Global priority multidrug-resistant pathogens do not resist photodynamic therapy.

Microbial drug-resistance demands immediate implementation of novel therapeutic strategies. Antimicrobial photodynamic therapy (aPDT) combines the administration of a photosensitizer (PS) compound with low-irradiance light to induce photochemical reactions that yield reactive oxygen species (ROS). Since ROS react with nearly all biomolecules, aPDT offers a powerful multitarget method to avoid selection of drug-resistant strains. In this study, we assayed photodynamic inactivation under a standardized method, combining methylene blue (MB) as PS and red light, against global priority pathogens. The species tested include Acinetobacter baumannii, Klebsiella aerogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus, Candida albicans and Cryptococcus neoformans. Our strain collection presents resistance to all tested antimicrobials (>50). All drug-resistant strains were compared to their drug-sensitive counterparts. Regardless of resistance phenotype, MB-aPDT presented species-specific dose-response kinetics. More than 5log10 reduction was observed within less than 75 s of illumination for A. baumannii, E. coli, E. faecium, E. faecalis and S. aureus and within less than 7 min for K. aerogenes, K. pneumoniae, P. aeruginosa, C. albicans and C. neoformans. No signs of correlations in between drug-resistance profiles and aPDT sensitivity were observed. Therefore, MB-aPDT can provide effective therapeutic protocols for a very broad spectrum of pathogens. Hence, we believe that this study represents a very important step to bring aPDT closer to implementation into mainstream medical practices

WHO Critical Priority Escherichia coli as One Health Challenge for a Post-Pandemic Scenario: Genomic Surveillance and Analysis of Current Trends in Brazil.

The dissemination of carbapenem-resistant and third generation cephalosporin-resistant pathogens is a critical issue that is no longer restricted to hospital settings. The rapid spread of critical priority pathogens in Brazil is notably worrying, considering its continental dimension, the diversity of international trade, livestock production, and human travel. We conducted a nationwide genomic investigation under a One Health perspective that included Escherichia coli strains isolated from humans and nonhuman sources, over 45 years (1974-2019). One hundred sixty-seven genomes were analyzed extracting clinically relevant information (i.e., resistome, virulome, mobilome, sequence types [STs], and phylogenomic). The endemic status of extended-spectrum β-lactamase (ESBL)-positive strains carrying a wide diversity of variants, and the growing number of colistin-resistant isolates carrying -type genes was associated with the successful expansion of international ST10, ST38, ST115, ST131, ST354, ST410, ST648, ST517, and ST711 clones; phylogenetically related and shared between human and nonhuman hosts, and polluted aquatic environments. Otherwise, carbapenem-resistant ST48, ST90, ST155, ST167, ST224, ST349, ST457, ST648, ST707, ST744, ST774, and ST2509 clones from human host harbored and genes. A broad resistome to other clinically relevant antibiotics, hazardous heavy metals, disinfectants, and pesticides was further predicted. Wide virulome associated with invasion/adherence, exotoxin and siderophore production was related to phylogroup B2. The convergence of wide resistome and virulome has contributed to the persistence and rapid spread of international high-risk clones of critical priority E. coli at the human-animal-environmental interface, which must be considered a One Health challenge for a post-pandemic scenario. A One Health approach for antimicrobial resistance must integrate whole-genome sequencing surveillance data of critical priority pathogens from human, animal and environmental sources to track hot spots and routes of transmission and developing effective prevention and control strategies. As part of the Grand Challenges Explorations: New Approaches to Characterize the Global Burden of Antimicrobial Resistance Program, we present genomic data of WHO critical priority carbapenemase-resistant, ESBL-producing, and/or colistin-resistant Escherichia coli strains isolated from humans and nonhuman sources in Brazil, a country with continental proportions and high levels of antimicrobial resistance. The present study provided evidence of epidemiological and clinical interest, highlighting that the convergence of wide virulome and resistome has contributed to the persistence and rapid spread of international high-risk clones of E. coli at the human-animal-environmental interface, which must be considered a One Health threat that requires coordinated actions to reduce its incidence in humans and nonhuman hosts

Carboxymethylcellulose acetate butyrate/poly(4-vinyl-N-pentyl pyridinium bromide) blends as antimicrobial coatings

