Analysis of Managers' Perception Regarding the Use of Traceability Tools in the Context of Brazilian Health.

Our society has advanced in terms of technology, and health could not be different. Despite the benefits and advantages that such improvements entail, it is unknown what contributions have been added to the hospital environment and whether such technological engineering has managed to generate value and adapt to different factors within such institutions' professional culture to establish relevance to the base of utilitarian nature. The use of tools can be conditioned to the view that the managerial sectors have such instruments. The work aims to identify and understand the perception that health managers have traceability tools such and their view on their efficiency and effectiveness in the hospital environment. The results direct us that the traceability tools have a significant expression in the hospital context, collaborating for efficiency and efficacy. Traceability tools can help the entire health system to be more uniform in service, in accountability, and in inspection processes.

Social participation in the unified health system of Brazil: an exploratory study on the adequacy of health councils to resolution 453/2012.

INTRODUCTION: Social participation is one of the guidelines of the Brazilian health system. Health councils are collegiate instances of participation established by Law 8.142/90. The most recent legal regulation for council organization and functioning was established through Resolution 453/2021. The institution of health councils has a permanent and deliberative nature to act in the formulation, deliberation and control of health policy implementation, including in economic and financial aspects. OBJECTIVE: To evaluate the compliance of health councils with the directives for the establishment, restructuring and operation of the councils from Brazil, based on Resolution 453/2012. METHODS: An exploratory, descriptive study that used the Health Council Monitoring System as a data source. Qualitative variables were selected to identify the characteristics related to the councils' establishment (legal instruments for establishment), the strategies adopted for restructuring (budget allocation, existence of an executive secretariat, provision of a dedicated office) and the characteristics of the health councils' operation (frequency of regular meetings, existence of a board of directors, the election of the board of directors). RESULTS: The study analyzed three groups of characteristics related to the constitution, strategies adopted for restructuring and the functioning of the councils. Regarding the constitution of the councils, the findings revealed that the vast majority was constituted in accordance with the legislation and, therefore, is in compliance with Resolution 453/2021. In the second group of characteristics that describe the restructuring of councils, the study found that less than half of registered councils are in compliance with the standard. And, finally, in the third group of characteristics, it was found that the boards have adopted different frequencies for regular meetings and approximately 50% of the boards studied have a board of directors. CONCLUSIONS: The councils still do not meet the minimum conditions necessary to fulfil their role in the Unified Health System (SUS), as stipulated in Resolution 453/2021. This situation requires monitoring by public oversight agencies. Despite the increase in popular participation with the creation of the health councils, this study demonstrated that most councils still do not meet the minimum conditions for monitoring public health policy. The improvement of the Health Councils Monitoring System (SIACS) to become an instrument for monitoring the councils, with the definition of goals and results, may contribute to the organization of the councils and, therefore, to the realization of social participation in Brazil.

Social participation: a look at the representativeness of health councils in Brazil, from Resolution 453/2012 / Participação social: um olhar sobre a representatividade nos conselhos de saúde no Brasil, a partir da Resolução 453/2012

Abstract The text addresses the representativeness in health councils in Brazil, based on guidelines proposed by the National Health Council. This study aimed to verify the adequacy of the councils to the criteria described in Resolution 453/2012, which demonstrate the representativeness of the segments that make up the collective. A descriptive cross-sectional study was conducted during May and June 2017. The study population was composed of health councils registered in the Health Councils Monitoring System, with public access and available on the Internet. The results obtained were organized considering the geographical distribution of the councils. The regions with the highest rates of non-compliance with the parity criterion were identified. It has been demonstrated that the guidelines for reformulating the councils are aligned with the notion of representativeness, but they are not a guarantee for the effectiveness of the representation. Future studies may deepen the analyses on representativeness in health councils in Brazil, and identify which mechanisms are adopted by entities to ensure the effectiveness of representation, as well as whether representation is renewed. It is recommended that the rules ordering the functioning of councils be permanently updated to promote social participation in health.

