Antibiotics and Clostridium difficile.
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Biomedical subjects
Publications and source records attributed to S L Gorbach.
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In AIDS patients, wasting in adults and failure to thrive in children are common and devastating problems. Weight loss in rhesus macaques infected with simian immunodeficiency virus (SIV) has not been well characterized. The purpose of this study was to determine growth curves in SIV-infected juvenile macaques to determine the effects of SIV infection on body weight and growth. Medical records of seven juvenile male SIV-infected macaques were retrospectively reviewed to determine body weights, survival time, CD4 count, and viral load. Mean age and body weight at the time of inoculation were 63.3 weeks and 2.4 kg, respectively. Mean survival was 73.7 weeks, and mean body weight at the time of death was 3.0 kg, whereas the published mean body weight for this age of male rhesus macaque is 4.1 kg. Compared with the linear growth pattern of normal animals, the growth pattern for the SIV-infected animals exhibited strong nonlinearity with an inflection point at the mean survival of 74 weeks. After this time point, the discrepancy between growth curves for infected and healthy animals increased at a greater rate. Body weight correlated inversely with viral load (r = -0.368; p = .003) but there was no correlation between body weight and CD4 count. The results of this study suggest that failure to thrive is a consequence of SIV infection and may be related to severity of infection.
OBJECTIVES: To ascertain the relationships between resting energy expenditure (REE), HIV RNA in plasma, and highly active antiretroviral therapy (HAART). DESIGN: Cross-sectional analysis using data of a large cohort study of nutrition in relation to HIV disease. METHODS: HIV RNA in plasma, REE, fat-free mass (FFM), and medication regimens were assessed at 530 visits among 372 participants in a cohort study of HIV-seropositive men and women. RESULTS: HIV RNA in plasma was directly correlated with REE. After adjustment for FFM, age, CD4 cell count and HAART use, there was an increase in REE of 90 kJ/day per log10 copies/ml increase in HIV RNA [95% confidence interval (CI) 16-164; P = 0.02). HAART use had an independent effect on REE. In patients reporting HAART use, adjusted REE was 339 kJ/day higher than in those not reporting HAART use (95% CI 177-501; P = 0.0001). CONCLUSIONS: Viral load and HAART appear to exert independent effects on REE. Although HAART may decrease metabolic rate by lowering viral burden, it appears to increase metabolic demands through some mechanism(s) independent of its effect on viral burden. This may result in elevated REE despite control of viral replication.
Antimicrobial resistance, including plasmid-mediated resistance, among the species of the Bacteroides fragilis group is well documented. An analysis of the in vitro susceptibility of B. fragilis group species referred between 1995 and 1996 as well as during a 7-year (1990 to 1996), prospective, multicenter survey of over 4,000 clinical isolates of B. fragilis group species was undertaken to review trends in the percent resistance to and geometric mean MICs of the antibiotics tested. There was a trend toward a decrease in the geometric mean MICs of most beta-lactam antibiotics, while the percent resistance to most agents was less affected. Within the species B. fragilis, the geometric mean MICs showed significant (P < 0.05) decreases for piperacillin-tazobactam, ticarcillin-clavulanate, piperacillin, ticarcillin, ceftizoxime, cefotetan, and cefmetazole; a significant increase was observed for clindamycin and cefoxitin. For the non-B. fragilis species, a significant decrease in the geometric mean MICs was observed for meropenem, ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin, ticarcillin, ceftizoxime, and cefmetazole; a significant increase was observed for cefoxitin. Significant increases in percent resistance were observed within the B. fragilis strains for ticarcillin and ceftizoxime and within the non-B. fragilis isolates for cefotetan. Significant increases in percent resistance among all B. fragilis group species were observed for clindamycin, while imipenem showed no significant change in resistance trends. The trend analysis for trovafloxacin was limited to 3 years, since the quinolone was tested only in 1994, 1995, and 1996. During the 7 years analyzed, there was no resistance to metronidazole or chloramphenicol observed. The data demonstrate that resistance among the B. fragilis group species has decreased in the past several years, the major exception being clindamycin. The majority of the resistance decrease has been for the beta-lactams in B. fragilis, compared to other species. The reasons for these changes are not readily apparent.
OBJECTIVES: To determine the nutritional changes that occur in HIV-infected patients receiving protease inhibitor (PI) therapy and to determine the effects of PI treatment on physical functioning and health perceptions in patients with HIV infection. DESIGN: Longitudinal data analysis of 38 patients from a large Nutrition and HIV cohort. METHODS: Patients were included if they had started PI therapy after enrollment in the cohort, if they had taken the drug for at least 4 months without interruption and if data on weight, body composition and viral loads were available. RESULTS: Mean person-months of follow-up was 8.1 months before and 12.2 months after PI treatment. Weight (1.54 kg, P < 0.0001), body mass index (0.50 kg/m2, P < 0.0001), physical functioning (8.52 points, P = 0.0006) and current health perception (6.7 points, P = 0.01) increased significantly, and the daily caloric intake increase was close to significance (915.5 kJ/day, P = 0.06), after treatment with PI. Lean body mass did not change. Patients who responded to PI therapy with decreased viral load (n = 28) had significantly greater weight gain per month than non-responders. CONCLUSIONS: PI therapy of HIV infection is associated with weight gain and improvement in quality of life indices. The weight gain is mainly in fat mass, with no change in lean body mass (skeletal muscle). Optimal therapy of HIV-infected patients with weight loss may require highly active antiretroviral therapy combined with an anabolic stimulus such as exercise, anabolic steroids or human growth hormone.
