Perioperative antibiotic use is a common reason for antibiotic misuse. Evidence suggests that adherence to SAP guidelines may improve outcomes. The purpose of this study was to analyze the impact of pharmacist-led antibiotic stewardship interventions on SAP guideline compliance. The study was conducted at an Orthopedic Department of a tertiary care medical center. SAP compliance and antibiotic exposure in the pre-intervention and intervention period was compared using chi-square, Fisher exact, and Mann-Whitney tests, as appropriate. Prophylactic antibiotic use in orthopedic joint arthroplasties (overall guideline adherence: agent, dose, frequency, duration), clinical outcomes (length of stay-LOS, number of surgical site infections-SSIs), antibiotic exposure and direct antibiotic costs were compared between pre-intervention and intervention periods. Significant improvement in mean SAP duration (by 42.9%, 4.08 ± 2.08 vs. 2.08 ± 1.90 days, p ˂ 0.001), and overall guideline adherence regarding antibiotic use (by 56.2%, from 2% to 58.2%, p ˂ 0.001) were observed. A significant decrease was observed in antibiotic exposure in SAP (by 41%, from 6.07 ± 0.05 to 3.58 ± 4.33 DDD/patient, p ˂ 0.001), average prophylactic antibiotic cost (by 54.8%, 9278.79 ± 6094.29 vs. 3598.16 ± 3354.55 HUF/patient), and mean LOS (by 37.2%, from 11.22 ± 6.96 to 7.62 ± 3.02 days, p < 0.001); and a slight decrease in the number of confirmed SSIs was found between the two periods (by 1.8%, from 3% to 1.2%, p = 0.21). Continuous presence of the clinical pharmacist led to significant improvement in SAP guideline adherence, which was accompanied by decreased antibiotic exposure and cost.

Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. This retrospective observational study evaluated the antibiotic prescription patterns and associations between guideline adherence and outcomes in patients hospitalized with CAP in Hungary. Main outcome measures were adherence to national and international CAP guidelines (agent choice, dose) when using empirical antibiotics, antibiotic exposure, and clinical outcomes. Demographic and clinical characteristics of patients with CAP in the 30-day mortality and 30-day survival groups were compared. Fisher’s exact test and t-test were applied to compare categorical and continuous variables, respectively. Adherence to the national CAP guideline for initial empirical therapies was 30.61% (45/147) for agent choice and 88.89% (40/45) for dose. Average duration of antibiotic therapy for CAP was 7.13 ± 4.37 (mean ± SD) days, while average antibiotic consumption was 11.41 ± 8.59 DDD/patient (range 1–44.5). Adherence to national guideline led to a slightly lower 30-day mortality rate than guideline non-adherence (15.56% vs. 16.67%, p > 0.05). In patients aged ≥ 85 years, 30-day mortality was 3 times higher than in those aged 65–84 years (30.43% vs. 11.11%). A significant difference was found between 30-day non-survivors and 30-day survivors regarding the average CRP values on admission (177.28 ± 118.94 vs. 112.88 ± 93.47 mg/L, respectively, p = 0.006) and CCI score (5.71 ± 1.85 and 4.67 ± 1.83, p = 0.012). We found poor adherence to the national and international CAP guidelines in terms of agent choice. In addition, high CRP values on admission were markedly associated with higher mortality in CAP.

Background: Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Antibiotic stewardship program (ASP) has been implemented to improve rational and responsible antibiotic use by encouraging guideline adherence.Objective: This retrospective observational before–after study aimed to evaluate whether the ASP may improve guideline adherence, antibiotic exposure, and clinical outcomes in patients hospitalized due to CAP in Hungary.Methods: The study was conducted at a pulmonology department of a tertiary care medical center in Hungary. The ASP implementation consisted of written and published guidelines available to all professionals, continuous supervision, and counseling services on antibiotic therapies at an individual level, with the aim of ensuring compliance with CAP guidelines. Overall guideline adherence (agent selection, route of administration, and dose), clinical outcomes (length of stay and 30-day mortality), antibiotic exposure, and direct costs were compared between the two periods. Fisher’s exact test and t-test were applied to compare categorical and continuous variables, respectively. P-values below 0.05 were defined as significant.Results: Significant improvement in overall CAP guideline adherence (30.2%), sequential therapy (10.5%), and a significant reduction in the total duration of antibiotic therapy (13.5%) were observed. Guideline non-adherent combination therapies with metronidazole decreased significantly by 28.1%. Antibiotic exposure decreased by 7.2%, leading to a significant decrease in direct costs (23.6%). Moreover, the ASP had benefits for clinical outcomes, and length of stay decreased by 13.5%.Conclusion: The ASP may play an important role in optimizing empirical antibiotic therapy in CAP having a sustained long-term effect.