Resumo O texto aborda a representatividade nos conselhos de saúde no Brasil, a partir de diretrizes propostas pelo Conselho Nacional de Saúde. O objetivo do estudo foi verificar a adequação dos conselhos aos critérios descritos na Resolução 453/2012, que demonstram a representatividade dos segmentos que compõem o coletivo. Foi realizado estudo descritivo, do tipo transversal, durante os meses de maio e junho de 2017. A população do estudo foi composta pelos conselhos de saúde cadastrados no Sistema de Acompanhamento dos Conselhos de Saúde, de acesso público e disponível na internet. Os resultados obtidos foram organizados considerando a distribuição geográfica dos conselhos. Foram identificadas as regiões com maiores índices de descumprimento do critério de paridade. Ficou demonstrado que as diretrizes para reformulação dos conselhos estão alinhadas a noção de representatividade, porém, não são garantia para a efetividade da representação. Estudos futuros poderão aprofundar as análises sobre a representatividade nos conselhos de saúde no Brasil, e identificar quais mecanismos são adotados pelas entidades para garantir efetividade da representação, bem como se ocorre renovação da representação. É recomendável que as normas que ordenam o funcionamento dos conselhos sejam permanentemente atualizadas para favorecer a participação social na saúde.

Ceftolozane-tazobactam and ceftazidime-avibactam activity against ß-lactam-resistant Pseudomonas aeruginosa and extended-spectrum ß-lactamase-producing Enterobacterales clinical isolates from U.S. medical centres.

BACKGROUND: Despite availability of ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) for several years, the individual spectrum of activity of each agent may not be widely known. We compared the activity of C/T and CZA against convenience samples of 119 extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales and 60 ß-lactam-resistant Pseudomonas aeruginosa clinical isolates collected from three U.S. institutions. METHODS: Minimal inhibitory concentrations (MICs) for C/T and CZA were determined by broth microdilution. Molecular identification of nine ß-lactamase gene targets was conducted for Enterobacterales and P. aeruginosa isolates with increased MICs to C/T or CZA. RESULTS: More than 90% of Enterobacterales isolates demonstrated susceptibility to both C/T and CZA, in contrast to the other traditional ß-lactam agents tested, which were much less active. The MIC50/90 values were nearly equivalent between agents. The most common ß-lactamase genes identified in Enterobacterales isolates with MIC values ≥2 mg/L were the CTX-M-1 group (85%) and CMY-2-like (23%) ß-lactamases. Both agents were active against >80% of ß-lactam-resistant P. aeruginosa isolates tested, most of which had oprD mutations identified. One P. aeruginosa isolate was positive for a Klebsiella pneumoniae carbapenemase-type gene but remained meropenem-susceptible. The MIC50 values were four-fold lower in favour of C/T (1 mg/L vs. 4 mg/L) against P. aeruginosa. CONCLUSIONS: Our data suggest that either agent may be a reasonable choice for centres with a high proportion of ESBL producers; however, C/T may have improved activity against P. aeruginosa and may be preferred in institutions with a higher frequency of resistant pseudomonal isolates.

Health Professionals' Perception Related to Communication Technologies for Access to Information about Crack.

BACKGROUND: The aim of this study is to identify the information and communication technologies used by health professionals to assist in training and updating of technical and scientific knowledge about crack, exchange of experiences, and development of programs to prevent consumption and treatment of addicts. METHODS: The qualitative methodology was used, constructed an intentional sample by criteria and applied research techniques through semi-structured interviews, triangulation of the analysis, and key informants. The study resulted in the presentation of differences between the way key informants and health professionals sought information. RESULTS: Internet was the preferred source; however, key informants sought information on sites of scientific journals and reference centers, while health professionals did free searches on the internet to consume information. CONCLUSIONS: The literature does not reflect a broad scope of the specific area, but relates the problem of access to health information to other characteristics. The sources of information about crack are focused on digital technologies, the internet and its specific tools. It also finds that health professionals are not being capacitate solidly on the subject of study.

Permanent education as an inalienable responsibility of health councils: the current scenario in the Unified Health System.

