Detection and prevention of bacteria in bone and joints - on microbial diagnostics and cloxacillin prophylaxis

<p dir="ltr">Bone and joint infections (BJI) are challenging concerning diagnostics, treatment, and outcome. While physicians struggle to diagnose and manage BJI, patients often suffer pain, disability and require long-term antibiotic treatments.</p><p dir="ltr">To increase the knowledge on which bacteria cause BJIs, a retrospective study on 363 patients from Södersjukhuset was performed. Staphylococcus aureus was the dominating cause, even in patients receiving antibiotics to avoid staphylococci, through cloxacillin prophylaxis. However, in 25% of the cases the bacterial aetiology could not be defined. 16S rDNA sequencing has been proposed to reduce the proportion of cases where the bacterial cause of BJI is not found. To assess this, a prospective study was designed, analysing 28 episodes of post-operative BJI, comparing conventional culture with sequencing, in patients on antibiotics. Sequencing was helpful in 5/28 cases (18%). Multiple samples per patient helped distinguishing contaminating bacteria from bacteria causing infection .</p><p dir="ltr">Cloxacillin prophylaxis is dosed with little consideration of kidney function, duration of surgery or weight. Hypothesising that this dosing manner leads to insufficient concentrations to inhibit the growth of methicillin susceptible staphylococci in certain individuals, 204 patients subjected to primary hip or knee arthroplasty were prospectively assessed concerning free cloxacillin concentrations throughout surgery. Fifteen percent of the patients had concentrations <2x the minimal inhibitory concentration (MIC) for wild type Staphylococcus aureus at the end of surgery, possibly placing them at a larger risk of post operative infections with staphylococci. Predictors of low concentrations were ASA score I, estimated glomerular filtration rate /eGFR) >90, weight >100 kg and duration of surgery 90-120 minutes from the pre-operative dose of cloxacillin. Results also showed that the present guideline for dosing was poorly followed. To propose a new guideline for cloxacillin dosing in joint arthroplasty, safeguarding adequate levels throughout surgery in all patients, pharmacodynamic modelling was done, showing that even with optimal guideline adherence, patients would be at risk of inadequate cloxacillin levels during surgery. Monte Carlo simulation concluded that administering cloxacillin via a short bolus infusion of 1 to 2 grams before surgery, followed by a continuous infusion of 1 gram/hour , could ensure adequate levels in all patients. This without increasing the total dose given, compared to present dosing guidelines.</p><h3>List of scientific papers</h3><p dir="ltr">I. <b>Wallander K,</b> Jorup-Rönström C, Ullberg M, Törnblom I, Ottosson C, Giske CG. Etiology of bone and joint infections: a case series of 363 consecutive patients from an orthopaedic infection unit. Infect Dis (Lond). 2016 Aug, 48(8), 618-625. <a href="https://doi.org/10.1080/23744235.2016.1183814" target="_blank">https://doi.org/10.1080/23744235.2016.1183814</a></p><p dir="ltr">II. <b>Wallander K,</b> Vondracek M, Giske CG. Evaluation of multi-sample 16S ribosomal DNA sequencing for the diagnosis of postoperative bone and joint infections during antimicrobial treatment. BMC Research Notes. 2022 Mar(22);15(1):113. <a href="https://doi.org/10.1186/s13104-022-05992-7" rel="noreferrer" target="_blank">https://doi.org/10.1186/s13104-022-05992-7</a></p><p dir="ltr">III. <b>Wallander K,</b> Beijer G, Eliasson E, Giske CG, Ponzer S, Söderquist B, Eriksen J. Is current guidance for cloxacillin prophylaxis dosages in hip and knee arthroplasty adequate? Evidence from a prospective Swedish cohort. Journal of antimicrobial chemotherapy. [Submitted]</p><p dir="ltr">IV. Beijer G, <b>Wallander K,</b> Söderquist B, Giske CG, Breuer O, Eriksen J, Eliasson E. Optimising cloxacillin prophylaxis in hip and knee arthroplasty based on population pharmacokinetics of unbound plasma concentrations. [Manuscript]</p>