Impact of collaborative physician-pharmacist stewardship strategies on prophylactic antibiotic practices: a quasi-experimental study.

BACKGROUND: An effective use of surgical antibiotic prophylaxis (SAP) appears essential to prevent the development of infections linked to surgery while inappropriate and excessive prescriptions of prophylactic antibiotics increase the risk of adverse effects, bacterial resistance and Clostridium difficile infections. In this study, we aimed to analyze SAP practices in an acute secondary hospital in Belgium during the years 2016-2021 in order to evaluate the impacts of combined stewardship interventions, implemented thanks to a physician-pharmacist collaboration. METHODS: A quasi-experimental study on SAP practices was conducted during 5 years (2016-2021) in a Belgian University Hospital. We first performed a retrospective observational transversal study on a baseline group (2016.1-2016.4). Then, we constituted a group of patients (2017.1-2017.4) to test a combined intervention strategy of stewardship which integrated the central role of a pharmacist in antibiotic stewardship team and in the pre-operative delivery of nominative kits of antibiotics adapted to patient factors. After this test, we collected patient data (2018.1-2018.4) to evaluate the sustained effects of stewardship interventions. Furthermore, we evaluated SAP practices (2019.1-2019.4) after the diffusion of a computerized decision support system. Finally, we analyzed SAP practices in the context of the COVID-19 pandemic (2020.1-2020.4 and 2021.1-2021.4). The groups were compared from year to year in terms of compliance to institutional guidelines, as evaluated from seven criteria (χ2 test). RESULTS: In total, 760 surgical interventions were recorded. The observational study within the baseline group showed that true penicillin allergy, certain types of surgery and certain practitioners were associated with non-compliance (p < 0.05). Compared with the baseline group, the compliance was significantly increased in the test group for all seven criteria assessed (p < 0.05). However, the effects were not fully sustained after discontinuation of the active interventions. Following the diffusion of the computerized decision support system, the compliance to guidelines was not significantly improved. Finally, the COVID-19 pandemic did not appear to affect the practices in terms of compliance to guidelines. CONCLUSIONS: This study shows that optimization of SAP practices is achievable within a proactive multidisciplinary approach including real-time pharmaceutical interventions in the operating area and in the care units practicing SAP.

Antibiotic use in patients with Coronavirus disease 2019 (COVID-19): outcomes and associated factors.

OBJECTIVES: To characterise the factors, outcomes and infections associated with antibiotic use in COVID-19 patients. METHODS: Records of patients with RT-PCR-confirmed COVID-19, hospitalized at the CHU Charleroi (Belgium) between 11 March and 3 May 3 2020, were retrospectively reviewed. Factors associated with antibiotic treatment, outcomes and bacterial infections were analysed. RESULTS: Among the 164 hospitalized COVID-19 patients (median age 60.5 years [IQR] 46-79), twenty-five (15.2%) were admitted to the ICU. Twenty-six (15.9%) died in the hospital. One hundred (61%) received antibiotic treatment. Combination therapies with macrolides were more common in the early part of the study period (26/67, 38.8%). Twenty-eight patients (17.1%) had a confirmed infection, mostly of the urinary tract (18/28, 64.3%). Only 2 (1.2%) had a documented respiratory coinfection. Six of the 7 ICU infections (85.7%) were superinfections. Gram-negative bacteria were most frequently isolated. In multivariate analysis, six factors were associated with antibiotic use: being hospitalized in the ICU (OR: 4.59; 95% CI 1.07-19.71), age > 65 years (OR: 4.16; 95% CI 1.72-10.05), arrival from a nursing home (OR: 4.59; 95% CI 1.11-19.71), diabetes (OR: 4.35; 95% CI 1.26-14.93), bilateral consolidation on chest CT (OR: 9.92; 95% CI 2.40-41.06) and a C-reactive protein level > 60 mg/L (OR:2.46; 95% CI 1.13-5.37). Antibiotic treatment did not reduce the length of stay or the mortality rate. CONCLUSION: Antibiotics have been overused during the COVID-19 pandemic, despite a low rate of coinfections . Integrating the antimicrobial stewardship (AMS) programme into the COVID-19 response is essential.

Synthesis of Quercetin-imprinted Polymer Spherical Particles with Improved Ability to Capture Quercetin Analogues.

