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Fluoroquinolones are widely prescribed antibiotics with well-known, mostly transient adverse effects, the most common of which are gastrointestinal disturbances, headaches, dizziness, rash, etc. However, a less recognized yet profoundly debilitating complication exists known as fluoroquinolone-associated disability (FQAD), operationally defined as impacting at least two systems (neurological, musculoskeletal, psychiatric, and/or cardiovascular) for at least 30 days post-cessation of a fluoroquinolone and with an outcome reported as disability. Unfortunately, this syndrome has yet to be formally recognized by the medical community. As such, FQAD patients are rarely diagnosed and undergo extensive diagnostic testing, leading to unnecessary costs to the patient and our healthcare system. Herein, we present the case of a 41-year-old male patient who developed acute bilateral numbness and tingling in his upper and lower extremities after just two doses of ciprofloxacin for epididymitis. Despite extensive evaluations from various specialists and therapists over the following 18 months, his symptoms continued to progress without any clear insight into the cause of his symptoms. He eventually reached out to an FQAD specialist due to his own suspicions and began therapy with hyperbaric oxygen, IV magnesium, and IV glutathione. Mild improvement was noted from these therapies, but he was unable to undergo regular treatments due to the financial debt acquired from his extensive medical workups and ultimately stopped treatment completely without any further improvements. Our case report highlights the importance of early recognition of FQAD to start prompt treatment and avoid costly testing. Overall, we aim to raise awareness of FQAD among clinicians as a potential complication of fluoroquinolone use.

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INTRODUCTION:  Antibiotics are vital in managing infectious diseases that significantly burden health infrastructure in a developing country like India. However, the widespread and irrational use of antibiotics has given rise to the menace of antibiotic resistance that threatens to take us back to the pre-antibiotic era. Our study aimed to evaluate the baseline compliance to antibiotic policy in the pediatric inpatient ward and analyze the impact of interventions on compliance with the policy. MATERIALS AND METHODS:  The prospective study was done at MGM Medical College and Hospital, Aurangabad. The study included infants and children from one month to 18 years of age admitted to the pediatric ward. Patients' prescription charts were evaluated in 375 patients during the first three months of the study, and prescribed antibiotics were recorded and compared with standard treatment guidelines. The intervention included awareness, educational, and feedback sessions regarding antibiotic prescription policies. The antibiotics prescribed were analyzed in 375 patients during the next three months. RESULTS:  We found out that in the pre-intervention and post-intervention phases, out of a total of 375 patients, 60% and 46.1% were on antimicrobials, respectively. Out of those who were on antimicrobials, only 46% were compliant with the policy initially. That increased to 61% after the intervention. CONCLUSION:  Awareness, education, and feedback regarding antibiotic prescription policy as an intervention helped increase compliance, though not to the desired level of more than 90%. Continuous cycles of awareness and feedback help achieve better compliance.

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Bacterial growth and metabolic rates are often closely related. However, under antibiotic selection, a paradox in this relationship arises: antibiotic efficacy decreases when bacteria are metabolically dormant, yet antibiotics select for resistant cells that grow fastest during treatment. That is, antibiotic selection counterintuitively favors bacteria with fast growth but slow metabolism. Despite this apparent contradiction, antibiotic resistant cells have historically been characterized primarily in the context of growth, whereas the extent of analogous changes in metabolism is comparatively unknown. Here, we observed that previously evolved antibiotic-resistant strains exhibited a unique relationship between growth and metabolism whereby nutrient utilization became more efficient, regardless of the growth rate. To better understand this unexpected phenomenon, we used a simplified model to simulate bacterial populations adapting to sub-inhibitory antibiotic selection through successive bottlenecking events. Simulations predicted that sub-inhibitory bactericidal antibiotic concentrations could select for enhanced metabolic efficiency, defined based on nutrient utilization: drug-adapted cells are able to achieve the same biomass while utilizing less substrate, even in the absence of treatment. Moreover, simulations predicted that restoring metabolic efficiency would re-sensitize resistant bacteria exhibiting metabolic-dependent resistance; we confirmed this result using adaptive laboratory evolutions of Escherichia coli under carbenicillin treatment. Overall, these results indicate that metabolic efficiency is under direct selective pressure during antibiotic treatment and that differences in evolutionary context may determine both the efficacy of different antibiotics and corresponding re-sensitization approaches.IMPORTANCEThe sustained emergence of antibiotic-resistant pathogens combined with the stalled drug discovery pipelines highlights the critical need to better understand the underlying evolution mechanisms of antibiotic resistance. To this end, bacterial growth and metabolic rates are often closely related, and resistant cells have historically been characterized exclusively in the context of growth. However, under antibiotic selection, antibiotics counterintuitively favor cells with fast growth, and slow metabolism. Through an integrated approach of mathematical modeling and experiments, this study thereby addresses the significant knowledge gap of whether antibiotic selection drives changes in metabolism that complement, and/or act independently, of antibiotic resistance phenotypes.

