Browsing by Author "Bajčetić, Milica (15727461400)"

Background: As the only non-European Union (EU) country, Serbia participated in a second point prevalence survey of healthcare-associated infections (HAIs) and antimicrobial use (AMU) organized by the European Centre for Disease Prevention and Control (ECDC) in the EU countries. Here, we aimed to estimate the prevalence of HAI and AMU in patients who had recently undergone a surgery and to compare risk profile, HAI rates, and AMU among surgical patients and non-surgical patients. Methods: A national PPS was performed in 65 Serbian acute-care hospitals, in November 2017. In this paper, the data of 61 hospitals for adult acute-care were analyzed. To ensure the comparability of study design we used the Serbian translation of ECDC case definitions and ECDC PPS protocol. The trained infection control staff, led by a hospital coordinator, reviewed medical records to identify HAI active at the time of the survey and AMU. Only inpatients admitted to the ward before 8 a.m. on the day if the survey were included. Results: A total of 12,478 patients from 61 hospitals for adult acute-care were eligible for inclusion in this study. Significantly higher proportions of surgical patients were female, belonged to the 60-to-79 age group, and were less severely ill. Also, extrinsic factors (invasive devices, hospitalization at the ICU, and prior antibiotics therapy) were more frequent in surgical patients. Prevalence of HAIs was higher among surgical patients (261/3626; 7.2%) than among non-surgical patients (258/8852; 2.9%) (p < 0.0001). The highest prevalence of all HAIs was noted in patients who had kidney transplantation (4/11; 36.4%), while SSIs were the most prevalent among patients who had peripheral vascular bypass surgery (3/15; 20.0%). Non-surgical patients received treatment for community-acquired infections in significantly higher proportion (2664/8852; 64.3) (p < 0.001). Surgical prophylaxis for more than 1 day was applied in 71.4% of surgical patients. Conclusion: We have provided an insight into the burden of HAIs and AMU among Serbia acute-care hospitals, and highlighted several priority areas and targets for quality improvement. © 2021, The Author(s).

OBJECTIVES: The aim of this study is to analyze the availability and coverage by health insurance reimbursement of pediatric formulations labeled for children up to the age of 12 in Serbia. To provide good insight in general availability of pediatric medicines, results were compared with the World Health Organization's (WHO) 'Model List of Essential Medicines for Children' and with published evidence. MATERIALS AND METHODS: Sources of information about medicines are the Summary of Product Characteristics, National Health Insurance Fund (NHIF) Drug Lists, WHO Model Lists of Essential Medicines for Children, and Serbia's official drug registry (2013). RESULTS: Out of total number of medicines in Serbia, only 49% (496) were available for children. Of all available drugs for children, 66% were with license and majority were parenteral formulation (57%), followed by drugs for local use (28%) and formulations for oral use (23%). The lowest availability of medicines was for children 0-27 days. From the total number of licensed medicines for children up to 12 years old, NHIF covers 64% of drugs. The availability of the WHO essential medicines for children in Serbia was 51%, from which 92% were licensed for pediatric use. CONCLUSIONS: Our results demonstrated the alarming lack of pediatric suitable formulations in Serbia. Significant differences in the availability of drugs suitable for children exist worldwide. From global health point of view, the differences in the access to children formulations should, therefore, be of the highest priority. © 2017 Indian Journal of Pharmacology Published by Wolters Kluwer - Medknow.

OBJECTIVES: The aim of this study is to analyze the availability and coverage by health insurance reimbursement of pediatric formulations labeled for children up to the age of 12 in Serbia. To provide good insight in general availability of pediatric medicines, results were compared with the World Health Organization's (WHO) 'Model List of Essential Medicines for Children' and with published evidence. MATERIALS AND METHODS: Sources of information about medicines are the Summary of Product Characteristics, National Health Insurance Fund (NHIF) Drug Lists, WHO Model Lists of Essential Medicines for Children, and Serbia's official drug registry (2013). RESULTS: Out of total number of medicines in Serbia, only 49% (496) were available for children. Of all available drugs for children, 66% were with license and majority were parenteral formulation (57%), followed by drugs for local use (28%) and formulations for oral use (23%). The lowest availability of medicines was for children 0-27 days. From the total number of licensed medicines for children up to 12 years old, NHIF covers 64% of drugs. The availability of the WHO essential medicines for children in Serbia was 51%, from which 92% were licensed for pediatric use. CONCLUSIONS: Our results demonstrated the alarming lack of pediatric suitable formulations in Serbia. Significant differences in the availability of drugs suitable for children exist worldwide. From global health point of view, the differences in the access to children formulations should, therefore, be of the highest priority. © 2017 Indian Journal of Pharmacology Published by Wolters Kluwer - Medknow.

