alternate diagnosis explaining evidence of infective endocarditis; or (2) Resolution of infective endocarditis syndrome with antibiotic therapy for < 4 days; or (3) No pathologic evidence of infective endocarditis at surgery or autopsy, with antibiotic therapy for < 4 days; or (4) Does not meet criteria for possible infective endocarditis, as above * See Table II for definitions of major and minor criteria. y Li JS, Sexton DJ, Mick N, Nettles R et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000; 30: 633±638.
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Results Patient characteristics Ninety-one patients with a discharge diagnosis of IE were identified. The male to female ratio was 1.8:1. The mean age was 48 years (range 13±87 years). Thirty patients (33%) were known to have one or more chronic illnesses, the most common of which was diabetes mellitus followed by hypertension (Table III). Endocarditis was acquired nosocomially in 8 patients (9%). Dental procedures were performed in 17 patients (19%) within 3 months of presentation. At the beginning of the current episode of IE, 10 patients (11%) had intravenous lines and/or central venous catheters. The cases were equally distributed throughout the study period ranging from January 1986 to April 2001. The overall number of admissions to AUB-MC during that period of time was 295,878; so IE was responsible for 3 cases per 10,000 hospital admissions. The total number of patients admitted was 184,728Ðsome patients were admitted more than once, making the incidence of IE in the hospitalized population at our centre 5 cases per 10,000 patients.
Underlying heart lesions Overall, 54 patients (59%) had an underlying cardiac condition, the most common being rheumatic heart disease (RHD) in 30 cases (33%); only 11 patients (12%) had previously documented normal echocardiographs. Concerning the initial valve status, 18 patients (20%) had prosthetic valves; 30 patients (33%) had rheumatic valves and 16 (18%) were known to have normal valves. In addition, congenital heart lesions were present in 12 patients (13%).
Clinical manifestations (Table IV) The most frequent symptoms on presentation were fever in 83 cases (91%) with a mean of 39.4 C (range 38.1±42 C), chills in 49 (54%), night sweats in 36 (40%), weight loss in 31 (34%), dyspnoea in 31 (34%), and headaches in 31 cases (34%). On physical examination, splenomegaly was reported in 23 cases (25%), Roth spots in 15 (16%), hepatomegaly in 14 (15%) and Osler nodes in only 2 cases (2%). On cardiac auscultation, 19 patients (21%) had a new murmur and 15 (16%) had a worsening murmur. Twenty-nine patients (32%) were found to have vascular phenomena: 14 (15%) had strokes or transient ischaemic attacks
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Z. A. Kanafani et al. Table II. Definition of terms used in the modified Duke criteria for the diagnosis of infective endocarditis (IE)y. Major criteria Blood culture positive for IE Typical microorganisms consistent with IE from 2 separate blood cultures: Viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or Community-acquired enterococci, in the absence of a primary focus; or Microorganisms consistent with IE from persistently positive blood cultures, defined as follows: At least 2 positive cultures of blood samples drawn >12 h apart; or All of 3 or a majority of >4 separate cultures of blood (with first and last sample drawn at least 1 h apart) Single positive blood culture for Coxiella burnetii or antiphase IgG antibody titer >1:800 Evidence of endocardial involvement Echocardiogram positive for IE (TEE recommended in patients with prosthetic valves, rated at least `possible IE' by clinical criteria, or complicated IE [paravalvular abscess]; TTE as first test in other patients), defined as follows: Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; or Abscess; or New partial dehiscence of prosthetic valve New valvular regurgitation (worsening or changing of pre-existing murmur not sufficient) Minor criteria Predisposition: predisposing heart condition or injection drug use Fever: temperature >38 C Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial haemorrhage, conjunctival haemorrhages, and Janeway's lesions Immunologic phenomena: glomerulonephritis, Oslers nodes, Roth spots, and rheumatoid factor Microbiological evidence: positive blood culture but does not meet a major criterion as noted above* or serological evidence of active infection with organism consistent with IE Echocardiographic minor criteria eliminated TEE transoesophageal echocardiography; TTE transthoracic echocardiography. *Excludes single positive cultures for coagulase-negative staphylococci and organisms that do not cause endocarditis. yLi JS, Sexton DJ, Mick N, Nettles R, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000; 30: 633±638.
Table III.
General characteristics of patients.
Characteristic
Value
No. of patients Age in years (mean SD) Sex (male:female) Chronic illness (no. of patients) Cancer CAD/CHF Diabetes Hypertension Immunosuppression Chemotherapy Steroids Renal failure Haemodialysis
91 48 19 1.8:1 30 4 6 9 8 4 2 2 4 2
SD standard deviation; CAD coronary artery disease; CHF congestive heart failure.
(TIA), 13 (14%) had systemic embolisations, and 6 (7%) had Janeway lesions. Laboratory findings Anaemia was present in 71 (78%) and leukocytosis in 47 patients (52%). An elevated erythrocyte sedimentation
rate (ESR) was present in 91%, with a mean of 82 (range 20±150). Furthermore, rheumatoid factor (RF) was positive in 64%, C-reactive protein (CRP) in 83% and haematuria in 37.5% of patients for whom these tests were requested.
Microbiology Blood cultures were taken in 89 patients and were positive in 69 cases (77.5%) (Table V). There were 35 isolates of Streptococcus spp, which accounted for the majority of recovered organisms (51%); 20 (57%) of these were identified as viridans streptococci. The second most commonly isolated organisms were staphylococci in 25 cases (36%); out of the 25 isolates of staphylococci, 7 were coagulase-negative and 18 were S. aureus, 5 (28%) of which were methicillin-resistant. Other isolates included Pseudomonas spp., Enterococcus spp., Enterobacter cloacae, Neisseria mucosa and candida non-albicans. Valves were cultured in 24 patients (26%) and were positive in 2: one grew coagulase-negative staphylococci and the other grew Trichosporon beigelii. Other cultures yielding growth included bone marrow, catheter tips,
Infective Endocarditis at a Tertiary Care Centre Table IV. Clinical manifestations and laboratory findings from the current study compared to data from other studies.
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Table V. Distribution of organisms recovered from blood cultures of patients with infective endocarditis.
Percentage of patients affected
Organism
No. of isolates n 6
Current study
Other studies*
54 34 40 35 33
40 25 25 40 20
91 2 3 16 24 12 9
90 10±23 15 2±10 20±57 3±5 5±10
Vascular phenomena Stroke Janeway lesions Systemic embolisation Mycotic aneurysms
12 7 14 1
20 <10 >50 20
Streptococci alpha-haemolytic viridans S. others beta-haemolytic Staphylococci S. aureus MSSA MRSA Coagulase-negative staphylococci Enterococci E. faecalis Unspecified Pseudomonas spp. P. aeruginosa P. stutzeri Enterobacter cloacae Neisseria mucosa Candida non-albicans
35 33 18 15 2 25 18 13 5 7 3 1 2 3 1 2 1 1 1
Laboratory findings Anaemia Leukocytosis Elevated ESR Positive RF Haematuria
78 52 91 64 37.5
70±90 20±30 90±100 40±50 30±60
Symptoms Chills Weight loss Night sweats Dyspnoea Headache Signs Fever Osler nodes Splinter haemorrhages Retinal lesions Splenomegaly New murmur Changing murmur
ESR erythrocyte sedimentation rate; RF rheumatoid factor. * Adapted from: Bayer AS, Scheld WM. Endocarditis and intravascular infections. In: Mandell GL, Bennett JE, Dolin R (eds) Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 5th edn. Philadelphia: Churchill Livingstone, 2000: 857±884.
