Update on resistance of Bacteroides fragilis group and related species with special attention to carbapenems 2006-2009.

The susceptibility trends for the species of the Bacteroides fragilis group against various antibiotics were determined using data from 4 years [2006-2009] on 1957 isolates referred by 8 medical centers participating in a National Survey for the Susceptibility of B. fragilis. The antibiotic test panel included doripenem, ertapenem, imipenem, meropenem, ampicillin:sulbactam, piperacillin:tazobactam, cefoxitin, clindamycin, moxifloxacin, tigecycline, chloramphenicol and metronidazole. MICs were determined using agar dilution methods following CLSI recommendations. Genetic analysis of isolates from 2008 with elevated MICs (>2 µg/mL) to one or more of the carbapenems to detect presence of the cfiA gene was performed using PCR methodology. The results showed an increase in the resistance rates to the ß-lactam antibiotics. High resistance rates were seen for clindamycin and moxifloxacin (as high as 60% for clindamycin and >80% for moxifloxacin), with relatively stable low resistance (5.4%) for tigecycline. For carbapenems, resistance in B. fragilis was 1.1%-2.5% in 2008-9. One isolate resistant to metronidazole (MIC 32 µg/mL) was observed as well as isolates with elevated MICs to chloramphenicol (16 µg/mL). Genetic analysis indicated that the cfiA gene was present in some but not all of the isolates with high MICs to the carbapenems. These data indicate that there continue to be changes in susceptibility over time, and that resistance can be seen among the carbapenems. High antibiotic resistance rates tend to be associated with specific species.

Safety, tolerance, and pharmacokinetic studies of OPT-80 in healthy volunteers following single and multiple oral doses.

Current therapies for Clostridium difficile infection (CDI) are encumbered by treatment failures and recurrences. Due to its high in vitro activity against C. difficile but low activity against the typical intestinal flora, minimal absorption, and durable cure in the hamster model of C. difficile infection, OPT-80 was considered for clinical development as a therapy for CDI. This trial consisted of two phases. Four single oral doses of OPT-80 (100, 200, 300, and 450 mg) were administered in a crossover manner to 16 healthy volunteers in a double-blind, placebo-controlled phase 1A study; a 1- to 2-week washout interval separated the treatments. In the double-blind phase 1B study, 24 healthy subjects were randomized to receive OPT-80 (150, 300, or 450 mg) or placebo for 10 days. In both studies, OPT-80's safety and tolerability were evaluated and the concentrations of OPT-80 and its primary metabolite (OP-1118) in plasma and feces were determined. OPT-80 levels in the urine were also analyzed for the phase 1A study. In both the single-dose and the multiple-dose studies, OPT-80 was well tolerated by all subjects in all dose groups. Maximal plasma concentrations were near or below the limit of quantification (5 ng/ml) across the dose range; urine concentrations were below the detection limit. The fecal total recovery of OPT-80 plus its major metabolite, OP-1118, approximated 100%. The tolerability, high fecal concentration, and low systemic exposure data from these studies support the further clinical development of OPT-80 as an oral therapy for CDI.

Clinical indications for probiotics: an overview.

Probiotic bacteria are used to treat or prevent a broad range of human diseases, conditions, and syndromes. In addition, there are areas of medical use that have been proposed for future probiotic applications. Randomized double-blind studies have provided evidence of probiotic effectiveness for the treatment and prevention of acute diarrhea and antibiotic-induced diarrhea, as well as for the prevention of cow milk-induced food allergy in infants and young children. Research studies have also provided evidence of effectiveness for the prevention of traveler's diarrhea, relapsing Clostridium difficile-induced colitis, and urinary tract infections. There are also studies indicating that probiotics may be useful for prevention of respiratory infections in children, dental caries, irritable bowel syndrome, and inflammatory bowel disease. Areas of future interest for the application of probiotics include colon and bladder cancers, diabetes, and rheumatoid arthritis. The probiotics with the greatest number of proven benefits are Lactobacillus rhamnosus strain GG and Saccharomyces boulardii.

