Economic impact of infections and antibiotics

In this chapter, we review several aspects with respect to the burden of infectious diseases, its impact in morbidity and mortality, and its economic burden. Furthermore, we referenced the actual situation with relation to the use of antimicrobial, the resistance problem and misuse of antibiotic, and the economic impact in the health systems

Microfluidic smartphone quantitation of <i>Escherichia coli</i> in synthetic urine

In spite of the clinical need, there is a major gap in rapid diagnostics for identification and quantitation of E. coli and other pathogens, also regarded as the biggest bottleneck in the fight against the spread of antimicrobial resistant bacterial strains. This study reports for the first time an optical, smartphone-based microfluidic fluorescence sandwich immunoassay capable of quantifying E. coli in buffer and synthetic urine in less than 25 min without sample preparation nor concentration. A limit of detection (LoD) up to 240 CFU/mL, comensurate with cut-off for UTIs (103-105 CFUs/mL) was achieved. Replicas of full response curves performed with 100-107 CFUs/mL of E. coli K12 in synthetic urine yielded recovery values in the range 80-120%, assay reproducibility below 30% and precision below 20%, therefore similar to high-performance automated immunoassays. The unrivalled LoD was mainly linked to the 'open fluidics' nature of the 10-bore microfluidic strips used that enabled passing a large volume of sample through the microcapillaries coated with capture antibody. The new smartphone based test has the potential of being as a rapid, point-of-care test for rule-in of E. coli infections that are responsible for around 80% of UTIs, helping to stop the over-prescription of antibiotics and the monitoring of patients with other symptomatic communicable diseases caused by E. coli at global scale.</p

Storytelling as a research tool and intervention around public health perceptions and behaviour: a protocol for a systematic narrative review

INTRODUCTION There is a growing trend to use storytelling as a research tool to extract information and/or as an intervention to effect change in the public knowledge, attitudes and behaviour (KAB) in relation to public health issues, primarily those with a strong element of disease prevention. However, evidence of its use in either or both capacities is limited. This protocol proposes a systematic narrative review of peer-reviewed, published literature on the use of storytelling as a research tool within the public health arena. METHODS AND ANALYSIS Medline, EMBASE, PsycINFO, ERIC (Educational Resources Information Center), Web of Science, Art and Humanities database (ProQuest), Scopus and Google Scholar will be searched for studies that look at the use of storytelling in the research of pressing current public health issues, for example, vaccinations, antimicrobial resistance, climate change and cancer screening. The review will synthesise evidence of how storytelling is used as a research tool to (a) gain insights into KAB and (b) to effect change in KAB when used as an intervention. Included studies will be selected according to carefully defined criteria relevant to public health issues of interest, and data from qualitative, quantitative and mixed-methods studies will be extracted with a customised data extraction form. A narrative synthesis will be performed according to Economic and Social Research Council guidance from Popay, J, 2006.The study protocol follows the recommendations by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). ETHICS AND DISSEMINATION Formal ethical approval is not required for this study, as no primary data will be collected. Dissemination will involve publishing results of this study in relevant peer-reviewed journal(s). Where possible, the study results will also be presented as posters or talks at relevant medical conferences and meetings. PROSPERO REGISTRATION NUMBER CRD4201912470

Sources of antibiotic resistance: zoonotic, human, environment

Antibiotic resistance is a global problem that must be managed under the One Health perspective. Retrospectively, it is assumed that microbial populations able to cope with compounds with antimicrobial activity and susceptible bacteria lived in equilibrium for a thousand years. This situation would change in the middle 1940s of the twentieth century when one of the most important revolutions of modern medicine started - the use of a natural antimicrobial compound, the penicillin, to treat infectious bacterial diseases. Over the years, the massive use of antibiotics in human and animal medicine, as well as in animal production for both growth promotion and infection prophylaxis/metaphylaxis, accelerated and shaped one of the most successful evolutionary case studies. As a result of an impressive combination of genome and community dynamics, bacteria with acquired antibiotic resistance are nowadays widespread across different environmental compartments (water, soil, wildlife) as well as in the human food chain (poultry, livestock, aquaculture, produce). Hence, the evolutionary success of these bacteria turned to represent a major threat to the human health. This review discusses some of the drivers and paths of antibiotic resistance dissemination across zoonotic, human, and environmental sources.info:eu-repo/semantics/acceptedVersio

Analyses of bacteriophages to Yersinia ruckeri and the salmon (Salmo salar L.) antibody response to the bacteriophages.

