Proteomic Dynamics of Multidrug Resistance Mechanisms in Lucena 1 Cell Line.

The Lucena 1 cell line, derived from the human chronic myeloid leukemia cell line K562 under selective pressure of vincristine supplementation, exhibits multidrug resistance (MDR). This study aims to explore and elucidate the underlying mechanisms driving MDR in the Lucena 1 cell line. A proteomic analysis comparing K562 and Lucena 1 revealed qualitative differences, with a focus on the ATP-dependent efflux pump, Translocase ABCB1, a key contributor to drug resistance. Tubulin analysis identified two unique isoforms, Tubulin beta 8B and alpha chain-like 3, exclusive to Lucena 1, potentially influencing resistance mechanisms. Additionally, the association of Rap1A and Krit1 in cytoskeletal regulation and the presence of STAT1, linked to the urea cycle and tumor development, offered insights into Lucena 1's distinctive biology. The increased expression of carbonic anhydrase I suggested a role in pH regulation. The discovery of COP9, a tumor suppressor targeting p53, further highlighted the Lucena 1 complex molecular landscape. This study offers new insights into the MDR phenotype and its multifactorial consequences in cellular pathways. Thus, unraveling the mechanisms of MDR holds promise for innovating cancer models and antitumor targeted strategies, since inhibiting the P-glycoprotein (P-gp)/ABCB1 protein is not always an effective approach given the associated treatment toxicity.

Exploring extended-spectrum beta lactamase resistance in Vibrio parahaemolyticus and Vibrio cholerae within the tropical mangrove ecosystem of southwest India.

Multidrug-resistant pathogenic vibrios are a crisis of concern as they cause multiple illnesses, including gastroenteritis in humans and acute hepatopancreatic necrosis in aquaculture. In the current study, we investigated the prevalence of the beta-lactamase gene CTX-M-group 1 in Vibrio spp. (Vibrio cholerae and Vibrio parahaemolyticus) from the water and sediment of urban tropical mangrove ecosystems of Kerala, southwest India. A total of 120 isolates of Vibrio spp. were tested for antibiotic susceptibility to 14 antibiotics. In water, ampicillin resistance was very high in isolates of V. cholerae (94.1%, n = 17) and V. parahaemolyticus (89.1%, n = 46). 26.9% of V. parahaemolyticus and 14.2% of V. cholerae harbored the CTX-M-group 1 gene in water samples. Compared to V. cholerae, the CTX-M-group 1 gene was exclusively hosted by V. parahaemolyticus (49%) in sediment samples. A significant difference in the prevalence of the CTX-M-group 1 gene was observed among Vibrio spp. in both water and sediment samples (p < 0.05). The results revealed the presence of multidrug-resistant and beta-lactamase harboring Vibrio spp. in mangrove ecosystems, which may have evolved as a consequence of the misuse and abuse of broad-spectrum antibiotics as prophylaxis in human health care and aquaculture.

Characterization of Antibiotic-Resistance Antarctic Pseudomonas That Produce Bacteriocin-like Compounds.

In this study, bacterial isolates C1-4-7, D2-4-6, and M1-4-11 from Antarctic soil were phenotypically and genotypically characterized, and their antibacterial spectrum and that of cell-free culture supernatant were investigated. Finally, the effect of temperature and culture medium on the production of antimicrobial compounds was investigated. The three bacteria were identified as different strains of the genus Pseudomonas. The three bacteria were multi-drug resistant to antibiotics. They exhibited different patterns of growth inhibition of pathogenic bacteria. M1-4-11 was remarkable for inhibiting the entire set of pathogenic bacteria tested. All three bacteria demonstrated optimal production of antimicrobial compounds at 15 °C and 18 °C. Among the culture media studied, Nutrient broth would be the most suitable to promote the production of antimicrobial compounds. The thermostability exhibited by the antimicrobial molecules secreted, their size of less than 10 kDa, and their protein nature would indicate that these molecules are bacteriocin-like compounds.

