Influence of rifaximin treatment on the susceptibility of intestinal Gram-negative flora and enterococci.

The development of rifaximin- and rifampicin-resistant intestinal coliforms was studied in 27 subjects receiving rifaximin for 3 days by plating stool samples on media containing rifaximin 200 mg/L or rifampicin 64 mg/L before treatment (day 0), after treatment was completed (day 3), and after a further 2 days (day 5). The susceptibility of enterococci grown on day 0 and day 3 was also studied in 71 subjects. Significant increases in antimicrobial-resistant coliform flora were not seen in either the rifaximin-treated or the placebo-treated subjects. Enterococci recovered pre- and post-treatment showed similar susceptibilities. Rifaximin did not select for significant resistance in the Gram-negative and Gram-positive intestinal flora during therapy.

Rifaximin versus ciprofloxacin for the treatment of traveler's diarrhea: a randomized, double-blind clinical trial.

Rifaximin is a poorly absorbed rifamycin derivative under investigation for treatment of infectious diarrhea. Adult students from the United States in Mexico and international tourists in Jamaica were randomized to receive either rifaximin (400 mg twice per day) or ciprofloxacin (500 mg twice per day) for 3 days, following a double-blinded model, from June 1997 to September 1998. A total of 187 subjects with diarrhea were studied. Time from initiation of therapy to passage of last unformed stool was comparable for those receiving rifaximin or ciprofloxacin (median, 25.7 hours versus 25.0 hours, respectively). There was no significant difference in the proportion of subjects in the 2 groups with respect to clinical improvement during the first 24 hours (P=.199), failure to respond to treatment (P=.411), or microbiological cure (P=.222). The incidence of adverse events was low and similar in each group. Rifaximin is a safe and effective alternative to ciprofloxacin in the treatment of traveler's diarrhea.

Enteroaggregative Escherichia coli as a cause of traveler's diarrhea: clinical response to ciprofloxacin.

The purpose of this study was to determine the role of enteroaggregative Escherichia coli (EAEC) in the development of traveler's diarrhea and the clinical response of patients with EAEC diarrhea following treatment with ciprofloxacin. Sixty-four travelers with diarrhea and no other recognized enteropathogen were enrolled in treatment studies in Jamaica and Mexico from July 1997 to July 1998. EAEC was isolated from 29 travelers (45.3%). There was a significant reduction in the duration of posttreatment diarrhea in the 16 patients treated with ciprofloxacin, as compared with that in the 13 patients who received placebo (mean of 35.3 versus 55.5 hours; P = .049). There was a nonsignificant reduction in the mean number of unformed stools passed during the 72 hours after enrollment in the ciprofloxacin-treated group (5.6), as compared with that in the placebo group (7.5) (P = .128). This study provides additional evidence that EAEC should be considered as a cause of antibiotic-responsive traveler's diarrhea.

Prophylactic effect of bovine anti-Cryptosporidium hyperimmune colostrum immunoglobulin in healthy volunteers challenged with Cryptosporidium parvum.

Bovine hyperimmune anti-Cryptosporidium colostrum immunoglobulin (BACI) decreases the intensity of Cryptosporidium parvum infection in vitro. We investigated the prophylactic effect of BACI in healthy adults challenged with C. parvum. After we established an oocyst dose that resulted in 100% infection in four volunteers (baseline group), 16 volunteers were randomized to receive (1) BACI prior to C. parvum challenge (BACI group) and a nonfat milk placebo 30 minutes later, (2) BACI prior to and 30 minutes after challenge (reinforced BACI group), or (3) nonfat milk placebo prior to and 30 minutes after challenge. Subjects received BACI (10 g) or nonfat milk placebo three times a day for a total of 5 days and were followed for clinical symptoms and oocyst excretion for 30 days. A trend toward less diarrhea (P = .08) was observed for subjects receiving BACI in comparison with occurrences in placebo recipients. Subjects receiving BACI or nonfat milk placebo had a 100-fold reduction in oocyst excretion as compared with excretion in the baseline group.

Breast-feeding in Egypt.