cerebrospinal fluid, pleural fluid, abdominal abscess and wound cultures. All these specimens yielded the same organisms isolated from blood. One patient had positive serology for brucella and was thought to have brucella endocarditis. Overall, the incriminating organism for IE was identified in 71 patients (78%), 69 by blood cultures and/or valve/other cultures, one by valve culture and another by serology. Echocardiography Echocardiography was performed in 89 patients, transthoracic echocardiography (TTE) in 82 (90%) and transoesophageal echocardiography (TEE) in 36 patients (40%). Both studies were done in 29 patients (32%). Echocardiography findings defined as positive included presence of vegetation, new valvular regurgitation, intracardiac abscess, fistulous tract, ruptured chordae, valve perforation, new perivalvular leak or valve dehiscence. TTE was positive in 51/82 (62%) and TEE in
MSSA methicillin-sensitive S. aureus; MRSA methicillin-resistant S. aureus. Table VI. Results of echocardiography in 29 patients who underwent both TTE and TEE. TEE (no.) Positive
Negative
Total
TTE (no.) Positive Negative Total
14 12 26
1 2 3
15 14 29
Sensitivity 53.8% Specificity 66.7%
PPV 93.3% NPV 14.3%
TTE transthoracic echocardiography; TEE transoesophageal echocardiography; PPV positive predictive value; NPV negative predictive value.
32/36 cases (89%). Overall, echocardiography was positive in 71/% patients (80%). Vegetations were seen in 61 (68.5%), new valvular regurgitations in 16 (18%) and perivalvular complications (perforation, abscess, fistulous tract, valve dehiscence, new perivalvular leak) in 19 patients (21%). The mitral valve alone was involved in 37 (42%) and the aortic valve in 23 patients (26%); there was disease on both valves in 8 patients (9%). In addition, the tricuspid valve was affected in 6 cases (7%). None of the patients had pulmonic valve involvement. One patient had concomitant right- and left-sided endocarditis. Pericardial effusion was observed in 12 cases (13%). Tables VI and VII illustrate the findings of TTE in comparison to TEE in the subset of patients who underwent both echocardiographic
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Table VII. Detailed comparison between findings on TTE versus TEE in 29 patients who underwent both echocardiographic modalities.
Table VIII. Complications and mortality observed in patients with infective endocarditis.
Location of vegetations
Complication
% of patients
Death Heart failure Drug-related toxicities Rise in serum creatinine New valvular regurgitation Systemic embolization Spleen Vascular periphery Kidney Stroke Embolic Haemorrhagic Intracardiac abscess TIA New conduction abnormality Other complications
17.6 27.5 19.8 15.4 17.6 14.3 6.6 4.4 4.4 12.1 8.8 3.3 11 3.3 3.3 16.5
TTE Pos 4
MV
2
AV TV
TEE Def
4
2
1
Intracardiac
1
Chordae
1
Perivalvulvar complications*
4
No
Def
No 1
21
3 4 6
25
1 2 5
19
28
2
1 26
29
1 1
27
Pos
1
1 2
15 1
28
25
13
TTE transthoracic echocardiography; TEE transoesophageal echocardiography; MV mitral valve; AV aortic valve; TV tricuspid valve; Pos possible; Def definite. * Perivalvular complications include: valve perforation, abscess formation, fistulous tract, valve dehiscence, or new perivalvular leak.
modalities. The sensitivity of TTE in this study was 54%. We report a positive predictive value of TTE versus TEE of 93% however, the negative predictive value is only 14%. Classification When applying the revised Duke criteria (Tables I and II) for the diagnosis of IE, 75 patients (82%) were classified as definite and 15 (16.5%) as possible endocarditis. One case did not fulfill the Duke criteria but could not be rejected and was treated for IE because of the high clinical suspicion. In 7 patients (8%), the definitive diagnosis of IE was confirmed by valve pathology or culture; in all 7 patients, echocardiography showed abnormal findings. Treatment The mean duration of antibiotic therapy was 40 days (range 0±429 days). In patients with streptococcal endocarditis, 17 (49%) received a combination of penicillin and an aminoglycoside and 17 (49%) received penicillin alone. Patients with staphylococcal endocarditis were treated most commonly with vancomycin, alone or with an aminoglycoside in 12 cases (48%) or a combination of a penicillinase-resistant penicillin and an aminoglycoside in 7 cases (28%). In 7 patients (28%),
TIA transient ischaemic attack.
rifampin was added to the antibiotic regimen for synergy. Forty-four patients (64%) without a microbiological diagnosis received an empiric regimen consisting of penicillin and an aminoglycoside. Surgery was performed in 29 patients (32%). In addition, in 3 patients surgical intervention was clearly indicated but was not done because of the high operative risk. The most commonly encountered indications for surgery were valvular regurgitation in 25 (27.5%), heart failure in 15 (16.5%) and intracardiac abscess formation in 7 patients (8%). Other indications included systemic embolisation, valve dehiscence, ventricular septal defect, failure of medical treatment, mitral valve thrombosis, severe aortic stenosis and ruptured chordae. In 25 patients (86%), the decision to operate was based on more than one factor. The mean duration of stay in hospital was 33 days (range 1±180 days). Complications and outcome Complications occurred in 63 patients (69%) (Table VIII), the most common of which were congestive heart failure in 25 cases (27.5%), drug-related toxicities in 18 (20%), new valvular regurgitation in 16 (18%), systemic embolisation in 13 (14%), stroke in 11 (12%) and intracardiac abscess in 10 cases (11%). Other complications of IE included new conduction abnormalities, pericarditis and pericardial tamponade, atrial fibrillation, ventricular fibrillation, glomerulonephritis, meningitis, encephalitis, phlebitis, pneumonia, respiratory failure, renal failure, and relapse of disease. Embolisations involved the spleen, vascular periphery, kidney, lung,
Infective Endocarditis at a Tertiary Care Centre retina and penis. Drug toxicities and complications related to treatment consisted most commonly of aminoglycoside-induced nephrotoxicity in 14 cases (15%). Other drug-related side effects included interstitial nephritis, nausea and vomiting, and allergic reactions. Overall, 16 patients passed away, bringing the in-hospital mortality rate to 18%. In 6 cases (37.5%), the etiologic organism was S. aureus; and over 6 patients (33%) with S. aureus endocarditis died.
