RESUMO
Introduction: The Mycobacterium chelonae species and the M. avium and M. abscessus complexes are emerging pathogens that cause mycobacteriosis. Treatment depends on the species and subspecies identified. The drugs of choice are macrolides and aminoglycosides. However, due to the resistance identified to these drugs, determining the microbe's sensitivity profile will allow clinicians to improve the understanding of the prognosis and evolution of these pathologies. Objective: To describe the macrolide and aminoglycoside susceptibility profile of cultures identified by Colombia's Laboratorio Nacional de Referencia de Mycobacteria from 2018 to 2022, as Mycobacterium avium complex, M. abscessus complex, and M. chelonae. Materials and methods. This descriptive study exposes the susceptibility profile to macrolides and aminoglycosides of cultures identified as M. avium complex, M. abscessus complex, and M. chelonae using the GenoType® NTM-DR method. Materials and methods: This descriptive study exposes the susceptibility profile to macrolides and aminoglycosides of cultures identified as M. avium complex, M. abscessus complex, and M. chelonae using the GenoType® NTM-DR method. Results: We identified 159 (47.3 %) cultures as M. avium complex, of which 154 (96.9 %) were sensitive to macrolides, and 5 (3.1 %) were resistant; all were sensitive to aminoglycosides. From the 125 (37.2 %) cultures identified as M. abscessus complex, 68 (54.4 %) were sensitive to macrolides, 57 (45.6 %) were resistant to aminoglycosides, and just one (0.8 %) showed resistance to aminoglycosides. The 52 cultures (15.5 %) identified as M. chelonae were sensitive to macrolides and aminoglycosides. Conclusions: The three studied species of mycobacteria have the least resistance to Amikacin. Subspecies identification and their susceptibility profiles allow the establishment of appropriate treatment schemes, especially against M. abscessus.
Introducción. Mycobacterium chelonae y los complejos Mycobacterium avium y M. abscessus, son agentes patógenos emergentes causantes de micobacteriosis. El tratamiento de esta infección depende de la especie y la subespecie identificadas. Los fármacos de elección son los macrólidos y aminoglucósidos, contra los cuales se ha reportado resistencia; por esta razón, el determinar el perfil de sensibilidad le permite al médico tratante comprender mejor el pronóstico y la evolución de estas infecciones. Objetivo. Describir los perfiles de sensibilidad ante macrólidos y aminoglucósidos, de los cultivos identificados como complejo Mycobacterium avium, complejo M. abscessus o especie M. chelonae, en el Laboratorio Nacional de Referencia de Micobacterias durante los años 2018 a 2022. Materiales y métodos. Se llevó a cabo un estudio descriptivo del perfil de sensibilidad a macrólidos y aminoglucósidos, de los cultivos identificados como complejo M. avium, complejo M. abscessus o M. chelonae, mediante la metodología GenoType® NTM-DR. Resultados. Los cultivos del complejo M. avium fueron 159 (47,3 %), de los cuales, 154 (96,9 %) fueron sensibles y 5 (3,1 %) resistentes a los macrólidos; todos fueron sensibles a los aminoglucósidos. Del complejo M. abscessus se estudiaron 125 (37,2 %) cultivos, 68 (54,4 %) resultaron sensibles y 57 (45,6 %) resistentes a los macrólidos; solo un cultivo (0,8 %) fue resistente a los aminoglucósidos. De M. chelonae se analizaron 52 cultivos (15,5 %), todos sensibles a los macrólidos y aminoglucósidos. Conclusiones. En las tres especies de micobacterias estudiadas, la resistencia contra la amikacina fue la menos frecuente. La identificación de las subespecies y los perfiles de sensibilidad permiten instaurar esquemas de tratamiento adecuados, especialmente en las micobacteriosis causadas por M. abscessus.
Assuntos
Aminoglicosídeos , Macrolídeos , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Complexo Mycobacterium avium , Mycobacterium chelonae , Macrolídeos/farmacologia , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium abscessus/genética , Mycobacterium abscessus/isolamento & purificação , Colômbia/epidemiologia , Mycobacterium chelonae/efeitos dos fármacos , Mycobacterium chelonae/genética , Mycobacterium chelonae/isolamento & purificação , Aminoglicosídeos/farmacologia , Humanos , Complexo Mycobacterium avium/efeitos dos fármacos , Complexo Mycobacterium avium/genética , Complexo Mycobacterium avium/isolamento & purificação , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Prevalência , Farmacorresistência Bacteriana MúltiplaRESUMO
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.
