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BACKGROUND: Pathophysiological changes post-liver transplantation impact the pharmacokinetics and pharmacodynamics of antibiotics. Piperacillin, often used in combination with tazobactam, is a key antibiotic after transplantation to its broad-spectrum activity, but there is a lack of specific pharmacokinetic data in this population. This study aims to describe the pharmacokinetic parameters and target attainment of piperacillin in pediatric liver transplant recipients. METHODS: Patients with preserved renal function (estimated glomerular filtration rate > 50 mL/min/1.73 m2) receiving intravenous piperacillin-tazobactam at 112.5 mg/kg every 8 h (100 mg piperacillin/12.5 mg tazobactam), with a rapid infusion (0.5-1 h), were included. Two blood samples per child were collected during the same interval within 48 h of starting therapy. A Bayesian approach was applied to estimate individual pharmacokinetic parameters and perform dosing recommendations against Enterococcus spp., Enterobacterales and Pseudomonas aeruginosa. RESULTS: Eight patients with median age of 8 months were included. Median piperacillin clearance and central volume of distribution for the cohort were 11.11 L/h/70 kg and 9.80 L/70 kg, respectively. Seven patients (87.5%) presented with concentrations below the target of 100% fT > MIC. Simulations suggested that these patients required more frequent dosing and extended duration of infusion to ensure target attainment. One patient (12.5%) had trough concentrations that exceed 16 mg/L and could receive a lower daily dose. CONCLUSIONS: This case series highlights the importance of personalized therapy in pediatric liver transplant recipients due to the unpredictable and highly variable piperacillin pharmacokinetics in this population.
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Antibacterianos , Trasplante de Hígado , Combinación Piperacilina y Tazobactam , Piperacilina , Humanos , Masculino , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Femenino , Lactante , Piperacilina/administración & dosificación , Piperacilina/farmacocinética , Piperacilina/uso terapéutico , Combinación Piperacilina y Tazobactam/administración & dosificación , Combinación Piperacilina y Tazobactam/uso terapéutico , Combinación Piperacilina y Tazobactam/farmacocinética , Preescolar , Teorema de Bayes , NiñoRESUMEN
OBJECTIVE: Analyse the incidence, risk factors, antimicrobial susceptibility profile, and fatality in neonates infected with oxacillin-resistant Staphylococcus spp. (ORS). METHODS: In this retrospective observational descriptive cohort study, the medical records of neonates admitted to the Neonatal Intensive Care Unit (NICU) from January 2015 to June 2022 were analysed. Participants were monitored daily through the National Healthcare Safety Network. RESULTS: Among the 1610 neonates, 193 (12â¯%) developed ORS infections, primarily in the bloodstream (96.8â¯%). The incidence of these infections/patient-days decreased by 51.8â¯% between 2016 (8.3) and 2022 (4). The median age of affected neonates was 17.5 days (IQR:12-28.7). Pre-emptive prescription of fourth-generation cephalosporins (OR=14.36; P<0.01) emerged as a risk factor in the multivariate analysis. Staphylococcus epidermidis was the most prevalent species (60.1â¯%), with one isolate showing a "susceptible, increased exposure" profile to vancomycin. Additionally, 2â¯% of pathogens were extensively drug-resistant (XDR). ORS infections were associated with prolonged hospital stays (from 10 to 46 days) and increased mortality (from 10.2â¯% to 19.2â¯%). The median time between infection and the fatal outcome was 15 days (IQR:8-40), and Staphylococcus capitis was the most lethal species (26.7â¯%). CONCLUSIONS: The high incidence of ORS infections was linked to extended hospitalisation and increased mortality, highlighting the complexity of this situation - a "perfect storm." This underscores the urgency of implementing effective interventions for managing and preventing ORS infections in the NICU.
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Antibacterianos , Unidades de Cuidado Intensivo Neonatal , Oxacilina , Infecciones Estafilocócicas , Staphylococcus , Femenino , Humanos , Recién Nacido , Masculino , Antibacterianos/uso terapéutico , Brasil/epidemiología , Farmacorresistencia Bacteriana/efectos de los fármacos , Incidencia , Pruebas de Sensibilidad Microbiana , Oxacilina/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/mortalidad , Infecciones Estafilocócicas/epidemiología , Staphylococcus/efectos de los fármacos , Staphylococcus/aislamiento & purificaciónRESUMEN
BACKGROUND: Enzymatic degradation mediated by beta-lactamases constitutes one of the primary mechanisms of resistance to beta-lactam antibiotics in gram-negative bacteria. This enzyme family comprises four molecular classes, categorized into serine beta-lactamases (Classes A, C, and D) and zinc-dependent metallo-beta-lactamases (Class B). Gram-negative bacteria producing beta-lactamase are of significant concern, particularly due to their prevalence in nosocomial infections. A comprehensive understanding of the evolution and dissemination of this enzyme family is essential for effective control of these pathogens. In this study, we conducted the prospecting, phylogenetic analysis, and in silico analysis of beta-lactamases and homologous proteins identified in 1827 bacterial genomes with phenotypic data on beta-lactam resistance. These genomes were distributed among Klebsiella pneumoniae (45%), Acinetobacter baumannii (31%), Pseudomonas aeruginosa (14%), Escherichia coli (6%), and Enterobacter spp. (4%). Using an HMM profile and searching for conserved domains, we mined 2514, 8733, 5424, and 2957 proteins for molecular classes A, B, C, and D, respectively. This set of proteins encompasses canonical subfamilies of beta-lactamases as well as hypothetical proteins and other functional groups. Canonical beta-lactamases were found to be phylogenetically distant from hypothetical proteins, which, in turn, are closer to other representatives of the penicillin-binding-protein (PBP-like) and metallo-beta-lactamase (MBL) families. The catalytic amino acid residues characteristic of beta-lactamases were identified from the sequence alignment and revealed that motifs are less conserved in homologous groups than in beta-lactamases. After comparing the frequency of protein groups in genomes of resistant strains with those of sensitive ones applying Fisher's exact test and relative risk, it was observed that some groups of homologous proteins to classes B and C are more common in the genomes of resistant strains, particularly to carbapenems. We identified the beta-lactamase-like domain widely distributed in gram-negative species of the ESKAPEE group, which highlights its importance in the context of beta-lactam resistance. Some hypothetical homologous proteins have been shown to potentially possess promiscuous activity against beta-lactam antibiotics, however, they do not appear to expressly determine the resistance phenotype. The selective pressure due to the widespread use of antibiotics may favor the optimization of these functions for specialized resistance enzymes.
