The effect of the acute phase of infection on absorption of and exposure to orally administered antibiotics in non-critically ill, hospitalized patients

Objectives: During the acute phase of infection, IV antibiotics are preferred to ensure adequate systemic exposure. To assess whether adequate exposure may also be achieved with oral antibiotics, we investigated exposure to oral antibiotics and PTA during the acute phase of infection and after defervescence. Methods: We enrolled hospitalized, non-critically ill febrile patients treated with IV antibiotics other than amoxicillin or ciprofloxacin. The study consisted of two visits: when patients had received <24 h IV treatment; and when patients had become afebrile. On both visits, patients received one additional dose of 750 mg amoxicillin, or 500 mg ciprofloxacin, depending on the presumed infection, after which serial blood samples were obtained. The primary endpoint was the ratio of the AUC during the febrile and the afebrile phase. The AUCs were considered to be equivalent when the ratio of the mean AUCs and its 90% CI was contained within the acceptance interval of 80%–125%. The secondary endpoint was PTA. Results: Forty-four patients (15 amoxicillin, 29 ciprofloxacin) completed both study visits. The median time between the two study visits was 65.8 h (range 33.8–427.4). The ratio of the mean AUCs (study visit 1/study visit 2) was 97% (90% CI of 80%–117%) for amoxicillin and 112% (90% CI of 108%–116%) for ciprofloxacin. The PTA for amoxicillin and ciprofloxacin did not differ between the two phases and was adequate to treat common pathogens. Conclusions: The acute phase of infection in non-critically ill febrile patients does not influence the exposure to, or PTA of, orally administered amoxicillin and ciprofloxacin. This might justify earlier IV-to-oral switching.