Association between Antibiotic Use and Hospital-Onset Clostridioides difficile Infection in University Tertiary Hospital in Serbia, 2011-2021: An Ecological Analysis.

This ecological study is the largest to date examining the association between rates of antibiotic use (AU) and hospital-onset (HO) Clostridioides difficile infection (CDI) in a tertiary university hospital in Serbia. There was no clear trend in the incidence of HO-CDI over time. Total utilization of antibacterials for systemic use increased from 38.57 DDD/100 bed-days (BD) in 2011 to 56.39 DDD/100 BD in 2021. The most commonly used antibiotics were third-generation cephalosporins, especially ceftriaxone, with maximum consumption in 2021 (19.14 DDD/100 BD). The share of the Access group in the total utilization of antibiotics ranged from 29.95% to 42.96% during the observed period. The utilization of the Reserve group of antibiotics indicated a statistically significant increasing trend (p = 0.034). A statistically significant difference in the consumption of medium-risk antibiotics from 2011 to 2021 was shown for penicillins and a combination of sulfamethoxazole and trimethoprim. The consumption of cefotaxime showed a statistically significant negative association with the rate of HO-CDI (r = -0.647; p = 0.031). Ampicillin and the combination of amoxicilline with clavulanic acid have shown a negative statistically significant correlation with the ID of HO-CDI (r = -0.773 and r = -0.821, respectively). Moreover, there was a statistically significant negative correlation between consumption of "medium-risk antibiotics" and the rate of HO-CDI (r = -0.677). The next challenging step for the hospital multidisciplinary team for antimicrobials is to modify the antibiotic list according to the Access, Watch, and Reserve classification, in such a way that at least 60% of the AU should be from the Access group, according to the World Health Organization recommendation.

Influence of Gender, Body Mass Index, and Age on the Pharmacokinetics of Itraconazole in Healthy Subjects: Non-Compartmental Versus Compartmental Analysis.

Itraconazole is a triazole antifungal agent with highly variable pharmacokinetics, with not yet fully identified factors as the source of this variability. Our study aimed to examine the influence of body mass index, gender, and age on the first dose pharmacokinetics of itraconazole in healthy subjects, using pharmacokinetic modeling, non-compartmental versus compartmental ones. A total of 114 itraconazole and hydroxy-itraconazole sets of plasma concentrations of healthy subjects of both genders, determined using a validated liquid chromatographic method with mass spectrometric detection (LC-MS), were obtained for pharmacokinetic analyses performed by the computer program Kinetica 5®. Genetic polymorphism in CYP3A4, CYP3A5, CYP1A1, CYP2C9, and CYP2C19 was analyzed using PCR-based methods. Multiple linear regression analysis indicated that gender had a significant effect on AUC as the most important pharmacokinetics endpoint, whereas body mass index and age did not show such an influence. Therefore, further analysis considered gender and indicated that both geometric mean values of itraconazole and hydroxy-itraconazole plasma concentrations in men were prominently higher than those in women. A significant reduction of the geometric mean values of Cmax and AUC and increment of Vd in females compared with males were obtained. Analyzed genotypes and gender differences in drug pharmacokinetics could not be related. Non-compartmental and one-compartmental models complemented each other, whereas the application of the two-compartmental model showed a significant correlation with the analysis of one compartment. They indicated a significant influence of gender on itraconazole pharmacokinetics after administration of the single oral dose of the drug, given under fed conditions. Women were less exposed to itraconazole and hydroxy-itraconazole than men due to poorer absorption of itraconazole, its more intense pre-systemic metabolism, and higher distribution of both drug and its metabolite.

IMPLEMENTATION OF THE NATIONWIDE ELECTRONIC HEALTH RECORD SYSTEM IN SERBIA: CHALLENGES, LESSONS LEARNED, AND EARLY OUTCOMES.

