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Ann Med Surg (Lond)
Ann Med Surg (Lond)
MS9
Annals of Medicine and Surgery
2049-0801
Lippincott Williams & Wilkins Hagerstown, MD

10.1097/MS9.0000000000000249
00034
3
Case Reports
Culture-negative tricuspid valve endocarditis in an intravenous drug abuser masquerading as pulmonary tuberculosis in Nepal: a case report
http://orcid.org/0000-0003-3441-1193
Rajkarnikar Ruja aruza.raj13@gmail.com

http://orcid.org/0000-0003-4273-9228
Sharma Shriya bshriya.sharma@naihs.edu.np

http://orcid.org/0000-0002-9985-0931
Yadav Sumit csumit.kumar.yadav@naihs.edu.np

Ghimire Nirmal drnirmal10452@gmail.com
d
a Kathmandu Medical College
b Nepalese Army Institute of Health Sciences
c Shree Birendra Hospital
d Nepal Police Hospital, Kathmandu, Nepal
*Corresponding author. Address: Nepalese Army Institute of Health Sciences, Kathmandu, Nepal. Tel.: +9779840012594. E-mail: shriya.sharma@naihs.edu.np (S. Sharma).
3 2023
17 2 2023
85 3 523527
9 9 2022
25 12 2022
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
2023
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/

Introduction:

Infective endocarditis is an infection of the heart valves or endocardium caused by bacterial, viral, or fungal microorganisms. Blood cultures are used to detect the bacteria causing infective endocarditis, and echocardiography is performed to find the damaged heart valves. In blood culture-negative endocarditis, no endocarditis-causing organisms can be found in blood cultures, and blood cultures using usual laboratory methods remain sterile after inoculation of at least three independent blood samples.

Case presentation:

A 24-year-old male with a history of polysubstance abuse presented with complaints of fever, cough, and shortness of breath. He had a past history of pulmonary tuberculosis 4 years ago, for which he was treated with antitubercular therapy. High-resolution computed tomography of the chest revealed multiple cavitary lesions and consolidative areas in the bilateral lungs. Based on these findings, a provisional diagnosis of reactivation of pulmonary tuberculosis was considered, and antitubercular therapy was started. Due to his deteriorating condition, he was readmitted and evaluated. Bronchoalveolar lavage was done and sent for culture and sensitivity testing, which showed the presence of Staphylococcus aureus, and treatment was started accordingly. Despite continuing intravenous antibiotics for 5 days, the patient was not improving. Three sets of samples were withdrawn for blood culture and sensitivity testing, which came out to be negative. Transthoracic echocardiography was done, which revealed vegetation in the tricuspid valve. The patient was diagnosed with culture-negative tricuspid valve endocarditis based on the clinical criteria.

Discussion:

Blood culture-negative endocarditis is difficult to diagnose and presents challenges. When faced with a diagnosis like culture-negative endocarditis in the context of a condition that can appear very similar, like tuberculosis, a broad differential diagnostic approach is important.

Conclusion:

Intravenous drug use is the main cause of right-sided valvular infective endocarditis. Endocarditis should be considered in intravenous drug users even in the absence of positive blood cultures. An appropriate antibiotic regimen and long-term follow-up with a multidisciplinary team are necessary for a good outcome.

Keywords:

culture negative
infective endocarditis
intravenous drug abuser
vegetation
SDCT
OPEN-ACCESSTRUE
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pmcHighlights

In culture-negative endocarditis, no endocarditis-causing organisms can be found in the blood cultures of three independent blood samples.

Intravenous Drug User (IVDU) is a risk factor thought to affect right-sided valves and is the main cause of right-sided valvular infectious endocarditis.

In the case of IVDU, the possibility of infectious endocarditis is always there, even after the normal initial transthoracic echocardiography.

Introduction

Infective endocarditis is defined as an infection of a native or prosthetic heart valve, the endocardium, or an indwelling cardiac device caused by bacterial, viral, or fungal microorganisms. The most frequently isolated bacteria are Staphylococcus spp., Streptococcus spp., and Enterococcus spp., which account for 80–90% of cases of infective endocarditis1.

The diagnosis of infectious endocarditis (IE) is made based on the appearance of vegetation on echocardiography and positive blood cultures in patients who have a fever and a new or changing heart murmur. Endocarditis is typically identified in feverish patients with persistent bacteremia and vegetation on echocardiogram, on gross examination, or in histologic testing of the excised valve2.

Blood culture-negative endocarditis (BCNE) is endocarditis with sterile blood culture using the usual laboratory methods with around 7 days of incubation, and out of all cases of endocarditis, 2.5–70% account for BCNE3,4. The sterility of blood cultures varies according to the country, which is explained by many factors like differences in the diagnostic criteria used, epidemiological factors, or the use of antibiotics before blood sampling4. BCNE can be challenging to diagnose, and the fatality is high2, especially in regions with high rates of other infectious diseases like tuberculosis. We present a case of BCNE that was initially treated for a possible tuberculosis flare. This case report has been reported in line with the SCARE 2020 criteria5 (Supplemental Digital Content 1, http://links.lww.com/MS9/A26).

