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PubMed2005

Diarrhea in liver transplant recipients: etiology and management.

Diarrhea is common after liver transplantation (LT). The true incidence of diarrhea in liver transplant recipients is unknown but possibly ranges from 10% to 43% based on a few published studies in other solid organ and bone marrow transplantation. Infectious etiologies, including cytomegalovirus (CMV), Clostridium difficile, and occasional atypical intestinal infections, are the most common causes. Diarrhea is also a frequent side effect of immunosuppressive medications. To variable extents, mycophenolate mofetil (MMF), cyclosporine A (CSA), tacrolimus, and sirolimus are all known to be associated with diarrhea. Rarely, graft-versus-host disease (GVHD), lymphoproliferative disorder, de novo inflammatory bowel disease (IBD), or colon cancer may present as diarrhea. Flare-up of preexisting IBD is also not uncommon after LT. However, the cause of acute diarrhea remains unidentified in 1 of 3 patients. This review summarizes the literature and provides recommendations on the management of acute diarrhea after LT. Although our focus is on LT, the etiology and management recommendations apply to most transplant recipients.

Colonic Neoplasms↗

PubMed2000

Effects of olestra and sorbitol consumption on objective measures of diarrhea: impact of stool viscosity on common gastrointestinal symptoms.

The aim of this study was to determine the effects of olestra and sorbitol consumption on three accepted objective measures of diarrhea (stool output >250 g/day, liquid/watery stools, bowel movement frequency >3/day), and how stool composition influences reports of common gastrointestinal symptoms. A double-blind, placebo-controlled study compared the effects of sorbitol (40 g/day in candy), a poorly absorbed sugar-alcohol with known osmotic effects, with those of olestra (20 or 40 g/day in potato chips), a nonabsorbed fat, on objective measures of stool composition and GI symptoms. Sixty-six subjects resided on a metabolic ward for 12 days: 2 days lead-in, 4 days baseline, 6 days treatment. Sorbitol 40 g/day resulted in loose/liquid stools within 1-3 h of consumption. In contrast, olestra resulted in a dose-responsive stool softening effect after 2-4 days of consumption. Subjects reported "diarrhea" when mean stool apparent viscosity (peak force (PF), g) decreased from a perceived "normal" (mean +/- SE, 1355 +/- 224 g PF; firm stool) to loose (260 +/- 68 g PF) stool. Mean apparent viscosity of stool during treatment: placebo, 1363 +/- 280 g (firm); olestra 20 g/day 743 +/- 65 g (soft); olestra 40 g/day, 563 +/- 105 g (soft); and sorbitol 40 g/day, 249 +/- 53 g (loose). Of the 1098 stool samples collected, 38% (419/1098) were rated by subjects as "diarrhea," yet only 2% of treatment days (all in the sorbitol treatment group) met commonly accepted criteria for a clinical diarrhea. Sorbitol, but not olestra, increased the severity of abdominal cramping, urgency and nausea compared to placebo. Olestra consumption, at levels far in excess of normal snacking conditions, resulted in a gradual stool softening effect after several days of consumption, did not meet any of the three objective measures of diarrhea, and did not increase GI symptoms. Sorbitol consumption, at only 80% of the dose requiring a "laxative effect" information label, resulted in rapid onset loose/liquid stools and a significant increase in abdominal cramping, urgency and nausea. Overall, subjects categorized stool as "diarrhea" when stool decreased from their perceived "normal," but the vast majority of these reports were not associated with clinically significant diarrhea.

Adolescent↗

PubMed1993

A preparation from bovine colostrum in the treatment of HIV-positive patients with chronic diarrhea.

In a prospective, open, uncontrolled study 25 patients infected with the human immunodeficiency virus with chronic refractory diarrhea and either confirmed cryptosporidiosis (n = 7) or absence of demonstrable pathogenic organisms (n = 18) were treated with a daily oral dose of 10 g of an immunoglobulin preparation from bovine colostrum over a period of 10 days. Among the 7 patients with cryptosporidiosis, this treatment led to complete remission in 3 and partial remission in 2. Among the 18 patients with diarrhea and negative stool culture, complete remission of diarrhea was obtained in 7 and partial remission in 4. In the remaining 2 patients with cryptosporidiosis and the 7 patients with diarrhea but no demonstrable pathogens treatment produced no significant improvement of the diarrhea. Subsequent doubling of the Lactobin dose (2 x 10 g daily) in 8 of the nonresponders led to complete remission in one case and at least partial remission in a further 4 patients. Treatment of refractory diarrhea with 10 g immunoglobulins from bovine colostrum per day constitutes an important therapeutic approach and led to complete (40%) or partial (24%) remission of diarrhea in 64% of the patients described here.

