# Impact of pharmacist-led interventions in a multidisciplinary consultation meeting for bone and joint infection

Anne Elisabeth Royere, Xavier Pourrat, Louis-Romée Le Nail, Marie-Frédérique Lartigue, Adrien Lemaignen, Vianney Tuloup, Marion Lacasse

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## ► To cite this version:

Anne Elisabeth Royere, Xavier Pourrat, Louis-Romée Le Nail, Marie-Frédérique Lartigue, Adrien Lemaignen, et al. Impact of pharmacist-led interventions in a multidisciplinary consultation meeting for bone and joint infection. *Infectious Diseases Now*, 2024, 54 (7), pp.104958. 10.1016/j.idnow.2024.104958. hal-04741684

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Submitted on 17 Oct 2024

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Original article

# Impact of pharmacist-led interventions in a multidisciplinary consultation meeting for bone and joint infection

<figure><img src="image_3.png" /></figure>

Anne Elisabeth Royere<sup>a</sup>, Xavier Pourrat<sup>a</sup>, Louis-Romée Le Nail<sup>b</sup>, Marie-Frederique Lartigue<sup>c,d</sup>, Adrien Lemaignen<sup>e,f</sup>, Vianney Tuloup<sup>a,g,*</sup>, Marion Lacasse<sup>f</sup>, upon members of the Tours CRIOAC

## ARTICLE INFO

**Keywords:**

Drug related problems

Bone and Joint Infection

Drug-Drug Interactions

Multidisciplinary team meetings

## ABSTRACT

**Introduction:** Management of bone and joint infections (BJI) requires prolonged and high-dose antibiotic therapy to achieve target concentrations in bone tissue. However, these therapies often lead to adverse effects in patients who are frequently fragile, with multiple comorbidities and associated medications. The decision to treat these complex cases is made during a multidisciplinary team meeting at the reference centre for complex osteoarticular infections (CRIOAC).

**Material and Methods:** Elaborated by a pharmacist during CRIOAC meetings, a single-centre before-and-after comparative study of drug-related issues observed during pharmaceutical interventions (PIs), was conducted. For each patient included, a retrospective case was added. PIs were independently evaluated by a committee of infectiologists and pharmacists to assess their criticality.

**Results:** Sixty patients were included in the intervention group, with 59 controls. The population was homogeneous, with a median age of 65 years. Most BJI cases were complex (65.5 %), primarily involving prosthetic joint infections. Staphylococcus species were the predominant pathogens. Antibiotic therapy adapted to antibiograms was orally relayed for 74 % of patients, with 5.9 % requiring re-hospitalization due to adverse effects. Sixty-two PIs were performed, representing an average of 1.8 PIs per meeting or 34.4 % of patients. Dosage adjustment accounted for 42 % of PIs, drug interactions for 46 %, and treatment availability in community pharmacies for 8 %.

Regarding criticality, three PIs were classified as vital, 22 as major, 22 as moderate, and 15 as minor in both groups, with the same distribution between the intervention and control groups.

**Conclusion:** This study demonstrates that by collaborating with surgeons and infectiologists, pharmacists participating in CRIOAC meetings can strongly help to prevent drug-related problems in patients with BJIs.

## 1. Introduction

Bone and joint infections (BJI), including osteomyelitis with or without a device, prosthetic joint infection, and septic arthritis, represent a group of complex and heterogeneous pathologies that can impact the functional prognosis of inpatients [1-3]. Patient care relies on a combination of surgery and tailored long-term antibiotic therapy.