National survey on the susceptibility of Bacteroides fragilis group: report and analysis of trends in the United States from 1997 to 2004.

The susceptibility trends for the species of the Bacteroides fragilis group against various antibiotics from 1997 to 2004 were determined by using data for 5,225 isolates referred by 10 medical centers. The antibiotic test panel included ertapenem, imipenem, meropenem, ampicillin-sulbactam, piperacillin-tazobactam, cefoxitin, clindamycin, moxifloxacin, tigecycline, chloramphenicol, and metronidazole. From 1997 to 2004 there were decreases in the geometric mean (GM) MICs of imipenem, meropenem, piperacillin-tazobactam, and cefoxitin for many of the species within the group. B. distasonis showed the highest rates of resistance to most of the beta-lactams. B. fragilis, B. ovatus, and B. thetaiotaomicron showed significantly higher GM MICs and rates of resistance to clindamycin over time. The rate of resistance to moxifloxacin of B. vulgatus was very high (MIC range for the 8-year study period, 38% to 66%). B. fragilis, B. ovatus, and B. distasonis and other Bacteroides spp. exhibited significant increases in the rates of resistance to moxifloxacin over the 8 years. Resistance rates and GM MICs for tigecycline were low and stable during the 5-year period over which this agent was studied. All isolates were susceptible to chloramphenicol (MICs < 16 microg/ml). In 2002, one isolate resistant to metronidazole (MIC = 64 microg/ml) was noted. These data indicate changes in susceptibility over time; surprisingly, some antimicrobial agents are more active now than they were 5 years ago.

Fat distribution in relation to drug use, human immunodeficiency virus (HIV) status, and the use of antiretroviral therapies in Hispanic patients with HIV infection.

Human immunodeficiency virus (HIV)-associated fat-redistribution syndrome is still a subject of controversy. There is, as yet, little agreement on the definition, etiology, and prevalence of the syndrome. Many studies have examined medication or disease-related factors. Fewer studies have examined patient-related factors. Illicit drug use is an important risk factor for HIV infection, yet the role of drug use in fat distribution has not been well described. We examined fat distribution, measured by dual energy x-ray absorptiometry, in relation to drug use, smoking, and alcohol use in Hispanic patients with HIV infection and control group of HIV-negative drug users. Our results suggest that neither drug use nor alcohol consumption are predictors of fat distribution. However, among men, smoking was independently associated with less total fat, less trunk fat, and more appendicular fat. The role of patient-specific factors in the etiology of HIV-associated fat-redistribution syndrome warrants further investigation.

Role of acquired immune deficiency syndrome-defining conditions in human immunodeficiency virus-associated wasting.

To evaluate the contribution of acquired immune deficiency syndrome-defining conditions (ADCs) in human immunodeficiency virus (HIV)-associated wasting, we analyzed longitudinal data from 671 participants in a nutrition and HIV cohort study. Data on ADCs, height, and weight were collected at baseline and during 6 monthly study visits. The frequency of ADCs decreased over time, but the relative risk (RR) of wasting (decrease in body mass index [BMI] to <20 kg/m(2)) increased with a history of >1 ADC; the RR of wasting increased 1.3-fold with each additional historical ADC. Any ADC during the 6 months prior to a study visit was associated with a decrease in BMI to <20 kg/m(2). The risk of wasting increased 2.7-fold with each additional recent ADC. These risks were not altered when adjusted for socioeconomic status, CD4 cell count, energy intake, or baseline BMI. Although ADCs contribute to the development of wasting, their contribution is relatively small.

Probiotics in the third millennium.

