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Astrovirus-associated diarrhea among Guatemalan ambulatory rural children.

Fecal excretion of astroviruses was monitored in 321 children, 0 to 3 years old, living in the rural highlands of Guatemala. During the longitudinal study, from February 1987 to February 1989, we examined 5,000 stool specimens, including 1,805 collected during 1,369 episodes of diarrhea, 830 collected during the convalescent week, and 216 and 244 collected 2 weeks and 1 week, respectively, before the onset of diarrhea. Routine specimens were taken once a month from every child who had been free from diarrhea for at least three consecutive weeks. Of the children, 124 (38.6%) excreted astroviruses during the study. In total, we identified 184 infections by astroviruses. Of the samples collected 2 weeks and 1 week before the initiation of symptoms, 0.9 and 4.9%, respectively, were positive, while 7.3% of the diarrhea episodes were associated with astroviruses. Of the convalescent specimens, 3.4% were shown to be positive; 2.4% of the 1,905 specimens taken in diarrhea-free periods contained astroviruses. Infections by other potential enteropathogens were documented in 54 and 65% of the asymptomatic and symptomatic astrovirus infections, respectively. Diarrhea associated with astroviruses alone had a median duration of 5 days and was associated with vomiting in 8.6%, with fever in 17.1%, with dehydration in 5.7%, and with loss of appetite in 34.3% of the episodes. Diarrhea due to astroviruses was accompanied by negative changes in weight gain. Astrovirus diarrhea contributes to the high morbidity observed in young children living under poor conditions and has a deleterious effect on their nutritional status.

Body Weight↗

Investigation of diarrhea in AIDS.

Chronic diarrhea is a common problem in patients with acquired immune deficiency syndrome (AIDS), resulting in significant morbidity and potential mortality. In the early stages of immunodeficiency, human immunodeficiency virus (HIV)-infected patients are susceptible to infection with the same enteric pathogens that cause diarrhea in immunocompetent hosts, but with progressive immunodeficiency, these patients become susceptible to numerous opportunistic disorders. The main factor to consider when tailoring the work-up of diarrhea in the HIV-infected patient is the immune status, which is reflected by the total CD4 lymphocyte cell count. A CD4 count of less than 100 cells/microL is significantly correlated with opportunistic disorders. For the HIV-infected patient with diarrhea, repeated stool studies to investigate for bacteria, ova and parasites should be the first step. When either upper or lower gastrointestinal tract symptoms are present and stool studies are negative, endoscopy directed to the probable organ of involvement is appropriate. If localizing symptoms are absent, the most appropriate next test is sigmoidoscopy with biopsies. Not infrequently, despite extensive evaluation, the cause of diarrhea in patients with AIDS remains unexplained. Recently, the widespread use of highly active antiretroviral therapy, including protease inhibitors, has led to a change in the epidemiology of diarrhea in AIDS patients. As their immune status improves, HIV-infected patients treated with combination therapy become less prone to opportunistic disorders. However, diarrhea appears to be frequent because several antiretroviral agents can themselves cause diarrhea.

Acquired Immunodeficiency Syndrome↗

Estimating the cost of illness in colorectal cancer patients who were hospitalized for severe chemotherapy-induced diarrhea.

BACKGROUND: Previous studies have suggested that grade III/IV diarrhea is a common complication in colorectal cancer, occurring in 20% to 30% of patients receiving chemotherapy. In some of these patients, hospitalization for supportive care is often required. However, the impact that these hospitalized patients have on overall use of health care resources has not been quantified. In the present study, a cost of illness analysis was conducted to estimate the overall cost of patients with colorectal cancer who were hospitalized for supportive care secondary to severe diarrhea. METHODS: This was a retrospective cohort study consisting of patients with colorectal cancer that had received fluoropyrimidines, irinotecan or oxaliplatin (or a combination thereof) and had developed grade III or IV diarrhea that resulted in hospital admission for supportive care. Data collection included patient demographics, disease-related information and use of health care resources to manage the grade III/IV diarrhea event. RESULTS: Patients had a mean age of 64.2 years, and 32 of 63 (50.8%) were receiving adjuvant chemotherapy with a curative intent. The severe diarrhea developed after the first cycle of chemotherapy in 58% of the patients and contributed to a dose reduction, change or discontinuation of chemotherapy in 9.5%, 15.9% and 34.2% of patients, respectively. Overall, the median length of hospital stay was eight days (range one to 49 days) translating to a mean cost of $8,230 per patient (95% CI $6,519 to $9,942). The diarrhea successfully resolved in 54 of 63 patients (85.7%). CONCLUSIONS: Severe diarrhea requiring hospital admission is a costly and potentially fatal complication of chemotherapy in colorectal cancer. The identification of predictive factors and the implementation of prophylactic measures could reduce the morbidity and mortality associated with diarrhea.

