Systematic Review and Meta-Analysis of Second-Generation Sham-Controlled Randomized Trials of Renal Denervation Therapy for Patients with Hypertension.

INTRODUCTION: Renal denervation has been associated with substantial and sustained blood pressure reduction and is considered to serve as an alternative treatment for patients with resistant hypertension. However, the first published SHAM-controlled trial assessing RDN safety and efficacy showed no difference between groups. AIM: We aimed to perform a meta-analysis quantifying the magnitude of blood pressure decrease secondary to renal denervation in patients with resistant hypertension. METHODS: Databases were searched for RCTs that compared RDN therapy to SHAM procedure and reported the outcomes of (1) 24-hour ambulatory blood pressure; (2) Office systolic blood pressure; (3) Daytime systolic blood pressure; and (4) Night-time systolic blood pressure. Mean differences with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was examined with I² statistics. P values of < 0.05 were considered statistically significant. Statistical analyses were performed using RStudio 4.2.3. RESULTS: Nine studies and 1622 patients were included. The AMBP [MD -3.72 95%CI -5.44, -2.00 p < 0.001; I²=34%] and DSBP [MD -4.10 95%CI -5.84, -2.37 p < 0.001; I²=0%] were significantly reduced in the RDN arm. ODBP [MD -6.04 95%CI -11.31, -0.78 p = 0.024; I²=90%] and NSBP [MD -1.81 95%CI -3.90, 0.27 p = 0.08; I²=0%] did not reach a statistically significant difference between groups. CONCLUSION: Renal denervation demonstrates greater efficacy in reducing 24-hour ambulatory and daytime systolic blood pressure in patients diagnosed with resistant hypertension.

Orange Cookies with Type-4 Resistant Starch: Physical, Nutritional, and Sensorial Characteristics as Evaluated by Patients with Irritable Bowel Syndrome.

A low-fermentable oligo-, di-, monosaccharide and polyol (low-FODMAP) diet for patients with irritable bowel syndrome (IBS) should include an adequate fiber source. Our aim was to formulate orange cookies using maize flour and type-4 resistant starch (RS4) from maize and to evaluate their properties and sensorial attributes by IBS patients. We prepared two formulations: 37.7% RS4 and 14.7% maize flour and a control with normal maize starch (MS) instead of RS4. We added orange juice and zest instead of water and evaluated their properties. The viscosity, water absorption capacity, and solubility were lower for RS4 than for MS. The width, thickness, L* and a* values of both cookies were comparable (p > 0.05), although RS4-C had a decreased b* value and higher hardness (90.6 vs. 80.1 N). The nutrient content was similar between RS4-C and MS-C, but the glycemic index of RS4-C was 63 compared to 95 of MS-C. According to IBS patients, the appearance, taste, hardness, overall quality, and perception of healthiness and nutritional value of both types of cookies were similarly high (p > 0.05). Panelists recommend the cookies. Therefore, RS4 cookies could be further investigated for their ability to improve bowel habits and re-equilibrate the microbiota of IBS patients.

Nanocomposites: silver nanoparticles and bacteriocins obtained from lactic acid bacteria against multidrug-resistant Escherichia coli and Staphylococcus aureus.

Drug-resistant bacteria such as Escherichia coli and Staphylococcus aureus represent a global health problem that requires priority attention. Due to the current situation, there is an urgent need to develop new, more effective and safe antimicrobial agents. Biotechnological approaches can provide a possible alternative control through the production of new generation antimicrobial agents, such as silver nanoparticles (AgNPs) and bacteriocins. AgNPs stand out for their antimicrobial potential by employing several mechanisms of action that can act simultaneously on the target cell such as the production of reactive oxygen species and cell wall rupture. On the other hand, bacteriocins are natural peptides synthesized ribosomally that have antimicrobial activity and are produced, among others, by lactic acid bacteria (LAB), whose main mechanism of action is to produce pores at the level of the cell membrane of bacterial cells. However, these agents have disadvantages. Nanoparticles also have limitations such as the tendency to form aggregates, which decreases their antibacterial activity and possible cytotoxic effects, and bacteriocins have a narrow spectrum of action, require high doses to be effective, and can be degraded by proteases. Given these limitations, nanoconjugates of these two agents have been developed that can act synergistically in the control of pathogenic bacteria resistant to antibiotics. This review focuses on knowing relevant aspects of the antibiotic resistance of E. coli and S. aureus, the characteristics of these new generation antibacterial agents, and their effect alone or forming nanoconjugates that are more effective against the multiresistant mentioned bacteria.

