Increase and Change in the Pattern of Antibiotic Use in Serbia (2010-2019).

The aim of this study was to determine and describe trends in antibiotics utilization in Serbia over a ten-year period. Data were retrieved from publicly available annual reports (2010-2019). The results were expressed as Defined Daily Dose (DDD) per 1000 inhabitants per day (DID). All calculations were performed using the DDD values for the 2020 Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) version for each year of the study, to account for the DDD changes during the study period. Antibiotics were classified using the WHO Access, Watch, Reserve (AWaRe) classification. Total utilization of antibacterials for systemic use increased from 17.25 DID in 2010 to 28.65 DID in 2019. A statistically significant increasing trend in the use of the Watch category antibiotics was observed. A tendency towards use of broad-spectrum antibiotics, apparent by a statistically significant increase in the rate of utilization of broad-spectrum macrolides, quinolones and third-generation cephalosporins vs. narrow-spectrum ones, as well as a significant increasing trend in the use of quinolones was identified. Total antibiotic utilization was found to be well above the European average. Several specific problem areas were identified, which requires further efforts to improve antibiotic prescribing. The present study provides the information needed to facilitate antibiotic stewardship in Serbia further and proposes specific interventions to optimize antibiotic use in Serbia.

Chemical composition, nutritional profile and in vivo antioxidant properties of the cultivated mushroom Coprinus comatus.

This study investigated the chemical and nutritional profile and antioxidative properties of cultivated Coprinus comatus. Proximate analysis revealed that C. comatus is rich in carbohydrates, dietary fibres and proteins, and could also be a valuable source of phenolics. Additionally, fat content is low, consisting mainly of polyunsaturated and omega-3 fatty acids. Furthermore, the safety profile of C. comatus is satisfactory, with all elements of toxicological importance within the proposed limits. Oral treatment with C. comatus for 42 days improved the antioxidant capabilities and ameliorated carbon tetrachloride-induced liver damage in rats, marked by decreased serum aminotransferase levels and lipid peroxidation intensity. Glutathione concentrations increased in a dose-dependent manner. Histological morphometric and immunohistochemical analysis confirmed antioxidative and hepatoprotective potential. These findings imply that cultivated C. comatus could be considered a nutraceutical, having beneficial nutrient and therapeutic properties.

Five-year surveillance and correlation of antibiotic consumption and resistance of Gram-negative bacteria at an intensive care unit in Serbia.

A surveillance study was performed in an intensive care unit in the largest tertiary health care center in Vojvodina, Serbia from 2014 to 2018. Antibiotic prescription data were collated in the WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) format, while antibiotic resistance was expressed as incidence density adjusted for total inpatient-days. Individual trends were determined by linear regression, while possible associations between antibiotic prescription and resistance were evaluated using cross-correlation analysis. An overall decrease in antibiotic utilization was observed. The prescription rates of piperacillin-tazobactam increased significantly, while consumption of 3rd and 4th generation cephalosporins and fluoroquinolones decreased. There were rising incidence densities of doripenem resistant Acinetobacter spp., piperacillin-tazobactam resistant Pseudomonas aeruginosa and carbapenem and colistin resistant Klebsiella pneumoniae. These results can serve as a basis for the development of antimicrobial stewardship strategies in the current setting.

Use of microdialysis for the assessment of fluoroquinolone pharmacokinetics in the clinical practice.

Antibacterial drugs, including fluoroquinolones, can exert their therapeutic action only with adequate penetration at the infection site. Multiple factors, such as rate of protein binding, drug liposolubility and organ blood-flow all influence ability of antibiotics to penetrate target tissues. Microdialysis is an in vivo sampling technique that has been successfully applied to measure the distribution of fluoroquinolones in the interstitial fluid of different tissues both in animal studies and clinical setting. Tissue concentrations need to be interpreted within the context of the pathogenesis and causative agents implicated in infections. Integration of microdialysis -derived tissue pharmacokinetics with pharmacodynamic data offers crucial information for correlating exposure with antibacterial effect. This review explores these concepts and provides an overview of tissue concentrations of fluoroquinolones derived from microdialysis studies and explores the therapeutic implications of fluoroquinolone distribution at various target tissues.

Are There Striking Differences in Outpatient Use of Antibiotics Between South Backa District, Serbia, and Some Scandinavian Countries?