RESUMO
INTRODUCTION: Aminoglycosides are vital antibiotics for treating Brucella infections, because they interfere with bacterial protein production and are often combined with other antibiotics. They are cost-effective, have fewer side effects, and can penetrate biofilms. The prevalence of brucellosis has increased in recent years, increasing the need for effective treatments. In addition, the emergence of multidrug-resistant Brucella strains has highlighted the need for an updated and comprehensive understanding of aminoglycoside resistance. This systematic review aimed to provide a comprehensive overview of the global prevalence of aminoglycoside resistance in B. melitensis and B. abortus. METHODS: A systematic search of online databases was conducted and eligible studies met certain criteria and were published in English. Quality assessment was performed using the JBI Checklist. A random-effects model was fitted to the data, and meta-regression, subgroup, and outlier/influential analyses were performed. The analysis was performed using R and the metafor package. RESULTS: The results of this systematic review and meta-analysis suggested that the average prevalence rates of streptomycin, gentamicin, and amikacin resistance were 0.027 (95% confidence interval [CI], 0.015-0.049), 0.023 (95% CI, 0.017-0.032), and 0.008 (95% CI, 0.002-0.039), respectively. The prevalence of streptomycin resistance was higher in the unidentified Brucella group than in the B. abortus and B. melitensis groups (0.234, 0.046, and 0.017, respectively; p < 0.02). The prevalence of gentamicin resistance increased over time (r = 0.064; 95% CI, 0.018 to 0.111; p = 0.007). The prevalence of resistance did not correlate with the quality score for any antibiotic. Funnel plots showed a potential asymmetry for streptomycin and gentamicin. These results suggest a low prevalence of antibiotic resistance in the studied populations. CONCLUSION: The prevalence of aminoglycoside resistance in B. melitensis and B. abortus was low. However, gentamicin resistance has increased in recent years. This review provides a comprehensive and updated understanding of aminoglycoside resistance in B. melitensis and B. abortus.
Assuntos
Aminoglicosídeos , Antibacterianos , Brucella abortus , Brucella melitensis , Brucelose , Aminoglicosídeos/farmacologia , Brucella abortus/efeitos dos fármacos , Brucella abortus/genética , Brucella abortus/isolamento & purificação , Antibacterianos/farmacologia , Brucelose/microbiologia , Brucelose/epidemiologia , Brucella melitensis/efeitos dos fármacos , Brucella melitensis/isolamento & purificação , Brucella melitensis/genética , Humanos , Prevalência , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , AnimaisRESUMO
Background and Objectives: during the COVID-19 pandemic, the number of critical patients requiring intensive care increased considerably, resulting in an increase in infections due to multi-resistant microorganisms. In Brazil, in 2021, due to the high demand for polymyxin B use, there was a national shortage of the medication. One strategy used to overcome this situation was aminoglycoside use. The work aimed to analyze the impact of replacing polymyxin B with amikacin and gentamicin in the final stage of patients. Method: an analytical study with an observational, cross-sectional design, with a quantitative approach, through a retrospective analysis through the analysis of medical records, with the primary stages being discharges or deaths. Results: mortality was similar between the group treated with aminoglycoside and the group treated with polymyxin B. Within the aminoglycoside group, mortality was higher in the group that had bacteria resistant to the drug than in the group that had infection with an organism sensitive to this drug. Mortality was not affected by comorbidities, age, or number of hospital infections. The main factor that led to the need for dialysis was the combination of two nephrotoxic medications. Conclusion: two hypotheses emerged: the first would be that replacing polymyxin B with aminoglycosides did not impact mortality; the other would be that, regardless of the antibiotic group used, patients had a high risk of death. Despite sample limitations, the study corroborates the adoption of strategies for the rational use of antimicrobials.(AU)
