Towards a better detection of patients at-risk of linezolid toxicity in clinical practice: a prospective study in three Belgian hospital centers.

Introduction: Linezolid is a last-resort antibiotic for infections caused by multidrug-resistant microorganisms. It is widely used for off-label indications and for longer than recommended treatment durations, exposing patients at higher risk of adverse drug reactions (ADRs), notably thrombocytopenia. This study aimed to investigate ADR incidence and risk factors, identify thrombocytopenia-related trough levels based on treatment duration, and evaluate the performance of predictive scores for ADR development. Methods: Adult in- and outpatients undergoing linezolid therapy were enrolled in three hospitals and ADRs and linezolid trough levels prospectively monitored over time. A population pharmacokinetic (pop-PK model) was used to estimate trough levels for blood samples collected at varying times. Results: A multivariate analysis based on 63 treatments identified treatment duration ≥10 days and trough levels >8 mg/L as independent risk factors of developing thrombocytopenia, with high trough values correlated with impaired renal function. Five patients treated for >28 days did not develop thrombocytopenia but maintained trough values in the target range (<8 mg/L). The Buzelé predictive score, which combines an age-adjusted Charlson comorbidity index with treatment duration, demonstrated 77% specificity and 67% sensitivity to predict the risk of ADR. Conclusion: Our work supports the necessity of establishing guidelines for dose adjustment in patients with renal insufficiency and the systematic use of TDM in patients at-risk in order to keep trough values ≤8 mg/L. The Buzelé predictive score (if ≥7) may help to detect these at-risk patients, and pop-PK models can estimate trough levels based on plasma samples collected at varying times, reducing the logistical burden of TDM in clinical practice.

Development of quality indicators for antimicrobial stewardship in Belgian hospitals: a RAND - modified Delphi procedure.

INTRODUCTION: Inappropriate antibiotic use is a major cause of antibiotic resistance. Therefore, optimizing antibiotic usage is essential. In Belgium, optimization of antimicrobials for the fight against multidrug resistant organisms (MDROs) is followed up by national surveillance by public health authorities. To improve appropriate antimicrobial use in hospitals, an effective national Antimicrobial Stewardship (AMS) program should include indicators for measuring both the quantity and quality of antibiotic use. OBJECTIVES: The aim of this study was to develop a set of process quality indicators (QIs) to evaluate and improve AMS in hospitals. METHODS: A RAND-modified Delphi procedure was used. The procedure consisted of a structured narrative literature review to select the QIs, followed by two online questionnaires and an intermediate multidisciplinary panel discussion with experts in infectious diseases from general and teaching hospitals in Belgium. RESULTS: A total of 38 QIs were selected after the RAND-modified Delphi procedure, from which 11 QIs were selected unanimously. These QIs address compliancy of antibiotic therapy and prophylaxis with local guidelines, documentation of the rationale for antibiotic treatment in the medical record, the availability of AMS Programs and Outpatient Parenteral Antibiotic Therapy, resistance patterns and antimicrobial prescribing during focused ward rounds. CONCLUSION: Our study selected 38 relevant process QIs, from which 11 were unanimously selected. The QIs can contribute to the improvement of quality of antibiotic use by stimulating hospitals to present better outcomes and by providing a focus on how to intervene and to improve prescribing of antimicrobials.

Perceptions, attitudes, and practices of a Belgian teaching hospital's physicians, pharmacists, and nurses regarding antibiotic use and resistance: survey towards targeted actions for Antimicrobial Stewardship.

OBJECTIVES: This study aimed to identify barriers to the proper use of antibiotics by healthcare professionals and to help the hospital Antimicrobial Stewardship develop suitable actions for the staff. METHODS: In a Belgian teaching hospital, a survey was conducted among physicians, pharmacists, and nurses involved in antibiotherapy. Questions from the 2019 European Center for Disease Prevention and Control (ECDC) survey were analyzed based on components of the COM-B model (capabilities, opportunities, and motivations). First, collected data were reviewed with the Ethnos software to analyze the different COM-B model components. For statistical analyses, responses were grouped into three clear-cut answers in a Fisher's exact test. RESULTS: Overall, 400 staff members were included. We found that our professions, combined, have a good perception of antibiotic resistance (97.8%). For capabilities, however, only 77.2% state that they have sufficient knowledge, with 91.3%, 71.5%, and 63.0% for physicians, nurses, and pharmacists, respectively. For opportunities (access to resources, information, and training), it is observed that 72.2% report having easy access to the guidelines they need to manage infections. In comparison, for 64.2% of the respondents, this information changed their opinion on the useless or inappropriate prescription, administration, and delivery of antibiotics. For 55.0%, this information has enabled them to change their practices. Finally, for motivations, 92.8% of respondents state that they know about the link between their practices and the emergence and spread of antibiotic resistance. However, only 65.0% of participants say they have a role in managing antibiotic resistance. We found that 5 out of 8 questions are significantly dependent on the profession: 2 inquiries related to capability, 1 to opportunity, and 2 to motivation. CONCLUSION: We found that responses to the ECDC questionnaire are related to the profession. While some topics are universal/cross-functional, others must be explicitly tailored to each professional category. Information is useless if not accessible. Communication and provision of documents are thus paramount.