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Antibacterianos , Escherichia coli , Antibacterianos/farmacología , Escherichia coli/genética , Farmacorresistencia Microbiana

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Objective: Assess urgent care (UC) clinician prescribing practices and factors associated with first-line antibiotic selection and recommended duration of therapy for sinusitis, acute otitis media (AOM), and pharyngitis. Design: Retrospective cohort study. Participants: All respiratory UC encounters and clinicians in the Intermountain Health (IH) network, July 1st, 2019-June 30th, 2020. Methods: Descriptive statistics were used to characterize first-line antibiotic selection rates and the duration of antibiotic prescriptions during pharyngitis, sinusitis, and AOM UC encounters. Patient and clinician characteristics were evaluated. System-specific guidelines recommended 5-10 days of penicillin, amoxicillin, or amoxicillin-clavulanate as first-line. Alternative therapies were recommended for penicillin allergy. Generalized estimating equation modeling was used to assess predictors of first-line antibiotic selection, prescription duration, and first-line antibiotic prescriptions for an appropriate duration. Results: Among encounters in which an antibiotic was prescribed, the rate of first-line antibiotic selection was 75%, the recommended duration was 70%, and the rate of first-line antibiotic selection for the recommended duration was 53%. AOM was associated with the highest rate of first-line prescriptions (83%); sinusitis the lowest (69%). Pharyngitis was associated with the highest rate of prescriptions for the recommended duration (91%); AOM the lowest (51%). Penicillin allergy was the strongest predictor of non-first-line selection (OR = 0.02, 95% CI [0.02, 0.02]) and was also associated with extended duration prescriptions (OR = 0.87 [0.80, 0.95]). Conclusions: First-line antibiotic selection and duration for respiratory UC encounters varied by diagnosis and patient characteristics. These areas can serve as a focus for ongoing stewardship efforts.

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Introduction: Decision-making for inpatient antibiotic prescribing is complex due to many considerations to be taken. So far, clinical decision support systems (CDSS) have been rarely used in antibiotic stewardship (ABS) and even less integrated in computerized physician order entry systems (CPOE). Methods: We developed a guideline-based, CPOE-integrated CDSS (ID ANTIBIOTICS) to support antibiotic selection and dosing. We compared routine antibiotic inpatient prescribing data with CDSS-generated recommendations in the initial antibiotic selection, the duration of therapies, and costs. Finally, we assessed possible benefits of the CDSS by its performance in German ABS-guideline quality indicators (ABS-QIs). Results: The requirements of several ABS-QIs can be supported with ID ANTIBIOTICS: electronic local guidelines, electronic decision-support, renal dosage adjustments, local guideline-based initial selection (all not quantified), and therapy durations for the treatment of pneumonia (significantly) without increasing costs. Performance in ABS-QIs for extensive therapies for community-acquired pneumonia could be improved with the CDSS by 20.2% (OR 0.134; 95% CI: 0.101-0.178); for hospital-acquired pneumonia by 3.7% (OR 0.742; 95% CI: 0.629-0.877). There was no difference in median daily drug costs between real-world prescriptions and CDSS recommendations (both: € 4.78, p=0.081). Conclusions: In retrospective analyses, antibiotic CDSS can show possible performance in antibiotic stewardship through quality indicators (ABS-QIs). Further research and pilot testing of the software are needed to provide more insights into ABS-QI evaluation, user acceptance, and real-world effectiveness. Deep integration of antibiotic CDSS into existing medication processes without using multiple systems could contribute to the necessary acceptance of clinical practitioners.