Planning, implementation and evaluation of programmes to promote appropriate infant feeding practices require detailed, current information about these practices in the target populations. To estimate the prevalences and identify the correlates of overall breast-feeding and of exclusive breast-feeding in different age periods during infancy, a cohort of 152 apparently healthy neonates and their mothers were followed during October 1987 through April 1989 in rural Bilbeis, Sharqiya Governorate, Egypt. Feeding data were collected through twice weekly home visits thus reducing the potential for bias in our findings due to respondent recall errors. The prevalence of overall breastfeeding in the infants declined from 100% in age period 0-11 weeks to 89% in age period 36-47 weeks. Mothers with previous living children were associated with significantly higher (odds ratio [OR]: 6.53, 95% confidence interval [CI]: 1.33-32.09) and ownership of refrigerators was associated with significantly lower (OR: 0.18, 95% CI: 0.05-0.67) overall breast-feeding prevalences in age periods 24-35 and 36-47 weeks, respectively. The prevalence of exclusive breast-feeding in breast-fed infants dropped from 20% in age period 0-11 weeks to 0% in age period 36-47 weeks. After multivariate adjustment, prelacteal feeding was significantly negatively (OR: 0.12, 95% CI: 0.04-0.37) associated with exclusive breast-feeding in age period 0-11 weeks. Nearly 90% of Bilbeis infants were breast-fed at age 47 weeks, but the initiation of supplementation at 0-11 weeks in 80% of breast-fed infants is contrary to current recommendations.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: To estimate the prevalence of breast feeding in rural Egypt, a prospective cohort study involving 152 healthy neonates from four villages in Bilbeis was conducted. Infant feeding data were collected at twice weekly home visits from October 1987-April 1989; new infant-mother pairs were added to the study each month during the first year of research. The study infants represented 57% of the total births in the four villages during the recruitment period. All infants were exclusively or partially breast-fed during the first 11 months of life; this prevalence dropped to 98% in weeks 12-23 and to 89% in weeks 36-47. However, only 20% of infants were exclusively breast-fed in the first 11 weeks of life. Multivariate analyses indicated that involvement of a wet nurse, avoidance of prelacteal feeds, previous living children, non-ownership of a refrigerator, delivery by traditional birth attendants, and an uncomplicated labor and delivery were associated with higher prevalences of partial or exclusive breast feeding. There was no association of maternal ability to read and write, prenatal care use, and television ownership to breast feeding patterns. Mothers of higher socioeconomic status tended to terminate breast feeding significantly earlier than their less well-off counterparts. These findings point to a need for programs that discourage the supplementation of breast milk in the first four months of life.

Quinolones in Salmonella typhi infection.

The quinolones possess a high degree of in vitro activity against enteric bacteria, including Salmonella. This observation, coupled with the limitations of current antityphoid agents, has resulted in the evaluation of quinolones in the therapy of S. typhi infection, including both enteric fever and chronic intestinal carriage. In open uncontrolled trials, norfloxacin, ciprofloxacin, ofloxacin and pefloxacin have been used successfully to treat more than 200 patients with culture-proven typhoid fever. In comparative clinical trials, ciprofloxacin, ofloxacin, pefloxacin or fleroxacin were equivalent or superior to standard antityphoid therapy. In separate studies, norfloxacin and ciprofloxacin were each effective in eliminating intestinal excretion of S. typhi in chronic carriers. Because of increasing resistance worldwide to conventional antityphoid drugs, and in view of the efficacy of the quinolones in the therapy of both typhoid fever and typhoid intestinal carriage, these drugs may become the treatment of choice for these important enteric infections.

Use of norfloxacin in the treatment of acute diarrheal disease.

In studies conducted in seven countries, 392 persons with acute diarrhea were enrolled and randomly assigned to one of three regimens. In order to compare the effectiveness of various therapies for acute gastroenteritis, patients were treated for five days with either norfloxacin, 400 mg twice daily, norfloxacin, 400 mg three times a day, or trimethoprim/sulfamethoxazole, (160 mg/800 mg) twice daily. Clinical cure occurred in 89 percent (lower dose) and 91 percent (higher dose) of those treated with norfloxacin, compared with 78 percent of those receiving trimethoprim/sulfamethoxazole; cure rates in each treatment group were greater when the patient's stool contained fecal leukocytes. In 105 of 106 (99 percent) patients treated with either dose of norfloxacin and in 49 of 52 (94 percent) trimethoprim/sulfamethoxazole-treated subjects, the bacterial enteropathogen identified in the pretreatment stool was eradicated on the posttreatment specimen. Two percent (two patients) of those receiving the lower dose of norfloxacin, 3 percent (two patients) of those receiving trimethoprim/sulfamethoxazole, and 4 percent (three patients) of those receiving the higher dose of norfloxacin experienced minor and transient adverse hematologic or blood chemistry reactions. In addition, mild cutaneous reactions that were attributed to the study medications developed in two patients receiving the higher dose of norfloxacin and in three patients who received trimethoprim/sulfamethoxazole. These studies indicate that norfloxacin is safe and effective therapy for bacterial diarrhea.