Discussion Infective endocarditis presents a challenge to physicians from all specialties; it manifests in so many diverse and confusing ways. However, advances in echocardiography and surgical techniques have given us additional diagnostic and therapeutic tools to manage this infection. Changes in the epidemiology and microbiology of IE continue to occur. Over the last thirty years, IE has been most commonly seen in older age groups, with a predominance of male patients and an increased incidence of acute cases caused by virulent organisms such as S. aureus, gram-negative bacilli and fungi. On the other hand, cases caused by oral streptococcal spp. are on the decrease. The patient population is also changing; most of these changes relate to the numbers and types of susceptible hosts, with an increased number of IE diagnosed in the setting of intravenous drug abuse (IVDA), prosthetic valves, arteriovenous shunts for haemodialysis, and Human Immunodeficiency Virus (HIV) infection. In addition, IE is increasingly described as a nosocomial infection, acquired in the hospital setting due to advances in medical technology (vascular devices, intravenous catheters, invasive procedures, and so forth) that have increased the risk of bacteraemia and related complications [4]. When comparing our results with other reports, the male to female ratio was in agreement with most case series [2]. However, our patient population was relatively young, unlike recent reports from the United States showing that more than one-half of all IE cases were seen in patients over the age of 60, with a steady increase in the median age [5]. This trend in the developed countries is likely due to two factors: the increasing proportion of elderly subjects in the general population and the decline in the incidence and importance of RHD as a risk factor. In fact, recent studies from developed countries showed a decline of RHD as the underlying structural heart abnormality in patients with IE from 37±76% in the past to 25% or less in the last two decades [2,6]. In contrast, our study showed that RHD
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was the most common underlying cardiac condition. A recent study from Israel showed similar trends [7]. The incidence of prosthetic valve endocarditis (PVE) was much higher than reports from the western world [4]. Only 19% of the patients in this study had undergone dental procedures within 3 months of hospital admission, as compared to 23% reported in a recent casecontrol study [8]. However, the distribution of organisms in these patients was similar to those without prior dental procedures. We did not observe any trend in the number of cases reported each year, and there was no statistically significant difference in the risk factors for endocarditis over the study period. This implies that, with the absence of IVDA and HIV infection among our patients, no new predisposing factors have emerged over the years to alter the incidence or the epidemiology of IE in this country. A comparison between the clinical manifestations of IE in our study and in other reports from the literature [9] is shown in Table IV. The various signs and symptoms were comparable except for a lower incidence of systemic embolisation in our study. We found no correlation between the occurrence of vascular phenomena and the presence of vegetation by echocardiography, however on further analysis, there was a statistically significant increase in the incidence of vascular phenomena in patients who had mitral valve vegetations (odds ratio, 2.6; 95% confidence interval, 1.1±6.6). Patients who had one or more of the following findings including; splenomegaly, hepatomegaly, elevated ESR, positive CRP, haematuria, anaemia and leukocytosis were more likely to be later classified as definite rather than possible endocarditis (odds ratio, 17.08; 95% confidence interval, 1.7±177.1). None of these clinical findings are specific for IE, which is why they are not included as minor criteria in the revised Duke criteria for IE; yet they might have some importance in diagnostically challenging cases. In this study, the yield of positive blood cultures (77.5%) was lower than the rate of over 90% reported from a review of 206 cases of IE seen over a 15-year period at a New York hospital [10]. Unlike several reports from developed countries of increasing incidence of staphylococcal endocarditis [11±14], there was a predominance of streptococcal isolates in our series, which could be explained by the high prevalence of RHD as underlying cardiac disease in our community, as well as by the absence of IVDA and HIV infection among our patients. This finding is also supported by other reports from developing countries [7]. Over the last 20 years, the use of echocardiography has been instrumental in confirming the diagnosis of
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endocarditis. The sensitivity of TTE in this study was 62% and is within the reported range of 50±75% from other studies. The low negative predictive value confirms that TEE would be essential to the diagnosis of IE when TTE is normal. It should be kept in mind, however, that echocardiography is an operator-dependent diagnostic modality; the sensitivity and specificity that we report are therefore affected by the multiplicity of the echocardiographers (3 in total), especially that the echocardiogram results were recorded from the patients' medical records and were not re-reviewed for the purpose of this study. The distribution of involved valves with a predominance of mitral valve disease is also similar to previous studies in the literature [15±18]. Despite reports from the literature linking the presence of intravenous catheters to right-sided endocarditis, in this study, there were no tricuspid or pulmonary valve vegetations in any of the 10 patients who had intravenous catheters at the time of diagnosis of IE. The diagnosis of infective endocarditis is usually based upon a constellation of clinical findings rather than upon a single definitive test result. The Duke criteria (Tables I and II) are valuable in assisting clinicians with the diagnosis of IE; in 1994 investigators from Duke University modified the old von Reyn criteria to include the role of echocardiography in diagnosis. Multiple studies have since validated the Duke criteria and compared their utility to that of the von Reyn criteria [19±23]. Each of these reports evaluated patients in whom the diagnosis of IE was established. When applying the Duke criteria to validate our cases, all patients, except for one, fell into the possible or definitive diagnosis, once again confirming the value of these criteria in the clinical diagnosis of endocarditis. The antibiotic therapy used in our patients conforms in most cases to the guidelines of the American Heart Association for the treatment of IE [24]. However, there was overuse of glycopeptide antibiotics unjustified by the low percentage of methicillin-resistant staphylococcal isolates. In the era of emergence of antibiotic resistance, the misuse and abuse of glycopeptides is highly discouraged. In certain clinical situations, a combined medical and surgical approach is necessary for the successful treatment of IE. During the last three decades, valve replacement and repair have become commonplace in the management of selected complications of IE, and the combination of antibiotic therapy and timely surgical intervention has substantially reduced the mortality from IE. Our results demonstrate that 32% of the cases of IE have required surgical intervention. Reports in the literature quote a figure of at least 25%. Over time,
the indications for surgery have expanded and valve replacement surgery has been undertaken progressively earlier in the course of the illness. The indications for surgery in our patients were consistent with the guidelines of the American College of Cardiology/American Heart Association, namely congestive heart failure, systemic embolic events, significant valve dysfunction, failure of medical therapy and perivalvular complications such as abscess formation [25]. A myriad of complications can result from IE and occur in the majority of patients. Our data indicate that 31% of patients had one complication, 29% two, and 10% three or more complications. We also established that patients who had echocardiographic evidence of vegetations were at a higher risk of developing systemic vascular embolisation than patients who had no vegetations demonstrable by echocardiography (odds ratio, 5.9; 95% confidence interval, 1.3±27.4). For comparison, it is difficult to assess the true incidence of complications of IE in other studies because of the retrospective nature of most reports and the different diagnostic criteria used to define cases of IE. Moreover, the frequency of specific complications depends upon the infecting pathogen, duration of illness prior to therapy, and the type of treatment facility (e.g. referral versus community hospital). All complications described in our study were reported in the literature; in a review of 223 episodes of IE, 57% of patients had one complication, 26% two, and 8% three or more complications [26]. The in-hospital mortality in this study is comparable to the 15% reported in a retrospective study of 212 cases of IE [27]. It is noteworthy that the high mortality rate in our cases of S. aureus endocarditis is consistent with other reports in the literature quoting a figure of at least 40% [28±31]. There was no significant difference in mortality based on the valve involved.
Conclusion This study describes the clinical presentation, microbiology, complications and treatment of adult patients with infective endocarditis admitted to a university hospital in Lebanon. RHD remains the most important predisposing cardiac condition. This finding has important implications for antibiotic prophylaxis prior to invasive procedures. Moreover, and as opposed to other recent series, we continue to have a predominance of streptococci in IE. The main limitation of this study is its retrospective design; some patient records were incomplete and this has impeded the process of data collection to a certain extent. IE, however, is a rare disease entity
Infective Endocarditis at a Tertiary Care Centre and devising a one-centre prospective trial would be fairly difficult. Future studies should be therefore designed to prospectively follow patients with IE from different centres in the country; this would allow us to assess for homogeneity of the patient population in Lebanon with respect to risk factors for endocarditis and the microbiology of the disease. A large prospective multinational, multi-centred study is highly desirable, and is currently underway with the International Collaboration on Endocarditis (ICE) study. AUB-MC is one of over 30 centres from 13 countries participating in ICE, with the aim to establish an international database for endocarditis [32].
