the incidence , severity , and resulting mortality of clostridium difficile infection are increasing worldwide . in spite of the considerable increase in the incidence and severity of c. difficile infection , metronidazole is generally used for mild and moderate c. difficile infection , but treatment failure is a growing problem . furthermore , antibiotic therapy has recurrence rates of at least 20% , which increase with each subsequent c. difficile infection . els van nood et al . reported that in patients with recurrent c. difficile infection , fecal transplantation resulted in better treatment outcomes compared with conventional antibiotic treatment . fecal transplantation had a cure rate of 81.3% following a single nasoenteric infusion and 93.8% following a second infusion , while standard vancomycin therapy with or without bowel lavage had a 23.1 - 30.8% cure rate . fecal transplantation may be a treatment option for recurrent c. difficile infection ; moreover , it may be an early treatment option for severe c. difficile infection . in korea , two cases of severe refractory c. difficile infection treated with fecal transplantation during an initial episode have been reported . , we report the first case of severe initial c. difficile infection , refractory to antibiotics , that was treated with fecal transplantation using a nasoenteric tube in korea . a 65-year - old man visited the emergency room with a 3-day history of bilateral leg weakness and fever . his blood pressure was 86/43 mmhg , and his body temperature was 39.3 at presentation . he had a history of hypertension and recent surgery for lumbar spinal stenosis three months before admission . initial peripheral blood count showed a white blood cell count of 4,710/mm ( neutrophils , 92.2% ; lymphocytes , 5.2% ; monocytes , 1.4% ) , hemoglobin level of 11.3 g / dl and platelet count of 137,000/mm . prothrombin time ( pt ) and activated partial thromboplastin time ( aptt ) were 13.2 sec and 34.8 sec , respectively , and c - reactive protein level was 286.06 mg / l . blood chemistry showed a total protein level of 5.1 g / dl , albumin level of 2.9 g / dl , total bilirubin level of 0.5 mg / dl , aspartate aminotransferase / alanine aminotransferase 27/17 iu / l , bun / cr 56.6/2.42 mg / dl , na / k 138/4.1 meq / l and ca / p 7.6/2.7 mg / dl . lumbar magnetic resonance imaging ( mri ) was performed and revealed infective spondylitis and multiple paraspinal abscesses . the patient received empiric intravenous antibiotic treatment with 2.0 g ceftriaxone every 24 hours and 200 mg teicoplanin every 24 hours after peripheral blood culture and urine culture . streptococcus intermedius was identified in all three initial blood cultures , and the minimal inhibitory concentration ( mic ) for penicillin g was 0.016 g / ml . antibiotics were changed to 4 million units penicillin g every 4 hours . on the 35th hospital day , he had urinary tract infection and bacteremia from an extended - spectrum beta - lactamase ( esbl ) organism and was treated with 500 mg imipenem every 6 hours . on the 59th hospital day , during conservative treatment for infective spondylitis , the patient developed a fever of 38.1 and diarrhea ; his blood pressure was 89/58 mmhg . due to suspicion of c. difficile infection , oral 500 mg metronidazole was given every 8 hours empirically . stool c. difficile toxin a / b and culture were confirmed to be positive . on the 60th hospital day , laboratory results revealed a white blood cell count of 39,560/mm ( neutrophils , 89.4% ; lymphocytes , 6.2% ; monocytes , 2.8% ) , hemoglobin level of 11.8 g / dl , platelet count of 292,000/mm , bun / cr of 18.0/0.65 mg / dl , and albumin level of 1.8 g / dl . on the 61st hospital day , oral metronidazole was switched to 250 mg oral vancomycin every 6 hours due to increased severity of diarrhea and the detection of paralytic ileus on abdominal x - ray despite administration of oral metronidazole . intravenous metronidazole ( every 8 hours ) and vancomycin enema 500 mg ( every 6 hours ) were also added to the treatment course . unfortunately , symptoms did not improve , and disseminated intravascular coagulation ( dic ) progressed although leukocytosis was improved . on the 74th hospital day , laboratory results showed a white blood cell count of 3,240/mm ( neutrophils , 71.0% ; lymphocytes , 20.1% ; monocytes , 6.8% ) , a hemoglobin level of 7.8 g / dl , platelet count of 67,000/mm , pt / aptt of 22.6 sec/65.4 sec , albumin level of 1.9 g / dl and c - reactive protein level of 77.2 mg / l . the patient 's wife , who had no relevant medical history and no symptoms of acute disease , was selected as the donor . on the 75th hospital day the tip of a nasoenteric tube was placed in the third portion of the duodenum by egd . fifty grams of stool collected from the donor was diluted with 500 ml normal saline and the supernatant was filtered out with gauze . this solution was placed into the feeding bag and infused through a nasoenteric tube for 30 minutes ( fig . 