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Background: Despite advances in infection control measures, surgical site infections (SSIs) remain a real and present danger to patients. In most studies addressing SSI prevention measures, recommendations are often made in the absence of information such as culture results, the antibiotic agents used for prophylaxis, and antibiotic sensitivity data. The aim of this study is to document this latter claim by reviewing studies published in the last five years in highly read and cited surgical journals. Methods: A systematic review evaluating SSIs from four highly cited surgical journals, Annals of Surgery, the British Journal of Surgery, JAMA Surgery, and the Journal of the American College of Surgeons was conducted for articles published between 2016 and 2021. We focused our analysis on the following key features: how SSI is defined; bacterial culture information; antibiotic sensitivity data; and identification of the antibiotic chosen for prophylaxis. We hypothesized that, in most cases among the journals queried, this information would be unavailable. Results: Of the 71 studies included, 32 diagnosed SSIs based on criteria developed by the U.S. Centers for Disease Control and Prevention while five provided no definition of SSI. Of the 27 articles recommending increasing antibiotic usage, only one study performed antibiotic sensitivity testing to guide the antibiotic choice. Of 71 studies reviewed, only one reported all key features we considered to be important for SSI antibiotic decision-making; 46 reported none of the key features. Conclusions: Among publications addressing SSIs in four highly cited surgical journals, key information regarding diagnosis and with which to base antibiotic recommendations, is routinely unavailable.

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Antibacterianos , Infección de la Herida Quirúrgica , Estados Unidos , Humanos , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/prevención & control , Antibacterianos/uso terapéutico

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Candida albicans is a pathobiont fungus that can colonize multiple niches in the human body but is also a frequent cause of both mucosal and systemic disease. Despite its clinical importance, a paucity of dominant selectable markers has hindered the development of tools for genetic manipulation of the species. One factor limiting the utilization of dominant selectable markers is that C. albicans is inherently more resistant to antibiotics used for selection in other species. Here, we showed that the inclusion of suitable adjuvants can enable the use of two aminoglycoside antibiotics, hygromycin B and G418, for positive selection in C. albicans. Combining these antibiotics with an adjuvant, such as quinine or molybdate, substantially suppressed the background growth of C. albicans, thereby enabling transformants expressing CaHygB or CaKan markers to be readily identified. We verified that these adjuvants were not mutagenic to C. albicans and that CaHygB and CaKan markers were orthogonal to the existing marker NAT1/SAT1, and so provide complementary tools for the genetic manipulation of C. albicans strains. Our study also established that adjuvant-based approaches can enable the use of selectable markers that would otherwise be limited by high background growth from susceptible cells. IMPORTANCE Only a single dominant selectable marker has been widely adopted for use in the opportunistic fungal pathogen Candida albicans. This is in stark contrast to model fungi where a repertoire of dominant markers is readily available. A limiting factor for C. albicans has been the high levels of background growth obtained with multiple antibiotics, thereby limiting their use for distinguishing cells that carry an antibiotic-resistance gene from those that do not. Here, we demonstrated that the inclusion of adjuvants can reduce background growth and enable the robust use of both CaHygB and CaKan markers for genetic selection in C. albicans.

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Antibacterianos , Candida albicans , Biomarcadores , Candida albicans/genética , Farmacorresistencia Microbiana/genética , Humanos

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Although the isolation of Treponema pallidum subsp. pallidum (T. pallidum) from a syphilis patient dates to 1912, for the duration of the 20th century, this pathogen has remained an exceedingly difficult organism to study due to the lack of a system to support its viability in vitro. This limitation, in turn, has precluded the application of genetic engineering techniques via transformation and subsequent selection of T. pallidum transformants. A recently described method for in vitro cultivation of T. pallidum, however, has made it possible for us to experiment with transformation and selection methods. Here we describe the approach that we adopted to successfully transform T. pallidum with foreign DNA and select the resulting recombinant strain using kanamycin. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Transformation of T. pallidum Support Protocol 1: Quantification of T. pallidum in suspensions using dark-field microscopy Support Protocol 2: Counting cells using a hemacytometer Basic Protocol 2: Selection, initial passaging, and expansion of transformed cultures Basic Protocol 3: Isolation of a clonal strain through limiting dilution.

