Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY)

Long-bone sarcomas were historically managed with amputation. In the current era of
osteosarcoma management, amputations are generally avoided by complex surgeries in which the
malignancy is removed and the limb is reconstructed with advanced surgical techniques. This
process of limb salvage is possible with improvements in chemotherapeutic regimens, advanced
imaging techniques and surgical innovations such as modular metallic implants. However, the
risk for surgical complications is high due to the complexity of the surgeries themselves.
The most common and devastating complication is a surgical site infection. Background work
and data from our pilot study indicates that infection rates approach 15%. Multiple surgical
attempts at eradication of the infection fail in 50% of these cases, resulting in
amputation. Published guidelines for post-operative antibiotic prophylaxis following many
standard and less complex elective surgical procedures dictate that prophylactic antibiotics
be discontinued after 24 hours. However, the most effective duration of treatment in sarcoma
surgery has not previously been examined. Given the limitations of the evidence, it has not
been possible for orthopaedic oncologists to draw firm conclusions and, therefore, clinical
practice is highly varied, particularly with respect to antibiotic duration. Our
international, multi-center randomized controlled trial will determine whether a 5-day
regimen of post-operative prophylactic antibiotics in comparison to a standard 24-hour
regimen decreases the rate of surgical site infections after limb salvage surgery within
1-year follow-up.

Inclusion Criteria:

- primary malignant or aggressive benign bone tumors of the lower extremity, or
soft-tissue sarcomas which have invaded the bone; and

- treatment by surgical excision and endoprosthetic replacement.

Exclusion Criteria:

- current known Methicillin-resistant Staphylococcus Aureus (MRSA) colonization;

- current known Vancomycin Resistant Enterococcus (VRE) colonization;

- documented anaphylaxis or angioedema to penicillin or cefazolin (Ancef);

- prior surgery within the surgical field of the affected limb (excluding biopsy);

- prior local infection within the surgical field of the affected limb;

- current known immunologically-deficient disease conditions (not including recent
chemotherapy);

- known renal insufficiency with estimated creatinine clearance (eGRF) of less than 54
mL/min;

- reconstruction to include allograft;

- enrolled in a competing study; and

- weight of less than or equal to 45 kg (for sites using cefuroxime only).