Probiotics are "living microorganisms which upon ingestion in certain numbers exert health benefits beyond inherent general nutrition". Since 1987, when the first publication on the properties of the Lactobacillus GG was done, overall, there have been over 200 publications in peer-reviewed scientific journals. This paper will report the status and the prospectus of probiotics research at the beginning of the Third Millennium. Probiotics have proven benefits in treatment and prevention of rotavirus diarrhoea in children and reduction of antibiotic-associated intestinal side-effects. Interesting results have recently been published regarding food allergies and atopic eczema in children. Prevention of vaginitis and of travellers' diarrhoea have also been reported. Promising results are being reported in patients with inflammatory bowel disease, cystic fibrosis, dental caries and irritable bowel syndrome. It has also been suggested that probiotics could enhance oral vaccine administration, and that they may help treatment against Helicobacter pylori infection, but further studies are needed. Future areas of research regard probiotics' role in the process of carcinogenesis, given their influence on the gut microflora, and as immune modulators in autoimmune disorders. The possibility of introducing appropriate genes to the probiotics to make them produce various compounds is also under investigation. However, there is still confusion in the minds of the authorities over whether a probiotic is a drug, a food, or a dietary supplement. The challenge is to continue research to define the appropriate uses of probiotics and discover new applications which will bring benefit to humankind.

Changes in lean body mass and total body weight are weakly associated with physical functioning in patients with HIV infection.

CONTEXT: For clinicians managing weight loss in patients with HIV, it would be useful to understand how changes in lean body mass (LBM) effect physical functioning, and whether LBM is more strongly related to physical functioning than total body weight (TBW). OBJECTIVE: To determine the relationship of changes in LBM and changes in total body weight (TBW) to changes in self-reported physical functioning in men and women with HIV infection. METHODS: Study design was longitudinal analysis of 1474 patient-intervals (each interval was approximately 6 months long) in 486 persons. Patients were participants in Nutrition for Healthy Living, a cohort study of HIV positive persons in Massachusetts and Rhode Island. The main outcome measure was change in self-reported physical functioning. RESULTS: Of the 1,474 intervals, 1,165 were contributed by men and 309 by women. The mean CD4 count for the 1,474 intervals was 383 cells/ micro L. In men, 5 kg changes in LBM and TBW were associated with 2.2 (95% confidence interval, 0.9, 3.4, P= 0.001) and 2.6 (95% confidence interval, 1.3, 3.9, P= 0.0002) point changes in physical functioning (on a 100-point scale), respectively, after adjusting for covariates. The relationships of changes in LBM and TBW to changes in physical functioning were linear. In women, there were no significant relationships between changes in LBM or TBW to changes in physical functioning. CONCLUSIONS: In this longitudinal analysis of relatively healthy persons with HIV infection, changes in LBM and TBW were significantly related to changes in physical functioning in men, but the magnitude of the relationship was small. In women, changes in LBM and TBW were not related to changes in physical functioning. Our data suggest that it is not necessary to measure body composition (lean and fat compartments) to understand the impact of changes in weight on physical functioning - it is sufficient to follow total body weight.

In vitro activities of newer quinolones against bacteroides group organisms.

The activities of BMS-284576, clinafloxacin, moxifloxacin, sitafloxacin, trovafloxacin, imipenem, cefoxitin, and clindamycin against 589 Bacteroides fragilis group isolates were determined. The activity of BMS-284576 was comparable to that of trovafloxacin. Sitafloxacin and clinafloxacin were the most active quinolones, and moxifloxacin was the least active. B. fragilis was the most susceptible of the species, and Bacteroides vulgatus was the most resistant. Association of specific antibiotic resistance with Bacteroides species was noted for all quinolones.

National survey on the susceptibility of Bacteroides Fragilis Group: report and analysis of trends for 1997-2000.

The results of a multicenter US survey using the National Committee for Clinical Laboratory Standards currently recommended methodology for measuring in vitro susceptibility of 2673 isolates of Bacteroides fragilis group species were compared from 1997 to 2000. The test panel consisted of 14 antibiotics: 3 carbapenems, 3 beta-lactam-beta-lactamase inhibitors, 3 cephamycins, 2 fluoroquinolones, clindamycin, chloramphenicol, and metronidazole. Declines in the geometric mean minimum inhibitory concentrations were seen with imipenem, meropenem, ampicillin-sulbactam, and the cephamycins. Increased geometric means were observed with the fluoroquinolones and were usually accompanied by an increase in resistance rates. Bacteroides distasonis shows the highest resistance rates among beta-lactam antibiotics, whereas Bacteroides vulgatus shows the highest resistance levels among fluoroquinolones. B. fragilis shows the lowest resistance rates for all antibiotics. All strains were susceptible to chloramphenicol and metronidazole concentrations <8 microgram/mL. The data underscore the need for species identification and continued surveillance to monitor resistance patterns.