Detection mecA gene and Staphylococcus aureus resistance to several antibiotics isolated from cat ear swabs at a veterinary hospital located at Surabaya ­ Indonesia / Detecção do gene mecA e resistência a diversos antibióticos em Staphylococcus aureus isolados do ouvido de gatos em um hospital localizado em Surabaya ­ Indonesia

Cats are susceptible to S. aureus, which mainly colonizes the nose and ears of these feline species. Otitis externa in cat ears is one of the illnesses produced by S. aureus in animals. Antibiotic therapy for affected animals is the conventional treatment for infections by S. aureus. Antibiotic use during prolonged treatment and given at the wrong doses can cause germs to become resistant. Given this context, research on S. aureus isolated from cat ears and tests for antibiotic resistance and the mecA gene is required. Samples of cat ears were obtained from the Amies media using a sterile cotton swab. Bacterial isolation was done on MSA media, and then the catalase and coagulase assays were used to identify the bacteria. S. aureus isolates were evaluated for sensitivity using disks of the antibiotics cefoxitin, tetracycline, erythromycin, gentamicin, and chloramphenicol connected to MHA media. All positive isolates of S. aureus underwent MRSA testing, and then the mecA gene was detected. The sample investigation revealed that 91% (91/100) were positive for S. aureus, and 3.30% (3/91) were confirmed to be multidrug-resistant (MDR) because they are resistant to 3­4 antibiotic classes. Out of the 12 MRSA isolates analyzed, the mecA gene was detected in one isolate. Inappropriate antibiotic use causes bacterial resistance in pets. Additionally, excessive antibiotic use in a population might develop acquired bacterial resistance to an antibiotic. Antibiotic use in animals must be assessed to administer medication and prevent the development of antibiotic resistance appropriately.(AU)

Gatos são suscetíveis a adquirir S.aureus que colonizam principalmente as narinas e os ouvidos de espécies de felinos. A otite externa no ouvido dos gatos é uma das doenças produzidas pelo S.aureus nos animais. A terapia com antibióticos é o tratamento convencional para as infecções produzidas pelo S.aureus. Os antibióticos utilizados durante o prolongado tratamento e o emprego de sub doses podem selecionar microorganismos resistentes. Com base em tais argumentos torna-se necessária a pesquisa de S.aureus isolados do ouvido dos gatos, bem como, a realização de testes para a resistência a antibióticos e do gene mecA. Empregando swabs estéreis de algodão foram obtidas amostras dos ouvidos dos gatos em meio de Amies. O isolamento bacteriano foi efetuado em meio MAS e os testes catalase e coagulase foram realizados para a identificação das bactérias. A sensibilidade dos isolados de S.aureus foi avaliada com o emprego de discos dos antibióticos cefoxitin, tetraxiclina, eritromicina, gentamicina e cloranfenicol, incorporados no meio MHA. Todos os isolados positivos de S.aureus foram submetidos ao test MRSA para a detecção do gene mecA. A amostra investigada revelou 91% (91/100) de positivos para S.aureus, dos quais, 3,30% (3/91) foram resistentes a múltiplas drogas (MDR) pois foram resistentes a 3-4 classes de antibióticos. De 12 MRSA isolados analisados o gene mecA foi detectado em um isolado. O uso inapropriado de antibióticos é a causa da resistência bacteriana em pets. Adicionalmente o emprego excessivo de antibióticos em uma população pode resultar no desenvolvimento de resistência bacteriana adquirida a antibióticos. O uso de antibióticos em animais deve ser ordenado por uma administração de medicamentos apropriada para prevenir o desenvolvimento da resistência.(AU)

Deciphering the Role of WWTPs in Cold Environments as Hotspots for the Dissemination of Antibiotic Resistance Genes.

