Safety and Efficacy of Adjunctive Prophylactic Nitroimidazoles in Low-Risk Intraoral Tumor Resection: A Randomized Controlled Trial.

BACKGROUND: Surgical site infections (SSIs) in oral and maxillofacial surgery are predominantly polymicrobial, with anaerobes are involved in more than 70% of cases but are poorly detected by routine culture. Although guideline endorse nitroimidazoles as first-line prophylaxis, the considerable variation in resistance rates and safety profiles observed in practice has created a gap between evidence-based recommendations and clinical decision-making.

OBJECTIVE: To compare the safety and efficacy of metronidazole, tinidazole and ornidazole as adjunctive prophylactic agents for the prevention of SSI after low-risk intraoral tumor resection, and to provide evidence supporting the rational use of antibiotics.

MATERIAL AND METHODS: In this prospective, randomized, single-blind, single-center, exploratory trial, 160 adults undergoing low-risk intraoral tumor resection without flap reconstruction or implant placement were randomly assigned in a 1:1:1:1 ratio to receive ornidazole, metronidazole, tinidazole, or cephalosporin-only control treatment. All participants received perioperative cefazolin prophylaxis. The primary outcome was the cumulative incidence of SSI within 30 days postoperatively. Secondary outcomes included surgical incision healing, patient tolerance, and safety profile.

RESULTS: Of the 160 randomized patients, 3 were excluded after randomization because they met an exclusion criterion, leaving 157 patients in the full analysis set (ornidazole, n=38; metronidazole, n=39; tinidazole, n=40; control, n=40), of whom 146 (93.0%) completed the 30-day follow-up. The cumulative incidence of SSI, defined as an infection documented on postoperative day 3 or newly documented between day 3 and day 30, did not differ significantly among the four groups (P = 0.781): 2.6% (1/38) in the ornidazole group, 5.1% (2/39) in the metronidazole group, 2.5% (1/40) in the tinidazole group, and 7.5% (3/40) in the control group. Compared with the control group, the absolute risk differences in 30-day SSI were -4.9% (95% CI, -17.4 to 7.1) for ornidazole, -2.4% (95% CI, -15.3 to 10.4) for metronidazole, and -5.0% (95% CI, -17.5 to 6.5) for tinidazole; the corresponding conditional odds ratios were 0.33 (95% CI, 0.01-4.43), 0.67 (95% CI, 0.05-6.21) and 0.32 (95% CI, 0.01-4.20), respectively. One deep incisional infection occurred in the tinidazole group and one in the control group; no organ/space infection occurred in any group. No statistically significant differences were observed in surgical incision healing or patient tolerance among the groups. Adverse events were recorded in 9 patients (5.7%) within the first 3 days and in 45 of the 146 patients (30.8%) who completed follow-up by day 30, these were predominantly local wound-related reactions, with no significant difference among the groups (P = 0.525 for the day-3 comparison and P = 0.078 for the day-30 comparison) and mild gastrointestinal discomfort was reported in 8 patients (5.1%).

DISCUSSION: In this exploratory study, which was underpowered to detect small differences, adjunctive nitroimidazole prophylaxis did not significantly reduce the incidence of SSI. However, given the wide confidence intervals and limited statistical power, clinically meaningful benefit or harm cannot be excluded. These findings warrant confirmation in larger, adequately powered trials.