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1.
Artículo en Inglés | MEDLINE | ID: mdl-39889851

RESUMEN

BACKGROUND: Tuberculosis disease is a major global health concern. In Mexico, information regarding the genomic variants of Mycobacterium tuberculosis (MTB) prevailing in the country and the existence of specific biogeographical patterns remains extremely scarce. OBJECTIVE: This study aimed to identify the genotypic patterns of MTB isolates in Mexico and determine the genes and specific single nucleotide polymorphisms involved in the evolution of these populations. METHODS: Phylogenomic and pan-genomic analyses were performed using publicly available Mexican MTB genomes along with 33 newly sequenced genomes from Jalisco, considering a global context. RESULTS: The L4 sublineages of MTB, such as L4.1.1 (X), L4.1.2 (H), and L4.3 (LAM), were the most prevalent in Mexico. We found exclusive mutations and gene clusters in a virulent sublineage L4.1.1.3 (X3), which is endemic to Mexico. These genes encoded three PE/PPE family proteins: a multidrug transporter, thioredoxin domain-containing protein, quinone-dependent L-lactate dehydrogenase, DUF1725 domain-containing protein, amidase, poly (A) polymerase, and six hypothetical/uncharacterized proteins. Additionally, the genes encode an ESX-1 secretion-associated protein and a deazaflavin-dependent nitroreductase (ddn). CONCLUSION: X3 was distinguished from the rest of the sublineages by containing genes related to pathogenicity and virulence, as well as a gene linked to delamanid, an antibiotic for active multidrug-resistant tuberculosis. These findings provide valuable insight into the circulation and spread of MTB in Mexico.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39873874

RESUMEN

Wastewater treatment plants (WWTPs) currently face major challenges toward the removal of microcontaminants and/or microbial matrices and consequently play an important role in the potential dissemination of biological resistance in freshwater. The ultraviolet (UV) system is a tertiary treatment strategy increasingly applied worldwide, although many studies have shown that disinfected effluent can still contain antibiotic-resistant bacteria and resistance genes. Therefore, to better understand the effects of UV radiation doses on the removal of all resistance elements (antibiotics, antibiotic-resistant bacteria, and antibiotic resistance genes), the present study was designed using a pilot-scale photoreactor. The UV doses could be varied to investigate whether there is an optimal UV dose capable of removing all resistance elements and also if the UV dose frequently applied in full-scale systems is able to reduce the resistance elements. The effect of different UV doses (A, 0-10 mJ/cm2; B, 10-15 mJ/cm2; and C, > 15 mJ/cm2) in a pilot-scale photoreactor on the removal of antibiotics, antibiotic-resistant bacteria, and genes from the effluent of a UASB reactor followed by a biological trickling filter system (UASB-TF) fed with real sanitary sewage was investigated. Samples of influent and effluent from the UVC photoreactor were collected, and the concentration levels of norfloxacin (NOR), ciprofloxacin (CIP), and levofloxacin (LEV) were assessed. The qnrB, sul1, ermB, integron-integrase (intI1), and 16S rRNA genes, total heterotrophic bacteria (THB), and bacterial resistance to azithromycin and sulfamethoxazole were also investigated. Results indicated that LEV and intI1 were found in the highest median concentrations in the photoreactor influent. Although most antibiotics (NOR and CIP) and ARGs (intI1, 16S rRNA, and qnrB) were apparently better removed with the highest UV dose (> 15 mJ/cm2) applied, except for LEV, sul1, and ermB genes, the Kruskal-Wallis test reported no significant difference between low and high doses. ARB removal (from 80 to 100%) was observed at all UV doses. Principal component analysis (PCA) suggested a clear pattern of pollutant groups, i.e., antibiotics, ARG, and ARB, which exhibited low (median of 8-16%), medium (37-96%), and high (> 97%) removal percentages, respectively. These results demonstrated that UVC photoreactors can be an alternative to complement biological treatment in sewage treatment plants at the dose normally applied in full-scale WWTPs (> 15 mJ/cm2). However, there was no optimal single dose capable of removing all the resistance elements investigated.

3.
PLoS One ; 20(1): e0318007, 2025.
Artículo en Inglés | MEDLINE | ID: mdl-39847603

RESUMEN

Salmonella Dublin is a serovar that causes severe infections and cattle. Despite the importance of this agent, research on achieving its elimination from dairy farms is limited, which complicates risk mitigation and control efforts. This study thus aimed to assess the prevalence of S. Dublin on a farm with a history of outbreaks, to understand the dynamics of the infection, characterize the antimicrobial resistance of the isolates, and evaluate their genetic similarity. Multiparous cows in the postpartum phase are nearly five times more likely to shed Salmonella sp. A total of 39 cases of fatal septicemic salmonellosis caused by S. Dublin were confirmed in calves aged 3-5 months. Antimicrobial susceptibility was evaluated in 45 strains of S. Dublin, with 48.9% of the isolates classified as multidrug resistant, including resistance to penicillin (48.9%), tetracyclines (42.2%), and fluoroquinolones (33.3%). Seven multidrug-resistant isolates were selected for genomic sequencing. Among the resistance determinants identified, a mutation in the gyrA gene, present in all sequenced isolates, was notable. Analyses of cgMLST and SNPs revealed that the isolates from healthy animals were closely related to those found in animals with confirmed cases of S. Dublin, confirming that the agent was circulating among healthy animals across various categories. A high similarity was also found between the isolates in this study and strains causing salmonellosis in humans in Brazil, thus reinforcing the zoonotic nature and possible epidemiological link between cattle, and the occurrence of this disease in humans.