Cold environments are the most widespread extreme habitats in the world. However, the role of wastewater treatment plants (WWTPs) in the cryosphere as hotspots in antibiotic resistance dissemination has not been well established. Hence, a snapshot of the resistomes of WWTPs in cold environments, below 5 °C, was provided to elucidate their role in disseminating antibiotic resistance genes (ARGs) to the receiving waterbodies. The resistomes of two natural environments from the cold biosphere were also determined. Quantitative PCR analysis of the aadA, aadB, ampC, blaSHV, blaTEM, dfrA1, ermB, fosA, mecA, qnrS, and tetA(A) genes indicated strong prevalences of these genetic determinants in the selected environments, except for the mecA gene, which was not found in any of the samples. Notably, high abundances of the aadA, ermB, and tetA(A) genes were found in the influents and activated sludge, highlighting that WWTPs of the cryosphere are critical hotspots for disseminating ARGs, potentially worsening the resistance of bacteria to some of the most commonly prescribed antibiotics. Besides, the samples from non-disturbed cold environments had large quantities of ARGs, although their ARG profiles were highly dissimilar. Hence, the high prevalences of ARGs lend support to the fact that antibiotic resistance is a common issue worldwide, including environmentally fragile cold ecosystems.

Adenoviral Vector Codifying for TNF as a Co-Adjuvant Therapy against Multi-Drug-Resistant Tuberculosis.

Mycobacterium tuberculosis is the main causal agent of pulmonary tuberculosis (TB); the treatment of this disease is long and involves a mix of at least four different antibiotics that frequently lead to abandonment, favoring the surge of drug-resistant mycobacteria (MDR-TB), whose treatment becomes more aggressive, being longer and more toxic. Thus, the search for novel strategies for treatment that improves time or efficiency is of relevance. In this work, we used a murine model of pulmonary TB produced by the MDR-TB strain to test the efficiency of gene therapy with adenoviral vectors codifying TNF (AdTNF), a pro-inflammatory cytokine that has protective functions in TB by inducing apoptosis, granuloma formation and expression of other Th1-like cytokines. When compared to the control group that received an adenoviral vector that codifies for the green fluorescent protein (AdGFP), a single dose of AdTNF at the chronic active stage of the disease produced total survival, decreasing bacterial load and tissue damage (pneumonia), which correlated with an increase in cells expressing IFN-γ, iNOS and TNF in pneumonic areas and larger granulomas that efficiently contain and eliminate mycobacteria. Second-line antibiotic treatment against MDR-TB plus AdTNF gene therapy reduced bacterial load faster within a week of treatment compared to empty vector plus antibiotics or antibiotics alone, suggesting that AdTNF is a new potential type of treatment against MDR-TB that can shorten second-line chemotherapy but which requires further experimentation in other animal models (non-human primates) that develop a more similar disease to human pulmonary TB.

Household environment and animal fecal contamination are critical modifiers of the gut microbiome and resistome in young children from rural Nicaragua.

BACKGROUND: Early life plays a vital role in the development of the gut microbiome and subsequent health. While many factors that shape the gut microbiome have been described, including delivery mode, breastfeeding, and antibiotic use, the role of household environments is still unclear. Furthermore, the development of the gut antimicrobial resistome and its role in health and disease is not well characterized, particularly in settings with water insecurity and less sanitation infrastructure. RESULTS: This study investigated the gut microbiome and resistome of infants and young children (ages 4 days-6 years) in rural Nicaragua using Oxford Nanopore Technology's MinION long-read sequencing. Differences in gut microbiome diversity and antibiotic resistance gene (ARG) abundance were examined for associations with host factors (age, sex, height for age z-score, weight for height z-score, delivery mode, breastfeeding habits) and household environmental factors (animals inside the home, coliforms in drinking water, enteric pathogens in household floors, fecal microbial source tracking markers in household floors). We identified anticipated associations of higher gut microbiome diversity with participant age and vaginal delivery. However, novel to this study were the significant, positive associations between ruminant and dog fecal contamination of household floors and gut microbiome diversity. We also identified greater abundance of potential pathogens in the gut microbiomes of participants with higher fecal contamination on their household floors. Path analysis revealed that water quality and household floor contamination independently and significantly influenced gut microbiome diversity when controlling for age. These gut microbiome contained diverse resistome, dominated by multidrug, tetracycline, macrolide/lincosamide/streptogramin, and beta-lactam resistance. We found that the abundance of ARGs in the gut decreased with age. The bacterial hosts of ARGs were mainly from the family Enterobacteriaceae, particularly Escherichia coli. CONCLUSIONS: This study identified the role of household environmental contamination in the developing gut microbiome and resistome of young children and infants with a One Health perspective. We found significant relationships between host age, gut microbiome diversity, and the resistome. Understanding the impact of the household environment on the development of the resistome and microbiome in early life is essential to optimize the relationship between environmental exposure and human health. Video Abstract.

