The study explored the prevalence of biofilm formers and its association with multidrug resistance in Klebsiella Pneumonia, a gram-negative bacterium that has high propensity to form antibiotic resistant strains and forms biofilms. Biofilms are complex microbial community with attributes that vary from planktonic cells. Antibiotic resistance is a property that has shown evidence to be higher in biofilms as compared to planktonic cells. Multi-drug resistance, a higher form of antibiotic resistance, is defined as resistance to at least one agent in three or more antibiotic categories. A single-armed and a two-armed meta-analysis was done to assess prevalence of biofilm formers and to find association between biofilm formation capacity and multi drug resistance. The one-armed meta-analysis revealed 74% (95% CI: 64%-83%) prevalence of biofilm formers among clinical isolates of Klebsiella Pneumonia. The prevalence rate is comparable with that of prevalence rate attained by other bacterium by similar meta-analysis studies. This high prevalence of biofilm formers warrants for a paradigm shift in treatment strategies for treatment of infections. The two-armed meta-analysis showed that there was identical risk of multi drug resistance among the biofilm formers and non-biofilm formers. The result challenges the intrinsic capacity of planktonic cells to resist against antibiotics to achieve multi drug resistance. Further research to update the biofilm formation profiles and to understand the resistance mechanism in commonly occurring bacterial infections in of utmost importance.

Until now, tracing the genealogical lines of EEC/EU Antibiotic Resistance policy has been a gap in social science research that has focused on the policies of individual countries. This Working Paper raises the question how Antimicrobial Resistance (AMR) has developed as an epistemic object in terms of biopolitical and spatial regulatory design of EEC/EU. It also asks what cultural ideas and imaginations have been associated with antibiotics since their introduction. To this end, a historical discourse analysis was conducted combining the perspectives of human geography and historical sociology. First cases of resistance occurred at short intervals with the introduction of new antibiotics in both human and veterinary medicine, and the discovery of the mechanism of horizontal gene transfer attracted global attention in the 1960s. Nevertheless, the belief in the need for an expansionary mode of production outweighed scientific doubt and the longer-term health of the population, so that regulatory interventions were more appearance than substance. Only in the wake of the geopolitical rise of the EU and BRICS countries and new ‘pandemic risks’, a general turn to security dispositif and neoliberal-individualist governmentality rearranged the coordinates of AMR policy to some extent. The interpretation of our present as a “multi-crisis”, which has become increasingly established in the “West” in the wake of climate crisis and Covid19, is apparently contributing to an increasing assessment of AMR as an unintended side-effect of an expansionary economy and lifestyle, with no regulatory responses to date that address systemic causes rather than suggesting a fiction of control.

Bakgrund: Antibiotikaresistens är ett allt större globalt problem och ett hot mot människan och deras hälsa. Utan antibiotika kommer rutinmässiga behandlingsmetoder och ingrepp inte längre kunna utföras utan stora risker och dödligheten av bakteriella infektioner kommer öka signifikant. Syfte: Syftet var att beskriva sjuksköterskans roll i att förebygga utveckling av antibiotikaresistens inom vården. Metod: En litteraturöversikt genomfördes av tio vetenskapliga artiklar. Databaserna CINAHL och PubMed användes till datainsamlingen och resultatet analyserades enligt Fribergs metod. Resultat: Utifrån dataanalysen framkom fyra teman: upprätthålla och följa riktlinjer, kommunicera och arbeta som patientförespråkare, använda uppdaterad och evidensbaserad kunskap och utbilda patienter och närstående. Slutsats: Sjuksköterskan spelar en viktig roll i förebyggandet av antibiotikaresistens. Med hänsyn till en hållbar framtid har sjuksköterskan ett ansvar för att främja hälsa hos dagens patienter samtidigt som framtida patienters hälsa inte ska äventyras. / Background: Antibiotic resistance is a growing problem globally and a threat to people and their health. Without antibiotics, routine treatment and interventions will no longer be without great risk and mortality rates from bacterial infections will increase significantly. Aim: The aim was to describe nurse’s role in preventing development of antibiotic resistance within the healthcare system. Method: A literature review of ten scientific articles was conducted. Databases CINAHL and PubMed were used for data collection and the results were analysed according to Friberg’s method. Results: Based on the data analysis, four themes emerged: maintaining and following guidelines, communicating and working as patient advocate, using updated and evidence-based knowledge, and educating patients and their families. Conclusions: The nurse plays a crucial role in preventing antibiotic resistance. Considering a sustainable future, the nurse has a responsibility to promote the health of today's patients while ensuring that the health of future patients is not compromised.