The correlates of dietary intake among HIV-positive adults.

BACKGROUND: Dietary adequacy, as distinct from weight loss, has not been examined thoroughly in a diverse cohort of HIV-infected individuals. OBJECTIVE: An analysis was undertaken to determine the correlates of inadequate dietary intake among HIV-infected adults. DESIGN: In a cross-sectional study of 463 men and 170 women (aged 21-70 y) with HIV infection, dietary adequacy was evaluated by using 3-d diet records. RESULTS: Among nondieting males, whites had higher energy intakes than did nonwhites. Injection drug users consumed less energy than did nonusers. Among nondieting females, only the absence of nausea and vomiting was marginally associated with higher energy intakes. Inadequate energy intake, which occurred in 38% of this population, was independently associated with female sex among nondieters. A significant proportion of the study cohort (52%) was consuming less than the recommended dietary allowance of vitamin A. Inadequate protein intake, found in 11% of the study population, occurred more often in females, those without a caregiving adult in the household, and individuals with reduced appetite. A considerable proportion of the participants (23%) reported that they were dieting to lose weight. CONCLUSIONS: Dietary inadequacy was strongly correlated with being in the sociodemographic groups that are at heightened risk of adverse clinical outcomes. It may be worthwhile to study dietary intake as a potential determinant of the clinical outcomes of HIV infection.

Weight and body composition in a cohort of HIV-positive men and women.

OBJECTIVE: At issue is whether weight loss in HIV infection is a cachectic process, characterised by loss of lean body mass with conservation of fat, or a process of starvation. We present data on body composition from 516 persons at different stages of HIV infection as determined by CD4 counts. DESIGN: Cross-sectional analyses of body composition in relation to CD4 count. SETTING: The baseline data from a prospective cohort study of outcomes in HIV/AIDS in relation to nutritional status in Boston, Massachusetts, USA. SUBJECTS: : The first 516 subjects with HIV/AIDS to enroll in the study. RESULTS: Differences in weight in relation to CD4 counts were present only at CD4 counts of 600 or less (slope below : 1.9 kg per 100 CD4 cells, On average, 68% of the difference in weight over CD4 counts was fat (slope: 1.3 kg fat per 100 CD4 cells, CONCLUSIONS: This cross-sectional analysis suggests that weight loss consists principally of fat loss in those persons with adequate fat stores. This observation will need to be confirmed in longitudinal analyses.

The effect of protease inhibitor therapy on growth and body composition in human immunodeficiency virus type 1-infected children.

