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

Abstract

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.

Oral versus intravenous antibiotic treatment of moderate-to-severe community-acquired pneumonia: a propensity score matched study

“…Oral treatment of CAP has already been widely evaluated and implemented for the treatment of mild-to-moderate cases 6 – 10 , 13 . However, the role of oral antibiotics in the upfront treatment of more severe cases has not been sufficiently assessed despite the high bioavailability of oral antibiotics like amoxicillin, doxycycline and moxifloxacin 17 – 19 , 35 . Only two studies with a large majority of moderate-to-severe CAP patients showed similar or even better outcomes for oral treatment compared to intravenous treatment, but did not specify the disease severity for patients with treatment failure 14 , 15 .…”

Population pharmacokinetic/pharmacodynamic target attainment of ceftriaxone 2 g once daily in non‐critically ill hospitalized adult patients during the acute phase of infection

“…This was a population PK (PPK) substudy of the prospectively executed EXPO‐AB study. The EXPO‐AB study was a multicentre prospective intervention study, investigating the oral absorption of and systemic exposure to 2 single doses of amoxicillin or ciprofloxacin administered in addition to intravenous (IV) antibiotic treatment—during the febrile phase of infection and during convalescence, respectively—in noncritically ill hospitalized patients 14 . From the EXPO‐AB study population, we identified patients empirically treated with IV ceftriaxone.…”

“…At both study visits the subjects received a single oral dose of amoxicillin 750 mg or ciprofloxacin 500 mg for the purpose of the main study. At both visits, up to 4 blood samples were obtained according to the protocol of the EXPO‐AB study, 14 in which ceftriaxone could be measured besides amoxicillin and ciprofloxacin. This resulted in complete random sampling for the current ceftriaxone PPK substudy.…”

“…The EXPO-AB study was a multicentre prospective intervention study, investigating the oral absorption of and systemic exposure to 2 single doses of amoxicillin or ciprofloxacin administered in addition to intravenous (IV) antibiotic treatmentduring the febrile phase of infection and during convalescence, respectively-in noncritically ill hospitalized patients. 14 • Insufficient data are available on whether this also accounts for severely ill non-ICU patients in a highincome setting.…”

Oral Antibiotics for Bacteremia and Infective Endocarditis: Current Evidence and Future Perspectives

“…Fever and acute infection in non-critically ill patients do not seem to affect oral absorption of antibiotics when the infection is outside the gastrointestinal tract [10]. In addition, a retrospective study from two Brazilian intensive care units showed no difference in mortality when in-hospital step-down to oral antimicrobials was applied in initially septic patients (most often from pneumonia) that had reached clinical stability [11].…”