Objectives: Many countries around the world have recognized the need for using an electronic health record (EHR) system. However, there is limited literature that could serve as a guide during a lengthy and challenging process of planning, development, and implementation of the e-Health system. Since the EHR system was recently introduced in Serbia, the purpose of this communication is to describe our experience and lessons learned along the way. Methods: The key personnel involved in the implementation of the EHR system in Serbia that began in 2015 conducted in 2019 a retrospective narrative review of the process and early outcomes. Results: An incremental approach in the planning, development, and implementation of the nationwide EHR system was taken. The process was split into phases with the gradual introduction of different regions of the country. The gradual shift from the existing to a new workflow for the prospective users was also implemented. The significant milestones were the achievement of quick legislative changes, the hiring of a professional team of experts in the field, the provision of timely and appropriate information and training to prospective users, the close collaboration between the implementation team and the Ministry of Health and mutual understanding of the aims and expectations, and the flexibility in accepting the evolving nature of the process, goals, and the system model. Conclusions: A successful implementation of the nationwide EHR system is feasible providing careful planning, the assembly of a multi-disciplinary team, the use of a stepwise approach, the early and continued involvement of the intended users, and the willingness to make adjustments along the way. The end-result sets the stage for the reform of the health care system itself.

Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study.

BACKGROUND: Clostridioides difficile infection (CDI) is one of the most common healthcare-associated (HA) infections. Cancer patients, particularly haemato-oncological patients, have an increased risk for CDI due to more risk factors compared with non-cancer patients. The aim of this study was to investigate differences in outcomes associated with HA CDI in patients with solid and haematological malignancies compared with patients with no underlying malignant disease in a tertiary healthcare centre in Serbia. METHODS: A prospective cohort study was conducted including adult patients diagnosed with an initial episode of HA CDI. Their demographic and clinical characteristics associated with risk factors for CDI were documented. Outcomes such as all-cause 30-day mortality, cure of infection, diarrhoea relaps and recurrence of disease were followed. Patients were assigned to cancer and non-cancer groups. Within the cancer group, patients were divided into the solid tumour subgroup and haematological malignancy subgroup. RESULTS: During a 7-year period, HA CDI was observed in 28 (5.1%) patients with haematological malignancy, 101 (18.3%) patients with solid tumours and 424 (76.7%) non-cancer patients. Older age (OR 1.04, 95% CI 1.02 to 1.07, p<0.001), admission to the intensive care unit (ICU) (OR 2.61, 95% CI 1.37 to 4.95, p=0.003), mechanical ventilation (OR 5.19, 95% CI 2.78 to 9.71, p<0.001) and use of antibiotics prior to CDI (OR 1.04, 95% CI 1.02 to 1.06, p=0.02) were associated with increased mortality. Compared with patients with solid tumours, patients with haematological malignancy were younger (65 vs 57 years, p=0.015), did not require ICU admission (25.0% vs 0%) or mechanical ventilation (8.9% vs 0%) and were treated longer with antibiotics prior to CDI (14 vs 24 days, p=0.002). CONCLUSIONS: Patients with haematological malignancy were exposed to different risk factors for CDI associated with mortality compared with patients with solid tumours and non-cancer patients. Older age, ICU stay and mechanical ventilation, but not presence or type of cancer, predicted the all-cause 30-day mortality.

Cost Analysis of Health Examination Screening Program for Ischemic Heart Disease in Active-Duty Military Personnel in the Middle-Income Country.