There is little published information about antibiotic utilization in outpatients in Serbia. The objective of this study was to determine the amount and structure of outpatient antibiotic use in South Backa District (SBD) in Serbia, to assess prescibing quality of antibiotics and to compare with results from Scandinavian countries. Data on the antibiotic use were collected from all private and state-owned pharmacies from January through March 2008 in SBD. Results were expressed as the number of defined daily doses/1,000 inhabitants/day. The drug utilization 90% method was also used. Penicillins were the most frequently used antibiotic subgroup in SBD (35.20%), followed by cephalosporins (19.16%) and macrolides (13.18%). Thirteen drugs accounted for 90% of total antibiotics consumption (DU90% segment). The average cost/DDD within the DU90% segment was 0.95 euros, whereas the average cost/DDD beyond the DU90% segment was 1.89 euros, indicating that less expensive antibiotics were more frequently used. High use of ampicillin, third-generation cefalosporins, co-trimoxazole, and gentamicin, will aggravate the alarming problem of resistance in Serbia. Differences in the amount and structure of antibiotic consumption between SBD and Scandinavian countries indicate the need of updated national guidelines for rational antimicrobial drug use in Serbia.

Factors associated with non-adherence among type 2 diabetic patients in primary care setting in eastern Bosnia and Herzegovina.

AIMS: The aims of this study were to assess patients' non-adherence and associated factors to antidiabetic medication in the primary care setting in the eastern part of Bosnia and Herzegovina (BiH). METHODS: We conducted a retrospective chart review of 323 patients with type 2 diabetes mellitus (T2DM) attending the primary health care center of the Foca municipality in eastern part of BiH and measured adherence to antidiabetic medication. Adherence was measured using a pill count method. RESULTS: The majority of patients were treated with oral therapy (84.21%). Half of the patients (48%) treated pharmacologically were non-adherent and patients on oral and insulin combination therapy showed better adherence than those on oral therapy. Age (B=-0.749; p=0.004), copayment (B=0.549; p=0.028) and oral therapy (B=0.827; p=0.045) were the strongest predictors of poor adherence. CONCLUSION: About half of the patients were non-adherent to antidiabetic medication. Interventions oriented towards policy changes regarding availability of antidiabetic medication through copayment reductions, and providing healt education to younger population and patients on oral therapy could lead to better adherence among T2DM patients in eastern part of BiH.

Is the level of knowledge a predictor of rational antibiotic use in Serbia?

INTRODUCTION: The objective of this study was to investigate the knowledge, attitudes and behavior regarding antibiotics of the general population. METHODS: The study sample consisted of adult subjects who consulted general practitioners at health centers in Serbia and agreed to complete the questionnaire. A total of 668 questionnaires were distributed; 500 respondents completed the entire questionnaire (response rate 74.85%). RESULTS: The average age was 51.65 ± 16.56 years, 60.80% of the respondents were women. The median antibiotic knowledge score was 9. Predictors of adequate antibiotic knowledge were higher education level and a family member whose ocuppation was related to health-care. Overall, 58.4% of respondents believed that antibiotics could be used to treat common cold. Around a half of the respondents (47.2%) self-medicated with antibiotics at least once during their life-time, and around a quarter (24.2%) during the last treatment of infection. Patients with inadequate knowledge had 3 times higher chances of self-medicating with antibiotics compared to those with adequate knowledge. Although 98.20% of respondents claimed that antibiotic treatment should be started after a visit to a doctor and receiving a prescription, only 65.8% obtained antibiotics with prescription from a doctor during the last infection. CONCLUSIONS: Although these results demonstrate that respondents had a relatively adequate level of knowledge regarding antibiotics use, some areas of misconceptions and improper behavior were identified. Therefore, further rationalization should be focused on educational campaigns targeting the behavior of patients with regard to antibiotic use.

Self-medication with antibiotics in Serbian households: a case for action?