Asunto(s)
Antibacterianos , Enfermedades de los Bovinos , Salmonelosis Animal , Animales , Bovinos , Salmonelosis Animal/epidemiología , Salmonelosis Animal/microbiología , Salmonelosis Animal/tratamiento farmacológico , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Femenino , Farmacorresistencia Bacteriana Múltiple/genética , Industria Lechera , Pruebas de Sensibilidad Microbiana , Salmonella/efectos de los fármacos , Salmonella/aislamiento & purificación , Salmonella/genética
4.
Lancet Reg Health Eur ; 50: 101197, 2025 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39850254

RESUMEN

Background: It is unclear whether changes in antimicrobial resistance (AMR) in primary care influence AMR in hospital settings. Therefore, we investigated the dynamic association of AMR between primary care and hospitals. Methods: We studied resistance percentages of Escherichia coli and Klebsiella pneumoniae isolates to co-amoxiclav, ciprofloxacin, fosfomycin, nitrofurantoin and trimethoprim submitted by primary care, hospital outpatient and hospital inpatient settings to the Dutch National AMR surveillance network (ISIS-AR) from 2008 to 2020. For each bacterium-antibiotic combination, we first conducted multivariable logistic regressions to calculate AMR odds ratios (ORs) by month and healthcare setting, adjusted for patient-related factors and a time term. Second, multiple time series analysis was done using vector autoregressive models including the (log) ORs for each bacterium-antibiotic combination. Models were interpreted by impulse response functions and Granger-causality tests. Findings: The main AMR association was unidirectional from primary care to hospital settings with Granger-causality p-values between <0.0001 and 0.029. Depending on the bacterium-antibiotic combination, a 1% increase of AMR in E. coli and K. pneumoniae in primary care leads to an increase of AMR in hospital settings ranging from 0.10% to 0.40%. For ciprofloxacin resistance in K. pneumoniae, we found significant bidirectional associations between all healthcare settings with Granger-causality p-values between <0.0001 and 0.0075. Interpretation: For the majority of bacterium-antibiotic combinations, the main AMR association was from primary care to hospital settings. These results underscore the importance of antibiotic stewardship at the community level. Funding: ISIS-AR is supported by the Ministry of Health, Welfare and Sport of the Netherlands and the first author by the Central University of Ecuador to follow a PhD program in Erasmus MC.

5.
Infect Prev Pract ; 7(1): 100432, 2025 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39816444

RESUMEN

Background: Mobile phones used by healthcare workers (HCWs) in hospitals are significant reservoirs of drug-resistant bacteria responsible for hospital-acquired infections (HAIs). Aim: The objective of this study was to assess the level of contamination with such bacteria in outpatient clinics. Methods: Swabs from 83 HCWs' mobile phones were processed using standard biochemical and enzymatic procedures to identify pathogenic bacteria. ß-Lactamase tests, antimicrobial susceptibility tests, screening for extended-spectrum ß-lactamase (ESBL), and carbapenemase production were performed according to CLSI guidelines. Molecular detection of multi-drug-resistant genes (mecA in Staphylococcus aureus and kpc/ndm carbapenemases in Klebsiella pneumoniae and Acinetobacter spp.) was performed using multiplex real-time polymerase chain reaction. Findings: The overall prevalence of mobile phone contamination with one or more bacteria was 100%. A total of 51 Gram-positive and 44 Gram-negative isolates, including 20 coagulase-negative staphylococci (CoNS), 20 S. aureus (0 meticillin-resistant S. aureus), 11 Acinetobacter spp. and 10 K. pneumoniae were isolated. ß-Lactamase production was detected in 45% of CoNS and 30% of S. aureus. Panton-Valentine Leukocidin (PVL) toxin gene in S. aureus was found in 20% (4/20) of the isolates. Twenty (20%) and 13% of the Acinetobacter spp. and K. pneumoniae isolates, respectively, were ESBL but not carbapenemase producers. Conclusions: The presence of HAI-causing organisms on mobile phones used by HCWs in outpatient clinics necessitates the implementation of infection control measures to mitigate the risk of cross-contamination in critical healthcare settings.