References 1 Bayer AS. Infective endocarditis. Clin Infect Dis 1993; 17: 313±320. 2 Harris SL. Definitions and demographic characteristics. In: Kaye D, ed. Infective Endocarditis. Raven Press, 1992; 1. 3 Bitar FF, Jawdi RA, Dbaibo GS et al. Paediatric infective endocarditis: 19-year experience at a tertiary care hospital in a developing country. Acta Paediatr 2000; 89: 427±430. 4 Berlin JA, Abrutyn E, Strom BL et al. Incidence of infective endocarditis in the Delaware Valley, 1998±1990. Am J Cardiol 1995; 76: 933±936. 5 Cantrell M, Yoshikawa TT. Infective endocarditis in the aged patient. Gerontology 1984; 30: 316±326. 6 Kaye D. Changing pattern of infective endocarditis. Am J Med 1985; 78(suppl 6B): 157±162. 7 Borer A, Riesenberg K, Uriel N et al. Infective endocarditis in a tertiary-care hospital in southern Israel. Public Health Rev 1998; 26: 317±330. 8 Strom BL, Abrutyn E, Berlin JA et al. Dental and cardiac risk factors for infective endocarditis. A population-based, case-control study. Ann Intern Med 1998; 129: 761±769. 9 Bayer AS, Scheld WM. Endocarditis and intravascular infections. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 5th edn. Churchill Livingstone, 2000; 857±884. 10 Werner AS, Cobbs CG, Kaye D et al. Studies on the bacteremia of bacterial endocarditis. JAMA 1967; 202: 199±203. 11 Watanakunakorn C, Burkert T. Infective endocarditis at a large community teaching hospital, 1980±1990. A review of 210 episodes. Medicine (Baltimore) 1993; 72: 90±102. 12 Kim EL, Ching DL, Pien FD. Bacterial endocarditis at a small community hospital. Am J Med Sci 1990; 299: 87±93. 13 Kazanjian PH. Infective endocarditis: review of sixty cases treated in community hospitals. Infect Dis Clin Pract 1993; 2: 41. 14 Sanabria TJ, Alpert JS, Goldberg R, Pape LA, Cheeseman SH. Increasing frequency of staphylococcal endocarditis. Experience at a
15 16 17 18 19
20 21 22 23 24
25
26 27 28 29 30 31 32
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university hospital, 1981 through 1988. Arch Intern Med 1990; 150: 1305±1309. Garvey GJ, Neu HC. Infective endocarditisÐan evolving disease. A review of endocarditis at the Columbia-Presbyterian Medical Center, 1968±1973. Medicine (Baltimore) 1978; 57: 105±127. Come PC. Infective endocarditis: current perspectives. Compr Ther 1982; 8: 57±70. Pelletier LL Jr, Petersdorf RG. Infective endocarditis: a review of 125 cases from the University of Washington Hospitals, 1963±1972. Medicine (Baltimore) 1977; 56: 287±313. Roberts WC, Buchbinder NA. Right-sided valvular infective endocarditis. A clinicopathologic study of twelve necropsy patients. Am J Med 1972; 53: 7±19. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilisation of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 1994; 96: 200±209. Bayer AS, Ward JI, Ginzton LE, Shapiro SM. Evaluation of new clinical criteria for the diagnosis of infective endocarditis. Am J Med 1994; 96: 211±219. Hoen B, Selton-Suty C, Danchin N et al. Evaluation of the Duke criteria versus the Beth Israel criteria for the diagnosis of infective endocarditis. Clin Infect Dis 1995; 21: 905±909. Sandre RM, Shafran SD. Infective endocarditis: review of 135 cases over 9 years. Clin Infect Dis 1996; 22: 276±286. Nettles RE, McCarty DE, Corey GR, Li J, Sexton DJ. An evaluation of the Duke criteria in 25 pathologically confirmed cases of prosthetic valve endocarditis. Clin Infect Dis 1997; 25: 1401±1403. Wilson WR, Karchmer AW, Dajani AS et al. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. American Heart Association. JAMA 1995; 274: 1706±1713. Bonow RO, Carabello B, de Leon AC Jr et al. Guidelines for the management of patients with valvular heart disease executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease). Circulation 1998; 98: 1949±1984. Mansur AJ, Grinburg M, da Luz PL, Bellotti G. The complications of infective endocarditis. A reappraisal in the 1980s. Arch Intern Med 1992; 152: 2428±2432. Netzer RO, Zollinger B, Seiler C, Cerny A. Infective endocarditis: clinical spectrum, presentation and outcome. An analysis of 212 cases 1980±1995. Heart 2000; 84: 25±30. Watanakunakorn C, Tan JS, Phair JP. Some salient features of Staphylococcus aureus endocarditis. Am J Med 1973; 54: 473±481. Musher DM, McKenzie SO. Infection due to Staphylococcus aureus. Medicine (Baltimore) 1977; 56: 383±409. Bayer AS. Staphylococcal bacteremia and endocarditis. State of the art. Arch Intern Med 1982; 142: 1169±1177. Thompson RL. Staphylococcal infective endocarditis. Mayo Clin Proc 1982; 57: 106±114. Cabell C, Abrutyn E. Towards a global database for IE-early lessons from ICE. Infectious Disease Clinics of North America 2002 June; in press.
Infective Endocarditis at a Tertiary Care Centre in Lebanon: Predominance of Streptococcal Infection Z. A. Kanafani, T. H. Mahfouz and S. S. Kanj* Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Centre, PO Box 113-6044, Hamra 110 32090, Beirut, Lebanon Objectives: Infective endocarditis (IE) remains a disease associated with high morbidity and mortality. Many epidemiological studies have been reported worldwide; however, data from the Middle East is scarce. Most studies have recently shown a trend towards increasing incidence of Staphylococcus aureus endocarditis and decreasing prevalence of rheumatic heart disease as a predisposing condition. Methods: We conducted a retrospective review of all recorded cases of IE in adult patients admitted between 1986 and 2001 to the American University of Beirut-Medical Centre. Results: The total number of cases was 91. The mean age was 48 years. Fifty-nine percent of patients had a predisposing cardiac condition, rheumatic heart disease being the most common (33%). Blood cultures were positive in 77.5% of the cases: the most commonly isolated organisms were Streptococcus spp. (51%; of which 57% were viridans streptococci.) and Staphylococcus spp. (36%; of which 72% were S. aureus and 28% were coagulase-negative staphylococci). Transoesophageal echocardiography was performed in 36 patients (40%), of which 32 (89%) showed positive findings. When applying the revised Duke criteria, 82% of the patients were classified as definite and 16.5% as possible endocarditis. Surgery was performed in 32% of cases mostly for valvular regurgitation, followed by heart failure. The complication rate was 69% with congestive heart failure, drug-related toxicities, new valvular regurgitation and systemic embolisation being the most common. The in-hospital mortality rate was 18%. Conclusions: Unlike data reported from the United States and northern Europe, this study confirms that in Lebanon, a developing country, we continue to have a predominance of streptococci as aetiologic agents in IE, and rheumatic heart disease as the most common underlying heart condition. Application of the revised Duke criteria was useful in confirming the diagnosis of IE. # 2002 The British Infection Society. Published by Elsevier Science Ltd. All rights reserved.