Treatment decisions are made by a specialized multidisciplinary team network, designated by the French Health Ministry as Reference Centres for Complex Bone and Joint Infection: the CRIOAC network [4,5]. CRIOACs comprise infectious disease specialists, orthopaedic surgeons, microbiologists, and hospital pharmacists, providing medical opinions for 2000 to 5000 BJI cases annually. In addition to determining the surgical approach for infected patients, the CRIOAC determines the most

<footnote><sup>a</sup> Pharmacy Department, Logipôle Trousseau, CHRU Tours, France</footnote>

<footnote><sup>b</sup> Orthopedic and Traumatology Surgery Service, Trousseau Hospital, France</footnote>

<footnote><sup>c</sup> Bacteriology-Virology-Hygiene Service, Trousseau Hospital, CHRU Tours, France</footnote>

<footnote><sup>d</sup> ISP, UMR1282, Tours University, INRAE, Tours, F-37032, France</footnote>

<footnote><sup>e</sup> Infectious Disease and Internal Medicine Service, Bretonneau Hospital, CHRU Tours, France</footnote>

<footnote><sup>f</sup> Education - Ethic - Health, EA7505, Tours University, Tours, France</footnote>

<footnote><sup>g</sup> Inserm U1327 ISCHEMIA "Membrane signalling and inflammation in reperfusion injuries", Université de Tours, Tours, France</footnote>

<footnote>* Corresponding author at: Pharmacy Department, Logipôle Trousseau, CHRU Tours, France.
E-mail address: v.tuloup@chu-tours.fr (V. Tuloup).</footnote>
appropriate antibiotic therapy based on clinical and biological data and comorbidities [6,7]. The latter is specific to osteoarticular infections due to its duration of six weeks to three months, depending on type of infection, its high dosage to achieve satisfactory bone diffusion, and its elevated risk of drug-drug interactions with patients' co-medications. Drug combinations are sometimes necessary, increasing the risk of adverse effects [8–10]. Prescribing methods often deviate from the scope of market access authorization (AMM), in terms of both indication and treatment duration, insofar as industrial research on BJI is insufficient to justify dedicated AMMs.

Drug interactions are a leading cause of iatrogenic events in France, contributing to a high rate of re-hospitalization [11]. Antibiotic therapies administered to patients with bone and joint infections (BJI) not only induce drug interactions through their effects on cytochromes P450 or efflux transporters such as P-glycoprotein, but also frequently serve as substrates for the same enzymes, necessitating adjustments so as to maintain therapeutic levels [5,8].

Given this scenario, the expertise of a pharmacist may be of invaluable in help to clinicians in thrift tailoring and individualizing of drug dosages, not only for antibiotics within the scope of expertise of the CRIOAC, but also for additional treatments impacting patients' concomitant medications. Although only limited data exist on the role of pharmacists in multidisciplinary infectious disease teams, some studies have suggested that pharmacist involvement could lead to reduced re-hospitalization through more prudent use of antimicrobial agents [8,11,12].

This study seeks to evaluate the contributions of clinical pharmacists on drug-related problems during their pharmaceutical interventions in CRIOAC Meetings.

## 2. Material and methods

This study was a before/after monocentric comparative study conducted between July 2022 and April 2023. The retrospective control group included all patients discussed in CRIOAC multidisciplinary team Meetings, abbreviated as “Meetings”, without the presence of a pharmacist, from July to October 2022. At first, the CRIOAC comprised infectious disease specialists, orthopaedic surgeons, and microbiologists. The intervention group entailed the same meeting schedule, with the attendance of a senior clinical pharmacist, from January to April 2023. The composition of the meetings remained unchanged between the two periods, except for the addition of a clinical pharmacist in the intervention group. Inclusion criteria were consistent for both groups: Every adult patient over 18 years of age with an osteoarticular infection requiring antibiotic therapy for more than 10 days, with documented meeting decisions. All included patients had undergone medication reconciliation within the last 6 months. Medication reconciliation is a formal process based on the most complete list of a patient's current medication, and is routinely performed in surgical wards by pharmacy students. Patients without medication reconciliation were excluded so as to ensure a clear overview of the treatments actually taken by patients in the retrospective group, thereby avoiding any loss in terms of drug interaction intervention.

