Vancomycin Taper and Pulse Regimen With Careful Follow-up for Patients With Recurrent Clostridium difficile Infection.

We retrospectively studied vancomycin taper and pulse treatment on 100 consecutive, evaluable patients with recurrent Clostridium difficile infection. Following taper to once-daily vancomycin dosing, 22 of 36 patients (61%) who received every-other-day dosing (QOD) and 50 of 64 (81%) who received QOD followed by every-third-day dosing were cured (P = .03).

A Quantitative Analysis of FDA Adverse Event Reports with Oral Bisphosphonates and Clostridium difficile.

BACKGROUND: Studies have shown associations between Clostridium difficile infection (CDI) and non-antimicrobial medications including proton pump inhibitors, osteoporosis medications, and antidepressants. OBJECTIVES: Our primary objective was to evaluate oral bisphosphonates and reported CDI adverse drug reactions in the United States using the Food and Drug Administration Adverse Event Reporting System data (FAERS). METHODS: We performed a disproportionality analysis evaluating the proportion of reports with bisphosphonates and CDI compared with other adverse drug reactions in the database. A relatively increased number of reports for a given adverse drug reaction (ADR) is termed a "signal." Four major measures of association are used to describe reports: reporting odds ratio, proportional reporting ratio, information component, and empirical Bayes geometric mean. Drugs with statistically significant safety signals were stratified by age (18-40, 41-65, and 65+ years) and gender. RESULTS: Alendronate had 0.4% (103/23,603) reports with CDI. There were 0.4% (16/3672) and 0.2% (17/7945) of reports for risedronate and ibandronate, respectively. Alendronate (Fosamax) was the only drug with a significant signal using all four calculation methods. For reports with gender available, alendronate CDI ADRs were more common for women (0.45% [93/20,586]) versus men (0.25% [4/1568]), and a signal was detected with all four methods. For reports with age available, there were limited alendronate reports for those 18-39 years of age, and CDI reports were present in 0.50% (27/5350) of cases of 40-64 years and 0.49% (42/8525) of cases aged 65 or older. CONCLUSION: Alendronate was associated with a high number of CDI ADRs relative to other drugs in FAERS. This signal was strongest for women and those 40 years or older. This interesting finding should be interpreted with caution, and further research is warranted.

Pharmacokinetics of ceftaroline in normal body weight and obese (classes I, II, and III) healthy adult subjects.

The pharmacokinetic profile of ceftaroline has not been well characterized in obese adults. The purpose of this study was to evaluate the pharmacokinetics of ceftaroline in 32 healthy adult volunteers aged 18 to 50 years in the normal, overweight, and obese body size ranges. Subjects were evenly assigned to 1 of 4 groups based on their body mass index (BMI) and total body weight (TBW) (ranges, 22.1 to 63.5 kg/m(2) and 50.1 to 179.5 kg, respectively). Subjects in the lower-TBW groups were matched by age, sex, race/ethnicity, and serum creatinine to the upper-BMI groups. Serial plasma and urine samples were collected over 12 h after the start of the infusion, and the concentrations of ceftaroline fosamil (prodrug), ceftaroline, and ceftaroline M-1 (inactive metabolite) were assayed. Noncompartmental and population pharmacokinetic analyses were used to evaluate the data. The mean plasma ceftaroline maximum concentration and area under the curve were ca. 30% lower in subjects with a BMI of ≥40 kg/m(2) compared to those <30 kg/m(2). A five-compartment pharmacokinetic model with zero-order infusion and first-order elimination optimally described the plasma concentration-time profiles of the prodrug and ceftaroline. Estimated creatinine clearance (eCLCR) and TBW best explained ceftaroline clearance and volume of distribution, respectively. Although lower ceftaroline plasma concentrations were observed in obese subjects, Monte Carlo simulations suggest the probability of target attainment is ≥90% when the MIC is ≤1 µg/ml irrespective of TBW or eCLCR. No dosage adjustment for ceftaroline appears to be necessary based on TBW alone in adults with comparable eCLCR. Confirmation of these findings in infected obese patients is necessary to validate these findings in healthy volunteers. (This study has been registered at ClinicalTrials.gov under registration no. NCT01648127.).

Treatment of Clostridium difficile infections.

