by 
Ra JH, Rattan R, Patel NJ, Bhattacharya B, Butts CA, Gupta S, et al. Duration of Antimicrobial Treatment for Complicated Intra-abdominal Infections after Definitive Source Control: A Systematic Review, Meta-Analysis, and Practice Management Guideline from the Eastern Association for the Surgery of Trauma. J Trauma Acute Care Surg 2023;Publish Ah:603–12. doi:10.1097/ta.0000000000003998.
Introduction
Definitive source control is defined as a procedure (surgical intervention or percutaneous drainage) to remove the infected fluid and/or tissue and to prevent further infection and contamination. Definitive source control is defined here as both operative and percutaneous procedures targeting the source of cIAI.
Per the FDA recommendations, noninferiority was confirmed when short course antibiotics preserved at least 90% of the lower bound 95% confidence interval (CI) of the long course antibiotics effect. These are the noninferiority margins: abscess, 5%; unplanned IR or surgery, 5%; readmission, 7.5%.
A total of 16 studies were included in this guideline for qualitative analysis.
A short duration ranged from one dose to ≤ 10 days with an average of 4 days and the long duration ranged from >1 day to 28 days with an average of 8 days. Even with the outliers for both the short and long duration removed, the short duration average was still 4 days and the long duration was 7.9 days.
Quantitative Analysis
Mortality
There were six studies that reported mortality, three of which were RCTs. Taken separately, none of the included studies reported statistically significant difference between the short- and long-term antibiotics courses. The initial pooled analysis of those six studies showed no difference between a short and long duration of antibiotics (OR, 0.90; 95% CI, 0.56–1.44). The heterogeneity was 0% among the studies. The subgroup analyses of the RCTs and the observational and retrospective studies (O/R), did not demonstrate statistically significant difference between short and long duration for mortality. Subgroup analysis performed by cohorting the studies into similar short and long treatment duration (4 days vs. 10 days and 8–10 days vs. 15–18 days) groups, showed no significant difference in mortality.
Surgical Site Infection
There were six studies that looked at the surgical site infection outcome, three of which were RCTs. The initial pooled analysis of the six included studies showed no difference between a short and long duration of antibiotics (OR, 0.88; 95% CI, 0.56–1.38). Also, when separating the RCTs and the observational and retrospective (O/R) studies, there was no statistically significant difference between short and long duration for SSIs. The heterogeneity among these studies was 0%. Sub-group analysis, cohorting the studies by similar short and long treatment duration (1 day vs. 1–6 days; 3 days vs. 5 days, 4 days vs. 10 days), failed to demonstrate statistical significance.
Persistent/Recurrent Abscess
Ten studies evaluated the outcome of persistent and recurrent abscess, and four of them were RCTs. The initial pooled analysis of the 10 included studies showed no difference between short and long duration of antibiotics (OR, 0.76; 95% CI, 0.45–1.29). There was high heterogeneity among the studies at 69%. When separating the RCTs and observation and retrospective (O/R) studies, there was no statistically significant difference between short and long duration for persistent and recurrent abscess among the RCTs. However, there was a significant statistically difference among the observational and retrospective studies that favored short duration of antimicrobial treatment with some heterogeneity (I2 = 33%) among the studies. Subgroup analysis cohorting the studies by similar short and long treatment duration showed no statistical significance in 3 days versus 5 days; 4 days versus 10 days; 8 days to 10 days versus 15 days to 28 days. For the ≤7-day versus >7-day cohort, the abscess outcome favored shorter duration.
Unplanned Interventional Radiology/ Operative Intervention
Four studies looked at the outcome of unplanned interventional radiology/operative intervention, three of which were RCTs and one observational. The initial pooled analysis of four included studies showed no difference between the short and long duration of treatment (OR, 0.53; 95% CI, 0.12–2.26). The subgroup analysis cohorting the RCTs showed no difference between short and long duration of antibiotics (OR, 0.88; 95% CI, 0.22–3.44). The heterogeneity among the studies was 89%. The subgroup analysis; cohorting the studies by similar short, 8 days to 10 days, versus long, 15 days to 28 days, treatment duration; demonstrated no statistically significant difference between the groups.
Readmission
Three studies reported the readmission outcome, one of which was an RCT and two observational. The initial pooled analysis including all three studies showed no statistical differences between short and long-term course of antibiotics (OR, 0.92; 95% CI, 0.50–1.69). The heterogeneity among the studies was 0%. A subsequent pooled analysis cohorting the two observational studies showed no difference between short and long duration of antibiotics (OR, 0.90; 95% CI, 0.47–1.73). The heterogeneity among the studies was low at 0%.
Hospital Length of Stay
Five studies looked at hospital LOS, three of which were RCTs and two were observational. The initial pooled analysis of the five studies showed no statistical difference between the short and long duration (OR, −2.62; 95% CI, −7.08 to 1.83). The heterogeneity was very high at 100%. The separate pooled analyses of RCT versus observational and retrospective studies showed no difference between short and long duration of antibiotics. The heterogeneity among the observation and retrospective studies were 100%, and for RCTs the heterogeneity was 0%. Subgroup analysis cohorting the studies by similar short and long treatment duration showed no statistical significance between the 4-day and 10-day; 8- to 10-day and 15- to 28-day cohort. The heterogeneity for the 4-day versus 10-day cohort was high at 96% and was low for the other cohort at 0%.
Sepsis/Septic Shock
One RCT reported sepsis and septic shock outcome. Montravers et al. studied antibiotic duration in critically ill intensive care unit (ICU) patients with postoperative intra-abdominal infections. Short duration was defined as 8 days and long duration was defined as 15 days. There was no clinical benefit for the longer vs. shorter duration in critically ill ICU patients (OR, 2.69; 95% CI, 0.86–9.96; p = 0.06).
Recommendation
In adult patients with complicated intra-abdominal infections who have undergone definitive source control, we recommend a short (4 days) versus long (8 days) duration of antimicrobial treatment. The definition of definitive source control included both operative and percutaneous procedures. This recommendation is based on the noninferior effect of a short versus long antibiotic course duration, taking into account the lower risk of antibiotic related complications along with reduced cost.