Animals↗

PubMed1995

Validation of a new measure of diarrhea.

Adequate measures of diarrheal disease are important to assess severity for clinical use and outcomes research. We developed a questionnaire to assess diarrhea severity and complications, and administered it to 205 HIV positive patients with diarrhea, fever, or weight loss. Noteworthy variations in stool form were reported by individuals and across subjects. Self-reported diarrhea correlated with the occurrence of any stool pictured without form. However, verbal descriptors "loose" and "semiformed" had little value in assessment of diarrheal disease. Both verbal and pictorial stool descriptors correlated well with diarrhea complications (pain, urgency, tenesmus, incontinence, and nocturnal diarrhea). By factor analysis, discomfort and nondiscomfort diarrhea complications loaded on different factors, consistent with clinical experience that discomfort is a distinct problem in diarrheal disease. In summary we have developed an instrument to precisely characterize diarrhea severity that correlates well with clinically important events such as incontinence and abdominal pain.

Abdominal Pain↗

PubMedDate not supplied

Etiology of chronic diarrhea.

With worldwide use of oral rehydration solutions, the treatment of acute diarrhea does not pose much of a problem. However, chronic diarrhea is still harmful, especially for the growth and development status of the children. Between January 1993 to December 1996, patients who suffered from chronic diarrhea for more than one month duration and admitted to Dr. Sami Ulus Children's Hospital were evaluated for epidemiological and etiologic factors. Seventy consecutive patients were evaluated. The mean age was 40.8 months and 52% were males. Malnutrition was detected in 80% of cases. Etiologic factors included celiac disease 30%, cow milk allergy 17%, bacterial and parasitic factors 26%, cystic fibrosis 10% and postinfectious gastroenteritis 10%. Eosinophilic gastroenteritis, chronic nonspecific diarrhea, pseudo-obstruction, neurofibromatosis and inflammatory bowel disease were rarely detected. Celiac disease and cow milk allergy were implicated as the most common causes of chronic diarrhea. The vicious cycle of faulty nutrition, malnutrition and infection and postinfectious enteropathy were also significant factors in the etiology of chronic diarrhea. It may be considered that cow milk protein prick test, sweat test, immunologic tests and mucosal biopsies should be performed for the definite diagnosis of chronic diarrhea.

Child↗

PubMedDate not supplied

Evaluation of vitamin K deficiency in children with acute and intractable diarrhea.

The purposes of this study were to determine the frequency of vitamin K deficiency and to assess its effects on bleeding in patients with acute and intractable diarrhea. A total of 90 children with diarrhea and 30 healthy children (group C) were included in this study. Patients were divided into 2 groups, according to the duration of diarrhea. Complete blood count; prothrombin time (PT); activated prothrombin time (APTT); Factors II, VII, IX, and X; and protein C levels were studied in all patients. A total of 3 mg of vitamin K was administrated to patients with prolonged PT and/or APTT. Coagulation parameters were restudied 8 to 12 h after vitamin K was administered. Mean age, sex, weight, and breastfeeding percentage, as well as history of fever and vitamin K administration at birth, were similar in the 2 groups. The duration of antibiotic administration in group B (intractable diarrhea) was significantly longer than that in group A (acute diarrhea). Gastrointestinal (GI) bleeding was observed in 3 (4.9%) infants in group A and 6 (20.7%) in group B (P<.05). The duration of diarrhea was significantly longer in infants with GI bleeding. Intracranial bleeding occurred in 1 infant with intractable diarrhea. Prolonged PT levels were noted in groups A and B. Significant improvement in PT and APTT and an increase in coagulation factors were observed after vitamin K had been administered. Investigators in this study conclude that coagulation parameters can be improved by the administration of vitamin K to children with deranged PT and APTT and diarrheal illness.

Acute Disease↗

PubMed2003

Enteroaggregative and cell-detaching Escherichia coli strains among Polish children with and without diarrhea.

