antibiotics Article Intraoperative Bacterial Contamination and Activity of Different Antimicrobial Prophylaxis Regimens in Primary Knee and Hip Replacement Alba Rivera 1,2 , Alba Sánchez 1,2 , Sonia Luque 3 , Isabel Mur 4,5,6 , Lluís Puig 7 , Xavier Crusi 8 , José Carlos González 8 , Luisa Sorlí 6,9,10 , Aránzazu González 8 , Juan Pablo Horcajada 4,9 , Ferran Navarro 1,2 and Natividad Benito 4,5,6, *   Citation: Rivera, A.; Sánchez, A.; Luque, S.; Mur, I.; Puig, L.; Crusi, X.; González, J.C.; Sorlí, L.; González, A.; Horcajada, J.P.; Navarro, F.; et al. Intraoperative Bacterial Contamination and Activity of Different Antimicrobial Prophylaxis Regimens in Primary Knee and Hip Replacement. Antibiotics 2021, 10, 18. https://doi.org/10.3390/antibiotics 10010018 Received: 2 November 2020 Accepted: 23 December 2020 Published: 27 December 2020 Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional clai- ms in published maps and institutio- nal affiliations. Copyright: © 2020 by the authors. Li- censee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and con- ditions of the Creative Commons At- tribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Microbiology, Hospital de la Santa Creu i Sant Pau—Institut d’Investigació Biomèdica Sant Pau, 08025 Barcelona, Spain; mrivera@santpau.cat (A.R.); asanchezmor@santpau.cat (A.S.); FNavarror@santpau.cat (F.N.) 2 Department of Genetic and Microbiology, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain 3 Department of Pharmacy, Hospital del Mar—Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain; sluque@parcdesalutmar.cat 4 Department of Medicine, Faculty of Medicine, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain; imur@santpau.cat (I.M.); jhorcajada@parcdesalutmar.cat (J.P.H.) 5 Infectious Disease Unit, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau—Institut d’Investigació Biomèdica Sant Pau, 08025 Barcelona, Spain 6 Bone and Joint Infection Study Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (GEIO-SEIMC), 28003 Madrid, Spain; lsorli@parcdesalutmar.cat 7 Department of Orthopedic Surgery and Traumatology, Hospital del Mar—Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain; lpuig@parcdesalutmar.cat 8 Department of Orthopedic Surgery and Traumatology, Hospital de la Santa Creu i Sant Pau—Institut d’Investigació Biomèdica Sant Pau, 08025 Barcelona, Spain; XCrusi@santpau.cat (X.C.); JGonzalezR@santpau.cat (J.C.G.); agonzalezo@santpau.cat (A.G.) 9 Department of Infectious Diseases, Hospital del Mar—Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain 10 Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain * Correspondence: nbenito@santpau.cat Abstract: Surgical antimicrobial prophylaxis (SAP) is important for the prevention of prosthetic joint infections (PJIs) and must be effective against the microorganisms most likely to contaminate the surgical site. Our aim was to compare different SAP regimens (cefazolin, cefuroxime, or vancomycin, alone or combined with gentamicin) in patients undergoing total knee (TKA) and hip (THA) arthro- plasty. In this preclinical exploratory analysis, we analyzed the results of intraoperative sample cultures, the ratio of plasma antibiotic levels to the minimum inhibitory concentrations (MICs) for bacteria isolated at the surgical wound and ATCC strains, and serum bactericidal titers (SBT) against the same microorganisms. A total of 132 surgical procedures (68 TKA, 64 THA) in 128 patients were included. Cultures were positive in 57 (43.2%) procedures (mostly for coagulase-negative staphylococci and Cutibacterium spp.); the rate was lower in the group of patients receiving combi- nation SAP (adjusted OR 0.475, CI95% 0.229–0.987). The SAP regimens evaluated achieved plasma levels above the MICs in almost all of intraoperative isolates (93/94, 98.9%) and showed bactericidal activity against all of them (SBT range 1:8–1:1024), although SBTs were higher in patients receiving cefazolin and gentamicin-containing regimens. The potential clinical relevance of these findings in the prevention of PJIs remains to be determined. Keywords: surgical antimicrobial prophylaxis; knee arthroplasty; hip arthroplasty; prosthetic joint infection; surgical site infection prevention; prosthetic joint infection prevention; intraoperative cultures; antibiotic levels; serum bactericidal titer Antibiotics 2021, 10, 18. https://doi.org/10.3390/antibiotics10010018 https://www.mdpi.com/journal/antibiotics