BJI patients were presented at weekly meetings to discuss upstream medical or surgical management and postoperative intravenous (IV) probabilistic antibiotic therapy (referred to as “first takeover meetings”) and/or to discuss adaptation of antibiotic therapy and PO switch if necessary (referred to as “oral transition meetings”). From a pharmaceutical perspective, a clinical pharmacist was present daily in the orthopaedics department and conducted pharmaceutical analysis of prescriptions but without participating in the CRIOAC meetings. We decided to involve pharmacists due to their ability to provide comprehensive pharmaceutical expertise.

The primary endpoints were the number of drug-related problem (DRPs) per patient and the risk associated with each DRP before and after including a pharmacist in the meeting. Retrospective DRPs of the

group based on meeting reports and current hospitalization prescriptions at the time of the decision were assessed by a pair of pharmacists specialized in osteoarticular infections. Prospective DRPs were collected during meetings by a pharmacy resident with the assistance of the senior pharmacist in charge of the CRIOAC. The risk associated with each DRP was determined by an independent committee of two pharmacists and one infectious disease specialist not involved in the CRIOAC, using the CLEO criticality scale of the French Society of Clinical Pharmacy (SFPC), divided into five levels of criticality [13].

0C=Nil: The pharmaceutical intervention had no influence on the patient's clinical condition, knowledge, satisfaction, medication adherence, and/or quality of life.

1C=Minor: The intervention improved knowledge, satisfaction, medication adherence, and/or quality of life OR prevented harm that did not require monitoring/treatment.

2C=Moderate: The intervention prevented harm that necessitated increased monitoring or treatment but did not result in or prolong the patient's hospital stay.

3C=Major: The intervention prevented harm that resulted in or prolonged the patient's hospital stay OR caused permanent incapacity or disability.

4C=Vital: The intervention prevented an incident that could have potentially led to intensive care or death for the patient.

Clinical data from the meetings were extracted from structured notes from the CRIOAC meeting in the informatic patient file, using the informatized patient file, DPI (Millenium ® Cerner, KC, USA). Biological details, missing clinical data, and patient history were also retrieved from DPI. Pharmaceutical interventions were analyzed based on current international recommendations, Product Characteristic Summaries, the French Drug Interaction Thesaurus, and drug comparison algorithms such as Drugs® or Theriaque®. The clinical impact of PIs was assessed using the CLEO part 1 rating scale of the SFPC [13]. Adverse events occurring during oral antibiotic therapy were reported according to the 2017 Common Terminology for Adverse Events version 5 (CTCAE) criteria of the National Cancer Institute [14].

This study is registered in the French CNIL database under n° 2023_007, and all patients were notified by a non-opposition letter. Data were analyzed using Microsoft Excel Software and R software, employing the Chi² or Fisher tests for nominal qualitative variables with small samples, the Kruskal-Wallis test for ordinal qualitative variables, and the Mann-Whitney test for quantitative variables. Results with a p-value < 0.05 were considered significant.

## 3. Results

All in all, 334 cases of patients with osteoarticular infections were evaluated during the study period in CRIOAC meetings, out of which 35.6 % (119/334) were included. For the 2022 period, the meetings reviewed the records of 169 patients, with 34.9 % (59/169) of patient records included in the control group. For various reasons, the remaining 65 % of patient records were not included: absence of a medication reconciliation entry fewer than 6 months previous to the meeting; lack of a computerized meeting form; or discontinuation of antibiotics before or within 10 days, indicating the absence of a bone and joint infection (BJI). In 2023, the meetings reviewed the records of 165 patients, with 39.4 % (60/165) of patient records included in the interventional group. For similar reasons, as observed in the control group, the remaining 63.6 % of patient records were not included (Fig. 1).

A majority of patients were men (77/119, 65 %), with a median age of 65 years [min-max: 20-89]. No clinical or socio-demographic statistical differences appeared between the two groups, presented in Table 1. The majority of BJIs involved monomicrobial *Staphylococcus aureus* hip infections on prostheses or native hips. Only two patients presented a fungal infection, both of them in the intervention group.