Case presentation

A 24-year-old male presented to the hospital with complaints of fever for 1 month, cough for 14 days, and shortness of breath for 12 days. The fever was intermittent, with an evening rise accompanied by chills and rigors and a maximum recorded temperature of 102 degrees Fahrenheit. He complained of a productive cough, mucopurulent in nature, and occasionally mixed with blood. His shortness of breath was exertional without orthopnea or paroxysmal nocturnal dyspnea. There was no history of chest pain, palpitations, swelling of the limbs, joint pain, or rashes. He had a history of pulmonary tuberculosis 4 years ago for which he was treated with antitubercular therapy (ATT). He is an active smoker and drinks 2 units of locally prepared alcohol daily. He started abusing intravenous (i.v.) drugs 2 years ago and currently uses pethidine, phenergan, tramadol, and diazepam two to three times a week. The patient denies any high-risk sexual behavior or needle-sharing behavior.

On general examination, he appeared pale and ill-looking, with tattoo marks on the left upper chest and arm. There was no clubbing, cyanosis, edema, or dehydration. His vital parameters were normal. Examination of the respiratory, cardiovascular, abdominal, and nervous systems showed no abnormalities. A panel of laboratory investigators was sent to evaluate his case.Variable	Results	
Hemoglobin	9.1 g/dl	
White cell count	13 000/mm3	
Platelets	156 000/mm3	
Urea	29 mg/dl	
Creatinine	0.9 mg/dl	
Sodium	123 mEq/l	
Potassium	3.1 mEq/l	
Total bilirubin	4 mg/dl	
Direct bilirubin	2.3 mg/dl	
Aspartate aminotransferase	63 U/l	
Alanine aminotransferase	100 U/l	
Erythrocyte sedimentation rate	32 mm/h	
C-reactive protein	30 mg/dl	
Procalcitonin	20 ng/ml	
Antinuclear antibody	Negative	
HIV/HbSAg/anti-HCV antibody	Negative	

Chest radiography on the day of admission showed cavitary lesions and consolidation in bilateral lungs (Fig. 1).

Figure 1 Chest radiography showing cavitary and consolidative areas.

A high-resolution computed tomography of the chest was performed, which revealed multiple cavitary and consolidative areas in the bilateral lungs, fluffy airspace nodular opacities in the left lung, and mediastinal lymphadenopathy with mild right pleural effusion. Focal fibrotic changes in bilateral lungs were also seen (Fig. 2).

Figure 2 High-resolution computed tomography chest showing multiple cavitary lesions and consolidative areas, fluffy airspace nodular opacities in the left lung, and mediastinal lymphadenopathy.

Based on these findings, a provisional diagnosis with reinfection of pulmonary TB was considered. Subsequently, the intensive phase of ATT was started. However, he was not improving after one month of starting ATT. So, further workup was planned. With a medical history significant for active Intravenous Drug User (IVDU), and a high degree of suspicion, three sets of samples were withdrawn for blood culture and sensitivity which came out to be negative. The transthoracic echocardiography (TTE) obtained was normal with an Left Ventricular Ejection Fraction of 60% and did not reveal any intracardiac vegetations. Bronchoscopy reports were normal. Bronchoalveolar lavage was done and sent for culture and sensitivity. The results came back positive for Staphylococcus aureus. An antimicrobial susceptibility test was done, and treatment was started with injection ceftriaxone 1 g i.v. twice daily, injection clindamycin 600 mg i.v. thrice daily, injection gentamycin 80 mg i.v. twice daily, along with other supportive measures. Despite continuing i.v. antibiotics for 5 days, the patient was not improving. A cardiologist’s consultation was sought, and some investigations were sent. The diagnosis was still inconclusive, so a repeat TTE was done, which revealed vegetation in the tricuspid valve. Short videos of the apical four chamber and parasternal short-axis view of TTE, showing flowing vegetation in anterior leaflet of the tricuspid valve, are included in Supplement File 1, Supplemental Digital Content 2, http://links.lww.com/MS9/A27 and Supplement File 2, Supplemental Digital Content 3, http://links.lww.com/MS9/A28 respectively (Fig. 3).

Figure 3 Echocardiography showing vegetation in the tricuspid valve.

