Open Tibial Fracture — Two or Three Days of Antibiotics?

Does a third day of prophylactic antibiotics reduce infection after severe open tibial fractures compared with two days? The PROACT trial did not show such a benefit. It also does not establish that the two regimens are equivalent, because the confidence intervals remain wide.

Why is this study clinically interesting?

The duration of antibiotic prophylaxis in open fractures remains debated. A regimen that is too short raises concern about infection, whereas unnecessary extension increases exposure to adverse effects and antimicrobial selection pressure. In Gustilo-Anderson IIIA and IIIB open tibial fractures, this question is particularly relevant because the soft-tissue injury is extensive and the baseline risk of infection is substantial.

PROACT was a pragmatic randomised trial conducted in a centre with integrated orthopaedic and reconstructive care. It did not compare antibiotics with no antibiotics. Instead, it tested two closely related durations: 48 versus 72 hours.

Question and methods

Adults with Gustilo-Anderson type IIIA or IIIB open tibial fractures were eligible. Of 241 patients assessed for initial eligibility, 204 were randomised 1:1 to either two or three days of intravenous cefuroxime and amikacin prophylaxis. Metronidazole was added when contamination was related to agricultural exposure.

The two-day group included 104 patients and the three-day group 100. All were analysed according to their original allocation. Outcome assessors were unaware of treatment allocation, whereas the nature of the intervention did not allow full blinding of the treating team. Orthoplastic care was standardised.

The primary endpoint was surgical-site infection within 90 days. Secondary outcomes included unplanned reoperation within one year and secondary amputation.

Results

• Infection within 90 days occurred in 15 of 104 patients after the two-day regimen (14%) and in 18 of 100 after the three-day regimen (18%).
• The risk difference was −3.6 percentage points, with a 95% confidence interval from −14.0 to 7.0 percentage points; p=0.60.
• Time-to-infection analysis likewise showed no statistically significant difference: HR 1.22; 95% CI 0.60–2.46.
• Unplanned reoperation within 12 months occurred in 24 of 104 patients in the two-day group (23%) and 19 of 100 in the three-day group (19%).
• Each group had one secondary amputation because of failure of soft-tissue coverage.

Clinical interpretation for an orthopaedic surgeon

The most defensible conclusion is that in this centre, extending prophylaxis from two to three days was not shown to reduce infections. This is an important signal against routinely adding another day simply “to be safe”.

However, a non-significant result must not be converted into proof of equivalence. The confidence interval remains compatible with clinically relevant effects in either direction. The trial also answers a narrow question: one additional day within a specific antibiotic protocol and within a well-organised orthoplastic pathway.

Limitations

• The study was single-centre and conducted in India, so care pathways, infection epidemiology and antimicrobial susceptibility may differ in other healthcare systems.
• The sample was too small to exclude clinically important differences with high precision.
• Only 48 and 72 hours of one antibiotic regimen were compared; the findings cannot be extrapolated to other agents or very short prophylaxis.
• Only IIIA and IIIB fractures were included. The trial does not resolve management in IIIC injuries, other anatomical sites, delayed presentation or unusual contamination.
• It does not replace decisions about rapid administration of the first antibiotic dose, radical debridement, fracture stabilisation and timely soft-tissue coverage.

What could this change in practice?

PROACT supports re-examining protocols in which a third day of prophylaxis is added automatically despite adequate debridement and standardised care. It does not justify independently shortening treatment outside local protocols. A larger multicentre trial, ideally designed to assess non-inferiority or equivalence of the shorter regimen, is still needed.

The study does not show that antibiotics can compensate for inadequate surgical debridement, nor that prophylactic dosing is sufficient once infection has developed. It also does not answer whether an even shorter regimen would be safe.

Source

Devendra A, Imran A, Irfan Pc M, et al. Two-day versus three-day systemic antibiotic prophylaxis for Gustilo-Anderson type IIIA and IIIB open tibial fractures (PROACT): a randomised controlled trial. Lancet Regional Health – Southeast Asia. 2026;53:100830. DOI: 10.1016/j.lansea.2026.100830. PubMed.

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Content prepared by: Tomasz Poboży - orthopaedic surgeon.