Dog Breed and Starch Gelatinisation Correlation in Food Digestibility and Faecal Traits.

Large dog breeds commonly produce unformed faeces. The present study hypothesised that foods for large dog breeds require higher starch gelatinisation (SG) to reduce organic matter flow to colon. Fifteen Rottweilers (Ro; 49.4 ± 6.12 kg), 18 Beagles (Be; 12.13 ± 1.75 kg) and 20 Shih-Tzus (ST; 4.62 ± 1.15 kg) were fed one of three diets, all based on the same sorghum formulation, processed to obtain three levels of SG: SG90 (91.8% SG), SG50 (50.7% SG) and SG30 (27.4% SG). Foods were provided for 23 days, and the coefficient of total tract apparent digestibility (CTTAD) of nutrients, faecal production and fermentation products, Na, K and Cl apparent absorption and gastrointestinal transit time (GTT) were evaluated. Results were submitted to analysis of variance considering SG, breed and their interactions, and means compared by the Tukey test (p < 0.05). All dogs promptly ate the foods. Faeces scores were lower for Ro than for Be and ST, and lower for SG30 than SG90 (p < 0.05). Faeces pH was higher, and total short-chain fatty acids were lower for SG90 than for SG50 and SG30 (p < 0.01), regardless of breed. No diet effect was observed for GTT (p > 0.05), but it was lower for Ro (41.7 ± 6.2 h) than for ST (48.7 ± 8.6 h). The CTTAD of nutrients was lower for SG30, intermediary for SG50 and higher for SG90 (p < 0.05), and among breeds CTTAD was higher for Be than ST and Ro (p < 0.05), which did not differ from each other, except for crude protein CTTAD which was lower for Ro (p < 0.05). The apparent absorption of Na and K was higher for the SG90 treatment, and for Be in comparison with Ro and ST (p < 0.05). Food SG had a remarkable influence on Ro faeces formation and on the CTTAD in all breeds. Greater fermentation in the colon and lower protein CTTAD may be involved in Ro unformed faeces formation.

Latin American Challenges and Recommendations for Poly Adenosine Diphosphate Ribose Polymerase Inhibitor Treatment in Metastatic Castration Resistant Prostate Cancer: An Expert Overview.

In Latin America, prostate cancer is the third most common cancer overall and the most common in men, with the highest mortality rate of all cancers. In 2022, there were approximately 22,985 new prostate cancer cases and 61,056 deaths from prostate cancer in the region. Patients with metastatic disease that is resistant to cure by castration now have multiple therapeutic options, including poly-ADP ribose polymerase inhibitors. These treatment advances present new challenges, such as developing monitoring protocols for early detection of disease progression to castration resistance. The Americas Health Foundation organized a 3-day meeting with 8 regional oncologists and pathologists to create a paper on metastatic castration-resistant prostate cancer diagnosis and therapy, including the new poly-ADP ribose polymerase inhibitors. The panel examined metastatic castration-resistant prostate cancer in Latin America and recommended ways to improve patient care using published literature and their expertise. Gene mutations play an important role in prostate cancer development. Precision medicine innovations highlight the importance of genotyping DNA variants and tumor biomarkers for targeted treatment. Access to appropriate genetic testing is difficult, medications are available but expensive, and there is a lack of infrastructure and regulatory frameworks that prevent patients from benefiting from innovative therapies. The panel recommends developing a population database and biobank and creating tumor tissue collection, processing, and storage facilities. Multi-stakeholder collaboration is needed to integrate the information gathered, train staff, select target populations, improve patient accessibility, and reduce the cost burden of drugs, genetic counselors, and cancer geneticists in Latin America. Collaboration is essential among healthcare professionals, policymakers, patient advocacy groups, pharmaceutical companies, and international organizations to address these challenges and needs in Latin America.

Catastrophic floods and antimicrobial resistance: Interconnected threats with wide-ranging impacts.

•Climate change and AMR combined worsen vulnerabilities, accelerating AMR spread.•Floods can spread AMR-related pathogens, impacting health, agriculture, and ecosystems.•Integrated strategies are needed to address climate change and AMR, enhancing sanitation.

In vitro and in vivo efficacy of zinc oxide green nanoparticles against multidrug-resistant Salmonella Typhi.

