Oral antimicrobial agents in patients with short bowel syndrome: worth a try!

BACKGROUND: The use of oral antimicrobial agents in patients with short bowel syndrome (SBS) is challenging due to the changes in gastrointestinal anatomy that may result in diminished absorption and altered drug bioavailability. Prospective studies evaluating bioavailability of antimicrobial agents after oral administration in SBS patients are lacking. OBJECTIVES: To determine the bioavailability of orally administered antimicrobial agents commonly used for treatment in SBS patients to guide clinical decision making when faced with infections. METHODS: We performed an explorative, clinical study investigating the pharmacokinetics (PK) of clindamycin, ciprofloxacin, flucloxacillin and fluconazole in SBS patients with intestinal failure. Participants received a combination of two antimicrobial agents simultaneously. To determine the oral bioavailability, participants received a single oral and IV dose of both agents on two occasions, after which they underwent intensive PK sampling on six predefined time points up to 12 hours after administration. Primary outcome was the oral bioavailability of these antimicrobial agents. Secondary outcomes were intravenous PK characteristics following non-compartmental analysis. RESULTS: Eighteen SBS patients were included: the mean (SD) age was 59 (17) years and 61% of participants were female. The median observed (IQR) bioavailability of ciprofloxacin, clindamycin, flucloxacillin and fluconazole were 36% (24-50), 93% (56-106), 50% (32-76) and 98% (61-107), respectively. CONCLUSION: The bioavailability of selected antimicrobial agents in certain patients with SBS appeared to be better than expected, providing a feasible treatment option. Due to the large observed differences between patients, therapeutic drug monitoring should be part of the treatment to safeguard adequate exposure in all patients. TRIAL REGISTRATION: Registered in the Dutch Trial Register (NL7796) and EudraCT number 2019-002587-28.

Having breakfast has no clinically relevant effect on bioelectrical impedance measurements in healthy adults.

BACKGROUND: Bioelectrical impedance analysis (BIA) is commonly used to evaluate body composition as part of nutritional assessment. Current guidelines recommend performing BIA measurements in a fasting state of at least 2 h in a clinical setting and 8 h in a research setting. However, since asking patients with malnutrition or sarcopenia to fast is not desirable and literature to support the strategy in the guidelines is lacking, this study aimed to assess the impact of breakfast on BIA measurements. METHODS: We performed an explorative, prospective study in healthy volunteers aged between 18 and 70 years, with a normal fluid balance and a body mass index between 18.5 and 30 kg/m2. BIA measurements were performed according to the standard operating procedure in the fasting state, and 1, 2, 3, and 4 h after ingesting a standardized breakfast meal of about 400 kcal with a 150 mL drink, using the hand-to-food single-frequency BIA (Bodystat500 ®). The Kyle formula was used to calculate the primary outcome, i.e. fat-free mass (FFM, kg). A linear mixed model was used to compare baseline values with other time points. A difference of 1 kg in FFM was considered clinically relevant. RESULTS: Thirty-nine (85% female) volunteers were included, with a median age of 28 years (IQR 24-38). In 90% of the participants, having breakfast had no clinically relevant impact on the estimated FFM. For the group, the most pronounced mean difference, a statistically but not clinically significant higher value of 0.2 kg (0.4%), was observed after 3 h of fasting compared to baseline. No statistically significant differences were found at the other time points. CONCLUSION: Eating affects single-frequency BIA measurements, but differences in FFM remain below clinical relevance for most participants when using a standardized breakfast. Thus, the current study suggests performing a BIA measurement in a fasting state is not required.