Both groups received the same empiric intravenous antibiotic therapy protocol, consisting of piperacillin-tazobactam and linezolid (112/
<figure><img src="image_4.png" /><figcaption>Fig. 1. Study flowchart of file inclusion. MDTM: multidisciplinary Team Meeting.</figcaption></figure>

119, 94.1 %), except in cases where patients had documented allergies (those allergic to beta-lactams were prescribed aztreonam instead of piperacillin-tazobactam) or in cases of suspected microbial resistance. All in all, 73.9 % of patients (88/119) were transitioned to oral administration with an adjusted antibiotic regimen. The distribution of antibiotic therapy is outlined in Table 2. Among these patients, 43.2 % (38/88) received a six-week course of antibiotics, while 46.6 % (41/88) underwent a three-month treatment when surgery to change the prosthetic implant was not feasible or was incomplete. Additionally, suppressive antibiotic therapy was initiated for 8 % (7/88) of patients.

Concerning DRPs, 29 were identified during meetings in the intervention group, affecting 33.3 % (20/60) of patients. This equates to an average of 1.7 DRPs per meeting, with prevalence of 52.1 % of patients (95 % CI=[0.52 ± 0.08]). Each DRP prompted a pharmaceutical intervention, all of which were accepted by the clinicians. Out of these, 48.3 % (14/29) pertained to treatment adaptations based on renal or hepatic function, 24.1 % (7/29) were related to drug interactions, and 27.6 % (8/29) involved supply shortages or management modalities.

In the control group, 33 DRPs were identified retrospectively by the pharmacist, resulting in an average of 1.9 DRPs per meeting affecting 35.6 % of patients (21/59). Among these, drug interactions accounted for 63.6 % (21/33) of DRPs, while 36.4 % (12/33) involved adaptations to the patient's pathophysiology.

The breakdown of pharmaceutical interventions is illustrated in Fig. 2. In the intervention group, the majority of interventions were classified as minor in 41.4 % (12/29) of occurrences, followed by major interventions in 34.5 % (10/29) of cases, and moderate interventions in 17.2 % (5/29). Additionally, 6.9 % (2/29) of occurrences were classified as vital. In contrast, in the control group, the majority of interventions were of moderate severity, accounting for 51.5 % (17/33) of cases, followed by major interventions in 36.4 % (12/33), and minor interventions in 9.1 % (3/33) of cases. One pharmaceutical intervention, accounting for 3 % (1/33), was categorized as vital.

The distribution of drug-related problems leading to pharmaceutical interventions is summarized in Fig. 3.

With regard to drug-related problems, particularly drug-drug interactions, all DRPs targeted rifampicin in the intervention group. In the control group, 76.2 % of DRPs (16/21) involved rifampicin, 19.1 % (4/21) levofloxacin, and 4.7 % (1/21) linezolid. These interactions spanned various drug classes, including cardiology (notably oral anticoagulants

and statins), neurology, and psychiatry. Interactions ranged from the lowest level of “to be taken into account” to the highest level of “contraindication”. Patients with DRPs related to drug interactions received reinforced clinical and/or biological monitoring, dosage adjustments, or replacement by another molecule not affected by drug-drug interactions (DDIs). Clinically, all DDI-related DRPs were rated at levels 2C and 3C, indicating a moderate to major impact on patient management.

In terms of optimizing therapies, specifically antibiotic management methods, 37.5 % (3/8) of DRPs formulated by the pharmacist were focused on setting up home infusions for ertapenem and ceftazidime-avibactam in a home hospitalization structure or via a service provider. Additionally, 80 % (4/5) of DRPs related to out-of-stock supplies of drugs targeted levofloxacin, and 20 % (1/5) targeted amoxicillin. The antibiotics were replaced by alternative molecules available in community pharmacies, namely moxifloxacin and clindamycin. Clinically, all DRPs related to therapeutic optimization were rated at a minor severity level with minimal impact on patient management.