Extranodal NK-/T-cell lymphoma, nasal type: what advances have been made in the last decade?

Extranodal NK-/T-cell lymphoma (ENKTCL) is a rare and highly aggressive malignancy with significant racial and geographic variations worldwide. In addition to the formerly "nasal-type" initial description, these lymphomas are predominantly extranodal in origin and typically cause vascular damage and tissue destruction, and although not fully understood, Epstein-Barr virus (EBV) has an important role in its pathogenesis. Initial assessment must include a hematopathology review of representative and viable tumor areas without necrosis for adequate immunohistochemistry studies, including EBV-encoded small RNA (EBER) in situ hybridization (ISH). Positron emission tomography with 18-fluorodeoxyglucose (18F-FDG-PET/CT) for accurate staging is essential, and most patients will have localized disease (IE/IIE) at diagnosis. Apart from other T-cell malignancies, the best treatment even for localized cases is combined modality therapy (chemotherapy plus radiotherapy) with non-anthracycline-based regimens. For advanced-stage disease, l-asparaginase-containing regimens have shown improved survival, but relapsed and refractory cases have very poor outcomes. Nowadays, even with a better understanding of pathogenic pathways, up-front therapy is completely based on chemotherapy and radiotherapy, and treatment-related mortality is not low. Future strategies targeting signaling pathways and immunotherapy are evolving, but we need to better identify those patients with dismal outcomes in a pre-emptive way. Given the rarity of the disease, international collaborations are urgently needed, and clinical trials are the way to change the future.

Genomic Features of Antimicrobial Resistance in Staphylococcus pseudintermedius Isolated from Dogs with Pyoderma in Argentina and the United States: A Comparative Study.

Staphylococcus pseudintermedius is the most common opportunistic pathogen in dogs and methicillin resistance (MRSP) has been identified as an emerging problem in canine pyoderma. Here, we evaluated the antimicrobial resistance (AMR) features and phylogeny of S. pseudintermedius isolated from canine pyoderma cases in Argentina (n = 29) and the United States (n = 29). 62% of isolates showed multi-drug resistance. The AMR genes found: mecA, blaZ, ermB, dfrG, catA, tetM, aac(6')-aph(2″), in addition to tetK and lnuA (only found in U.S. isolates). Two point mutations were detected: grlA(S80I)-gyrA(S84L), and grlA(D84N)-gyrA(S84L) in one U.S. isolate. A mutation in rpoB (H481N) was found in two isolates from Argentina. SCCmec type III, SCCmec type V, ΨSCCmec57395 were identified in the Argentinian isolates; and SCCmec type III, SCCmec type IVg, SCCmec type V, and SCCmec type VII variant in the U.S. cohort. Sequence type (ST) ST71 belonging to a dominant clone was found in isolates from both countries, and ST45 only in Argentinian isolates. This is the first study to comparatively analyze the population structure of canine pyoderma-associated S. pseudintermedius isolates in Argentina and in the U.S. It is important to maintain surveillance on S. pseudintermedius populations to monitor AMR and gain further understanding of its evolution and dissemination.

