Antibacterial and antifungal drug concentrations in intra-abdominal abscesses: a prospective clinical study.

Abstract

Secondary peritonitis with intra-abdominal abscesses (IAA) is difficult to treat because of the supposed low rate of penetration of antimicrobial drugs at the site of infection. However, clinical data about the actual bioavailability of antimicrobial drugs in IAA are scarce. This prospective observational study aimed at assessing the drug penetration in IAA of the antibiotics (piperacillin-tazobactam, carbapenems) and antifungals (fluconazole, echinocandins) that are usually recommended for the treatment of intra-abdominal infections. Patients with IAA who underwent a radiological or surgical drainage procedure were included. Antimicrobial drug concentrations were measured in IAA (C_IAA) and in a simultaneous plasma sample (C_plasma) to assess the C_IAA/C_plasma ratio. The pharmacodynamic target was defined as a C_IAA equal or superior to the clinical breakpoints of susceptibility of the most relevant intra-abdominal pathogens. Clinical outcomes were assessed at hospital discharge. A total of 54 antimicrobial drug measurements were performed in 39 IAA samples originating from 36 patients. Despite important inter-individual variability, piperacillin-tazobactam exhibited the highest C_IAA/C_plasma ratios (median 2). The rates of target achievement were 75%-80% for piperacillin-tazobactam and meropenem but 0% for imipenem and ertapenem. These results tended to correlate with clinical outcomes (96% success rate versus 73%, respectively, P = 0.07). Among antifungals, fluconazole exhibited higher C_IAA/C_plasma ratios and rates of target achievement compared to echinocandins. However, no differences in clinical outcomes were observed. These results provide unique information about antimicrobial drug penetration in IAA in real clinical conditions and suggest that piperacillin-tazobactam and meropenem may have better efficacy compared to imipenem or ertapenem.