New technologies for producing Atlantic salmon like the recirculation aquaculture systems (RAS) have gained popularity, and has overthrown the traditional flow through systems used in the freshwater stages of the Atlantic salmon production. This is a closed system with less water consumption, but extended water treatment. Despite the many advantages, opportunistic bacteria seem to thrive in in such closed and biological system. Since 2007 there have been an increase in the number of yersiniosis outbreaks. Many of these outbreaks have been in RAS, or in fish in sea cages that originated from infected RAS. The causative bacterium Yersinia ruckeri is capable of forming biofilm, thus making it hard to remove during disinfection. The bacterium can be treated with antibiotics, but facing the worldwide problem of antibiotic resistance, other alternatives are highly needed. One of the alternatives suggested is phage therapy. The long-forgotten method of using bacteria infecting viruses for biocontrol is now being studied again in aquaculture. Bacteriophages infecting Y. ruckeri were investigated in this study. Four different lytic phages and a cocktail including the four were delivered by ACD Pharmaceuticals. They were all tested in growing cultures of Y. ruckeri, where they all showed a good bacteriostatic effect. This indicates that the bacteriophages have a god potential for application in bio treatment of water and filters used in rearing of fish larva and fish. We studied the ability of salmon to produce anti-phage specific antibodies. This was done by immunization of salmon with phage as antigen, and the fish was injected three times with inactivated bacteriophages. The fish antisera were tested with enzyme-linked immunosorbent assay (ELISA), and all sera showed a high production of anti-phage antibodies in the fish given injection with phages alone or combined with adjuvance. The non-vaccinated (no phage antigen) control fish groups did not show any anti-phage antibody production. A neutralization test was performed using sera containing anti-phage antibodies, which proved that antibodies are highly neutralizing the bacteriolytic ability of the phages. In summary the results showed that the phages used alone or in combination were highly bacteriostatic for Y. ruckeri. The ELISA test using bacteriophage as antigen can be used for screening of salmon sera after various exposure to bacteriophages. The immunsera can serve as positive controls. Thus, a screening method for anti-phage antibodies has been established.Store fremskritt innen Norsk akvakultur har ført til nye teknologier innenfor produksjon av Atlantisk laks. De siste 10 årene har resirkuleringsanlegg økt massivt i popularitet, og har erstattet de tradisjonelle gjennomstrømsanleggene som brukes i ferskvannsfasen av lakse produksjonen. Dette er lukkede systemer med mindre forbruk av vann men krever mer vannbehandling. Til tross for mange fordeler, ser det ut til at opportunistiske bakterier trives godt i slike lukkede biologiske systemer. Siden 2007 har det vært en økning i antall utbrudd av yersiniose hvor de fleste har vært i resirkuleringsanlegg, eller i sjøanlegg hvor fisken kommer fra et infisert resirkuleringsanlegg. Yersinia ruckeri er den forårsakende bakterien til yersiniose, og den er i stand til å danne biofilm, noe som gjør den i stand til å overleve desinfeksjon. Bakterien kan behandles med antibiotika, men nå som verden står ovenfor problemer rundt antibiotikaresistens, er andre alternativer ønsket. Et av disse alternativene er fag terapi. Den gamle metoden der bakterie infiserende virus brukes til biokontroll blir nå forsket på igjen. Bakteriofager mot Y. ruckeri ble i dette studiet undersøkt. Fire forskjellige lytiske fag samt en cocktail som inneholdt alle fire ble levert av ACD Pharmaceuticals. De ble alle testet i voksende kulturer av Y. ruckeri, hvor de alle viste en god bakteriostatisk effekt. Dette indikerer en at bakteriofager har et stort potensiale for bruk innen biokontroll av vann og filter brukt i akvakultur av fisk og fiskelarver. I dette studiet ble laksens evne til å produsere bakteriofag spesifikke antistoff studert. Dette ble gjort ved å immunisere laks med fag som antigen. For å oppnå en høy antistoffrespons, ble fisken injisert tre ganger med inaktiverte bakteriofager. Fiskenes antiserum ble deretter testet med enzyme-linked immunosorbent assay (ELISA), hvor alle fiskene som hadde blitt injisert med inaktiverte fag viste en høy anti-fag antistoffrespons. De uinjiserte kontrollfiskene viste ingen antistoff produksjon. En nøytralisasjonstest ble gjort på antistoffene fra fisken med høy antistoffrespons, som viste at antistoffene er svært nøytraliserende på den bakteriolytiske effekten til bakteriofagene. Resultatene viste at fag brukt alene eller i kombinasjon er svært bakteriostatisk for Y. ruckeri. ELISA testen med bakteriofager som antigen kan brukes for screening av lakseserum etter ulike eksponeringer for fag. Immunserumet kan brukes som en positiv kontroll. Dermed har en screening metode for anti-fag antistoff blitt etablert.Masteroppgave i fiskehelseMAMN-FISKFISK39

