The aim of this study was to determine quantities of antibiotics used mainly or exclusively for urinary tract infections in Croatia between 2005 and 2014, to describe utilisation trends, and general ...consequences of antibiotic consumption on antimicrobial resistance.
Antibiotic utilisation data were obtained from annual reports of both the Croatian Drug Agency and Croatian Academy of Medical Sciences. Antibiotic consumption was expressed in DDD/1000 inhabitants/day (DDD TID). Antimicrobial resistance was analysed for E. coli, E. faecalis, E. faecium, P. aeruginosa, Klebsiella spp., P. mirabilis. Descriptive statistics were used to process data and calculate trends.
Overall, utilisation of antibacterials decreased by 4.8% (from 3,35 to 3,19 DDD TID), while trends of individual agents varied substantially - from 87% decline for ceftibuten to 160% rise for levofloxacin. The consumption of quinolones increased by 32.3%. This was mostly due to increased ciprofloxacin consumption (144% raise). Sulfamethoxazole-trimethoprim declined by 57%, while nitrofurantoin increased by 86%. The use of fosfomycin was marginal. Antimicrobial resistance of E. coli increased against quinolones by 54.5%, and against nitrofurantoin by 2-3%. Quinolone resistance of other pathogens (Klebiella spp, Proteus mirabilis), increased variably - between 17.2% (Klebsiella) and 90% (Proteus), while for P. aeruginosa remained the same at 22%.
High rates of antimicrobial utilisation require prescribing restrictions and educational interventions. The increased use of fluoroquinolones is a potentially serious public health threat due to the rapid development of resistance among uropathogens. This threat can be avoided by greater use of nitrofurantoin and fosfomycin.
This edition is intended to provide better understanding of antibacterial drugs and their mechanism, the role of a few metal drug complexes as antibacterials, cross-checking of a few compounds and ...biomaterials against drug-resistant bacterial strains as well as a few alternative approaches using medicinal plant based formulations in the control of antibiotic-resistant bacteria. The information in this book provides clues for upcoming trends in treating antibiotic resistance problems with which one can explore new approaches in the treatment of common infections with drug-resistant strains.
In the last decade antibiotic usage in animal production systems has received a considerable public attention. The use, overuse and misuse of antibiotics provided an excellent environment for the ...selection and dissemination of antibiotic resistant bacteria and resistance genes across a wide diversity of bacteria, mainly through horizontal gene transfer. Resistance genes move between animal and human bacteria mainly through the food chain. Thus resistance generated in animal production environments could result in the loss of effectiveness of antibiotics used for the treatment of human diseases. The increasing threat of emerging bacterial pathogens resistant to a variety of antibiotics and the economic and human burden have moved the legislators in EU to ban antibiotic usage in animal food production as growth promoters in 2006 and recently proposed further non-binding recommendations to ban antibiotics for prophylactic use too. The costs for such actions will presumably be much lower in comparison to the costs of leaving the issue as it is. However, in non EU countries such measures have not been adopted yet. The mechanisms and examples of antibiotic resistance development and dissemination are described, focusing on antibiotics used both in human and veterinary medicine and animal food production.
V zadnjem desetletju je uporaba antibiotikov v živinoreji pritegnila pozornost širše javnosti. Nenadzorovana, prekomerna in nenamenska uporaba antibiotikov je, predvsem preko mehanizma horizontalnega prenosa genov, omogočila selekcijo in širjenje proti antibiotikom odpornih bakterij in genov z zapisi za odpornost. Prenos odpornih bakterij oziroma genov z zapisi za odpornost med človekom in živalmi poteka predvsem preko prehranjevalne verige. Posledično lahko odporne bakterije ali geni z zapisom za odpornost, ki izvirajo iz živinorejskega okolja, zmanjšajo učinkovitost zdravljenja bakterijskih okužb z antibiotiki pri človeku. Vse večja grožnja pojavljanja novih večkratno odpornih patogenih bakterij, ter kot posledica vpliv na zdravje ljudi in tudi ekonomska škoda, so pripeljali do odločitve Evropske skupnosti, da od leta 2006 prepove uporabo antibiotikov kot pospeševalcev rasti v živinoreji. Nedavno pa so sprejeli tudi priporočilo, po katerem naj se antibiotikov v živinoreji ne bi uporabljalo več niti za profilakso. V večini držav izven EU podobne zakonodaje še niso sprejeli. V tem preglednem članku so opisani primeri razvoja in pojavljanja odpornosti proti antibiotikom, ki se uporabljajo tako v humani medicini in veterini, kot posledica množične uporabe v živinoreji.
