Antibiootikumide kasutamine ja antimikroobne resistentsus COVID-19-pandeemia ajajärgul

COVID-19-st põhjustatud hingamisraskustega patsientidele määratakse sageli antibiootikumravi. Ometigi kinnitavad nüüdseks kogunenud andmed, et COVID-19-ga kaasnevate respiratoorsete haigusnähtude põhjustaja on üksnes harva bakteriaalne või fungaalne sekundaarinfektsioon. Mõnedes haiglates on COVID-19 raviks kasutatud asitromütsiini, ehkki selleks puudub praeguse seisuga teaduslik alus. Kuna antibiootikumravi määratakse sageli ja ilma tegeliku vajaduseta, on paljud teadlased väljendanud muret, et COVID-19-pandeemia võimendab antimikroobse resistentsuse (AMR) üleilmset levikut. AMRi levikut mõjutavaks lisateguriks on maailmas järsult suurenenud biotsiidide kasutamine. Antibiootikumide ebavajaliku kasutamise vähendamiseks ja AMRi leviku ohjeldamiseks tuleb COVID-19-patsientide ravis lähtuda antibiootikumide vastutustundliku kasutamise põhimõtetest. &nbsp

Haiglaväliste infektsioonitekitajate antibiootikumiresistentsus

Taust ja eesmärk. Antibiootikumiresistentsus (AMR) on tänapäeva tervishoius oluline probleem, mille ohjamise eelduseks on AMRi järelevalve. Uuringu eesmärk oli kirjeldada Eestis haiglaväliseid infektsioone põhjustavate mikroobitüvede resistentsust ning võrrelda seda Venemaa ja Soome vastavate näitajatega ning Eestis haiglatest isoleeritud invasiivsete mikroobitüvede AMRiga. Metoodika. Uuringusse kaasati AMRi andmed erinevatest Eesti laboritest, teaduspublikatsioonidest ja Euroopa antibiootikumiresistentsuse seire võrgustikust. Tulemused. Hingamisteede infektsioone põhjustavate S. pneumoniae mikroobitüvede resistentsus penitsilliini suhtes oli 1,5% ja H. influenzae tüvede resistentsus ampitsilliini suhtes 16,7%. Eesti S. pneumoniae ja H. influenzae AMR oli sarnane Soomega, kuid Venemaa mikroobitüved olid resistentsemad. Uroinfektsioone põhjustava E. coli mikroobitüvedest oli üle 30% resistentsed ampitsilliini ja piperatsilliini suhtes, üle 20% resistentsed trimetoprimi ja trimetoprimisulfametoksasooli suhtes, üle 10% norfloksatsiini ja levofloksatsiini suhtes ning alla 2% nitrofurantoiini suhtes. E. coli antibiootikumiresistentsus oli suurem meestel ja suurenes naistel vanusega. Venemaalt isoleeritud E. coli ja K. pneumoniae mikroobitüved olid resistentsemad kui Eesti ja Soome mikroobitüved. Eesti ambulatoorsetest proovimaterjalidest isoleeritud E. coli mikroobitüved olid tundlikumad ja S. pneumoniae mikroobitüved resistentsemad kui haiglast isoleeritud invasiivsed mikroobitüved. Kokkuvõte. Eesti ambulatoorsetest materjalidest isoleeritud mikroobitüvede AMR on väike, sarnanedes Soomega. Venemaa haiglavälised mikroobitüved on resistentsemad kui Eesti ja Soome tüved. Eesti haiglaväliste tüvede AMR ei korreleeru otseselt haiglas isoleeritud invasiivsete mikroobitüvede AMRiga. &nbsp

