From Cement to Tablets: Five Decades of Systemic Antibiotic Therapy for Periprosthetic Joint Infection: A Narrative Review

This review traces 5 decades of systemic antibiotic therapy for periprosthetic joint infection (PJI) and classifies each element of current regimens by the evidence behind it. In the 1970s, one-stage exchange with antibiotic-loaded cement was developed in Hamburg, initially without systemic antibiotics. North American two-stage exchange adopted the 6 weeks of intravenous therapy used for osteomyelitis. The first randomised trial of an antibiotic combination (1998) reported cure in 12 of 12 patients given rifampicin–ciprofloxacin and 7 of 12 given ciprofloxacin alone (24 of 33 randomised patients analysed; wide confidence interval). We identified 14 randomised trials of systemic therapy that enrolled patients with PJI and assessed their risk of bias; 10 randomised trials enrolled fewer than 200 patients. Of the three with more than 400 patients, OVIVA (2019) found early oral therapy non-inferior to intravenous therapy in bone and joint infection; DATIPO (2021) did not show 6 weeks to be non-inferior to 12, with the largest difference after debridement and implant retention; and SOLARIO (2026) found 7 days or less of systemic therapy non-inferior to 4 weeks or more when a local antibiotic carrier was implanted. A trial of oral therapy after reimplantation reported less reinfection, with 15% of patients lost to follow-up. The 3- and 6-month durations recommended since 2004 have been compared with a shorter course in one trial of 63 patients. Certainty of evidence was moderate for early oral therapy and low or very low for most questions of duration and agent; several components of current practice remain untested.