An Antibiotic Discovery Campaign Targeting VirF, the Main Transcriptional Regulator of Virulence in Shigella flexneri

Shigella flexneri is a gram-negative enteropathogen that infects the human colonic epithelium. It is estimated that Shigella spp. infect 165 million people a year worldwide. Symptoms of shigellosis include bloody dysentery, dehydration, and ultimately death if the infection is not treated properly. The current recommended first-line treatment for shigellosis is ciprofloxacin; however, many new multi-drug resistant strains of Shigella have begun to emerge. The emergence of these strains, along with the lack of novel antibiotics in the drug pipeline, makes the need for new effective treatments for shigellosis a priority. Genetic knockout studies have shown that VirF, the main transcriptional activator of the Shigella pathogenesis cascade, is necessary for virulence, but not bacterial viability. We hypothesized that a novel anti-virulence therapy for shigellosis could be developed through the inhibition of VirF. To identify inhibitors of VirF, we performed a high-throughput screening (HTS) campaign testing over 140,000 small molecules and 20,000 natural product extracts using a Shigella-based, VirF-driven, β-galactosidase reporter assay. Following a series of confirmation screens, we identified five compounds from the HTS campaign that had VirF inhibitory properties. Using tissue culture-based models of the S. flexneri infection process, we were able to show that three of compounds were able to attenuate the virulence of S. flexneri, thereby, validating VirF as a target for the treatment of shigellosis. To further characterize the hits from the HTS campaign a series of established in vitro assays were adapted and optimized for VirF. An electrophoretic mobility shift assay and a fluorescence polarization assay were used to monitor VirF binding to the virB promoter, and a fluorescence intercalator displacement assay was used to determine if the hits could directly bind DNA. Using these assays, we were able to determine the mechanism of inhibition (blockade of VirF binding to the virB promoter) and preliminary structure-activity relationship trends for one of the hits, and report the first dissociation constant for VirF binding to the virB promoter (2.8 ± 1.0 μM).PhDMedicinal ChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/120884/1/aae_1.pd