Background Irregular antibiotic use, including self-medication contributes to the development of antibiotic resistance. One method of accessing antibiotic use in the community is through obtaining an in house inventory of drugs. Objective The aim of this study was to investigate the extent of storage and self-medication with antibiotics agents in households in Novi Sad, Serbia. Setting Households in Novi Sad. Method The study was performed during a 4-month period (October 2015-January 2016) using a sample of 112 households in Novi Sad, Serbia. Two trained interviewers performed the survey by visiting each household. The study consisted of making an inventory of all drugs in household and a semi-structured interview about drug use practices and perceptions. Main outcome measure Number of antibiotics obtained without prescription. Results Out of 112 surveyed households, antibiotics were encountered in 55 (49.1%). Antibiotics constituted 11.98% (92/768) of total number of drug items in households. Out of all antibiotics in households, 41 (44.57%) were not in current use, and presented left-overs from previous treatment. Antibiotics were usually acquired with prescription (67, 67.7%), while about a quarter of packages were used for self-medication-purchased at pharmacy without prescription (19, 20.65%) or obtained through friends or family member (6, 6.52%).The most commonly used antibiotics for self-medication was amoxicillin (reported indications included common cold, cough, pharyngitis and tooth-ache). Conclusion Antibiotics were present in large share of households in Novi Sad. Self-medication with antibiotics and sale of antibiotics without prescription represent an important problem in Serbia.

Disposal of Unused Drugs: Knowledge and Behavior Among People Around the World.

The purpose of this systematic review was to determine the practice of medication disposal around the world and get insight into possible association between environmental awareness and people's behavior regarding this issue. A literature search (2005-2015) was performed to identify reports with quantitative data on disposal practices published in peer-reviewed literature. The most common method for disposal of unused medications in households is disposal in the garbage (Kuwait, United Kingdom, Lithuania, Qatar, Serbia, Ghana, Bangladesh, Malta and Saudi Arabia). The practice of flushing drugs into the sewage system still takes place in New Zealand, USA and Bangladesh. Only in Sweden and Germany, practice of returning drugs to pharmacy was practiced to a larger extent. The environmental impact of improper medication disposal is expected in countries with poorly functioning waste management schemes (Middle Eastern, Asian and African countries). Lack of the adequate information and clear instructions on proper manners of drug disposal was reported in many surveyed countries (USA, New Zealand, Bangladesh, Malta and Ireland). Clear and definite connection between knowledge about environmental detrimental effects of improper drug disposal and the preference towards disposal methods could not be established. Many respondents were generally concerned with issues of inadequate medicines discarding but the behavior regarding disposal of unused drugs often did not equate the awareness (Serbia, USA, Kuwait, Malta and UK). The current data emphasizes the global issue of improper medicine disposal, prevalent in environmentally-aware people.

Analysis of expired medications in Serbian households.

INTRODUCTION: An ongoing issue of expired medications accumulating in some households is a universal problem around the world. The aim of the study was to investigate the extent and structure of expired medications in Serbian households, and to determine which therapeutic groups generated the most waste. METHODS: This was an observational, cross-sectional study conducted in households in the city of Novi Sad, Serbia. The study had been performed over 8 month period (December 2011 - July 2012) and it consisted of personal insights into the medication inventory in households. RESULTS: Of 1008 families, 383 agreed to participate and complete the questionnaire (38.3% response rate). In almost a half of households (44.4%), expired medications were maintained. The amount of expired medications was 402 items, corresponding to 9.2% of total medications presented in surveyed households. The majority of expired medications (64.7%) was in solid dosage (tablets, capsules, granules, lozenges), following semisolid (ointments, creams, gel, suppositories) and liquid dosage forms (drops, syrups). Expired medications in the households belonged mostly to 3 categories: antimicrobials for systemic use (16.7%), dermatological preparation (15.9%) and medications for alimentary tract and metabolism (14.2%). CONCLUSIONS: This study revealed that there were relatively large quantities of expired medications in Serbian households, with a high prevalence of antibiotics for systemic use, anti-inflammatory and antirheumatic products, and medications for alimentary tract and metabolism.

Patterns of prescription antihypertensive drug utilization and adherence to treatment guidelines in the city of Novi Sad.

