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• W2809562012 abstract "Brucellosis is being increasingly recognized after solid organ transplantation but has not been reported after orthotopic heart transplantation. We present the case of a 51-year-old farmer who underwent orthotopic heart transplantation and was readmitted after 3 months in a severely immunosuppressed state with significant nonspecific complaints. He posed a diagnostic and management dilemma to all disciplines, but finally turned out to be harboring Brucella infection. He responded well to medical management and was discharged in a stable clinical status. Although rare, brucellosis should be included in the investigative workup for nonspecific symptoms after cardiac transplantation. Brucellosis is being increasingly recognized after solid organ transplantation but has not been reported after orthotopic heart transplantation. We present the case of a 51-year-old farmer who underwent orthotopic heart transplantation and was readmitted after 3 months in a severely immunosuppressed state with significant nonspecific complaints. He posed a diagnostic and management dilemma to all disciplines, but finally turned out to be harboring Brucella infection. He responded well to medical management and was discharged in a stable clinical status. Although rare, brucellosis should be included in the investigative workup for nonspecific symptoms after cardiac transplantation. Solid organ transplantation has evolved as a viable option for many end-stage organ diseases in humans. Better understanding of microbiology and immunosuppression has resulted in improved long-term survival. However, infection and rejection continue to be major concerns in any transplant recipient. Opportunistic infections as zoonosis have shown an ascending trend due to increase in the number of immunosuppressed patients. Brucellosis is an uncommon zoonosis reported after solid organ transplantation and, so far, are limited to reports after renal [1Ting I.W. Ho M.W. Sung Y.J. et al.Brucellosis in a renal transplant recipient.Transpl Infect Dis. 2013; 15: E191-E195Google Scholar, 2Ay N. Kaya S. Anil M. et al.Pulmonary involvement in brucellosis, a rare complication of renal transplant: case report and brief review.Exp Clin Transplant. 2016 May 17; ([Epub ahead of print])Google Scholar], bone marrow [3Ertem M. Kürekci A.E. Aysev D. Unal E. Ikinciogullari A. Brucellosis transmitted by bone marrow transplantation.Bone Marrow Transplant. 2000; 26: 225-226Crossref PubMed Scopus (38) Google Scholar], and liver transplantation [4Xie M. Rao W. Shen Z. Jia J. Brucellosis infection in an adult liver transplant recipient.Transpl Infect Dis. 2014; 16: 516-518Crossref PubMed Scopus (5) Google Scholar]. Brucellosis with a variable incubation period (days to months) can present acutely, in a chronic form, as subclinical or asymptomatic, or as a severe systemic infection posing a real diagnostic challenge to the physician. Being a rare occurrence, brucellosis is often underdiagnosed and undertreated in India [5Smits H.L. Kadri S.M. Brucellosis in India: a deceptive infectious disease.Indian J Med Res. 2005; 122: 375-384Google Scholar]. A 51-year-old gentleman, a farmer by occupation, underwent orthotopic heart transplantation for ischemic cardiomyopathy and was discharged after 1 month with a negative endomyocardial biopsy. Three months afterward, he was admitted with fever and chills with leukopenia and neutropenia (total white blood cell count 2,200, differential count N10L88E2). He had high tacrolimus trough levels (20 ng/dL), deranged renal function (serum creatinine 1.9 mg/dL), and high C-reactive protein (85 mg/L [normal reference range, 2 to 6 mg/L]). His varied complaints included anorexia, malaise, lassitude, occasional headache, large joint pains without arthritis, myalgia, low backache, dizziness, depressed mood, dyspepsia, nausea, 1 to 2 episodes of vomiting, diffuse abdominal pain, and cough. After admission, all immunosuppressant drugs were stopped (tacrolimus and mycophenolate) except steroids. He was hydrated well and routine as well as systemic investigations including pan body cultures and induced sputum examination to exclude pulmonary tuberculosis were sent. He was started on empirical broad-spectrum antibiotics and all relevant medical disciplines were involved in his clinical workup. A Transthoracic and subsequent transesophageal echocardiography revealed good biventricular function with competent valves without any evidence of infective endocarditis or pericardial effusion. Magnetic resonance imaging of the spine and computed tomography of the abdomen ruled out spine- and abdomen-related illnesses. All blood cultures and body fluid cultures were sterile. In view of persistent symptoms, an increasing polymorphonuclear leukocytosis, and rising C-reactive protein values greater than 150 mg/L, he was started on empirical antifungals also but showed a poor therapeutic response. We reevaluated his symptoms, and being a farmer with domestic cows on his farm and his consumption of dairy products from sources outside the hospital, we did a IgM Brucella, which was positive. IgM antibodies against Brucella lipopolysaccharide were detected by serum enzyme