OBJECTIVE: To verify whether health councils in Brazil carry out permanent education activities for municipal, state and federal district councilors. METHOD: This was a cross-sectional study with secondary data collection in the Health Council Monitoring System (Sistema de Acompanhamento dos Conselhos de Saúde - Siacs) from May to August 2017. The Siacs is publicly accessible and available on the internet. It provides data from thousands of health councils throughout Brazil. Analysis and interpretation of the data were based on the literature and the enacted legislation, particularly Resolution 453/2012 and the National Policy of Permanent Education for Social Control in the Unified Health System (Política Nacional de Educação Permanente para o Controle Social no Sistema Único de Saúde). RESULTS: Despite the fact that Resolution 453/2012 establishes the deliberation, elaboration, support and promotion of permanent education for social control as functions of the councils (in accordance with the guidelines of the National Policy of Permanent Education), approximately 40% of councils do not carry out permanent education. CONCLUSIONS: It is necessary to strengthen the role of health councils in the elaboration of educational initiatives across the national territory. This includes the allocation of financial resources to increase access to and participation in these initiatives, which would strengthen social control in the Unified Health System. This study emphasizes that the discussion of permanent education is not given sufficient attention in the agendas and routines of health councils. This compromises the effectiveness of councils' monitoring and deliberation of public health policy.

Permanent education as an inalienable responsibility of health councils: the current scenario in the Unified Health System

OBJECTIVE: To verify whether health councils in Brazil carry out permanent education activities for municipal, state and federal district councilors. METHOD: This was a cross-sectional study with secondary data collection in the Health Council Monitoring System (Sistema de Acompanhamento dos Conselhos de Saúde - Siacs) from May to August 2017. The Siacs is publicly accessible and available on the internet. It provides data from thousands of health councils throughout Brazil. Analysis and interpretation of the data were based on the literature and the enacted legislation, particularly Resolution 453/2012 and the National Policy of Permanent Education for Social Control in the Unified Health System (Política Nacional de Educação Permanente para o Controle Social no Sistema Único de Saúde). RESULTS: Despite the fact that Resolution 453/2012 establishes the deliberation, elaboration, support and promotion of permanent education for social control as functions of the councils (in accordance with the guidelines of the National Policy of Permanent Education), approximately 40% of councils do not carry out permanent education. CONCLUSIONS: It is necessary to strengthen the role of health councils in the elaboration of educational initiatives across the national territory. This includes the allocation of financial resources to increase access to and participation in these initiatives, which would strengthen social control in the Unified Health System. This study emphasizes that the discussion of permanent education is not given sufficient attention in the agendas and routines of health councils. This compromises the effectiveness of councils' monitoring and deliberation of public health policy.

Thyroid cancer burden and economic impact on the Brazilian public health system.

OBJECTIVE: Recent data indicates an increasing incidence of thyroid cancer not accompanied by a proportional increase in mortality, suggesting overdiagnosis, which may represent a big public health problem, particularly where resources are scarce. This article aims to describe and evaluate the procedures related to investigation of thyroid nodules and treatment and follow-up of thyroid cancer and the costs for the Brazilian public health system between 2008 and 2015. MATERIALS AND METHODS: Data on procedures related to investigation of thyroid nodules and treatment/follow-up of thyroid cancer between 2008 and 2015 in Brazil were collected from the Department of Informatics of the Brazilian Unified Health System (Datasus) website. RESULTS: A statistically significant increase in the use of procedures related to thyroid nodules investigation and thyroid cancer treatment and follow-up was observed in Brazil, though a reduction was noted for procedures related to the treatment of more aggressive thyroid cancer, such as total thyroidectomy with neck dissection and higher radioiodine activities such as 200 and 250 milicuries (mCi). The procedures related to thyroid nodules investigation costs increased by 91% for thyroid ultrasound (p = 0.0003) and 128% in thyroid nodule biopsy (p < 0.001). Costs related to treatment and follow-up related-procedures increased by 120%. CONCLUSION: The increase in the incidence of thyroid cancer in Brazil is directly associated with an increased use of diagnostic tools for thyroid nodules, which leads to an upsurge in thyroid cancer treatment and followup-related procedures. These data suggest that substantial resources are being used for diagnosis, treatment and follow-up of a potentially indolent condition.