Cardiovascular diseases, including ischemic heart disease, are the most common causes of morbidity and death in the world, including Serbia, as a middle-income European country. The aim of the study was to determine the costs of preventive examinations for ischemic heart disease in active-duty military personnel, as well as to assess whether this was justified from the point of view of the limited health resources allocated for the treatment of the Republic of Serbia population. This is a retrospective cost-preventive study which included 738 male active-duty military personnel, aged from 23 to 58. The costs of primary prevention of ischemic heart disease in this population were investigated. Out of 738 subjects examined, arterial hypertension was detected in 101 subjects (in 74 of them, arterial hypertension was registered for the first time, while 27 subjects were already subjected to pharmacotherapy for arterial hypertension). Average costs of all services during the periodic-health-examination screening program were €76.96 per subject. However, average costs of all services during the periodic-health-examination screening program for patients with newfound arterial hypertension and poorly regulated arterial hypertension were €767.54 per patient and €2,103.63 per patient, respectively. Since periodic-health-examination screening program in military personnel enabled not only discovery of patient with newfound arterial hypertension but also regular monitoring of those who are already on antihypertensive therapy, significant savings of €690.58 per patient and €2,026.67 per patient can be achieved, respectively. As financial resources for providing health care in Serbia, as a middle-income country, are limited, further efforts should be put on screening programs for ischemic heart disease due to possible significant savings.

An overview of antiviral strategies for coronavirus 2 (SARS-CoV-2) infection with special reference to antimalarial drugs chloroquine and hydroxychloroquine.

At present, neither specific antiviral drugs, nor vaccine is recommended for coronavirus disease 2019 (COVID-19) treatment. In this review we discuss the drugs suggested as therapy for COVID-19 infection, with a focus on chloroquine and hydroxychloroquine. The list of drugs used for COVID-19 treatment includes a combination of lopinavir and ritonavir, remdesivir, favipiravir, alpha-interferon, ribavirin, atazanavir, umifenovir, and tocilizumab. As their efficacy and safety are under investigation, none of the regulatory agencies approved them for the treatment of COVID-19 infection. Although chloroquine and hydroxychloroquine possess antiviral and immunomodulatory effects, in practice benefit of their use for COVID-19 treatment is controversial. Several studies investigating hydroxychloroquine were stopped and the French national medicines regulator suspended its use in clinical trials because of safety concerns. The results from the double-blind, randomised clinical trials, including large number of participants, will add better insight into the role of these two drugs as already available and affordable, antimalarial therapy. The ethical issue on emergency use of chloroquine and hydroxychloroquine in the settings of COVID-19 should be carefully managed, with adherence to the "monitored emergency use of unregistered and experimental interventions" (MEURI) framework or be ethically approved as a trial, as stated by the WHO. Potential shortage of chloroquine/hydroxychloroquine on the market can be overbridged with regular prescriptions by medical doctors and national drug agency should ensure sufficient quantities of these drugs for standard indications.

Gross Domestic Product and Health Expenditure Growth in Balkan and East European Countries-Three-Decade Horizon.

Background: Dynamics of health care has changed over time along with development of the countries themselves. The aim of the study is to compare macroeconomic and health expenditure indicators of interest, such as total health expenditure (THE) as percentage of global domestic product, global domestic product per capita in US$, and private households' out-of-pocket payments of Balkan and Eastern European countries on health, as well as to assess their progress over the observed period. Methods: This research report represents a descriptive data analysis of indicators extracted from the European Health for All database. The data were analyzed using a linear trend and regression analysis to estimate the timeline changes. Results: Greece and Slovenia have the largest median values of global domestic product per capita throughout the whole period, and the largest increment trend was in Lithuania. Median value in out-of-pocket payment of THE was the highest in Albania and Ukraine, while the largest decrease in trend was noticed in Albania and Bosnia and Herzegovina. Bosnia and Herzegovina and Greece had the largest median value of THE as percentage of Gross Domestic Product (GDP) in the observed period, while regression trend analysis showed that Serbia had the largest increase. Most of the countries showed a significant correlation between observed indicators. Conclusion: Trends in the economy must be constantly monitored due to the fact that the population is aging and non-communicable diseases are multiplying, which requires innovations in medical treatment and pharmaceutical development.

Anesthesia for patients with psychiatric illnesses: a narrative review with emphasis on preoperative assessment and postoperative recovery and pain.