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Bacterias Gramnegativas , Filogenia , beta-Lactamasas , beta-Lactamasas/metabolismo , beta-Lactamasas/genética , beta-Lactamasas/química , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/genética , Bacterias Gramnegativas/enzimología , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , beta-Lactamas/farmacología , beta-Lactamas/metabolismo , Antibacterianos/farmacología , Genoma Bacteriano , Resistencia betalactámica/genética , Antibióticos BetalactámicosRESUMEN
The rise of multidrug-resistant bacteria is a global concern, leading to a renewed reliance on older antibiotics like polymyxins as a last resort. Polymyxins, cationic cyclic peptides synthesized nonribosomally, feature a hydrophobic acyl tail and positively charged residues. Their antimicrobial mechanism involves initial interaction with Gram-negative bacterial outer-membrane components through polar and hydrophobic interactions. Outer membrane vesicles (OMVs), nano-sized proteoliposomes secreted from the outer membrane of Gram-negative bacteria, play a crucial role in tolerating harmful molecules, including cationic peptides such as polymyxins. Existing literature has documented environmental changes' impact on modulating OMV properties in Salmonella Typhimurium. However, less information exists regarding OMV production and characteristics in Salmonella Typhi. A previous study in our laboratory showed that S. Typhi ΔmrcB, a mutant associated with penicillin-binding protein (PBP, a ß-lactam antibiotic target), exhibited hypervesiculation. Consequently, this study investigated the potential impact of ß-lactam antibiotics on promoting polymyxin tolerance via OMVs in S. Typhi. Our results demonstrated that sub-lethal doses of ß-lactams increased bacterial survival against polymyxin B in S. Typhi. This phenomenon stems from ß-lactam antibiotics inducing hypervesiculation of OMVs with higher affinity for polymyxin B, capturing and diminishing its biologically effective concentration. These findings suggest that ß-lactam antibiotic use may inadvertently contribute to decreased polymyxin effectivity against S. Typhi or other Gram-negative bacteria, complicating the effective treatment of infections caused by these pathogens. This study emphasizes the importance of evaluating the influence of ß-lactam antibiotics on the interaction between OMVs and other antimicrobial agents.
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Chili powder is an important condiment around the world. However, according to various reports, the presence of pathogenic microorganisms could present a public health risk factor during its consumption. Therefore, microbiological quality assessment is required to understand key microbial functional traits, such as antibiotic resistance genes (ARGs). In this study, metagenomic next-generation sequencing (mNGS) and bioinformatics analysis were used to characterize the comprehensive profiles of the bacterial community and antibiotic resistance genes (ARGs) in 15 chili powder samples from different regions of Mexico. The initial bacterial load showed aerobic mesophilic bacteria (AMB) ranging between 6 × 103 and 7 × 108 CFU/g, sporulated mesophilic bacteria (SMB) from 4.3 × 103 to 2 × 109 CFU/g, and enterobacteria (En) from <100 to 2.3 × 106 CFU/g. The most representative families in the samples were Bacillaceae and Enterobacteriaceae, in which 18 potential pathogen-associated species were detected. In total, the resistome profile in the chili powder contained 68 unique genes, which conferred antibiotic resistance distributed in 13 different classes. Among the main classes of antibiotic resistance genes with a high abundance in almost all the samples were those related to multidrug, tetracycline, beta-lactam, aminoglycoside, and phenicol resistance. Our findings reveal the utility of mNGS in elucidating microbiological quality in chili powder to reduce the public health risks and the spread of potential pathogens with antibiotic resistance mechanisms.
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Nosocomial infections caused by Escherichia coli pose significant therapeutic challenges due to the high expression of genes encoding antimicrobial drug resistance. In this study, we investigated the conformation of the beta-lactam resistome responsible for the specific pattern of resistance against beta-lactam antibiotics. A total of 218 Escherichia coli strains were isolated from in-hospital patients diagnosed with nosocomial infections, obtained from various sources such as urine (n = 49, 22.48%), vaginal discharge (n = 46, 21.10%), catheter tips (n = 14, 6.42%), blood (n = 13, 5.96%), feces (n = 12, 5.50%), sputum (n = 11, 5.05%), biopsies (n = 8, 3.67%), cerebrospinal fluid (n = 2, 0.92%) and other unspecified discharges (n = 63, 28.90%). To characterize the beta-lactam resistome, all strains were subjected to antibiotic dilution tests and grown in beta-lactam antibiotics supplemented with Luria culture medium. Subsequently, multiplex PCR and next-generation sequencing were conducted. The results show a multi-drug-resistance phenotype, particularly against beta-lactam drugs. The primary determinant of this resistance was the expression of the blaTEM gene family, with 209 positive strains (95.87%) expressing it as a single gene (n = 47, 21.6%) or in combination with other genes. Common combinations included blaTEM + blaCTX (n = 42, 19.3%), blaTEM + blaCTX + blaSHV (n = 13, 6%) and blaTEM + blaCTX + blaBIL (n = 12, 5.5%), among others. The beta-lactam resistome of nosocomial Escherichia coli strains isolated from inpatients at the "October first" Regional Hospital of ISSSTE was predominantly composed of members of the blaTEM gene family, expressed in various configurations along with different members of other beta-lactamase gene families.
