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Background Carbapenems are recommended treatment for serious infections caused AmpC-producing gram-negative bacteria but can select for carbapenem resistance. Piperacillin-tazobactam may be a suitable alternative. Methods We enrolled adult patients with bloodstream infection due to chromosomal AmpC-producers in a multicenter randomized controlled trial. Patients were assigned 1:1 to receive piperacillin-tazobactam 4.5 g every 6 hours or meropenem 1 g every 8 hours. The primary efficacy outcome was a composite of death, clinical failure, microbiological failure and microbiological relapse at 30 days. Results Seventy-two patients underwent randomization and were included in the primary analysis population. 11 of 38 patients (29%) randomized to piperacillin-tazobactam met the primary outcome compared with 7 of 34 patients (21%) in the meropenem group (risk difference, 8%, [95% CI –12% to 28%]). Effects were consistent in an analysis of the per-protocol population. Within the subcomponents of the primary outcome, 5 of 38 (13%) experienced microbiological failure in the piperacillin-tazobactam group compared to 0 of 34 patients (0%) in the meropenem group (risk difference, 13% [95% CI 2% to 24%]). In contrast, 0% versus 9% of microbiological relapses were seen in the piperacillin-tazobactam and meropenem arms, respectively. 96.5% and 100% were susceptible to piperacillin-tazobactam and meropenem, respectively using broth microdilution. The most common AmpC beta-lactamase genes identified were blaCMY-2, blaDHA-17, blaCMH-3 and blaACT-17. No ESBL, OXA or other carbapenemase genes were identified. Conclusion Among patients with bloodstream infection due to AmpC-producers, piperacillin-tazobactam may lead to more microbiological failures, although less microbiological relapses were seen.

Background Periprosthetic joint infection (PJI) is a devastating complication of joint replacement surgery. Most observational studies of PJI are retrospective or single-center, and reported management approaches and outcomes vary widely. We hypothesized that there would be substantial heterogeneity in PJI management and that most PJIs would present as late acute infections occurring as a consequence of bloodstream infections. Methods The Prosthetic joint Infection in Australia and New Zealand, Observational (PIANO) study is a prospective study at 27 hospitals. From July 2014 through December 2017, we enrolled all adults with a newly diagnosed PJI of a large joint. We collected data on demographics, microbiology, and surgical and antibiotic management over the first 3 months postpresentation. Results We enrolled 783 patients (427 knee, 323 hip, 25 shoulder, 6 elbow, and 2 ankle). The mode of presentation was late acute (>30 days postimplantation and <7 days of symptoms; 351, 45%), followed by early (≤30 days postimplantation; 196, 25%) and chronic (>30 days postimplantation with ≥30 days of symptoms; 148, 19%). Debridement, antibiotics, irrigation, and implant retention constituted the commonest initial management approach (565, 72%), but debridement was moderate or less in 142 (25%) and the polyethylene liner was not exchanged in 104 (23%). Conclusions In contrast to most studies, late acute infection was the most common mode of presentation, likely reflecting hematogenous seeding. Management was heterogeneous, reflecting the poor evidence base and the need for randomized controlled trials.

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