Justificativa e Objetivos: durante a pandemia de COVID-19, o número de pacientes críticos que necessitaram de cuidados intensivos aumentou consideravelmente, resultando em aumento de infecções por microrganismos multirresistentes. No Brasil, em 2021, devido à grande demanda pelo uso da polimixina B, houve escassez nacional do medicamento. Uma estratégia utilizada para superar essa situação foi o uso de aminoglicosídeos. O trabalho teve como objetivo analisar o impacto da substituição da polimixina B por amicacina e gentamicina na fase final dos pacientes. Método: estudo analítico com desenho observacional, transversal, com abordagem quantitativa, por meio de análise retrospectiva por meio de análise de prontuários, sendo as etapas primárias as altas ou óbitos. Resultados: a mortalidade foi semelhante entre o grupo tratado com aminoglicosídeo e o grupo tratado com polimixina B. Dentro do grupo aminoglicosídeo, a mortalidade foi maior no grupo que apresentava bactérias resistentes ao medicamento do que no grupo que apresentava infecção por organismo sensível a este medicamento. medicamento. A mortalidade não foi afetada por comorbidades, idade ou número de infecções hospitalares. O principal fator que levou à necessidade de diálise foi a combinação de dois medicamentos nefrotóxicos. Conclusão: surgiram duas hipóteses: a primeira seria que a substituição da polimixina B por aminoglicosídeos não impactou a mortalidade; a outra seria que, independentemente do grupo de antibióticos utilizado, os pacientes apresentavam alto risco de morte. Apesar das limitações amostrais, o estudo corrobora a adoção de estratégias para o uso racional de antimicrobianos.(AU)
Antecedentes y Objetivos: durante la pandemia de COVID-19, el número de pacientes críticos que requirieron cuidados intensivos aumentó considerablemente, resultando en un aumento de infecciones por microorganismos multirresistentes. En Brasil, en 2021, debido a la alta demanda del uso de polimixina B, hubo escasez nacional del medicamento. Una estrategia utilizada para superar esta situación fue el uso de aminoglucósidos. El trabajo tuvo como objetivo analizar el impacto de la sustitución de la polimixina B por amikacina y gentamicina en la etapa final de los pacientes. Método: estudio analítico con diseño observacional, transversal, con enfoque cuantitativo, mediante un análisis retrospectivo mediante el análisis de historias clínicas, siendo las etapas primarias las altas o defunciones. Resultados: la mortalidad fue similar entre el grupo tratado con aminoglucósido y el grupo tratado con polimixina B. Dentro del grupo de aminoglucósido, la mortalidad fue mayor en el grupo que tenía bacterias resistentes al fármaco que en el grupo que tenía infección con un organismo sensible a este. droga. La mortalidad no se vio afectada por las comorbilidades, la edad o el número de infecciones hospitalarias. El principal factor que llevó a la necesidad de diálisis fue la combinación de dos medicamentos nefrotóxicos. Conclusión: surgieron dos hipótesis: la primera sería que la sustitución de polimixina B por aminoglucósidos no impactó la mortalidad; la otra sería que, independientemente del grupo de antibióticos utilizado, los pacientes tenían un alto riesgo de muerte. A pesar de las limitaciones de la muestra, el estudio corrobora la adopción de estrategias para el uso racional de antimicrobianos.(AU)
Assuntos
Humanos , Polimixina B/provisão & distribuição , COVID-19/mortalidade , Aminoglicosídeos/uso terapêutico , Estudos Transversais , Uso de MedicamentosRESUMO
The spread of nosocomial infections caused by antibiotic-resistant Enterococcus faecalis is one of the major threats to global health at present. While aminoglycosides are often used to combat these infections, their effectiveness is reduced by various resistance mechanisms, including aminoglycoside modifying enzymes, and there are currently no drugs to inhibit these enzymes. To address this issue, this study was conducted to identify potential aminoglycoside adjuvants from a database of 462 flavones. The affinity of these molecules with the nucleotide-binding site (NBS) of aminoglycoside phosphotransferase type IIIa of E. faecalis (EfAPH(3')-IIIa) was evaluated, and the five molecules with the highest binding energies were identified. Of these, four were naphthoflavones, suggesting that their backbone could be useful in designing potential inhibitors. The highest-ranked naphthoflavone, 2-phenyl-4H-benzo[h]chromen-4-one, was modified to generate two new derivatives (ANF2OHC and ANF2OHCC) to interact with the NBS similarly to adenine in ATP. These derivatives showed higher binding free energies, better stability in molecular dynamics analysis and superior pharmacokinetic and toxicological profiles compared to the parent molecule. These findings suggest that these alpha-naphthoflavone derivatives are potential inhibitors of EfAPH(3')-IIIa and that this core may be a promising scaffold for developing adjuvants that restore the sensitivity of aminoglycosides.