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Abstract Introduction: Urinary tract infections (UTI) are the second most frequent disease caused by bacteria, mainly Escherichia coli and Klebsiella pneumoniae. Furthermore, the emergence of multidrug-resistant extended-spectrum ß-lactamases (ESBL)-producing bacteria is a serious public health issue. Objective: To describe the molecular characteristics of ESBL-producing E. coli and K. pneumoniae isolates obtained from urinary samples of Peruvian patients with UTI. Materials and methods: Retrospective, descriptive, cross-sectional study, in which 118 isolates obtained from urine cultures of patients with UTI treated at 2 hospitals located in the province of Lima and 1 in the province of Callao between April and August, 2019, were analyzed. A MicroScan™ automated system and a conventional polymerase chain reaction (PCR) test were used to identify resistance profiles and detect ESBL genes, respectively. Results: All the bacteria isolated in the 3 hospitals were multi-drug resistant (105 E. coli and 13 K. pneumoniae). Coexistence of ESBL genes (blarEM, blacrx-M, blasHv) was observed in 32.20% of the isolates (28.57% of E. coli and 61.53% of K. pneumoniae isolates). Coexistence of 2 and 3 genes was found in 12.71 % and 21.18 % of isolates, respectively. In addition, blarEM was the ESBL gene most frequently expressed in the isolates (45.76%). Conclusions: Multiple drug resistance was found in all isolates analyzed. Additionally, coexistence of ESBL genes was observed in almost one third of the isolates, showing that antibiotic resistance is a real problem in public hospitals in the provinces of Lima and Callao.
Resumen Introducción. Las infecciones del tracto urinario (ITU) son la segunda enfermedad más frecuente causada por bacterias, principalmente por Escherichia coli y Klebsiella pneumoniae; además, la aparición de bacterias multidrogorresistentes productoras de betalactamasas de espectro extendido (BLEE) representa un serio problema de salud pública. Objetivo. Describir las características moleculares de aislamientos de E. coli y K. pneumoniae productoras de BLEE obtenidos de muestras de orina de pacientes peruanos con ITU. Materiales y métodos. Estudio retrospectivo, transversal y descriptivo. Se analizaron 118 aislamientos de urocultivos de pacientes con ITU atendidos en 2 hospitales de la provincia de Lima y 1 de la provincia del Callao procesados entre abril y agosto del 2019. Los perfiles de resistencia se identificaron utilizando el sistema automatizado MicroScan™ y para la detección de los genes BLEE se empleó una prueba de reacción de cadena de la polimerasa convencional. Resultados. El 100% de las bacterias aisladas en los tres hospitales fueron multidrogorresistentes (105 de E. coli y 13 de K. pneumoniae). La coexistencia de genes BLEE (blarEM, blacrx-M, blasHv) se observó en 32.20% de los aislamientos (28.57% de los de E. coli y 61.53% de los de K. pneumoniae), hallándose coexistencia de 2 genes y 3 genes en 12.71% y 21.18%, respectivamente; además, blarEM fue el gen BLEE más frecuentemente expresado en los aislamientos (45.76%). Conclusiones. Se halló multidrogoresistencia en todos los aislamientos analizados. Además, se observó coexistencia de genes BLEE en casi un tercio de todos los aislamientos, lo que evidencia que la resistencia a los antibióticos es una problemática real en los hospitales públicos de las provincias de Lima y Callao.
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The isolation of multidrug-resistant Klebsiella pneumoniae in hospitals is a major public health threat, increasing patient hospitalization costs, morbidity and mortality. Therefore, this work investigated the resistance mechanisms that produced different carbapenems susceptibility profiles in two isogenic strains of K. pneumoniae isolated from the same patient in a public hospital in Recife, Pernambuco. The genes that encode the main porins in K. pneumoniae, ompK35 and ompK36, and several beta-lactamase genes were analyzed. The expression of these genes was evaluated by quantitative real time PCR (polymerase chain reaction) with reverse transcriptase (RT-qPCR). SDS-PAGE (sodium dodecyl sulphatepolyacrylamide gel electrophoresis) was performed to analyze the outer membrane proteins. The analysis of the ompK36 genetic environment disclosed an IS903 insertion sequence disrupting this gene in the ertapenem resistant isolate (KPN133). The blaKPC-2 gene showed down-regulated expression in both isolates. Our findings show that changes in porins, especially OmpK36, are more determinant to carbapenems susceptibility profile of bacterial isolates than variations in blaKPC gene expression.
O isolamento de Klebsiella pneumoniae multirresistente em hospitais é uma grande ameaça à saúde pública, aumentando os custos de internação, morbidade e mortalidade dos pacientes. Portanto, este trabalho investigou os mecanismos de resistência que produziram diferentes perfis de suscetibilidade aos carbapenêmicos em duas cepas isogênicas de K. pneumoniae isoladas do mesmo paciente em um hospital público em Recife, Pernambuco. Foram analisados ââos genes que codificam as principais porinas em K. pneumoniae, ompK35 e ompK36, e diversos genes de beta-lactamases. A expressão desses genes foi avaliada por PCR (reação em cadeia da polimerase quantitativa em tempo real) com transcriptase reversa (RT-qPCR). SDS-PAGE (dodecil sulfato de sódio-poliacrilamida gel eletroforese) foi realizada para analisar as proteínas da membrana externa. A análise do ambiente genético ompK36 revelou uma sequência de inserção IS903 interrompendo este gene no isolado resistente ao ertapenem (KPN133). O gene blaKPC-2 apresentou expressão negativamente regulada em ambos os isolados. Nossos achados mostram que alterações nas porinas, especialmente OmpK36, são mais determinantes no perfil de suscetibilidade aos carbapenêmicos de isolados bacterianos do que variações na expressão do gene blaKPC.