Antibiotic resistance is an increasing threat, requiring novel therapeutic solutions. Metal nanoparticles e.g., zinc oxide nanoparticles (ZnO NPs) exhibited the potential against many bacterial pathogens. Strains of Salmonella enterica serovar Typhi resistant to ceftriaxone were reported first from Pakistan in 2016. Since then, S. Typhi is a pathogen of concern globally owing to its rapidly emerging resistance potential against many last resort antibiotics. In the present study, in vitro and in vivo antimicrobial activity of ZnO NPs against multidrug resistant (MDR) and extensively drug resistant (XDR) Salmonella Typhi strains from Pakistan was evaluated. Zinc oxide green nanoparticles (ZnO GNPs), synthesized from Aloe vera, were characterized by SEM, XRD, UV-vis and Raman spectroscopy. In vitro antibacterial activity of two different concentrations of ZnO GNPs (7 and 15%) was checked using agar well diffusion method. Further, broth microdilution and time kill assays were performed using the ZnO GNPs. In vivo assays were conducted in BALB/c mice sepsis models. In all the three methods, agar well diffusion assay broth microdilution and time kill assay, different zinc oxide dihydrate precursor concentrations had shown the antibacterial activity. The minimum inhibitory concentration (MIC) of ZnO GNPs nanoparticles against MDR and XDR S. Typhi strains was found as 16 to 64 µg/ml. In vivo experiment has shown a significant decrease in CFU/ml in the mice treated with ZnO GNPs as compared to the control group. Our findings have revealed that ZnO GNPs have significant antibacterial activity against MDR and XDR S. Typhi, both in vitro and in vivo.

Polymyxin combined with Ocimum gratissimum essential oil: one alternative strategy for combating polymyxin-resistant Klebsiella pneumoniae.

Introduction. Multidrug-resistant infections present a critical public health due to scarce treatment options and high mortality. Ocimum gratissimum L. essential oil (O.geo) is a natural resource rich in eugenol known for its antimicrobial activity.Hypothesis/Gap Statement. O.geo may exert effective antimicrobial activity against polymyxin-resistant Klebsiella pneumoniae and, when combined with Polymyxin B (PMB), may exhibit a synergistic effect, enhancing treatment efficacy and reducing antimicrobial resistance.Aim. This study aims to investigate the antimicrobial activity of O.geo against polymyxin-resistant K. pneumoniae using in vitro tests and an in vivo Caenorhabditis elegans model.Methodology. The O.geo was obtained by hydrodistillation followed by gas chromatography. The MIC and antibiofilm activity were determined using broth microdilution. Checkerboard and time-kill assays evaluated the combination of O.geo and polymyxin B (PMB), whereas a protein leakage assay verified its action.Results. Eugenol (39.67%) was a major constituent identified. The MIC of the O.geo alone ranged from 128 to 512 µg ml-1. The fractional inhibitory concentration index (0.28) and time-kill assay showed a synergism. In addition, O.geo and PMB inhibited biofilm formation and increased protein leakage in the plasma membrane. The treatment was tested in vivo using a Caenorhabditis elegans model, and significantly increased survival without toxicity was observed.Conclusion. O.geo could be used as a potential therapeutic alternative to combat infections caused by multidrug-resistant bacteria, especially in combination with PMB.

Colonisation by multidrug-resistant organisms in health workers in primary care: narrow spectrum oral antimicrobials are a risk factor.

BACKGROUND: Limited information exists on carriage of multidrug-resistant organisms (MDRO) by health workers (HWs) in primary care settings. This study aims to determine the prevalence of MDRO carriage among HWs in primary care and to identify associated risk factors. METHODS: A cross-sectional study was conducted across all 12 primary care units in São Caetano do Sul-SP, Brazil, from October to December 2023. Self-collected samples (nasal, oropharyngeal, and inguinal) were obtained. Environment cultures (potable water, sewage and stream water) were evaluated. Stenotrophomonas maltophilia isolates (human and environmental) were typed. RESULTS: The study included 265/288 (92%) of HWs in primary care teams, mostly women with a median age of 47 years (IQR 38-57); 78% had no comorbidities. MDRO colonisation was found in 8.7% (23 HWs). The following bacteria were found: S. maltophilia (n = 9; 3.4%) in inguinal swabs; methicillin-resistant Staphylococcus aureus (n = 8; 3%) from all sites; extended-spectrum ß-lactamase-producing bacteria (n = 5; 2%) in inguinal swabs; and vancomycin-resistant enterococci in an inguinal swab (n = 1; 0.4%). Previous antibiotic use was significantly associated with MDRO colonisation (OR 2.91, 95% CI 1.19-7.09, p = 0.018), mainly narrow spectrum oral beta-lactams and macrolides. S. malthophilia was polyclonal and human and environmental isolates differed. CONCLUSION: Colonisation by MRSA, VRE, and ESBL-producing bacteria was low; however, 4% were surprisingly colonized by polyclonal S. maltophilia. This pathogen may also suggest using narrow-spectrum rather than the expected broad-spectrum antimicrobials. Antibiotic use was the only risk factor found, mainly with oral narrow-spectrum drugs.