Introduction Infective endocarditis (IE) remains a relatively rare disease worldwide. An estimated 10,000±15,000 new cases of infective endocarditis (IE) are diagnosed each year in the United States [1]. However, the precise incidence of IE is difficult to ascertain because case definitions have varied over time, between authors, and among different medical centres. In a review of 10 large surveys, IE was responsible for 1 case per 1000 hospital admissions (range 0.16±5.4) [2]. Nevertheless, it is still associated with high morbidity and mortality rates and the incidence of predisposing conditions has varied over time and between different areas. A wealth of medical literature * Please address all correspondence to: Souha S. Kanj, Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Centre, PO Box 113-6044, Hamra 110 32090, Beirut, Lebanon. Tel.: 961-1-350000 ext 5353; Fax: 961-1-370814. E-mail address: [email protected]. (S. S. Kanj). 0163±4453/02/$35.00
has been devoted to the study of this condition. However, data from Lebanon and the surrounding region is scarce and the epidemiology of IE in this part of the world remains largely unknown. In fact, the only available epidemiological data from Lebanon has addressed the paediatric age group [3]; the authors have shown the importance of rheumatic heart disease as risk factor for IE, and reported an equal share for viridans streptococci and S. aureus as etiologic agents. Herein, we report the first study from Lebanon investigating IE in adult patients.
Materials and Methods Patients older than 13 years admitted to the American University of Beirut-Medical Centre (AUB-MC) between January 1, 1986 and April 30, 2001 with the discharge diagnosis of IE were included in the analysis. AUB-MC is one of two tertiary care referral centres in Beirut; it serves a large proportion of the population of Beirut and
# 2002 The British Infection Society. Published by Elsevier Science Ltd. All rights reserved.
Infective Endocarditis at a Tertiary Care Centre the surrounding regions. Patients were treated by a cardiologist and/or an Infectious Disease specialist. Relevant clinical and laboratory data, as well as echocardiographic findings were recorded from the patients' medical records.
Statistical methods Data were collected and entered into a database using Microsoft1 Access 2000. Statistical analysis was conducted using SPSS 10.0 for Windows and Microsoft1 Excel 2000. When applicable, phi coefficient, Cramer's V, contingency coefficient and chi-square test were performed. Odds ratios were calculated from two-by-two contingency tables and the respective 95% confidence intervals were obtained.
Definitions In this study, we used the revised Duke criteria for the diagnosis of infective endocarditis to validate our results (Tables I and II).
Table I. Definition of infective endocarditis according to the modified Duke criteria.y Definite infective endocarditis Pathologic criteria (1) Microorganisms demonstrated by culture or histologic examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen; or (2) Pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis Clinical criteria* (1) 2 major criteria; or (2) 1 major criterion and 3 minor criteria; or (3) 5 minor criteria Possible infective endocarditis (1) 1 major criterion and 1 minor criterion; or (2) 3 minor criteria Rejected (1) Firm alternate diagnosis explaining evidence of infective endocarditis; or (2) Resolution of infective endocarditis syndrome with antibiotic therapy for < 4 days; or (3) No pathologic evidence of infective endocarditis at surgery or autopsy, with antibiotic therapy for < 4 days; or (4) Does not meet criteria for possible infective endocarditis, as above * See Table II for definitions of major and minor criteria. y Li JS, Sexton DJ, Mick N, Nettles R et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000; 30: 633±638.
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Results Patient characteristics Ninety-one patients with a discharge diagnosis of IE were identified. The male to female ratio was 1.8:1. The mean age was 48 years (range 13±87 years). Thirty patients (33%) were known to have one or more chronic illnesses, the most common of which was diabetes mellitus followed by hypertension (Table III). Endocarditis was acquired nosocomially in 8 patients (9%). Dental procedures were performed in 17 patients (19%) within 3 months of presentation. At the beginning of the current episode of IE, 10 patients (11%) had intravenous lines and/or central venous catheters. The cases were equally distributed throughout the study period ranging from January 1986 to April 2001. The overall number of admissions to AUB-MC during that period of time was 295,878; so IE was responsible for 3 cases per 10,000 hospital admissions. The total number of patients admitted was 184,728Ðsome patients were admitted more than once, making the incidence of IE in the hospitalized population at our centre 5 cases per 10,000 patients.
Underlying heart lesions Overall, 54 patients (59%) had an underlying cardiac condition, the most common being rheumatic heart disease (RHD) in 30 cases (33%); only 11 patients (12%) had previously documented normal echocardiographs. Concerning the initial valve status, 18 patients (20%) had prosthetic valves; 30 patients (33%) had rheumatic valves and 16 (18%) were known to have normal valves. In addition, congenital heart lesions were present in 12 patients (13%).
Clinical manifestations (Table IV) The most frequent symptoms on presentation were fever in 83 cases (91%) with a mean of 39.4 C (range 38.1±42 C), chills in 49 (54%), night sweats in 36 (40%), weight loss in 31 (34%), dyspnoea in 31 (34%), and headaches in 31 cases (34%). On physical examination, splenomegaly was reported in 23 cases (25%), Roth spots in 15 (16%), hepatomegaly in 14 (15%) and Osler nodes in only 2 cases (2%). On cardiac auscultation, 19 patients (21%) had a new murmur and 15 (16%) had a worsening murmur. Twenty-nine patients (32%) were found to have vascular phenomena: 14 (15%) had strokes or transient ischaemic attacks
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Z. A. Kanafani et al. Table II. Definition of terms used in the modified Duke criteria for the diagnosis of infective endocarditis (IE)y. Major criteria Blood culture positive for IE Typical microorganisms consistent with IE from 2 separate blood cultures: Viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or Community-acquired enterococci, in the absence of a primary focus; or Microorganisms consistent with IE from persistently positive blood cultures, defined as follows: At least 2 positive cultures of blood samples drawn >12 h apart; or All of 3 or a majority of >4 separate cultures of blood (with first and last sample drawn at least 1 h apart) Single positive blood culture for Coxiella burnetii or antiphase IgG antibody titer >1:800 Evidence of endocardial involvement Echocardiogram positive for IE (TEE recommended in patients with prosthetic valves, rated at least `possible IE' by clinical criteria, or complicated IE [paravalvular abscess]; TTE as first test in other patients), defined as follows: Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; or Abscess; or New partial dehiscence of prosthetic valve New valvular regurgitation (worsening or changing of pre-existing murmur not sufficient) Minor criteria Predisposition: predisposing heart condition or injection drug use Fever: temperature >38 C Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial haemorrhage, conjunctival haemorrhages, and Janeway's lesions Immunologic phenomena: glomerulonephritis, Oslers nodes, Roth spots, and rheumatoid factor Microbiological evidence: positive blood culture but does not meet a major criterion as noted above* or serological evidence of active infection with organism consistent with IE Echocardiographic minor criteria eliminated TEE transoesophageal echocardiography; TTE transthoracic echocardiography. *Excludes single positive cultures for coagulase-negative staphylococci and organisms that do not cause endocarditis. yLi JS, Sexton DJ, Mick N, Nettles R, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000; 30: 633±638.
Table III.
General characteristics of patients.
Characteristic
Value
No. of patients Age in years (mean SD) Sex (male:female) Chronic illness (no. of patients) Cancer CAD/CHF Diabetes Hypertension Immunosuppression Chemotherapy Steroids Renal failure Haemodialysis
91 48 19 1.8:1 30 4 6 9 8 4 2 2 4 2
SD standard deviation; CAD coronary artery disease; CHF congestive heart failure.
(TIA), 13 (14%) had systemic embolisations, and 6 (7%) had Janeway lesions. Laboratory findings Anaemia was present in 71 (78%) and leukocytosis in 47 patients (52%). An elevated erythrocyte sedimentation
rate (ESR) was present in 91%, with a mean of 82 (range 20±150). Furthermore, rheumatoid factor (RF) was positive in 64%, C-reactive protein (CRP) in 83% and haematuria in 37.5% of patients for whom these tests were requested.