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Farmacorresistencia Microbiana , Carbapenémicos , Klebsiella pneumoniae/aislamiento & purificaciónRESUMEN
ABSTRACT Escherichia coli and Klebsiella pneumoniae are the most common pathogens causing urinary tract infections in humans and animals. Close contact between humans and companion animals can facilitate the spread of multidrug resistant pathogens between both species. The objective of the research was to characterize extended-spectrum ß-lactamases (ESBL) -producing E. coli and K. pneumoniae isolated from dogs with urinary tract infections in the metropolitan area of Valle del Aburrá (Antioquia, Colombia). Three-hundred seventy-one urine samples collected from March 2018 to March 2019 in a veterinary clinical laboratory were analyzed. E. coli and K. pneumoniae isolates were detected in chromogenic agar and identified by biochemical tests. Susceptibility testing was performed by disc diffusion and ESBL production was evaluated by the double disk test in all isolates. MIC determination of ESBL-positive isolates were performed on the automated VITEK®2 system. Multiple PCR was used for the detection of CTX-M beta-lactamases (group 1, 2, 9 and 8/25), SHV, TEM, and AmpC of plasmid origin in ESBL-positive isolates. In total 22 out 371 isolates were positive for ESBL production by double disc test, 11 E. coli (ESBL-Ec) and 11 K. pneumoniae (ESBL-Kp). The multiple PCR detected CTX-M group 1 in the 22 ESBL-positive isolates. Multi-drug resistance was observed in all ESBL-producing isolates. In conclusion, a high frequency of antibiotic multi-resistance was found in ESBL-Ec and ESBL-Kp. The main ESBL detected was CTX-M group 1, which also prevails in human isolates.
RESUMEN Escherichia coli y Klebsiella pneumoniae son los patógenos más comunes causantes de infecciones en tracto urinario en humanos y animales. El contacto estrecho con los animales de compañía puede favorecer la diseminación de patógenos multiresistentes entre ambas especies. El objetivo de la investigación fue caracterizar E. coli (Ec -BLEE) y K. pneumo-niae (Kp -BLEE) productores de betalactamasas de espectro extendido provenientes de aislados de caninos con infecciones del tracto urinario del Área Metropolitana del Valle de Aburrá. 371 muestras de orina de caninos colectadas entre marzo de 2018 y marzo 2019 en un laboratorio clínico veterinario fueron analizadas. E. coli y K. pneumoniae se detectaron en agar cromogénico y se identificaron mediante pruebas bioquímicas. La prueba de susceptibilidad se realizó por difusión en disco y la producción de BLEE se evaluó por test de doble disco en todos los aislados. La determinación de la CIM en aislados positivos a BLEE se realizó en el sistema automatizado VITEK®2. Se utilizó PCR múltiple para la detección de betalactamasas tipo CTX-M (grupo 1, 2, 9 y 8/25), SHV, TEM y AmpC de origen plasmídico en aislados positivos a BLEE. Un total de 22 de 371 aislados fueron positivos a BLEE por test de doble disco, 11 E. coli (Ec -BLEE) y 11 K. pneumoniae (Kp-BLEE). La PCR detectó CTX-M grupo 1 en los 22 aislados positivos a BLEE. Se observó multirresistencia en todos los aislamientos productores de BLEE. En conclusión, se encontró una alta frecuencia de multirresistencia en Ec-BLEE y Kp-BLEE. La principal BLEE detectada fue CTX-M grupo 1, que también predomina en aislados humanos.
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Introduction: Healthcare-associated infections are a public health problem due to the increased morbimortality of patients, especially those with risk factors such as immunosuppression due to oncological diseases. It is essential to determine the genetic diversity of the main microorganisms causing healthcare infections by combining traditional epidemiological surveillance and molecular epidemiology for better outbreak follow-up and early detection. Objective: To determine the phylogenetic group and antibiotic resistance of Escherichia coli isolated from hospitalized oncologic patients. Materials and methods: We conducted a cross-sectional study of 67 strains of ESBL-producing Escherichia coli to determine their phylogenetic group and described their antibiotic resistance profile, beta-lactam resistance genes, as well as the type of sample and the hospitalization areas from which they were recovered. Results: The most frequent phylogenetic group was B2 (36%); 57% of B2 strains were isolated from urine and 33% came from the urology department. Resistance to ciprofloxacin and gentamicin was 92% and 53%, respectively, and 79% of the strains had the blaCTX-M gene. A significant association (p<0.05) was found between the phylogenetic groups, ciprofloxacin resistance, and the age of the patients. Conclusion: The predominant E. coli phylogroup was B2. We evidenced high resistance to ciprofloxacin and gentamicin, a high proportion of ESBL strains with the blaCTX-M gene, and a significant association between the phylogenetic group and the resistance to ciprofloxacin.
Introducción. Las infecciones asociadas con la atención en salud constituyen un problema de salud pública porque aumentan la morbimortalidad de los pacientes, sobre todo de aquellos con factores de riesgo, como la inmunosupresión debida a enfermedades oncológicas. Es importante conocer la diversidad genética de los principales microorganimos causantes de infecciones hospitalarias mediante la vigilancia epidemiológica tradicional y la epidemiología molecular, para hacer un mejor seguimiento y detectar brotes tempranamente. Objetivo. Determinar el grupo filogenético y la resistencia a antibióticos de las cepas de Escherichia coli aisladas de pacientes con cáncer hospitalizados. Materiales y métodos. Se hizo un estudio de tipo transversal que incluyó 67 cepas de Escherichia coli productoras de betalactamasas de espectro extendido (BLEE). Se determinó el grupo filogenético, el perfil de resistencia a los antibióticos, los genes de resistencia a betalactámicos, el tipo de las muestras y los servicios de hospitalización de donde fueron recuperadas. Resultados. El grupo filogenético más frecuente fue el B2 (36 %). El 57 % de las cepas B2 fueron aisladas de muestras de orina y el 33 % provenía del servicio de urología. La resistencia a ciprofloxacino y gentamicina fue de 91 y 53 %, respectivamente, y el 79 % de las cepas tenía el gen blaCTX-M. Se encontró una relación significativa (p<0,05) entre los grupos filogenéticos y la resistencia a ciprofloxacina, así como a la edad del paciente. Conclusión. El filogrupo de E. coli predominante fue el B2. Se evidenció una gran resistencia a ciprofloxacina y gentamicina, una proporción elevada de cepas BLEE con el blaCTX-M, y una relación entre el grupo filogenético y la resistencia a ciprofloxacino.
