IntroductionInfective endocarditis (IE) is a severe and life-threatening disease worldwide (1). However, because of non-specific clinical presentations, confirmation and prescription of effective treatment are sometimes not simple tasks. History may help significantly in the diagnosis of IE; for example, it is more common among drug addicts, particularly Intravenous drug users (2, 3).Approximately 5% of IE cases have negative blood cultures (4, 5), and its risk factors are exposure to slow-growing bacteria such as Bartonella species, fastidious nonbacterial organisms, previous antibiotic use, underlying valvular heart disease, and intracardiac or vascular device or other foreign bodies in contact with the blood (6).Most patients have nonspecific symptoms such as fever, fatigue, and weight loss. In a case series comprising 348 blood culture-negative endocarditis cases from France, almost all the patients had a fever as a presenting symptom. In contrast, about 50 to 70% had symptoms of heart failure, such as exertional dyspnea, and about 50% had insidious weight loss(9).Bartonella spp. is a small, intracellular, gram-negative, and very fastidious rod mainly transmitted by vectors; they are the second most common cause of culture-negative endocarditis. Among the cases of Bartonella endocarditis, two species predominantly implicated in causing culture-negative endocarditis are B. henselae and B. quintana(7).These bacteria have been isolated from many mammalian species, including cats and dogs. It can cause mild infection to severe and life-threatening endocarditis in humans and dogs. In dogs, several Bartonella species have been identified; one of the most common ones is B. henselae.It should be mentioned that in recent years, more cases of culture-negative endocarditis have been reported from developing countries(8).This report presents a case of a patient with culture-negative B. henselae endocarditis from Iran, diagnosed using a combined diagnostic approach that included clinical evaluation, imaging, epidemiology, serology, echocardiography, and transthoracic echocardiography (TTE).Patient InformationThe patient was a 38 years old male, single and unemployed with a history of addiction, who had received care from a treatment camp for six months. He was discharged when he was on methadone maintenance therapy just before his first hospital admission. He was an IV drug abuser with a history of regularly using amphetamine, cocaine, and heroin. He also smoked cigarettes for 20 years. He also exposed that he had unsafe sex and lost contact with dogs and cats.Clinical Findings TimelineThe symptoms onset was 20 days before admission when he had fever and chills besides shortness of breath in the camp. The patient was hospitalized in another care center for five days as a suspected COVID-19 case and he was treated with Remdesivir, but his nasopharyngeal and oropharyngeal COVID-PCR tests were negative. Having been discharged from the hospital, he started using amphetamine again, which deteriorated his condition.This time he was admitted to our center, as a referral center, with severe dyspnea, high fever (40), chills, chest pain, myalgia, and hemoptysis. The patient was ill and, on physical examination, he had tachycardia (Heart rate=107) and tachypnea (Respiratory rate=28), with low blood pressure (90/60), fluctuated oxygen saturation which was less than 92%, normal heart auscultation, no clubbing, no splenomegaly, and no lymphadenopathy. Table 1 summarizes the lab results.