A large network meta-analysis suggests that not all antibiotic regimens offer equivalent protection against surgical site infections in elective colorectal surgery, with broad-spectrum penicillins and cephalosporin-based combinations emerging as the most consistently effective options. Broad-spectrum penicillins were also associated with a reduction in mortality.
In the systematic review and network meta-analysis, Motaghi and colleagues evaluated 105 randomized clinical trials encompassing 18,273 adult patients undergoing elective colorectal procedures. The investigators compared antibiotic classes and class combinations administered within 24 hours prior to surgery, focusing primarily on 30-day surgical site infection (SSI) risk, as well as mortality, adverse events, and length of hospital stay.
SSIs remain among the most common complications following colorectal surgery, with reported incidence rates ranging from 10% to 25%, contributing to increased morbidity, prolonged hospitalization, and greater antimicrobial use. While existing guidelines emphasize appropriate timing and spectrum of coverage, direct comparisons among antibiotic classes have been limited.
The analysis incorporated 32 distinct antibiotic nodes grouped by class or combination. Using a frequentist random-effects model and grading the certainty of evidence with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework, the researchers found moderate- to high-certainty evidence that several regimens significantly reduced SSI risk compared with placebo or no prophylaxis.
Broad-spectrum penicillins were associated with a 74% relative reduction in SSI risk. Third-generation cephalosporins and the combination of metronidazole plus a second-generation cephalosporin demonstrated similar reductions. Tetracyclines and metronidazole combined with aminoglycosides were also associated with significant decreases in SSI risk.
Broad-spectrum penicillins were the only antibiotic class associated with reductions in both SSI and all-cause mortality. In analyses of 43 trials including 9,219 patients, broad-spectrum penicillins were linked to lower mortality compared with placebo, supported by moderate-certainty evidence. A combination of fluoroquinolones and penicillins was also associated with reduced mortality, though the certainty of evidence was rated as low.
No significant differences were observed among antibiotic classes with respect to length of hospital stay. Across 17 trials involving 2,830 patients, no regimen demonstrated a statistically significant impact on hospitalization duration relative to placebo or other active comparators.
Similarly, pooled analyses of 24 trials found no meaningful differences in overall adverse event rates across most regimens. One exception was the combination of metronidazole and a broad-spectrum penicillin, which was associated with a lower risk of adverse events compared with at least one active comparator.
The researchers acknowledged several important limitations of the meta-analysis. Many comparisons were based on trials that were small or few in number, and risk of bias was frequent, particularly with respect to allocation concealment and blinding. Reporting of comorbidities, cancer status, and bowel preparation protocols was inconsistent, limiting the ability to conduct subgroup analyses.
Nevertheless, the findings reinforce the importance of antibiotic class selection in colorectal surgery prophylaxis. While current guidelines emphasize ensuring both aerobic and anaerobic coverage, this analysis suggests that broad-spectrum penicillins and certain cephalosporin-based combinations may offer the most consistent protection against SSIs. The researchers noted that these comparative data may help inform future guideline updates and refine antibiotic selection in elective colorectal surgery.
Disclosures can be found in the study.
Source: JAMA Network Open