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Infecciones por Escherichia coli , Neoplasias , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ciprofloxacina , Estudios Transversales , Farmacorresistencia Bacteriana , Escherichia coli/genética , Infecciones por Escherichia coli/epidemiología , Gentamicinas , Humanos , Perú , Filogenia , beta-Lactamasas/genéticaRESUMEN
OBJECTIVES: Increasing colonization by beta-lactam-resistant Gram-negative bacilli (BR-GNB) represents a risk for infections and bacterial resistance spread, both in hospitals and the community. Hemodialysis patients and their household contacts regularly transit between these environments. This study investigated the clinical and epidemiological characteristics of BR-GNB colonization in hemodialysis patients and their household contacts, as well as the genetic relationship between their isolates. METHODS: A cross-sectional study was conducted on hemodialysis patients at a hospital-associated dialysis center in Medellín, Colombia and their household contacts. Clinical and epidemiological information was collected. Colonization was assessed from stool or rectal swab samples. Bacterial identification and susceptibility were determined using chromogenic media and Vitek-2. Molecular characterization included beta-lactamase detection by polymerase chain reaction, multiple-locus sequence typing (MLST), pulsed-field gel electrophoresis, and identification of Escherichia coli phylogroups by the Clermont protocol. RESULTS: This study included 36 hemodialysis patients and 90 household contacts. Colonization by BR-GNB occurred in 58.3% of patients and 22.2% of household contacts. The main beta-lactamase detected was CTX-M group-1 (40.5%). In 3 of the 9 homes that had more than 1 colonized individual, a genetic relationship was found. MLST showed a high diversity in E. coli isolates, and the most frequent phylogroups were B1 and B2. CONCLUSIONS: These results show a high frequency of colonization and the presence of potentially pathogenic BR-GBN both in hospitals and the community. This highlights the importance of populations who move between those 2 environments, and the need to prevent the spread of bacterial resistance outside hospitals.
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Escherichia coli , Bacterias Gramnegativas , Humanos , Escherichia coli/genética , Tipificación de Secuencias Multilocus , Colombia/epidemiología , Estudios Transversales , Bacterias Gramnegativas/genética , Hospitales , beta-Lactamasas/genética , Diálisis RenalRESUMEN
Introducción. Las infecciones asociadas con la atención en salud constituyen un problema de salud pública porque aumentan la morbimortalidad de los pacientes, sobre todo de aquellos con factores de riesgo, como la inmunosupresión debida a enfermedades oncológicas. Es importante conocer la diversidad genética de los principales microorganimos causantes de infecciones hospitalarias mediante la vigilancia epidemiológica tradicional y la epidemiología molecular, para hacer un mejor seguimiento y detectar brotes tempranamente. Objetivo. Determinar el grupo filogenético y la resistencia a antibióticos de las cepas de Escherichia coli aisladas de pacientes con cáncer hospitalizados. Materiales y métodos. Se hizo un estudio de tipo transversal que incluyó 67 cepas de Escherichia coli productoras de betalactamasas de espectro extendido (BLEE). Se determinó el grupo filogenético, el perfil de resistencia a los antibióticos, los genes de resistencia a betalactámicos, el tipo de las muestras y los servicios de hospitalización de donde fueron recuperadas. Resultados. El grupo filogenético más frecuente fue el B2 (36 %). El 57 % de las cepas B2 fueron aisladas de muestras de orina y el 33 % provenía del servicio de urología. La resistencia a ciprofloxacino y gentamicina fue de 91 y 53 %, respectivamente, y el 79 % de las cepas tenía el gen blaCTX-M. Se encontró una relación significativa (p<0,05) entre los grupos filogenéticos y la resistencia a ciprofloxacina, así como a la edad del paciente. Conclusión. El filogrupo de E. coli predominante fue el B2. Se evidenció una gran resistencia a ciprofloxacina y gentamicina, una proporción elevada de cepas BLEE con el blaCTX-M, y una relación entre el grupo filogenético y la resistencia a ciprofloxacino.
Introduction: Healthcare-associated infections are a public health problem due to the increased morbimortality of patients, especially those with risk factors such as immunosuppression due to oncological diseases. It is essential to determine the genetic diversity of the main microorganisms causing healthcare infections by combining traditional epidemiological surveillance and molecular epidemiology for better outbreak follow-up and early detection. Objective: To determine the phylogenetic group and antibiotic resistance of Escherichia coliisolated from hospitalized oncologic patients. Materials and methods: We conducted a cross-sectional study of 67 strains of ESBL-producing Escherichia coli to determine their phylogenetic group and described their antibiotic resistance profile, beta-lactam resistance genes, as well as the type of sample and the hospitalization areas from which they were recovered. Results: The most frequent phylogenetic group was B2 (36%); 57% of B2 strains were isolated from urine and 33% came from the urology department. Resistance to ciprofloxacin and gentamicin was 92% and 53%, respectively, and 79% of the strains had the blaCTX-Mgene. A significant association (p<0.05) was found between the phylogenetic groups, ciprofloxacin resistance, and the age of the patients. Conclusion: The predominant E. coli phylogroup was B2. We evidenced high resistance to ciprofloxacin and gentamicin, a high proportion of ESBL strains with the blaCTX-M gene, and a significant association between the phylogenetic group and the resistance to ciprofloxacin.