immunoassay: reference value of the ratio is less than 0.9 is negative, 0.9 to 1.1 is borderline, and greater than 1.1 is positive. The patient’s detected value was 1.4. We started him on doxycycline in combination with co-trimoxazole (trimethoprim-sulfamethoxazole [TMP-SMZ]) for 12 weeks. A disappearance of the symptom complex with sustained clinical therapeutic response was seen in a few days. The C-reactive protein and leukocytosis normalized and a repeat IgM Brucella turned negative after 12 weeks of drug therapy. We are not sure as to whether the infection was resurgence of a previously acquired organism or a newly acquired one, as he was severely immunosuppressed at the time of presentation. The clinical presentation was also very nonspecific, leading to undue delays and confusion in the diagnosis. There is still no consensus on the treatment of brucellosis after solid organ transplantation, as it needs a careful balance between antimicrobials and immunosuppressants in view of drug interactions. An Internet search of published English literature showed 8 cases of solid organ transplantation (3 liver and 5 kidney) treated for brucellosis by various groups until 2016 [2Ay N. Kaya S. Anil M. et al.Pulmonary involvement in brucellosis, a rare complication of renal transplant: case report and brief review.Exp Clin Transplant. 2016 May 17; ([Epub ahead of print])Google Scholar, 4Xie M. Rao W. Shen Z. Jia J. Brucellosis infection in an adult liver transplant recipient.Transpl Infect Dis. 2014; 16: 516-518Crossref PubMed Scopus (5) Google Scholar]. Doxycycline and rifampin in combination were the most commonly used drug regimens, with treatment durations ranging from 6 to 8 weeks (4 groups: 1 liver, 3 kidney). TMP-SMZ and rifampin was prescribed for 2 liver transplant recipients (8 weeks, 12 weeks), while doxycycline added to this was used in another kidney transplant recipient. Only 1 group treated their recipient with tigecycline, minocycline, and TMP-SMZ, yielding success. The use of tigecycline has been increasingly reported recently when the usual antimicrobials are ineffective and in recurrence [6Cocchi S. Bisi L. Codeluppi M. et al.Brucellosis in a patient with end-stage liver disease undergoing liver transplantation: successful treatment with tigecycline.Liver Transpl. 2010; 16: 1215-1216Crossref PubMed Scopus (6) Google Scholar]. Considering the higher incidence of rifampin-induced hepatotoxicity in Indian patients [7Devarbhavi H. Antituberculous drug-induced liver injury: current perspective.Trop Gastroenterol. 2011; 32: 167-174PubMed Google Scholar], we preferred to use a regimen consisting of doxycycline and TMP-SMZ. Though the patient made a complete clinical and biochemical recovery after 12 weeks of medical therapy, he needs close follow-up to detect recurrence. Modifying the immunosuppressants is a real challenge in these patients especially, tacrolimus dosing due to drug interactions. Various antimicrobials against Brucella may induce or impair its metabolism, and accordingly tacrolimus dose needs to be escalated [8Islek A. Sayar E. Yilmaz A. Günseren F. Artan R. Relapsing brucellosis after liver transplantation in a child: what is the appropriate regimen and duration of therapy?.Transplantation. 2013; 96: e6-e7Crossref PubMed Scopus (6) Google Scholar] or deescalated [1Ting I.W. Ho M.W. Sung Y.J. et al.Brucellosis in a renal transplant recipient.Transpl Infect Dis. 2013; 15: E191-E195Google Scholar]. At the same time, some agents may need to be restarted to prevent a rejection [8Islek A. Sayar E. Yilmaz A. Günseren F. Artan R. Relapsing brucellosis after liver transplantation in a child: what is the appropriate regimen and duration of therapy?.Transplantation. 2013; 96: e6-e7Crossref PubMed Scopus (6) Google Scholar]. All the previously described case reports mention modifying the immunosuppression protocol with the minimum dose of multidrug therapy and more frequent drug-level monitoring to achieve a clinical balance between infection and rejection. We modified our protocol with the minimum dosage of drug cocktail (tacrolimus, mycophenolate, and prednisolone) with an intent to keep tacrolimus 12-hour trough levels between 5 and 8 ng/mL. The follow-up protocol was altered, with frequent drug-level monitoring and tailoring of the drugs as per the report of endomyocardial biopsies. This report signifies the need for considering all infections carefully irrespective of the transplant status, with a detailed history and reevaluation of symptoms when in dilemma. A limitation of this report is that we could not confirm the organism with dedicated blood cultures, but cultures are also time consuming and the sensitivity is low. A bone marrow culture was not done, considering the posttransplant state with immunosuppression and a positive serology. As this zoonosis is not very frequently seen and is not previously reported in literature after cardiac transplantation, and this case highlights the need to include brucellosis in the differentials for unwellness after cardiac transplantation." @default.
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• W2809562012 title "Brucellosis After Cardiac Transplantation" @default.
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