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OBJECTIVE: To determine the clinical characteristics of patients with extraintestinal Clostridium difficile (ECD). MATERIAL AND METHODS: All cultures obtained during a 10.5-year period (from Jan. 1, 1985, to Jun. 30, 1995) at a tertiary-care hospital were retrospectively examined. The medical records of patients from whom ECD was isolated were then reviewed. RESULTS: Fourteen patients from whom ECD was cultured were identified. Thirteen of these patients (93%) had underlying systemic disease. All but one patient had recent exposure to antibiotics, and all had major bowel pathologic conditions. Nine patients had colon perforation. Of the eight patients in whom the colonic mucosa was directly inspected at operation or endoscopy, only two had evidence of pseudomembranous colitis. Five patients (36%) had documentation of recent diarrhea. ECD was isolated from intraperitoneal sites (in nine patients), blood cultures (in three), a perianal abscess, and a prosthetic hip joint. In 13 patients (93%), the infection was polymicrobial. Seven of the 13 inpatients (54%) survived to dismissal. CONCLUSION: C. difficile is a rare isolate outside of the gastrointestinal tract. ECD is found in patients with systemic illness who have been hospitalized (usually for an extended period), have intestinal pathologic conditions, and have received antibiotics. The isolation of ECD portends a poor prognosis.
Olestra, a dietary fat substitute, was recently made available to consumers in savory snacks in three cities. Early reports of gastrointestinal complaints attributed to olestra attracted media coverage and fostered confusion among physicians and consumers about the nature of olestra and its effects on the digestive system. We reviewed all published studies of olestra's gastrointestinal effects and all relevant unpublished studies submitted to the Food and Drug Administration. Each study was analyzed by a group of expert gastroenterologists and epidemiologists. The symptoms reported with olestra ingestion are similar to those reported with ingestion of fiber and sorbitol, although the mechanisms involved in changing stool characteristics differ among these food additives. Olestra's effects on stool habit and characteristics are due to its presence in the stool. Large amounts are more likely to induce gastrointestinal symptoms than small amounts. There is no evidence that olestra induces pathological change in bowel function: there is no increased fluid or electrolyte nor is there altered gastrointestinal motility or microflora. Olestra and triglyceride ingestion resulted in a similar frequency of symptoms in normal adults and children and in people with chronic inflammatory bowel disease in remission. Olestra traverses the digestive tract intact to become a stool additive. Some subjects develop a change in bowel habit and stool characteristics due to the presence of more olestra in the stool. These changes resemble those associated with ingestion of sorbitol and fiber.
Necrotizing fasciitis, by nature of its high inoculum of aggressive bacteria and the depth of the fascial involvement, is one of the most serious infections known to humans. Rapid tissue destruction of skin and fascia, along with bacteremia, is common. The mortality for this disease is much higher than that for cellulitis. Unfortunately, delay in diagnosis occurs commonly. The emergence of toxic shock strains of Streptococcus leading to fasciitis with organ dysfunction makes it necessary to make a rapid diagnosis and institute early antibiotic and surgical interventions.
BACKGROUND: In the United States, 5-year survival rates of 69% and 84%, respectively, have recently been reported for African-American and Caucasian women diagnosed with breast cancer. Differences in the levels of endogenous sex hormones in these populations could explain some of the variation in survival rates, since estrogen is recognized as a risk factor for this type of cancer. PURPOSE: Dietary factors are known to affect endogenous hormone levels; therefore, our study was designed to determine the serum hormone levels of African-American women consuming a typical North American diet, to determine the effect of a low-fat and high-fiber diet on their serum hormone levels, and to compare the base-line serum hormone levels in the African-American women with hormone data from our study of Caucasian women (n = 68) consuming the same control diet. METHODS: Twenty-one healthy, premenopausal, African-American women who agreed to eat only food prepared in a clinical study unit were recruited into the study. The control diet was similar to their usual diet, being high in fat (40% of calories from fat) and low in fiber (12 g/day), and was consumed on average for 3 weeks. The concentrations of estrone (E1), estrone sulfate (E1SO4), estradiol (E2), free E2, androstenedione, and sex hormone-binding globulin (SHBG) in serum samples obtained from the participants during the last week of the control diet and during the follicular phase of their menstrual cycle were determined. The women were then switched to a diet low in fat (20% of calories as fat) and high in fiber (40 g/day); they consumed this diet for two menstrual cycles before blood samples were collected for determination of serum hormone levels. Repeated-measures regression modeling was used to investigate the relationship between diet and hormone levels in African-American and Caucasian women. All P values resulted from two-sided statistical tests. RESULTS: Analysis of serum hormone levels in the African-American women indicated that the change in diet caused a significant decrease in E2 (-8.5%; 95% confidence interval [CI] = -16.1% to -0.3%; P < or = .03) and E1SO4 (-16.2%; 95% CI = -22.1% to -9.8%; P < .0001) and a significant increase in androstenedione levels (+18.3%; 95% CI = +10.3% to +26.8%; P < .0001). SHBG levels of the African-American women were 5.6% (95% CI = -14.0% to +3.7%) lower for those on the experimental diet compared with those on the control diet, but the difference was not statistically significant. Comparison of control serum hormone values in the African-American women in this study with those in Caucasian women previously studied indicated that the Caucasian women had statistically significant lower levels of E1 (-37%; 95% CI = -61.2% to -16.4%; P < or = .0002), E2 (-54.5%; 95% CI = -90.9% to -25.1%; P < or = .0001), free E2 (-30.2%; 95% CI = -65.7% to -2.3%; P < .03), and androstenedione (-48.3%; 95% CI = -83.7% to -19.7%; P < or = .0004). CONCLUSION: African-American women appear to have higher levels of serum hormones than Caucasian women, and dietary modification can result in a lowering of serum estrogens.