The physical and psychological fragility of patients with psychiatric illness poses critical importance in the preoperative assessment, evaluation, and choice of premedication, which includes regular therapy, as well as concerns about polypharmacy with possible interactions of anesthetics, analgesics, and psychiatric medications. A considerable effort is to reduce risks for exacerbations or relapses of imminent illness in the postoperative period. In this narrative review, the goal was also set towards the use of proper tools for the preoperative assessment of anxiety and management of postoperative pain. Indeed anxiety can be a manifestation of primary comorbidity within the spectrum of a major psychiatric condition and affects dramatically the presentations of other symptoms as well evolution. Pain perception is changed in patients with psychiatric illness; therefore, the postoperative bundle of measures including assessment of pain using tools adjusted to the patient's cognitive state and regular nonopioid analgesics is important aiming to minimize opioid use. Ketamine, esketamine, xenon, nitrous oxide, dexmedetomidine, and propofol seem to have a novel role and benefit the management of certain types of psychiatric illness during the perioperative period. Psychiatrist involvement is necessary throughout the perioperative period, starting preoperatively and continuing after discharge. Clinical pharmacologists should be part of the team during the management of critically ill patients when polypharmacy can cause undesirable effects. Psychosocial wellbeing of surgical patients with psychiatric co-morbidity depends deeply on the collaboration of medical staff, family, and friends and international guidelines aim to establish standards, including but not limited to postoperative management.

A Correlation Study of the Colorectal Cancer Statistics and Economic Indicators in Selected Balkan Countries.

Colorectal cancer (CRC) is one of the most commonly diagnosed malignant neoplasms. The aim of the study was to evaluate and correlate most important epidemiological and economic indicators of CRC in 11 selected Balkan countries. The number of new CRC cases was 56,960, and the highest 5-year CRC prevalence was in Slovenia, Croatia, and Greece. Age-standardized CRC incidence rates were highest in Slovenia, Serbia, and Croatia, and age-standardized mortality rates were highest in Croatia, Serbia, and Bulgaria. Current Health Expenditure as % of Gross Domestic Product was the highest in Bosnia and Herzegovina and Serbia. The GDP per capita levels have shown positive correlation with the CRC incidence rate and prevalence. Absolute numbers of new and death-related CRC cases and 5-year prevalence in absolute numbers have shown strong positive correlation with GDP in million current US$. It has been shown that various economic indicators can be linked to the rate of incidence and prevalence of the CRC patients in the selected Balkan countries. Therefore, economic factors can influence the epidemiology of CRC, and heavy CRC burden in the Balkan region may be one of the indexes of the economic development.

Alcohol Consumption among the Elderly Citizens in Hungary and Serbia-Comparative Assessment.

Studies in the alcohol consumption area are mostly related to the (ab)use of alcohol in young people. However, today, a growing number of researchers are emphasizing the clinical and public health significance of alcohol consumption in the elderly. In the WHO reports, harmful alcohol consumption is responsible for 5.3% of the global burden of the disease. The aim of this study was to investigate the prevalence of alcohol consumption among men and women aged 55 and over in Serbia and Hungary, leveraging data from the 2013 Serbian National Health Survey and from the 2014 Hungarian National Health Survey. Respondents aged 55 and over were analysed based on logistic multivariate models. The prevalence of alcohol consumption was 41.5% and 62.5% in Serbia and Hungary, respectively. It was higher among men in both countries, but among women, it was significantly higher in Hungary than in Serbia. The statistically significant predictors affecting alcohol consumption in Serbia included age, education, well-being index, long-term disease and overall health status, with marital status being an additional factor among men. In Hungary, education and long-term disease affected alcohol consumption in both sexes, while age and employment were additional factors among women. In both countries for both sexes, younger age, more significantly than primary education and good health, was associated with a higher likelihood of alcohol consumption.

The Evaluation of Antibiotic Consumption at the Inpatient Level in Kazakhstan from 2011 to 2018.