BACKGROUND/AIM: Hypertension is one of the leading causes of cardiovascular morbidity and mortality and more than a half of all health insurance expenditures for reimbursed medicines are allocated to antihypertensive drugs in Serbia. The aim of this study was to identify the antihypertensive drug utilization patterns among hypertensive outpatients in the city of Novi Sad, Serbia, determine the adherence to clinical guidelines and address the economic aspects of current prescribing practices. METHODS: This retrospective observational study was conducted in Novi Sad over a period of six months. The data on the number of packages, size their, and retail price of antihypertensives issued on prescription in outpatients with the diagnosis of essential arterial hypertension was collected from all state-owned pharmacies in Novi Sad. Drug consumption was analyzed using the Anatomical Therapeutic Chemical (ATC)/ defined daily dose (DDD) methodology. RESULTS: Total consumption of antihypertensives issued on prescription over a 6-month period in the city of Novi sad, Serbia was 283.48 DDD per 1,000 inhabitans per day (DID). Angiotensin converting enzyme inhibitors (ACEi) were most commonly prescribed drugs, and were used 3 times more often than calcium channel blockers and 5 times more than beta-blockers. The consumption of diuretics and angiotensin receptor antagonists was low within all the groups of outpatients. Both national and international guidelines state superiority and effectiveness of diuretics in treatment of hypertension in the elderly, but their consumption was unreasonable low despite the fact that over 70% of all antihypertensive drugs in the city of Novi Sad were dispensed in people aged > 60. The use of more expensive ACEi was observed despite the guidelines deeming all the drugs of this class equally effective in treatment of hypertension. CONCLUSION: Large differences in utilization of different groups of antihypertensive agents were noted in this study. Underutilization of valuable, efficacious, and cost-effective thiazide diuretics and overuse of expensive ACE inhibitors is unjustifiable. There is a potential for large savings with switching to low-price ACEi, modeling the practice of Scandinavian countries.

DRUG UTILIZATION IN TREATMENT OF THYROID DISORDERS DURING PREGNANCY IN SERBIA.

INTRODUCTION: Depleted uranium radiation and pollution with polychlorinated biphenyls resulting from bombings the territories of Serbia as well as the additional long-term stress may have affected the function of thyroid gland. The objective of this study was to determine the trend of drug utilization in the treatment of thyroid dysfunction during pregnancy in Novi Sad. MATERIAL AND METHODS: Women who had given birth at the Department of Gynecology in 1989, 1999, 2007 and 2011 were interviewed during a one-month period about thyroid diseases in the pregnancy as well as the drugs they had taken. RESULTS: Not a single pregnant woman was reported to have a thyroid disorder in 1989 and 1999, while in 2007 four women were reported to have a thyroid dysfunction. In 2011, fourteen out of 18 women with thyroid dysfunction were using levothyroxine and in most cases hypothyroidism was diagnosed as autoimmune Hashimoto thyroiditis. CONCLUSION: The study results suggest the necessity of performing more detailed analyses of the correlation between the frequency of the thyroid gland dysfunction and the effects of environmental pollution in Serbia.

Do We Bury Antibacterials When Launching? Cefaclor Example.

This study aimed to compare existing dosing regimens of cefaclor with recommended pharmacokinetic/pharmacodynamic (PK/PD) parameters and to see if the proposed dosing regimen could have been the reason for development of bacterial resistance. PKs of cefaclor were determined after administrating the highest therapeutic dose of 750 mg in standard release (SF) and modified release form (MRF) in 12 volunteers. The study was performed on clinical isolates of the most frequent causative agents in urinary and respiratory infections. Minimum inhibitory concentration (MIC), postantibiotic effect, and PK/PD efficacy indices were determined. Peak plasma concentrations of 23.142 ± 5.67 (SF) and 8.7 ± 2.09 µg/mL (MRF) were observed after 40-60 min and 3.04 ± 0.75 h, respectively. MIC for investigated bacterial strains ranged from 1 to 4 mg/L. Postantibiotic effect lasted from 2.10-2.18 ± 0.2 h for Gram-positive to 0.58-0.90 ± 0.05 h for Gram-negative bacteria. PK/PD indices (t > MIC) ranged from 27.08 ± 5.93% to 43.23 ± 6.54% of 8-h dosing interval (SF) and 22.57 ± 8.93% to 49.65 ± 1.95% of 12-h dosing interval (MRF). Plasma levels were below MIC for more than 50% of the dosing interval even for the most sensitive pathogens (MIC = 1 mg/L). During both dosing intervals the total "antibacterial activity" was not longer than 6 h for Gram-positive and 5 h for Gram-negative bacteria for SF and 9 h for Gram-positive and 5 h for Gram-negative bacteria for MRF.

