Trends and patterns of antibiotics use in Serbia from 2006 to 2021: Pre-COVID-19 period versus COVID-19 pandemic.

BACKGROUND: Global rise in antibiotic utilization has been strongly associated with the resistance of bacteria to antibiotics. The COVID-19 saw an increase in the use of antibiotics in some countries. The aim of this study was to evaluate antibiotic utilization from 2006 to 2021 in the Republic of Serbia. METHODS: Data on antibiotic use were retrieved from the national annual reports on the official website of the Medicines and Medical Devices Agency of Serbia during the period 2006 to 2021. To evaluate trends in the use of antibiotics in Serbia, linear, and joint regression analyses were performed. RESULTS: The analysis of the antibiotics use over a sixteen-year period included a total of 50 antibiotics. A significant increase during the COVID-19 pandemic was observed for glycylcyclines that is, new-generation tetracyclines (tigecycline), third-generation cephalosporins (ceftazidime, ceftriaxone, and cefixime), respiratory fluoroquinolones (levofloxacin and moxifloxacin), carbapenems (ertapenem), and oxazolidinones (linezolid) utilization. Moreover, an almost negligible use of new ß-lactam/ß-lactamase inhibitors during the prepandemic period increased significantly during the COVID-19 pandemic period. CONCLUSIONS: A significant increasing trend in the use of specific antibiotics classified as the "Watch" and "Reserve" antibiotics during the pandemic period was observed.

Public Knowledge, Attitudes, and Practices towards Antibiotic Use and Antimicrobial Resistance in Eastern Region of Bosnia and Herzegovina in the COVID-19 Pandemic.

The constant worsening of antimicrobial resistance (AMR) imposes the need for an urgent response. Use of antibiotics (AB), both due to irrational prescribing by doctors and irrational use by patients, is recognized as one of the leading causes of this problem. This study aimed to identify knowledge, attitudes, and practices about AB use and AMR within the general population, stratified by age, gender, and urban/rural areas during the COVID-19 pandemic. This questionnaire-based cross-sectional study was conducted in April 2022 among patients who visited three health centers in the eastern region of Bosnia and Herzegovina. A high frequency of AB use was observed during the COVID-19 pandemic (64.2% of respondents were treated with AB). Age and place of residence have not been shown to be factors associated with AB use practices that pose a risk for AMR. However, female gender (ß = 0.063; p = 0.041), better knowledge (ß = 0.226; p < 0.001), and positive attitudes (ß = 0.170; p < 0.001) about use of AB and towards to AMR proved to be factors associated with better practice by respondents. Women, younger respondents, and respondents from urban areas showed better knowledge, attitudes, and behavior about the use of AB and AMR during the COVID-19 pandemic.

Antibiotic consumption and antimicrobial resistance in the SARS-CoV-2 pandemic: A single-center experience.

Introduction: Antimicrobial resistance and the rapid spread of multiresistant bacteria represent one of the main public health problem in limited resources countries. This issue is significantly worsening since the COVID-19 pandemic due to the unreasonably increased antibiotics prescription to patients with confirmed SARS-CoV-2 infection. The aim of this study was to examine whether COVID-19 pandemic (2020, 2021) was associated with increased antibiotic consumption in inpatient and outpatient settings in the middle size urban region (Republic of Srpska/Bosnia and Herzegovina) in comparison to period before the pandemic (2019). Additionally, we aimed to determine antimicrobial resistance and the presence of multiresistant bacteria in the regional hospital ("Saint Apostol Luka" Hospital Doboj) in 2021. Methodology: The consumption of antibiotics in inpatient was calculated as Defined Daily Dose per one hundred of patient-days. The consumption of antibiotics in outpatient was calculated as Defined Daily Dose per thousand inhabitants per day. Resistance of bacteria to antibiotics is expressed as a rates and density for each observed antibiotic. The rate of resistance was calculated as a percentage in relation to the total number of isolates of individual bacteria. The density of resistance of isolated bacteria against a specific antibiotic was expressed as the number of resistant pathogens/1000 patient days. Results: Antibiotic consumption in hospital setting registered during 2019, 2020 and 2021 was as follows: carbapenems (meropenem: 0.28; 1.91; 2.33 DDD/100 patient-days, respectively), glycopeptides (vancomycin: 0.14; 1.09, 1.54 DDD/100 patient-days, respectively), cephalosporins (ceftriaxone: 6.69; 14.7; 14.0 DDD/100 patient-days, respectively) and polymyxins (colistin: 0.04; 0.25; 0.35 DDD/100 bed-days, respectively). Consumption of azithromycin increased drastically in 2020, and dropped significantly in 2021 (0.48; 5.61; 0.93 DDD/100 patient-days). In outpatient setting, an increase in the consumption of oral forms of azithromycin, levofloxacin and cefixime, as well as parenteral forms of amoxicillin-clavulanic acid, ciprofloxacin and ceftriaxone, was recorded. In 2021, antimicrobial resistance to reserve antibiotics in hospital setting was as follows: Acinetobacter baumanii to meropenem 66.0%, Klebsiella spp to cefotaxime 67.14%, Pseudomonas to meropenem 25.7%. Conclusion: Recent COVID-19 pandemic was associated with increased antibiotic consumption in inpatient and outpatient settings, with characteristic change of pattern of azithromycin consumption. Also, high levels of antimicrobial resistance to reserve antibiotics were registered in hospital setting with low prevalence of identified pathogen-directed antimicrobial prescription. Strategies toward combat antimicrobial resistance in the Doboj region are urgently needed.

