Recent trends, clinical characteristics, and outcome of infective endocarditis among intravenous drug users of a tertiary hospital in the east region of Malaysia

Mohd Ridzuan Mohd Said; Mohd Al-Baqlish Mohd Firdaus; Muhammad Ateeq Md Jalil; Ismail Ibrahim; Wan Nurliyana Wan Ramli; Nurul Aulia Zakaria

doi:10.4103/heartindia.heartindia_33_20

ORIGINAL ARTICLE

Year : 2021 | Volume : 9 | Issue : 1 | Page : 72-77

Recent trends, clinical characteristics, and outcome of infective endocarditis among intravenous drug users of a tertiary hospital in the east region of Malaysia

Mohd Ridzuan Mohd Said, Mohd Al-Baqlish Mohd Firdaus, Muhammad Ateeq Md Jalil, Ismail Ibrahim, Wan Nurliyana Wan Ramli, Nurul Aulia Zakaria
Department of Internal Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia

Date of Submission	24-Aug-2020
Date of Decision	25-Aug-2020
Date of Acceptance	21-Sep-2020
Date of Web Publication	30-Mar-2021

Correspondence Address:
Dr. Mohd Ridzuan Mohd Said
Department of Internal Medicine, International Islamic University Malaysia, Kuantan, Pahang
Malaysia

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/heartindia.heartindia_33_20

Abstract

Background: Infective endocarditis (IE) is an infection affecting the endocardial lining and contributed to socioeconomic burden due to prolonged admission, invasive procedure, and expensive treatment. The high prevalence of intravenous drug user intravenous drug user (IVDU) shifts the paradigm of the disease, and thus, we aim to determine the clinical characteristics, outcome, and inhospital mortality of IE among IVDU patients.
Materials and Methodology: This is a retrospective cohort by analyzing case records for IVDU patients admitted to Hospital Tengku Ampuan Afzan diagnosed with IE from January 2014 until June 2017.
Results: A total of 32 patients were included, with a median age of 35 years old (standard deviation: 6.5). Only 56.3% presented with fever, whereas most of them complained of nonspecific symptoms such as reduced exercise tolerance (59.4%) and weight loss (56.3%). Seventy-five percent had concomitant hepatitis C, but only 6.3% of them were HIV positive. Valvular heart disease accounted for 46.9%, while chronic rheumatic heart diseases and previous IE infection accounted for 28.1% and 18.8%, respectively. For microbiological characteristics, Staphylococcus aureus accounted for 62.5%, followed by streptococci (15.4%) and others (2%). The most common valve affected in IVDU was tricuspid valve (62.5%), followed by mitral valve (21.9%) and pulmonary valve (9.4%). Furthermore, mortality was reported at 25%, while severe valvular complications (62.5%) were observed with elevated episodes of emboli (62.5%) and cardiogenic shock (40.6%).
Conclusion: Hence, IVDU is an essential predictive factor and is associated with various severe complications and thus warranted for aggressive preventive measurement to reduce the morbidity.

Keywords: Clinical characteristics, infective endocarditis, intravenous drug user, Malaysia

How to cite this article:
Said MR, Firdaus MA, Jalil MA, Ibrahim I, Ramli WN, Zakaria NA. Recent trends, clinical characteristics, and outcome of infective endocarditis among intravenous drug users of a tertiary hospital in the east region of Malaysia. Heart India 2021;9:72-7

How to cite this URL:
Said MR, Firdaus MA, Jalil MA, Ibrahim I, Ramli WN, Zakaria NA. Recent trends, clinical characteristics, and outcome of infective endocarditis among intravenous drug users of a tertiary hospital in the east region of Malaysia. Heart India [serial online] 2021 [cited 2021 Apr 17];9:72-7. Available from: https://www.heartindia.net/text.asp?2021/9/1/72/312480

