ABSORB-2:An exploratie study determining the oral antibiotic drug absorption in patients with short bowel syndrome.

Administering oral antibiotics In patients with short bowel syndrome can be
problematic since the changes in anatomy of the gastrointestinal tract with a
diminished absorptive capacity result in alterations in drug disposition.
Besides this, the bioavailability of oral drugs is primarily affected by
reduced bowel length. For this reason, the American Gastroenterological
Association (AGA, 2003) advises prolonged intravenous therapy in patients with
SBS. Other concomitant factors influence drug absorption and metabolism in the
case of short bowel as well, such as mucosal integrity, intestinal motility,
site of drug absorption, type of formulation, presence of co-morbidities, pH
and parenteral nutrition-associated metabolic changes (Ward et al. 2010).
However, successful treatment with orally administered antimicrobial agents has
been reported in selected, mostly pediatric, cases with SBS (Dressman et al.
1993, Iacono et al. 1993, Joe et al. 1994, Parsons et al. 1977, Thielman et al.
1998). Unfortunately, more recent, let alone well-designed interventional
studies researching biologic availability and other pharmacokinetic parameters
of antimicrobial agents in HPN patients with SBS are completely lacking

The primary objective is to determine the absorption of orally administered
antibiotics in patients with SBS, to guide in clinical decision making when
faced with catheter related infections.

Explorative single-centre study (research with a medicinal product)

Intervention : A single dose of two registered antibiotics will be
administered. At four time points blood will be drawn. The CC-Group (n=8) will
receive a single oral (day 1) and IV (day 3) dose of Clindamycin 600mg and
Ciprofloxacin 750 (400mg IV) mg. Group FF (n=8) will receive a single oral (day
1) and IV (day 3) dose of Flucloxacillin 1000mg and Fluconazol 400mg .

Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: Possible risks associated with participation are
adverse reactions to the administration of antibiotics, however as all
antibiotics are given as a single dose, and patients will be questioned about
allergic reactions to antibiotics, we deem this risk to be low. Since we mostly
will obtain blood from the patient*s own central venous access, occurrence of
side effects or adverse events related to vena punctures will be rare. Blood
will be obtained (withdrawal of approximately 10 ml in total) at four time
intervals, mostly during a routine scheduled daytime care visit or hospital
admission (for HPN training). There are no extra site visits necessary.

HPN patients, and likely other patient groups with reduced bowel length, will
benefit from an evidence-based individualized antibiotic treatment guideline
in case of an infection. Ultimately, this will lead to a reduced
hospitalization rate with reduced length of stay and subsequently, a reduction
in health care related costs. Also this study will provide guidance for further
policy development and implementation of antibiotic drug administration
protocols specific for patients with reduced bowel length.