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Resistencia betalactámica , Escherichia coli , Filogenia , Gentamicinas , CiprofloxacinaRESUMEN
Antibiotics may trigger alterations in mitochondrial function, which has been explored in cells culture, and in animal model of sepsis. This study sought to evaluate whether antibiotic therapy affects mitochondrial bioenergetics in a 68-patients clinical study. We studied mitochondrial respiratory rates at two time points: the first day of antibiotic administration and three days after. The Δbasal, ΔCI, ΔCII respiration, and ΔBCE respiratory rates were not different between patients administered with polymyxin, vancomycin, amoxicillin-clavulanate, and azithromycin compared to those who were not administered. Specific beta-lactams are associated with specific modifications in mitochondrial respiratory endpoints - patients who used meropenem had higher delta C2 values compared to those who did not (p = 0.03). Patients who used piperacillin-tazobactam had lower delta C1 (p = 0.03) values than those who did not, but higher delta C2 values (p = 0.02). These mitochondrial metabolic signatures in isolated lymphocytes challenges the proposed effects of antibiotics in mitochondrial bioenergetics of cell cultures, but at current status have an uncertain clinical significance.
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Choque Séptico , Amoxicilina/uso terapéutico , Antibacterianos , Azitromicina/uso terapéutico , Ácido Clavulánico/uso terapéutico , Metabolismo Energético , Humanos , Linfocitos , Meropenem/uso terapéutico , Mitocondrias , Combinación Piperacilina y Tazobactam/uso terapéutico , Polimixinas/uso terapéutico , Estudios Prospectivos , Choque Séptico/tratamiento farmacológico , Vancomicina/uso terapéutico , beta-Lactamas/uso terapéuticoRESUMEN
RESUMEN Los asilos de ancianos son instituciones con una alta prevalencia de infecciones del tracto urinario ocasionado por Escherichia coli productoras de ß-lactamasas de espectro extendido (BLEE), con diversos factores de virulencia. El objetivo del estudio fue determinar la frecuencia del gen bla CTX-M y de ocho genes de virulencia en 35 E. coli uropatógenas productoras de BLEE provenientes de seis asilos en Perú, durante el 2018. El 57,1% (20/35) de las E. coli fueron portadores del gen bla CTX-M. Además, se obtuvo una frecuencia del 46% (15/35) y 37% (13/35) de hly-alfa y cnf-1, respectivamente; elevada presencia de los genes iucC (63%, 22/35), aer (94%, 33/35) y chuA (94%, 33/34) y una frecuencia del 46% (16/35) y del 91% (32/34) de los genes pap GII y nanA, respectivamente. Existe predominancia en la distribución del gen bla CTX-M, además de una alta frecuencia de exotoxinas que le confieren una ventaja competitiva para diseminarse hacia el torrente sanguíneo.
ABSTRACT Nursing homes are institutions with high prevalence of urinary tract infections caused by ESBL-producing E. coli with several virulence factors. The aim of this study was to determine the frequency of the bla CTX-M gene and eight virulence genes in 35 ESBL-producing uropathogenic E. coli from six nursing homes in Peru during 2018. Of the E. coli samples, 57.1% (20/35) were carriers of the bla CTX-M gene. Furthermore, we obtained frequencies of 46% (15/35) and 37% (13/35) for hly-alpha and cnf-1, respectively; we also found high presence of the iucC (63%, 22/35), aer (94%, 33/35) and chuA genes (94%, 33/34) as well as a frequency of 46% (16/35) and 91% (32/34) for the pap GII and nanA genes, respectively. The bla CTX-M gene is predominant and a high frequency of exotoxins gives it a competitive advantage for spreading into the bloodstream.
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Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Virulencia , Escherichia coli , Escherichia coli Uropatógena , Antibacterianos , Infecciones Urinarias , Resistencia betalactámica , Factores de Virulencia , Infecciones por Enterobacteriaceae , Hogares para Ancianos , InfeccionesRESUMEN
This study aimed to describe the presence and geographical distribution of Gram-negativebacteria considered critical on the priority list of antibiotic-resistant pathogens publishedby the World Health Organization, including carbapenem-resistant Enterobacteriaceae,carbapenem-resistant Acinetobacter spp., and carbapenem-resistant Pseudomonas aeruginosa.A systematic review of original studies published in 5 databases between 2010 and 2021 wasconducted, including genotypically confirmed carbapenem-resistant isolates obtained fromcanines, felines, and their settings. Fifty-one articles met the search criteria. Carbapenemresistant isolates were found in domestic canines and felines, pet food, and on veterinarymedical and household surfaces. The review found that the so-called "big five"-that is, the5 major carbapenemases identified worldwide in Enterobacterales (New Delhi metallo-ßlactamase, active-on-imipenem, Verona integron-encoded metallo-ß-lactamase, Klebsiellapneumoniae carbapenemase, and oxacillin [OXA]-48-like)-and the 3 most importantcarbapenemases from Acinetobacter spp. (OXA-23-like, OXA-40-like, and OXA-58-like) hadbeen detected in 8 species in the Enterobacteriaceae family and 5 species of glucose nonfermenting bacilli on 5 continents. Two publications used molecular analysis to confirmcarbapenem-resistant bacteria transmission between owners and dogs. Isolating criticallyimportant human carbapenem-resistant Gram-negative bacteria from domestic canines andfelines highlights the importance of including these animal species in surveillance programsand antimicrobial resistance containment plans as part of the One Health approach.