Multidrug-resistant gram-negative bacteria in patients with COVID-19: An epidemiological and clinical study.

Epidemiological data regarding the incidence of secondary multidrug-resistant (MDR) Gram-negative infection in patients with coronavirus disease (COVID-19) in Brazil are still ambiguous. Thus, a case-control study was designed to determine factors associated with the acquisition of MDR Gram-negative bacteria (GNB) in patients with and without COVID-19 and describe the mortality rates and clinical features associated with unfavorable outcomes. In total, we assessed 280 patients admitted to Brazilian intensive care units from March/2020 to December/2021. During the study, 926 GNB were isolated. Out of those, 504 were MDR-GNB, representing 54.4% of the resistance rate. In addition, out of 871 patients positive for COVID-19, 73 had secondary MDR-GNB infection, which represented 8.38% of documented community-acquired GNB-MDR infections. The factors associated with patients COVID-19-MDR-GNB infections were obesity, heart failure, use of mechanical ventilation, urinary catheter, and previous use of ß-lactams. Several factors associated with mortality were identified among patients with COVID-19 infected with MDR-GNB, including the use of a urinary catheter; renal failure; and the origin of bacterial cultures such as tracheal secretion, exposure to carbapenem antibiotics, and polymyxin. Mortality was significantly higher in patients with COVID-19-MDR-GNB (68.6%) compared to control groups, where COVID-19 was 35.7%, MDR-GNB was 50%, and GNB was 21.4%. Our findings demonstrate that MDR-GNB infection associated with COVID-19 has an expressive impact on increasing the case fatality rate, reinforcing the importance of minimizing the use of invasive devices and prior exposure to antimicrobials to control the bacterial spread in healthcare environments to improve the prognosis among critical patients.

Antibiotic resistance profile of wastewater treatment plants in Brazil reveals different patterns of resistance and multi resistant bacteria in final effluents.

Wastewater treatment plants (WWTPs) are recognized as important sources of Antibiotic Resistant Bacteria (ARBs) and Antibiotic Resistant Genes (ARGs), and might play a role in the removal and dissemination of antimicrobial resistance (AMR) in the environment. Detailed information about AMR removal by the different treatment technologies commonly applied in urban WWTPs is needed. This study investigated the occurrence, removal and characterization of ARBs in WWTPs employing different technologies: WWTP-A (conventional activated sludge-CAS), WWTP-B (UASB reactor followed by biological trickling filter) and WWTP-C (modified activated sludge followed by UV disinfection-MAS/UV). Samples of raw sewage (RI) and treated effluent (TE) were collected and, through the cultivation-based method using 11 antibiotics, the antibiotic resistance profiles were characterized in a one-year period. MAS was effective in reducing ARB counts (2 to 3 log units), compared to CAS (1 log unit) and UASB/BTF (0.5 log unit). The composition of cultivable ARB differed between RI and TE samples. Escherichia was predominant in RI (56/118); whilst in TE Escherichia (31/118) was followed by Bacillus (22/118), Shigella (14/118) and Enterococcus (14/118). Most of the isolates identified (370/394) harboured at least two ARGs and in over 80 % of the isolates, 4 or more ARG (int1, blaTEM, TetA, sul1 and qnrB) were detected. A reduction in the resistance prevalence was observed in effluents after CAS and MAS processes; whilst a slight increase was observed in treated effluents from UASB/BTF and after UV disinfection stage. The multi-drug resistance (MDR) phenotype was attributed to 84.3 % of the isolates from RI (27/32) and 63.6 % from TE (21/33) samples and 52.3 % of the isolates (34/65) were resistant to carbapenems (imipenem, meropenem, ertapenem). The results indicate that treated effluents are still a source for MDR bacteria and ARGs dissemination to aquatic environments. The importance of biological sewage treatment was reinforced by the significant reductions in ARB counts observed. However, implementation of additional treatments is needed to mitigate MDR bacteria release into the environment.