Machine Learning in FTIR Spectrum for the Identification of Antibiotic Resistance: A Demonstration with Different Species of Microorganisms.

Recent studies introduced the importance of using machine learning algorithms in research focused on the identification of antibiotic resistance. In this study, we highlight the importance of building solid machine learning foundations to differentiate antimicrobial resistance among microorganisms. Using advanced machine learning algorithms, we established a methodology capable of analyzing the FTIR structural profile of the samples of Streptococcus pyogenes and Streptococcus mutans (Gram-positive), as well as Escherichia coli and Klebsiella pneumoniae (Gram-negative), demonstrating cross-sectional applicability in this focus on different microorganisms. The analysis focuses on specific biomolecules-Carbohydrates, Fatty Acids, and Proteins-in FTIR spectra, providing a multidimensional database that transcends microbial variability. The results highlight the ability of the method to consistently identify resistance patterns, regardless of the Gram classification of the bacteria and the species involved, reinforcing the premise that the structural characteristics identified are universal among the microorganisms tested. By validating this approach in four distinct species, our study proves the versatility and precision of the methodology used, in addition to bringing support to the development of an innovative protocol for the rapid and safe identification of antimicrobial resistance. This advance is crucial for optimizing treatment strategies and avoiding the spread of resistance. This emphasizes the relevance of specialized machine learning bases in effectively differentiating between resistance profiles in Gram-negative and Gram-positive bacteria to be implemented in the identification of antibiotic resistance. The obtained result has a high potential to be applied to clinical procedures.

ST105 Lineage of MRSA: An Emerging Implication for Bloodstream Infection in the American and European Continents.

Sequence-type 5 (ST5) of methicillin-resistant Staphylococcus aureus (MRSA), harboring the staphylococcal chromosomal cassette mec type IV (SCCmecIV), was first detected in Portugal. It emerged as a significant cause of healthcare-associated (HA) infection in pediatric units and was hence named the pediatric clone. Another ST5 lineage, which carries SCCmecII, also prevailed in the USA and Japan for multiple years. More recently, another MRSA lineage, ST105-SCCmecII, part of the evolution of clonal complex 5 (CC5) MRSA, has emerged as the cause of hospital-acquired bloodstream infection outbreaks in countries including Portugal, the USA, and Brazil. This article reviews studies on the epidemiology and evolution of these newly emerging pathogens. To this end, a search of PUBMED from inception to 2024 was performed to find articles reporting the occurrence of ST105 MRSA in epidemiologic studies. A second search was performed to find studies on MRSA, CC5, ST5, and SCCmecII. A search of PUBMED from 1999 to 2024 was also performed to identify studies on the genomics and evolution of ST5, CC5, and ST105 MRSA. Further studies were identified by analyzing the references of the previously selected articles from PUBMED. Most articles on ST105 MRSA were included in this review. Only articles written in English were included. Furthermore, only studies that used a reliable genotyping method (e.g., whole genome sequencing, or MLST) to classify the CC5 lineages were selected. The quality and selection of articles were based on the consensus assessment of the three authors in independent evaluations. In conclusion, ST105-SCCmecII is an emerging MRSA in several countries, being the second/third most important CC5 lineage, with a relatively high frequency in bloodstream infections. Of concern is the increased mortality from BSI in patients older than 15 years and the higher prevalence of ST105-SCCmecII in the blood of patients older than 60 years reported in some studies.

Impact of Central Line-Associated Bloodstream Infections on Mortality and Hospital Stay in Adult Patients at a Tertiary Care Institution in Cali, Colombia, 2015-2018.