Introduction

Over the years, the incidence of health-care-related infective endocarditis (IE) is escalating contributed by increasing amount of implantable cardiac devices and hemodialysis-related complications.^{[1],[2],[3],[4],[5]} The risk factors for IE are in concordance among a developed country although Malaysia reported a different etiology. Both Sunil et al. and Yousuf et al. reported that intravenous drug user (IVDU) remained an essential risk factor in our population, and the figure is alarming as the prevalence of IVDU is approaching 1.1% and is expected to escalate due to the feasibility of illegal distribution networks within Southeast Asia.^{[1],[2],[6],[7],[8],[9]} Furthermore, additional new addicts of 11,477 were recorded during 2002 in Malaysia and are reflecting an increasing IVDU-related illness.^[2]

The landscape of IE has changed over decades driven by IVDU, and these changes are reflected through microbiological data or causative organism.^[10],[11] Netzer et al. previously described that the most common causative organism among IVDU was Streptococcus viridans,^[12] but a different organism (Staphylococcus aureus) was observed with current literatures indicating the transition of microbiological data.^{[2],[3],[4],[5],[13],[14]} However, the pattern of microbiological data remained unchanged in decades for nil or low prevalence of IVDU cohort as non-Staphylococcus species including S. viridans, Enterococcus faecalis, and Coxiella burnetii were the most common.^{[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15]}

Furthermore, IE among IVDU reflected a unique cluster with a higher risk of acquiring extracardiac complications, suboptimal treatment, and prolonged hospital stays and less likely to be managed surgically.^{[12],[16],[17]} Thus, it resulted in higher inhospital mortality by 67% compared to non-IVDU-related IE (29%–37%).^{[2],[10],[11]} Moreover, our mortality rate remained relatively high compared to the Western population (5%–9%).^[12] Up until moment of writing, existing data on trends of IE among IVDU in our country are still limited, and hence, we aimed to describe clinical characteristics, recent trends, and outcome of IE in a tertiary center in the east coast of Malaysia.

Materials and Methodology

This was a retrospective descriptive study of IVDU cohort who were admitted to Hospital Tengku Ampuan Afzan (HTAA) from January 2014 until June 2018. HTAA is a general hospital and also a referral center for various disciples including cardiology and cardiothoracic services. Ethical approval was attained from the Medical Research and Ethics Committee of the Malaysian Ministry of Health (reference number of NMRR-18-1924-42167 IIR).

All records pertaining to admission of IE (I33.0) between January 2014 and June 2018 were retrieved from the Hospital Electronic Database of International Classification of Diseases-10 (International Statistical Classification of Diseases and Related Health Problems). Patients with more than 18 years old who fulfilled the modified Duke's criteria for IE with a history of IVDU were analyzed for baseline characteristics, transthoracic echocardiogram (TTE) imaging, and clinical outcome. However, patients with incomplete information, especially blood cultures and TTE findings, were excluded from the analysis. We defined a good outcome as patients were discharged after completed treatment while poor outcome as inhospital mortality.

Data obtained were analyzed using the Statistical Package for the Social Sciences version 23.0 (SPSS Inc., Chicago, IL, US) and displayed as frequencies and percentages. Numerical variables will be recorded as mean and standard deviation (SD) unless otherwise stated. Simple logistic regression was used to calculate crude odds ratio (OR) for inferential statistics with outcome (discharged vs. inhospital mortality) as a dependent variable, and the significant value was <0.05. The results were subsequently compared with previously published data involving IVDU patients with IE during the past decades.^[2],[11]

Results

A total of 455 medical records were screened, and 32 patients who fulfilled Duke's criteria for definite IE were included for evaluation. Definite Duke's criteria are defined by evidence of bacteremia, clinical criteria, and established TTE finding of vegetations or abscess.^[15]

Patients' demographics

All of our patients were male and of Malay ethnicity, with a mean age of 27 (SD = 6.5). In regard to predispose factors, 28.1% (n = 9) were diagnosed with underlying chronic rheumatic heart disease and 18.8% (n = 6) were re-admitted for recurrent IE [Table 1]. In addition, 75% (n = 24) of them had concomitant hepatitis C infection although HIV only accounts for 6.3% (n = 2).

Table 1: Characteristics of 32 patients

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Clinical findings

We observed that 56.3% (n = 18) of our patients complained of fever while more than half presented with reduced exercise tolerance (56.3%, n = 18) and reduction of weight (59.4%, n = 19) [Table 2]. Furthermore, 28.1% (n = 9) of them were reported with hepatomegaly.

