Letter to the Editor
Fecal transplantation for the treatment of relapsing diarrhea associated with Clostridium difficile infection in a liver transplantation patient
Trasplante de heces como tratamiento de diarrea recurrente asociada a infección por Clostridium difficile en un paciente con trasplante hepático
Elena Múñeza,c,
, Antonio Ramosa,c, Isolina Bañosb,c, Valentín Cuervas-Monsc,d,e
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a Unidad de Enfermedades infecciosas, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
b Unidad de Trasplante Hepático, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
c Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
d Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
e Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
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"Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Trasplante de heces como tratamiento de diarrea recurrente asociada a infección por <span class="elsevierStyleItalic">Clostridium difficile</span> en un paciente con trasplante hepático" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We report a case of diarrhea associated with recurrent <span class="elsevierStyleItalic">Clostridium difficile</span> infection (CDI) (<span class="elsevierStyleItalic">C. difficile)</span> with conventional treatment failure.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 62-year-old male with a history of liver transplantation for decompensated alcoholic cirrhosis in C-13 Child-Pugh functional stage and Model for End-stage Liver Disease (MELD) value: 26 points. The patient had a history of hypertension, hypertensive heart disease, hypercholesterolemia, moderate renal impairment (serum creatinine 1.5<span class="elsevierStyleHsp" style=""></span>mg/dl; 47<span class="elsevierStyleHsp" style=""></span>ml/min MDRD estimated glomerular filtration rate). Receiving immunosuppressive therapy with tacrolimus (trough levels 9<span class="elsevierStyleHsp" style=""></span>ng/ml), methylprednisolone (8<span class="elsevierStyleHsp" style=""></span>mg/day), valganciclovir (900<span class="elsevierStyleHsp" style=""></span>mg/day), enalapril, lormetazepam and pantoprazole. Five months after the transplant, the patient presented the first episode of CDI, during a rehospitalisation for sepsis secondary to pneumonia caused by <span class="elsevierStyleItalic">Klebsiella pneumoniae</span>, treated with meropenem and ceftazidime. Diagnose of CDI associated to diarrhea was based on the presence of more than 3 watery stools in 24<span class="elsevierStyleHsp" style=""></span>h, and the detection of <span class="elsevierStyleItalic">C. difficile</span> toxin in feces by ELISA. This first episode was resolved after treatment with metronidazole (500<span class="elsevierStyleHsp" style=""></span>mg/8<span class="elsevierStyleHsp" style=""></span>h orally) for 10 days. Two weeks later he presented a new episode of CDI, with good clinical response and stool negativisation of the <span class="elsevierStyleItalic">C. difficile</span> toxin after treatment with vancomycin (125<span class="elsevierStyleHsp" style=""></span>mg/6<span class="elsevierStyleHsp" style=""></span>h orally) for 14 days. Two weeks after completing treatment with vancomycin, the patient had a new episode of fever and diarrhea with watery and greenish stools, detecting <span class="elsevierStyleItalic">C. difficile</span> toxin in feces and CMV viremia in blood (12,800 copies). Treatment was initiated with ganciclovir (5<span class="elsevierStyleHsp" style=""></span>mg/kg intravenously) and combined treatment was started with vancomycin (500<span class="elsevierStyleHsp" style=""></span>mg/6<span class="elsevierStyleHsp" style=""></span>h orally) and metronidazole (500<span class="elsevierStyleHsp" style=""></span>mg/8<span class="elsevierStyleHsp" style=""></span>h intravenously). The patient's general condition worsens progressively over the next few days, remaining febrile (38<span class="elsevierStyleHsp" style=""></span>°C) and with diarrhea. On physical examination tympany and abdominal distension is observed. An abdomen CT scan shows the thickening of the colon wall compatible with pseudomembranous colitis. Simultaneously, the patient develops an episode of left heart failure. After 17 days of treatment with oral vancomycin and intravenous metronidazole, no clinical response was observed for the diarrhea associated with CDI, so a fecal transplant from a family donor (son) was indicated and performed. Prior to the transplant, a donor stool study was performed to rule out the presence of pathogens (enteric pathogens, parasites) and serology to hepatitis A, hepatitis B, HIV and syphilis. Fecal transplant was performed through a naso-jejunal tube, a stool solution of 30<span class="elsevierStyleHsp" style=""></span>g from the donor were diluted in 100<span class="elsevierStyleHsp" style=""></span>ml of physiological saline and then instillated. There were no complications associated with the procedure. Three days after the fecal transplantation the patient was afebrile and performing a doughy and non-smelly deposition a day, without pathological agents. At that point, no fecal <span class="elsevierStyleItalic">C. difficile</span> toxin was detected. The patient died 8 days after fecal transplantation as a result of the progression of his heart failure.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The CDI is a gastrointestinal disorder caused by disturbances in the intestinal flora, allowing pathogenic strains of <span class="elsevierStyleItalic">C. difficile</span> to infect the intestine,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> which often occurs in patients with exposure to antibiotics, age over 65 years, after prolonged hospitalization, with any type of immunosuppression, chronic suppression of gastric acid, prior renal disease and gastrointestinal surgery.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> Treatment consists of oral or intravenous metronidazole, oral vancomycin or recently fidaxomicin and, whenever clinically possible, the patient's antibiotic treatment suspension.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> After the resolution of the episode of diarrhea, more than 20% of patients have a recurrence of the same, and even 65% of these patients develop a chronic relapsing pattern of diarrhea associated with CDI.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> Recurrence of diarrhea associated with CDI is usually treated with prolonged regimens of metronidazole or vancomycin, with descending (recurrence rate of 31%) or pulsed (recurrence rate of 14%) dose. The usefulness of fecal transplantation in treating CDI associated diarrhea was recently described.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">3,5</span></a> The goal of fecal transplantation, also called fecal bacteriotherapy, is to restore the intestinal flora of the patient with endogenous intestinal microorganisms from a healthy donor.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> The donor should have not taken any antibiotics for at least 2 months prior to the transplant and any active infection by HAV, HBV, HCV, syphilis and HIV should be ruled out, together with any presence of parasites and enteric pathogens in his/her stool (<span class="elsevierStyleItalic">Salmonella</span>, <span class="elsevierStyleItalic">Shigella</span>, <span class="elsevierStyleItalic">Campylobacter</span> and toxigenic <span class="elsevierStyleItalic">C. difficile</span>). Vancomycin is administered to the receiver for 4 or 5 days prior to transplant and any other antibiotic administration is interrupted. The day before transplantation the receiver's bowel is prepared with an evacuant solution. The fecal infusion can be done by enema, colonoscopy or nasojejunal tube.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">5,6</span></a> Fecal transplant has been effective in some large series of patients with severe or recurrent <span class="elsevierStyleItalic">C. difficile</span> disease or with recurrent <span class="elsevierStyleItalic">C. difficile</span> disease in which other treatments have failed.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">6–9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">To our knowledge, this patient is the first case reported in Spain of fecal transplantation as treatment of recurrent <span class="elsevierStyleItalic">C. difficile</span> diarrhea in a liver transplanted patient. The procedure was well tolerated, with no associated side effects and with good response to it, although, because the patient died, we could not evaluate its long-term efficacy.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Múñez E, Ramos A, Baños I, Cuervas-Mons V. Trasplante de heces como tratamiento de diarrea recurrente asociada a infección por <span class="elsevierStyleItalic">Clostridium difficile</span> en un paciente con trasplante hepático. 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