RESUMO
A patient with acute myeloid leukemia presented various episodes of febrile neutropenia, for which there was no positive response to antibiotic treatments. Following an episode of bacteremia by extensively drug-resistant Klebsiella pneumoniae, amikacin was prescribed, pharmacokinetic analyses of its plasma concentrations were performed and the dosage interval was narrowed to 12 and 8 h in order to counteract the reduced postantibiotic effect due to the patient being immunocompromised. The patient responded positively, with procalcitonin decreasing and body temperature normalizing. Recovery was finally achieved, without renal or auditory damage. This case proposes tightening dosage intervals for aminoglycosides as an effective strategy in immunocompromised patients. Aminoglycosides are given over extended intervals (24 h), considering concentration-dependent effectiveness, nephrotoxicity and postantibiotic effect. Leukocytes appear to play a determining role in the postantibiotic effect, with no proposed dosing strategy for strongly immunocompromised patients.
Assuntos
Neutropenia Febril , Neoplasias Hematológicas , Humanos , Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Amicacina , Neoplasias Hematológicas/tratamento farmacológico , Neutropenia Febril/tratamento farmacológicoRESUMO
NucS/EndoMS-dependent noncanonical mismatch repair (MMR) ensures the stability of genomic DNA in mycobacteria and acts as a guardian of the genome by preventing the accumulation of point mutations. In order to address whether the inactivation of noncanonical MMR could increase the acquisition of drug resistance by mutation, a ΔnucS strain was constructed and explored in the emerging pathogen Mycobacterium abscessus. Deletion of nucS resulted in a mutator phenotype with increased acquisition of resistance to macrolides and aminoglycosides, the two main groups of antimycobacterial agents for M. abscessus treatment, and also to second-line drugs such as fluoroquinolones. Inactivation of the noncanonical MMR in M. abscessus led to increases of 10- to 22-fold in the appearance of spontaneous mutants resistant to the macrolide clarithromycin and the aminoglycosides amikacin, gentamicin, and apramycin, compared with the wild-type strain. Furthermore, emergence of fluoroquinolone (ciprofloxacin) resistance was detected in a nucS-deficient strain but not in a wild-type M. abscessus strain. Acquired drug resistance to macrolides and aminoglycosides was analyzed through sequencing of the 23S rRNA gene rrl and the 16S rRNA gene rrs from independent drug-resistant colonies of both strains. When the acquisition of clarithromycin resistance was examined, a different mutational profile was detected in the M. abscessus ΔnucS strain compared with the wild-type one. To summarize, M. abscessus requires the NucS-dependent noncanonical MMR pathway to prevent the emergence of drug-resistant isolates by mutation. To our knowledge, this is the first report that reveals the role of NucS in a human pathogen, and these findings have potential implications for the treatment of M. abscessus infections. IMPORTANCE Chronic infections caused by M. abscessus are an emerging challenge in public health, posing a substantial health and economic burden, especially in patients with cystic fibrosis. Treatment of M. abscessus infections with antibiotics is particularly challenging, as its complex drug resistance mechanisms, including constitutive resistance through DNA mutation, lead to high rates of treatment failure. To decipher the evolution of antibiotic resistance in M. abscessus, we studied NucS-dependent noncanonical MMR, a unique DNA repair pathway involved in genomic maintenance. Inactivation of NucS is linked to the increase of DNA mutations (hypermutation), which can confer drug resistance. Our analysis detected increased acquisition of mutations conferring resistance to first-line and second-line antibiotics. We believe that this study will improve the knowledge of how this pathogen could evolve into an untreatable infectious agent, and it uncovers a role for hypermutators in chronic infectious diseases under antibiotic pressure.
Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Claritromicina/uso terapêutico , Mycobacterium abscessus/genética , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , RNA Ribossômico 16S/genética , Reparo de Erro de Pareamento de DNA , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Macrolídeos/uso terapêutico , Resistência Microbiana a Medicamentos , Aminoglicosídeos/uso terapêutico , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana/genéticaRESUMO
Antimicrobial resistance (AMR) remains a major global public health crisis. The food animal industry will face escalating challenges to increase productivity while minimizing AMR, since the global demand for animal protein has been continuously increasing and food animals play a key role in the global food supply, particularly broiler chickens. As chicken products are sources of low-cost, high-quality protein, poultry production is an important economic driver for livelihood and survival in developed and developing regions. The globalization of the food supply, markedly in the poultry industry, is aligned to the globalization of the whole modern society, with an unprecedented exchange of goods and services, and transit of human populations among regions and countries. Considering the increasing threat posed by AMR, human civilization is faced with a complex, multifaceted problem compromising its future. Actions to mitigate antimicrobial resistance are needed in all sectors of the society at the human, animal, and environmental levels. This review discusses the problems associated with antimicrobial resistance in the globalized food chain, using the poultry sector as a model. We cover critical aspects of the emergence and dissemination of antimicrobial resistance in the poultry industry and their implications to public health in a global perspective. Finally, we provide current insights using the multidisciplinary One Health approach to mitigate AMR at the human-animal-environment interface.
Assuntos
Saúde Única , Aves Domésticas , Animais , Antibacterianos/farmacologia , Galinhas/microbiologia , Farmacorresistência Bacteriana , Cadeia Alimentar , Humanos , Aves Domésticas/microbiologiaRESUMO
Abstract Instrumental techniques are preferred over bioassay methods for antibiotic quantification mainly due to speed and ability to quantify metabolites in biological samples; however, the potency and biological activity of these drugs cannot be assessed. Two methods - agar well diffusion (bio-assay) and spectrophotometric methods were used to evaluate amikacin sulfate injection. Agar plates were inoculated with S. aureus inoculum; zones of inhibition from its susceptibility to amikacin were obtained, while spectrophotometric absorption at 650 nm of ninhydrin- derivatized amikacin in phosphate buffer (pH 8) was measured. Methods performance showed linearity from 1 - 16 µgmL-1 (bioassay, r = 0.9994) and 10-50 µgmL-1 (spectrophotometric, r = 0.9998). Molar absorptivity was 2.595 x 104 Lmol-1cm-1. Limits of detection and quantification were 1.07 and 3.24 µgmL-1 respectively for bioassay method, while corresponding values for spectrophotometric method were 0.98 and 2.97 µg mL-1. Relative standard deviations were ≤ 2.0% for both methods, with recoveries from 95.93 - 100.25%. Amikacin in brands ranged from 97.53 ± 2.68 to 100.84 ± 1.82%, student's t-test was ≤ 2.78 (n = 4) with respect to label claim for both methods. Experimental paired t-test (t = 2.07; n = 4) and F-test (F = 3.94; n = 4) values indicated no significant difference between both methods, hence comparable and can jointly be used in quality control assessment of antibiotics
Assuntos
Injeções/classificação , Bioensaio/métodos , Preparações Farmacêuticas/classificação , Ágar/farmacologia , Aminoglicosídeos/agonistas , Antibacterianos/farmacologia , Ninidrina/administração & dosagemRESUMO
Resumen Pseudomonas aeruginosa es uno de los principales patógenos que causa infecciones asociadas a la atención en salud (IAAS). Su capacidad de adaptación, diseminación, resistencia intrínseca a los antimicrobianos y de adquirir nuevos mecanismos a través de elementos genéticos móviles, hacen que el tratamiento de las infecciones por este microorganismo sea un desafío para el médico clínico. Intrínsecamente, P. aeruginosa, presenta una reducida permeabilidad en la membrana externa, debido a la expresión de bombas de expulsión, y una cefalosporinasa tipo AmpC inducible. Además, P. aeruginosa es capaz de adquirir nuevos determinantes de resistencia por transferencia horizontal en forma de casetes situados en integrones, y a su vez, localizados en transposones o plásmidos. Dentro de la resistencia enzimática que presenta P. aeruginosa destacan las β-lactamasas, incluyendo aquellas de espectro extendido (BLEE) y las carbapenemasas. Pero también enzimas modificadoras de los aminoglucósidos, haciendo que este microorganismo pueda presentar fenotipos de multi-resistencia (MDR), resistencia extrema (XDR) y panresistencia (PDR) a los antimicrobianos denominados antipseudomonas, incluyendo a las nuevas cefalosporinas con inhibidores de beta-lactamasas.