Table 2: Clinical findings during admission

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Microbiological data and site of vegetation

In terms of microbiological data, S. aureus (62.5%) was the predominant microorganism, followed by Streptococcus group, as demonstrated in [Table 3]. Moreover, tricuspid valve was the most common site for vegetation with 62.5% (n = 20), followed by mitral valve of 21.9% (n = 7).

Table 3: Microbiological data and site of vegetation based from echocardiography

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Complications

Unfortunately, we observed a high mortality rate (25%) and cardiogenic shock of 40.6% [Table 4]. In addition, severe valve pathology (62.5%) was detected involving tricuspid valve (37.5%, n = 12) and significant septic embolization events (62.5%) predominantly to pulmonary (15.6%). Among all of our patients (n = 32), none was managed surgically. Moreover, half of our patients presented with hematological abnormality including anemia and thrombocytopenia of 53.1% (n = 17).

Table 4: Complications of infective endocarditis patients during admission

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Severe valvular regurgitation (crude OR: 6; confidence interval [CI] = 1.7–20.3) and septic embolization events (crude OR: 6; CI = 1.8–20.4) were the strongest predictor for poor outcome while completed antibiotic treatments (crude OR: 1.6; CI = 0.9–8.4) showed encouraging correlation with good outcome. However, nil association was observed with other parameters including age, comorbidities, cardiogenic shock, and hematological involvement.

Discussion

Clinical characteristics

IE posted a diagnostic dilemma by presenting with diverse and nonspecific clinical manifestation.^{[18],[19],[20]} From our data, fever and reduced effort tolerance were the most common manifestation, although a previous study reported predominant symptom of fever by 90%.^[21] Undeniably fever is a marker of an inflammatory response toward infection, but we postulated that different clinical characteristics were observed in our cohort due to impaired immune response. Overwhelming infection contributed by impaired immune response leads to high catabolic state and hence explained high occurrence of unspecific symptoms including lethargy and loss of weight.^{[22],[23],[24]} Moreover, most of our patients had hepatitis C co-infection (75%), and a positive correlation between cirrhosis and increased susceptibility to infection did indeed exist in this population.^{[25],[26],[27]}

In general, clinical characteristics were almost comparable among IVDU and non-IVDU cohorts, but variations did exist due to immune modulation and susceptibility to infection related to substance abuse and hepatitis C co-infection.^[28],[29] This needs to be highlighted so that clinicians will be more vigilance in diagnosing IE in the IVDU population.

Microbiological data

Our data show that S. aureus, with 62.5%, is the predominant microorganism causing IE among IVDU in Kuantan. This correlated with previous studies conducted in Malaysian urban areas.^{[1],[2],[10],[11]} The first study done in Kuala Lumpur by Jayamalar et al. showed that 66.7% of the IE cases were caused by the Gram-positive organism.^[11] Yousuf et al. in 2006 also found similar results in 61.5% of the cases in Kuantan.^[2] In recent studies done in Kuala Lumpur,^[1],[10] the rate is reduced to below 40%.

Globally, Staphylococcus spp. have superseded streptococci as the main causative organism. The International Collaboration on Endocarditis–Prospective Cohort Study in 2009 revealed that in regions other than South America, 31% of the IE cases are caused by staphylococci and 68% of them were IVDU.^[30] Our data are echoed in other countries with a high prevalence of drug overdose. In the US, the national incidence has increased from 15% in 2010^[31] to 29.1% in 2015,^[32] with 30.6% of the cases caused by Staphylococcus spp. In urban Africa, De Villiers et al. showed that 14.2% of the IE cases were among drug users, with 73% of the cultures positive for the aforementioned organism.^[33]

IVDUs are more predisposed because they have a higher rate of skin colonization of S. aureus compared to non-IVDUs.^[34] Poor skin hygiene and damaged skin increase the risk of introducing the bacteria into the bloodstream during injecting drugs with unsterilized needles.^[12] This is proven by Tuazon et al. which revealed that the same strain of S. aureus was isolated on the skin cultures of IVDU patients with IE.^[35]

However, in some countries, Streptococcus species are still more predominant bacteria. In France,^[36] Vietnam,^[8] Laos,^[37] India,^[38] and Pakistan,^[39] IE occurs majorly in patients with valvular heart disease. A recent Norwegian study revealed that 36.4% of the IE patients had prosthetic valves.^[40] All of these countries have much lower IVDU IE cases, <10%. Other uncommon microorganisms implicated in IE may also be isolated in IVDU patients such as HACEK, fungal, and other Gram-negative bacteria which can be up to 15%.^[3] Polymicrobial infection can also occur.