Current problems in antimicrobial therapy for bacterial enteric infection.

Trimethoprim/sulfamethoxazole is currently considered the treatment of choice for shigellosis and severe travelers' diarrhea. The problem with this combination regimen is inactivity against Campylobacter jejuni strains and other bacterial enteropathogens showing in vitro resistance to the drug. Resistance to trimethoprim/sulfamethoxazole among enteric pathogens has occurred frequently in certain areas of the world. A study of the in vitro susceptibility of enteric bacterial pathogens isolated from multiple countries was recently performed. The minimal inhibitory concentration of ciprofloxacin required to inhibit 90 percent of the 210 bacterial enteropathogens ranged from 0.25 micrograms/ml for C. jejuni to 0.016 micrograms/ml for enterotoxigenic Escherichia coli, Salmonella, and Shigella. In a clinical trial carried out in a United States student population that acquired diarrhea while in Mexico, it was shown that ciprofloxacin was as effective as trimethoprim/sulfamethoxazole and both were significantly (p less than 0.001) more effective than placebo. The average duration of diarrhea was 29 or 20 hours after initiation of treatment with ciprofloxacin or trimethoprim/sulfamethoxazole, respectively, compared with 81 hours in the placebo group. The antimicrobial agents were more efficacious than placebo in treating diarrhea caused by enterotoxigenic E. coli, invasive enteropathogens, and unknown pathogens. Ciprofloxacin and the quinolone derivatives are uniquely suited to the therapy of acute bacterial diarrhea in areas where C. jejuni is commonly found and where trimethoprim/sulfamethoxazole-resistant strains regularly occur.

Ciprofloxacin or trimethoprim-sulfamethoxazole as initial therapy for travelers' diarrhea. A placebo-controlled, randomized trial.

The efficacy of ciprofloxacin was compared with that of trimethoprim-sulfamethoxazole in a placebo-controlled trial of the 5-day treatment of acute diarrhea among 181 adults recently arrived in Guadalajara, Mexico. Both antimicrobial agents were significantly (p less than 0.0001) more efficacious than placebo in the treatment of diarrhea, with the average duration of diarrhea being 29, 20, and 81 hours, respectively, in the ciprofloxacin, trimethoprim-sulfamethoxazole, and placebo treatment groups. The antimicrobial agents were also more efficacious than placebo in treating diarrhea caused by enterotoxigenic Escherichia coli, invasive enteropathogens, and unknown pathogens. Both antimicrobials were effective in treating mild-to-moderate and moderate-to-severe disease, and both were well tolerated. Ciprofloxacin appears to be a logical alternative to trimethoprim-sulfamethoxazole in the initial treatment of acute travelers' diarrhea.

Cytotoxicity of leukocytes from normal and Shigella-susceptible (opium-treated) guinea pigs against virulent Shigella sonnei.

Intraepithelial lymphocytes were collected from the ileum of adult Hartley strain guinea pigs and used as effector cells in a 60-min bactericidal assay with virulent Shigella sonnei as target cells. Natural killer cytotoxicity (NKC) and antibody-dependent cellular cytotoxicity (ADCC) were measured and correlated with the resistance of the animals to infection by S. sonnei. Normal guinea pig intraepithelial lymphocytes exhibited mean NKC and ADCC values of 22.8 +/- 5.0 and 34.1 +/- 13.6, respectively. These animals were resistant to oral challenge with virulent S. sonnei. Intraepithelial lymphocytes from guinea pigs which were fasted for 4 days demonstrated NKC and ADCC values similar to those of normal animals (31.0 +/- 8.1 and 41.7 +/- 6.7, respectively). These animals also were resistant to oral challenge. Intraepithelial lymphocytes from guinea pigs which were given 1 ml of deodorized tincture of opium 2 h before cell collection demonstrated deficient NKC (4.7 +/- 4.2) and ADCC (5.3 +/- 4.9) values but remained resistant to infection by S. sonnei. When guinea pigs were fasted for 4 days and given opium, deficient NKC (2.0 +/- 2.0) and ADCC (1.3 +/- 1.3) values were demonstrated; this group of animals was susceptible to infection by S. sonnei (P less than 0.04). These experiments demonstrated that opium treatment depresses one form of gut immunity. When combined with starvation, opium treatment may increase susceptibility to infection by shigellae by modulation of immunity in addition to the effects on gut motility and bacterial flora.

Cytotoxicity of human peripheral blood and colostral leukocytes against Shigella species.

