Effect of Single vs Multiple Prophylactic Antibiotic Doses on PJI Following Primary THA in Patients With OA

The definition of PJI is based on revision surgery. Revision surgery is defined as a new surgical intervention the first time after the primary intervention including debridement alone or in combination with complete or partial removal or exchange of the implant.

• Two or more intraoperative deep-tissue samples of phenotypically indistinguishable bacteria isolated from at least 3 deep-tissue samples
• One or more positive intraoperative samples from a closed fluid aspirate AND a biopsy (fluid AND tissue) of phenotypically indistinguishable bacteria isolated
• A PJI when an indication of deep infection is reported to The Danish Hip Arthroplasty Registry (DHR) by the surgeon upon revision surgery

SAEs are defined according to the ICH-GCP guidelines. SAE refers to an event involving a significant risk of death or disability of the patient (or their offspring), including, but not limited to, an event that:

• results in death
• is life-threatening - in the investigator's opinion the patient was in immediate risk of death from the adverse event when it appeared
• requires hospitalization or prolongs existing hospitalization
• results in permanent or significant disability
• is a congenital anomaly SAEs are recorded from The Danish National Patient Registry (DNPR)

PJI-likely is defined as at least one of the two criteria:

• One single intraoperatively obtained positive culture (aspiration fluid OR tissue biopsy) regardless of microorganism
• One single positive culture obtained from aspiration of synovial fluid regardless of microorganism AND any antibiotic prescriptions (ATC category J01) redeemed

LOS defined as number of postoperative overnight stays, including transferals to other departments and hospitals. Data on LOS is acquired from DNPR.

A MACE is defined a priori to include thromboembolic complications including venous thromboembolism, myocardial infarction, atrial fibrillation and stroke based on the diagnostic ICD10 codes listed in Appendix B. VTE is defined a priori as both deep venous thromboembolisms confirmed by compression ultrasound and pulmonary embolism confirmed by spiral computed tomography (CT), ventilation-perfusion scintigraphy or pathological removal of an embolus and based on the following diagnostic ICD10 codes: I26, I80.1-I80.9, I82.1-I82.9, or T81.7B-D. Data will be extracted from DNPR.

Any Hospital-treated infection is defined as any first-time hospital admission with a primary or secondary infection diagnosis after discharge from index THA surgery. Hospital-treated infections are identified from DNPR.

The list of infections includes chronic and more rare infections, to detect possible flare-up in any possible ongoing infections.

The list will exclude urinary tract infections (UTI) due to a high risk of different registration praxis registration for UTI among hospitals in Denmark.

Community-based antibiotic use (any community-treated infection or antibiotic use after discharge) is defined as at least one dispensing after discharge from index THA surgery within 90 days for narrow- and broad-spectrum antibiotics based on the Anatomical Therapeutic Chemical classification (ATC) codes. All antibiotics in Denmark require prescriptions from a physician. The Danish National Health Service Prescription Database has registered all reimbursed prescriptions from all community pharmacies since 2004. Medications are coded according to the following ATC codes: J01CE, J01CF, J01DB, J01DC, J01DD, J01DE, J01DH, J01DI, J01CR, J01CA, J01F. J01E, J01MA ,J01AA

Prescriptions will be identified using NPR. The following ATC codes (including all subcodes) are included: N01AH (opioid anesthetics), N02A (opioids), N07BC02 (methadone), and R05DA04 (codeine). We defined opioid users as patients who redeemed two opioid prescriptions within six months prior to THA surgery. Conversely, patients who did not redeem two or more opioid prescriptions within this timeframe were classified as opioid naïve. For opioid naïve patients, opioid use post-THA is defined as the redemption of two opioid prescriptions within 90 days following surgery. We assert that two separate redeemed prescriptions confirm actual medication use. We will calculate the treatment dosage based on the number of packages and volume redeemed within 90 days post-surgery. To investigate dosages, all doses will be converted to morphine milligram equivalents using a conversion factor specific to the type of opioid.

Patients who received at least one prescription for acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) following THA surgery. Prescriptions of analgesics will be identified using NPR (41). All analgesics in Denmark except 10-tablet packages of acetaminophen / ibuprofen of dose 200mg ibuprofen require prescriptions from a physician. Following ATC codes (including all subcodes) are included M01A (NSAIDs) and N02BE01 (paracetamol). Duration of treatment will be calculated based on number of packages and volume. Since there is no clear definition of acetaminophen or non-steroidal anti-inflammatory users, we define these users as patients who redeemed two prescriptions within 6 months before THA.

Revision surgery is defined as a new surgical intervention the first time after the primary intervention including debridement alone or in combination with complete or partial removal or exchange of any implants. Rate of revision is defined as revision due to any cause within 90 days from primary THA surgery. Any revision will be recorded from DHR and DNPR.

The incremental cost-effectiveness will be calculated based on the costs per patient in the two antibiotic practices. Costs related to antibiotic prophylaxis, hospital admissions and readmissions, hospital outpatient visits, visits to General practitioner and costs related to sick leave from work will be included.

Data will be collected from:

• The Danish National Patient Registry (DNPR)
• The Civil Registration System (CRS)
• The Danish Agency for Labor Market and Recruitment registry STAR

Revision surgery is defined as a new surgical intervention the first time after the primary intervention including debridement alone or in combination with complete or partial removal or exchange of the implant. The rate of revision is recorded from The Danish Hip Arthroplasty Registry (DHR) and The Danish National Patient Registry (DNRP). Revision due to any cause including PJI and aseptic loosening will be included.

1-year mortality rate is defined by date of death due to any cause after index surgery. Data is collected from The Civil Registration System (CRS).

To be defined