Background: Central line-associated bloodstream infections (CLABSIs) are a significant healthcare challenge globally, increasing mortality risk and complicating central vascular catheter use. In Colombia, few studies have assessed the impact of CLABSIs on hospital stay and mortality. Objective: To determine the association between CLABSIs and discharge outcomes and hospital stay duration in adult patients at a tertiary care institution in Cali, Colombia, from 1 January 2015 to 31 December 2018. Methods: A nested case-control study was conducted. The odds of mortality associated with CLABSIs were estimated using conditional logistic regression. Non-conditional logistic regression was used to determine the odds of mortality when CLABSIs were caused by resistant microorganisms. Hospital stay duration, catheter duration, and time from catheter insertion to discharge were compared between patients with and without CLABSIs. The most frequent etiological agents were identified. Results: Patients with CLABSIs had 3.89 times the odds of mortality (95% CI [1.33-11.31], p = 0.013) compared to those without CLABSIs. The odds of mortality for patients with resistant microorganism CLABSIs were 4.04 times (95% CI [1.17-13.96], p = 0.027) higher than those with sensitive microorganism CLABSIs. Hospital stay duration (median = 51 days vs. 17 days; p = 0.000), catheter duration (median = 19 days vs. 7 days; p < 0.001), and time from catheter insertion to discharge (median = 40 days vs. 9 days; p < 0.001) were significantly longer in CLABSI patients. Klebsiella pneumoniae was the most isolated pathogen (20.2%), followed by Staphylococcus aureus (14.9%). Implications: CLABSI patients have longer catheter and hospitalization durations and higher mortality risk. Resistant microorganism CLABSIs are associated with elevated mortality risk. Conclusions: This study corroborates the positive relation between CLABSI and the mortality risk, which is influenced by resistant bacteria, though causality is not established. CLABSI is also linked to longer hospital stays, underscoring the need for improving infection control strategies.

Comparative in vitro activity of Delafloxacin and other antimicrobials against isolates from patients with acute bacterial skin, skin-structure infection and osteomyelitis.

The aim of this study was to compare the in vitro activity of delafloxacin with other fluoroquinolones against bacterial pathogens recovered from inpatients with osteomyelitis, Acute Bacterial Skin and Skin-Structure Infections (ABSSSI). In total, 100 bacterial isolates (58 % Gram-negative and 42 % Gram-positive) recovered from inpatients between January and April 2021, were reidentified at species level by MALDI-TOF MS. Antimicrobial susceptibility testing was conducted using the broth microdilution method and the detection of biofilm formation was assessed through the microtiter plate assay. The screening for mecA was carried out by PCR, while mutations in the Quinolone Resistance Determining Regions (QRDR), specifically gyrA and parC, were analyzed using PCR followed by Sanger sequencing. Results showed that delafloxacin exhibited greater in vitro potency (at least 64-times) than the other tested fluoroquinolones (levofloxacin and ciprofloxacin) when evaluating Staphylococcus aureus (MIC50 ≤0.008 mg/L) and coagulase-negative Staphylococcus (MIC50 0.06 mg/L). Furthermore, delafloxacin (MIC50 0.25 mg/L) was at least 4 times more potent than other tested fluoroquinolones (MIC50 1 mg/L) against P. aeruginosa. No difference in delafloxacin activity (MIC50 0.03 mg/L) was observed against Enterobacter cloacae when compared with ciprofloxacin (MIC50 0.03 mg/L). Despite presenting low activity against K. pneumoniae isolates (22.2 %), delafloxacin exhibited twice the activity compared to both levofloxacin and ciprofloxacin. Delafloxacin also exhibited a strong activity (71.4 %‒85.7 %.) against biofilm producing bacterial pathogens tested in this study. Interestingly, 82.14 % of the staphylococci tested in this study harbored mecA gene. In addition, the gyrA and parC genes in fluoroquinolone-resistant Gram-negative isolates displayed different mutations (substitutions and deletions). Herein, we showed that delafloxacin was the most active fluoroquinolone against staphylococci (including MRSA) and P. aeruginosa when compared to other fluoroquinolones such as ciprofloxacin and levofloxacin.

Prevalence of azole-resistant Aspergillus fumigatus and other aspergilli in the environment from Argentina.

Azole resistance has emerged as a new therapeutic challenge in patients with aspergillosis. Various resistance mutations are attributed to the widespread use of triazole-based fungicides in agriculture. This study explored the prevalence of azole-resistant Aspergillus fumigatus (ARAF) and other aspergilli in the Argentine environment. A collection of A. fumigatus and other aspergilli strains isolated from soil of growing crops, compost, corn, different animal feedstuffs, and soybean and chickpea seeds were screened for azole resistance. No ARAF was detected in any of the environmental samples studied. However, five A. flavus, one A. ostianus, one A. niger and one A. tamarii recovered from soybean and chickpea seeds showed reduced susceptibility to medical azole antifungals (MAA). The susceptibility profiles of five A. flavus isolates, showing reduced susceptibility to demethylase inhibitors (DMIs), were compared with those of 10 isolates that exhibited susceptibility to MAA. Aspergillus flavus isolates that showed reduced MAA susceptibility exhibited different susceptibility profiles to DMIs. Prothioconazole and tebuconazole were the only DMIs significantly less active against isolates with reduced susceptibility to MAA. Although no ARAF isolates were found in the samples analysed, other aspergilli with reduced susceptibility profile to MAA being also important human pathogens causing allergic, chronic and invasive aspergillosis, are present in the environment in Argentina. Although a definitive link between triazole-based fungicide use and isolation of azole-resistant human pathogenic aspergilli from agricultural fields in Argentina remains elusive, this study unequivocally highlights the magnitude of the environmental spread of azole resistance among other Aspergillus species.

