Cancela Costa Alicia, Grass Fabian, Andres Cano Ignacio, Desgranges Florian, Delabays Constant, Kritikos Antonios, Glampedakis Emmanouil, Buclin Thierry, Duran Rafael, Guery Benoit, Pagani Jean-Luc, Uldry Emilie, Decosterd Laurent Arthur, Lamoth Frederic
Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Department of Visceral Surgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Antimicrob Agents Chemother. 2025 Jan 31;69(1):e0117824. doi: 10.1128/aac.01178-24. Epub 2024 Dec 5.
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) and in a simultaneous plasma sample (C) to assess the C/C ratio. The pharmacodynamic target was defined as a C 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/C 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, = 0.07). Among antifungals, fluconazole exhibited higher C/C 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.
伴有腹腔内脓肿（IAA）的继发性腹膜炎难以治疗，因为据推测抗菌药物在感染部位的渗透率较低。然而，关于抗菌药物在IAA中实际生物利用度的临床数据却很匮乏。这项前瞻性观察性研究旨在评估通常推荐用于治疗腹腔内感染的抗生素（哌拉西林-他唑巴坦、碳青霉烯类）和抗真菌药（氟康唑、棘白菌素类）在IAA中的药物渗透率。纳入了接受放射学或外科引流手术的IAA患者。在IAA（C）和同时采集的血浆样本（C）中测量抗菌药物浓度，以评估C/C比值。药效学目标定义为C等于或高于最相关腹腔内病原体敏感性临床断点。在出院时评估临床结局。对来自36例患者的39个IAA样本共进行了54次抗菌药物测量。尽管个体间存在重要差异，但哌拉西林-他唑巴坦的C/C比值最高（中位数为2）。哌拉西林-他唑巴坦和美罗培南的目标达成率为75%-80%，而亚胺培南和厄他培南的目标达成率为0%。这些结果倾向于与临床结局相关（成功率分别为96%和73%，P = 0.07）。在抗真菌药中，与棘白菌素类相比，氟康唑的C/C比值和目标达成率更高。然而，未观察到临床结局有差异。这些结果提供了关于实际临床条件下抗菌药物在IAA中渗透率的独特信息，并表明与亚胺培南或厄他培南相比，哌拉西林-他唑巴坦和美罗培南可能具有更好的疗效。