Antimicrobial agents have a rather special position due to their importance as essential medicines for the treatment of infectious diseases. Evidence-based prescriptions are needed to optimize the use of antimicrobials in humans, as well as to decrease antimicrobial resistance. The aim of this study was to assess the inpatient consumption of antimicrobial drugs for systemic use in the period 2011-2018 in Kazakhstan. This article presents the results of an evaluation of the inpatient use of antibacterial drugs for systemic use (group J01) for the period 2011-2018 using the anatomical therapeutic chemical (ATC) classification)/defined daily dose (DDD) methodology recommended by the World Health Organization. Inpatient antimicrobial utilization is expressed as DDDs/1000 inhabitants/day (DID). The results of the assessment for inpatient antibiotic use (over an eight-year period) showed a decrease in the total consumption of antibiotics for systemic action in Kazakhstan (2011: 12.72 DID; 2018: 2.74 DID). Among oral formulations, levofloxacin was consumed the most, and cefazolin was consumed the most among the parenteral formulations of antimicrobials. The three drugs consumed the most included cefazolin (first-generation cephalosporin), ceftriaxone (third-generation cephalosporin), and cefuroxime (second-generation cephalosporin). The total consumption of antibacterials for systemic action in Kazakhstan decreased during the analyzed period, but there was an irrational use of certain groups of drugs.

Patient-Controlled Intravenous Morphine Analgesia Combined with Transcranial Direct Current Stimulation for Post-Thoracotomy Pain: A Cost-Effectiveness Study and A Feasibility For Its Future Implementation.

This prospective randomized study aims to evaluate the feasibility and cost-effectiveness of combining transcranial direct current stimulation (tDCS) with patient controlled intravenous morphine analgesia (PCA-IV) as part of multimodal analgesia after thoracotomy. Patients assigned to the active treatment group (a-tDCS, n = 27) received tDCS over the left primary motor cortex for five days, whereas patients assigned to the control group (sham-tDCS, n = 28) received sham tDCS stimulations. All patients received postoperative PCA-IV morphine. For cost-effectiveness analysis we used data about total amount of PCA-IV morphine and maximum visual analog pain scale with cough (VASP-Cmax). Direct costs of hospitalization were assumed as equal for both groups. Cost-effectiveness analysis was performed with the incremental cost-effectiveness ratio (ICER), expressed as the incremental cost (RSD or US$) per incremental gain in mm of VASP-Cmax reduction. Calculated ICER was 510.87 RSD per VASP-Cmax 1 mm reduction. Conversion on USA market (USA data 1.325 US$ for 1 mg of morphine) revealed ICER of 189.08 US$ or 18960.39 RSD/1 VASP-Cmax 1 mm reduction. Cost-effectiveness expressed through ICER showed significant reduction of PCA-IV morphine costs in the tDCS group. Further investigation of tDCS benefits with regards to reduction of postoperative pain treatment costs should also include the long-term benefits of reduced morphine use.

Healthcare associated Clostridioides difficile infection in adult surgical and medical patients hospitalized in tertiary hospital in Belgrade, Serbia: a seven years prospective cohort study.

Introduction: Clostridioides difficile (C. difficile) infection (CDI) is one of the most common healthcare-associated (HA) infections in contemporary medicine. The risk factors (RFs) for HA CDI in medical and surgical patients are poorly investigated in countries with a limited resource healthcare system. Therefore, the aim of the study was to investigate differences in patients' characteristics, factors related to healthcare and outcomes associated with HA CDI in surgical and medical patients in tertiary healthcare centre in Serbia.Materials and Methods: A prospective cohort study was conducted including adult patients diagnosed with initial episode of HA CDI, first recurrence of disease, readmission to hospital, while deaths within 30 days of CDI diagnosis and in-hospital mortality were also recorded. Patients hospitalized for any non-surgical illness, who developed initial HA CDI were assigned to medical group, whereas those who developed initial HA CDI after surgical procedures were in surgical group. The data on patients' characteristics and factors related to healthcare were collected, too.Results: During 7-year period, from 553 patients undergoing in-hospital treatment and diagnosed with CDI, 268 (48.5%) and 285 (51.5%) were surgical and medical patients, respectively. Age ≥ 65 years, use of proton pump inhibitors, chemotherapy and fluoroquinolones were positively associated with being in medical group, whereas admission to intensive care unit and use of second- and third-generation cephalosporins were positively associated with being in surgical group.Conclusions: Based on obtained results, including significant differences in 30-day mortality and in-hospital mortality, it can be concluded that medical patient were more endangered with HA CDI than surgical ones.