Antineoplastic Agents↗

Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose.

The purpose of these studies was to gain insight into the pathophysiology of pure osmotic diarrhea and the osmotic diarrhea caused by carbohydrate malabsorption. Diarrhea was induced in normal volunteers by ingestion of polyethylene glycol (PEG), which is nonabsorbable, not metabolized by colonic bacteria, and carries no electrical charge. In PEG-induced diarrhea, (a) stool weight was directly correlated with the total mass of PEG ingested; (b) PEG contributed 40-60% of the osmolality of the fecal fluid, the remainder being contributed by other solutes either of dietary, endogenous, or bacterial origin; and (c) fecal sodium, potassium, and chloride were avidly conserved by the intestine, in spite of stool water losses exceeding 1,200 g/d. Diarrhea was also induced in normal subjects by ingestion of lactulose, a disaccharide that is not absorbed by the small intestine but is metabolized by colonic bacteria. In lactulose-induced diarrhea, (a) a maximum of approximate 80 g/d of lactulose was metabolized by colonic bacteria to noncarbohydrate moieties such as organic acids; (b) the organic acids were partially absorbed in the colon; (c) unabsorbed organic acids obligated the accumulation of inorganic cations (Na greater than Ca greater than K greater than Mg) in the diarrheal fluid; (d) diarrhea associated with low doses of lactulose was mainly due to unabsorbed organic acids and associated cations, whereas with larger doses of lactulose unmetabolized carbohydrates also played a major role; and (e) the net effect of bacterial metabolism of lactulose and partial absorption of organic acids on stool water output was done dependent. With low or moderate doses of lactulose, stool water losses were reduced by as much as 600 g/d (compared with equimolar osmotic loads of PEG); with large dose, the increment in osmotically active solutes within the lumen exceeded the increment of the ingested osmotic load, and the severity of diarrhea was augmented.

Adult↗

[Study on the mechanisms of diarrhea induced by a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats].

We investigated the mechanisms of CPT-11-induced diarrhea. 1) CPT-11 (80 mg/kg, i.v.) induced watery diarrhea within 1 hr after dosing in saline-loaded (10 ml/kg, p.o.) rats. This was partially inhibited by subcutaneous injection of atropine (1 mg/kg) or ondansetron (1 mg/kg) and almost completely inhibited by a combination of atropine and ondansetron or by clonidine (0.3 mg/kg) or morphine (10 mg/kg) alone. 2) CPT-11 at the same dose reduced intestinal fluid absorption, which was blocked by the anti-diarrheal agents mentioned above. Intraluminal injection of CPT-11 (20 mg/2 ml) inhibited fluid absorption and induced fluid secretion. 3) CPT-11, 60 mg/kg, by single intravenous injection induced fewer enzymological and histological changes in the small intestine than 5-FU at 270 mg/kg, while 4 consecutive dosings of CPT-11 induced delayed diarrhea (days 5-7) associated with disruption of intestinal integrity. Co-administration with anti-diarrheal agents, except for ondansetron, protected against watery diarrhea appearing within 1 hr after CPT-11 on days 3 and 4, but worsened delayed diarrhea. These results suggest that single injection of higher doses of CPT-11 causes watery diarrhea at an acute phase at least partly by reducing fluid absorption or increasing secretion, and that while conventional anti-diarrheal agents protect against watery diarrhea, their co-administration in repeated CPT-11 administration has no ameliorative effect on CPT-11-induced delayed diarrhea.