Microbiology Blood cultures were taken in 89 patients and were positive in 69 cases (77.5%) (Table V). There were 35 isolates of Streptococcus spp, which accounted for the majority of recovered organisms (51%); 20 (57%) of these were identified as viridans streptococci. The second most commonly isolated organisms were staphylococci in 25 cases (36%); out of the 25 isolates of staphylococci, 7 were coagulase-negative and 18 were S. aureus, 5 (28%) of which were methicillin-resistant. Other isolates included Pseudomonas spp., Enterococcus spp., Enterobacter cloacae, Neisseria mucosa and candida non-albicans. Valves were cultured in 24 patients (26%) and were positive in 2: one grew coagulase-negative staphylococci and the other grew Trichosporon beigelii. Other cultures yielding growth included bone marrow, catheter tips,
Infective Endocarditis at a Tertiary Care Centre Table IV. Clinical manifestations and laboratory findings from the current study compared to data from other studies.
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Table V. Distribution of organisms recovered from blood cultures of patients with infective endocarditis.
Percentage of patients affected
Organism
No. of isolates n 6
Current study
Other studies*
54 34 40 35 33
40 25 25 40 20
91 2 3 16 24 12 9
90 10±23 15 2±10 20±57 3±5 5±10
Vascular phenomena Stroke Janeway lesions Systemic embolisation Mycotic aneurysms
12 7 14 1
20 <10 >50 20
Streptococci alpha-haemolytic viridans S. others beta-haemolytic Staphylococci S. aureus MSSA MRSA Coagulase-negative staphylococci Enterococci E. faecalis Unspecified Pseudomonas spp. P. aeruginosa P. stutzeri Enterobacter cloacae Neisseria mucosa Candida non-albicans
35 33 18 15 2 25 18 13 5 7 3 1 2 3 1 2 1 1 1
Laboratory findings Anaemia Leukocytosis Elevated ESR Positive RF Haematuria
78 52 91 64 37.5
70±90 20±30 90±100 40±50 30±60
Symptoms Chills Weight loss Night sweats Dyspnoea Headache Signs Fever Osler nodes Splinter haemorrhages Retinal lesions Splenomegaly New murmur Changing murmur
ESR erythrocyte sedimentation rate; RF rheumatoid factor. * Adapted from: Bayer AS, Scheld WM. Endocarditis and intravascular infections. In: Mandell GL, Bennett JE, Dolin R (eds) Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 5th edn. Philadelphia: Churchill Livingstone, 2000: 857±884.
cerebrospinal fluid, pleural fluid, abdominal abscess and wound cultures. All these specimens yielded the same organisms isolated from blood. One patient had positive serology for brucella and was thought to have brucella endocarditis. Overall, the incriminating organism for IE was identified in 71 patients (78%), 69 by blood cultures and/or valve/other cultures, one by valve culture and another by serology. Echocardiography Echocardiography was performed in 89 patients, transthoracic echocardiography (TTE) in 82 (90%) and transoesophageal echocardiography (TEE) in 36 patients (40%). Both studies were done in 29 patients (32%). Echocardiography findings defined as positive included presence of vegetation, new valvular regurgitation, intracardiac abscess, fistulous tract, ruptured chordae, valve perforation, new perivalvular leak or valve dehiscence. TTE was positive in 51/82 (62%) and TEE in
MSSA methicillin-sensitive S. aureus; MRSA methicillin-resistant S. aureus. Table VI. Results of echocardiography in 29 patients who underwent both TTE and TEE. TEE (no.) Positive
Negative
Total
TTE (no.) Positive Negative Total
14 12 26
1 2 3
15 14 29
Sensitivity 53.8% Specificity 66.7%
PPV 93.3% NPV 14.3%
TTE transthoracic echocardiography; TEE transoesophageal echocardiography; PPV positive predictive value; NPV negative predictive value.
32/36 cases (89%). Overall, echocardiography was positive in 71/% patients (80%). Vegetations were seen in 61 (68.5%), new valvular regurgitations in 16 (18%) and perivalvular complications (perforation, abscess, fistulous tract, valve dehiscence, new perivalvular leak) in 19 patients (21%). The mitral valve alone was involved in 37 (42%) and the aortic valve in 23 patients (26%); there was disease on both valves in 8 patients (9%). In addition, the tricuspid valve was affected in 6 cases (7%). None of the patients had pulmonic valve involvement. One patient had concomitant right- and left-sided endocarditis. Pericardial effusion was observed in 12 cases (13%). Tables VI and VII illustrate the findings of TTE in comparison to TEE in the subset of patients who underwent both echocardiographic
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Table VII. Detailed comparison between findings on TTE versus TEE in 29 patients who underwent both echocardiographic modalities.
Table VIII. Complications and mortality observed in patients with infective endocarditis.
Location of vegetations
Complication
% of patients
Death Heart failure Drug-related toxicities Rise in serum creatinine New valvular regurgitation Systemic embolization Spleen Vascular periphery Kidney Stroke Embolic Haemorrhagic Intracardiac abscess TIA New conduction abnormality Other complications
17.6 27.5 19.8 15.4 17.6 14.3 6.6 4.4 4.4 12.1 8.8 3.3 11 3.3 3.3 16.5
TTE Pos 4
MV
2
AV TV
TEE Def
4
2
1
Intracardiac
1
Chordae
1
Perivalvulvar complications*
4
No
Def
No 1
21
3 4 6
25
1 2 5
19
28
2
1 26
29
1 1
27
Pos
1
1 2
15 1
28
25
13
TTE transthoracic echocardiography; TEE transoesophageal echocardiography; MV mitral valve; AV aortic valve; TV tricuspid valve; Pos possible; Def definite. * Perivalvular complications include: valve perforation, abscess formation, fistulous tract, valve dehiscence, or new perivalvular leak.
modalities. The sensitivity of TTE in this study was 54%. We report a positive predictive value of TTE versus TEE of 93% however, the negative predictive value is only 14%. Classification When applying the revised Duke criteria (Tables I and II) for the diagnosis of IE, 75 patients (82%) were classified as definite and 15 (16.5%) as possible endocarditis. One case did not fulfill the Duke criteria but could not be rejected and was treated for IE because of the high clinical suspicion. In 7 patients (8%), the definitive diagnosis of IE was confirmed by valve pathology or culture; in all 7 patients, echocardiography showed abnormal findings. Treatment The mean duration of antibiotic therapy was 40 days (range 0±429 days). In patients with streptococcal endocarditis, 17 (49%) received a combination of penicillin and an aminoglycoside and 17 (49%) received penicillin alone. Patients with staphylococcal endocarditis were treated most commonly with vancomycin, alone or with an aminoglycoside in 12 cases (48%) or a combination of a penicillinase-resistant penicillin and an aminoglycoside in 7 cases (28%). In 7 patients (28%),
TIA transient ischaemic attack.