Blends of carboxymethyl cellulose acetate butyrate (CMCAB), a cellulose derivative, and poly(4-vinyl-N-pentyl pyridinium bromide) (QPVP-C5), an antimicrobial polymer, were prepared by casting method and characterized by means of Fourier transform infrared vibrational spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and contact angle measurements. Miscibility between CMCAB and QPVP-C5 was evidenced by DSC measurements of blends, which showed a single thermal event of Tg, and SEM images, which revealed homogenous morphology, regardless the blend composition. Moreover, thermal stability of QPVP-C5 was substantially enhanced, when it was mixed with CMCAB. Upon increasing the QPVP-C5 content in the blend the wettability and antimicrobial activity against Gram-positive bacteria Micrococcus luteus increased, indicating the surface enrichment by pyridinium groups. In fact, blends with 70 wt% QPVP-C5 reduced 5 log and 4 log the colony-forming units of Micrococcus luteus and Escherichia coli, respectively

Carbapenem-resistant Acinetobacter baumannii outbreak at university hospital Caracterização de cepas de Acinetobacter baumannii durante um surto de infecção hospitalar

Nineteen clonally related imipenem-resistant Acinetobacter baumannii isolates were recovered from eight intensive care unit patients. All isolates harboured blaOXA-51-like &#946;-lactamase genes and showed the absence of 22 kDa fraction in outer membrane porin profile analysis. It suggests a combination of two mechanisms as responsible for carbapenemresistant phenotypes.<br>Foram isoladas 19 cepas monoclonais de 8 pacientes da unidade de terapia intensiva, resistentes aos carbapenêmicos. Todas as cepas apresentaram o gene blaOXA-51-like e por análise do perfil de proteínas de membrana notou-se ausência da fração de 22 kDa, sugerindo a combinação de dois mecanismos de resistência aos carbapenêmicos

Study of the antigenic cross-reactivity between Neisseria meningitidis and commensal Neisseria species using dioctadecyldimethylammonium bromide bilayer fragments (DDA-BF) as adjuvant.

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Detection of metallo-beta-lactamases-encoding genes in environmental isolates of Aeromonas hydrophila and Aeromonas jandaei

Aims: To determine the prevalence and expression of metallo-beta-lactamases (MBL)-encoding genes in Aeromonas species recovered from natural water reservoirs in southeastern Brazil. Methods and Results: Eighty-seven Aeromonas isolates belonging to Aeromonas hydrophila (n = 41) and Aer. jandaei (n = 46) species were tested for MBL production by the combined disk test using imipenem and meropenem disks as substrates and EDTA or thioglycolic acid as inhibitors. The presence of MBL genes was investigated by PCR and sequencing using new consensus primer pairs designed in this study. The cphA gene was found in 97.6% and 100% of Aer. hydrophila and Aer. jandaei isolates, respectively, whereas the acquired MBL genes bla(IMP), bla(VIM) and bla(SPM-1) were not detected. On the other hand, production of MBL activity was detectable in 87.8% and 10.9% of the cphA-positive Aer. hydrophila and Aer. jandaei isolates respectively. Conclusions: Our results indicate that cphA seems to be intrinsic in the environmental isolates of Aer. hydrophila and Aer. jandaei in southeastern Brazil, although, based on the combined disk test, not all of them are apparently able to express the enzymatic activity. Significance and Impact of the Study: These data confirm the presence of MBL-producing Aeromonas species in natural water reservoirs. Risk of water-borne diseases owing to domestic and industrial uses of freshwater should be re-examined from the increase of bacterial resistance point of view.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[2007/02266-7]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[2007/02238-3]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Financiadora de Estudos e Projetos (FINEP)Financiadora de Estudos e Projetos (FINEP)[0934/07

Zooanthroponotic Transmission of Drug-Resistant Pseudomonas aeruginosa, Brazil

We recovered VIM-2 carbapenemase-producing Pseudomonas aeruginosa isolates from an infected dog, its owner, and the domestic environment. Genomic investigation revealed household transmission of the high-risk hospital clone sequence type 233 in the human–animal–environment interface. Results suggest zooanthroponotic transmission of VIM-2–producing P. aeruginosa in the household following the patient's hospital discharge