6.
bioRxiv ; 2025 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-39829914

RESUMEN

Trichomoniasis, caused by the parasite Trichomonas vaginalis, is the most common non-viral sexually transmitted infection. Current treatment relies exclusively on 5-nitroimidazole drugs, with metronidazole (MTZ) as the primary option. However, the increasing prevalence of MTZ-resistant strains poses a significant challenge, particularly in the current absence of alternative therapies. Several studies have revealed that the development of metronidazole resistance in T. vaginalis is linked to genomic and transcriptional alterations. Given the role of epigenetic regulation in controlling gene expression, we investigated whether targeting histone deacetylase (HDAC) enzymes could influence drug resistance. Treatment of an MTZ-resistant strain (B7268) with the HDAC inhibitor, trichostatin A (TSA), in combination with MTZ enhanced drug sensitivity and induced significant genome-wide transcriptional changes, as revealed by RNA-seq analysis. To identify drug-related genes epigenetically silenced in the resistant strain but highly active in a sensitive strain, we compared the expression levels of the genes affected by TSA and MTZ treatment with their baseline expression profiles in both resistant and sensitive strains. This analysis identified 130 candidate genes differentially expressed in the sensitive strain NYH209, less expressed in the resistant B7268 strain, that exhibited significant expression changes upon TSA and MTZ treatment. Functional validation involved transfecting the B7268 strain with plasmids encoding four individual candidate genes: a thioredoxin reductase (TrxR), a cysteine synthase (CS), and two genes containing Myb domains (Myb5 and Myb6). Overexpression of three of these genes resulted in a marked reduction in MTZ resistance, demonstrating their role in modulating drug sensitivity. Our findings identified three novel genes that modulate drug resistance in T. vaginalis. This study reveals a previously unknown epigenetic mechanism underlying drug resistance and highlights the therapeutic potential of targeting epigenetic factors, such as HDACs, to overcome resistance and improve treatment efficacy.

7.
Sci Rep ; 15(1): 2811, 2025 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-39843896

RESUMEN

It was a general belief that drug resistance in Mycobacterium tuberculosis (Mtb) was associated with lesser virulence, particularly rifampicin resistance, which is usually produced by mutations in the RNA polymerase Beta subunit (RpoB). Interestingly, this kind of bacterial mutations affect gene transcription with significant effects on bacterial physiology and metabolism, affecting also the bacterial antigenic constitution that in consequence can produce diverse immune responses and disease outcome. In the present study, we show the results of the Mtb clinical isolate A96, which is resistant to rifampicin and when used to infect BALB/c mice showed hypervirulence, apparently by rapidly polarization of the Th2 immune response through early and high production of IL-4. The 2D-PAGE analysis of the secretome of Mtb A96 showed 204 spots, and by immunoproteome, seven proteins that were differentially recognized with the sera of infected mice on day 28 were identified by LC-MS/MS. The proteins correspond to surface antigens, virulence factors, and energy metabolism enzymes. Some of them are immunodominant antigens, such as LpqH lipoprotein that induces IL-4 secretion in cell suspensions from the lung and spleen of mice infected with Mtb A96 at 28 days postinfection, suggesting that LpqH could be one of the main antigens involved in the Th2 polarization. The reduction of Mtb A96 hypervirulence in IL-4Rα-/- BALB/c mice highlights the importance of IL-4 induction and Th2 response polarization and the immunopathological response. Thus, high and rapid bias to Th2 response is a mechanism of Mtb virulence, which could be mediated by rifampicin-resistant Mtb isolates, probably by high production and secretion of specific antigens.


Asunto(s)
Farmacorresistencia Bacteriana , Interleucina-4 , Ratones Endogámicos BALB C , Mycobacterium tuberculosis , Rifampin , Células Th2 , Animales , Mycobacterium tuberculosis/efectos de los fármacos , Rifampin/farmacología , Interleucina-4/metabolismo , Células Th2/inmunología , Ratones , Farmacorresistencia Bacteriana/genética , Tuberculosis/microbiología , Tuberculosis/inmunología , Femenino , Aptitud Genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética
8.
Heliyon ; 11(1): e41533, 2025 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-39834420

RESUMEN

Introduction: Contamination of drinking water by Helicobacter pylori can cause serious diseases, including cancer. The determinants of the infection rate are socioeconomic status, low standard of living and overcrowding. In addition, exposure to environmental sources contaminated with feces, such as water and vegetables, is another risk factor for infection. We analyzed the occurrence of H. pylori in drinking water sources and the antimicrobial resistance profile in central Peru. Methods: Water samples were collected from taps in four provinces of the Junín region. Previously, biofilm sampling was performed from the internal surface of the taps. The samples were cultured on modified brain heart infusion blood agar at 37 °C under microaerophilic conditions for seven days. Antibiotic sensitivity of H. pylori was determined by the Kirby Bauer diffusion method. Results: The results revealed that pH (9.25) and turbidity (5.15 NTU) exceeded the Peruvian environmental quality standards for drinking water. The amount of free chlorine residual in the H. pylori positive water samples ranged from 0.02 to 0.12 mg/L. H. pylori was present in 2/192 tap water samples (1.04 %) and in 3/192 tap biofilm samples (1.56 %). It was observed that 100 % of H. pylori isolates from water samples from the Chilca district showed resistance to nalidixic acid and 66.67 % to both amoxicillin and chloramphenicol. Resistance to nalidixic acid of H. pylori isolates obtained from biofilm samples from taps in the El Tambo district ranged from 66.67 % to 100 %. Conclusion: The study findings reveal that water samples and tap biofilms in the Chilca, El Tambo and Huamancaca chico districts in the Junín region harbor H. pylori. They also reveal variability in the pattern of resistance to more than one antibiotic tested from one district to another.

