  Citation: Daoud, F.C.; Goncalves, R.; Moore, N. How Long Do Implanted Triclosan Sutures Inhibit Staphylococcus aureus in Surgical Conditions? A Pharmacological Model. Pharmaceutics 2022, 14, 539. https://doi.org/10.3390/ pharmaceutics14030539 Academic Editor: Koyo Nishida Received: 7 January 2022 Accepted: 22 February 2022 Published: 28 February 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). pharmaceutics Article How Long Do Implanted Triclosan Sutures Inhibit Staphylococcus aureus in Surgical Conditions? A Pharmacological Model Frederic Christopher Daoud 1, * , Ruben Goncalves 1,2 and Nicholas Moore 1 1 INSERM U1219, Bordeaux Population Health, Bordeaux University, 146 rue Léo Saignat, CEDEX, F-33076 Bordeaux, France; ruben.goncalves@u-bordeaux.fr (R.G.); nicholas.moore@u-bordeaux.fr (N.M.) 2 CHU de Bordeaux, Laboratoire de Pharmacologie et Toxicologie, Place Amélie Raba Léon, CEDEX, F-33076 Bordeaux, France * Correspondence: frederic.daoud-pineau@u-bordeaux.fr or fcdaoud@gmail.com; Tel.: +33-(0)6-0300-6898 Abstract: (1) Background: Sutures with triclosan (TS) are used to reduce the risk of surgical site infections (SSI), but most clinical trials are inconclusive. The traceability of SSI risk to antimicrobial activity in operated tissues is needed. (2) Objectives: This study aimed to predict triclosan anti- staphylococcal activity in operated tissues. (3) Methods: Three TS were exposed to static water for 30 days, and triclosan release was recorded. Polyglactin TS explanted from sheep seven days after cardiac surgery according to 3Rs provided ex vivo acceleration benchmarks. TS immersion up to 7 days in ethanol-water cosolvency and stirring simulated tissue implantation. Controls were 30-day immersion in static water. The release rate over time was measured and fitted to a predictive function. Antistaphylococcal activity and duration were measured by time-kill analysis with pre-immersed polyglactin TS. (4) Fifteen to 60-fold accelerated in vitro conditions reproduced the benchmarks. The rate prediction with double-exponential decay was validated. The antistaphylococcal activity was bactericidal, with TS pre-immersed for less than 12 h before then S. aureus began to grow. The residual triclosan level was more than 95% and played no detectable role. (5) Conclusions: Polyglactin, poligle- caprone, and polydioxanone TS share similar triclosan release functions with parametric differences. Polyglactin TS is antistaphylococcal in surgical conditions for 4 to 12 h. Keywords: sutures; triclosan; 3Rs; in vitro model; release kinetics 1. Introduction Triclosan (2,4-dichlorophenoxyphenol) is a broad-spectrum antimicrobial that inhibits bacterial fatty acid synthesis. The target receptor in various Gram-positive and negative species such as Staphylococcus aureus and Escherichia coli is NADH-dependent enoyl-[acyl carrier protein] reductase (FabI) [1–3]. Triclosan is an optional adjuvant in absorbable surgical sutures such as polyglactin 910 (Vicryl PLUS “V+”), polydioxanone (PDS PLUS “P+”), and poliglecaprone 25 (Monocryl PLUS “M+”) [4–6]. The structural polymers provide different mechanical and absorption properties that drive suture selection given the surgical circumstances [7]. The intended effect from adding triclosan is to inhibit suture microbial colonisation. In vitro and animal experiments have shown that triclosan sutures (TS) exhibit antimi- crobial activity in microorganisms commonly associated with surgical site infections (SSI) such as S. aureus, S. epidermidis and E. coli [8–12]. The expected clinical efficacy is a reduced incidence of surgical site infections (SSIs). Comprehensive meta-analyses of clinical trials have consistently shown a significantly lower incidence of SSIs after wound closure with TS as compared to non-triclosan sutures (NTS) [13,14]. The meta-analysis with the most randomised controlled trials (RCTs) re- ported a pooled relative risk (RR) of 0.73 [0.65, 0.82], but individual study RRs ranged Pharmaceutics 2022, 14, 539. https://doi.org/10.3390/pharmaceutics14030539 https://www.mdpi.com/journal/pharmaceutics