MALDI-TOF mass spectrometry technology in the diagnosis of antibiotic resistance

MALDI-TOF; Mass spectrometry technology; Diagnosis; Infectious diseaseMALDI-TOF; Espectrometria de masses; Resistència als antibiòtics; Diagnòstic; Malaltia infecciosaMALDI-TOF; Espectometría de masas; Resistencia a antibióticos; Diagnóstico; Enfermedad infecciosaEn cualquier enfermedad infecciosa, la administración de un tratamiento antibiótico adecuado en el momento oportuno y necesario es clave para la curación y evolución del paciente, y también para reducir su morbimortalidad. Por ello, es determinante que el diagnóstico y tratamiento de la enfermedad se lleven a cabo con la máxima celeridad posible. El creciente aumento de la incidencia de infecciones causadas por microorganismos resistentes (o multirresistentes) a los antibióticos disponibles actualmente provoca una alta probabilidad de error en su tratamiento como ocurre, por ejemplo, en los casos de infecciones graves, el tratamiento de las cuales, debido a su urgencia, suele elegirse empíricamente, sin esperar los resultados de sensibilidad. De hecho, se estima que la elección del antibiótico, las indicaciones y la duración del tratamiento para las enfermedades infecciosas son erróneas en un 30-50% de los casos1. Esto no solo conduce a un incremento de la morbimortalidad de estas enfermedades, sino que, aún más importante, promueve la aparición y diseminación de resistencias antimicrobianas entre los microorganismos patógenos. Precisamente, la elevada tasa de error en el tratamiento de las enfermedades infecciosas, junto con el uso descontrolado de los antibióticos de las últimas décadas tanto por parte de los profesionales clínicos prescriptores, como por los pacientes y la industria agropecuaria, es lo que ha causado que en el presente exista un número alarmante de microorganismos resistentes y, en consecuencia, haya incrementado la incidencia de enfermedades infecciosas de difícil tratamiento y la mortalidad asociada a estas. Por consiguiente, es prioritario adoptar medidas que permitan revertir y controlar esta situación.En qualsevol malaltia infecciosa, l’administració d’un tractament antibiòtic adequat en el moment oportú i necessari és clau per a la curació i evolució del pacient, i també per reduir la seva morbimortalitat. Per això, és determinant que el diagnòstic i tractament de la malaltia es duguin a terme amb la màxima celeritat possible. El creixent augment de la incidència d’infeccions causades per microorganismes resistents (o multiresistents) als antibiòtics disponibles actualment provoca una alta probabilitat d’error en el seu tractament com passa, per exemple, en els casos d’infeccions greus, el tractament de les quals, a causa de la seva urgència, sol elegir-se empíricament, sense esperar els resultats de sensibilitat. De fet, s’estima que l’elecció de l’antibiòtic, les indicacions i la durada del tractament per a les malalties infeccioses són errònies en un 30-50% dels casos. Això no només condueix a un increment de la morbimortalitat d’aquestes malalties, sinó que, encara més important, promou l’aparició i disseminació de resistències antimicrobianes entre els microorganismes patògens. Precisament, l’elevada taxa d’error en el tractament de les malalties infeccioses, juntament amb l’ús descontrolat dels antibiòtics de les últimes dècades tant per part dels professionals clínics prescriptors, com pels pacients i la indústria agropecuària, és el que ha causat que en el present existeixi un nombre alarmant de microorganismes resistents i, en conseqüència, hagi incrementat la incidència de malalties infeccioses de difícil tractament i la mortalitat associada a aquestes. Per tant, és prioritari adoptar mesures que permetin revertir i controlar aquesta situació.In any infectious disease, the administration of a suitable antibiotic treatment in the appropriate and necessary moment is key for the care and evolution of the patient, and also to reduce its morbimortality. Because of that, it is determining that the diagnostic and treatment of the disease were carried out as soon as possible. The increasing incidence of caused infections for resistant pathogens (or multiresistant) to the available antibiotics provokes a high probability of error in its treatment. For instance it happens in the cases of severe infections, the treatment of which, because of being urgent, is usually chosen empirically, without expecting the outcomes of sensitivity. In fact, it is estimated that the choice of the antibiotic, the indications and the duration of the treatment for the infectious diseases are erroneous in 30-50% of the cases. This not only it drives to an increase of the morbimortality of these diseases, but, still more important, it promotes the appearance and dissemination of antimicrobic resistances among the pathogenic microorganisms. Precisely, the high error rate in the treatment of the infectious diseases, together with the uncontrolled use of antibiotics in the last decades has caused that today there is an alarming number of resistant pathogens and, consequently, an increase of the incidence of infectious diseases of difficult treatment and the mortality associated with these ones. Therefore, it is preferential to adopt measures that allow to revert and to control this situation