2 ) . on the 84th hospital day , 9 days after fecal transplantation , laboratory test results were as follows : white blood cell count 6,280/mm ( neutrophils , 65.3% ; lymphocytes , 24.2% ; monocytes , 5.3% ) , hemoglobin 8.1 g / dl , platelets 224,000/mm , pt / aptt 14.8 sec/34.4 sec and albumin 2.7 g / dl . the patient 's diet was slowly advanced , and oral vancomycin was tapered to 125 mg every 12 hours . on the 94th hospital day , the patient was discharged with oral vancomycin after his symptoms had resolved . when he visited outpatient clinic 12 days after discharge , he had no symptoms of pmc ; therefore , oral vancomycin was discontinued . the destruction of normal intestinal flora after antibiotic use is the likely cause of most c. difficile infections . reestablishment of normal gut flora makes fecal transplant a logical treatment option for c. difficile infection . els van nood et al . reported that the decreased microbial diversity of infected patients recovered to the level of the donors after fecal transplantation . in current clinical practice , fecal transplantation is indicated for recurrent c. difficile infection and severe infection with no response to standard antibiotic therapy . the efficacy of fecal transplantation in recurrent c. difficile infection has been established in many case reports and meta - analyses and one recent randomized controlled study . there is a lack of data supporting fecal transplantation use in severe or fulminant c. difficile infection , but emerging data indicate that fecal transplantation is also effective in such cases . one recent retrospective study reported the effectiveness of fecal transplantation in 14 patients with severe , refractory c. difficile infection . patients were categorized as having severe c. difficile infection if they met two or more of the following criteria : age > 60 years , serum albumin < 2.5mg / dl , body temperature > 38.3 , or a white blood cell count > 15,000/mm within 48 hours of diagnosis ; or if they met one of the following criteria : endoscopic evidence of pseudomembranous colitis or treatment in the intensive care unit for c. difficile infection . refractory infection was defined as non - resolution of c. difficile infection despite 7 days of therapy with oral vancomycin . because of its cost effectiveness , high cure rate , minimal risk and reestablishment of normal flora , fecal transplantation has even been proposed as the initial treatment modality for severe c. difficile infection . in korea , two cases were recurrent c. difficile infections , and the other two cases were refractory c. difficile infections . two cases used egd and infused stool via the biopsy channel of egd . the other two cases used enema . in all four cases , c. difficile infection resolved . one patient who received egd experienced vomiting , and another patient who received enema had mild diarrhea after fecal transplantation . in our case , we used a nasogastric tube placed in the third portion of the duodenum by egd to perform the fecal transplantation . fecal transplantation can be performed using a nasogastric tube , nasoenteric tube , egd , colonoscopy , flexible sigmoidoscopy , or enema . two review studies compared fecal transplantation outcomes based on the route of administration of donor feces . one systematic review reported that fecal transplantation by egd or nasoenteric tube had a lower resolution rate than that by colonoscopy and enema ( 76.4% vs > 88.7% ) . most patients received treatment or preparation before fecal transplantation ; therefore , estimating the effect of fecal transplantation alone was difficult . the other review study compared colonoscopic fecal transplantation with nasogastric fecal transplantation from 12 published studies . colonoscopic fecal transplantation had a superior resolution rate ( 93.2% ) compared with nasogastric fecal transplantation ( 85.3% ) , but the difference was statistically nonsignificant . there has been no randomized , controlled trial comparing outcomes based upon the route of administration of fecal transplantation . transient gi symptoms are common , including decreased bowel movement , abdominal cramping , increased bowel sounds and abdominal discomfort . in fecal transplantation via the upper gastrointestinal tract , the risks of aspiration and vomiting should be considered . the colonoscopic approach could be dangerous in patients with severe colitis or colonic distension . a randomized controlled study by els van nood et al . reported acute adverse events including diarrhea ( 94% ) , cramping ( 31% ) and belching ( 19% ) in nasoenteric infusion , but these symptoms improved within 3 hours . generally , oral vancomycin is stopped before fecal transplantation ; however , oral vancomycin was continued and tapered in our case due to concerns regarding the potential failure of fecal transplantation . nevertheless , we are confident that fecal transplantation resulted in the resolution of c. diffcile infection because the patient exhibited no improvement during the previous 14 days of oral vancomycin therapy , but recovered dramatically after fecal transplantation . in conclusion , fecal transplantation could be a viable treatment option not only for recurrent c. difficile infection , but also for severe initial infection . further investigation is required to establish the optimal method of fecal transplantation and to ensure long - term safety .
the incidence of clostridium difficile infection is increasing worldwide , and its severity and resulting mortality are also on the rise . 
 metronidazole and oral vancomycin remain the treatments of choice , but there are concerns about treatment failure and the appearance of resistant strains . 
 furthermore , antibiotic therapy results in recurrence rates of at least 20% . 
 fecal transplantation may be a feasible treatment option for recurrent c. difficile infection ; moreover , it may be an early treatment option for severe c. difficile infection . 
 we report a case of severe c. difficile infection treated with fecal transplantation using a nasoenteric tube during an initial episode . 
 this is the first reported case of fecal transplantation using a nasoenteric tube during an initial episode of c. difficile infection in korea .