Conjugative transfer of multi-drug resistance IncN plasmids from environmental waterborne bacteria to Escherichia coli.

Watersheds contaminated with municipal, hospital, and agricultural residues are recognized as reservoirs for bacteria carrying antibiotic resistance genes (ARGs). The objective of this study was to determine the potential of environmental bacterial communities from the highly contaminated La Paz River basin in Bolivia to transfer ARGs to an Escherichia coli lab strain used as the recipient. Additionally, we tested ZnSO4 and CuSO4 at sub-inhibitory concentrations as stressors and analyzed transfer frequencies (TFs), diversity, richness, and acquired resistance profiles. The bacterial communities were collected from surface water in an urban site close to a hospital and near an agricultural area. High transfer potentials of a large set of resistance factors to E. coli were observed at both sites. Whole-genome sequencing revealed that putative plasmids belonging to the incompatibility group N (IncN, IncN2, and IncN3) were predominant among the transconjugants. All IncN variants were verified to be mobile by a second conjugation step. The plasmid backbones were similar to other IncN plasmids isolated worldwide and carried a wide range of ARGs extensively corroborated by phenotypic resistance patterns. Interestingly, all transconjugants also acquired the class 1 integron intl1, which is commonly known as a proxy for anthropogenic pollution. The addition of ZnSO4 and CuSO4 at sub-inhibitory concentrations did not affect the transfer rate. Metal resistance genes were absent from most transconjugants, suggesting a minor role, if any, of metals in the spread of multidrug-resistant plasmids at the investigated sites.

WGS-Based Lineage and Antimicrobial Resistance Pattern of Salmonella Typhimurium Isolated during 2000-2017 in Peru.

Salmonella Typhimurium is associated with foodborne diseases worldwide, including in Peru, and its emerging antibiotic resistance (AMR) is now a global public health problem. Therefore, country-specific monitoring of the AMR emergence is vital to control this pathogen, and in these aspects, whole genome sequence (WGS)­based approaches are better than gene-based analyses. Here, we performed the antimicrobial susceptibility test for ten widely used antibiotics and WGS-based various analyses of 90 S. Typhimurium isolates (human, animal, and environment) from 14 cities of Peru isolated from 2000 to 2017 to understand the lineage and antimicrobial resistance pattern of this pathogen in Peru. Our results suggest that the Peruvian isolates are of Typhimurium serovar and predominantly belong to sequence type ST19. Genomic diversity analyses indicate an open pan-genome, and at least ten lineages are circulating in Peru. A total of 48.8% and 31.0% of isolates are phenotypically and genotypically resistant to at least one antibiotic, while 12.0% are multi-drug resistant (MDR). Genotype−phenotype correlations for ten tested drugs show >80% accuracy, and >90% specificity. Sensitivity above 90% was only achieved for ciprofloxacin and ceftazidime. Two lineages exhibit the majority of the MDR isolates. A total of 63 different AMR genes are detected, of which 30 are found in 17 different plasmids. Transmissible plasmids such as lncI-gamma/k, IncI1-I(Alpha), Col(pHAD28), IncFIB, IncHI2, and lncI2 that carry AMR genes associated with third-generation antibiotics are also identified. Finally, three new non-synonymous single nucleotide variations (SNVs) for nalidixic acid and eight new SNVs for nitrofurantoin resistance are predicted using genome-wide association studies, comparative genomics, and functional annotation. Our analysis provides for the first time the WGS-based details of the circulating S. Typhimurium lineages and their antimicrobial resistance pattern in Peru.

First detection and origin of multi-drug resistant Klebsiella pneumoniae ST15 harboring OXA-48 in South America.