Gesundheitsökonomische Evaluation von Krankenhausinfektionen

Nosokomiale Infektionen oder Krankenhausinfektionen sind eine schwerwiegende Komplikation im Krankenhaus und erhöhen sowohl die Morbidität als auch die Mortalität (Klevens et al., 2007, Hagel et al., 2013). Sie führen zu zusätzlichen Behandlungen und Schmerzen, darüber hinaus verlängern sie die Verweildauer für die betroffenen Patienten (De Angelis et al., 2010, Manoukian et al., 2018). Weiterhin verursachen sie zusätzliche Kosten für den Krankenhausträger und für das Gesundheitssystem (Marchetti und Rossiter, 2013, Stone, 2009). Wenn eine Infektion bei Krankenhausaufnahme weder vorhanden noch in der Inkubationsphase war, wird sie als nosokomial bezeichnet (Geffers et al., 2002). Eine nosokomiale Infektion ist nach § 2 Infektionsschutzgesetz–IfSG wie folgt definiert: „eine Infektion mit lokalen oder systemischen Infektionszeichen als Reaktion auf das Vorhandensein von Erregern oder ihrer Toxine, die im zeitlichen Zusammenhang mit einer stationären oder einer ambulanten medizinischen Maßnahme steht, soweit die Infektion nicht bereits vorher bestand“ (Robert Koch Institut, 2011b). Lokale oder systemische Anzeichen einer Infektion müssen nach Definition des Center for Disease Control and Prevention (CDC) bei der Diagnose einer nosokomialen Infektion nachgewiesen werden. Sie werden erst als nosokomial bezeichnet, wenn die Patienten mindestens 48 Stunden im Krankenhaus verbracht haben (Robert Koch Institut, 2011a). Es ist zu berücksichtigen, dass unterschiedliche Infektionen unterschiedliche Inkubationszeiten aufweisen, so dass jedes Ereignis einzeln ausgewertet werden muss, um die Beziehung zwischen seinem Auftreten und dem Krankenhausaufenthalt festzustellen (Gastmeier, 2016)

Investigating wastewater treatment plant impact on antibiotic resistance within UK river systems.

Antimicrobial resistance (AMR) presents one of the most important threats to human health of the 21st century. The recent report on AMR predicted that by 2050 10 million deaths a year will be directly attributable to AMR bacterial infections. The dissemination of antibiotic resistance genes (ARG) in to the environment has previously been highlighted as an important route of transmission and was investigated in the current study. Wastewater treatment plants (WWTP) have been highlighted to contribute to ARG pollution of rivers focusing on effluent impact on receiving water bodies. In this study the aim was to further investigate the effects of WWTP effluent on the receiving river, but also investigate the release of raw sewage resulting from combined sewer overflow (CSO) events on the receiving river. This study found that sediment samples carried a higher abundance of all ARG and therefore present a greater risk compared to water and that CSO spills are important in the spread of ARG likely contributing more substantially to the environmental spread of resistance than continuous release of treated wastewater. In addition, the present study aimed to investigate the genetic potential of viable, potentially pathogenic Escherichia coli isolates from the river sediment to determine whether these human opportunistic pathogens carried the genetic capacity to spread resistance and cause disease. E. coli strains were shown to carry extensive resistance to many clinically relevant antibiotics, metals and biocides as well as carrying vast virulence-associated genes. This study identified ST940 as an important sequence type (ST) in the dissemination of the ESBL blaCTX-M-15 gene and suggests further work to investigate the importance of this ST type in the transmission of this clinically important ARG. The work presented here supports previous studies demonstrating extensive environmental ARG dissemination in rivers as a direct result of WWTP impacts and further highlights rivers as an important reservoir of ARG and antibiotic resistant bacteria (ARB). The discovery of clinically important viable E. coli isolates in sediment suggests more rigorous methods of wastewater treatment, specifically a reduction in the number of CSO release events, must be employed if further dissemination of ARB is to be prevented