9.
PLoS Negl Trop Dis ; 19(1): e0012830, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39888971

RESUMEN

BACKGROUND: Occurrence of antimicrobial-resistant Salmonella strains has been reported worldwide, because of inappropriate use of antimicrobial products in either humans or animals. The presence of multidrug resistant Salmonella in pig production systems had been reported in Antioquia, Colombia. AIM: To identify antimicrobial resistance genes (ARG) in different Salmonella spp. strains isolated from pig productions in Antioquia, Colombia. Methods: Samples were received at the Diagnostic Unit of the Faculty of Agrarian Sciences at the University of Antioquia, from January 1, 2019, to January 2021. A total of 28 isolates of Salmonella spp. were included, which presented phenotypic resistance to more than one antibiotic used in pig farms. Whole genome sequencing (WGS) was performed in the Unit of Genomic of Agrosavia using an automated pipeline from the GHRU- Sanger Institute, employing the Illumina MiSeq platform. RESULTS: WGS revealed 34 ARGs among these isolates. In 25 isolates (89%) more than two ARGs were found. Genes encoding resistance were found for 10 different groups of antibiotics (beta-lactam, aminoglycosides, chloramphenicol, rifampicins, lincosamides, fluoroquinolones, tetracyclines, sulfonamides and trimethoprim). The most frequently observed MDR profile in Typhimurium isolates was AMP-CEX-CEP-CEF-EFT-CEQ-FLU-ENR-TE-FFC-SXT. CONCLUSION: The presence of multi-drug resistant Salmonella strains in pigs destined for human consumption in Antioquia, Colombia was determined. This research emphasizes the utmost importance of epidemiological tools to understand the presence and spreading of antimicrobial resistance genes in pig farms. Additionally, it highlights the critical need for developing educational programs and public policies to help reduce the spread of antimicrobial resistance in production systems.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Salmonelosis Animal , Salmonella , Enfermedades de los Porcinos , Factores de Virulencia , Animales , Porcinos , Colombia/epidemiología , Salmonella/genética , Salmonella/efectos de los fármacos , Salmonella/aislamiento & purificación , Factores de Virulencia/genética , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Salmonelosis Animal/microbiología , Salmonelosis Animal/epidemiología , Enfermedades de los Porcinos/microbiología , Granjas , Secuenciación Completa del Genoma , Pruebas de Sensibilidad Microbiana , Genómica
10.
Int Health ; 2025 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-39883069

RESUMEN

BACKGROUND: Antimicrobial resistance (AMR) has emerged as a priority for both public health and the global economy. Moreover, information on AMR is scarce, particularly in low/middle-income countries. We evaluated the direct economic cost of microorganisms and AMR. METHODS: We performed a cross-sectional study to assess the economic costs of neonatal cases diagnosed with bacteremia at the Instituto Nacional Materno Perinatal in Lima, Peru, from January 2017 to June 2018. We used cost invoices calculated by the micro-costing bottom-up approach, as well as the strain identification and antimicrobial susceptibility data, to estimate the direct costs. RESULTS: The average costs of bacteremia were US$349 (SD 403) for multidrug-resistant (MDR) strains and US$276 (SD 349) for non-MDR strains. Costs were higher for microorganisms associated with late-onset sepsis (LOS). We found that LOS, multidrug resistance and age were significantly associated with bloodstream infection (BSI) costs. Also, all microorganism groups were associated with increased costs, with the highest average costs for Acinetobacter, followed by Pseudomonas. CONCLUSIONS: In Peru, BSI costs are strongly associated with AMR. Furthermore, costs increase significantly with LOS, multidrug resistance and the patient's age. We urge health authorities to strengthen measures and strategies against the pressing threat of AMR.