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Resumen La bacteria Klebsiella pneumoniae es la causante de infecciones intrahospitalarias multirresistentes, posee diversos mecanismos de resistencia como la producción de enzimas betalactamasas cuya acción afecta a los antibióticos betalactámicos. Objetivo: Caracterizar los mecanismos de resistencia presentes en aislados clínicos con Klebsiella pneumoniae identificados mediante métodos fenotípicos en el Hospital Monte Sinai desde enero de 2018 hasta agosto de 2020. Materiales y métodos: Estudio positivista con un enfoque cuantitativo de corte transversal descriptivo de diseño documental. La población estuvo conformada por 274 datos de aislados clínicos identificados con Klebsiella pneumoniae. Los cuales conformaron la totalidad de la muestra con un muestreo por cobertura total. Mismos que fueron recopilados de fuentes secundarias ingresados en la base de datos del departamento de Microbiología. Para el análisis se utilizó estadística descriptiva. Resultados: Klebsiella pneumoniae mostró mayor frecuencia en el año 2020 con el 35%. Se identificó al mecanismo de resistencia BLEE con el 27,7% y carbapenemasas tipo KPC con el 7.7 %, con mayor presencia en el sexo masculino. Presentó una mayor resistencia a Penicilinas, una sensibilidad moderada a Cefalosporinas, Aminoglucósidos, Quinolonas y una alta sensibilidad a los Carbapenémicos, Tigeciclina y Colistina. Los aislados se clasificaron como multidrogorresistentes, con mayor frecuencia en Urocultivo, Aspirado bronquial, Líquido corporal, Punta de Catéter y Hemocultivo en áreas de Hospitalización, UCI y Neonatología. Conclusiones: Los mecanismos de resistencia de K. pneumoniae a los antibióticos son un hallazgo común en ambientes hospitalarios independientemente de sexo, servicio hospitalario o tipo de muestra, convirtiéndose en un problema de salud pública.
Abstract The bacterium Klebsiella pneumoniae is the cause of multiresistant intrahospital infections, it has various resistance mechanisms such as the production of beta-lactamase enzymes whose action affects beta-lactam antibiotics. Objective: To characterize the resistance mechanisms present in clinical isolates with Klebsiella pneumoniae identified by phenotypic methods at Monte Sinai Hospital from January 2018 to August 2020. Materials and methods: Positivist study with a descriptive cross-sectional quantitative approach to documentary design. The population consisted of 274 data from clinical isolates identified with Klebsiella pneumoniae. Which made up the entire sample with a total coverage sampling. The same ones that were collected from secondary sources entered in the database of the Microbiology department. Descriptive statistics were used for the analysis. Results: Klebsiella pneumoniae showed a higher frequency in 2020 with 35%. The ESBL resistance mechanism was identified with 27.7% and KPC-type carbapenemases with 7.7%, with a higher presence in males. It presented a greater resistance to Penicillins, a moderate sensitivity to Cephalosporins, Aminoglycosides, Quinolones and a high sensitivity to Carbapenems, Tigecycline and Colistin. The isolates were classified as multidrug resistant, more frequently in Urine culture, Bronchial aspirate, Body fluid, Catheter Tip and Blood culture in Hospitalization, ICU and Neonatology areas. Conclusions: The resistance mechanisms of K. pneumoniae to antibiotics are a common finding in hospital settings regardless of sex, hospital service or type of sample, becoming a public health problem.
Resumo A bactéria Klebsiella pneumoniae é causa de infecções intra-hospitalares multirresistentes, possui diversos mecanismos de resistência como a produção de enzimas beta-lactamase cuja ação afeta os antibióticos beta-lactâmicos. Objetivo: Caracterizar os mecanismos de resistência presentes em isolados clínicos de Klebsiella pneumoniae identificados por métodos fenotípicos no Hospital Monte Sinai de janeiro de 2018 a agosto de 2020. Materiais e métodos: Estudo positivista com abordagem quantitativa transversal descritiva do design documental. A população consistia em 274 dados de isolados clínicos identificados com Klebsiella pneumoniae. O que constituiu toda a amostra com uma amostra de cobertura total. Os mesmos que foram coletados em fontes secundárias e cadastrados no banco de dados do departamento de Microbiologia. Estatísticas descritivas foram utilizadas para a análise. Resultados: Klebsiella pneumoniae apresentou maior frequência em 2020 com 35%. O mecanismo de resistência a ESBL foi identificado com 27,7% e carbapenemases do tipo KPC com 7,7%, com maior presença no sexo masculino. Apresentou maior resistência às Penicilinas, sensibilidade moderada às Cefalosporinas, Aminoglicosídeos, Quinolonas e alta sensibilidade aos Carbapenêmicos, Tigeciclina e Colistina. Os isolados foram classificados como multirresistentes, com maior frequência em Urocultura, Aspirado Brônquico, Fluido Corporal, Ponta de Cateter e Hemocultura em Hospitalização, UTI e Neonatologia. Conclusões: Os mecanismos de resistência de K. pneumoniae aos antibióticos são um achado comum em ambientes hospitalares independentemente do sexo, serviço hospitalar ou tipo de amostra, tornando-se um problema de saúde pública.
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Introduction. The emergence of multiresistant enterobacteria producing extendedspectrum beta-lactamase (ESBL) in outpatients with urinary tract infections represents a public health problem in Perú. Objectives. To characterize multiresistant enterobacteria isolated from patients diagnosed with urinary tract infection in two Peruvian jungle departments using molecular techniques. Materials and methods. We conducted a descriptive, observational, and retrospective study of 61 urine culture isolates from two departments in the Peruvian jungle during 2017-2018. Resistance profiles were identified using the MicroScan™ automated system and a conventional polymerase chain reaction (PCR) was used for the detection of blaCTX-M, blaTEM and blaSHV genes. Results. The most common positive ESBL enterobacteria for each department were Escherichia coli in Madre de Dios (10/40; 25%) and Ucayali (16/21; 76.2%). Gene blaCTX-M was the most prevalent in both departments (25/61; 41%), followed by blaTEM (15/61; 24.6%), and blaSHV (10/61; 16.4%). As for the antimicrobial susceptibility profile, we detected resistance levels of 72.6% for ampicillin, 82.3% for cephalothin, and 88.7% for nitrofurantoin. Conclusions. BLEE-producing multi-resistant enterobacteria strains in both departments were 57.4% and blaCTX-M was the most common gene.
