Effect of surgical antimicrobial prophylaxis duration on complications following colic surgery and the faecal bacterial resistome

Antimicrobial (AMD) stewardship is an increasingly important concern. Based on human studies, surgical AMD prophylaxis (SAP) beyond 24 hours (h) is unnecessary and potentially detrimental. Studies to date have been inconclusive regarding SAP duration for colic surgery.Objective: To compare clinical and microbiological outcomes in patients receiving 24- or 72-h of SAP for colic surgery and to better understand how the faecal microbiome/resistome changes over time (admission to discharge).Horses that recovered from colic surgery were considered. Exclusion criteria were 1) age <2 years; 2) Miniature Horses, pony and draught breeds; 3) azotaemia (creatinine > 88.42 umol/L); 4) hospitalisation, colic surgery, or AMD therapy in the previous 3 months; 5) intraperitoneal or periincisional AMD administration. Eligible horses were randomly assigned to receive SAP with potassium penicillin and gentamicin for 24- or 72-h. Clinical data and postoperative complications were compared between SAP groups. Admission and discharge faecal samples from a subset of horses (N=49) underwent shotgun metagenomic sequencing on an Illumina platform. Reads were aligned to reference databases using the Burrows-Wheeler Aligner and taxonomic classification was performed with kraken2. Sequencing reads were also aligned to the Comprehensive Antimicrobial Resistance Database (CARD) and characterized using the AMR++ pipeline. The faecal microbiome/resistome was characterized and compared between SAP groups over time.One hundred and forty horses completed the study (24-h N=71 and 72-h N=69). The only clinical variable that was different between SAP groups was age (24-h median age 16 [IQR 9, 20] years and 72-h 12 [6, 18] years, P=0.03). There was no significant difference between groups for any complications including incisional infection (24-h 17 [95% CI 10-27]% and 72-h 16 [9-26]%, P=0.9). Time was the main driver of changes in the microbiome/resistome: alpha diversity decreased while AMD resistance genes associated with administered AMD increased between admission and discharge. Discharge beta-lactam resistance genes were significantly higher in the 72- than the 24-h group.