Ambulatoorne antibiootikumide kasutus Eestis

Eesmärk. Uuringu eesmärk oli kirjeldada muutusi antibiootikumide ambulatoorses kasutamises Eestis aastatel 2008–2018 ning võrrelda antibiootikumide kasutust Põhjamaadega. Metoodika. Ravimikasutuse andmed põhinevad hulgimüüjate kvartaliaruannetel ja on esitatud defineeritud päevadooside (DPD, inglise keeles defined daily dose, DDD) arvuna 1000 inimese kohta ööpäevas. Antibiootikumide kasutamise kvaliteeti hinnati Euroopa mikroobivastaste ainete tarbimise järelevalve võrgustiku (European Surveillance of Antimicrobial Consumption Network, ESAC-Net ehk ESAC-võrgustik) kvaliteedinäitajate kaudu. Tulemused. Antibiootikumide ambulatoorne kasutus oli Eestis 2018. aastal 10,2 DPDd 1000 inimese kohta ööpäevas, olles sarnane Soome, Rootsi, Taani ja Norra näitajatega (vastavalt 13,2; 10,8; 13,7 ja 14,0). Kogukasutuses ei ole Eestis aastatel 2008–2018 suuri muutusi aset leidnud, kuid muutunud on kasutatavate preparaatide spekter – ilma beetalaktamaasi inhibiitorita penitsilliinide kasutus väheneb ja beetalaktamaasi inhibiitoriga kombineeritud penitsilliinide kasutamine suureneb. Tsefalosporiinide kasutus on 11 aasta jooksul veidi suurenenud, kinoloonide kasutus aga vähenenud. Antibiootikumide kasutamine oli Eestis 2018. aastal ESACi näitajate põhjal enamasti sarnane Põhjamaadega, kuid viimastes kasutatakse rohkem beetalaktamaasi suhtes tundlikke penitsilliine. Laia ja kitsa toimespektriga penitsilliinide, tsefalosporiinide ja makroliidide kasutamise suhe on Eestis võrreldes Põhjamaadega märkimisväärselt kaldu laia toimespektri poole. Talvekuudel kasutatakse antibiootikume Eestis võrreldes Põhjamaadega rohkem. Kokkuvõte ja järeldused. Antibiootikumide üldine kasutus on Eestis väiksem kui Euroopas keskmiselt ning sarnane Põhjamaade kasutusnäitajatega, mis on ka keskmisest väiksemad. Olulist kasutuse suurenemist pole vaadeldud aastatel toimunud. Samas suureneb Eestis laia toimespektriga penitsilliinide kasutamine kitsa toimega antibiootikumide arvelt ning selle põhjus vajab edaspidi täpsemat analüüsi. &nbsp

Discovery and development of safe-in-man broad-spectrum antiviral agents

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of the general population from emerging and re-emerging viral diseases, reinforcing the arsenal of available antiviral options. Here, we review discovery and development of BSAAs and summarize the information on 120 safe-in-man agents in a freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand the spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.Non peer reviewe

Low Temperature and Low UV Indexes Correlated with Peaks of Influenza Virus Activity in Northern Europe during 2010–2018

With the increasing pace of global warming, it is important to understand the role of meteorological factors in influenza virus (IV) epidemics. In this study, we investigated the impact of temperature, UV index, humidity, wind speed, atmospheric pressure, and precipitation on IV activity in Norway, Sweden, Finland, Estonia, Latvia and Lithuania during 2010–2018. Both correlation and machine learning analyses revealed that low temperature and UV indexes were the most predictive meteorological factors for IV epidemics in Northern Europe. Our in vitro experiments confirmed that low temperature and UV radiation preserved IV infectivity. Associations between these meteorological factors and IV activity could improve surveillance and promote development of accurate predictive models for future influenza outbreaks in the region

Low Temperature and Low UV Indexes Correlated with Peaks of Influenza Virus Activity in Northern Europe during 2010–2018