11.
Curr Microbiol ; 82(3): 104, 2025 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-39875692

RESUMEN

Staphylococcaceae are a diverse bacterial family with important implications for human and animal health. This study highlights the One Health relevance of their environmental dispersal, particularly, by identifying closely related or genetically identical strains circulating between farm and community environments. Environmental Staphylococcaceae strains were isolated from animal farms and interconnected areas within a university setting, both influenced by anthropogenic activities. Genetic diversity analysis via GTG5-PCR revealed that specific strains circulated across these environments, likely facilitated by human interaction, supporting the potential for cross-environmental bacterial transfer. The strains were further tested for antimicrobial resistance against a panel of antibiotics, biofilm formation, and the presence of resistance-associated genes. We identified a wide array of Staphylococcaceae species (n = 16), with over half being pathogenic to humans and animals, including S. aureus, S. epidermidis, S. haemolyticus, and S. saprophyticus. Notably, 55.5% of the strains exhibited multidrug resistance, and 15.9% harbored the methicillin resistance gene mecA, underscoring the challenges these infections might pose to treatment. Biofilm-forming capabilities further enhance the environmental persistence of these strains. These findings underscore the critical need for surveillance and targeted intervention strategies in a One Health framework to mitigate antimicrobial resistance across shared environments.


Asunto(s)
Antibacterianos , Biopelículas , Granjas , Animales , Antibacterianos/farmacología , Biopelículas/crecimiento & desarrollo , Biopelículas/efectos de los fármacos , Humanos , Staphylococcus/efectos de los fármacos , Staphylococcus/genética , Staphylococcus/aislamiento & purificación , Staphylococcus/clasificación , Staphylococcus/fisiología , Staphylococcaceae/genética , Staphylococcaceae/efectos de los fármacos , Staphylococcaceae/aislamiento & purificación , Staphylococcaceae/clasificación , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/veterinaria , Pruebas de Sensibilidad Microbiana , Variación Genética , Microbiología Ambiental , Farmacorresistencia Bacteriana , Farmacorresistencia Bacteriana Múltiple/genética
12.
Epilepsia ; 2025 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-39804155

RESUMEN

OBJECTIVE: Identifying factors influencing cannabidiol (CBD) exposure can optimize treatment efficacy and safety. We aimed to describe the population pharmacokinetics of CBD in children with drug-resistant developmental and epileptic encephalopathies (DEEs) and assess the influence of environmental, pharmacological, and clinical characteristics on CBD systemic exposure. METHODS: Data from two pharmacokinetic studies of patients aged 2-18 years with DEEs were included (N = 48 patients). Serial blood samples were collected during maintenance treatment, before and after the morning dose, and up to 6 h after a dose of a purified CBD oil formulation, with or without a normocaloric breakfast. CBD plasma concentrations were also available following administration of a CBD-enriched formulation. Samples were quantified using a validated liquid chromatography/tandem mass spectrometry assay. A CBD population pharmacokinetic model was developed using nonlinear mixed-effects modeling. The effects of formulation, concomitant food intake, and demographic, clinical, and pharmacological factors on CBD pharmacokinetics were evaluated. Simulated maximum plasma concentration (Cmax) and area under the concentration-time curve between 0 and 12 h (AUC0-12) were calculated. RESULTS: A one-compartment model with transit compartments and first-order elimination best described CBD pharmacokinetics. Mean values for CBD apparent clearance (CL/F) and volume of distribution (V/F) were 143.5 L/h and 1892.4 L, respectively. Weight was allometrically scaled for V/F and CL/F, sex was associated with V/F, and both formulation and food condition were associated with F (relative bioavailability). CBD Cmax increased by 41% and AUC0-12 by 45% when CBD was administered with food compared to fasting. Dose-normalized AUC0-12 was approximately 50% lower with CBD-enriched oil compared to purified CBD. SIGNIFICANCE: In the present study, we described the effects of food and formulation on CBD exposure in children with DEEs. Increased CBD exposure with food intake and significant changes in drug exposure when switching between CBD formulations should be considered in patient management.

13.
Res Microbiol ; : 104266, 2025 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-39793844

RESUMEN

Little is known about how subinhibitory concentrations of antibiotics to which bacteria are resistant affect bacterial virulence. In this study, the effect of subinhibitory concentrations of ampicillin on the virulence of E. coli O104:H4 was analyzed. Bacteria were pre-exposed to 0.1, 0.3, or 0.5 mg/mL of ampicillin in LB media and incubated for 4 h at 37 °C. Transformation capacity (using plasmids and PCR-amplified DNA sequences), swarming motility, biofilm production, curli formation, and virulence gene expression were determined. Ampicillin increased the transformation of E. coli O104:H4, with the highest number of transformants (>104 CFU/ng DNA; p ≤ 0.05) detected after exposure to DNA sequences of spectinomycin. In addition, bacteria pre-treated with 0.5 mg/mL of ampicillin exhibited higher swarming motility (7.6 cm, vs 6.0 cm for control; p ≤ 0.05) and biofilm production (up to 1.9-fold; p ≤ 0.05) when subsequently exposed to 0.1 and 0.3 mg/mL of antibiotic compared with the control. Also, significant overexpression of the virulence-related genes flhC (≤16.1-fold), fliA (≤22.1-fold), csgA (≤3.6-fold), csgD (≤9.1-fold), stx2a (≤32.2-fold), and the antibiotic resistance gene blaTEM-1 (≤5.5-fold) was observed. In conclusion, ampicillin-resistant E. coli O104:H4 increased the expression of its virulence factors when exposed to most subinhibitory concentrations of ampicillin analyzed in this study.

