ORIGINAL ARTICLE

THE PATTERN OF INFECTIVE ENDOCARDITIS IN A TERTIARY CARE 
HOSPITAL IN OMAN:  A TEN-YEAR PROSPECTIVE STUDY

K.J.Suleiman, FRCPI, P.Prashanth MD 
Department of Cardiology, Royal Hospital, Muscat, Oman.

Abstract

Background:  The previous 50 years have seen major changes in the epidemiology of infective endocarditis (IE).
Aim:  To evaluate local risk factors, clinical manifestations, microbiology, echocardiographic features, morbidity and mortality in patients with definite IE.
Design:  Prospective observational study.
Method: Over a ten year period, patients referred with probable IE were evaluated.  All had received a standardized diagnostic evaluation as per department protocol. Epidemiological data were documented; underlying risk factors for IE were noted.  Initial evaluation and follow-up included documentation of vascular or immunological phenomena, morbidity and mortality.
Results:  Of 90 patients referred with probable IE, 50 had definite IE.  The mean age was 36 yrs with a male predominance (1.2:1).  Rheumatic heart disease was present in 20 (40%).  Eight had mitral valve prolapse and congenital heart disease respectively, and three had prosthetic valves.  All had denied the use of intravenous recreational drugs and 11 had normal valve endocarditis.  Cardiac murmur (98%) and fever (96%) were commonly observed.  Six patients had renal involvement and ten patients had embolic episodes.  Vegetations were seen in 80% of patients.  70% were managed medically, 10% surgically, and mortality was 20%.  An etiological diagnosis was made in 29 patients with viridans streptococci the most common isolate.
Conclusions:  Infective endocarditis in Oman is a disease of younger adults, with a male predominance. Rheumatic heart disease is the major predisposing factor.  Degenerative heart disease and intravenous drug abuse are not important risk factors.  Local mortality rates are similar to published rates but the proportion of “culture-negative” IE was higher. Large vegetations were important prognostically.
Heart Views. 2003;4(3):89-93 © 2003 Gulf Heart Association

Key words: Infective endocarditis Rheumatic heart disease vegetations

Introduction

   The later part of the 20th century has seen predominant changes in the epidemiology, bacteriology and clinical presentation of infective endocarditis and major advances in the diagnosis and management of this disease (1,2).  The changes observed in the patient profile of the disease in the developed world, as well as decline in “culture-negative” endocarditis have been highlighted extensively.  IE was previously described as a disease of younger adults with underlying rheumatic heart disease (RHD), but now its distribution has shifted as a disease of older patients with a different spectrum of risk factors and clinical sequelae (1).  Changes in patient profile have largely been attributed to a declining incidence of rheumatic fever, a greater prevalence of degenerative heart disease and accompanying increased longevity, intravenous drug abuse, the increasing number of patients with prosthetic valves, and longer survival of patients with congenital heart disease(1).

   Despite the high prevalence of rheumatic heart disease in Oman, few data have been published on the epidemiological relationship of infective endocarditis and rheumatic heart disease or any other potential risk factors seen in Oman.  In this study, patients with infective endocarditis (IE) were evaluated with regard to epidemiological characteristics, identifiable risk factors and their clinical presentation, microbiology, morbidity, and mortality.

Methods

   All patients referred to the Department of Cardiology , Royal Hospital with the presumptive diagnosis of IE were studied prospectively over a period of ten years between 1992 to 2002. IE was diagnosed according to the Duke’s criteria (3) from 1994.

   Royal Hospital is a 650-bed teaching hospital in Muscat,Oman.

Diagnostic evaluation

   All subjects were clinically evaluated on the day of referral, and daily while in hospital thereafter.  Baseline characteristics were collected and a detailed history was taken. Specific attention was paid to potential risk factors, which included a history of previous rheumatic fever or valvular heart disease, previous infective endocarditis, congenital heart disease, mitral valve prolapse, cardiac surgery (valve replacement or repair), intravenous drug use, degenerative heart disease, indwelling intravenous catheters, medical or surgical procedure at risk of bacteremia within one month prior to hospitalization or other potential risk factors.  During the physical examination, the presence or absence of any vascular or immunological phenomena (as defined by the Duke criteria) were actively sought and documented.