Background. High consumption of benzodiazepines (BDZ) occurs in populations exposed to stress. In the last decade of the 20th century, when the population of Serbia experienced increasing economic hardships due to the civil war in former Yugoslavia, UN sanctions and air raids in 1999, diazepam became the most frequently prescribed drug. This period was also characterized by the free marketing of all drugs, which made them available without prescription. Objective. To investigate the consumption and the pattern of use of BDZ in the population of Belgrade and Serbia in the period of 1990-2001. Materials and Methods. Data on benzodiazapines prescribing and on wholesale in general population of Belgrade and Serbia were collected. In a cross-sectional study of drug prescribing in general practice data were obtained from 1800 patient records in the primary health care centers in Serbia. Statistical analysis was performed by using standard non-parametric tests. Results. Annual rates of BDZ prescribing in Belgrade from 1990 to 1999 were rather uniform (approx. 25 DDD/1000 inhabitants/day), with slight tendency to decrease. In Serbia as a whole, there were significant differences in the annual prescribing rates over the period 1998-2000. The wholesale of BDZ in Serbia significantly increased between 1991 and 2001, with the peak of 133 DDD/1000 inhabitants/day in 1999. The wholesale of BDZ was significantly greater that the rates of prescribing in corresponding years. Over the 10 year period, the numbers of visits to GPs and psychiatrists and the number of neurotic diagnoses were significantly reduced. The use of BDZ in psychiatric hospital increased significantly in 1999 as compared to 1998, although the number of admissions and the occupancy of hospital beds were reduced. In primary health care, diazepam was the most frequently prescribed drug predominantly for non-psychiatric diagnoses. Conclusions. It is concluded that in the last decade, the utilization of BDZ was increased in the population of Belgrade and Serbia, indicating a clear trend to self-medication, particularly in the period of acute war crisis. Copyright © 2004 John Wiley & Sons, Ltd.

Objectives: Comparison of redox conditions in malignant and benign tumours is essential for understanding the role of reactive oxygen species in the pathophysiology of aggressive cancer profiles. Here we compare antioxidative systems in highly malignant brain tumour - glioblastoma multiforme (GBM), and in meningioma, a benign brain tumour. Methods: Tumour tissues and blood of 67 GBM patients (mean age: 52.9 ±11.5 years) and 67 meningioma patients (59.2 ±10.2 years), and blood of 30 control subjects (50.8 ±12.8 years) were analysed via biochemical assays. Results: Components of glutathione system, which is responsible for H2O2 removal, showed lower activity/ level in GBM: glutathione peroxidase (GBM: 9.90 ± 0.22; meningioma: 11.78 ± 0.23 U/mg of proteins; P< 0.001), glutathione reductase (GBM: 3.83 ±0.13; meningioma: 4.67 ±0.11 U/mg of proteins; P< 0.001), and glutathione (GBM: 6.70 ±0.12; meningioma: 7.58 ± 0.14 umol/g of tissue; P< 0.001). In contrast, the rank order of glutathione reductase activity and glutathione level in erythrocytes was: GBM > meningioma > control. Superoxide dismutase and catalase activities were lower in the blood of cancer patients compared to controls. Discussion: Cells of malignant brain tumour show down-regulated antioxidative system which might result in increased levels of H2O2 compared to benign tumour tissue. © W. S. Maney & Son Ltd 2015.