Regarding adverse events, four cases were identified in the control group, all associated with levofloxacin prescriptions. Half of these cases required hospitalization for further explorations due to grade 3 out of 5 vomiting and pancreatitis. In the intervention group, three cases of adverse events were discussed during meetings, all involving severe nausea and vomiting that significantly impaired daily life and necessitated a switch of antibiotic therapy. The drugs involved were amoxicillin, clindamycin, and levofloxacin, all administered as monotherapy. Clinical symptoms resolved upon switching treatments.

## 4. Discussion

This study demonstrates that involving a pharmacist in CRIOAC meetings working alongside surgeons and infectious disease specialists, helps to prevent drug-related problems (DRPs) in patients with bone and joint infections (BJI). In this new framework, pharmacists conducted an average of 1.8 pharmaceutical interventions (PIs) per meeting. While there are few studies on pharmaceutical interventions in infectious disease meetings, work by Bouchand et al. in 2016 showed similar findings, with pharmacists providing pharmaceutical opinions leading to at least one PI per meeting. Additionally, they reported 90 DRPs, with 50 % related to anti-infectives [15]. Similarly, our study found 8 PIs
<table><caption>**Table 1**
Clinical and socio-demographic data for the two populations.</caption><thead><tr><th></th><th>Total population</th><th>Intervention group</th><th>Control group</th><th>p-value</th></tr></thead><tbody><tr><td>Population size</td><td>119</td><td>60</td><td>59</td><td></td></tr><tr><td><u>Socio-demographic data</u></td><td></td><td></td><td></td><td></td></tr><tr><td>Gender</td><td></td><td></td><td></td><td></td></tr><tr><td>Male</td><td>77 (64.7 %)</td><td>39 (65.0 %)</td><td>38 (64.4 %)</td><td rowspan="2">0.94</td></tr><tr><td>Female</td><td>42 (35.3 %)</td><td>21 (35.0 %)</td><td>21 (35.6 %)</td></tr><tr><td>Age (median, min-max, IQR)</td><td>65 [20-89] [24]</td><td>65 [21-89] [23]</td><td>68 [20-86] [26]</td><td>0.94</td></tr><tr><td>Comorbidities</td><td></td><td></td><td></td><td></td></tr><tr><td>Charlson score (median, min-max)</td><td>3 [0-11]</td><td>3 [0-11]</td><td>3 [0-8]</td><td rowspan="2">0.96</td></tr><tr><td>Renal impairment (eGFR 30-&lt;60 ml/min)</td><td>4 (3.4 %)</td><td>2 (3.3 %)</td><td>2 (3.4 %)</td></tr><tr><td>Renal impairment (eGFR&lt;30 ml/min)</td><td>5 (4.2 %)</td><td>3 (5.0 %)</td><td>2 (3.4 %)</td><td rowspan="2">0.99</td></tr><tr><td>Cirrhosis - Liver impairment</td><td>3 (2.5 %)</td><td>1 (1.7 %)</td><td>2 (3.4 %)</td></tr><tr><td>Hypertension</td><td>55 (46.2 %)</td><td>27 (45 %)</td><td>28 (46.7 %)</td><td></td></tr><tr><td>Diabetes mellitus</td><td>25 (21 %)</td><td>12 (20 %)</td><td>13 (22 %)</td><td></td></tr><tr><td>History of atrial fibrillation</td><td>21 (17.6 %)</td><td>10 (16.6 %)</td><td>11 (18.7 %)</td><td></td></tr><tr><td>Coronary artery disease</td><td>10 (8.4 %)</td><td>5 (8.3 %)</td><td>5 (8.5 %)</td><td></td></tr><tr><td>Psychiatric disorder</td><td>21 (17.6 %)</td><td>9 (15 %)</td><td>12 (20.3 %)</td><td></td></tr><tr><td>Dementia</td><td>5 (4.2 %)</td><td>3 (5.0 %)</td><td>2 (3.4 %)</td><td></td></tr><tr><td>Epilepsy</td><td>2 (1.7 %)</td><td>1 (1.7 %)</td><td>1 (1.7 %)</td><td></td></tr><tr><td>Hematological disorder</td><td>7 (5.9 %)</td><td>2 (3.3 %)</td><td>5 (8.5 %)</td><td></td></tr><tr><td>Severe allergy to antibiotics: Anaphylactic shock or Angioedema</td><td>4 (3.4 %)</td><td>3 (5.0 %)</td><td>1 (1.7 %)</td><td rowspan="2">0.61</td></tr><tr><td>Non-severe allergy to antibiotics: Skin rashes, erythema</td><td>5 (4.2 %)</td><td>1 (1.7 %)</td><td>4 (6.8 %)</td></tr><tr><td>BMI</td><td></td><td></td><td></td><td></td></tr><tr><td>Normal (&lt;25 kg/m²)</td><td>39 (36.1 %)</td><td>18 (32.1 %)</td><td>21 (40.4 %)</td><td rowspan="3">0.26</td></tr><tr><td>overweight (25 - &lt;30 kg/m²)</td><td>39 (36.1 %)</td><td>20 (35.8 %)</td><td>19 (36.5 %)</td></tr><tr><td>Obesity (≥30 kg/m²)</td><td>30 (27.8 %)</td><td>18 (32.1 %)</td><td>12 (23.1 %)</td></tr><tr><td>Missing values</td><td>11 (9.2 %)</td><td>4 (6.6 %)</td><td>7 (11.9 %)</td><td></td></tr><tr><td>Medication Count</td><td></td><td></td><td></td><td></td></tr><tr><td>0 - &lt; 3</td><td>36 (30.2 %)</td><td>19 (31.7 %)</td><td>17 (28.8 %)</td><td rowspan="3">0.57</td></tr><tr><td>≥ 3 - &lt; 5</td><td>20 (16.9 %)</td><td>11 (18.3 %)</td><td>9 (15.3 %)</td></tr><tr><td>≥ 5</td><td>63 (52.9 %)</td><td>30 (50 %)</td><td>33 (55.9 %)</td></tr></tbody></table>