OBJECTIVE: To determine the effect of protease inhibitors (PIs) on growth and body composition in children with human immunodeficiency virus type 1 (HIV-1) infection. BACKGROUND: HIV-1-infected children have chronic problems with both linear growth and weight gain. Viral load may directly influence growth and nutritional status of HIV-1-infected children with reduction of viral load improving the nutritional condition. DESIGN/METHODS: Data from 67 patients who initiated PI therapy between 1996 and 1999 and who were enrolled in a prospective, longitudinal study of growth and nutrition in HIV-1-infected children were analyzed. Outcomes included pre-PI versus post-PI measures of height, weight, weight-for-height, triceps skinfold thickness, and arm muscle circumference. Predictor covariates included age, race, gender, Tanner stage, CD4 z score, Centers for Disease Control and Prevention stage, route of infection, plasma HIV-1 RNA, other antiretroviral therapy, recommended daily allowances for calories, treatment with megestrol acetate, and PI therapy. RESULTS: Sixty-seven children were followed for a median of 2.4 years with a total of 362 visits (median: 5 visits; range: 1-12). During follow-up, they received PIs for a median of 5 months. Fifty-one percent were girls, 54% black, 15% Hispanic, and 25% white. The mean age at first visit was 6.8 years. In a univariate analysis, weight z score (-0.67 to -0.35) and weight/height z score (0.25-0.76) improved on PI therapy. Using repeated-measures regression analysis, controlling for the above named covariates, PI treatment showed a significant effect on weight z score (increase in z score by 0.46), weight/height z score (increase in z score by 0.49), and arm muscle circumference (increase in percentile by 11.5). A borderline effect was found for height z score (increase in z score by 0.17) and no effect was found for triceps skinfold thickness. In a separate analysis, PI therapy increased CD4 counts twofold and reduced plasma HIV-1 RNA copies by 79%. CONCLUSION: In addition to a significant reduction in viral load, PI therapy in children has a positive effect on several growth parameters, including weight, weight/height, and muscle mass.

Sex hormone levels in premenopausal African-American women with upper and lower body fat phenotypes.

Body fat distribution may be a better marker of a hormonal pattern associated with increased breast cancer risk than obesity. This cross-sectional study of 106 healthy premenopausal African-American (AA) women compared the midfollicular phase sex hormone and sex hormone-binding globulin levels in upper body fat (UBF) and lower body fat (LBF) phenotype and obese and nonobese women. Multivariate regression analyses were used to control for various confounders, including dietary factors. UBF phenotype women had 37% (P = 0.02), 50% (P = 0.01), 52% (P = 0.007), and 50% (P = 0.009) higher levels of estradiol (E2), free E2, testosterone (T), and free T, respectively, than LBF phenotype women. Only %free T was higher in obese than in nonobese women (P = 0.02). The levels of E2, free E2, %free E2, T, and free T were higher [by 42% (P = 0.01), 68% (P = 0.001), 18% (P = 0.04), 36% (P = 0.04), and 61% (P = 0.01), respectively] and the level of sex hormone-binding globulin was lower [by 28% (P = 0.04)] in obese UBF than in nonobese LBF phenotype women. These findings support the hypothesis that body fat distribution may be a better marker of a hormonal pattern associated with increased breast cancer risk than obesity. Obese UBF phenotype AA women, in particular, have a high-risk hormonal profile. Future breast cancer studies might consider controlling for measures of obesity and body fat distribution to minimize confounding.

Body composition and dietary intake in relation to drug abuse in a cohort of HIV-positive persons.

We examined the relationships between drug abuse, weight, body composition, and dietary intake in persons infected with HIV in a cross-sectional analysis of baseline data from a longitudinal study of nutritional status and HIV. Body composition was measured by bioelectrical impedance analysis. Dietary data were collected by 3-day food records or 24-hour recalls. We analyzed data from 39 current intravenous drug users (IVDU), 103 past intravenous drug users (past-IVDU), 239 users of nonintravenous drugs (users-NIVD), and 61 nonusers (reference category). In the men, there were no differences in weight, body mass index (BMI), or body composition among the drug-use groups. In the women, there was a trend to lower weight and BMI across the drug use categories: IVDU women had lower average weight (-13.7 kg; p = .006), BMI (-5.6 units; p = .003) and less fat mass than non-users (-9.8 kg; p = .0001). In women, drug users had higher weight-adjusted energy intakes than nonusers, whereas in the men both drug using groups, NIVD and IVDU, had higher energy intakes than nonusers. These data suggest that intravenous drug-abuse is associated with lower weight and fat mass in women with HIV infection despite adequate self-reported energy intake.

Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy.