Objectives: Comparison of redox conditions in malignant and benign tumours is essential for understanding the role of reactive oxygen species in the pathophysiology of aggressive cancer profiles. Here we compare antioxidative systems in highly malignant brain tumour - glioblastoma multiforme (GBM), and in meningioma, a benign brain tumour. Methods: Tumour tissues and blood of 67 GBM patients (mean age: 52.9 ±11.5 years) and 67 meningioma patients (59.2 ±10.2 years), and blood of 30 control subjects (50.8 ±12.8 years) were analysed via biochemical assays. Results: Components of glutathione system, which is responsible for H2O2 removal, showed lower activity/ level in GBM: glutathione peroxidase (GBM: 9.90 ± 0.22; meningioma: 11.78 ± 0.23 U/mg of proteins; P< 0.001), glutathione reductase (GBM: 3.83 ±0.13; meningioma: 4.67 ±0.11 U/mg of proteins; P< 0.001), and glutathione (GBM: 6.70 ±0.12; meningioma: 7.58 ± 0.14 umol/g of tissue; P< 0.001). In contrast, the rank order of glutathione reductase activity and glutathione level in erythrocytes was: GBM > meningioma > control. Superoxide dismutase and catalase activities were lower in the blood of cancer patients compared to controls. Discussion: Cells of malignant brain tumour show down-regulated antioxidative system which might result in increased levels of H2O2 compared to benign tumour tissue. © W. S. Maney & Son Ltd 2015.

An increase in the copper pool in body fluids has been related to a number of pathological conditions, including infections. Copper ions may affect antibiotics via the formation of coordination bonds and/or redox reactions. Herein, we analyzed the interactions of Cu2+ with eight β-lactam antibiotics using UV–Vis spectrophotometry, EPR spectroscopy, and electrochemical methods. Penicillin G did not show any detectable interactions with Cu2+. Ampicillin, amoxicillin and cephalexin formed stable colored complexes with octahedral coordination environment of Cu2+ with tetragonal distortion, and primary amine group as the site of coordinate bond formation. These β-lactams increased the solubility of Cu2+ in the phosphate buffer. Ceftazidime and Cu2+ formed a complex with a similar geometry and gave rise to an organic radical. Ceftriaxone-Cu2+ complex appears to exhibit different geometry. All complexes showed 1:1 stoichiometry. Cefaclor reduced Cu2+ to Cu1+ that further reacted with molecular oxygen to produce hydrogen peroxide. Finally, meropenem underwent degradation in the presence of copper. The analysis of activity against Escherichia coli and Staphylococcus aureus showed that the effects of meropenem, amoxicillin, ampicillin, and ceftriaxone were significantly hindered in the presence of copper ions. The interactions with copper ions should be taken into account regarding the problem of antibiotic resistance and in the selection of the most efficient antimicrobial therapy for patients with altered copper homeostasis. © 2018 Elsevier Inc.

An increase in the copper pool in body fluids has been related to a number of pathological conditions, including infections. Copper ions may affect antibiotics via the formation of coordination bonds and/or redox reactions. Herein, we analyzed the interactions of Cu2+ with eight β-lactam antibiotics using UV–Vis spectrophotometry, EPR spectroscopy, and electrochemical methods. Penicillin G did not show any detectable interactions with Cu2+. Ampicillin, amoxicillin and cephalexin formed stable colored complexes with octahedral coordination environment of Cu2+ with tetragonal distortion, and primary amine group as the site of coordinate bond formation. These β-lactams increased the solubility of Cu2+ in the phosphate buffer. Ceftazidime and Cu2+ formed a complex with a similar geometry and gave rise to an organic radical. Ceftriaxone-Cu2+ complex appears to exhibit different geometry. All complexes showed 1:1 stoichiometry. Cefaclor reduced Cu2+ to Cu1+ that further reacted with molecular oxygen to produce hydrogen peroxide. Finally, meropenem underwent degradation in the presence of copper. The analysis of activity against Escherichia coli and Staphylococcus aureus showed that the effects of meropenem, amoxicillin, ampicillin, and ceftriaxone were significantly hindered in the presence of copper ions. The interactions with copper ions should be taken into account regarding the problem of antibiotic resistance and in the selection of the most efficient antimicrobial therapy for patients with altered copper homeostasis. © 2018 Elsevier Inc.

Pharmacotherapy of pediatric diseases represents a major challenge considering that the majority of medicines in everyday practice have not been pediatrically evaluated. The efficacy of therapy depends to a large extent on the knowledge of pathophysiological processes in the children organism at different ages. Therefore, research in that direction is of the utmost importance. An imbalance in the production of free oxygen/nitrogen species and parameters of antioxidative protection is a significant factor in many diseases (e.g. heart failure, pulmonary hypertension, asthma, neonatal sepsis, cancer etc.) in children of different age groups. Reactive oxygen/nitrogen species serve as cell signaling molecules for normal biologic processes. An increase in their generation can cause damages which can disrupt normal physiological cellular processes and eventually cause cell death. This review outlines the previous assessments of oxidative stress parameters in children of different ages for some diseases. Also, the potential diagnostic and therapeutic possibilities for the oxydative stress parameters in children have been considered.