INTRODUCTION: Molecularly imprinted polymers (MIPs) are composed of specific cavities able to selectively recognise a template molecule. Used as chromatographic sorbents, MIPs may not trap related structures due to the high rigidity of their cross-linking. OBJECTIVE: To improve the capture of quercetin analogues by modulating the synthesis strategy for a quercetin-imprinted polymer (Qu MIP). METHODOLOGY: An additional comonomer bearing a short oligoethylene glycol (OEG) unit was used to prepare a Qu MIP that was compared to a traditional one formulated in a similar fashion, but without the OEG-comonomer. The Qu MIPs were prepared in bead form through fluorocarbon suspension polymerisation. After solid phase extraction (SPE) assessment of their imprinted cavities, the MIPs were evaluated by HPLC for their recognition properties towards quercetin and other polyphenols, including flavonoids, phenolic acids and curcumin. The Qu MIPs were finally SPE-tested on a white onion extract. RESULTS: The incorporation of OEG units modulated the selectivity of the Qu MIP by improving the recognition of quercetin related structures (12-61% increase in the imprinting effect for distant analogues). It also allowed limiting or suppressing non-specific hydrophobic interactions (decrease of about 10% in the rate of quercetin retention on the non-imprinted polymer). The SPE application of the MIP to a white onion extract indicates its interest for the selective extraction of quercetin and its analogues. CONCLUSION: The OEG-modified Qu MIP appears to be an attractive tool to discover new drug candidates from natural sources by extracting, amongst interfering compounds, structural analogues of quercetin. Copyright © 2017 John Wiley & Sons, Ltd.

Quercetin-imprinted chromatographic sorbents revisited: optimization of synthesis and rebinding protocols for application to natural resources.

Molecularly imprinted polymers (MIPs) based on quercetin and synthesized by either bulk, precipitation or suspension polymerization were characterized in terms of size and shape by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). After a study of rebinding protocols, the optimal materials were evaluated as sorbents for solid-phase extraction (SPE) and high-performance liquid chromatography (HPLC) to confirm the presence of imprinted cavities and to assess their selectivity. Besides quercetin, other structurally related natural compounds, naringenin, daidzein and curcumin, were employed for selectivity tests of MIPs. Although rebinding protocols previously described for such MIPs are typically based on binding, washing and eluting methanol-based solutions, we show that this highly polar solvent leads to weak specific interactions (imprinting factor<1) and poor sorbent properties, most probably because of hydrogen-bonding interferences between the MIP and MeOH. Similar experiments performed in tetrahydrofuran yield to much more improved properties (imprinting factor>2.4). This calls for reviewing most of previously published data on quercetin-MIPs; in proper binding conditions, published MIPs may prove more performing than initially assessed. As expected, tested MIPs exhibited the highest selective rebinding towards quercetin template (imprinting effect, quercetin, 3.41; naringenin, 1.54; daidzein, 1.38; curcumin, 1.67); the differences in selectivity between quercetin analogues were explained by the ligand geometries and H-bonding patterns obtained from quantum-chemical calculations. The evaluation of MIPs under identical analytical conditions allowed investigating the effect of the production method on chromatographic performances. The MIPs in bead materials (for quercetin, peak width, 0.69; number of theoretical plates, 143; symmetry factor, 2.22) provided a significant improvement in chromatographic efficiency over the bulk materials (for quercetin, peak width, 1.25; number of theoretical plates, 115; symmetry factor, 2.92). Using the quercetin-beaded MIP as SPE sorbent, quercetin was selectively extracted from Allium cepa L. extract. The MIP developed in this work therefore appears highly promising for the enrichment and determination of quercetin in natural products.

Molecularly imprinted polymers: compromise between flexibility and rigidity for improving capture of template analogues.

New synthetic strategies for molecularly imprinted polymers (MIPs) were developed to mimic the flexibility and mobility exhibited by receptor/enzyme binding pockets. The MIPs were prepared by bulk polymerization with quercetin as template molecule, acrylamide as functional monomer, ethylene glycol dimethacrylate as cross-linker, and THF as porogen. The innovative grafting of specific oligoethylene glycol units onto the imprinted cavities allowed MIPs to be obtained that exhibit extended selectivity towards template analogues. This synthetic strategy gives promising perspectives for the design of molecular recognition of molecules based on a congruent pharmacophore, which should be of interest for drug development.