OBJECTIVES: The emergence and spread of carbapenem resistant clones is of major concern for global health. This study aimed to characterize the first detected Klebsiella pneumoniae ST15 harboring the epidemic carbapenemase OXA-48 in South America. METHODS: During a routine colonization screening with carbapenem-resistant bacteria, one K. pneumoniae strain (CGHM01) was isolated from the urine of a hospitalized patient suffering from a neurodegenerative disease in Uruguay. We used long-read whole-genome sequencing and a phylogenomic approach to characterize the emergence of K. pneumoniae CGHM01. RESULTS: K. pneumoniae CGHM01 is a multi-drug resistant strain carrying an IncL/M plasmid that encodes the carbapenemase gene blaOXA-48 within the Tn1999.2 transposon. Also, it carries an IncR plasmid harboring a class I integron with an array of antibiotic resistance genes including the extended-spectrum beta-lactamase blaCTX-M-15. Two copies of blaCTX-M-15 were also inserted in different positions of the chromosome. CGHM01 belongs to a ST15 sublineage that likely originated in continental Spain around 2012. CONCLUSIONS: The asymptomatic carriage of this strain in the urinary tract warns of difficulties for detection and reporting of emerging carbapenem-resistant clones in new geographic areas where these are not endemic.

Tertiary Nanosystem Composed of Graphene Quantum Dots, Levofloxacin and Silver Nitrate for Microbiological Control.

BACKGROUND: Infectious diseases have the highest mortality rate in the world and these numbers are associated with scarce and/or ineffective diagnosis and bacterial resistance. Currently, with the development of new pharmaceutical formulations, nanotechnology is gaining prominence. METHODS: Nanomicelles were produced by ultrasonication. The particle size and shape were evaluated by scanning electron microscopy and confirmed by dynamic light scattering, also thermogravimetric analysis was performed to evaluate the thermal stability. Finally, antibacterial activity has been performed. RESULTS: The results showed that a rod-shaped nanosystem, with 316.1 nm and PDI of 0.243 was formed. The nanosystem was efficient against Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis subsp. spizizenii with MIC inferior to 0.98 and a synergistic effect between silver graphene quantum dots and levofloxacin was observed. CONCLUSION: The nanosystem produced may rise as a promising agent against the bacterial threat, especially regarding bacterial resistance.

Fungal Bloodstream Co-infection by Trichosporon asahii in a COVID-19 Critical Patient: Case Report and Literature Review.

Opportunistic infections are serious complications in critically ill COVID-19 patients, especially co-infections with bacterial and fungal agents. Here we report a rare case of bloodstream co-infection by Trichosporon asahii, an emerging yeast, and Acinetobacterbaumannii, an opportunistic nosocomial pathogen, both multidrug resistant, in a tertiary hospital from southern Brazil. A review of the literature regarding similar cases is also included. Treatment with multiple antimicrobials failed, and the patient progressed to death four days after the diagnosis of bacteremia and fungemia.

Genomic Comparison of Eight Closed Genomes of Multidrug-Resistant Salmonella enterica Strains Isolated From Broiler Farms and Processing Plants in Trinidad and Tobago.

Salmonella enterica is an important foodborne pathogen worldwide. We used long and short-read sequencing to close genomes of eight multidrug-resistant (MDR) S. enterica strains, belonging to serovars Infantis (2), Albany, Oranienburg, I 4,[5],12:i:-, Javiana, Schwarzengrund, and Kentucky from broiler chicken farms and processing plants in Trinidad and Tobago. They also belonged to seven different sequence types (STs- 32, 292, 1510, 19, 24, 152, and 96). Among the strains, seven had demonstrated multi-drug resistance with the presence of at least three AMR genes, whereas three isolates contained the quinolone resistance gene qnr B19 in plasmids (CFSAN103840, CFSAN103854, and CFSAN103872). The extended-spectrum ß-lactamase genes bla CTX-M-65 (CFSAN103796) and bla TEM-1 (CFSAN103852) were detected in this study. The genomes closed in this study will be useful for future source tracking and outbreak investigations in Trinidad and Tobago and worldwide.