BMI: body-mass-index. P-value is expressed with an alpha risk of 5%.

aimed at optimizing therapeutics and identified 54 DRPs, all of which were accepted by clinicians during meetings. These results align with observations in other medical specialties such as oncology, where pharmacists identified DRPs in 95 % of patients and helped reduce these problems by 20 to 40 %, as shown by Herledan et al [16].

While the number of DRPs identified was similar in the two groups, their nature differed. In the intervention group, DRPs primarily focused on optimizing therapeutics to promote patient medication compliance and improve quality of life, particularly through home care. Pharmacists play a crucial role in optimizing patient care by monitoring drug availability and treatment management [17]. While some centres involve pharmacists in consultations so as to ensure drug availability in local pharmacies and promote patient adherence to treatment [18],

<table><caption>**Table 2**
Distribution of prescribed antibiotics per period.</caption><thead><tr><th>Variable</th><th>Total Population</th><th>Intervention Group (IG)</th><th>Control Group (CG)</th><th>p-value</th></tr></thead><tbody><tr><td>Population size</td><td>119</td><td>60</td><td>59</td><td></td></tr><tr><td>Probabilistic post-operative IV antibiotics</td><td>112 (94.1 %)</td><td>56 (93.3 %)</td><td>56 (95 %)</td><td rowspan="2">0.71</td></tr><tr><td>Piperacillin - tazobactam</td><td>82 (73.2 %)</td><td>38 (67.8 %)</td><td>44 (78.6 %)</td></tr><tr><td>Linezolid</td><td>76 (67.8 %)</td><td>34 (60.7 %)</td><td>42 (75 %)</td><td></td></tr><tr><td>Aztreonam</td><td>3 (2.7 %)</td><td>1 (1.8 %)</td><td>2 (3.6 %)</td><td></td></tr><tr><td>Daptomycin</td><td>14 (12.5 %)</td><td>8 (14.3 %)</td><td>6 (10.7 %)</td><td></td></tr><tr><td>Cephalosporin</td><td>21 (18.8 %)</td><td>14 (25 %)</td><td>7 (12.5 %)</td><td></td></tr><tr><td>Amoxicillin - clavulanic acid</td><td>3 (2.7 %)</td><td>2 (3.6 %)</td><td>1 (1.8 %)</td><td></td></tr><tr><td>Vancomycin</td><td>3 (2.7 %)</td><td>2 (3.6 %)</td><td>1 (1.8 %)</td><td></td></tr><tr><td>Carbapenem</td><td>4 (3.6 %)</td><td>1 (1.8 %)</td><td>3 (5.3 %)</td><td></td></tr><tr><td>Probabilistic PO antibiotics from the outset</td><td>7 (5.9 %)</td><td>4 (6.7 %)</td><td>3 (5.1 %)</td><td>1</td></tr><tr><td>Switch to adapted IV antibiotics</td><td>15 (12.6 %)</td><td>5 (8.3 %)</td><td>10 (16.9 %)</td><td>0.15</td></tr><tr><td>Cephalosporin</td><td>7 (46.7 %)</td><td>4 (80 %)</td><td>3 (30 %)</td><td rowspan="2">0.03</td></tr><tr><td>Carbapenem</td><td>1 (6.6 %)</td><td>1 (20 %)</td><td>0 (0 %)</td></tr><tr><td>Dalbavancin</td><td>7 (46.7 %)</td><td>0 (0 %)</td><td>7 (70 %)</td><td></td></tr><tr><td>Switch to adapted PO antibiotics</td><td>88 (73.9 %)</td><td>44 (73.3 %)</td><td>44 (74.6 %)</td><td>0.87</td></tr><tr><td>Levofloxacin</td><td>33 (37.5 %)</td><td>7 (15.9 %)</td><td>26 (59.1 %)</td><td>0.00007</td></tr><tr><td>Ciprofloxacin</td><td>11 (12.5 %)</td><td>10 (22.7 %)</td><td>1 (2.3 %)</td><td></td></tr><tr><td>Moxifloxacin</td><td>8 (9.1 %)</td><td>7 (15.9 %)</td><td>1 (2.3 %)</td><td></td></tr><tr><td>Rifampicin</td><td>32 (36.4 %)</td><td>10 (22.7 %)</td><td>22 (50 %)</td><td>0.01</td></tr><tr><td>Clindamycin</td><td>21 (23.8 %)</td><td>14 (31.8 %)</td><td>7 (15.9 %)</td><td rowspan="2">0.14</td></tr><tr><td>Doxycycline</td><td>10 (11.4 %)</td><td>7 (15.9 %)</td><td>3 (6.8 %)</td></tr><tr><td>Amoxicillin</td><td>11 (12.5 %)</td><td>4 (9 %)</td><td>7 (15.9 %)</td><td></td></tr><tr><td>Bactrim</td><td>4 (4.5 %)</td><td>1 (2.3 %)</td><td>3 (6.8 %)</td><td></td></tr><tr><td>Tedizolid</td><td>1 (1.1 %)</td><td>1 (2.3 %)</td><td>0 (0 %)</td><td></td></tr><tr><td>Antifungal</td><td>2 (1.7 %)</td><td>2 (3.3 %)</td><td>0 (0 %)</td><td>0.49</td></tr><tr><td>Voriconazole</td><td>2 (100 %)</td><td>2 (100 %)</td><td>0 (0 %)</td><td></td></tr><tr><td>Continued probabilistic IV antibiotics</td><td>7 (5.9 %)</td><td>5 (8.3 %)</td><td>2 (3.4 %)</td><td>0.44</td></tr><tr><td>Continued probabilistic PO antibiotics</td><td>6 (5 %)</td><td>4 (6.7 %)</td><td>2 (3.4 %)</td><td>0.68</td></tr><tr><td>Stopped antibiotics due to amputation</td><td>3 (2.5 %)</td><td>2 (3.3 %)</td><td>1 (1.7 %)</td><td>1</td></tr><tr><td>Adverse effects of PO antibiotics</td><td>6 (5 %)</td><td>3 (5 %)</td><td>4 (6.8 %)</td><td>0.71</td></tr></tbody></table>

PO: *per os* administration, IV: intravenous administration.

interactions with community pharmacies regarding supply shortages remain sporadic.