Mortality trends of infective endocarditis

The prognosis of IE has changed substantially with standardization of care among health-care practitioners with introduction of Clinical Practice Guidelines,^[19] but the severity of mortality and morbidity remained relatively high. From our data, we observed an increased mortality rate by tenfold when compared to retrospective literature published 10 years before^[2] [Table 5]. We postulated that a higher percentage of cardiogenic shock (40.6%) lead to more undesirable outcome among our patients compared to Yousuf et al. (2.6%) potentially due to reduced cardiac output and compounded by septicemia event.^[2],[41] Another feasible explanation was related to the dissemination of infective emboli to other major organs suggesting disease progression^[14],[15]. Hence, devastating outcomes were observed among patients with cardiogenic compromised and dissemination of infective emboli.^{[14],[15],[41]} Furthermore, left-sided IE was associated with worse prognosis by 20%–30% mortality rate when compared to right-sided IE (5%), and among left-sided IE, mitral valve involvement is associated with better prognosis compared to the aortic valve.^[15],[42] We did not record any aortic valve involvement, however, 21.9% of them were reported with mitral valve involvement which may compromise left ventricular function.^[14],[15] Hence, undeniable, our inhospital mortality for IVDU was high when compared to the Western^[29],[43] cohort, but the percentage was in concordance with the finding from previous literature regarding IE with 15%–23% mortality rate.^{[1],[4],[5],[10]}

Table 5: Comparison of retrospective literatures on intravenous drug users with infective endocarditis

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Hematological disturbance in infective endocarditis

Hematological disturbance, especially anemia, was a common manifestation of IE, and the mechanism was rather complex and involved multiple factors. Increased inflammatory cytokines (interleukin [IL]-1, IL-6, and tumor necrosis factor) reduced erythropoietin level and erythropoietin sensitivity which lead to apoptosis of erythroid cells.^[44] In addition, a reduction of iron absorption is observed due to upregulation of plasma hepcidin stimulated by inflammatory cytokines.^[44]

Furthermore, IE may cause intravascular hemolysis via coagulopathy or mechanical hemolysis through the valvular lesions. It is characterized by the presence of red blood cell fragmentation in the peripheral blood cells and compensatory erythropoietic response.^[44] This also can lead to thrombocytopenia due to increased consumption. In addition, Enterococcus and Staphylococcus are more commonly associated with moderate and severe anemia compared to other organisms.^[45]

There was a limitation in our study mainly on technical aspect of getting sufficient samples. We had discarded few individuals due to inadequate data, especially on TTE and blood cultures. The rationale of removing this subject was in order to avoid any bias on sample collection.

Conclusion

IVDU is an essential risk factor and is associated with various devastating complications such as severe valve regurgitation and septic embolization. Unfortunately, the treatment is mainly conservative contributed by various unfavorable factors and hence may contribute to high inhospital mortality.

Availability of data and materials

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

Ethical approval was attained from the Medical Research and Ethics Committee of the Malaysian Ministry of Health (reference number of NMRR-18-1924-42167 IIR). The need for individual approval was waived.

Authors' Contributions

MRMS collected, analyzed, interpreted the patient data and is responsible for the overall content as a guarantor. MRMS, MABMF, and MAMJ prepared the manuscript. II, WNWR, and NAZ reviewed the manuscript.

Acknowledgments

We are grateful to Hospital Tengku Ampuan Afzan and International Islamic University Malaysia for its support.

Financial support and sponsorship

We acknowledged receiving a short-term research grant from International Islamic University Malaysia (reference no: RIGS17-080-0655).

Conflicts of interest

There are no conflicts of interest.

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