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.
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.
MgSO 4 is used as a tocolytic agent. It is considered to be a calcium channel antagonist, but a different mechanism of its action might be involved. The aim of this study was to examine the contribution of calcium concentrations and potassium channels in the mechanism of MgSO 4 -mediated uterine relaxation. Isolated uteri from female Wister rats were treated with increasing MgSO 4 concentrations (0.1-30 mM). MgSO 4 induced dose-dependent inhibition of spontaneous activity. Addition of Ca 2+ (6 mM and 12 mM) stimulated uterine contractile activity and attenuated the inhibitory activity of MgSO 4 . In order to analyze the role of different subtypes of potassium channels, Ca 2+ -stimulated uteri were pretreated with glibenclamide (Glib), a selective ATP-sensitive potassium channel inhibitor (K ATP ), tetraethylammonium (TEA), a non-specific inhibitor of large conductance calcium-activated potassium channels (BK Ca ), and 4-aminopyridine (4-AP), a voltage-sensitive potassium channel inhibitor (Kv), at concentrations that had no effect per se. Pretreatment with 4-AP had no effect on MgSO 4 -mediated relaxation of Ca 2+ -stimulated uteri. The relaxing effect of MgSO 4 was potentiated by pretreatment with glibenclamide. Pretreatment with TEA attenuated the MgSO 4 -mediated decrease in frequency. Our results suggest that MgSO 4 acts as a general calcium antagonist that influences Ca 2+ -mediated potassium channels. Furthermore, it seems that MgSO 4 uterine relaxation activity is partially mediated by selective ATP-sensitive potassium channels, suggesting an ATP-dependent role.
Kratak sadržajUvod. Podtip, ekspresija, distribucija i funkcija K + kanala u glatkim mišićima krvnih sudova su promjenljivi i vjerovatno zavise od očuvanosti endotela, azot monoksida (NO) i patoloških stanja kao što je hipertenzija. Ispitivali smo uticaj modulatora kalijumskih kanala i njihove interakcije sa NO na krvne sudove. Ovo ispitivanje je značajno za pronalaženje novih terapijskih koncepata u liječenju poremećaja kontraktilnosti krvnih sudova. Cilj rada je bio da se ispita uloga pola, endotela i hipertenzije u relaksantnom efektu pinacidila na izolovane mezenterične i renalne arterije, uzete od normotenzivnih (NT) i spontano hipertenzivnih (HT) pacova.Metode. Eksperimenti su izvedeni na izolovanim mezenteričnim i renalnim arterijama uzetim od mužjaka i ženki NT i HT Wistar pacova. Arterije su inkubirane 30 min u kupatilu za izolovane organe sa Krebs-Ringerovim rastvorom, na 36 0 C i aerisane smješom 95% O 2 i 5% CO 2 . Kontrakcije izolovanih krvnih sudova su izazivane fenilefrinom (10 -6 mol), a na stabilan tonus je dodavan pinacidil (10 -8 -10 -4 M). Funkcionalni integritet endotela je potvrđivan acetilholinom (10 -5 mol).Rezultati. Pinacidil je koncentracijski zavisno relaksirao mezenterične arterije, bez obzira da li su arterije uzete od mužjaka ili ženki pacova. Relaksantni efekat pinacidila je bio veoma izražen na segmentima arterija sa endotelom. Značaj endotela je bio manje izražen na krvnim sudovima uzetim od HT, nego od NT životinja. Stepen relaksacije je bio veći kod mezenteričnih, nego kod renalnih arterija.Zaključak. Pinacidil (10 -8 -10 -4 mol) je prouzrokovao koncentracijski i endotel zavisnu relaksaciju izolovanih renalnih i mezenteričnih arterija pacova, uzetih od NT i HT pacova bez obzira na pol.
Background. Pentoxifylline is a methylxanthine derivative that is used to treat peripheral vascular disease. One of the mechanisms of action of pentoxifylline is the vasodilatation of blood vessels. Th is study examined the eff ect of increasing pentoxifylline concentrations on the contractility of isolated rat uteri in the presence of a potassium channel antagonist. Methods. Th e uteri were isolated from virgin Wistar rats (180-220 g) and suspended in an isolated organ bath chamber containing De Jalon's solution and aerated with 95% O 2 and 5% CO 2. Th e temperature was maintained at 37ºC. Isometric contractions were recorded using an isometric force transducer (Ugo Basile). Th e preload of the preparation was approximately 1 g. Th e uteri were allowed to contract spontaneously or in the presence of Ca 2+ (0.018 and 0.36 mM) and acetylcholine (ACh) and were treated with pentoxifylline. Results. Pentoxifylline caused concentration-dependent inhibition of spontaneous rhythmic uterine activity and uterine activity caused by calcium Ca 2+ (0.018 mM and 0,36 mM). We showed that the inhibitory eff ects of pentoxifylline depend on the type of muscle contractions activated and that the inhibitory eff ect is signifi cantly stronger for spontaneous rhythmic activity and forin Ca 2-induced contractions of isolated rat uteri +. Th e relaxing eff ect of pentoxifylline depends on the calcium concentration in the medium. Pentoxifylline exerted the weakest relaxant eff ects on contractions induced by acetylcholine. In contrast to methylene blue, tetraethylammonium, or 4-aminopyridine, glibenclamide did not antagonise the relaxing eff ect of pentoxifylline on isolated rat uteri.. Conclusion. Th e results obtained suggest that the mechanism of action of pentoxifylline does not lead to the opening of K ATP channels. However, the opening of BKCa and voltage-dependent Ca 2+ channels had some role, but to varying degrees, in the mechanism of the relaxing eff ect of pentoxifylline on the spontaneous rhythmic activity and calcium-induced con
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