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In order to assess the potential of lactobacilli to cause serious infections, we studied the prevalence of bacteremia due to Lactobacillus species during a 4-year period (1989-1992) in southern Finland, which has a population of about 2.5 million. Among 3,317 blood culture isolates, lactobacilli were identified in eight patients, five of whom had a severe disease predisposing to bacteremic complications. The eight strains isolated were identified to the species level and typed by carbohydrate fermentation tests and by direct sequencing of enzymatically amplified 16S rRNA. The results did not provide evidence that any particular species or subspecies of Lactobacillus was the cause of the infections; no infections caused by isolates similar to the recently introduced dairy probiotic strain, Lactobacillus GG (ATCC 53103), were observed. The data show an infrequent association of lactobacilli with bacteremic infections in spite of the ubiquitous presence of these organisms in the gastrointestinal tract and their widespread consumption in fermented milks; thus, there is strong evidence that their pathogenic potential is very low.
Antimicrobial resistance, including plasmid-mediated resistance, among Bacteroides fragilis group species is well documented. A 5-year (1990-1994) prospective, eight-center survey of 3,177 clinical isolates of Bacteroides species was undertaken to review trends in resistance, using the breakpoints for full and intermediate susceptibility established by the National Committee for Clinical Laboratory Standards. No documented resistance to either metronidazole or chloramphenicol was found in this survey. Among B. fragilis isolates virtually no resistance was seen to imipenem, meropenem, ampicillin/sulbactam, piperacillin/tazobactam, or ticarcillin/clavulanate. Significant increases in resistance among B. fragilis isolates to cefotetan, ceftizoxime, and clindamycin (p < .01) were noted. Resistance to cefoxitin remained unchanged. Among the non-fragilis species of the B. fragilis group, there was virtually no resistance to imipenem, meropenem, chloramphenicol, or metronidazole. The three beta-lactamase inhibitors had increasing levels of resistance, although 95%-98% of strains were susceptible (p < .05). There was a significant decline in cefoxitin, cefmetazole, and clindamycin activity over time against these strains (p <.01). There was a significant (P < .001) increase in geometric mean minimum inhibitory concentration for most drugs and species tested from 1990 to 1994. Clusters in the eight institutions could not account for this rise in resistance. This survey demonstrates that rates of resistance of B. fragilis and non-fragilis species of B. fragilis group are increasing.
Metronidazole is a bactericidal antibiotic with strong activity against most anaerobes and certain parasites. The drug has excellent bioavailability and good penetration in most tissues, including the cerebrospinal fluid and brain abscess contents. It is usually well tolerated with few side effects. With a few exceptions, the percentage of anaerobes, including B. fragilis group, that are resistant to metronidazole remains low. Metronidazole has been used extensively in clinical practice for years, and its uses have expanded. Its exact role in the management of Crohn's disease and entities related to H. pylori is evolving.
Because many Western diseases are hormone-dependent cancers, we have postulated that the Western diet, compared with a vegetarian or semi-vegetarian diet, may alter hormone production, metabolism or action at the cellular level. Recently, our interest has been focused on the cancer-protective role of some hormone-like diphenolic phytoestrogens of dietary origin, the lignans and isoflavonoids. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids but also lignans), as well as whole grain cereals, seeds, probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds with weak estrogenic and antioxidative activity; they have now been shown to influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation and angiogenesis, making them strong candidates for a role as natural cancer protective compounds. Epidemiological investigations support this hypothesis, because the highest levels of these compounds are found in countries or regions with low cancer incidence. This report is a review of results that suggest that the diphenolic isoflavonoids and lignans are natural cancer-protective compounds.
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