Three sets of blood samples for culture and sensitivity were repeated and came back negative. The patient was diagnosed with a culture-negative tricuspid valve endocarditis based on the clinical criteria (one major criterion: an echocardiogram positive for vegetation and three minor criteria: injection drug use, fever >100.4 degrees Fahrenheit, and septic pulmonary infarcts). After the diagnosis, injection of vancomycin 1 g i.v. twice daily was started in addition to injection of ceftriaxone 2 g i.v. twice daily and injection of gentamycin 160 mg i.v. once daily. He then started improving gradually and became afebrile after 7 days. However, he developed acute kidney injury (creatinine: 2.5 mg/dl, ref: 0.74–1.35 mg/dl) after 3 weeks of antimicrobial, so gentamycin was temporarily discontinued with a dose adjustment for vancomycin. One week later, with the improvement of creatinine to 0.7 mg/dl, the full dose of medications was restarted without any complications thereafter. His chest radiography showed improvement as compared to the one at the time of admission (Fig. 4). The treatment was continued for 6 weeks, and discharge was planned. During discharge, he was advised to maintain dental and oral hygiene and was explained the need for three blood sample culture and sensitivity in the occurrence of any febrile episode.

Figure 4 Chest radiography taken after 6 weeks of antibiotic therapy.

Discussion

The three important causes of culture-negative bacterial endocarditis are inadequate laboratory techniques, infection with nonbacterial pathogens, and the administration of antibiotics before blood cultures. Some of the organisms that can cause culture-negative bacterial endocarditis are Bartonella, Brucella, Coxiella, and HACEK group, which may require further testing like PCR and serological testing specific to these organisms6. Any antimicrobial agent taken before the blood culture reduces the chance of a positive blood culture by 35–40%. The length of time that blood a culture remains negative is determined by the type and duration of the antibiotics used7. In a clinical epidemiological study done in France, pretreatment with antibiotics was found to be the reason for 48% of all culture-negative endocarditis8.

Although the exact incidence of IE in IVDUs is unknown, around 5–15% of acute infection episodes that leads to hospitalization in IVDUs are found to be due to IE7. Tricuspid valve endocarditis is mostly common in IVDUs, and around 5% of endocarditis in IVDUs is due to BCNE6. The visualization of vegetations on echocardiography and the presence of embolic phenomenon have been the most reliable predictors of IE in IVDUs7.

Our patient did not have any risk factors for fastidious organisms as listed above and had no exposure to farms, animals, animal products. Proper history can help elucidate epidemiological factors, and the history of prior infections, and exposure to antimicrobials is important after BCNE is considered7,9. With our patient’s prior history of pulmonary tuberculosis and the high incidence and prevalence of tuberculosis in Nepal, the initial consideration was possible reactivation or reinfection with Mycobacterium tuberculosis. M. tuberculosis is an extremely rare cause of valvular endocarditis, which is mostly reported in cases of miliary tuberculosis. A case of aortic valvulitis with disseminated tuberculosis and three cases of right-sided tuberculous endocarditis in HIV-positive i.v. drug users have been reported10. There has been only one case of tuberculous valve endocarditis in an immunocompetent alive patient and the rest have only been reported on autopsy reports11. Diagnosing miliary tuberculosis with a superadded infection could be quite challenging, as miliary tuberculosis itself is a diagnostic challenge due to its nonspecific presentation and relative rarity. The confirmatory test for TBE is histopathological findings of epithelioid cells and giant cells, which can be difficult to find due to the slow-growing nature of M. tuberculosis 12.

The concern for tubercular IE in our patient is low, as he improved with bacterial IE therapy. With the isolates of S. aureus in the bronchoalveolar lavage, these were likely septic emboli to the lungs, and the primary vegetation is also related to S. aureus. Infective endocarditis is one of the most misdiagnosed diseases, as seen from the study done on autopsies in 201813.

Our case highlights the need for keeping a broad differential and not prematurely closing the diagnostic thinking, especially when challenged with a diagnosis like culture-negative endocarditis in the background of a disease that can present very similarly to tuberculosis.

Conclusion

Culture-negative endocarditis is severe and difficult to diagnose and presents diagnostic and therapeutic challenges. IVDU is a risk factor thought to affect right-sided valves for infective endocarditis and is the main cause of right-sided valvular IE. In the case of IVDU, the possibility of IE is always there, even after the normal initial TTE. An appropriate antibiotic regimen and long-term follow-up with a multidisciplinary team including cardiologists, dentists, and psychiatrists are necessary for a good outcome. Patient care during the hospital stay and after the completion of antimicrobial treatment is important. In some scenarios, if surgery is needed, it should be considered.

Ethical approval

This is a case report; therefore, it did not require ethical approval from the ethics committee.

Sources of funding

The study did not receive any grants from funding agencies in the public, commercial, or not-for-profit sectors.

Consent

Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editor-in-chief of this journal on request.

Author contribution

All authors involved in writing the paper, collecting data, revising it critically for important intellectual content, reviewing, and editing.

Conflicts of interest disclosure

The authors report no conflicts of interest.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Shriya Sharma, Nepalese Army Institute of Health Sciences, Kathmandu, Nepal, E-mail: shriya.sharma@naihs.edu.np

Provenance and peer review

Not commissioned, externally peer-reviewed.

Supplementary Material

SUPPLEMENTARY MATERIAL

Acknowledgment

None.

Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.annalsjournal.com.

Published online 17 February 2023
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