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Sífilis , Treponema pallidum , Humanos , Treponema/genética , Treponema pallidum/genética

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Camelina sativa (Camelina) is an oilseed crop that in recent years has gained importance due to its closeness to the plant model organism Arabidopsis thaliana (Arabidopsis), its low agronomical requirements, and the ability to grow under temperate conditions. To explore all the agronomical and biotechnological possibilities of this crop, it is important to evaluate the usability of the molecular procedures currently available for plants. One of the main tools for plant genetic modification and genetic studies is stable plant transformation. In the case of Arabidopsis, as well as Camelina, floral dipping is the easiest and most used method, which is followed by a selection for stable transformants. Commonly used selection methods for Camelina involve Discosoma sp. red protein (DsRed) fluorescence screening. However, many widely used plant transformation vector systems, for example those used in Arabidopsis and grasses, rely on antibiotic resistance selection. In this study, we evaluated the usability of different antibiotics including kanamycin (Kan), hygromycin (Hyg) and BASTA, and propose optimised protocols for selecting T1 and subsequent generation Camelina transformants, as well as crossing of Camelina lines expressing different transgenes. Finally, we also showed that overexpression of genes encoding enzymes from the seco-iridoid pathway of Catharanthus roseus using Hyg or BASTA-based expression constructs could be successfully achieved in Camelina, demonstrating the potential of these methods for metabolic engineering. Overall, in this study we show an efficient way to sterilize seeds, handle and perform selection of Camelina for use with transformation vectors designed for Arabidopsis thaliana. We also demonstrate a successful method to cross Camelina sativa and provide qRT-PCR results to prove its effectiveness.

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Proteínas de Arabidopsis , Arabidopsis , Brassicaceae , Antibacterianos/farmacología , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Brassicaceae/genética , Plantas Modificadas Genéticamente/genética

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The directed evolution of proteins comprises a search of sequence space for variants that improve a target phenotype, yet identification of desirable variants is inherently limited by library size and screening ability. Selections that couple protein phenotype to cell viability accelerate identification of promising variants by depleting libraries of undesirable variants en masse. Here, we introduce GPCR-FEX, a stringent selection platform that couples G-protein coupled receptor (GPCR) signaling to expression of a fluoride ion exporter (FEX)-GFP fusion gene and concomitant cellular fluoride tolerance in yeast. The GPCR-FEX platform works to deplete inactive GPCR variants from the library prior to high-throughput fluorescence-based cell sorting for rapid, inexpensive screening of receptor libraries that sample an expanded sequence space. Using this system, FEX1 was placed under the control of either PFUS1 or PFIG1, promoters activated upon agonist binding by the native yeast GPCRs, Ste2p or Ste3p. Addition of a C-terminal degron to FEX1p enhanced the dynamic range of cell growth between agonist-treated and untreated cells. Using deep sequencing to enumerate population members, we show rapid selection of a previously engineered Ste2p receptor mutant strain over wild-type Ste2p in a model library enrichment experiment. Overall, the GPCR-FEX platform provides a mechanism to rapidly engineer GPCRs, which are important cellular sensors for synthetic biology.

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Fluoruros , Proteínas de Saccharomyces cerevisiae , Proteínas Portadoras/metabolismo , Fluoruros/farmacología , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo

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A thoracic mycotic aortic aneurysm is an uncommon entity that can complicate mediastinal abscesses. Gemella morbillorum and Capnocytophaga sp. are oral bacteria that are very rarely encountered in this setting, especially when occurring together and with other organisms, posing a difficult treatment challenge per the available guidelines and sensitivities. We present in detail this interesting case of a multi-organism mediastinal abscess and thoracic mycotic aortic aneurysm after a previous esophagogastroduodenoscopic procedure in a 51-year-old female with known achalasia who presented with upper abdominal pain, including a successful surgical and antibiotic treatment regimen and a literature review of the involved topics.

