SIS multicenter study of duration of antibiotics for intraabdominal infection

腹内感染抗生素治疗的最佳持续时间尚不清楚

The optimum duration of antibiotic therapy for intraabdominal infection remains unknown and has been identified by the Surgical Infection Society as a high priority for clinical research. The ultimate objective of our research is to optimize (and reduce) the duration of antibiotic therapy for intraabdominal infection throughout the world. The hypothesis to be tested is that four days of therapy for intraabdominal infection will lead to similar outcomes and a shorter duration of therapy when compared to a course based on the resolution of physiologic parameters in the setting of adequate operative or percutaneous intervention. This proposal is for a multicenter, randomized, double-blind (until the fourth day of therapy), non-inferiority clinical trial comparing a predetermined four days of antibiotic therapy to antibiotic therapy terminated one day after normalization of white blood cell count (¿ 11,000/ul) and normalization of systemic temperature (< 38.0¿ C) for one whole calendar day (and a maximum of 10 days of antibiotic therapy) in the setting of complicated intraabdominal infection treated with adequate source control. Inclusion criteria include age ¿ 16 years, ability to obtain informed consent from the patient or surrogate, presence of an intraabdominal infection requiring any duration of hospitalization and managed with open, laparoscopic, or percutaneous intervention, and, adequate source control in the opinion of the local investigator and Principal Investigator. 1,120 patients will be enrolled to ensure adequate power to assess equivalence of the two arms. The primary endpoint will be percentage failure conditioned by assigned duration of antibiotic therapy (intent to treat analysis). Failure will be defined as need for reintervention (surgical or percutaneous), surgical site infection, or death within 30 days of the original intervention for intraabdominal infection. In addition, multiple secondary endpoints will be assessed, including duration of antibiotic therapy and the incidence of infection at non-abdominal and non-surgical wound sites, particularly with antibiotic-resistant pathogens. The ultimate objective of our research is to change practice throughout the world, specifically by shortening the duration of antibiotic therapy for intraabdominal infections and thus decreasing resorurce utilization and decreasing the selection of antibiotic-resistant pathogens.