rifampin was added to the antibiotic regimen for synergy. Forty-four patients (64%) without a microbiological diagnosis received an empiric regimen consisting of penicillin and an aminoglycoside. Surgery was performed in 29 patients (32%). In addition, in 3 patients surgical intervention was clearly indicated but was not done because of the high operative risk. The most commonly encountered indications for surgery were valvular regurgitation in 25 (27.5%), heart failure in 15 (16.5%) and intracardiac abscess formation in 7 patients (8%). Other indications included systemic embolisation, valve dehiscence, ventricular septal defect, failure of medical treatment, mitral valve thrombosis, severe aortic stenosis and ruptured chordae. In 25 patients (86%), the decision to operate was based on more than one factor. The mean duration of stay in hospital was 33 days (range 1±180 days). Complications and outcome Complications occurred in 63 patients (69%) (Table VIII), the most common of which were congestive heart failure in 25 cases (27.5%), drug-related toxicities in 18 (20%), new valvular regurgitation in 16 (18%), systemic embolisation in 13 (14%), stroke in 11 (12%) and intracardiac abscess in 10 cases (11%). Other complications of IE included new conduction abnormalities, pericarditis and pericardial tamponade, atrial fibrillation, ventricular fibrillation, glomerulonephritis, meningitis, encephalitis, phlebitis, pneumonia, respiratory failure, renal failure, and relapse of disease. Embolisations involved the spleen, vascular periphery, kidney, lung,
Infective Endocarditis at a Tertiary Care Centre retina and penis. Drug toxicities and complications related to treatment consisted most commonly of aminoglycoside-induced nephrotoxicity in 14 cases (15%). Other drug-related side effects included interstitial nephritis, nausea and vomiting, and allergic reactions. Overall, 16 patients passed away, bringing the in-hospital mortality rate to 18%. In 6 cases (37.5%), the etiologic organism was S. aureus; and over 6 patients (33%) with S. aureus endocarditis died.
Discussion Infective endocarditis presents a challenge to physicians from all specialties; it manifests in so many diverse and confusing ways. However, advances in echocardiography and surgical techniques have given us additional diagnostic and therapeutic tools to manage this infection. Changes in the epidemiology and microbiology of IE continue to occur. Over the last thirty years, IE has been most commonly seen in older age groups, with a predominance of male patients and an increased incidence of acute cases caused by virulent organisms such as S. aureus, gram-negative bacilli and fungi. On the other hand, cases caused by oral streptococcal spp. are on the decrease. The patient population is also changing; most of these changes relate to the numbers and types of susceptible hosts, with an increased number of IE diagnosed in the setting of intravenous drug abuse (IVDA), prosthetic valves, arteriovenous shunts for haemodialysis, and Human Immunodeficiency Virus (HIV) infection. In addition, IE is increasingly described as a nosocomial infection, acquired in the hospital setting due to advances in medical technology (vascular devices, intravenous catheters, invasive procedures, and so forth) that have increased the risk of bacteraemia and related complications [4]. When comparing our results with other reports, the male to female ratio was in agreement with most case series [2]. However, our patient population was relatively young, unlike recent reports from the United States showing that more than one-half of all IE cases were seen in patients over the age of 60, with a steady increase in the median age [5]. This trend in the developed countries is likely due to two factors: the increasing proportion of elderly subjects in the general population and the decline in the incidence and importance of RHD as a risk factor. In fact, recent studies from developed countries showed a decline of RHD as the underlying structural heart abnormality in patients with IE from 37±76% in the past to 25% or less in the last two decades [2,6]. In contrast, our study showed that RHD
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was the most common underlying cardiac condition. A recent study from Israel showed similar trends [7]. The incidence of prosthetic valve endocarditis (PVE) was much higher than reports from the western world [4]. Only 19% of the patients in this study had undergone dental procedures within 3 months of hospital admission, as compared to 23% reported in a recent casecontrol study [8]. However, the distribution of organisms in these patients was similar to those without prior dental procedures. We did not observe any trend in the number of cases reported each year, and there was no statistically significant difference in the risk factors for endocarditis over the study period. This implies that, with the absence of IVDA and HIV infection among our patients, no new predisposing factors have emerged over the years to alter the incidence or the epidemiology of IE in this country. A comparison between the clinical manifestations of IE in our study and in other reports from the literature [9] is shown in Table IV. The various signs and symptoms were comparable except for a lower incidence of systemic embolisation in our study. We found no correlation between the occurrence of vascular phenomena and the presence of vegetation by echocardiography, however on further analysis, there was a statistically significant increase in the incidence of vascular phenomena in patients who had mitral valve vegetations (odds ratio, 2.6; 95% confidence interval, 1.1±6.6). Patients who had one or more of the following findings including; splenomegaly, hepatomegaly, elevated ESR, positive CRP, haematuria, anaemia and leukocytosis were more likely to be later classified as definite rather than possible endocarditis (odds ratio, 17.08; 95% confidence interval, 1.7±177.1). None of these clinical findings are specific for IE, which is why they are not included as minor criteria in the revised Duke criteria for IE; yet they might have some importance in diagnostically challenging cases. In this study, the yield of positive blood cultures (77.5%) was lower than the rate of over 90% reported from a review of 206 cases of IE seen over a 15-year period at a New York hospital [10]. Unlike several reports from developed countries of increasing incidence of staphylococcal endocarditis [11±14], there was a predominance of streptococcal isolates in our series, which could be explained by the high prevalence of RHD as underlying cardiac disease in our community, as well as by the absence of IVDA and HIV infection among our patients. This finding is also supported by other reports from developing countries [7]. Over the last 20 years, the use of echocardiography has been instrumental in confirming the diagnosis of
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endocarditis. The sensitivity of TTE in this study was 62% and is within the reported range of 50±75% from other studies. The low negative predictive value confirms that TEE would be essential to the diagnosis of IE when TTE is normal. It should be kept in mind, however, that echocardiography is an operator-dependent diagnostic modality; the sensitivity and specificity that we report are therefore affected by the multiplicity of the echocardiographers (3 in total), especially that the echocardiogram results were recorded from the patients' medical records and were not re-reviewed for the purpose of this study. The distribution of involved valves with a predominance of mitral valve disease is also similar to previous studies in the literature [15±18]. Despite reports from the literature linking the presence of intravenous catheters to right-sided endocarditis, in this study, there were no tricuspid or pulmonary valve vegetations in any of the 10 patients who had intravenous catheters at the time of diagnosis of IE. The diagnosis of infective endocarditis is usually based upon a constellation of clinical findings rather than upon a single definitive test result. The Duke criteria (Tables I and II) are valuable in assisting clinicians with the diagnosis of IE; in 1994 investigators from Duke University modified the old von Reyn criteria to include the role of echocardiography in diagnosis. Multiple studies have since validated the Duke criteria and compared their utility to that of the von Reyn criteria [19±23]. Each of these reports evaluated patients in whom the diagnosis of IE was established. When applying the Duke criteria to validate our cases, all patients, except for one, fell into the possible or definitive diagnosis, once again confirming the value of these criteria in the clinical diagnosis of endocarditis. The antibiotic therapy used in our patients conforms in most cases to the guidelines of the American Heart Association for the treatment of IE [24]. However, there was overuse of glycopeptide antibiotics unjustified by the low percentage of methicillin-resistant staphylococcal isolates. In the era of emergence of antibiotic resistance, the misuse and abuse of glycopeptides is highly discouraged. In certain clinical situations, a combined medical and surgical approach is necessary for the successful treatment of IE. During the last three decades, valve replacement and repair have become commonplace in the management of selected complications of IE, and the combination of antibiotic therapy and timely surgical intervention has substantially reduced the mortality from IE. Our results demonstrate that 32% of the cases of IE have required surgical intervention. Reports in the literature quote a figure of at least 25%. Over time,
the indications for surgery have expanded and valve replacement surgery has been undertaken progressively earlier in the course of the illness. The indications for surgery in our patients were consistent with the guidelines of the American College of Cardiology/American Heart Association, namely congestive heart failure, systemic embolic events, significant valve dysfunction, failure of medical therapy and perivalvular complications such as abscess formation [25]. A myriad of complications can result from IE and occur in the majority of patients. Our data indicate that 31% of patients had one complication, 29% two, and 10% three or more complications. We also established that patients who had echocardiographic evidence of vegetations were at a higher risk of developing systemic vascular embolisation than patients who had no vegetations demonstrable by echocardiography (odds ratio, 5.9; 95% confidence interval, 1.3±27.4). For comparison, it is difficult to assess the true incidence of complications of IE in other studies because of the retrospective nature of most reports and the different diagnostic criteria used to define cases of IE. Moreover, the frequency of specific complications depends upon the infecting pathogen, duration of illness prior to therapy, and the type of treatment facility (e.g. referral versus community hospital). All complications described in our study were reported in the literature; in a review of 223 episodes of IE, 57% of patients had one complication, 26% two, and 8% three or more complications [26]. The in-hospital mortality in this study is comparable to the 15% reported in a retrospective study of 212 cases of IE [27]. It is noteworthy that the high mortality rate in our cases of S. aureus endocarditis is consistent with other reports in the literature quoting a figure of at least 40% [28±31]. There was no significant difference in mortality based on the valve involved.