Antibiotic-resistant bacterial infections account for millions of human fatalities each year, with drug susceptibility testing (DST) affordability being limited by instrumentational constraints, monetary and/or time expenses. Molecular diagnostics performed at the point of care can provide a solution. Split probes coupled with label-free reporters like Fluorescent Light-up APtamers (FLAPs) are promising for point-of-care DST as they offer the needed selectivity towards point mutations inducive of drug resistance. This project aims at bridging the gap in FLAP applications for molecular diagnostics with a focus on multiplexing the analysis. Due to the limited number of DNA FLAPs available, we explored the ability of one of the most efficient DNA FLAPs - dapoxyl binding aptamer (DAP) - to bind fluorogens with different spectral properties. We performed the rational mutagenesis of the DAP dye-binding core to reveal any sequence-function correlations and to identify prospective orthogonal FLAP-dye pairs. Orthogonal FLAPs were used as scaffolds to design split dapoxyl aptameric (SDA) probes, which targeted a fragment of the katG gene from Mycobacterium tuberculosis complex associated with bacterial resistance to a first-line antituberculous drug isoniazid (INH). The probes were tested to differentiate the nucleic acid targets with single-nucleotide variations corresponding to isoniazid-susceptible (INHS) and isoniazid-resistant (INHR) bacterial phenotype in a multiplex fashion. With proper optimization of the probes, they can find an application in ratiometric analysis of heterogeneous bacterial populations composed of both drug-susceptible and drug-resistant strains and thus help in initial diagnosing of infectious diseases and in monitoring the therapy outcomes.

Neonatal sepsis caused by resistant bacteria is a worldwide concern due to the associated high mortality and increased hospitals costs. Bacterial pathogens causing neonatal sepsis and their antibiotic resistance patterns vary among hospital settings and at different points in time. This study aimed to determine the antibiotic resistance patterns of pathogens causing neonatal sepsis and to assess trends in antibiotic resistance. The study was conducted among neonates with culture proven sepsis at the University Hospital of Leipzig between November 2012 and September 2020. Blood culture was performed by BacT/ALERT 3D system. Antimicrobial susceptibility testing was done with broth microdilution method based on ISO 20776-1 guideline. Data were analyzed by SPSS version 20 software. From 134 isolates, 99 (74%) were gram positive bacteria. The most common gram positive and gram negative bacteria were S. epidermidis, 51 (38%) and E. coli, 23 (17%), respectively. S. epidermidis showed the highest resistance to penicillin G and roxithromycin (90% each) followed by cefotaxime, cefuroxime, imipenem, oxacillin, and piperacillin-tazobactam (88% each), ampicillin-sulbactam (87%), meropenem (86%), and gentamicin (59%). Moreover, S. epidermidis showed raising levels of resistance to amikacin, gentamicin, ciprofloxacin, levofloxacin, moxifloxacin, and cotrimoxazol. Gram positive bacteria showed less or no resistance to daptomycin, linezolid, teicoplanin, and vancomycin. E. coli showed the highest resistance to ampicillin (74%) followed by ampicillin-sulbactam (52%) and piperacillin (48%). Furthermore, increasing levels in resistance to ampicillin, ampicillin-sulbactam, piperacillin, and cefuroxime were observed over the years. Encouragingly, E. coli showed significantly declining trends of resistance to ciprofloxacin and levofloxacin, and no resistance to amikacin, colistin, fosfomycin, gentamicin, imipenem, piperacillin-tazobactam, and tobramycin. In conclusion, this study demonstrates that gram positive bacteria were the leading causes of neonatal sepsis. Bacterial isolates were highly resistant to first and second-line empiric antibiotics used in this hospital. The high levels of antibiotic resistance patterns highlight the need for modifying empiric treatment regimens considering the most effective antibiotics. Periodic surveillance in hospital settings to monitor changes in pathogens, and antibiotic resistance patterns is crucial in order to implement optimal prevention and treatment strategies.