It has been postulated that the use of highly active antiretroviral therapy (HAART) would reduce the occurrence of human immunodeficiency virus (HIV)-associated weight loss and wasting. To test this assumption, we evaluated, by means of longitudinal analysis, a prospective cohort of 469 HIV-infected individuals enrolled in a study of the impact of HIV on nutrition. Overall, 156 individuals in the cohort (33.5%) met at least 1 of these definitions of wasting. Furthermore, 58% of the cohort (289 patients) lost >1.5 kg of weight in a 6-month period between any 2 study visits. More than 50% of the cohort was receiving HAART at the time that they met 1 of the definitions of wasting; with regard to the occurrence of wasting; no differences were related to therapy.

Predictors of change in the functional status of children with human immunodeficiency virus infection.

OBJECTIVE: The purpose of this study was to identify important clinical predictors of change in the functional status of children with perinatally acquired human immunodeficiency virus (HIV) infection. METHODS: Children who were perinatally exposed to HIV underwent evaluation of growth, nutritional, and functional status parameters as part of a prospective study of HIV and nutrition in children. The main outcome measures for HIV-infected children were change over time in: 1) Total Health, 2) General Health, and 3) Responsiveness as measured by the Functional Status II(R) (FSII[R]). Candidate predictors included anthropometric measurements, social factors, HIV disease stage, CD4 T lymphocyte count, medications, and other clinical markers of illness. RESULTS: The parents or legal guardians of 35 perinatally HIV-infected children completed 2 FSII(R) surveys over a mean of 16 months. Functional Status scores were significantly correlated with number of times and days hospitalized in the past 6 months and with illness at the time of baseline evaluation. Functional status declined overtime on all 3 scales; however, only the change in Total Health score was statistically significant. Total, General Health, and Responsiveness scores declined by >/=5 points in 20.0%, 17.1%, and 14.3% of children, respectively. Significant univariate predictors of change in at least 1 component of the functional status survey included race, guardianship, height z score, prescription of antiviral medications other than antiretrovirals, and illness at time of baseline evaluation. In multivariate models, adjusting for baseline score and biologic relationship of guardian completing survey, significant predictors of a decline in Total Health scores included non-white race and lower baseline height z score. The General Health score declined with lower baseline absolute CD4 count and lower baseline height z score. Finally, Responsiveness scores declined in children whose guardian was their biologic parent and in children with lower baseline height z scores. CONCLUSION: The FSII(R) questionnaire correlates with other markers of disease severity in children with HIV infection. Growth parameters, immune status, and social factors are important predictors of functional status in HIV-infected children.

Relation of lean body mass to health-related quality of life in persons with HIV.

OBJECTIVE: To determine the nature and strength of the relation between lean body mass and measures of health-related quality-of-living (HRQL) including physical functioning in men and women with HIV. DESIGN: Cross-sectional analysis using 619 patients with HIV infection from two cities in the northeastern United States. MAIN OUTCOME MEASURES: Lean body mass (LBM) was assessed by bioimpedance analysis (BIA). Physical functioning, general health perceptions, energy/fatigue, and number of days spent in bed in the last month were determined by patient self-report. RESULTS: Data from 450 men and 169 women were analyzed. Mean age was 39 years, 37.6% were nonwhite, and mean CD4 counts were 352 cells/ml. In multivariable models, higher LBM was significantly associated with better physical functioning in men but not in women. In men, a 10-kg increment in LBM was associated with a 3.7 point (95% confidence interval [CI], 0.19-7.2) increment in physical functioning (0-100 scale). In similar analyses, higher LBM was significantly associated with better general health perceptions (10-kg increment in LBM associated with a 4.8 point [95% CI, 1.4-8.1] increment in general health perceptions), and fewer days in bed in the last month (10-kg increment in LBM associated with 0.9 [95% CI, -1.8-0] fewer days in bed). Lean body mass was not independently associated with energy/fatigue. CONCLUSIONS: In this diverse population of persons with HIV, LBM was significantly related to physical functioning and other measures of HQRL in men, but not in women. In men, the relation was linear but relatively weak. These data have potential implications for assessing the clinical impact of interventions aimed at increasing LBM. Even in men, increases in LBM in the ranges that are currently achievable may produce relatively small improvements in physical functioning and other measures of HRQL.