Metamizole Utilization and Expenditure During 6-Year Period: Serbia vs. Croatia.

Background: Metamizole is a medication with analgesic, antipyretic, spasmolytic, and weak anti-inflammatory effects. The aim of our study was to evaluate a six-year trend in the utilization and expenditure of metamizole in comparison to other group of licensed non-opioid analgesics in Serbia and Croatia, in order to rationalize its use and prescribing in these countries. Methods: The data of metamizole vs. all other non-opioid analgesics utilization and expenditure in Serbia and Croatia was analyzed according to the WHO methodology and expressed as defined daily doses per 1,000 inhabitants per day (DDD/1,000 inhabitants/per day) and total costs, respectively, during the 6-year period from 2010 to 2015. Results: In the observed period, utilization of metamizole was 3.31 fold higher in Serbia than in Croatia (median in Serbia was 2.238 vs. 0.675 in Croatia DDD/1,000 inhabitants/per day/per year). Expenditure of metamizole in the same period was 5.29-fold higher in Serbia than in Croatia (median in Serbia was 1,738,192.51 €/per year vs. 328,355.03 €/per year in Croatia). Conclusion: Utilization and expenditure of non-opioid analgesics, including metamizole, in Serbia was significantly higher comparing with Croatia.Further research is needed to determine whether the current analgesic consumption in Serbia meets the needs of the patient. The benefits of metamizole should be weighed against the risk of metamizole-induced adverse effects. Until then, its prescribing should be based on indications and the appropriate duration of therapy.

The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in Rats.

Amifostine is well known cytoprotector which is efficient when administered before a wide range of antineoplastic agents. The aim of our study was to investigate amifostine effects on doxorubicin-induced toxic changes in rats. Amifostine (75 mg/kg ip) was given 30 min before each dose of doxorubicin (cumulatively 20 mg/kg ip, for 28 days). The animals' whole-body, liver, and kidney weight, serum biochemical examination, as well as microscopic examination of bone marrow, peripheral blood, liver, and kidney, were done on day 56 of the study. Hepatic and renal alterations were carefully quantified by semiquantitative grading scales-hepatic and renal damage score, respectively. In amifostine-pretreated rats, the number of peripheral blood leukocytes was significantly higher in comparison to doxorubicin-only treated group, preferentially protecting neutrophils. In the same group of rats, hepatic and renal alterations associated with polymorphonuclear cell infiltrates were significantly less severe than those observed in animals receiving only doxorubicin. Our results showed that amifostine successfully protected rats against multiple-dose doxorubicin-induced toxicity by complex, and still not fully elucidated mechanisms of action.

Bioequivalence study of two formulations of itraconazole 100 mg capsules in healthy volunteers under fed conditions: a randomized, three-period, reference-replicated, crossover study.

BACKGROUND: The aim of the study was to evaluate the bioequivalence of two itraconazole 100 mg capsule formulations. RESEARCH DESIGN AND METHODS: The single-center, open-label, randomized, three-period, three-sequence, reference-replicated, cross-over study included 38 healthy subjects under fed conditions. In each study period (separated by a 14-day washout), a single oral dose of the test (T) or reference (R) product was administered. Blood samples were collected at pre-dose and up to 72.0 h after administration. The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxy itraconazole, were AUC0-72h, AUC0-∝, Cmax, Tmax, T1/2 and Kel. RESULTS: The 90% CI for the test/reference geometric means ratio for the parent compound, itraconazole, was in the range from 85.29% to 116.07% for AUC0-72h. Since the coefficient of variation (CV) for the reference product was 44.95% for Cmax, the 90% CI for this parameter for itraconazole was 93.49-133.78%, which was within the proposed limits of the EMA for bioequivalence of 72.15-138.59%. During the study, 4 subjects encountered a total of 14 mild adverse events. CONCLUSIONS: The use of the reference-scaling approach with 3-period design (TRR, RTR, and RRT) was an efficient way to demonstrate that two commercially available oral itraconazole formulations met the predetermined bioequivalence criteria.