Intravitreal bevacizumab injection alone or combined with macular photocoagulation compared to macular photocoagulation as primary treatment of diabetic macular edema.

BACKGROUND/AIM: Within diabetic retinopathy (DR), diabetic macular edema DIE) is one of the leading causes of the loss of visual acuity. The aim of this study was to determine the efficacy of the intravitreal vascular endothelial growth factor (VEGF) inhibitor application alone or combined with macular focal/grid lasephotocoagulation compared with laser treatment alone. METHODS: This prospective randomized clinical trial included 72 patients (120 treated eyes) with varying degrees of DR and DME. The DME treatment included intravitreal VEGF inhibitor bevacizumab (Avasting) application, with and without laser treatment. Bevacizumab (1.25 mg/0.05 mL) was administered intravitreally in 4-6-week intervals. Laser is applied 4-6 weeks after last dose of the drug as a part of combined treatment, or as the primary treatment. RESULTS: The mean reduction in central macular thickness (CMT) for the eyes (n = 31) treated with bevacizumab alone was 162.23 .rm, for the eyes (n = 53) treated with combined treatment the mean reduction in CMT was 124.24 pm, both statistically significant at p < 0.001. Laser macular photocolagulation as a part of combined treatment (in 53 eyes) significantly contributed to the CMT reduction, based on the paired t-test results (366.28 vs. 323.0 pLm at p < 0.05). In our study, the mean visual acuity improvement of 0.161 logMAR was achieved in the group of eyes treated with bevacizumab alone, and 0.093 logMAR in the group with combined treatment, both statistically significant atp < 0.05. The effect of laser photocolagulation alone on visual acuity and'CMT was not statistically significant. CONCLUSION: Treatment with bevacizumab alone or within combined treatment is more effective in treating DME than conventional macular laser treatment alone, both anatomically and functionally.

Home pharmacies in Serbia: an insight into self-medication practice.

BACKGROUND: Worldwide data indicate that self-medication is frequently used inappropriately. Although self-medication is encouraged in most of the countries by introducing over-the-counter drugs, it bears the risk of misuse of drugs issued on prescription due to low observance of legislation of medicines requiring prescription by some pharmacies. OBJECTIVE: The objective of this study was to explore the self-medication practice, with an emphasis on self-medication with prescription-only medications. SETTING: Households in Novi Sad city, Serbia. METHOD: The study was conducted over 8 month period (December 2011-July 2012) and involved a random sample of households. The questionnaire-based study and personal insight into household drug supplies was performed by a trained interviewer. Main outcome measure Number of drugs obtained without prescription or without consulting a physician in surveyed households. RESULTS: The total number of drug items present in the 383 households was 4,384 with a median of 11 drugs per household. More than a half of drugs in households were prescription-only medication (58.5 %). Approximately one third of prescription-only medications were obtained without prescription. The most common drugs obtained without prescription were anti-inflammatory and antirheumatic products and antibacterials for systemic use. Ibuprofen and diclofenac were the most common self-medicated drugs. Number of prescription-only medications bought with ought prescription was significantly higher in households with children under 12 years of age compared to other types of households. CONCLUSION: Our survey indicated that self-medication with prescription drugs appeared to be a rather common practice, which is far away from the concept of "responsible self-medication", especially regarding antibiotics.

Antibiotics in Serbian Households: a Source of Potential Health and Environmental Threats?

AIM: Worldwide data indicate that antibiotics are frequently used inappropriately. The objective of this study was to investigate the extent of storage and wastage of antibacterial agents in households in Novi Sad, Serbia. METHODS: The study was performed in 8 months period (December 2011-July 2012) in households in Novi Sad, Serbia. The households were randomly selected from the telephone directory. The interviewer performed the survey visiting each household. RESULTS: The total number of antibacterial agents in the 383 surveyed households was 318, constituting 7.3% of the total stored medications. From 383 families included in the study antibiotics were found in 178 (46.5%). In 13 (7.3%) families were found more than one pack of the same antibiotics. The median number of antibacterial agents per household was 1 (range 1-5). The most common antibacterial agents that were not in current use were cephalexin (22.1%) and amoxicillin (16.6%), followed by doxycycline (11.4%), sulfamethoxazole/trimethoprim (11.4%) and amoxicillin/clavulanic acid (9.2%). The percentage of expired antibacterial agents was 20.8%, while 85.2% were not currently in use. CONCLUSION: Antibacterial agents were commonly encountered in Serbian households, and a relatively large percentage was wasted. Informational and educational activities aimed at improving the public knowledge about antimicrobials play the leading role in reducing imprudent use of antibiotics.