14.
Proteomes ; 13(1)2025 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-39846637

RESUMEN

The tumor suppressor p53, in its wild-type form, plays a central role in cellular homeostasis by regulating senescence, apoptosis, and autophagy within the DNA damage response (DDR). Recent findings suggest that wild-type p53 also governs ferroptosis, an iron-dependent cell death process driven by lipid peroxidation. Post-translational modifications of p53 generate proteoforms that significantly enhance its functional diversity in regulating these mechanisms. A key target in this process is the cystine/glutamate transporter (xCT), which is essential for redox balance and ferroptosis resistance. Additionally, p53-induced miR-34c-5p suppresses cancer cell proliferation and drug resistance by modulating Myc, an oncogene further influenced by non-coding RNAs like circular RNA NOTCH1 (CricNOTCH1) and long non-coding RNA MALAT1. However, the exact role of these molecules in ferroptosis remains unclear. To address this, we introduce the first dynamic Boolean model that delineates the influence of these ncRNAs and p53 on ferroptosis, apoptosis, and senescence within the DDR context. Validated through gain- and loss-of-function perturbations, our model closely aligns with experimental observations in cancers such as oral squamous cell carcinoma, nasopharyngeal carcinoma, and osteosarcoma. The model identifies crucial positive feedback loops (CricNOTCH1/miR-34c/Myc, MALAT1/miR-34c/Myc, and Myc/xCT) and highlights the therapeutic potential of using p53 proteoforms and ncRNAs to combat drug resistance and induce cancer cell death.

15.
Washington, D.C.; OPS; 2025-01-28. (OPS/PUB/24-0010).
en Español | PAHO-IRIS | ID: phr-64207

RESUMEN

La resistencia a los antimicrobianos (RAM) se produce cuando los microorganismos que causan infecciones (bacterias, parásitos, virus y hongos) se vuelven resistentes a los medicamentos antimicrobianos que utilizamos en su tratamiento. Cuando esto ocurre, las infecciones duran más, son más graves y se tornan más contagiosas. La resistencia hace que los antimicrobianos, piedra angular de la medicina moderna, pierdan su eficacia, amenazando nuestra capacidad de tratar infecciones y realizar procedimientos seguros que salvan vidas. La RAM también es muy costosa en términos económicos. Se necesitan estancias hospitalarias mucho más prolongadas y fármacos más costosos para tratar las infecciones que presentan RAM, lo que se traduce en un aumento no solo de los costos de salud, sino también de la morbilidad y mortalidad de los pacientes hospitalizados, en especial en las unidades de cuidados intensivos, oncología y neonatología.


Asunto(s)
Farmacorresistencia Microbiana , Infecciones , Costos de la Atención en Salud , Sistemas de Salud , Enfermedades Transmisibles , Américas
16.
Artículo en Inglés | PAHO-IRIS | ID: phr-64100

RESUMEN

[ABSTRACT]. Objective. To conduct a point prevalence survey (PPS) of antibiotic use in the main pediatric tertiary-level hospital in Panama City to establish antibiotic prevalence and identify key areas for addressing antimicrobial resistance. Methods. This point prevalence survey (PPS) conducted in a tertiary-level hospital in Panama followed the Pan American Health Organization’s adaptation of the methodology proposed by the World Health Organization for PPSs on antibiotic use. Information obtained included patients’ demographic characteristics, antimicrobial prescriptions, indication for antimicrobial use, and prescription’s adherence to guidelines. Results. Of 298 patients surveyed from August to September 2023, 176 (59.0%) were treated with antibiotics. The pediatric ward (86.3%) and the neonatal intensive unit (80.0%) had the highest prevalence of antibiotic use. Hospital-acquired infections accounted for 32.6% of antibiotic prescriptions, with piperacillin/ tazobactam (29.4%), meropenem (15.3%), amikacin (15.3%), and ampicillin/sulbactam (10.2%) being the most prescribed. Treatment for community-acquired infections represented 55.9% of antibiotic prescriptions, with ampicillin (24.6%), gentamicin (22.6%), and ampicillin/sulbactam (14.0%) being the most frequently used. Of the prescriptions considered in the analysis, 61.0% adhered to hospital guidelines. Conclusions. This PPS observed a high prevalence of antibiotic use. The findings suggest it is necessary to assess the need for ampicillin, gentamicin, and piperacillin-tazobactam use in patients admitted to pediatric critical care units, with special emphasis on children with pneumonia or sepsis diagnosis, the most common pathologies for which an antimicrobial was prescribed.