Thyroid cancer burden and economic impact on the Brazilian public health system

ABSTRACT Objective: Recent data indicates an increasing incidence of thyroid cancer not accompanied by a proportional increase in mortality, suggesting overdiagnosis, which may represent a big public health problem, particularly where resources are scarce. This article aims to describe and evaluate the procedures related to investigation of thyroid nodules and treatment and follow-up of thyroid cancer and the costs for the Brazilian public health system between 2008 and 2015. Materials and methods: Data on procedures related to investigation of thyroid nodules and treatment/follow-up of thyroid cancer between 2008 and 2015 in Brazil were collected from the Department of Informatics of the Brazilian Unified Health System (Datasus) website. Results: A statistically significant increase in the use of procedures related to thyroid nodules investigation and thyroid cancer treatment and follow-up was observed in Brazil, though a reduction was noted for procedures related to the treatment of more aggressive thyroid cancer, such as total thyroidectomy with neck dissection and higher radioiodine activities such as 200 and 250 milicuries (mCi). The procedures related to thyroid nodules investigation costs increased by 91% for thyroid ultrasound (p = 0.0003) and 128% in thyroid nodule biopsy (p < 0.001). Costs related to treatment and follow-up related-procedures increased by 120%. Conclusion: The increase in the incidence of thyroid cancer in Brazil is directly associated with an increased use of diagnostic tools for thyroid nodules, which leads to an upsurge in thyroid cancer treatment and followup-related procedures. These data suggest that substantial resources are being used for diagnosis, treatment and follow-up of a potentially indolent condition.

Detection of high-risk carbapenem-resistant Klebsiella pneumoniae and Enterobacter cloacae isolates using volatile molecular profiles.

Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are alarming in the clinical setting, as CRE isolates often exhibit resistance to most clinically-available antibiotics. Klebsiella pneumoniae carbapenemase (KPC) is the most common carbapenemase carried by CRE in North America and Europe, frequently detected in isolates of K. pneumoniae, Escherichia coli, and Enterobacter cloacae. Notably, KPC-expressing strains often arise from clonal lineages, with sequence type 258 (ST258) representing the dominant lineage in K. pneumoniae, ST131 in E. coli, and ST78 and ST171 in E. cloacae. Prior studies have demonstrated that carbapenem-resistant K. pneumoniae differs from carbapenem-susceptible K. pneumoniae at both the transcriptomic and soluble metabolomic levels. In the present study, we sought to determine whether carbapenem-resistant and carbapenem-susceptible isolates of K. pneumoniae, E. coli, and E. cloacae produce distinct volatile metabolic profiles. We were able to identify a volatile metabolic fingerprint that could discriminate between CRE and non-CRE with an area under the receiver operating characteristic curve (AUROC) as high as 0.912. Species-specific AUROCs were as high as 0.988 for K. pneumoniae and 1.000 for E. cloacae. Paradoxically, curing of KPC-expressing plasmids from a subset of K. pneumoniae isolates further accentuated the metabolic differences observed between ST258 and non-ST258.

Analysis of the indicators of the Family Health Program in the Metropolitan Region of São Paulo.

OBJECTIVE: To analyze the Family Health Program replaced by the Family Health Strategy in 2011, based on health indicators and diseases classified as primary care sensitive. METHODS: This was a descriptive, analytical and documental study carried out in the Metropolitan Region of São Paulo between 2002 and 2007. We analyzed data from Health observatory for the Metropolitan Region of São Paulo. Pearson's correlation and the Statistical Package for the Social Sciences software version 17.0 were used to calculate data associations. RESULTS: We used 30 of the 31 health indicators of 24 from the 39 studied municipalities. A total of 720 (100%) health primary care sensitive indicators were analyzed in the Metropolitan Region of São Paulo. CONCLUSION: Percentages of improvements and worsening were low. In addition, some data were not presented. The majority of indicators remained stable.

Prevalence of dermatoses in patients referred for evaluation in an outpatient clinic of specialties.