Impact of the COVID-19 pandemic on Clostridioides difficile infection in a tertiary healthcare institution in Belgium.

OBJECTIVES: Clostridioides difficile infection (CDI) causes the greatest number of healthcare-associated infectious diarrhoea. CDIs are transmitted by direct and indirect patient-to-patient contact and risk increases with the use of antibiotics. Since early 2020, the COVID-19 pandemic has affected healthcare systems in many ways including substantial changes in hygiene behaviour. The aim of this study was to assess whether CDI incidence differed during the COVID-19 pandemic compared to a year before. METHODS: All tests for suspected CDI cases were recorded for a hospital in Brussels, Belgium. The percentage of CDI-positive results and incidences (total and healthcare-associated (HA)-CDI)) for years 2019, 2020, 2021, and 2022 were calculated. Antibiotic consumption was analysed for years 2019 and 2020. RESULTS: Since the COVID-19 pandemic struck, a significant reduction of up to 39% was observed in the number of Clostridioides difficile stool tests in our hospital. A significant decrease in the percentage of positive tests and a 50% decrease in the incidence of CDI (total and HA-CDI) was found for 2020 compared with 2019 and confirmed for years 2021 and 2022. The decrease in CDI incidence was mostly marked in haematology, nephrology, and gastroenterology units. No significant change in the use of antibiotics was found. CONCLUSION: The global decrease in CDI incidence observed in our hospital was not associated with a change in the use of antibiotics. The control measures implemented to prevent COVID-19 transmission may explain a reduction in CDI incidence. An underdiagnosis of CDI cannot be excluded.

Clinical Use and Adverse Drug Reactions of Linezolid: A Retrospective Study in Four Belgian Hospital Centers.

In Belgium, linezolid is indicated for pneumonia and skin and soft tissue infections, but is more broadly used, due to its oral bioavailability and activity against multiresistant organisms. This could increase the risk of adverse drug reactions (ADR), notably hematological disorders (anemia, thrombocytopenia), neuropathy, or lactic acidosis. We analyzed linezolid clinical use in relationship with occurrence of ADR in Belgian hospitals and highlighted risk factors associated with the development of thrombocytopenia. A retrospective analysis of electronic medical records and laboratory tests of adult patients treated with linezolid in four Belgian hospitals in 2016 allowed the collection of ADR for 248 linezolid treatments. Only 19.7% of indications were in-label. ADR included 43 thrombocytopenia, 17 anemia, 4 neuropathies, and 4 increases in lactatemia. In a multi-variate analysis, risk factors of thrombocytopenia were a treatment duration > 10 days, a glomerular filtration rate < 60 mL/min, and a Charlson index ≥ 4. Off-label use of linezolid is frequent in Belgium, and ADR more frequent than reported in the summary of product characteristics, but not statistically associated with any indication. This high prevalence of ADR could be related to a high proportion of patients presenting risk factors in our population, highlighting the importance of detecting them prospectively.

Comparative in vitro antimicrobial potency, stability, colouration and dissolution time of generics versus innovator of meropenem in Europe.

Meropenem generics are often imposed on prescribers, however scarce information is available on key properties such as antimicrobial potency, stability and colouration in solution, and dissolution time. This study aimed to generate comparative information for products available in Europe. The originator (ASTRA) and four generics (HOSPIRA, SANDOZ, FRESENIUS and AUROVIT) were compared for: (i) MICs against Pseudomonas aeruginosa clinical isolates (range, 0.125-191 mg/L); (ii) colouration (visual and photometry) and stability of concentrated solutions for prolonged or continuous infusion and maintained at 25-37 °C for up to 8 h (acceptable limit, ≥90% of original concentration); and (iii) dissolution time of concentrated solutions (50 mg/mL [for bolus administration]: turbidimetry and nursing personnel assessment). No significant difference was observed for MICs (except 2/80 isolates). For concentrated solutions storage: (i) SANDOZ produced about two times more yellow-coloured degradation products than the other preparations; (ii) meropenem loss was time-, concentration- and temperature-dependent; (iii) FRESENIUS was the least stable (limit for 1 g/48 mL, ~8 h at 25 °C and 4.5 h at 37 °C); (iv) at 2 g/48 mL, the storage time limit was 5-6 h at 25 °C and ~3 h at 37 °C for all preparations. Complete dissolution (turbidimetry) required 240 s for generics (120 s for ASTRA), and nurses reported longer but highly variable times for generics. Substantial differences between innovator and generics have been identified that could impact on their clinical use and/or make multicentric studies difficult to interpret, requiring suitability studies in the environments of their intended use.