To determine the association of enteroaggregative (EAEC) and cell-detaching (CDEC) Escherichia coli with diarrhea of unknown origin among children from Wrocław (Poland), E. coli strains isolated from stool specimens of children with diarrhea were examined for mannose-resistant adherence to HEp-2 cells. EAEC were isolated from 10 of 39 (26%) children examined with diarrhea and 4 of 20 (20%) age-matched controls. CDEC were present in 14 (36%) cases of diarrhea and 7 (35%) healthy subjects. Cell-detaching activity was distinctly associated with hemolysin production. Among hemolytic CDEC strains cytotoxic necrotizing factor 1 (CNF1) synthesis prevailed among isolates obtained from cases of diarrhea (57%) in comparison with isolates obtained from healthy controls (14.3%). Although neither EAEC nor CDEC E. coli strains were associated with diarrhea of children in this setting, there were differences among EAEC and CDEC strains isolated from children with and without diarrhea.

Bacterial Adhesion↗

PubMed2003

Preventive effect of Kampo medicine (Hangeshashin-to) against irinotecan-induced diarrhea in advanced non-small-cell lung cancer.

PURPOSE: Kampo medicine Hangeshashin-to (TJ-14) which contains baicalin, a beta-glucuronidase inhibitor, alleviates diarrhea induced by irinotecan (CPT-11). We conducted a randomized comparative trial to investigate whether support with TJ-14 would prevent and control CPT-11-induced diarrhea. METHODS: Of 44 previously untreated patients with advanced non-small-cell lung cancer randomized, 41 (18 TJ-14 group, 23 control group) were available for evaluation. The chemotherapy regimen consisted of a combination of cisplatin and CPT-11. TJ-14 (7.5 g/day) was administered orally. RESULTS: Of the 41 patients, 39 experienced diarrhea. Compared with the control group, the TJ-14 group showed a significant improvement in diarrhea grades ( P=0.044) as well as a reduced frequency of diarrhea grades 3 and 4 (one patient versus ten patients; P=0.018). However, the two groups showed no differences in the frequency of diarrhea or the number of days the symptoms continued. This study was stopped at an interim evaluation. CONCLUSION: TJ-14 was effective in preventing and controlling CPT-11-induced diarrhea.

Adult↗

PubMed2000

Modified irinotecan hydrochloride (CPT-11) administration schedule improves induction of delayed-onset diarrhea in rats.

PURPOSE: Clinically, diarrhea is the major dose-limiting toxicity of irinotecan hydrochloride (CPT-11). Using a rat model, we attempted to decrease the incidence of delayed-onset diarrhea by modifying the administration schedule of CPT-11, and studied the pharmacokinetics in this model in relation to the incidence of diarrhea. METHODS: CPT-11 (total dose, 240 mg/kg) was administered intravenously (i.v.) to rats according to various schedules, and the incidence of delayed-onset diarrhea was monitored. RESULTS: Administration of CPT-11 at a dose of 60 mg/kg once daily for four consecutive days induced severe diarrhea, while at 30 mg/kg twice daily at an interval of 9 h (daily dose 60 mg/kg) for four consecutive days alleviated the diarrheal symptoms, and at 30 or 40 mg/kg once daily for eight or six consecutive days, respectively. diarrhea was hardly induced. With the first schedule, mucosal impairment of the cecal epithelium was observed, including wall thickening, edema, decrease in crypt number and size, and formation of pseudomembrane-like substance, whereas these changes were less severe with the second schedule and were hardly observed with the other two schedules. The areas under the plasma and cecal tissue concentration-time curves (AUCpla and AUCcec), the maximum plasma concentrations (Cmax) and the biliary excretions of CPT-11 and its metabolites, 7-ethyl-10-hydroxycamptothecin (SN-38) and SN-38 glucuronide (SN-38G) in rats depended on the daily dose of CPT-11. Exceptionally, CPT-11 Cmax was significantly lower and SN-38 AUCcec was larger in the animals treated at 30 mg/kg twice daily than in those treated at 60 mg/kg once daily. CONCLUSION: These results suggested that the duration of exposure to both CPT-11 and SN-38 of the intestinal epithelium and CPT-11 plasma Cmax are closely related to the incidence and severity of CPT-11-induced delayed-onset diarrhea in rats.

Animals↗

PubMed2005

Diarrhea, CD4+ cell counts and opportunistic protozoa in Indian HIV-infected patients.