In this study, low-carbon soils collected from an altitude transect from 5000 m to 6000 m were adopted as a simple model system with lower interaction complexity. This could help disentangle the ...basic environmental factors shaping the abundance and distribution of expressed resistance traits in culturable portion of fast growing heterotrophic strains. Improved plate counts were performed at 4 °C using 0.01 diluted nutrient broth supplemented with cold soil extract as a general media and additionally supplemented with antibiotics Ampicillin, Erythromycin, Kanamycin and Tetracyclin. A number of colonies (500) isolated from six locations were also tested separately for their antibiotic resistance. The results show that these high-altitude cold soils contained bacterial populations culturable at 4 °C in the range of 106 cells / g that were resistant to the four antibiotics and their various combinations tested in this study. The highest prevalence of resistance was observed in vegetated soils, whereas almost two orders of magnitude lower abundance of resistant cells was cultured from barren soils. Redundancy analysis showed that vegetation, soil carbon and pH were successful in explaining the interaction between environmental parameters and various culturable fractions of cold soil bacteria used in this study.
V študiji sem uporabil vzorce tal z nizko vsebnostjo organskega ogljika iz višinskega transekta 5000 m-6000 m kot poenostavljen modelni sistem z nizko kompleksnostjo interakcij. Ta bi lahko pomagal razumeti osnovne okoljske dejavnike, ki uravnavajo porazdelitev in obseg izraženih rezistenčnih lastnosti gojljivega dela hitro rastočih heterotrofnih sevov. Izboljšano štetje na ploščah sem izvedel pri 4 °C na 0,01 koncentriranem hranilnem bujonu, dopolnjenim s hladnim ekstraktom tal, kot splošnim gojiščem, ki sem ga dopolnil z posameznimi antibiotiki (ampicilin, eritromicin, kanamicin in tetraciklin). Večje število izolatov (500) iz šestih lokacij sem prav tako testiral ločeno na njihovo odpornost na antibiotike. Ugotavljal sem tudi povezavo med okoljskimi dejavniki ter porazdelitvijo odpornih sevov in splošnega gojljivega deleža talnih bakterij. Rezultati kažejo, da visokogorska hladna tla vsebujejo pri nizkih temperaturah gojljive bakterijske populacije (106 / g), ki so odporni na posamezne antibiotike in razne njihove kombinacije, uporabljene v tej študiji. Poraščena tla imajo največji delež odpornih bakterij, skoraj dva reda manjši pa je prisoten v golih tleh. Statistična analiza je pokazala, da vegetacija, organski ogljik ter pH uspešno razložijo interakcijo med okoljskimi dejavniki in posameznimi gojenimi deleži bakterij, izoliranih iz hladnih tal.
Penicilinski antibiotiki delujejo baktericidno in spadajo med časovno odvisne antibiotike. Za večino penicilinov je značilna kratka razpolovna doba eliminacije. Benzilpenicilini se po peroralni ...aplikaciji ne absorbirajo, ampicilin in kloksacilin se sicer absorbirata, vendar slabo, medtem ko se amoksicilin skoraj v celoti absorbira. Pri slednjem je smotrno z intravenske terapije preklopiti na peroralno, če lahko s peroralno aplikacijo dosežemo plazemske koncentracije penicilina, primerljive s tistimi po intravenski aplikaciji, t. j. enako povprečno plazemsko koncentracijo penicilina v stacionarnem stanju. Posledično lahko pričakujemo enako učinkovitost obeh aplikacij. Smiselnost preklopne terapije je treba proučiti predvsem s stališča bolnika, saj ni primerna za bolnike, ki so v kritičnem stanju in imajo močno zvišano telesno temperaturo ali malabsorbcijski sindrom. Prednost preklopne terapije pa je v tem, da zmanjša pojavnost flebitisa in seps. V članku sta obravnavana dva primera preklopne terapije. Na osnovi farmakokinetičnih simulacij in indeksov učinkovitosti protibakterijskega zdravljenja je pokazana primerljivost intravenske terapije z ampicilinom in peroralne terapije z amoksicilinom, medtem ko preklopna terapija pri zdravljenju osteomielitisa s kloksacilinom ostaja nedorečena. Na podlagi predstavljenih primerov članek ilustrativno prikazuje, da ustrezna razlaga farmakokinetičnih parametrov bistveno pripomore k pravočasnemu preklopu z intravenske na peroralno terapijo s penicilinom. Takšna terapija je bolniku bolj prijazna, poleg tega pa prispeva k zniževanju stroškov za zdravljenje z zdravili v bolnišnicah ob še vedno varni in učinkoviti farmakoterapiji bakterijskih okužb.