UTIs (urinary tract infections) are common bacterial infections with a non-negligible hospitalization rate. The diagnosis of UTIs remains a challenge for prescribers and a common source of misdiagnosis. This retrospective observational study aimed to evaluate whether recorded diagnosis by clinicians and empirical antibiotic therapy met the EAU (European Association of Urology) guideline in patients hospitalized with UTI. The study was conducted at an internal medicine unit of a tertiary care medical center in Hungary. The diagnosis was assessed based on clinical presentation, physical examination, and laboratory (including microbiological) results, considering all the potential risk factors. Diagnosis was considered misdiagnosis when not confirmed by clinical presentation or clinical signs and symptoms. Evaluation of empirical antibiotic therapy was performed only for confirmed UTIs. Empirical treatment was considered guideline-adherent when complying with the relevant recommendations. Out of 185 patients, 41.6% failed to meet EAU-based UTI diagnosis criteria, of which 27.6% were misdiagnosed and 14.1% were ABU (asymptomatic bacteriuria). The diagnosis of urosepsis recorded at admission (9.7%, 18/185) was not confirmed either by clinical or microbiological tests in five (5/18) cases. The initial empirical therapies for UTI showed a relatively low rate (45.4%) of guideline adherence regarding agent selection. The most common guideline-non-adherent therapies were combinations with metronidazole (16.7%). Dosage appropriateness assessments showed a guideline adherence rate of 36.1%, and underdosing due to high body weight was common (9.3%). Overall (agent, route of administration, dose, duration) guideline adherence was found to be substantially low (10.2%). We found a relatively high rate of misdiagnosed UTIs. Written protocols on the ward may be crucial in reducing misdiagnosis and in optimizing antibiotic use.

Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid that can be found in Cannabis sativa and possesses numerous pharmacological effects. Due to these promising effects, CBD can be used in a wide variety of diseases, for instance cardiovascular diseases. However, CBD, like tetrahydrocannabinol (THC), has low bioavailability, poor water solubility, and a variable pharmacokinetic profile, which hinders its therapeutic use. Chemical derivatization of CBD offers us potential ways to overcome these issues. We prepared three new CBD derivatives substituted on the aromatic ring by Mannich-type reactions, which have not been described so far for the modification of cannabinoids, and studied the protective effect they have on cardiomyocytes exposed to oxidative stress and hypoxia/reoxygenation (H/R) compared to the parent compound. An MTT assay was performed to determine the viability of rat cardiomyocytes treated with test compounds. Trypan blue exclusion and lactate dehydrogenase (LDH) release assays were carried out to study the effect of the new compounds in cells exposed to H₂O₂ or hypoxia/reoxygenation (H/R). Direct antioxidant activity was evaluated by a total antioxidant capacity (TAC) assay. To study antioxidant protein levels, HO-1, SOD, catalase, and Western blot analysis were carried out. pIC₅₀ (the negative log of the IC₅₀) values were as follows: CBD1: 4.113, CBD2: 3.995, CBD3: 4.190, and CBD: 4.671. The newly synthesized CBD derivatives prevented cell death induced by H/R, especially CBD2. CBD has the largest direct antioxidant activity. The levels of antioxidant proteins were increased differently after pretreatment with synthetic CBD derivatives and CBD. Taken together, our newly synthesized CBD derivatives are able to decrease cytotoxicity during oxidative stress and H/R. The compounds have similar or better effects than CBD on H9c2 cells.

We followed up the interplay between antibiotic use and resistance over time in a tertiary-care hospital in Hungary. Dynamic relationships between monthly time-series of antibiotic consumption data (defined daily doses per 100 bed-days) and of incidence densities of Gram-negative bacteria (Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii) resistant to cephalosporins or carbapenems were followed using vector autoregressive models sequentially built of time-series ending in 2015, 2016, 2017, 2018, and 2019. Relationships with Gram-negative bacteria as a group were fairly stable across years. At species level, association of cephalosporin use and cephalosporin resistance of E. coli was shown in 2015–2017, leading to increased carbapenem use in these years. Association of carbapenem use and carbapenem resistance, as well as of carbapenem resistance and colistin use in case of A. baumannii, were consistent throughout; associations in case of Klebsiella spp. were rarely found; associations in case of P. aeruginosa varied highly across years. This highlights the importance of temporal variations in the interplay between changes in selection pressure and occurrence of competing resistant species.