No description available.

Antibiotic resistance (AR) is a pervasive crisis that is intricately woven into social and environmental systems. Its escalation is fueled by factors such overuse, poverty, climate change, and the heightened interconnectedness characteristic of our era of globalization. In this dissertation, the impact of antibiotic usage is addressed from the perspective of wastewater-based surveillance (WBS) at the wastewater treatment plant (WWTP) and microbial ecology. Antibiotic usage and contamination was found to influence the prevalence of antibiotic resistance genes (ARGs) and resistant bacteria in both lab-scale and full-scale wastewater treatment settings. Through application of novel bioinformatic approaches developed herein, metagenomics revealed associations between sewage-associated microbes and community antibiotic use that were in part mediated by microbial ecological processes and horizontal gene transfer (HGT). In sum, this dissertation increases the arsenal of bioinformatic tools for AR surveillance in wastewater environments and advances knowledge with respect to the contribution of antibiotic use to the spread of antibiotic resistance at the community-scale. Three studies served to evaluate and/or develop bioinformatic resources for molecular characterization of AR in wastewater. Hybrid assembly combining emerging long read DNA sequencing and short read sequencing was evaluated and found to improve accuracy relative to assembly of long or short reads alone. A novel database of mobile genetic element (MGE) marker genes, mobileOG-db, was compiled in order to address short-comings with pre-existing resources. A pipeline for detecting HGT in metagenomes, Kairos, was created in order to facilitate the detection of HGT in metagenome assemblies which greatly amplified coverage of ARGs. In Chapter 5, a lab-scale study of WWTP bioreactors revealed that elevated antibiotic contamination was correlated with increased prevalence of corresponding ARGs. In addition, multiple in situ HGT events of ARGs encoding resistance to the elevated antibiotics were predicted, including one HGT event likely mediated by a novel bacteriophage. In Chapter 6, influent and effluent from a full-scale municipal WWTP were collected twice-weekly for one year and subjected to deep shotgun metagenomic sequencing. In parallel, collaboration with clinicians enabled statistical modeling of antibiotic usage and resistance, revealing associations between antibiotic prescriptions patterns in the region and resistance at the WWTP. Finally, Chapter 7 details bioinformatic recovery of diverse extended spectrum beta-lactamase gene recovery from the influent and effluent metagenomes, shedding light on the dynamics of circulating resistance genes. In sum, this dissertation identifies bioinformatic evidence for the selection of AR in wastewater environments as a result of antibiotic use in the community and advances hypotheses for explaining the mechanisms of the observed phenomena. / Doctor of Philosophy / Antibiotics are key lifesaving drugs that have dramatically improved life expectancy throughout the 20th and 21st centuries. However, there has been an increased incidence of resistance among many important bacterial pathogens in recent decades. The more antibiotics are used, the more chance that resistant bacteria can evolve, survive, and spread. Outpatient care accounts for the vast majority of therapeutic antibiotic use, with more than 200 million prescriptions written for antibiotics in 2021 in the United States. While performing a vital function in combatting disease, oral antibiotics can inadvertently harm the resident microbes of the intestinal tract (i.e., the gut microbiome) by decreasing the diversity of the microbes present and increasing the number of resistant bacteria. At a community level, antibiotic usage also has the potential to induce increased prevalence of antibiotics and antibiotic resistant bacteria in the environment as well, primarily via human excreta (urine and feces). Wastewater represents a key interface between human-derived contaminants and the environment. In regions with centralized wastewater management, antibiotics- and resistant bacteria-containing excreta are typically transported via sewage conveyance systems to a wastewater treatment plant (WWTP). At the WWTP, diverse microbes interact with and degrade various organic contaminants in a series of processes combining physical, chemical, and biological treatments. Due to the intermingling of environmental microbes, antibiotics, and antibiotic resistant bacteria, wastewater is increasingly being recognized as an important venue for antibiotic resistance surveillance and for potential interventions. Awareness of wastewater-based surveillance and epidemiology has surged as a result of the COVID-19 pandemic and such efforts are enshrined in the National COVID-19 Preparedness Plan. However, such a task is fundamentally more challenging for antibiotic resistance than for SARS-CoV-2, as it comprises multiple bacterial strains, antibiotic resistance genes, and resistance mechanisms. In this respect, DNA sequencing of wastewater, i.e., "metagenomics," holds promise as a broad monitoring tool with an unprecedented degree of biological granularity. In this dissertation, we address the impact of antibiotic usage at the WWTP from the perspective of wastewater-based surveillance. We evaluate antibiotic usage at the community-scale as a selective force among bacteria inhabiting WWTPs and identify microbial interactions that influence the escape of resistant bacteria in the effluent. A field-study of wastewater entering the WWTP and cleaned effluent water discharged by the WWTP revealed certain antibiotics and corresponding forms of antibiotic resistance were particularly prone to proliferation in the WWTP. Novel bioinformatic tools were developed and applied to the study of wastewater to reveal these associations. In sum, this dissertation advances knowledge of wastewater as both a mediator of environmental health and as a reflection of community-health in the form of antibiotic resistance.