This study intended to inform about the prevalence of Aspergillus species showing triazole resistance in the Argentinian environment. Since azole fungicides are used for crop protection, it was expected that azole resistance in this species with cross-resistance to medical azoles could occur.

Evaluation of Antimicrobial Resistance Patterns of Pseudomonas aeruginosa Strains Isolated among COVID-19 Patients in Brazil Typed by Fourier-Transform Infrared Spectroscopy.

This study aimed to characterize Pseudomonas aeruginosa strains isolated from hospitalized patients during the COVID-19 pandemic. This was achieved using phenotypic and molecular techniques, including their antimicrobial resistance profile and biofilm formation. Eighteen strains were isolated from a hospital in Rio de Janeiro, Brazil, and identified by VITEK®2, MALDI-TOF/MS (VITEK MS® and MALDI Biotyper®), and 16S rRNA sequencing. Fourier-transform infrared (FTIR) spectroscopy, antimicrobial susceptibility testing, and biofilm formation and disinfectant tolerance tests were applied to evaluate the virulence characteristics of the strains. VITEK®2 (≥99%), VITEK MS® (≥82.7%), and MALDI Biotyper® (score ≥ 2.01) accurately identified the P. aeruginosa strains, but 16S rRNA sequencing did not differentiate the species P. aeruginosa from P. paraeruginosa. FTIR typing identified three different clusters, but no correlation between the phenotypical or antimicrobial susceptibility testing patterns was found. Most strains exhibited resistance to various antimicrobials. The exceptions were sensitivity to amikacin and norfloxacin, and consequently, these could be considered potential treatment options. Most strains (n = 15, 83.3%) produced biofilms on polystyrene. Sodium hypochlorite treatment (0.5%/15 min) was shown to be the most effective disinfectant for biofilm elimination. P. aeruginosa biofilm formation and tolerance to disinfectants demonstrate the need for effective cleaning protocols to eliminate contamination by this organism in the hospital environment and medical equipment.

A Genome-Focused Investigation Reveals the Emergence of a Mycobacterium tuberculosis Strain Related to Multidrug-Resistant Tuberculosis in the Amazon Region of Brazil.

A previous study in Pará, Northern Brazil, described a strain of Mycobacterium tuberculosis with a unique genotype (SIT2517/T1) associated with multidrug-resistant tuberculosis (MDR-TB). To improve our understanding of MDR-TB transmission dynamics of these strains within this region, we performed phenotypic and genotypic drug susceptibility testing (pDST/gDST), 24-loci mycobacterial interspersed repetitive units (MIRU-VNTR) genotyping, whole-genome sequencing (WGS) and geo-epidemiology analysis. Of the 28 SIT2517/T1 isolates, 19 (67.9%) could be genotyped by 24-loci MIRU-VNTR and 15 by WGS. All belonged to sublineage 4.1.1.3, distinct from other representative Lineage 4 isolates identified in Brazil. The MDR phenotype determined by pDST was confirmed by gDST, the latter also demonstrating the presence of additional mutations conferring pre-extensively drug-resistance (pre-XDR). Discrepancies between gDST and pDST were observed for pyrazinamide and fluoroquinolones. Thirteen out of 15 isolates analyzed by WGS were clustered when applying a 12 single nucleotide polymorphisms (SNPs) cutoff. The SIT2517/T1 isolates were distributed across the metropolitan regions of Belém and Collares municipalities, showing no geographic clustering. WGS-transmission network analysis revealed a high likelihood of direct transmission and the formation of two closely linked transmission chains. This study highlights the need to implement TB genomic surveillance in the Brazilian Amazon region.

Oral Staphylococcus Species and MRSA Strains in Patients with Orofacial Clefts Undergoing Surgical Rehabilitation Diagnosed by MALDI-TOF MS.