Consumption of Antibiotics in Primary Care Setting before and during COVID-19 Pandemic in Republic of Srpska, Bosnia and Herzegovina.

The pandemic of COVID-19 has brought many changes in health care systems at all levels of health care. The increase in the number of cases of COVID-19 has led to overuse and misuse of antibiotics.The aim of this study was to compare the consumption of antibiotics for systemic use in outpatients in the Republic of Srpska (RS), before and during the first year of the COVID-19 pandemic, as well as the association between antibiotic consumption and the rate of incidence and mortality of COVID-19. The total consumption of the antibiotics for systemic use (J01) in outpatients in the Republic of Srpska during 2019 was 19.40 DDD/TID, with an increase to 30.80 DDD/TID in 2020.Significantly higher use of penicillin (10.58 ± 11.01 DDD/TID in 2019 vs. 17.10 ± 13.63 DDD/TID in 2020), cephalosporins (2.68 ± 1.90 DDD/TID in 2019 vs. 5.93 ± 2.77 DDD/TID in 2020) and macrolides (2.14 ± 2.22 DDD/TID in 2019 vs. 3.40 ± 3.44 DDD/TID in 2020) was observed during the pandemic period. It is necessary to improve the prescribing practice of antibiotics at the primary health care level, public awareness about rational use of antibiotics, as well as the current antibiotic stewardship programs and control their implementation.

Sex Differences in the Use of Cardiovascular Drugs: A Survey of Patients in a Single Center.

OBJECTIVE: Patients and medical professionals have a common misconception that cardiovascular diseases (CVD) predominantly affect men, which can lead to less prescribing of cardiovascular drugs to women. This study examined whether there were sex differences in the administration of cardiovascular (CV) drugs in patients admitted to the intensive care unit of the Internal Medicine Clinic of Foca University Hospital (ICFUH). MATERIALS AND METHODS: The study comprised 332 patients hospitalized at the ICFUH from January 1st to June 30th, 2019. The following data on leading CVD and risks related to CV drug administration were collected: age, hyperlipidemia (HLD), diabetes mellitus (DM), chronic kidney disease (CKD), liver disease (LD), heart failure (HF), hypertension (HTN), myocardial infarction (MI), and stroke (S). The amount of the CV drugs of interest (statins, antiplatelet drugs, calcium channel blockers, ACE inhibitors, beta blockers, diuretics) administered during hospitalization was expressed as the Defined Daily Dose (DDD)/100 bed-days (BD) for patients of both sexes separately. RESULTS: During hospitalization in the intensive care unit of ICFUH, female patients were less likely to be treated with statins than male patients (30.1 vs. 57.5 DDD/100 BD, P<0.05). There was no difference between sexes regarding the use of antihypertensive drugs. Women were less likely to be treated by antiplatelet therapy, more precisely by acetylsalicylic acid (30.4 vs. 36.9 DDD/100 BD, P<0.05). CONCLUSION: Our study indicates that there were sex differences in CV drug administration in ICFUH. Presuming that drugs used during hospitalization were at least partially a continuation of the previous therapy prescribed by the family doctor, it is possible that such differences exist in primary care.

Variations in Chemical Composition, Vasorelaxant and Angiotensin I-Converting Enzyme Inhibitory Activities of Essential Oil from Aerial Parts of Seseli pallasii Besser (Apiaceae).

The present paper describes environmental and seasonal-related chemical composition variations, vasorelaxant and angiotensin I-converting enzyme (ACE) activities of essential oil from aerial parts of Seseli pallasii Besser. The composition was analyzed by GC and GC/MS. Monoterpenes were found to be the most abundant chemical class with α-pinene (42.7 - 48.2%) as the most prevalent component. Seseli pallasi essential oil relaxed isolated endothelium-intact mesenteric arteries rings precontracted with phenylephrine with IC50  = 3.10 nl/ml (IC50  = 2.70 µg/ml). Also, S. pallasii essential oil was found to exhibit a dose-dependent ACE inhibitory activity with an IC50 value of 0.33 mg/ml. In silico evaluation of ACE inhibitory activity of the individual components showed that spathulenol exhibited the best binding affinity with ACE, and the lowest binding energy of -7.5 kcal/mol. The results suggested that combination of vasorelaxing and ACE inhibitory effects of the analyzed S. pallasii essential oil might have the potential therapeutic significance in hypertension.