BACKGROUND: Brazilian Unified Health System presents a long waiting period for a dermatology appointment, varying from 34 to 239 days. OBJECTIVES: Analyze the prevalence of cutaneous diseases evaluated by dermatologists in a specialized center, in patients referred from the primary care, and to present possible interventions for the primary units. METHODS: Retrospective analyses of the International Codes of Diseases (ICD-10) described in every dermatology appointment in a specialty center in Sao Paulo from January 2014 to August 2015. RESULTS: A total of 7.350 consultations were included. Superficial mycosis corresponded to 1,058 (14.4%) of the main complaints and dermatophytosis was the most frequently used ICD, corresponding to 481 individual consultations (6.5%), followed by onychomycosis, responsible for 464 consultations (6.3%), acne in 347 (4,7%). and contact dermatitis in 311 consultations (4,2%). STUDY LIMITATIONS: The study was based on retrospective analysis of ICD described and no previous orientation for a solid use of the codes was performed to the dermatology team; consultations in which the ICD was not informed or a non-especific ICD was used were excluded; different dermatologists were responsible for the consultations. CONCLUSION: Superficial mycosis corresponded to 14.4% of the chief complaints in the studied period and was the most frequent cause of reference from primary care doctors to dermatologists. Prevalence data obtained in the present study could assist the capacitation policies in the primary care system, focusing the dermatology teaching in the most prevalent dermatological disorders.

Prevalence of dermatoses in patients referred for evaluation in an outpatient clinic of specialties

Abstract: Background: Brazilian Unified Health System presents a long waiting period for a dermatology appointment, varying from 34 to 239 days. Objectives: Analyze the prevalence of cutaneous diseases evaluated by dermatologists in a specialized center, in patients referred from the primary care, and to present possible interventions for the primary units. Methods: Retrospective analyses of the International Codes of Diseases (ICD-10) described in every dermatology appointment in a specialty center in Sao Paulo from January 2014 to August 2015. Results: A total of 7.350 consultations were included. Superficial mycosis corresponded to 1,058 (14.4%) of the main complaints and dermatophytosis was the most frequently used ICD, corresponding to 481 individual consultations (6.5%), followed by onychomycosis, responsible for 464 consultations (6.3%), acne in 347 (4,7%). and contact dermatitis in 311 consultations (4,2%). Study limitations: The study was based on retrospective analysis of ICD described and no previous orientation for a solid use of the codes was performed to the dermatology team; consultations in which the ICD was not informed or a non-especific ICD was used were excluded; different dermatologists were responsible for the consultations. Conclusion: Superficial mycosis corresponded to 14.4% of the chief complaints in the studied period and was the most frequent cause of reference from primary care doctors to dermatologists. Prevalence data obtained in the present study could assist the capacitation policies in the primary care system, focusing the dermatology teaching in the most prevalent dermatological disorders.

Analysis of the indicators of the Family Health Program in the Metropolitan Region of São Paulo / Análise dos indicadores do Programa Saúde da Família na Região Metropolitana de São Paulo

ABSTRACT Objective To analyze the Family Health Program replaced by the Family Health Strategy in 2011, based on health indicators and diseases classified as primary care sensitive. Methods This was a descriptive, analytical and documental study carried out in the Metropolitan Region of São Paulo between 2002 and 2007. We analyzed data from Health observatory for the Metropolitan Region of São Paulo. Pearson's correlation and the Statistical Package for the Social Sciences software version 17.0 were used to calculate data associations. Results We used 30 of the 31 health indicators of 24 from the 39 studied municipalities. A total of 720 (100%) health primary care sensitive indicators were analyzed in the Metropolitan Region of São Paulo. Conclusion Percentages of improvements and worsening were low. In addition, some data were not presented. The majority of indicators remained stable.

RESUMO Objetivo Analisar o Programa Saúde da Família, substituído pela Estratégia Saúde da Família em 2011, considerando os indicadores de saúde e as doenças classificadas como sensíveis à Atenção Primária. Métodos Trata-se de estudo descritivo, analítico e documental, realizado na Região Metropolitana de São Paulo, no período de 2002 a 2007. Foram analisados dados fornecidos pelo Observatório de Saúde da Região Metropolitana de São Paulo. Após a coleta, calcularam-se, com base na correlação de Pearson e por meio do software SPSS, versão 17.0, as associações entre os dados. Resultados Foram usados 30 dos 31 indicadores de saúde de 24 dos 39 municípios pesquisados. Foram analisados 720 (100%) indicadores de saúde sensíveis à Atenção Primária na Região Metropolitana de São Paulo. Conclusão Foram baixos os percentuais de melhoras e pioras, ou, ainda, os dados não foram apresentados. A maioria permaneceu estável.

Compound design guidelines for evading the efflux and permeation barriers of Escherichia coli with the oxazolidinone class of antibacterials: Test case for a general approach to improving whole cell Gram-negative activity.