[RESUMEN]. Objetivo. Realizar una encuesta de prevalencia puntual (EPP) del uso de antibióticos en el principal hospital pediátrico de nivel terciario de la ciudad de Panamá para establecer la prevalencia del uso de antibióticos y determinar cuestiones clave para abordar la resistencia a los antimicrobianos. Métodos. Esta EPP realizada en un hospital de nivel terciario de Panamá se llevó a cabo utilizando la adaptación de la Organización Panamericana de la Salud de la metodología propuesta por la Organización Mundial de la Salud para las EPP del uso de antibióticos. Se obtuvo información sobre las características demográficas de los pacientes, las prescripciones de antimicrobianos, la indicación para el uso de los antimicrobianos y la adhesión de la prescripción a las directrices. Resultados. De los 298 pacientes incluidos en la encuesta entre agosto y septiembre del 2023, 176 (59,0%) recibieron tratamiento antibiótico. La unidad de hospitalización de pediatría (86,3%) y la unidad de cuidados intensivos neonatales (80,0%) fueron las que presentaron la mayor prevalencia de uso de antibióticos. Las infecciones hospitalarias motivaron el 32,6% de las prescripciones de antibióticos, y las medicaciones más prescritas fueron la combinación de piperacilina y tazobactam (29,4%), el meropenem (15,3%), la amikacina (15,3%) y la combinación de ampicilina y sulbactam (10,2%). El tratamiento de las infecciones contraídas fuera del hospital supuso el 55,9% de las prescripciones de antibióticos, y las medicaciones más utilizadas fueron la ampicilina (24,6%), la gentamicina (22,6%) y la combinación de ampicilina y sulbactam (14,0%). El 61,0% de las prescripciones consideradas en el análisis se ajustaban a las directrices del hospital. Conclusiones. Esta EPP detectó una prevalencia alta del uso de antibióticos. Los resultados sugieren que es necesario evaluar la necesidad de uso de la ampicilina, la gentamicina y la combinación de piperacilina y tazobactam en los pacientes ingresados en unidades de cuidados intensivos pediátricos, con especial énfasis en los pacientes con diagnósticos de neumonía o sepsis, las patologías más frecuentes para las que se prescribió un antimicrobiano.


[RESUMO]. Objetivo. Realizar um estudo de prevalência pontual sobre o uso de antibióticos no principal hospital pediátrico de nível terciário da Cidade do Panamá para determinar a prevalência de antibióticos e identificar as principais áreas para abordar a resistência aos antimicrobianos. Métodos. Esse estudo de prevalência pontual realizado em um hospital de nível terciário no Panamá seguiu a adaptação feita pela Organização Pan-Americana da Saúde da metodologia proposta pela Organização Mundial da Saúde para esse tipo de estudo sobre o uso de antibióticos. As informações obtidas incluíram características demográficas dos pacientes, prescrições de antimicrobianos, indicação do uso de antimicrobianos e adesão das prescrições às diretrizes. Resultados. Dos 298 pacientes pesquisados de agosto a setembro de 2023, 176 (59,0%) foram tratados com antibióticos. A ala pediátrica (86,3%) e a unidade de terapia intensiva neonatal (80,0%) apresentaram a maior prevalência de uso de antibióticos. As infecções hospitalares foram responsáveis por 32,6% das prescrições de antibióticos. Os mais prescritos foram piperacilina/tazobactam (29,4%), meropeném (15,3%), amicacina (15,3%) e ampicilina/sulbactam (10,2%). O tratamento de infecções adquiridas na comunidade representou 55,9% das prescrições de antibióticos, e os mais usados foram ampicilina (24,6%), gentamicina (22,6%) e ampicilina/sulbactam (14,0%). Das prescrições consideradas na análise, 61,0% aderiram às diretrizes do hospital. Conclusões. Esse estudo de prevalência pontual apontou uma alta prevalência no uso de antibióticos. Os resultados sugerem que é necessário avaliar a necessidade do uso de ampicilina, gentamicina e piperacilina/ tazobactam em pacientes internados em unidades de terapia intensiva pediátrica, especialmente em crianças com diagnóstico de pneumonia e sepse, as patologias mais comuns para as quais foram prescritos antimicrobianos.


Asunto(s)
Farmacorresistencia Microbiana , Programas de Optimización del Uso de los Antimicrobianos , Prevalencia , Pediatría , Panamá , Farmacorresistencia Microbiana , Programas de Optimización del Uso de los Antimicrobianos , Prevalencia , Panamá , Programas de Optimización del Uso de los Antimicrobianos , Prevalencia , Pediatría
17.
J Antimicrob Chemother ; 80(1): 292-300, 2025 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-39556256