Antibiotic consumption and healthcare-associated infections in a tertiary hospital in Belgrade, Serbia from 2011 to 2016.

INTRODUCTION: Healthcare-associated infections (HAIs) and irrational use of antibiotics in healthcare settings are major global public health concerns. Surveillance of HAIs in intensive care units (ICU), surgical-site infections (SSIs), and Clostridium difficile infections (CDIs), together with implementation of antibiotic stewardship, are cornerstones of hospital infection prevention programs. The aim of this study was to evaluate antibiotic consumption, especially of broad spectrum antibiotics, in relation to HAI incidence density (ID). METHODOLOGY: The study was conducted from 2011 to 2016 in a tertiary hospital, the Military Medical Academy (MMA), in Belgrade, Serbia. Through regular hospital surveillance we identified all patients with a new HAI. Data on consumption of antibacterials for systemic use were expressed as defined daily dose per 100 bed days (DDD/100 BD). RESULTS: The highest incidence density (ID) of HAI was observed among patients in surgical ICUs (47.2 per 1000 patient-days), while the highest incidence rate among SSI was 3.7%. Moreover, the highest ID of CDI in medical patients was 6.2 per 10,000 patient-days, while in surgical patients it was 4.3 per 10,000 patient-days. The most frequently used antibiotics were cephalosporins, aminoglycosides and carbapenems (16.0 ± 2.3, 4.8 ± 0.7, 4.3 ± 0.7 DDD/100 BD, respectively). There was no significant correlation between consumption of any groups of antibiotics and ID of CDI in medical and surgical patients. CONCLUSION: The multidisciplinary healthcare team would have crucial importance in the implementation of the antibiotic stewardship program in order to decrease unnecessary exposures of patients treated in healthcare settings.

Tacrolimus Utilization and Expenditure in Serbia.

BACKGROUND: Increasing immunosuppressant consumption and expenditure is a quite a challenge in transplantation medicine. The aim of the study was to characterize the utilization and expenditure of tacrolimus, backbone, and standard of care in immunosuppression regimen in Serbian solid organ transplant recipients. METHODS: This study was performed as retrospective cross-sectional study during a 3-year period (from 2013 to 2015) in Serbia. The Anatomical Therapeutic Chemical Classification/Defined Daily Doses (ATC/DDD) international system was used for consumption evaluation. RESULTS: Two hundred and sixty-nine patients were transplanted in Serbia from 2013 to 2015 (185 recipients from deceased donors and 84 recipients from living donors). Total number of deceased donors in this period was 81. The consumption of tacrolimus increased (from 0.051 DDD/1,000 inhabitants/day to 0.069 DDD/1,000 inhabitants/day in 2013 and 2015, respectively). The total cost of tacrolimus was also increased; from 1,206,816€ to 1,483,472€ in 2013 and 2015, respectively. On the other hand, the number of all new solid organ transplants (from deceased and living donors) per million population per year was decreased from 17.39 to 10.02, from 2013 to 2015, respectively. CONCLUSION: In spite downward trend in the number of solid organ transplants, tacrolimus consumption and expenditure in the examined 3-year period in Serbia increased. Since tacrolimus is a high-cost and life-preserving drug, its increasing utilization and expenditure will most likely continue consuming an enhancing share of Serbian pharmaceutical expenditure, as well as its health care, as a whole.