With the increasing pace of global warming, it is important to understand the role of meteorological factors in influenza virus (IV) epidemics. In this study, we investigated the impact of temperature, UV index, humidity, wind speed, atmospheric pressure, and precipitation on IV activity in Norway, Sweden, Finland, Estonia, Latvia and Lithuania during 2010–2018. Both correlation and machine learning analyses revealed that low temperature and UV indexes were the most predictive meteorological factors for IV epidemics in Northern Europe. Our in vitro experiments confirmed that low temperature and UV radiation preserved IV infectivity. Associations between these meteorological factors and IV activity could improve surveillance and promote development of accurate predictive models for future influenza outbreaks in the region

Novel activities of safe-in-human broad-spectrum antiviral agents

Abstract According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.Peer reviewe

Prolonged outbreak of <it>Serratia marcescens</it> in Tartu University Hospital: a case–control study

Abstract Background The aim of our study was to investigate and control an outbreak and identify risk factors for colonization and infection with Serratia marcescens in two departments in Tartu University Hospital. Methods The retrospective case–control study was conducted from July 2005 to December 2006. Molecular typing by pulsed field gel electrophoresis was used to confirm the relatedness of Serratia marcescens strains. Samples from the environment and from the hands of personnel were cultured. Results The outbreak involved 210 patients, 61 (29%) developed an infection, among them 16 were invasive infections. Multivariate analysis identified gestational age, arterial catheter use and antibiotic treatment as independent risk factors for colonization and infection with Serratia marcescens. Molecular typing was performed on 83 Serratia marcescens strains, 81 of them were identical and 2 strains were different. Conclusions Given the occasionally severe consequences of Serratia marcescens in infants, early implementation of aggressive infection control measures involving patients and mothers as well as the personnel is of utmost importance.</p

Multidrug resistant Pseudomonas aeruginosa in Estonian hospitals

Abstract Background We aimed to identify the main spreading clones, describe the resistance mechanisms associated with carbapenem- and/or multidrug-resistant P. aeruginosa and characterize patients at risk of acquiring these strains in Estonian hospitals. Methods Ninety-two non-duplicated carbapenem- and/or multidrug-resistant P. aeruginosa strains were collected between 27th March 2012 and 30th April 2013. Clinical data of the patients was obtained retrospectively from the medical charts. Clonal relationships of the strains were determined by whole genome sequencing and analyzed by multi-locus sequence typing. The presence of resistance genes and beta-lactamases and their origin was determined. Combined-disk method and PCR was used to evaluate carbapenemase and metallo-beta-lactamase production. Results Forty-three strains were carbapenem-resistant, 11 were multidrug-resistant and 38 were both carbapenem- and multidrug-resistant. Most strains (54%) were isolated from respiratory secretions and caused an infection (74%). Over half of the patients (57%) were ≥ 65 years old and 85% had ≥1 co-morbidity; 96% had contacts with healthcare and/or had received antimicrobial treatment in the previous 90 days. Clinically relevant beta-lactamases (OXA-101, OXA-2 and GES-5) were found in 12% of strains, 27% of which were located in plasmids. No Ambler class B beta-lactamases were detected. Aminoglycoside modifying enzymes were found in 15% of the strains. OprD was defective in 13% of the strains (all with CR phenotype); carbapenem resistance triggering mutations (F170 L, W277X, S403P) were present in 29% of the strains. Ciprofloxacin resistance correlated well with mutations in topoisomerase genes gyrA (T83I, D87N) and parC (S87 L). Almost all strains (97%) with these mutations showed ciprofloxacin-resistant phenotype. Multi-locus sequence type analysis indicated high diversity at the strain level – 36 different sequence types being detected. Two sequence types (ST108 (n = 23) and ST260 (n = 18)) predominated. Whereas ST108 was associated with localized spread in one hospital and mostly carbapenem-resistant phenotype, ST260 strains occurred in all hospitals, mostly with multi-resistant phenotype and carried different resistance genotype/machinery. Conclusions Diverse spread of local rather than international P. aeruginosa strains harboring multiple chromosomal mutations, but not plasmid-mediated Ambler class B beta-lactamases, were found in Estonian hospitals. Trial registration This trial was registered retrospectively in ClinicalTrials.gov (NCT03343119)