Previously we reported the results from an effort to improve Gram-negative antibacterial activity in the oxazolidinone class of antibiotics via a systematic medicinal chemistry campaign focused entirely on C-ring modifications. In that series we set about testing if the efflux and permeation barriers intrinsic to the outer membrane of Escherichia coli could be rationally overcome by designing analogs to reside in specific property limits associated with Gram-negative activity: i) low MW (<400), ii) high polarity (clogD7.4 <1), and iii) zwitterionic character at pH 7.4. Indeed, we observed that only analogs residing within these limits were able to overcome these barriers. Herein we report the results from a parallel effort where we explored structural changes throughout all three rings in the scaffold for the same purpose. Compounds were tested against a diagnostic MIC panel of Escherichia coli and Staphylococcus aureus strains to determine the impact of combining structural modifications in overcoming the OM barriers and in bridging the potency gap between the species. The results demonstrated that distributing the charge-carrying moieties across two rings was also beneficial for avoidance of the outer membrane barriers. Importantly, analysis of the structure-permeation relationship (SPR) obtained from this and the prior study indicated that in addition to MW, polarity, and zwitterionic character, having ≤4 rotatable bonds is also associated with evasion of the OM barriers. These combined results provide the medicinal chemist with a framework and strategy for overcoming the OM barriers in GNB in antibacterial drug discovery efforts.

Prontuário Eletrônico do Paciente: como a teoria da difusão de inovações pode colaborar na sua implantação / Electronic Patient Record: how the diffusion of innovations theory can collaborate in its implementation / Registro Electrónico del Paciente: como la teoría de difusión de innovaciones pode colaborar en su aplicación

Este artigo traz um histórico da Teoria da Difusão de Inovações e uma revisão da literatura sobre sua aplicação na área de saúde, dando especial ênfase na adoção do Prontuário Eletrônico do Paciente. Seu objetivo é o de compilar os pontos mais importantes no processo de adoção de inovações mencionados nos casos pesquisados, como por exemplo: a identificação dos usuários com as categorias de adotantes, as ações a serem desenvolvidas junto a estes e o uso dos elementos dessa teoria para o entendimento da forma como as pessoas aderem à inovação. Conclui-se, dessa forma, que a implantação de prontuários eletrônicos requer métodos diferentes dos tradicionalmente usados na área de Tecnologia da Informação, envolvendo também as demais áreas da organização.

This article comprises an historic of Innovation Diffusion Theory and a review of existing literature regarding its use in Health Care, focusing on its application on Electronic Health Records adoption. Its aim is to provide a compilation of most important aspects in the innovation-adoption processes mentioned in the researched cases, for example: the users matching to the adopters categories, the actions to be developed within this users and the use of this theory elements to understand the way people adopt innovation. Concluding that EHR implementations must use different methods than those traditionally used in Information Technology area, involving other areas in the organization.

Este artículo presenta una historia de la teoría de la Difusión de Innovaciones y una revisión de la literatura sobre su aplicación en el cuidado de la salud, con especial énfasis en la adopción del Registro Electrónico del Paciente. Su objetivo es seleccionar los puntos más importantes en el proceso de adopción de las innovaciones mencionadas en los casos investigados, tales como: la identificación de los usuarios en las categorías de adoptantes, las acciones a desarrollar junto a ellos y el uso de los elementos de esta teoría para entender la forma en que las personas se adhieren a la innovación. Se concluye, por lo tanto, que la implementación de registros médicos electrónicos requiere métodos distintos de los utilizados tradicionalmente en la área de Tecnologia de la Informacion, así como la participación de otras áreas de la organización.

The two transmembrane regions of Candida albicans Dfi1 contribute to its biogenesis.