Animals↗

Calcium polycarbophil, a water absorbing polymer, increases bowel movement and prevents sennoside-induced diarrhea in dogs.

The effects of calcium polycarbophil (CP), a water-absorbing polymer, on bowel movement were examined in comparison with known laxatives and anti-diarrheal agents in dogs, a species that resembles humans for stool output. CP increased stool frequency, fecal water content and fecal weight in a dose-dependent manner, but did not induce diarrhea. Sennoside and carboxymethylcellulose sodium (CMC-Na) increased fecal water content and induced diarrhea at lower doses than that which enhanced stool frequency. Trimebutine decreased stool frequency, fecal weight and fecal water content, resulting in inhibition rather than stimulation of defecation. In sennoside-induced diarrhea, loperamide and CP improved stool consistency and this was accompanied by reduced fecal moisture and frequency of diarrhea. In contrast, CMC-Na aggravated stool consistency with increased fecal water content and frequency of diarrhea, and trimebutine had little noticeable effect apart from reducing fecal weight. Our results show that CP has both laxative and anti-diarrheal effects in dogs and differed from conventional laxatives and anti-diarrheal agents. CP may be a suitable agent for treatment of idiopathic constipation, secretory diarrhea and irritable bowel syndrome with alternating constipation and diarrhea and with either predominating in terms of less side effects such as diarrhea or constipation.

Acrylic Resins↗

L-glutamine supplementation improves nelfinavir-associated diarrhea in HIV-infected individuals.

PURPOSE: To determine whether L-glutamine decreases the severity of nelfinavir-associated diarrhea in HIV-infected individuals. Other endpoints include the effect on quality of life, muscle-wasting syndrome, CD4 counts, and viral load. METHOD: HIV-infected patients with nelfinavir-associated diarrhea for >1 month were randomized to receive L-glutamine 30 g/day or placebo for 10 days in a prospective, double-blind, crossover study. Diarrhea was measured on a scale ranging from grade 0 (no diarrhea) to grade 4 (severe diarrhea, > 7 stools/day). Quality of life was assessed by the Medical Outcome Study (MOS) HIV questionnaire. RESULTS: Twenty-five participants completed the study. There was a significant difference between the L-glutamine and placebo arms on the mean grade of diarrhea (0.762 vs. 1.850, p <.01) when placebo was administered first. When L-glutamine was administered first, there was a significant crossover effect (p <.02), with similar mean grades of diarrhea in the two groups. There was also a significant difference between L-glutamine and placebo in the mean change in MOS scores from baseline (1.48 vs. -2.19, p <.017). There were no significant differences between treatment groups for the other endpoints. CONCLUSIONS: In this population of HIV-positive participants, L-glutamine 30 g/day significantly (p <.01) reduced the severity of nelfinavir-associated diarrhea and produced improved quality of life compared with placebo.

Administration, Oral↗

Prevalence of diarrhea at a university hospital and association with modifiable risk factors.

OBJECTIVE: To assess the prevalence of diarrhea at a university-affiliated medical center and the presence of modifiable risk factors. METHODS: A point prevalence survey was conducted. All patients hospitalized for more than 24 hours were asked if they were experiencing diarrhea. Stools of patients not previously tested were assessed for Clostridium difficile (CD) toxins A and B. Univariate analysis and multivariate logistic regression analyses were used to identify modifiable variables associated with diarrhea (significance defined as p < 0.05). RESULTS: Four hundred eighty-five hospitalized patients were interviewed, of whom 60 (12.4%) reported 2 or more loose, unformed stools in the last 24 hours. Six of 81 (7.4%) patients tested positive for CD toxin. Three (50%) of the CD toxin-positive patients had not previously been tested during the current admission. Patients with diarrhea were more likely to have tested CD toxin-positive (OR 10.6; p = 0.01), received antibiotics (OR 1.79; p = 0.04), or been hospitalized for a longer period of time (p = 0.04). CONCLUSIONS: Diarrhea was prevalent in 12.4% of hospitalized patients at a large university hospital at one point in time. Patients with diarrhea were more likely to have CD infection, receive antibiotics, or experience a longer hospitalization. Half of the CD diarrhea cases occurring in the hospital had been previously unidentified. Hospitalized patients should be evaluated for diarrhea on an ongoing basis with appropriate interventions instituted.