   During the evaluation, three blood cultures for aerobic/anaerobic organisms were taken from three different sites, approximately half an hour apart.  Any exposure to oral or intravenous antibiotics during the two days prior to the attainment of blood cultures was documented.  All patients were examined by transthoracic echocardiography using Hewlett Packard S 1500.  Vegetations were defined according to Duke criteria. Transesophageal echocardiography (TEE) was performed in 30 patients.  Further investigations included an ECG, full blood count, ESR, routine biochemistry, Serology [C-reactive protein (CRP), Rheumatoid factor, Antinuclear factor], and urinalysis.

   The microbiology department of Royal Hospital performed all microbiological investigations.  Organisms were identified by standard laboratory practices.  Finally, the Duke criteria (as published in 1994) were strictly applied to classify all patients as either “definite”, “possible” or “rejected” infective endocarditis.

Patient management

   All patients were managed according to published guidelines(4,5,6).  Cultures and antimicrobial susceptibility testing guided the choice of antibiotics, whereas empirical therapy was given to culture-negative cases.  Patients who presented with subacute form of IE of native valves generally received 4-6 weeks IV penicillin G (20 MU/day ) or ampicillin IV (12Gm/day) and gentamicin (1mg/kg q8h IV x 2 weeks ), whereas cloxacillin IV (12Gm/day) was added to the treatment in those presenting with more acute disease. The B-lactam antibiotics were substituted by vancomycin if methicillin-resistant staphylococci were suspected or if penicillin allergy.  

   Prosthetic valve endocarditis was treated with a combination of intravenous vancomycin and oral rifampicin for 6 weeks in combination with intravenous gentamicin for the first 2 weeks.

   In culture-negative endocarditis, antibiotics were given for 6 weeks.  All patients were seen daily while in hospital and at 3 and 6 months after discharge.

Statistical analysis

   Collected data were stored in a Microsoft Access database.  The baseline characteristics of all patients were evaluated to identify known risk factors and to calculate the mean age and gender distribution.  Morbidity parameters were documented to attain their relative frequency in definite IE.  Patients lost to follow-up were excluded from the analysis of 6 month crude mortality rate.

Results

   Ninety patients with suspected IE were evaluated during the study period.  Of these, 50 were ultimately diagnosed as having definite IE.  Mean duration of hospital stay was 40+/-10 days.  Baseline characteristics and clinical manifestations are summarized in Table 1 and 2 respectively.

Table 1 . Baseline Characteristics (50 Patients)

Table 2. Clinical Manifestations (50 Patients)

   An etiological diagnosis was reached in 29 of 50 patients.  The positive blood cultures yielded the following organisms: viridans streptococci (n=16, 32%), staphylococci (n=10, 20%) and gram negative bacilli (n=3, 6 %).  Of the remaining 21 patients with culture negative IE, all had received oral or intravenous antibiotics during 48hrs preceding collection of blood cultures, whereas only 4 of 29 patients with positive blood cultures had received antimicrobial agents.  Figure 1 represents etiological diagnosis in 29 patients.

Fig.1.  Etiological diagnosis

   Echocardiography (TTE +/-TEE) was done in all 50 patients, vegetations were found in 40(80%) patients. Locations of vegetations were: native aortic valve 16 patients, native mitral valve 13 patients, combined native aortic and mitral valve 8 patients and prosthetic valves 3 patients.  21 of these patients had vegetation of > 10 mm.  After evaluating various variables, 70% of all hospital deaths, 75% of those with embolic manifestations and 100% of those requiring early surgery were among patients with large vegetation size > 10mm(7,8).

Prognosis

   Thirty-five of 50 patients (70%) were managed medically and improved on antibiotics, 5 patients (10%) needed valve replacement.  The six-month crude mortality rate of patients with definite IE was 20% including 2 patients operated and expired.  Among three patients with prosthetic valve endocarditis one needed redo valve replacement. Figure 2 represents prognosis in 50 patients.

Fig. 2. Prognosis

Discussion

Risk factors

   Patients with definite IE had a mean age of 36 years (SD 11 years ).  40% of patients with native valve endocarditis had rheumatic heart disease, which is comparable to other studies with similar incidence (7).  Previous studies in the developed world have reported more than half of all new cases of infective endocarditis occur in patients older than 50 years with RHD implicated in < 25% (1,2,11).  In our series, the incidence of RHD was much higher.  In the USA, it has been reported that mitral valve prolapse is the most common underlying abnormality in patients with IE.  (1) Intravenous drug abuse and degenerative heart disease are two commonly seen risk factors for IE in the US, which was not seen in our series.