This study investigated the occurrence and dynamics of oral Staphylococcus species in patients with orofacial clefts undergoing surgical rehabilitation treatment. Patients (n = 59) were statistically stratified and analyzed (age, gender, types of orofacial clefts, surgical history, and types of previous surgical rehabilitation). Salivary samples were obtained between hospitalization and the return to the specialized medical center. Microbiological diagnosis was performed by classical methods, and MALDI-TOF MS. MRSA strains (SCCmec type II, III, and IV) were characterized by the Decision Tree method. A total of 33 (55.9%) patients showed oral staphylococcal colonization in one, two, or three sampling steps. A high prevalence has been reported for S. aureus (including HA-, MRSA and CA-MRSA), followed by S. saprophyticus, S. epidermidis, S. sciuri, S. haemolyticus, S. lentus, S. arlettae, and S. warneri. The dynamics of oral colonization throughout surgical treatment and medical follow-up may be influenced by (i) imbalances in staphylococcal maintenance, (ii) efficiency of surgical asepsis or break of the aseptic chain, (iii) staphylococcal neocolonization in newly rehabilitated anatomical oral sites, and (iv) total or partial maintenance of staphylococcal species. The highly frequent clinical periodicity in specialized medical and dental centers may contribute to the acquisition of MRSA in these patients.

Clinical, demographic characteristics and antimicrobial resistance profile of Staphylococcus aureus isolated in clinical samples from pediatric patients in a tertiary hospital in Rio de Janeiro: 7-year longitudinal study.

BACKGROUND: In the pediatric population, Staphylococcus aureus infections are responsible for increased morbidity and mortality, length of hospitalization and the cost of inpatient treatment. The aim of this study is to describe the antimicrobial resistance profile of S. aureus isolated in clinical specimens from pediatric patients admitted to a tertiary hospital in Rio de Janeiro, Brazil. METHODS: Culture reports and medical records of hospitalized patients under 18 years of age with S. aureus infections between January 2015 and December 2022 were retrospectively analyzed. Information was collected on recent antibiotic use, previous hospital admission, inpatient unit, clinical specimen, time of infection (community or nosocomial), classification according to susceptibility to methicillin (methicillin sensitive - MSSA or methicillin resistant - MRSA) and sensitivity to other antimicrobials. We analyzed the distribution of the sensitivity profile of S. aureus infections over the 7 years evaluated in the study. RESULTS: Were included 255 unique clinical episodes, among which the frequencies of MSSA and MRSA were 164 (64%) and 91 (36%), respectively. Over the 7 years evaluated, there was stability in the prevalence percentage, with a predominance of MSSA in the range of 60 to 73.3%, except in 2020, when there was a drop in the prevalence of MSSA (from 73.3% in 2019 to 52.5%) with an increase in MRSA (from 26.7% in 2019 to 47.5%). Ninety-seven (38%) infections were community-acquired and 158 (62%) were healthcare-associated. The main clinical specimens collected were blood cultures (35.2%) and wound secretions (17%). The MRSA isolates presented percentages of sensitivity to trimethoprim-sulfamethoxazole from 90.4 to 100%, and to clindamycin from 77 to 89.8% in MRSA healthcare associated and MRSA community respectively. CONCLUSION: There was a constant predominance in the prevalence of MSSA with percentage values ​​maintained from 2015 to 2022, except in 2020, in which there was a specific drop in the prevalence of MSSA with an increase in MRSA. MSSA infections are still predominant in the pediatric population, but MRSA rates also present significant values, including in community infections, and should be considered in initial empiric therapy.

Repeated subcutaneous esketamine on treatment-resistant depression: An open-label dose titration study.

BACKGROUND: Ketamine has gained prominence as one of the most effective therapeutic options in unipolar treatment-resistant depression (TRD). However, most studies related to the antidepressant action of ketamine used intravenous (IV) or intranasal (IN) administration. The subcutaneous (SC) route of administration is a promising alternative, as it results in plasma levels comparable to IV, causes fewer side effects, and is easier and cheaper to administer than both IV and/or IN routes. METHODS: In this context, we conducted an open-label clinical trial for investigating the efficacy and safety of 8 weekly sessions of SC esketamine in TRD patients (n = 30). RESULTS: At the end of the treatment, a partial response rate of 26.09 %, a response rate of 52.17 % and remission rate of 34.78 % were observed, assessed by Montgomery-Åsberg Depression Rating Scale. Moreover, the self-reported depressive symptoms, as measured by the Beck Depression Inventory II (BDI-II), significantly decreased from the baseline to the final session, and the improvements were sustained throughout the week. Follow-up evaluations (BDI-II) up to the sixth month consistently showed scores lower than the baseline. LIMITATIONS: The small sample size and the drop-out during the follow-up phase may limit the generalizability of the findings. Additionally, the absence of a control group necessitates cautious interpretation of causality. CONCLUSIONS: This groundbreaking study, which addresses SC esketamine treatment for TRD, reported promising response and remission rates, as well as sustained antidepressant effects. It highlights the need for further research to improve and expand our knowledge of this innovative, more accessible, and cost-effective therapeutic approach.