A Ternary Copper (II) Complex with 4-Fluorophenoxyacetic Acid Hydrazide in Combination with Antibiotics Exhibits Positive Synergistic Effect against Salmonella Typhimurium.

Salmonella spp. continues to figure prominently in world epidemiological registries as one of the leading causes of bacterial foodborne disease. We characterised 43 Brazilian lineages of Salmonella Typhimurium (ST) strains, characterized drug resistance patterns, tested copper (II) complex as control options, and proposed effective antimicrobial measures. The minimum inhibitory concentration was evaluated for seven antimicrobials, isolated and combined with the copper (II) complex [Cu(4-FH)(phen)(ClO4)2] (4-FH = 4-fluorophenoxyacetic acid hydrazide and phen = 1,10-phenanthroline), known as DRI-12, in planktonic and sessile ST. In parallel, 42 resistance genes were screened (PCR/microarray). All strains were multidrug resistant (MDR). Resistance to carbapenems and polymyxins (86 and 88%, respectively) have drawn attention to the emergence of the problem in Brazil, and resistance is observed also to CIP and CFT (42 and 67%, respectively), the drugs of choice in treatment. Resistance to beta-lactams was associated with the genes blaTEM/blaCTX-M in 39% of the strains. Lower concentrations of DRI-12 (62.7 mg/L, or 100 µM) controlled planktonic and sessile ST in relation to AMP/SUL/TET and AMP/SUL/TET/COL, respectively. The synergistic effect provided by DRI-12 was significant for COL/CFT and COL/AMP in planktonic and sessile ST, respectively, and represents promising alternatives for the control of MDR ST.

Beyond to the Stable: Role of the Insertion Sequences as Epidemiological Descriptors in Corynebacterium striatum.

In recent years, epidemiological studies of infectious agents have focused mainly on the pathogen and stable components of its genome. The use of these stable components makes it possible to know the evolutionary or epidemiological relationships of the isolates of a particular pathogen. Under this approach, focused on the pathogen, the identification of resistance genes is a complementary stage of a bacterial characterization process or an appendix of its epidemiological characterization, neglecting its genetic components' acquisition or dispersal mechanisms. Today we know that a large part of antibiotic resistance is associated with mobile elements. Corynebacterium striatum, a bacterium from the normal skin microbiota, is also an opportunistic pathogen. In recent years, reports of infections and nosocomial outbreaks caused by antimicrobial multidrug-resistant C. striatum strains have been increasing worldwide. Despite the different existing mobile genomic elements, there is evidence that acquired resistance genes are coupled to insertion sequences in C. striatum. This perspective article reviews the insertion sequences linked to resistance genes, their relationship to evolutionary lineages, epidemiological characteristics, and the niches the strains inhabit. Finally, we evaluate the potential of the insertion sequences for their application as a descriptor of epidemiological scenarios, allowing us to anticipate the emergence of multidrug-resistant lineages.

Contribution of Governance and Socioeconomic Factors to the P. aeruginosa MDR in Europe.

This work aims to explain the behavior of the multi-drug resistance (MDR) percentage of Pseudomonas aeruginosa in Europe, through multivariate statistical analysis and machine learning validation, using data from the European Antimicrobial Resistance Surveillance System, the World Health Organization, and the World Bank. We ran a multidimensional data panel regression analysis and used machine learning techniques to validate a pooling panel data case. The results of our analysis showed that the most important variables explaining the MDR phenomena across European countries are governance variables, such as corruption control and the rule of law. The models proposed in this study showed the complexity of the antibiotic drugs resistance problem. The efforts controlling MDR P. aeruginosa, as a well-known Healthcare-Associated Infection (HCAI), should be focused on solving national governance problems that impact resource distribution, in addition to individual guidelines, such as promoting the appropriate use of antibiotics.