RESUMEN

BACKGROUND: The rising prevalence of pretreatment drug resistance (PDR) to non-nucleoside reverse-transcriptase inhibitors threatens the effectiveness of ART. In response, the WHO recommends dolutegravir-based ART regimens due to their high genetic barrier to resistance and better treatment outcomes. This is expected to contribute to achieving the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of 95% viral suppression in people on ART. OBJECTIVES: To estimate the prevalence of PDR among adults initiating ART and assess viral suppression and acquired HIV drug resistance (ADR) among individuals receiving ART in Belize. PATIENTS AND METHODS: Nationally representative cross-sectional PDR and ADR surveys were conducted between 2021 and 2022. Sixty-seven adults were included in the PDR survey, and 43 children and adolescents and 331 adults were included in the ADR survey. Demographic and clinic data and blood specimens were collected. HIV drug resistance (HIVDR) was predicted using the Stanford HIVdb tool. RESULTS: The prevalence of PDR to efavirenz or nevirapine in adults was 49.3% (95% CI 42.2%-56.4%) and was significantly higher in those with previous antiretroviral exposure (OR: 7.16; 95% CI 2.71-18.95; P = 0.002). Among children and adolescents receiving ART, 50.0% had viral suppression, with better rates for those receiving dolutegravir-based ART (OR: 5.31; 95% CI 3.02-9.34; P < 0.001). In adults, 79.6% achieved viral suppression. No resistance to integrase inhibitors was observed in those on dolutegravir-based ART. CONCLUSIONS: Prioritizing dolutegravir-based ART is critical for achieving HIV epidemic control in Belize. Efforts should focus on retention in care and adherence support to prevent HIVDR.


Asunto(s)
Fármacos Anti-VIH , Farmacorresistencia Viral , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Infecciones por VIH/epidemiología , Masculino , Adulto , Femenino , Estudios Transversales , Adolescente , Farmacorresistencia Viral/genética , Adulto Joven , Persona de Mediana Edad , Niño , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Belice/epidemiología , Prevalencia , Piridonas , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Alquinos , Oxazinas/uso terapéutico , Ciclopropanos , Benzoxazinas/uso terapéutico , VIH-1/efectos de los fármacos , VIH-1/genética , Piperazinas/uso terapéutico , Nevirapina/uso terapéutico , Carga Viral , Encuestas y Cuestionarios
19.
PeerJ Comput Sci ; 10: e2246, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39650511

RESUMEN

Tuberculosis (TB) is a disease caused by the bacterium Mycobacterium tuberculosis and despite effective treatments, still affects millions of people worldwide. The advent of new treatments has not eliminated the significant challenge of TB drug resistance. Repeated and inadequate exposure to drugs has led to the development of strains of the bacteria that are resistant to conventional treatments, making the eradication of the disease even more complex. In this context, it is essential to seek more effective approaches to fighting TB. This article proposes a model for predicting drug resistance based on the clinical profile of TB patients, using machine learning techniques. The model aims to optimize the work of health professionals directly involved with tuberculosis patients, driving the creation of new containment strategies and preventive measures, as it specifies the clinical data that has the greatest impact and identifies the individuals with the greatest predisposition to develop resistance to anti-tuberculosis drugs. The results obtained show, in one of the scenarios, a probability of development of 70% and an accuracy of 84.65% for predicting drug resistance.

20.
Microbiol Spectr ; : e0170624, 2024 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-39670761

RESUMEN

Surface waters function as ecological niches where Salmonella enterica can persist and disseminate to fresh produce production systems. We examined the genomic characteristics of S. enterica serotypes Agona (n = 86), Braenderup (n = 47), Muenchen (n = 53), and Panama (n = 69) isolates from surface waters in Chile, Mexico, and Brazil between 2019 and 2022. Mexican isolates consistently displayed a higher occurrence of genotypic antimicrobial resistance (AMR) than Chilean and Brazilian isolates. All S. Agona isolates exhibited the presence of fosA7.2, while qnrB19 emerged as the predominant AMR gene (ARG) among S. Braenderup isolates. S. Muenchen isolates from Chile displayed an absence of any ARGs, while those from Mexico and Brazil predominantly carried qnrB19. Among S. Panama isolates from Chile, aadA1, floR, sat2, and tet(B) were the most prevalent ARGs, whereas those from Mexico and Brazil harbored tet(A), and floR and tet(A) as the leading ARGs, respectively. ARG sharing among isolates and ARG co-occurrence within individual isolates were prevalent across countries and serotypes. All isolates containing integrons exhibited genotypic multidrug resistance. The principal coordinates analysis reveals distinct clustering patterns based on country, serotype, number of ARGs per isolate, and plasmid and integron presence/absence. The whole-genome phylogenetic analysis demonstrates clear clusters, each associated with their respective countries. However, a notable exception was observed with one S. Agona isolate from Brazil closely related to two isolates from Chile, differing by only 18 and 19 single-nucleotide polymorphisms, respectively.IMPORTANCEThis comprehensive study explored the intricate genomic landscapes of S. Agona, Braenderup, Muenchen, and Panama isolates from surface waters across Chile, Mexico, and Brazil. By filling important knowledge gaps related to the genomic characteristics of these serotypes, the research offers a nuanced understanding of these serotypes as potential reservoirs for multidrug resistance. Our findings emphasize the urgency of targeted interventions to mitigate the emergence and dissemination of multidrug-resistant Salmonella enterica. This work underscores the need for informed policies and collaborative efforts to address the risks posed by S. enterica in Latin American surface waters.

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