Objective: Currently, there does not exist a cohesive and predictive set of criteria that can be used to identify patients that are at risk of being non-adherent to antibiotic regimens. In this study, we sought to answer the question of whether patients’ knowledge of the scientific background of antibiotic resistance is related to their likelihood to adhere to antibiotic regimens. Additionally, we explored other facets of the profiles of adherent and non-adherent subjects. Methods: All responses were collected via questionnaire. Subjects were split into two groups (adherent and non-adherent) based upon four patient-behavior questions. These two groups of subjects were compared in a variety of ways to test for significant differences in categories such as science knowledge, age, and self-reported understanding of the problem of antibiotic resistance. Results: It was determined that the adherent group of subjects had significantly higher science scores (mean=5.46, n=384) than the non-adherent subjects (mean=4.99, n=460); t(842)= -2.73, p=0.0064. Subjects majoring in STEM were more likely to be adherent than biology or non-STEM majors. There were no differences in adherence or science scores across age groups. About 26% of subjects had not previously heard of the problem of antibiotic resistance. Discussion: Increasing patient education on the topic of antibiotic resistance could increase patient adherence, which could in turn lead to a reduction in the rate at which bacteria develop resistance. Initiatives to educate patients and health care professionals have the potential to increase understanding and improve rates of adherence.

Antibiotic resistant strains of bacteria continue to increase in prevalence, hindering the ability of clinicians to treat infection. One disease exacerbated by this trend is osteomyelitis, or bone infection. When osteomyelitis is induced by these antibiotic resistant strains, patients can experience prolonged hospital visits, greater economic burdens, amputation, and even death. Due to the limitations of antibiotics to clear these infections, we sought to identify new therapeutic options for osteomyelitis. Our aim was to first develop an in vivo implant-related model of osteomyelitis. We then wanted to explore the potential of novel CRISPR-Cas9 modified bacteriophage to treat infection. In vitro and in vivo investigations demonstrated that bacteriophage therapeutic may be a viable option for infection mitigation. Furthermore, our in vivo model of osteomyelitis proved to be reliable, consistent, and challenging. Future research will utilize this model as a platform for optimizing therapeutic regimen and delivery vehicle(s) for antimicrobial therapeutics.

No description available.