The aim of this study was to examine the relationships among diarrhea, CD4+ cell counts and opportunistic protozoa in HIV-infected patients in North India. In a retrospective study, blood and stool samples of 200 HIV-infected patients from March 2001 until 2003, submitted to the AIDS division of National Institute of Communicable Diseases (NICD), were analyzed. Each patient was examined for opportunistic protozoa, HIV-1 status and CD4+ cell counts, and screened for diarrheal symptoms. The rate of diarrhea was 38% in the stool examination. In HIV-infected patients in the groups CD4+ > 500 cells/microL, 200 cells/microL < CD4+ < 500 cells/muL and in the AIDS patients CD4+ < 200 cells/microL, diarrhea was 14.7, 29.8 and 56.1%, respectively. It is clear that the diarrhea in the AIDS patients was significant compared with the two former groups (P < 0.0005). In the AIDS patients CD4+ < 200 cells/microL with diarrhea, Cryptosporidium infection was, at 56.5%, the highest and statistically significant compared with the other parasites (P = 0.037). Microsporidium was detected in 30.4% of the AIDS patients. Diarrhea was common and most strongly associated in patients with low CD4+ cell counts. The data stress the importance of opportunistic protozoa in the HIV-infected patients, and that opportunistic protozoa should be expected in HIV-infected patients with low CD4+ and diarrhea.

AIDS-Related Opportunistic Infections↗

PubMed2004

Resolution of refractory chemotherapy-induced diarrhea (CID) with octreotide long-acting formulation in cancer patients: 11 case studies.

PURPOSE: Subcutaneous (SC) octreotide has been shown to effectively relieve chemotherapy-induced diarrhea (CID) refractory to conventional therapy but requires t.i.d. injections. A microencapsulated, long-acting formulation (LAR) of octreotide has been developed for once-monthly intramuscular (IM) dosing. Efficacy in resolving severe diarrhea and preventing further episodes of diarrhea in cancer patients was explored. PATIENTS AND METHODS: Patients with advanced cancer who developed CID and failed conventional antidiarrheal therapy (loperamide + diphenoxylate-atropine) received octreotide LAR IM. The starting dose was either 20 or 30 mg with possible dose escalation from 20 to 30 mg and from 30 to 40 mg. Treatment was repeated every 28 days during chemotherapy. RESULTS: Complete resolution of diarrhea within 1 to 4 weeks from injection time was seen in all cases with octreotide LAR 30 mg. With a subsequent prophylactic injection once every 28 days, CID was limited to NCI grade 1. This resulted in increased patient quality of life (QOL) and allowed better patient compliance with therapy. Therapy could then be completed at full dose and on schedule after resolution of often debilitating diarrhea. CONCLUSION: The ability of octreotide LAR 30 mg to speed the resolution of CID and limit further episodes of diarrhea to infrequent NCI grade 1 controlled with loperamide (prn) suggests that long-acting somatostatin homologues have the potential to be useful in the secondary prevention of diarrhea in patients undergoing chemotherapy.

Adult↗

PubMed2001

Control of irinotecan-induced diarrhea by octreotide after loperamide failure.

Diarrhea is a well-recognized side effect of chemotherapy, which affects the quality of life and when refractory is potentially life threatening. Irinotecan (CPT-11) is associated with an elevated incidence of chemotherapy-induced diarrhea and subsequent morbidity. Standard antidiarrheal treatment is based on high-dose loperamide, but this agent is associated with a significant failure rate. Octreotide is active against chemotherapy-induced diarrhea caused by fluoropyrimidines and irinotecan, with a distinct mechanism of action. We administered octreotide in a phase I trial in 37 patients who received irinotecan and experienced loperamide-refractory diarrhea, 23 of whom experienced grade III-IV diarrhea and were treated with loperamide. The 13 patients in whom to loperamide failed to control diarrhea received octreotide, with a high response rate (92%). We conclude that octreotide is effective against loperamide-refractory diarrhea resulting from irinotecan-based chemotherapy.

Adult↗

PubMed2006

Who are susceptible to pseudomembranous colitis among patients with presumed antibiotic-associated diarrhea?