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The genetic manipulation of cells followed by their selection is indispensable for cell biological research. Although antibiotics-resistant genes are commonly used as selection markers, optimization of the condition for each selective agent is required. Here we utilized split-inteins and the drug-selectable marker puromycin N-acetyltransferase (PAC) to develop a system that enables the selection of cells simultaneously or sequentially transfected with multiple genetic constructs, using only puromycin. The active PAC enzyme was reconstituted by intein-mediated trans-splicing at several inherent or engineered serine/cysteine residues. Multiple splitting and reconstitution of active PAC was readily achieved by selecting optimum division sites based on the cellular tolerance to various puromycin concentrations. To achieve the stepwise selection method, PAC-intein fragments were transduced into cells using a virus-like particle (VLP) composed of HIV-1 gag-pol and VSV-G. The PAC-intein-VLP successfully conferred sufficient PAC activity for puromycin selection, which was quickly diminished in the absence of the VLP. Our findings demonstrate a versatile strategy for establishing markers for all-at-once or stepwise selection of multiple genetic manipulations, which will be useful in many fields of biology.

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Acetiltransferasas/genética , Ingeniería Celular/métodos , Proteínas de Fusión gag-pol/genética , Inteínas/genética , Glicoproteínas de Membrana/genética , Selección Genética , Proteínas del Envoltorio Viral/genética , Acetiltransferasas/metabolismo , Partículas Similares a Virus Artificiales/química , Partículas Similares a Virus Artificiales/metabolismo , Línea Celular Tumoral , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Proteínas de Fusión gag-pol/metabolismo , Expresión Génica , Genes Reporteros , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Células HEK293 , Humanos , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Glicoproteínas de Membrana/metabolismo , Plásmidos/química , Plásmidos/metabolismo , Puromicina/farmacología , Transfección/métodos , Virus de la Estomatitis Vesicular Indiana/genética , Virus de la Estomatitis Vesicular Indiana/metabolismo , Proteínas del Envoltorio Viral/metabolismo , Proteína Fluorescente Roja

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The interest in producing pharmaceutical proteins in a nontoxic plant host has led to the development of an approach to express such proteins in transplastomic lettuce (Lactuca sativa). A number of therapeutic proteins and vaccine antigen candidates have been stably integrated into the lettuce plastid genome using biolistic DNA delivery. High levels of accumulation and retention of biological activity suggest that lettuce may provide and ideal platform for the production of biopharmaceuticals.

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Biolística/métodos , Ingeniería Genética/métodos , Lactuca/genética , Hojas de la Planta/genética , Plantas Modificadas Genéticamente/genética , Plastidios/genética , Transformación Genética , Productos Biológicos/administración & dosificación , Lactuca/crecimiento & desarrollo , Hojas de la Planta/crecimiento & desarrollo , Plantas Modificadas Genéticamente/crecimiento & desarrollo

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In order to prescribe an antibiotic, a physician must go through a series of decision-making processes that involve both the drug and the host. In this review article, we outline exactly what those decision-making processes are and some of their limitations. Before a medication can be prescribed, a physician has to determine if the antibiotic works against the host pathogen. To do this, basic science techniques are employed including phenotypic methods such as broth dilution methods, Kirby-Bauer susceptibility testing, Epsilometer test (E-test), and genotypic methods such as the new and upcoming automated tests. After determining if a drug has potential to work, the physician must consider the drug's mechanism of action in order to determine a dosing regimen. Some groups of drugs should be administered at high concentrations infrequently, others should be given more frequently in smaller doses, and others lie somewhere between this spectrum. Finally, external factors such as the patient's age, especially for pediatrics and geriatrics patients, need to be considered, as these groups have the highest health care burden but are among the most vulnerable when it comes to the side effects of drugs.