We examined the ability of human peripheral blood leukocytes to kill strains of Shigella sonnei and Shigella flexneri by using a modified bactericidal assay. Antibody-dependent cellular cytotoxicity (ADCC) was demonstrated in the presence of specific rabbit immune serum directed against S. sonnei. With peripheral blood leukocytes from adults, ADCC was found only in the mononuclear cell and purified lymphocyte populations. Monocyte-macrophages and polymorphonuclear leukocytes were unable to demonstrate ADCC. Lymphocyte ADCC, which was not affected by the addition of phenylbutazone (an inhibitor of phagocytosis), was mediated by a non-T, Fc receptor-positive, HNK-1- cell. ADCC (using antiserum directed against virulent S. sonnei) was demonstrated against virulent S. sonnei but not against virulent S. sonnei or virulent S. flexneri. In contrast to leukocytes from adults, both mononuclear and polymorphonuclear cells from neonatal cord blood and from a patient with chronic granulomatous disease mediated anti-Shigella ADCC. Breast milk leukocytes (BMLs) collected 1 to 3 days postpartum were used as effector cells against virulent S. sonnei. The entire BML population, BMLs which did not adhere to plastic and BMLs which passed through nylon wool columns mediated both natural killer cytotoxicity and ADCC. In paired experiments, natural killer cytotoxicity and ADCC were significantly lower (30 to 45% inhibition) but not ablated, when phenylbutazone was added to BMLs and nylon wool-purified BMLs (P less than 0.05). These experiments suggest that colostral leukocytes mediated both extracellular and intracellular bacteriolysis in the presence and absence of specific antiserum. These mechanisms may be active in vivo in protection against shigellosis.

In vitro and in vivo neutralizing activity of human colostrum and milk against purified toxins A and B of Clostridium difficile.

The neutralizing activity (NA) of supernates of colostral samples collected postpartum from 55 women and tested against a 50% cytopathic dose of purified toxins A and B of Clostridium difficile was evaluated in Y1 adrenal cells. Thirty-one (56%) of the samples had NA against one or both toxins. Samples of breast milk were collected postpartum from five women-three had colostral NA and two did not. All milk specimens from the three women with colostral NA had NA titers of 1:1-1:4 throughout the study (609 days in one case). Samples from the two women without colostral NA did not exhibit NA during a 60-day follow-up period. In suckling mice either toxin plus human milk with in vitro NA elicited significantly less fluid accumulation than did toxin plus diluent or toxin plus milk without in vitro NA (P less than .025 to P less than .05). Twelve (63%) of 19 milk samples with in vitro NA against toxin A and 15 (65%) of 23 with in vitro NA against toxin B inhibited fluid accumulation caused by the corresponding toxin. In vitro NA against toxin A appeared to reside in the secretory IgA fraction of one milk sample assessed by immune precipitation. The results suggest that human milk may protect newborn infants against toxins A and B of C. difficile.

Minocycline treatment failure in pneumonia caused by minocycline-sensitive Streptococcus pneumoniae.

A previously healthy 23-year-old white woman had fulminant pneumococcal pneumonia complicated by empyema and bilateral pneumothoraces. Despite early treatment with the recommended doses of minocycline, the disease progressed. The S pneumoniae isolate was resistant to a 30microgram tetracycline disk and showed an MIC of 3.13microgram/ml for minocycline and 12.5 microgram/ml for tetracycline; these levels are considered by the manufacturer to indicate sensitivity to minocycline and intermediate sensitivity to tetracycline. The tetracyclines, including minocycline, should not be used to treat bacterial pneumonia since resistant strains of pneumococci are not uncommon and inffective treatment can lead to rapid progression of the infection. This case suggests that the levels of minocycline considered to indicate sensitivity in vitro be reassessed.

Antidiarrheal agents in the treatment of acute diarrhea in children.

To evaluate the efficacy of antidiarrheal agents in the treatment of diarrheal illnesses, a study was conducted with children in Guatemala who had an acute diarrheal illness. Eighty patients, aged 3 to 11 years, were hospitalized and treated for two days with one of five agents: kaolin-pectin suspension concentrate (Kao-Con), kaolin suspension, pectin suspension, diphenoxylate-atropine liquid (Lomotil), or placebo. Although the patients receiving kaolin-pectin produced stools that tended to be more formed than those of the placebo-treated group patients, the study did not demonstrate any effect by any of the agents tested in influencing the frequency of bowel movement, the water content of the stools, or the weight of stools. Kaolin-pectin suspension and diphenoxylate-atropine liquid do not appear to be useful in the relief of acute nonspecific diarrhea in children.