Adult↗

Effectiveness and efficacy of zinc for the treatment of acute diarrhea in young children.

UNLABELLED: Intervention trials have shown that zinc is efficacious in treating acute diarrhea in children of developing countries. In a randomized, placebo-controlled trial, we assessed the effectiveness and efficacy of giving 3 Recommended Daily Allowances of elemental zinc to 6- to 35-month-old children with acute diarrhea. METHODS: Seventeen hundred ninety-two cases of acute diarrhea in Nepalese children were randomized to 4 study groups. Three groups were blinded and the children supplemented daily by field workers with placebo syrup, zinc syrup, or zinc syrup and a massive dose of vitamin A at enrollment. The fourth group was open and the caretaker gave the children zinc syrup daily. Day-wise information on morbidity was obtained by household visits every fifth day. RESULTS: The relative hazards for termination of diarrhea were 26% (95% confidence interval [CI]: 8%, 46%), 21% (95% CI: 4%, 38%), and 19% (95% CI: 2%, 40%) higher in the zinc, zinc-vitamin A, and zinc-caretaker groups, respectively, than in the placebo group. The relative risks of prolonged diarrhea (duration >7 days) in these groups were 0.57 (95% CI: 0.38, 0.86), 0.53 (95% CI: 0.35, 0.81), and 0.55 (0.37, 0.84); zinc accordingly reduced the risk of prolonged diarrhea with 43% to 47%. Five percent and 5.1% of all syrup administrations were followed by regurgitation in the zinc and zinc-vitamin A group, respectively, whereas this occurred after only 1.3% of placebo administrations. Vomiting during diarrhea was also more common in children receiving zinc. CONCLUSIONS: Three Recommended Daily Allowances of zinc given daily by caretakers or by field workers substantially reduced the duration of diarrhea. The effect of zinc was not dependent on or enhanced by concomitant vitamin A administration.

Acute Disease↗

Diarrhea- and rotavirus-associated hospitalizations among children less than 5 years of age: United States, 1997 and 2000.

OBJECTIVE: A new rotavirus vaccine may be licensed in the United States in early 2006. Estimates of the burden of severe rotavirus disease, particularly hospitalizations, will help evaluate the potential benefits of a national rotavirus immunization program. DESIGN: The Kids' Inpatient Database, a robust sample of 10% of the uncomplicated births and 80% of other pediatric discharges was used to estimate the number and rate of diarrhea- and rotavirus-associated hospitalizations among US children <5 years of age in 1997 and 2000. RESULTS: In 1997 and 2000, diarrhea was coded in 13% of all childhood hospitalizations, for an estimated cumulative incidence of 1 diarrhea hospitalization per 23 to 27 children by age 5. Most diarrhea-associated hospitalizations (62%) were coded as unspecified etiology, and 35% as viral. Rotavirus was the most common pathogen recorded for 18% and 19% of diarrhea-associated hospitalizations in 1997 and 2000, respectively. Diarrhea-associated hospitalizations coded as unspecified or viral exhibited a marked winter peak similar to that of hospitalizations coded as rotavirus, suggesting that the rotavirus-specific code captures a fraction of all rotavirus hospitalizations. Using indirect methods, we estimated that rotavirus was associated with 51142-60155 and 46839-56820 hospitalizations in 1997 and 2000, respectively. By these estimates, rotavirus is associated with 4% to 5% of all childhood hospitalizations, and 1 in 67 to 1 in 85 children will be hospitalized with rotavirus by 5 years of age. CONCLUSIONS: Diarrhea is an important cause of hospitalization in US children, and rotavirus is the most important etiology. Disease burden estimates have remained stable during the past decade. An effective rotavirus vaccine will likely reduce substantially the burden of severe rotavirus disease, estimated to account for 4% to 5% of all hospitalizations and approximately 30% of hospitalizations for watery diarrhea among children <5 years of age.