The opportunistic pathogen Candida albicans forms invasive filaments that grow into host tissues during disease. The glycosylated, integral plasma membrane protein Dfi1 is important for invasive filamentation in a laboratory model, and for lethality in murine disseminated candidiasis. However, Dfi1 topology and essential domains for Dfi1 biogenesis were undefined. Sequence analysis predicted that Dfi1 contains two transmembrane regions, located near the N- and C-termini. In this communication, we show that Dfi1 remains an integral membrane protein despite deletion of either predicted transmembrane region, whereas deletion of both regions results in a soluble protein. Additionally, Dfi1 that was properly oriented in the membrane, as indicated by N-linked glycosylation, was observed when either transmembrane region was deleted, but was absent when both transmembrane regions were deleted. Interestingly, deletion of the N-terminal transmembrane region resulted in production of two forms of Dfi1. Most of the protein molecules acquired normal N-linked glycosylation and a smaller population failed to become normally N-linked glycosylated. This defect was reversed by replacement of the N-terminal hydrophobic sequence with one synthetic transmembrane sequence but not another. Finally, microscopy studies revealed that Dfi1 lacking the N-terminal transmembrane region was observed at the cell periphery, where full-length Dfi1 normally localizes, whereas the double-truncation mutant was diffusely intracellular. Therefore, mature Dfi1 protein contains two transmembrane domains which contribute to its biogenesis.

Activity of minocycline against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae clinical isolates, with comparison to doxycycline and tigecycline.

We examined the in vitro activity of minocycline against 103 Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae isolates and found approximately half had susceptible (26%) or intermediate (26%) MICs. For a subset of 35 isolates, susceptibility was highest to tigecycline (71% FDA vs. 20% EUCAST) followed by minocycline (14%) and then doxycycline (6%).

Progress against Escherichia coli with the Oxazolidinone Class of Antibacterials: Test Case for a General Approach To Improving Whole-Cell Gram-Negative Activity.

Novel antibacterials with activity against the Gram-negative bacteria associated with nosocomial infections, including Escherichia coli and other Enterobacteriaceae, are urgently needed due to the increasing prevalence of multidrug-resistant strains. A major obstacle that has stalled progress on nearly all small-molecule classes with potential for activity against these species has been achieving sufficient whole-cell activity, a difficult challenge due to the formidable outer membrane and efflux barriers intrinsic to these species. Using a set of compound design principles derived from available information relating physicochemical properties to Gram-negative entry or activity, we synthesized and evaluated a focused library of oxazolidinone analogues, a currently narrow spectrum class of antibacterials active only against Gram-positive bacteria. In this series, we have explored the effectiveness for improving Gram-negative activity by identifying and combining beneficial structural modifications in the C-ring region. We have found polar and/or charge-carrying modifications that, when combined in hybrid C-ring analogues, appear to largely overcome the efflux and/or permeability barriers, resulting in improved Gram-negative activity. In particular, those analogues least effected by efflux and the permeation barrier had significant zwitterionic character.

The Activity of Antimicrobial Surfaces Varies by Testing Protocol Utilized.

BACKGROUND: Contaminated hospital surfaces are an important source of nosocomial infections. A major obstacle in marketing antimicrobial surfaces is a lack of efficacy data based on standardized testing protocols. AIM: We compared the efficacy of multiple testing protocols against several "antimicrobial" film surfaces. METHODS: Four clinical isolates were used: one Escherichia coli, one Klebsiella pneumoniae, and two Staphylococcus aureus strains. Two industry methods (modified ISO 22196 and ASTM E2149), a "dried droplet", and a "transfer" method were tested against two commercially available antimicrobial films, one film in development, an untreated control, and a positive (silver) control film. At 2 (only ISO) and 24 hours following inoculation, bacteria were collected from film surfaces and enumerated. RESULTS: Compared to untreated films in all protocols, there were no significant differences in recovery on either commercial brand at 2 or 24 hours after inoculation. The silver surface demonstrated significant microbicidal activity (mean loss 4.9 Log10 CFU/ml) in all methods and time points with the exception of 2 hours in the ISO protocol and the transfer method. Using our novel droplet method, no differences between placebo and active surfaces were detected. The surface in development demonstrated variable activity depending on method, organism, and time point. The ISO demonstrated minimal activity at 2 hours but significant activity at 24 hours (mean 4.5 Log10 CFU/ml difference versus placebo). The ASTEM protocol exhibited significant differences in recovery of staphylococci (mean 5 Log10 CFU/ml) but not Gram-negative isolates (10 fold decrease). Minimal activity was observed with this film in the transfer method. CONCLUSIONS: Varying results between protocols suggested that efficacy of antimicrobial surfaces cannot be easily and reproducibly compared. Clinical use should be considered and further development of representative methods is needed.