Analysis of antibiotic consumption for treating respiratory tract infections in children and compliance with the national clinical guidelines.

INTRODUCTION: Respiratory infections are the most common infections in children. The aims of the study were to analyze the use of antibiotics for respiratory infections in the period 2008-2010 in children's population in region of Nis and to estimate the rational use of antibiotics in relation to the recommendations of the National Guidelines for physicians in primary care. MATERIAL AND METHODS: Data source was a Pharmacy Nis database. Antibiotics prescriptions were selected for the following diagnoses: H65-H75 (acute otitis media, mastoiditis), J01 (acute sinusitis), J02-J03 (tonsillopharyngitis), J12-J18 (community acquired pneumonia), J20 (acute bronchitis), J32 (chronic sinusitis), J42 (chronic bronchitis). Antibiotic consumption was expressed in defined daily dose/1000 ihhabitants/day. RESULTS: The most widely prescribed antibiotic for the treatment of upper respiratory tract infections in children during the three years was amoxicillin (34.63; 32.50 and 31.00 defined daily dose/1000 inhabitants/day in 2008, 2009 and 2010, respectively). In the treatment of infections of the middle ear and mastoid, the combination of amoxicillin and clavulanic acid, was the most prescribed antibiotics (60% of total consumption of antibiotics for this indication). Azithromycin was the most widely prescribed antibiotic for the treatment of lower respiratory tract infections in children during the observed period (6.92; 8.20 and 7.18 defined daily dose/1000 inhabitans/day in 2008, 2009 and 2010, respectively). CONCLUSION: Recommendations of national guidelines are not complied with the treatment of upper and lower respiratory infections in the children population in region of Nis. This could be a sign of potentially irrational use of antibiotics that need to be further examined. Education of physicians can influence irrational use of antibiotics.

Hormonal contraception--habits and awareness female students of the University of Novi Sad, Vojvodina, Serbia.

INTRODUCTION: Despite a large number of modern contraceptive methods available in the market today, numerous studies have shown insufficient awareness of young women about these forms for birth control. The aim of this study was to compare characteristics of common use of contraceptives as well as the awareness of hormonal contraception among female students of the Faculty of Medicine and the Faculty of Technical Sciences in Novi Sad. MATERIALS AND METHODS: In the study which was conducted in 2012 240 female students of the Faculty of Medicine and the Faculty of Technical Sciences participated. The average age of students of the Faculty of Medicine and the Faculty of Technical Sciences was 24.06 ± 3.24 and 22.72 ± 0.90 years, respectively. They completed an anonymous questionnaire, which consisted of three parts. The first part comprised general questions, the second part included characteristics of the sexual life of students and their contraceptive habits, while in the third part students were asked to evaluate the accuracy of statements about hormonal contraception. The obtained data were statistically processed by using appropriate methods. RESULTS: The average age when the students of the Faculty of Medicine and the Faculty of Technical Sciences had the first sexual intercourse was 18.74 ± 2.61 and 18.75 ± 2.59, respectively. One third of students from both faculties (30.91% from the Faculty of Medicine and 35% from the Faculty of Technical Sciences) had only one sexual partner. Modern contraception was used by 83.64% of the medical students and by 80% of those from the Faculty of Technical Sciences. Contraception was used regularly by 54.54% of the medical students and 43% of those from the Faculty of Technical Sciences. The most frequently applied contraceptive method was condom (90% of the medical students and 93% of the Faculty of Technical Sciences students, respectively). Oral contraceptives were used by 24.54% of the medical students and 11% of those from the Faculty of Technical Sciences. There was a statistically significant difference in the knowledge level between the two groups since the medical students gave quantitatively higher range of expected responses than the students from the Faculty of Technical Sciences. CONCLUSION: It is necessary to increase the availability of adequate information on various types of contraception to student population in Vojvodina.