Child, Preschool↗

Impact of zinc supplementation on morbidity from diarrhea and respiratory infections among rural Guatemalan children.

OBJECTIVE: A community-based, randomized, double-blind intervention trial was conducted to measure the impact of zinc supplementation on young Guatemalan children's morbidity from diarrhea and respiratory infections. METHODS: Children aged 6 to 9 months were randomly assigned to receive 4 mL of a beverage containing 10 mg of zinc (as zinc sulfate) daily (7 d/wk) for 7 months (n = 45) or a placebo (n = 44). Morbidity data were collected daily. Diagnoses of diarrhea, fever, and anorexia were based on mothers' definitions. Respiratory infections were defined as the presence of at least two of the following symptoms: runny nose, cough, wheezing, difficulty breathing, or fever. RESULTS: High rates of diarrhea and respiratory infections were reported. Children from the placebo group had a 20% episodic prevalence of diarrhea, with 8 episodes/100 d, and a 7% episodic prevalence of respiratory infections, with 3 episodes/100 d. The median incidence of diarrhea among children who received zinc supplementation was reduced by 22% (Wilcoxon rank test), with larger reductions among boys and among children with weight-for-length at baseline lower than the median of the sample (39% reductions in both subgroups). Zinc supplementation also produced a 67% reduction in the percentage of children who had one or more episodes of persistent diarrhea (chi2 test). No significant effects were found on the episodic prevalence of diarrhea, the number of days per episode, or the episodic prevalence or incidence of respiratory infections. CONCLUSIONS: The large impact of zinc supplementation on diarrhea incidence suggests that young, rural Guatemalan children may be zinc deficient and that zinc supplementation may be an effective intervention to improve their health and growth.

Deficiency Diseases↗

Rotavirus diarrhea disease burden in Peru: the need for a rotavirus vaccine and its potential cost savings.

OBJECTIVE: To assess the disease burden of rotavirus diarrhea in Peru as well the need for and the potential cost savings with a rotavirus vaccine in that country. METHODS: To assess the burden of rotavirus diarrhea in Peru, we reviewed published and unpublished reports where rotavirus was sought as the etiologic agent of diarrhea in children. Rotavirus detection rates obtained from these studies were combined with diarrhea incidence rates from a number of national surveys in order to estimate both the burden of rotavirus diarrhea in the country and its associated medical costs. RESULTS: Rotavirus is a significant cause of morbidity and mortality in Peruvian children. In their first 5 years of life, an estimated 1 in 1.6 children will experience an episode of rotavirus diarrhea, 1 in 9.4 will seek medical care, 1 in 19.7 will require hospitalization, and 1 in 375 will die of the disease. Per year, this represents approximately 384,000 cases, 64,000 clinic visits, 30,000 hospitalizations, and 1,600 deaths. The annual cost of medical care alone for these children is approximately US$ 2.6 million--and that does not take into account the indirect or societal costs of the illness and the deaths. CONCLUSIONS: Rotavirus immunization provides the prospect of decreasing the morbidity and mortality from diarrhea in Peru, but a vaccine regimen would have to be relatively inexpensive, a few dollars or less per child. Future cost-effectiveness analyses should explore the total costs (medical as well as indirect or societal) associated with rotavirus diarrhea. Newly licensed vaccines should be tested according to both their ability to avert deaths and their efficacy with fewer than three doses. All three of these factors could increase the cost savings associated with a rotavirus vaccine.

Cost Savings↗

Metformin as a cause of late-onset chronic diarrhea.