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To fully understand the function of cytomegalovirus (CMV) genes, it is imperative that they are studied in the context of infection. Therefore, the targeted deletion of individual viral genes and the comparison of these loss-of-function viral mutants to the wild-type virus allow for the identification of the relevance and role for a particular gene in the viral replication cycle. Targeted CMV mutagenesis has made huge advances over the past 20 years. The cloning of CMV genomes into Escherichia coli as bacterial artificial chromosomes (BAC) allows for not only quick and efficient deletion of viral genomic regions, individual genes, or single-nucleotide exchanges in the viral genome but also the insertion of heterologous genetic sequences for gain-of-function approaches. The conceptual advantage of this strategy is that it overcomes the restrictions of recombinant technologies in cell culture systems. Namely, recombination in infected cells occurs only in a few clones, and their selection is not possible if the targeted genes are relevant for virus replication and are not able to compete for growth against the unrecombined parental viruses. On the other hand, BAC mutagenesis enables the selection for antibiotic resistance in E. coli, providing selective growth advantage to the recombined genomes and thus clonal selection of viruses with even extremely poor fitness. Here we describe the methods used for the generation of a CMV BAC, targeted mutagenesis of BAC clones, and transfection of human cells with CMV BAC DNA in order to reconstitute the viral infection process.

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Cromosomas Artificiales Bacterianos/genética , Clonación Molecular/métodos , Citomegalovirus/genética , Células Cultivadas , Escherichia coli/genética , Genes Virales/genética , Genoma Viral/genética , Humanos , Mutagénesis/genética , Transfección/métodos , Replicación Viral/genética

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OBJECTIVE: We used a data-driven methodology to decrease the departmental surgical site infection rate to a goal of 1%. METHODS: A prospective interventional study with historical controls comparing preimplementation/intervention (unknown methicillin-sensitive Staphylococcus aureus [MSSA]/methicillin-resistant Staphylococcus aureus [MRSA] status and standard weight and drug allergy-based preoperative antibiotics) with postimplementation/intervention (optimized preoperative chlorhexidine showers, MSSA/MRSA screening, MSSA/MRSA decolonization, and optimized preoperative antibiotic order set implementation). The American College of Surgeons National Surgical Quality Improvement Program was used for case surveillance. The primary outcome was the presence of a surgical site infection with a secondary outcome of cost(s) of implementation. RESULTS: A total of 317 National Surgical Quality Improvement Program abstracted neurosurgical cases were analyzed, 163 cases before implementation and 154 cases after implementation. There were no significant differences between the preimplementation and postimplementation cohorts regarding patient demographics and baseline comorbidities, with the exceptions of inpatient and functional status (P < 0.001). The most common procedures were lumbar decompression (31%), lumbar discectomy (27%), and anterior cervical discectomy and fusion (10.4%). After implementation, 30 patients were MSSA positive (20%) and 4 MRSA positive (2.6%). Thirty patients received preoperative intranasal mupirocin decolonization (88%), and 4 patients received adjusted preoperative antibiotics (12%). After protocol implementation, the surgical site infection rate decreased from 6.7% (odds ratio, 2.82) to 0.96% (odds ratio, 0.91). The cost of implementation was $27,179, or $58 per patient. CONCLUSIONS: The findings highlight the importance of systematically investigating areas of gap in existing clinical practice and quality improvement projects to increase patient safety and enhance the value of care delivered to neurosurgical patients.

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Procedimientos Neuroquirúrgicos/métodos , Infección de la Herida Quirúrgica/prevención & control , Anciano , Profilaxis Antibiótica , Clorhexidina/uso terapéutico , Servicios de Salud Comunitaria , Costos y Análisis de Costo , Descompresión Quirúrgica , Desinfectantes/uso terapéutico , Discectomía , Femenino , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/economía , Práctica Profesional/organización & administración , Estudios Prospectivos , Mejoramiento de la Calidad , Fusión Vertebral , Infecciones Estafilocócicas/prevención & control , Infección de la Herida Quirúrgica/economía , Resultado del Tratamiento