A pronounced reduction in PIs targeting DRPs, particularly drug-drug interactions (DDIs), was observed in the intervention group, especially those with moderate clinical impact. This reduction could be attributed to fewer prescriptions of antibiotics commonly associated with DDIs, such as levofloxacin and rifampicin. This may be partially explained by a supply shortage of levofloxacin in community pharmacies during the study period [19]. For rifampicin, the increase was attributed to a higher prevalence of enterobacterial healthcare-associated infections in 2023 compared to 2022, even though the difference was not statistically significant. However, certain drug-drug interactions (DDIs), particularly those with major clinical impact, persisted in fragile patients and prompted pharmaceutical interventions during meetings by the pharmacist. It is important to note that in 2022, due to the retrospective nature of the study, for 21 patients the outcomes of DRPs identified through PIs were unknown. The majority of these DRPs were of minor or moderate severity and involved patients under the monitoring of a clinical pharmacist in a ward or during orthopaedic and infectious disease visits and consultations.
<figure><img src="image_5.png" /><figcaption>Fig. 2. Breakdown of pharmaceutical intervention according to the CLEO severity scale.</figcaption></figure>

<figure><img src="image_6.png" /><figcaption>Fig. 3. Distribution of interventions regarding drug-related problems. DDI: drug-drug interactions.</figcaption></figure>

The primary limitations of the study were its duration and its single-centre design, which restricted the number of patients included. Additionally, a significant proportion of patients did not undergo recent medication reconciliation at the time of the meetings, especially those referred by outside centres for which the electronic medical records were not accessible for consultation. They were automatically excluded from the study. Particularly in the retrospective group, we limited ourselves to complete records, the objective being to avoid overlooking important information and to ensure we avoided a situation of incomplete representation of common treatments. This issue could be addressed by having a pharmacist present at the meetings to identify the most vulnerable patients, in collaboration with the relevant department pharmacist. Furthermore, patients with BJI typically undergo multiple follow-up visits for up to two years, as recommended when assessing recovery from BJI [3,20]. A longer-term study with broader scope and more comprehensive results could provide further validation of these findings.

This study demonstrates the significant impact on prevention of drug-related problems in patients with BJI of having a clinical pharmacist work alongside surgeons and infectious disease specialists in CRIOAC meetings. In this new framework, the pharmacist's dual role as an advisor and an intervenor adds substantial value to patient care, bolstering the standardized integration of pharmacist involvement in national meeting protocols.

With their pharmaceutical expertise, pharmacists enhance the care

of BJI patients, who are often elderly, frail, and taking multiple medications [8,12]. Multidisciplinary consultations, including infectious disease specialists, orthopaedic surgeons, and pharmacists, should be established to ensure comprehensive monitoring of patients throughout their infection treatment [15,18].

As the town-hospital link continues to develop, pharmacists are playing an increasingly crucial role in optimizing therapeutics and mitigating DRPs, ultimately enhancing patient outcomes. The operational integration of clinical pharmacists in CRIOAC meetings highlights the potential for further advancements in multidisciplinary care settings.

## Fundings

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors, and was performed as a part of CRIOAC routine activity.

## Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
## Acknowledgments

We would like to thank all the CRIOAC participants who contributed to production of this article, in particular I. LAPLAIGE for her secretarial work and data collection, Dr. S. JAMARD and Dr. E. BERTHY for their participation in the review of pharmaceutical interventions.

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