Clinical characteristics and outcomes of patients receiving outpatient parenteral antibiotic therapy in a Belgian setting: a single-center pilot study.

BACKGROUND: Outpatient parenteral antibiotic therapy (OPAT) was not used in Belgium before 2013, except for patients with cystic fibrosis. Thus, we have performed a pilot study to evaluate clinical characteristics and outcomes of patient receiving OPAT in a Belgian setting. METHODS: The study was a prospective observational single-center study of patients receiving OPAT between 1 September 2013 and 31 December, 2017. RESULTS: We included 218 OPATs. The median age was 58 years and 71% were men. At the end of the treatment, 92% of the patients on OPAT were cured. Risk factors for treatment failure were obesity, diabetes and diabetic foot infections, longer duration of hospitalization before OPAT, and duration of OPAT >16 days. An average of 24 days of hospitalization per patient discharge was saved, which amounted to 5205 days saved during the project. During the OPAT and 30 days thereafter, 71 (32.6%) of patients were readmitted, but only 26 (12%) readmissions were directly related to OPAT. Risk factors for readmissions were diabetes and diabetic foot infections, endovascular infections, longer duration of hospitalization before OPAT, duration of OPAT >30 days, and history of hospitalizations in the year before OPAT. There were 2.3 intravenous catheter-related events per 1000 days of catheter use. Patients' level of satisfaction was high (99.5%). CONCLUSIONS: In this pilot study, OPAT is found to be efficacious in saving hospitalization's days, with a low rate of readmissions and complications and a high patients' level of satisfaction. We therefore conclude that OPAT is feasible and safe. BACKGROUND: Outpatient parenteral antibiotic therapy (OPAT) was not used in Belgium before 2013, except for patients with cystic fibrosis. Thus, we have performed a pilot study to evaluate clinical characteristics and outcomes of patient receiving OPAT in a Belgian setting. METHODS: The study was a prospective observational single-center study of patients receiving OPAT between 1 September 2013 and 31 December, 2017. RESULTS: We included 218 OPATs. The median age was 58 years and 71% were men. At the end of the treatment, 92% of the patients on OPAT were cured. Risk factors for treatment failure were obesity, diabetes and diabetic foot infections, longer duration of hospitalization before OPAT, and duration of OPAT >16 days. An average of 24 days of hospitalization per patient discharge was saved, which amounted to 5205 days saved during the project. During the OPAT and 30 days thereafter, 71 (32.6%) of patients were readmitted, but only 26 (12%) readmissions were directly related to OPAT. Risk factors for readmissions were diabetes and diabetic foot infections, endovascular infections, longer duration of hospitalization before OPAT, duration of OPAT >30 days, and history of hospitalizations in the year before OPAT. There were 2.3 intravenous catheter-related events per 1000 days of catheter use. Patients' level of satisfaction was high (99.5%). CONCLUSIONS: In our study, OPAT is found to be efficacious in saving hospitalization's days, with a low rate of readmissions and complications and a high patients' level of satisfaction. We therefore conclude that OPAT is feasible and safe.

Perception of alopecia by patients requiring chemotherapy for non-small-cell lung cancer: a willingness to pay study.

OBJECTIVE: Chemotherapy-induced alopecia may have a substantial impact on the quality of life (QOL) of lung cancer patients, but very few data are available. The aim of this study was to assess the perceived impact of alopecia based on a "willingness to pay" (WTP) approach. METHODS: We conducted a prospective multicenter WTP study of patients receiving chemotherapy for non-small-cell lung cancer (NSCLC). The perceived impact of alopecia was assessed with a visual analogue scale (VAS; 0: no impact, 10: major impact), and from the patients' willingness to pay for chemotherapy that had the same efficacy, dosing schedule and tolerability as the standard treatment but that cut the risk of alopecia from 40% to 5%. RESULTS: Among the 135 patients enrolled in this study, the mean score on the VAS for the perceived likely impact of alopecia was 4.4 ± 0.3. The mean WTP for a 3-week chemotherapy cycle reducing the risk of alopecia from 40% to 5% was €83.4 ± 10.2 (€median 37.5), representing 2.1% of total income, while 27% of patients were unwilling to pay anything. There was a significant association between WTP and gender (women, p < 0.01), annual incomes (p < 0.01), but not with marital status, level of education or occupations. CONCLUSION: Alopecia appears to be an important outcome for patients receiving chemotherapy for NSCLC. Women and patients with high annual incomes were more willing to pay.