PURPOSE: Pseudomembranous colitis is a severe form of antibiotic-associated diarrhea. However, there have been no reports about the factors that make patients with presumed antibiotic-associated diarrhea susceptible to pseudomembranous colitis. This study was designed to determine the clinical risk factors for pseudomembranous colitis among the patients with presumed antibiotic-associated diarrhea. METHODS: This was a retrospective study of 150 consecutive patients admitted to our institution between January 2000 and December 2004 with a diagnosis of presumed antibiotic-associated diarrhea. All patients underwent sigmoidoscopy or colonoscopy because of diarrhea after administration of antibiotics. Pseudomembranous colitis was confirmed both endoscopically and histologically. Various clinical parameters were compared between the pseudomembranous colitis group and non-pseudomembranous colitis group. RESULTS: The mean age of patients was 61 years, and 60 percent (90/150) was female. Pseudomembranous colitis was diagnosed in 53 percent (80/150). On univariate analysis, older than aged 70 years (P = 0.014), antibiotic therapy for more than 15 days (P < 0.0001), hospital stay for more than 20 days (P < 0.0001), number of antibiotics used more than one (P = 0.01), and surgical procedures (P = 0.029) were significant parameters for pseudomembranous colitis. On multivariate analysis, the important clinical risk factors were advanced age (older than aged 70 years; adjusted odds ratio, 2.7; 95 percent confidence interval, 1.208-6.131; P < 0.016) and long hospital stay (more than 20 days; adjusted odds ratio, 5.1; 95 percent confidence interval, 2.1-12.259; P < 0.0001). When both risk factors were present, the positive predictive value of pseudomembranous colitis was 0.86. CONCLUSIONS: Advanced age and long hospital stay may make patients with presumed antibiotic-associated diarrhea susceptible to pseudomembranous colitis. Therefore, pseudomembranous colitis should be first suspected in cases with presumed antibiotic-associated diarrhea having such risk factors.

Aged↗

PubMed1981

Treatment of Clostridium difficile colitis and diarrhea with vancomycin.

Toxigenic Clostridium difficle is the major cause of antibiotic-associated colitis and is susceptible to vancomycin at fecal concentrations achieved with oral therapy. The effect of oral vancomycin was studied in 16 patients with C. difficile-related diarrhea or colitis, 12 of whom had colitis documented by endoscopy, biopsy, and/or barium enema. Four patients had antibiotic-associated diarrhea and possibly antibiotic-associated colitis, because sigmoidoscopy either showed normal results (two patients) or was not performed (two patients). Nineteen episodes of diarrhea were treated with oral vancomycin in two dosage regimens for three to 14 days. Twelve patients received 2 g daily, and four patients initially received 1 g or less per day. Within 48 hours of the start of vancomycin therapy, 14 of 16 patients (87 percent) showed a decrease in temperature, abdominal pain and diarrhea. Diarrhea ceased completely within two days of the start of vancomycin in nine episodes, within three to seven days in six episodes, and within eight to 14 days in the remaining four episodes, and within eight to 14 days in the remaining four episodes. Diarrhea recurred in two of these patients (12 percent) when the drug inciting the initial episode of colitis was given again 42 days or more after vancomycin therapy was stopped; both patients responded again to retreatment with vancomycin. Oral vancomycin is an effective treatment of C. difficile-related colitis and diarrhea.

Adolescent↗

PubMed2005

The effect of fermented yogurt on the prevention of diarrhea in a healthy adult population.

BACKGROUND: Probiotic dairy products are increasingly gaining popularity. Although the role of probiotic bacteria in the prevention and treatment of pediatric and antibiotic associated diarrhea is fairly well established, their role in the prevention of adult infectious diarrhea has not been well investigated. METHODS: Five hundred forty-one, young male military recruits were enrolled and randomly assigned to receive a yogurt containing Lactobacillus casei (n = 275) or a nonprobiotic yogurt (n = 266). The incidence and duration of diarrhea were documented and stool samples examined for bacteria and parasites. RESULTS: Five hundred and two participants were eligible for final analysis, 254 receiving probiotic yogurt and 248 in the control group. Seventy-one participants (14.14%) experienced diarrhea during the study period. The incidence of diarrhea in the probiotic group and the control group was 12.2% and 16.1%, respectively (P = .207). The mean duration of diarrhea was 3 +/- 1.95 days in the probiotic group and 2.6 +/- 1.08 days in the control group (P = .276). CONCLUSION: Our study demonstrated a nonsignificant trend for reduction of the incidence of diarrhea among healthy young adults consuming yogurt containing Lactobacillus casei . Further study is needed to evaluate the role of probiotics in adults.

Adolescent↗

PubMed2006

Etiology and epidemiology of diarrhea in children in Hanoi, Vietnam.