Conclusion This study describes the clinical presentation, microbiology, complications and treatment of adult patients with infective endocarditis admitted to a university hospital in Lebanon. RHD remains the most important predisposing cardiac condition. This finding has important implications for antibiotic prophylaxis prior to invasive procedures. Moreover, and as opposed to other recent series, we continue to have a predominance of streptococci in IE. The main limitation of this study is its retrospective design; some patient records were incomplete and this has impeded the process of data collection to a certain extent. IE, however, is a rare disease entity
Infective Endocarditis at a Tertiary Care Centre and devising a one-centre prospective trial would be fairly difficult. Future studies should be therefore designed to prospectively follow patients with IE from different centres in the country; this would allow us to assess for homogeneity of the patient population in Lebanon with respect to risk factors for endocarditis and the microbiology of the disease. A large prospective multinational, multi-centred study is highly desirable, and is currently underway with the International Collaboration on Endocarditis (ICE) study. AUB-MC is one of over 30 centres from 13 countries participating in ICE, with the aim to establish an international database for endocarditis [32].
References 1 Bayer AS. Infective endocarditis. Clin Infect Dis 1993; 17: 313±320. 2 Harris SL. Definitions and demographic characteristics. In: Kaye D, ed. Infective Endocarditis. Raven Press, 1992; 1. 3 Bitar FF, Jawdi RA, Dbaibo GS et al. Paediatric infective endocarditis: 19-year experience at a tertiary care hospital in a developing country. Acta Paediatr 2000; 89: 427±430. 4 Berlin JA, Abrutyn E, Strom BL et al. Incidence of infective endocarditis in the Delaware Valley, 1998±1990. Am J Cardiol 1995; 76: 933±936. 5 Cantrell M, Yoshikawa TT. Infective endocarditis in the aged patient. Gerontology 1984; 30: 316±326. 6 Kaye D. Changing pattern of infective endocarditis. Am J Med 1985; 78(suppl 6B): 157±162. 7 Borer A, Riesenberg K, Uriel N et al. Infective endocarditis in a tertiary-care hospital in southern Israel. Public Health Rev 1998; 26: 317±330. 8 Strom BL, Abrutyn E, Berlin JA et al. Dental and cardiac risk factors for infective endocarditis. A population-based, case-control study. Ann Intern Med 1998; 129: 761±769. 9 Bayer AS, Scheld WM. Endocarditis and intravascular infections. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 5th edn. Churchill Livingstone, 2000; 857±884. 10 Werner AS, Cobbs CG, Kaye D et al. Studies on the bacteremia of bacterial endocarditis. JAMA 1967; 202: 199±203. 11 Watanakunakorn C, Burkert T. Infective endocarditis at a large community teaching hospital, 1980±1990. A review of 210 episodes. Medicine (Baltimore) 1993; 72: 90±102. 12 Kim EL, Ching DL, Pien FD. Bacterial endocarditis at a small community hospital. Am J Med Sci 1990; 299: 87±93. 13 Kazanjian PH. Infective endocarditis: review of sixty cases treated in community hospitals. Infect Dis Clin Pract 1993; 2: 41. 14 Sanabria TJ, Alpert JS, Goldberg R, Pape LA, Cheeseman SH. Increasing frequency of staphylococcal endocarditis. Experience at a
15 16 17 18 19
20 21 22 23 24
25
26 27 28 29 30 31 32
159
university hospital, 1981 through 1988. Arch Intern Med 1990; 150: 1305±1309. Garvey GJ, Neu HC. Infective endocarditisÐan evolving disease. A review of endocarditis at the Columbia-Presbyterian Medical Center, 1968±1973. Medicine (Baltimore) 1978; 57: 105±127. Come PC. Infective endocarditis: current perspectives. Compr Ther 1982; 8: 57±70. Pelletier LL Jr, Petersdorf RG. Infective endocarditis: a review of 125 cases from the University of Washington Hospitals, 1963±1972. Medicine (Baltimore) 1977; 56: 287±313. Roberts WC, Buchbinder NA. Right-sided valvular infective endocarditis. A clinicopathologic study of twelve necropsy patients. Am J Med 1972; 53: 7±19. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilisation of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 1994; 96: 200±209. Bayer AS, Ward JI, Ginzton LE, Shapiro SM. Evaluation of new clinical criteria for the diagnosis of infective endocarditis. Am J Med 1994; 96: 211±219. Hoen B, Selton-Suty C, Danchin N et al. Evaluation of the Duke criteria versus the Beth Israel criteria for the diagnosis of infective endocarditis. Clin Infect Dis 1995; 21: 905±909. Sandre RM, Shafran SD. Infective endocarditis: review of 135 cases over 9 years. Clin Infect Dis 1996; 22: 276±286. Nettles RE, McCarty DE, Corey GR, Li J, Sexton DJ. An evaluation of the Duke criteria in 25 pathologically confirmed cases of prosthetic valve endocarditis. Clin Infect Dis 1997; 25: 1401±1403. Wilson WR, Karchmer AW, Dajani AS et al. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. American Heart Association. JAMA 1995; 274: 1706±1713. Bonow RO, Carabello B, de Leon AC Jr et al. Guidelines for the management of patients with valvular heart disease executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease). Circulation 1998; 98: 1949±1984. Mansur AJ, Grinburg M, da Luz PL, Bellotti G. The complications of infective endocarditis. A reappraisal in the 1980s. Arch Intern Med 1992; 152: 2428±2432. Netzer RO, Zollinger B, Seiler C, Cerny A. Infective endocarditis: clinical spectrum, presentation and outcome. An analysis of 212 cases 1980±1995. Heart 2000; 84: 25±30. Watanakunakorn C, Tan JS, Phair JP. Some salient features of Staphylococcus aureus endocarditis. Am J Med 1973; 54: 473±481. Musher DM, McKenzie SO. Infection due to Staphylococcus aureus. Medicine (Baltimore) 1977; 56: 383±409. Bayer AS. Staphylococcal bacteremia and endocarditis. State of the art. Arch Intern Med 1982; 142: 1169±1177. Thompson RL. Staphylococcal infective endocarditis. Mayo Clin Proc 1982; 57: 106±114. Cabell C, Abrutyn E. Towards a global database for IE-early lessons from ICE. Infectious Disease Clinics of North America 2002 June; in press.