Metformin is an effective and commonly administered drug for controlling plasma glucose concentrations in patients with type 2 diabetes mellitus. Gastrointestinal adverse effects such as abdominal pain, nausea, dyspepsia, anorexia, and diarrhea are common and widely accepted when occurring at the start of metformin therapy. Diarrhea occurring long after the dosage titration period is much less well recognized. Our patient began to experience nausea, abdominal cramping, and explosive watery diarrhea that occasionally caused incontinence after several years of stable metformin therapy A trial of metformin discontinuation resolved all gastrointestinal symptoms. A review of the literature revealed two reports that suggest diarrhea occurring long after the start of metformin therapy is relatively common, based on surveys of patients with diabetes. Metformin-induced diarrhea is differentiated from diabetic diarrhea, which is clinically similar, except diabetic diarrhea is rare in patients with type 2 diabetes. Patients with type 2 diabetes who are taking metformin and experience diarrhea deserve a drug-free interval before undergoing expensive and uncomfortable diagnostic tests, even when the dosage has been stable over a long period.

Chronic Disease↗

Antimicrobial use in the treatment of calf diarrhea.

Calves with diarrhea often have small intestinal overgrowth with Escherichia coli bacteria, regardless of the inciting cause for the diarrhea, and 30% of systemically ill calves with diarrhea have bacteremia, predominantly because of E coli. Antimicrobial treatment of diarrheic calves should therefore be focused against E coli in the small intestine and blood, the 2 sites of infection. Fecal bacterial culture and antimicrobial susceptibility testing is not recommended in calves with diarrhea because fecal bacterial populations do not accurately reflect small intestinal or blood bacterial populations and because the break points for susceptibility test results have not been validated. Antimicrobial efficacy is therefore best evaluated by the clinical response of a number of calves to treatment, with calves randomly assigned to treatment groups. Amoxicillin, chlortetracycline, neomycin, oxytetracycline, streptomycin, sulfachloropyridazine, sulfamethazine, and tetracycline administered PO are currently labeled in the United States for the treatment of calf diarrhea. On the basis of published evidence for the oral administration of these antimicrobial agents, only amoxicillin can be recommended for the treatment of diarrhea. Dosage recommendations are amoxicillin trihydrate (10 mg/kg PO q12h) or amoxicillin trihydrate-clavulanate potassium (12.5 mg combined drug/kg PO q12h) for at least 3 days; the latter constitutes extra-label drug use. Parenteral administration of broad-spectrum beta-lactam antimicrobials--ceftiofur (2.2 mg/kg IM or SC q12h) and amoxicillin or ampicillin (10 mg/kg IM q12h)--or potentiated sulfonamides (25 mg/kg IV or IM q24h) is recommended for treating calves with diarrhea and systemic illness; both constitute extra-label drug use. In calves with diarrhea and no systemic illness (normal appetite for milk, no fever), it is recommended that the health of the calf be monitored and that oral or parenteral antimicrobials not be administered.

Administration, Oral↗

Maternal feeding behavior and child acceptance of food during diarrhea, convalescence, and health in the central Sierra of Peru.

Feeding patterns by mothers and child acceptance of food were measured in a Peruvian village to determine changes on days when children had diarrhea as compared to days of convalescence and health. Morbidity surveillance identified 40 children, aged 4-36 months, with diarrhea. Children were followed using twelve-hour in-home structured observations during two to four days each of diarrhea, convalescence, and health. Using scales of maternal encouragement to eat and child acceptance of food and cumulative logistic regression analyses, maternal encouragement to eat decreased significantly during convalescence compared to diarrheal days (OR: 0.54, 90% CI: 0.35, 0.82) and health compared to diarrhea (OR: 0.65, 90% CI: 0.46, 0.93). In contrast, child acceptance of food increased during health compared to diarrhea (OR: 1.55, 90% CI: 1.02, 2.35). Results illustrate the importance of carefully examining the behavioral aspects of nutritional intake. Decreases in intake during diarrhea are due to anorexia and not withdrawal of food by mothers. In response to reductions in child appetite during illness, mothers are more likely to encourage children to eat, while they tend to become more passive feeders after the diarrhea has stopped. Program efforts should focus on messages to feed children more actively especially after diarrhea episodes, when appetite levels increase.

Adult↗

Novel agents that potentially inhibit irinotecan-induced diarrhea.