Vancomycin and metronidazole were historically considered equivalent therapies for the management of Clostridium difficile infections (CDI); however, recent data confirm more favorable outcomes with vancomycin. Fidaxomicin is a narrow spectrum antibiotic that has an advantage in reducing recurrence rates compared with vancomycin, possibly owing to its sparing effect on normal colonic microbiota. Data are limited for guiding management of CDI recurrences, particularly multiple recurrences. Several empiric approaches to manage these cases are reviewed.

Fruit and vegetable intake and body mass index in a large sample of middle-aged Australian men and women.

Dietary guidelines around the world recommend increased intakes of fruits and non-starchy vegetables for the prevention of chronic diseases and possibly obesity. This study aimed to describe the association between body mass index (BMI) and habitual fruit and vegetable consumption in a large sample of 246,995 Australian adults aged 45 + year who had been recruited for the "45 and Up" cohort study. Fruit and vegetable intake was assessed using validated short questions, while weight and height were self-reported. Multinomial logistic regression was used, by sex, to assess the association between fruit and vegetable intake and BMI. Compared to the referent normal weight category (BMI 18.5 to 24.9), the odds ratio (OR) of being in the highest vegetable intake quartile was 1.09 (95% confidence interval (CI) 1.04-1.14) for overweight women (BMI 25.0-29.9) and 1.18 (95% CI 1.12-1.24) for obese women. The association was in the opposite direction for fruit for overweight (OR 0.85; 95% CI 0.80-0.90) and obese women (OR 0.75; 95% CI 0.69-0.80). Obese and overweight women had higher odds of being in the highest intake quartile for combined fruit and vegetable intake, and were more likely to meet the "2 and 5" target or to have five or more serves of fruit and vegetables per day. In contrast, overweight men were less likely to be in high intake quartiles and less likely to meet recommended target of 5 per day, but there was no consistent relationship between obesity and fruit and vegetable intake. Underweight women and underweight men were less likely to be in the highest intake quartiles or to meet the recommended targets. These data suggest that improving adherence to dietary targets for fruit and vegetables may be a dietary strategy to overcome overweight among men, but that overweight and obese women are already adhering to these targets. The association between fruit and vegetable intake and underweight in adults suggests that improving fruit and vegetables intakes are important for the overall dietary patterns of people in this group.

Novel Fidaxomicin Treatment Regimens for Patients With Multiple Clostridium difficile Infection Recurrences That Are Refractory to Standard Therapies.

Reports of fidaxomicin treatment for patients with multiple recurrent Clostridium difficile infections ([mrCDI] ie, more than 2 CDI episodes) indicate symptomatic response to this agent, but 50% have subsequent mrCDI episodes. In an effort to improve outcomes in patients with mrCDI we used novel regimens of fidaxomicin based on strategies used with vancomycin. Of 8 patients who received a 10-day chaser of fidaxomicin given twice daily after a course of vancomycin, 3 (38%) experienced a subsequent recurrence. Two (18%) of 11 patients who completed a 14- to 33-day course of fidaxomicin in a tapering dose experienced a recurrence, both of whom received additional antibiotics before that recurrence. The median symptom-free interval (SFI) after fidaxomicin taper was greater than the median SFI after the most effective prior regimen for those patients (257 days [interquartile range, 280] vs 25 days [interquartile range, 30], respectively; P = .003). A fidaxomicin chaser or taper regimen may be effective in patients with mrCDI, but the number of patients treated is small, and randomized comparative data are not available.

Fidaxomicin: a minimally absorbed macrocyclic antibiotic for the treatment of Clostridium difficile infections.

Fidaxomicin was approved for the treatment of Clostridium difficile infections in 2011. It has a novel mechanism of action and narrow spectrum of activity that makes it unique among the currently used therapies for this disease. Phase III clinical studies demonstrated a benefit of fidaxomicin over vancomycin for the outcomes of recurrence and global cure or sustained clinical response. This observation was confirmed within specific populations, including those of older age, immunocompromised due to active cancers, and patients taking concomitant antibiotics. Additionally, fidaxomicin significantly reduced recurrence rates compared to vancomycin among patients receiving treatment for recurrent C. difficile episodes. Fidaxomicin represents an advance in therapy for the treatment of C. difficile infections.