   A number of large studies (5) reported that IE occurs more commonly in men, with a male:female ratio of 1.7:1 (range 1.0 -3.0: 1) and the ratio of 1.2 :1 in our study confirms this discrepancy in gender-associated risk.

Microbiology

   50 of the 90 patients enrolled satisfied the Duke criteria for definite IE, but an etiological diagnosis could be established in 58% of these cases.  In the USA, culture negative endocarditis constitutes only 2.5 - 30% of all IE diagnosed, while in the Netherlands, this figure is even as low as 1.1% (1).  We found that all 21 patients with culture negative IE had been exposed to antibiotics within 48 hrs prior to blood culture sampling.

   Contrary to the trends observed in industrialized countries (Group D streptococci / staphylococci ) (1,2,9), viridans streptococci was still the most common isolate in our study, probably due to poor dental health.  Staphylococcus epidermidis was isolated in patients with prosthetic valve endocarditis.

Clinical presentation, morbidity and mortality

   According to published data, 10% or more of patients with definite IE do not have an audible cardiac murmur (5), whereas 98% of patients with definite IE in this study presented with a cardiac murmur on auscultation.  The reasons for this discrepancy may reflect the differences in epidemiology and risk factors profile of our patients.

   We found immunological phenomena (Table 2) to be common and in keeping with the subacute presentation of IE seen in the majority of patients.  Our clinical data are remarkably similar to those previously published (1,5).  

   The all cause 6-month mortality rate of 20% found in our patients with definite IE was similar to published rates (range 16-27%) (1,2).  Among the five operated patients three survived, as they presented early and needed intervention (10).

Conclusions

   The pattern of Infective Endocarditis in the Royal Hospital in Oman has distinct epidemiological features.  It is still a disease of younger adults with a male predominance.  Chronic rheumatic heart disease is the major predisposing factor (in contrast to trends described in the developed world), whereas degenerative heart disease and intravenous drug abuse are not.  The high incidence of Culture negative endocarditis is probably attributed to the use of antibiotics prior to referral to Royal Hospital.  Among the various parameters studied, only vegetation size =/> 10 mm was associated with increased mortality, embolic manifestations and need for early surgery. ¨

References

1.  Mylonakis E , Calderwood SB. Infective Endocarditis in Adults. N Eng J Med 2001;234:            1318 -28.

2.  Hoen B, Alla F, Selton-Suty C, et al. Changing profile of infective endocarditis: results of a      1-year survey in France. JAMA 2002; 288:75-81.

3.  Durack DT , Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization      of specific echocardiographic findings. Am J Med 1994;96:200.

4.  Wilson WR, Kachmer AW, Dajani AS, et al. Antibiotic treatment of adults with infective      endocarditis due to streptococci, enterococci , staphylococci and HACEK microorganisms.      JAMA 1995; 274 :1706-13.

5.  Karchmer AW. Infective Endocarditis. In: Braunwald E, ed. Heart Disease: A Textbook of      Cardiovascular Medicine, 5th edn. WB Saunders,1997: 1769-74.

6.  Thomas H. Lee. Guidelines for prevention, evaluation and management of infective endocarditis.      In: Braunwald E, ed. Heart disease: A textbook of Cardiovascular medicine 6th edn. WB      Saunders, 200;1748-50.

7.  Keogelenberg CFN, Doubell AF, et al. Infective endocarditis in the Western Cape Province of      South Africa : a three-year prospective study. Q J Med 2003; 96:217-225.

8.  Bayer AS, Bolger AF , Taubert KA ,et al : Diagnosis and management of infective endocarditis      and itís complications. Circulation 1998; 98; 2936-48.

9.  Roder BL, Wandall DA, Frimodt-Moller N, et al. Clinical features of Staphylococcus aureus      endocarditis: a 10-year experience in Denmark. Arch Intern Med. 1999; 159:462.

10. Olaison L, Hogevik H, Myken P, Oden A. Early surgery in infective endocarditis. QJM. 1996;       89:267-278.

11. Sexton DJ, Bashore TM. Infective endocarditis. In : Eric.J.Topol, Textbook of cardiovascular      medicine, 2nd ed. LWW, 2002; 569-93.

ENGROSSED IN HIS WORLD

Kneeling Bull Holding Vessel

c. 2900 B.C., Proto-Elamite period, silver

Still, serene, self-contained and mysterious, the bull seems to know a lot . . . what secrets does he hold . . . what does he represent? A myth, in which animals acted as humans? An animal god? Or is the bull merely an elaborate handle for the long vase?