Pharmacotherapy of pediatric diseases represents a major challenge considering that the majority of medicines in everyday practice have not been pediatrically evaluated. The efficacy of therapy depends to a large extent on the knowledge of pathophysiological processes in the children organism at different ages. Therefore, research in that direction is of the utmost importance. An imbalance in the production of free oxygen/nitrogen species and parameters of antioxidative protection is a significant factor in many diseases (e.g. heart failure, pulmonary hypertension, asthma, neonatal sepsis, cancer etc.) in children of different age groups. Reactive oxygen/nitrogen species serve as cell signaling molecules for normal biologic processes. An increase in their generation can cause damages which can disrupt normal physiological cellular processes and eventually cause cell death. This review outlines the previous assessments of oxidative stress parameters in children of different ages for some diseases. Also, the potential diagnostic and therapeutic possibilities for the oxydative stress parameters in children have been considered.

Millions of patients acquire healthcare-associated infections (HAIs) every year, putting them at risk for serious complications and prolonged hospitalization. Point prevalence surveys (PPS), guided by the European Centre for Disease Prevention and Control framework, are one of the primary methods by which countries in the European Union conduct surveillance of HAIs. Serbia, though not in the EU, implemented this approach in its national PPS. The microbiological and antimicrobial resistance (AMR) analyses comprised patients in 61 out of 65 hospitals included in the fourth PPS conducted in November 2017. A total of 515/12,380 (4.2%) of the adult patients included in the PPS had at least one HAI, with intensive care units carrying the highest prevalence of 15.9%. Urinary tract and surgical site infections were the most frequently identified types of HAIs (23.9% and 23.0%, respectively). Enterobacterales comprised almost half (47.0%) of all causative agents, most notably Klebsiella spp. (16.7%). AMR was very high for most pathogens—80.5% of nonfermentative Gram-negative bacilli were resistant to carbapenems whereas 62.9% of Enterobacterales were resistant to third generation cephalosporins. The calculated AMR index of 61% is one of the highest in Europe. Further efforts are needed to reduce the burden of HAIs in Serbia that carry very high resistance rates to antibiotics currently used in clinical practice. © 2022 by the authors.

Millions of patients acquire healthcare-associated infections (HAIs) every year, putting them at risk for serious complications and prolonged hospitalization. Point prevalence surveys (PPS), guided by the European Centre for Disease Prevention and Control framework, are one of the primary methods by which countries in the European Union conduct surveillance of HAIs. Serbia, though not in the EU, implemented this approach in its national PPS. The microbiological and antimicrobial resistance (AMR) analyses comprised patients in 61 out of 65 hospitals included in the fourth PPS conducted in November 2017. A total of 515/12,380 (4.2%) of the adult patients included in the PPS had at least one HAI, with intensive care units carrying the highest prevalence of 15.9%. Urinary tract and surgical site infections were the most frequently identified types of HAIs (23.9% and 23.0%, respectively). Enterobacterales comprised almost half (47.0%) of all causative agents, most notably Klebsiella spp. (16.7%). AMR was very high for most pathogens—80.5% of nonfermentative Gram-negative bacilli were resistant to carbapenems whereas 62.9% of Enterobacterales were resistant to third generation cephalosporins. The calculated AMR index of 61% is one of the highest in Europe. Further efforts are needed to reduce the burden of HAIs in Serbia that carry very high resistance rates to antibiotics currently used in clinical practice. © 2022 by the authors.

Neonatal sepsis is one of the most fulminating conditions in neonatal intensive care units. Antipathogen and supportive care are administered routinely, but do not deliver satisfactory results. In addition, the efforts to treat neonatal sepsis with anti-inflammatory agents have generally shown to be futile. The accumulating data imply that intracellular redox changes intertwined into neonatal sepsis redox cycle represent the main cause of dysfunction of mitochondria and cells in neonatal sepsis. Our aim here is to support the new philosophy in neonatal sepsis treatment, which involves the integration of mechanisms that are responsible for cellular dysfunction and organ failure, the recognition of the most important targets, and the selection of safe agents that can stop the neonatal sepsis redox cycle by hitting the hot spots. Redox-active agents that could be beneficial for neonatal sepsis treatment according to these criteria include lactoferrin, interleukin 10, zinc and selenium supplements, ibuprofen, edaravone, and pentoxifylline.