Shelby Brigman, Mercer University College of Pharmacy
The current guidelines on treatment of intraabdominal infections prepared by the Surgical Infection Society and the Infectious Diseases Society of America (SIS-IDSA) in 2010 make recommendations based on severity of infection judged by the patient’s age and comorbidities. These guidelines recommend immediate fluid resuscitation upon diagnosis as well as rapid initiation of antimicrobial therapy. The area of abdomen that is infected dictates the empiric antibiotic regimen. The guidelines also recommend source control for nearly all patients. With adequate source control, the recommended duration of therapy of antimicrobial treatment is four to seven days. However, the guidelines leave open to the interpretation and judgment of the physician when a longer duration of treatment might be necessary.1
|Title: Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection2|
|Design||Open-label, randomized, investigator-initiated, multicenter trial; N = 518|
|Objective||To compare two strategies guiding the duration of antimicrobial therapy for the management of complicated intraabdominal infection|
|Study Groups||Subjects were randomized to receive four days of antimicrobial therapy after source-control procedure (experimental group, n = 258) or to receive antimicrobial therapy until two days after the resolution of systemic inflammatory response syndrome (SIRS) criteria (control group, n = 260).|
|Methods||Randomization was done with a web-based data system in a 1:1 ratio into either experimental or control groups. The choice of antimicrobial agent was not dictated by protocol but was considered acceptable if the physician followed the published SIS-IDSA guidelines. A maximum of ten days of therapy was allowed for treatment of the initial infection in the control group. The experimental group was followed closely for 30 days post-source-control procedure and assessed for SIRS criteria. Analysis was performed using the chi-square test in the intention-to-treat population.|
|Duration||August 2008 – August 2013|
|Primary Outcome Measure||Occurrence of surgical-site infection, recurrent intraabdominal infection, or death|
|Baseline Characteristics||Mean age = 52.2 ± 1.0, most were male (55%), composition of racial and ethnic groups were similar in both groups, most common origin of infection was colon or rectum (34%)
There were no statistically significant differences at baseline.
|Results||The composite primary end point of surgical-site infection, recurrent intraabdominal infection, or death occurred in 56 of 257 patients in the experimental group (21.8%), as compared with 58 of 260 patients in the control group (22.3%) (95% confidence interval [CI], −7.0 to 8.0; p = 0.92). No significant between-group differences were seen in the rates of the individual primary-endpoint components of surgical-site infection (95% CI, −2.4 to 7.0; p = 0.43), recurrent intraabdominal infection (95% CI, −4.5 to 7.8; p = 0.67), and death (95% CI, −1.7 to 2.7; p = 0.99).|
|Adverse Events||Common Adverse Events: N/A|
|Serious Adverse Events: N/A|
|Percentage that Discontinued due to Adverse Events: Death occurred in 5 of the 518 patients in the two groups combined (1.0%, 2 patients in the control group and 3 patients in the experimental group). All deaths were judged by the principal investigators to be related to underlying coexisting diseases.|
|Study Author Conclusions||A fixed duration of four days of antibiotic treatment resulted in outcomes that were similar to those of a traditional, longer course that was based on resolution of physiological abnormalities. The shorter course was associated with significantly fewer days of antibiotic exposure. After an adequate source-control procedure, the beneficial effects of systemic antimicrobial therapy are limited to the first few days after intervention.|
This trial had a large sample size across many centers, randomized design, and enrollment of patients with a broad range of severity of illness. However, since the calculated sample size of 505 patients per treatment arm needed to accept equal efficacy with 90% power was not achieved, proof of equivalence of the two treatment arms cannot be claimed. Therefore, this trial is of little clinical significance and further studies are required to show equivalence.
1.) Solomkin J, Mazuski J, Bradley J, et. al. Diagnosis and Management of Complicated Intra-abdominal Infection in Adults and Children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(2):133-164. doi: 10.1086/649554.
2.) Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med. 2015;372(21):1996-2005. doi: 10.1056/NEJMoa1411162.