Introducción. La aparición de enterobacterias multirresistentes y productoras de betalactamasas de espectro extendido (BLEE) en pacientes de consulta externa con infecciones urinarias, representa un problema de salud pública en Perú. Objetivos. Caracterizar molecularmente enterobacterias multirresistentes aisladas de pacientes con diagnóstico de infección urinaria y procedentes de dos departamentos de la selva peruana. Materiales y métodos. Se hizo un estudio descriptivo, observacional y retrospectivo de 61 aislamientos de urocultivo procedentes de la selva peruana durante 2017 y 2018. Los perfiles de resistencia se identificaron utilizando el sistema automatizado MicroScan™ y para la detección de los genes blaTEM, blaCTX-M, blaSHV se empleó una reacción en cadena de la polimerasa (PCR) convencional. Resultados. Las enterobacterias positivas para BLEE más frecuentes por departamento fueron Escherichia coli en Madre de Dios (25 %, 10/40) y Ucayali (76,2 %, 16/21). En ambos departamentos, el gen blaCTX-M fue el más frecuente (25/61; 41 %), seguido por blaTEM (15/61; 24,6 %) y blaSHV (10/61; 16,4 %). En el perfil de sensibilidad antimicrobiana, se detectó 72,6 % de resistencia contra ampicilina, 82,3 % contra cefalotina y 88,7 % contra nitrofurantoína. Conclusiones. El porcentaje de cepas de enterobacterias multirresistentes productoras de BLEE en ambos departamentos fue del 57,4 % y el gen bla CTX-M fue el más frecuente.
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Infecciones por Escherichia coli , Infecciones Urinarias , Antibacterianos/farmacología , Enterobacteriaceae/genética , Escherichia coli/genética , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Perú/epidemiología , Estudios Retrospectivos , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología , beta-Lactamasas/genéticaRESUMEN
Resumen | Introducción. La aparición de enterobacterias multirresistentes y productoras de betalactamasas de espectro extendido (BLEE) en pacientes de consulta externa con infecciones urinarias, representa un problema de salud pública en Perú. Objetivos. Caracterizar molecularmente enterobacterias multirresistentes aisladas de pacientes con diagnóstico de infección urinaria y procedentes de dos departamentos de la selva peruana. Materiales y métodos. Se hizo un estudio descriptivo, observacional y retrospectivo de 61 aislamientos de urocultivo procedentes de la selva peruana durante 2017 y 2018. Los perfiles de resistencia se identificaron utilizando el sistema automatizado MicroScan™ y para la detección de los genes blaTEM, blaCTX-M, blaSHV se empleó una reacción en cadena de la polimerasa (PCR) convencional. Resultados. Las enterobacterias positivas para BLEE más frecuentes por departamento fueron Escherichia coli en Madre de Dios (25 %, 10/40) y Ucayali (76,2 %, 16/21). En ambos departamentos, el gen blaCTX-Mfue el más frecuente (25/61; 41 %), seguido por blaTEM(15/61; 24,6 %) y blaSHV (10/61; 16,4 %). En el perfil de sensibilidad antimicrobiana, se detectó 72,6 % de resistencia contra ampicilina, 82,3 % contra cefalotina y 88,7 % contra nitrofurantoína. Conclusiones. El porcentaje de cepas de enterobacterias multirresistentes productoras de BLEE en ambos departamentos fue del 57,4 % y el gen bla CTX-M fue el más frecuente.
Abstract | Introduction. The emergence of multiresistant enterobacteria producing extended-spectrum beta-lactamase (ESBL) in outpatients with urinary tract infections represents a public health problem in Perú. Objectives. To characterize multiresistant enterobacteria isolated from patients diagnosed with urinary tract infection in two Peruvian jungle departments using molecular techniques. Materials and methods. We conducted a descriptive, observational, and retrospective study of 61 urine culture isolates from two departments in the Peruvian jungle during 2017-2018. Resistance profiles were identified using the MicroScan™ automated system and a conventional polymerase chain reaction (PCR) was used for the detection of blaCTX-M, blaTEMand blaSHV genes. Results. The most common positive ESBL enterobacteria for each department were Escherichia coli in Madre de Dios (10/40; 25%) and Ucayali (16/21; 76.2%). Gene blaCTX-Mwas the most prevalent in both departments (25/61; 41%), followed by blaTEM (15/61; 24.6%), and blaSHV (10/61; 16.4%). As for the antimicrobial susceptibility profile, we detected resistance levels of 72.6% for ampicillin, 82.3% for cephalothin, and 88.7% for nitrofurantoin. Conclusions. BLEE-producing multi-resistant enterobacteria strains in both departments were 57.4% and blaCTX-M was the most common gene.
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Farmacorresistencia Microbiana , Enterobacteriaceae , Resistencia betalactámica , GenesRESUMEN
Últimamente, se están detectando mutaciones en las proteínas ligadoras de penicilina (PBP) de los estreptococos beta-hemolíticos que corresponden a sitios que en Streptococcus pneumoniae han determinado sensibilidad disminuida a los antibióticos beta-lactámicos. Primero, se describieron cepas con sensibilidad intermedia a penicilina en Streptococcus agalactiae (estreptococos del grupo B), luego en Streptococcus dysgalactiae subsp. equisimilis (mayormente grupos C y G) y, más recientemente, cepas con sensibilidad disminuida a aminopenicilinas y cefalosporinas de tercera generación en Streptococcus pyogenes (grupo A). El costo biológico de estas modificaciones nos permite pensar que los niveles de resistencia no han de ser tan elevados como para comprometer por ahora la efectividad clínica de los beta-lactámicos (AU)
Recently, mutations in penicillin-binding proteins (PBPs) of beta-hemolytic streptococci have been detected corresponding to sites that in Streptococcus pneumoniae have been determined to have decreased sensitivity to beta-lactam antibiotics. First, strains with intermediate sensitivity to penicillin were described in Streptococcus agalactiae (group B streptococci), subsequently in Streptococcus dysgalactiae subsp. equisimilis (mainly groups C and G) and, more recently, strains with decreased sensitivity to third-generation aminopenicillins and cephalosporins were found in Streptococcus pyogenes (group A). The biological cost of these modifications suggests that, for now, resistance levels are not high enough to compromise the clinical effectiveness of beta-lactams (AU)