With the emerging threat of infections caused by multidrug resistant bacteria, phages have been reconsidered as an alternative for treating infections caused by tenacious pathogens. However, instead of replacing antibiotics, the combination of both types of antimicrobials can be superior over the use of single agents. Enhanced bacterial suppression, more efficient penetration into biofilms, and lowered chances for the emergence of phage resistance are the likely advantages of the combined strategy. While a number of studies have provided experimental evidence in support of this concept, negative interference between phages and antibiotics have been reported as well. Neutral effects have also been observed, but in those cases, combined approaches may still be important for at least hampering the development of resistance. In any case, the choice of phage type and antibiotic as well as their mixing ratios must be given careful consideration when deciding for a dual antibacterial approach. The most frequently tested bacterium for a combined antibacterial treatment has been Pseudomonas aeruginosa , but encouraging results have also been reported for Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Enterococcus faecalis , and Burkholderia cepacia . Given the immense play area of conceivable phage-antibiotic combinations and their potential excess value, it is time to recapitulate of what has been achieved so far. This review therefore gathers and compares the results from most relevant studies in order to help researchers and clinicians in their strategies to combat multidrug resistant bacteria. Special attention is given to the selected bacterial model organisms, the phage families and genera employed, and the experimental design and evaluation (e.g., in vitro vs. in vivo models, biofilm vs. planktonic culture experiments, order and frequency of administration etc.). The presented data may serve as a framework for directed further experimental approaches to ultimately achieve a resolute challenge of multidrug resistant bacteria based on traditional antibiotics and phages.

OBJETIVO: Avaliar o desenvolvimento de crianças de 2 meses a 2 anos de idade por meio da Atenção Integrada às Doenças Prevalentes na Infância (AIDPI), no contexto do Programa de Educação pelo Trabalho em Saúde (PET-Saúde). MÉTODO: Estudo transversal realizado com 122 crianças, com idades entre 2 meses e 2 anos, da área de abrangência do Centro de Saúde São Bernardo (CSSB) - Belo Horizonte (MG), em 2009. Os dados relativos ao desenvolvimento foram obtidos através da aplicação de dois questionários: AIDPI e Caderneta de Saúde da Criança (CSC). Foram comparadas as classificações do desenvolvimento pela AIDPI e pela CSC, a associação entre atraso do desenvolvimento e as variáveis estudadas. RESULTADOS: As características com maior frequência na população estudada foram a baixa escolaridade das mães (62,1%), seguida de parentes com deficiência mental (71,3%) e problemas na gestação (71,3%). A AIDPI evidenciou que 61,5% da população estudada encontra-se normal com fator de risco, 16,4% normal sem fator de risco, 11,5% com possível atraso e 10,7% com provável atraso do desenvolvimento infantil. A concordância observada entre a classificação da AIDPI e da CSC foi de 0,34, coeficiente Kappa igual a - 0,12 (p = 0,98). Não houve associação estatisticamente significativa entre as variáveis analisadas (frequenta creches; convívio com problemas emocionais; escolaridade da mãe; idade gestacional; e peso ao nascer) e atraso possível/provável do desenvolvimento identificado pela AIDPI. CONCLUSÃO: O PET-Saúde, como proposta de integração da educação pelo trabalho, permitiu uma oportunidade de convivência e troca de experiências entre alunos e profissionais de diferentes áreas de atuação, trabalhando em um projeto comum.

The antimicrobial resistance (AMR) crisis urgently requires countermeasures for reducing the dissemination of plasmid-borne resistance genes. Of particular concern are opportunistic pathogens of Enterobacteriaceae. One innovative approach is the CRISPR-Cas9 system which has recently been used for plasmid curing in defined strains of Escherichia coli. Here we exploited this system further under challenging conditions: by targeting the bla TEM−1 AMR gene located on a high-copy plasmid (i.e., 100-300 copies/cell) and by directly tackling bla TEM−1-positive clinical isolates. Upon CRISPR-Cas9 insertion into a model strain of E. coli harboring bla TEM−1 on the plasmid pSB1A2, the plasmid number and, accordingly, the bla TEM−1 gene expression decreased but did not become extinct in a subpopulation of CRISPR-Cas9 treated bacteria. Sequence alterations in bla TEM−1 were observed, likely resulting in a dysfunction of the gene product. As a consequence, a full reversal to an antibiotic sensitive phenotype was achieved, despite plasmid maintenance. In a clinical isolate of E. coli, plasmid clearance and simultaneous re-sensitization to five beta-lactams was possible. Reusability of antibiotics could be confirmed by rescuing larvae of Galleria mellonella infected with CRISPR-Cas9-treated E. coli, as opposed to infection with the unmodified clinical isolate. The drug sensitivity levels could also be increased in a clinical isolate of Enterobacter hormaechei and to a lesser extent in Klebsiella variicola, both of which harbored additional resistance genes affecting beta-lactams. The data show that targeting drug resistance genes is encouraging even when facing high-copy plasmids. In clinical isolates, the simultaneous interference with multiple genes mediating overlapping drug resistance might be the clue for successful phenotype reversal.

HighlightsMeasured and estimated VO2peak in CHF patients showed a moderate association.With the exception of equation 1, all equations underestimated VO2peak by up to 51%.The agreement evaluated using Bland–Altman was not consistent.

In the post-genomic era, molecular treatments and diagnostics have been envisioned as powerful techniques to tackle the antimicrobial resistance (AMR) crisis. Among the molecular approaches, aptamers and CRISPR-Cas have gained support due to their practicality, sensibility, and flexibility to interact with a variety of extra- and intracellular targets. Those characteristics enabled the development of quick and onsite diagnostic tools as well as alternative treatments for pan-resistant bacterial infections. Even with such potential, more studies are necessary to pave the way for their successful use against AMR. In this review, we highlight those two robust techniques and encourage researchers to refine them toward AMR. Also, we describe how aptamers and CRISPR-Cas can work together with the current diagnostic and treatment toolbox.

Trying to widen the discussion on the risks associated with dental waste, this study proposed to investigate and genetically compare yeast isolates recovered from dental solid waste and waste workers. Three samples were collected from workers' hands, nasal mucosa, and professional clothing (days 0, 30, and 180), and two from dental waste (days 0 and 180). Slide culture, microscopy, antifungal drug susceptibility, intersimple sequence repeat analysis, and amplification and sequencing of internal transcribed spacer regions were performed. Yeast strains were recovered from all waste workers' sites, including professional clothes, and from waste. Antifungal susceptibility testing demonstrated that some yeast recovered from employees and waste exhibited nonsusceptible profiles. The dendrogram demonstrated the presence of three major clusters based on similarity matrix and UPGMA grouping method. Two branches displayed 100% similarity: three strains of Candida guilliermondii isolated from different employees, working in opposite work shifts, and from diverse sites grouped in one part of branch 1 and cluster 3 that included two samples of Candida albicans recovered from waste and the hand of one waste worker. The results suggested the possibility of cross‐contamination from dental waste to waste workers and reinforce the need of training programs focused on better waste management routines.

Infectious dental waste can contain clinically relevant bacteria with important resistance and biofilm profiles. These micro-organisms could be transmitted to waste workers, other professionals and patients if the principles of biosafety measures are neglected. To our knowledge, no study has ever evaluated the microbial characterization and the potential contamination risk of dental infectious waste and waste handlers. The presence of clinically relevant bacteria in the hands and nasal mucosa of waste workers highlights the need for studies in this field to clarify the risk of these pathogens in dental healthcare services, and to stress the need for an efficient waste management.

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