Irinotecan (CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) has exhibited clinical activities against a broad spectrum of carcinomas by inhibiting DNA topoisomerase I (Topo I). However, severe and unpredictable dosing-limiting toxicities (mainly myelosuppression and severe diarrhea) hinder its clinical use. The latter consists of early and late-onset diarrhea, occurring within 24 hr or > or = 24 hr after CPT-11 administration, respectively. This review highlights novel agents potentially inhibiting CPT-11-induced diarrhea, which are designed and tested under guidance of disposition pathways and potential toxicity mechanisms. Early-onset diarrhea is observed immediately after CPT-11 infusion and probably due to the inhibition of acetylcholinesterase activity, which can be eliminated by administration of atropine. Late-onset diarrhea appears to be associated with intestinal exposure to SN-38 (7-ethyl-10-hydroxycamptothecin), the major active metabolite of CPT-11, which may bind to Topo I and induce apoptosis of intestinal epithelia, leading to the disturbance in the absorptive and secretory functions of mucosa. CPT-11 and SN-38 may also stimulate the production of pro-inflammatory cytokines and prostaglandins (PGs), thus inducing the secretion of Na(+) and Cl(-). Early treatment of severe late-onset diarrhea with oral high-dose loperamide has decreased patient morbidity. Extensive studies have been conducted to identify other potential agents to ameliorate diarrhea in preclinical and clinical models. These include intestinal alkalizing agents, oral antibiotics, enzyme inducers, P-glycoprotein (PgP) inhibitors, cyclooxygenase-2 (COX-2) inhibitors, tumor necrosis factor-alpha (TNF-alpha) inhibitors, or blockers of biliary excretion of SN-38. Further studies are needed to identify the molecular targets associated with CPT-11 toxicity and safe and effective agents for alleviating CPT-11-induced diarrhea.

Animals↗

Pseudomonas aeruginosa as a potential cause of antibiotic-associated diarrhea.

Although Pseudomonas aeruginosa is not generally considered as a cause of antibiotic-associated diarrhea, several cases of diarrhea caused by P. aeruginosa have been reported. We experienced seven cases of nosocomial diarrhea presumably caused by P. aeruginosa, which was the predominant organism isolated from stool cultures. Clostridium difficile toxin was also positive in one patient. No other potential or recognized enteropathogens were identified from stools. All patients had underlying diseases and had been receiving antibiotics before the diarrheal onset. All of the seven P. aeruginosa isolates were resistant to previously given antibiotics. Diarrhea stopped three days after withdrawal of probable offending antibiotics without specific treatment in two patients. The other five patients having continuous diarrhea despite withdrawal of probable offending antibiotics, were successfully treated with antipseudomonal agents. The median duration of diarrhea after the initiation of treatment was 6.3 days. These data suggest that P. aeruginosa can be a potential cause of antibiotic-associated diarrhea. Further investigations are warranted to evaluate the possible etiologic role of P. aeruginosa in antibiotic-associated diarrhea.

Adult↗

Effect of weaning time and associated management practices on postweaning chronic diarrhea in captive rhesus monkeys (Macaca mulatta).

OBJECTIVE: Our purpose was to assess the extent to which early weaning and other weaning-management factors affect development of postweaning chronic diarrhea in captive rhesus monkeys at the California Regional Primate Research Center between 1992 and 1995. METHODS: Data for weaning, management, and onset of diarrhea were obtained from daily records. The Cox proportional hazard model was used to assess whether the risk of chronic diarrhea was related to early weaning. RESULTS: Monkeys that were lighter at weaning had a threefold increase in risk of postweaning chronic diarrhea (P = 0.07), compared with that in heavier monkeys. An episode of preweaning diarrhea increased the risk of postweaning chronic diarrhea twofold (P = 0.08). Relocation of monkeys to outdoor facilities in the fall was associated with a fivefold decrease in risk (P < 0.001), compared with that of other seasons, and weaning in 1993 was associated with a twofold decrease in risk, compared with that of other years (P = 0.04). CONCLUSIONS: Multiple factors need to be considered for prevention of postweaning chronic diarrhea, including weaning weight, preweaning diarrhea, season weaned, and weaning conditions that change from year to year.

Animal Husbandry↗