Treatment for multidrug-resistant tuberculosis: A comparative analysis of programmatic outcome indicators between Buenaventura and other municipalities of Valle del Cauca, Colombia / Tratamiento para tuberculosis resistente a rifampicina o multirresistente: análisis comparativo de indicadores programáticos entre Buenaventura y otros municipios del Valle del Cauca, Colombia

Introduction. Proper management of multidrug-resistant tuberculosis is a prioritized strategy for tuberculosis control worldwide. Objective. To evaluate differences concerning demographic and clinical characteristics and programmatic indicators of Buenaventura patient cohort with confirmed diagnosis of multidrug-resistant tuberculosis, compared to those of the other municipalities from Valle del Cauca, Colombia, 2013-2016. Materials and methods. We conducted an analytical cohort study to compare records of patients older than 15 years with multidrug-resistant tuberculosis included in the Programa de Tuberculosis de Buenaventura (with para-aminosalicylic acid) versus the other municipalities of Valle del Cauca (without para-aminosalicylic). Results. Ninety-nine cases were recorded with a median age of 40 years (IQR = 26 - 53); in Buenaventura, 56% of the patients were women, while in the other municipalities, men predominated with 67%; 95% had health insurance. The most common comorbidity was diabetes (14%). Adverse reactions to antituberculosis medications in Buenaventura were 1.3 times more frequent than in the other municipalities (OR = 2.3; 95% CI = 0.993 - 5.568; p = 0.04). In Buenaventura, the mortality rate was 5% compared to the 15% reported in the other municipalities. Treatment failures were not reported in Buenaventura, but 35% did not continue with the follow-up. Treatment success was higher in Buenaventura (56 %). Conclusion. A strengthened program in Buenaventura presented better programmatic results than those from the other municipalities of Valle del Cauca. Access to molecular tests, availability of shortened treatments, and continuous monitoring to identify adverse reactions to antituberculosis medications are routes for all other control programs.

Introducción. El manejo adecuado de la tuberculosis multirresistente es una estrategia priorizada para el control de la tuberculosis en el mundo. Objetivo. Evaluar las diferencias entre las características demográficas y clínicas, y los indicadores programáticos de los pacientes con diagnóstico confirmado de tuberculosis pulmonar resistente a rifampicina o multirresistente en Buenaventura, frente a la cohorte de los demás municipios del Valle del Cauca entre 2013 y 2016. Materiales y métodos. Se desarrolló un estudio analítico de cohortes para comparar los registros de pacientes mayores de 15 años con tuberculosis multirresistente, del Programa de Tuberculosis de Buenaventura (con ácido paraaminosalicílico), frente a los demás municipios del Valle del Cauca (sin ácido paraaminosalicílico). Resultados. Se registraron 99 casos con una mediana de edad de 40 años (RIC = 26- 53); en Buenaventura, el 56 % eran mujeres; en los demás municipios, predominaron los hombres (67 %); el 95 % de los evaluados tenía aseguramiento en salud. La comorbilidad más frecuente fue diabetes (14 %). Las reacciones adversas a medicamentos antituberculosos en Buenaventura fueron 1,3 veces más frecuentes que en los demás municipios (OR = 2,3; IC95 %: 0,993 - 5,568; p = 0,04). En Buenaventura falleció el 5 % de los casos frente al 15 % reportado en los demás municipios. No hubo fracasos con el tratamiento en Buenaventura, pero se reportó un 35 % de pérdida del seguimiento. El éxito del tratamiento fue mayor en Buenaventura en el 56 %. Conclusión. El programa fortalecido de Buenaventura presentó mejores resultados programáticos que los demás municipios del Valle del Cauca. El acceso a pruebas moleculares, la disponibilidad de tratamientos acortados y el seguimiento continuo para identificar reacciones adversas a medicamentos antituberculosos son un derrotero para todos los programas de control.