Penicillin antibiotics are time-dependent bactericidal agents. Most of them have very short elimination half-life. As regards their bioavailability, benzylpenicillins are not absorbed following oral administration, while oral ampicillin and cloxacilin are poorly absorbed, and amoxicillin is almost completely absorbed. These drugs are suited for intravenous to oral switch provided that plasma concentrations after oral administration are comparable to those following intravenous application. The assessment is made by calculating the average steady-state plasma concentration. Consequently, the same bactericidal activity can be expected. Oral therapy has many advantages over intravenous administration, including lower treatment costs, shorter hospital stay, lower incidence of phlebitis and sepsis, and greater patient convenience. However, switch therapy is not possible in critically-ill patients, and in patients with fever, increased inflammatory parameters, or malabsorption syndrome. This paper presents two cases of intravenous to oral antibiotic switch therapy. On the basis of pharmacokinetic simulations and evaluation of the efficacy of antibacterial treatment, oral amoxicillin therapy was found to be comparable to intravenous amplicillin treatment; the suitability of switching intravenous to oral cloxacillin for the treatment of osteomyelitis remains unascertained. Based on appropriate interpretation of pharmacokinetic parameters, intravenous to oral antibiotic switch therapy has proved to be an effective and safe pharmacotherapy for bacterial infections.
V bližini skoraj vseh prokariontskih operonov, ki kodirajo peptidne sintetaze, so geni, katerih zaporedje je zelo podobno tioesterazam. Mehanizem delovanja in funkcija tioesteraz v sintezi peptidnih ...antibiotikov še nista znani. Bakterija Bacillus licheniformis sintetizira antibiotik bacitracin na multiencimskih kompleksih, ki so sestavljeni iz treh peptidnih sintetaz (BA1, BA2, BA3). Geni, ki kodirajo peptidne sintetaze, so združeni v operonu bac, pred katerim je gen btsT, ki kodira tioesterazo. Da bi lahko proučevali vpliv tioesteraze na biosintezo bacitracina, smo z verižno reakcijo s polimerazo DNK iz kromosomske DNK B. licheniformis izolirali odsek v velikosti 1,2 kb. Ta odsek je vključeval skoraj celoten gen btsT in promotorsko regijo operona bac. Odsek 1,2 kb smo hibridizirali s kromosomsko DNK bakterije B. licheniformis BA1. V gen btsT na odseku 1,2 kb smo vstavili tudi gen za odpornost proti tetraciklinu (tetM) in tako sestavili vektor za insercijsko mutagenezo gena btsT.
Bakterije rodu Bacillus so po Gramu pozitivni sporulirajoči bacili. Zelo dobro se prilagajajo različnim spremembam v okolju: pomanjkanju hranil, spremembam temperature in vrednosti pH. Pri ...bakteriji Bacillus licheniformis se proizvodnja peptidnega antibiotika bacitracina začne v pozni logaritemski fazi rasti in se konča med stacionarno fazo. Njegova biosinteza se ujema s proizvodnjo alkalne proteinaze. Da bi določili možne dejavnike s pozitivnim delovanjem glede na biosintezo bacitracina v bakteriji B. licheniformis, smo izvedli poskus z izražanjem genov, ki sodelujejo v procesih sporulacije in kompetence v B. subtilis. B. licheniformis smo transformirali s plazmidi pIS74 (sinIR) in pIS119 (sinR). Oba plazmida v bakterijah B. subtilis in B. licheniformis povzročata fenotip Spo-, zato se je pri rekombiniranih sevih B. licheniformis znižala aktivnost alkalne proteinaze in vsebnost bacitracina.
Peptidni antibiotiki, ki jih sintetizirajo mnogi mikroorganizmi, so strukturno izredno raznoliki. Med njimi je tudi bacitracin, proizvod bakterije Bacillus licheniformis. Teh peptidov ne kodirajo ...geni; njihova biosinteza poteka s pomočjo peptidnih sintetaz. Raven biosinteze bacitracina pozitivno korelira z ravnjo sinteze alkalne proteinaze. Naš namen je bil dvigniti raven sinteze poznih encimov in posledično s tem tudi raven biosinteze bacitracina. Celice bakterije B. licheniformis BA1 smo transformirali z genom degU bakterije B. subtilis, za katerega smo menili, da je globalni pozitivni regulator v procesih kompetence in sporulacije. Pričakovali smo, da bo povišana koncentracija beljakovine DegU zvišala raven biosinteze bacitracina. Klone rekombiniranih sevov smo analizirali in jim določili proteolizno aktivnost. Pri dveh klonih produkcijskega seva bakterije B. licheniformis BA1 smo ugotovili višjo raven proizvodnje peptidnega antibiotika bacitracina.