OBJECTIVES: This paper provides a preliminary picture of diarrhea with regards to etiology, clinical symptoms, and some related epidemiologic factors in children less than five years of age living in Hanoi, Vietnam. METHODS: The study population included 587 children with diarrhea and 249 age-matched healthy controls. The identification of pathogens was carried out by the conventional methods in combination with ELISA, immunoseparation, and PCR. The antibiotic susceptibility was determined by MIC following the NCCLS recommendations. RESULTS: Of those with diarrhea, 40.9% were less than one year old and 71.0% were less than two years old. A potential pathogen was identified in 67.3% of children with diarrhea. They were group A rotavirus, diarrheagenic Escherichia coli, Shigella spp, and enterotoxigenic Bacteroides fragilis, with prevalences of 46.7%, 22.5%, 4.7%, and 7.3%, respectively. No Salmonella spp or Vibrio cholerae were isolated. Rotavirus and diarrheagenic E. coli were predominant in children less than two years of age, while Shigella spp, and enterotoxigenic B. fragilis were mostly seen in the older children. Diarrheagenic E. coli and Shigella spp showed high prevalence of resistance to ampicillin, chloramphenicol, and to trimethoprim/sulfamethoxazole. Children attending the hospitals had fever (43.6%), vomiting (53.8%), and dehydration (82.6%). Watery stool was predominant with a prevalence of 66.4%, followed by mucous stool (21.0%). The mean episodes of stools per day was seven, ranging from two to 23 episodes. Before attending hospitals, 162/587 (27.6%) children had been given antibiotics. Overall, more children got diarrhea in (i) poor families; (ii) families where piped water and a latrine were lacking; (iii) families where mothers washed their hands less often before feeding the children; (iv) families where mothers had a low level of education; (v) families where information on health and sanitation less often reached their households. CONCLUSIONS: Group A rotavirus, diarrheagenic Escherichia coli, Shigella spp, and enterotoxigenic Bacteroides fragilis play an important role in causing diarrhea in children in Hanoi, Vietnam. Epidemiological factors such as lack of fresh water supply, unhygienic septic tank, low family income, lack of health information, and low educational level of parents could contribute to the morbidity of diarrhea in children.

Bacteroides Infections↗

PubMed2006

Epidemiology and strain characterization of rotavirus diarrhea in Malaysia.

OBJECTIVES: The objectives of the study were to describe the epidemiology and strain characterization of rotavirus (RV), to determine the proportion of hospitalizations for diarrhea attributable to RV among children under 5 years of age, and to estimate the disease burden of RV diarrhea in Malaysia. METHODS: All children 0-59 months of age admitted for acute gastroenteritis to Kuala Lumpur Hospital (KLH) or Hospital Umum Sarawak (HUS) were surveyed. The periods of surveillance were from February 1, 2001 to April 30, 2003 in KLH and April 1, 2001 to March 31, 2003 for HUS. RESULTS: The highest rate of RV-associated diarrhea was among children aged 6-17 months, accounting for 55% of RV-associated diarrhea. There was no seasonality observed in either hospital. P[8]G9 strains were predominant, accounting for 73% of all strains in both hospitals, 80% from KLH and 61% from HUS. There was no mortality. CONCLUSIONS: RV was responsible for 38% of hospitalizations for diarrhea. It was most common in the 6-17 months age group. There was no seasonality observed for RV-associated diarrhea. The most prevalent strain of RV was P[8]G9. The estimated incidence of RV-associated diarrhea was 27 per 10000 population under the age of 5 years per year.

Age Factors↗

PubMed2004

Increased tacrolimus trough levels in association with severe diarrhea, a case report.

It is well known that during diarrhea episodes decreased cyclosporine and tacrolimus levels are often observed, usually requiring an increase in dose. An increase in tacrolimus trough levels is infrequently recognized as a potential cause of the adverse effect of severe diarrhea. Herein, we report the case of a renal transplant patient who displayed increased tacrolimus trough levels during an episode of gastroenteritis with severe diarrhea. The patient is 32-year-old male who received a renal transplant from his mother. Immunosuppression was initiated with tacrolimus in combination with mycophenolate mofetil and prednisone. The postoperative course was uneventful. The function of the transplanted kidney was normal. Eight months after transplantation he presented to our hospital with a history of high fever, abdominal pain, nausea and severe diarrhea. He was admitted with a diagnosis of enterocolitis of unknown etiology. The blood trough level of tacrolimus had increased from 6.7 ng/mL to 28.7 ng/mL after the onset of diarrhea. A therapeutic trough level of tacrolimus was reached 6 weeks after complete relief of diarrhea. Tacrolimus shows large variability in bioavailability after oral administration, both due to intestinal metabolism by cytochrome P450 (CYP3A4) and active secretion from enterocyte into intestinal lumen by P-glycoprotein. The epithelial cells of the intestine, may be destroyed abrogating P-glycoproteins during the course of enterocolitis, thereby increasing the levels of tacrolimus. It is recommended to monitor trough levels of tacrolimus during severe diarrhea of any nature to prevent tacrolimus-related complications.

Adult↗