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The presence of antibiotics can exert significant selection pressure on the emergence and spread of antibiotic resistance genes (ARGs) and antibiotic resistant bacteria (ARB). However, co-selection effects for ARGs, the mobility of ARGs and the identification of ARG hosts under high antibiotic selection pressures are poorly understood. Here, metagenomic assembly and binning approaches were used to comprehensively decipher the prevalence of ARGs and their potential mobility and hosts in activated sludge reactors treating antibiotic production wastewater. We found the abundance of different ARG types in antibiotic treatments varied greatly and certain antibiotic pressure promoted the co-selection for the non-corresponding types of ARGs. Antibiotic selection pressures significantly increased the abundance and proportions of ARGs mediated by plasmids (57.9%), which were more prevalent than those encoded in chromosomes (19.2%). The results indicated that plasmids and chromosomes had a tendency to carry different types of ARGs. Moreover, higher co-occurrence frequency of ARGs and MGEs revealed that antibiotics enhanced the mobility potential of ARGs mediated by both plasmids and integrative and conjugative elements. Among the 689 metagenome-assembled genomes (MAGs) with high estimated quality, 119 MAGs assigning to nine bacterial phyla were identified as the ARG hosts and 33 MAGs exhibited possible multi-resistance to antibiotics. Some ARG types tended to be carried by certain bacteria (e.g. bacitracin resistance genes carried by the family Burkholderiaceae) and thus showed a pronounced host-specific pattern. This study enhances the understanding of the mobility and hosts of ARGs and provides important insights into the risk assessment and management of antibiotic resistance.

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Antibacterianos , Metagenoma , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Antibacterianos/farmacología , Bacterias/genética , Farmacorresistencia Microbiana/genética , Genes Bacterianos

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Diabetic foot ulcer (DFU) is considered as one of the most serious and prevailing complications of diabetes mellitus, while it is the major cause of amputations in diabetic patients. Herein, we reported an acquired severe traumatic DFU with an intermediate cuneiform hairline fracture and displacement in a 55-year old male (Grade IV of Wagner classification; Grade III of IWGDF classification). The Pseudomonas aeruginosa was identified in pus culture. Data of antibiotic susceptibility testing indicated that the isolates of Pseudomonas aeruginosa were multi-drug resistant. Routine debridement, clearing displaced intermediate cuneiform and drainage were performed to facilitate the outflow of pus and pressure mitigation. Dressing with Prontosan solution and gel was applied to the wound, and meropenem was systemically administrated in addition to effective glycemic control. The DFU has been fully healed after ~40-day treatment. For this case, clearing the displaced and fractured intermediate cuneiform is essential for the heal of the DFU in addition to the common strategy for DFU treatment, i.e., the combination of debridement, pressure mitigation, wound dressing with Prontosan, antibiotic selection and effective glycemic control. This case report might have value for the treatment of complex DFU with bone fracture and displacement, reducing the risk of amputation.

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Introduction Patients with diabetes mellitus (DM) in underserved communities are at greater risk for hand infections. We aimed to describe the features of hand infections presenting to an urban hospital via laboratories, microbiology, and antibiotic choice with respect to diabetic status. Materials and Methods Patients presenting with any hand infection were reviewed and stratified by DM status and infection location. Labs, culture results, antibiotic regimens, and significant predictors of laboratories or infection location were analyzed. Results Fifty-three patients were included: DM ( n = 24), no-DM ( n = 24), and unknown status ( n = 5). Culture rates were comparable between all groups. Mean erythrocyte sedimentation rate (ESR) was significantly higher in DM (76.19 vs. 51.33); mean white blood cell count (WBC) and C-reactive protein (CRP) were comparable. Diabetics had higher odds of increased ESR (odds ratio [OR] = 1.03). Diabetics received vancomycin/piperacillin/tazobactam (VAN/PTZ) significantly more often (52% vs. 8%). Providers treated DM with VAN/PTZ or any VAN-containing regimen more often than with any other regimen. Proximal infections had significantly higher mean CRP (136.9 vs. 50.5) and WBC (5.19 vs. 3.9) and higher CRP (OR = 1.02). Conclusion This study highlights the need for systematic criteria to better risk- stratify patients for appropriate antibiotic treatment. It may not be appropriate to treat both groups differently, as overly aggressive antibiotic selection may contribute to drug-resistance development.