Abstract Pseudomonas aeruginosa is one of the major pathogens causing healthcare-associated infections (HAI). Its capacity of adaptation, dissemination, intrinsic resistance to antimicrobials and of acquiring new mechanisms through mobile genetic elements, make the treatment of infections by this microorganism a challenge for the clinician. Intrinsically, P. aeruginosa, presents a reduced permeability in the external membrane, due to the expression of efflux pumps, and an inducible AmpC-type cephalosporinase. In addition, P. aeruginosa is able to acquire new resistance determinants by horizontal transfer in the form of cassettes located in integrons, and in turn located in transposons or plasmids. Within the enzymatic resistance that P. aeruginosa presents, betalactamases, including extended spectrum (ESBL) and carbapenemases. But also aminoglycoside modifying enzymes, stand out, causing this microorganism to present multi-resistance phenotypes (MDR), extreme resistance (XDR) and pan-resistance (PDR) to the called antipseudomonal antibiotics, including the new cephalosporins with betalactamase inhibitors.
Assuntos
Humanos , Pseudomonas aeruginosa , Infecções por Pseudomonas , Plasmídeos , Pseudomonas aeruginosa/genética , Infecções por Pseudomonas/tratamento farmacológico , beta-Lactamases/genética , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla/genética , Laboratórios , Antibacterianos/farmacologiaRESUMO
BACKGROUND: The presence of 16S rRNA methyltranferases (16S-RMTases) in carbapenemase-producing Enterobacterales (CPE) is a major concern because it inactivates all clinical use of aminoglycosides, including plazomicin. The aim of this study is to investigate the prevalence of 16S-RMTases in CPE nonsusceptible to plazomicin collected in different Brazilian hospitals. METHODS: All isolates with plazomicin MIC ≥ 4 µg/mL (nâ¯=â¯67) were screened for the presence of 16S-RMTases by sequencing. RESULTS: 54 (80.6%) isolates encoded 16S-RMTase genes (41 rmtB1, 7 armA, 3 rmtD2, 1 rmtD1 and 2 rmtC). Among 41 samples rmtB1 positive, 40 co-harbored blaKPC-2 and 1 blaOXA-48 gene. Of the seven isolates harboring armA gene, 6 were New Delhi Metallo-beta-lactamase (NDM)-producer. rmtD was only found in isolates Klebsiella pneumoniae Carbapenemase (KPC)-producers, one in Serratia marcescens with rmtD2, not reported in Brazil. CONCLUSION: The co-existence of 16S-RMTase and CPE is worrisome because of limited treatment options and the endemic characteristic of (KPC) and NDM in Brazil.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Metiltransferases/genética , Sisomicina/análogos & derivados , beta-Lactamases/metabolismo , Proteínas de Bactérias/genética , Brasil , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/enzimologia , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Sisomicina/farmacologia , beta-Lactamases/genéticaRESUMO
OBJECTIVES: Carbapenem resistance in Klebsiella pneumoniae is a major clinical challenge. Aminoglycosides remain an important asset in the current therapeutic arsenal to treat these infections. We examined aminoglycoside resistance phenotypes and genomics in a collection of 100 invasive KPC-producing K. pneumoniae isolates sequentially collected in a Brazilian tertiary hospital between 2014 and 2016. METHODS: Aminoglycoside susceptibility testing was performed. We used a combined long-read (MinION) and short-read (Illumina) whole-genome sequencing strategy to provide a genomic picture of aminoglycoside resistance genes, with particular emphasis on 16S rRNA methyltransferases and related plasmids. RESULTS: 68% of the strains were resistant to gentamicin and 42% to amikacin, with 35% resistant to both of these commonly used aminoglycosides. We identified the 16S rRNA methyltransferase gene rmtB in 30% of these isolates: 97% (29/30) belonged to sequence type 258 (ST258) and a single isolate to the emergent ST16 clone. In ST258 and ST16 the rmtB gene was located on large IncC plasmids of 177 kb and 174 kb, respectively, highly similar to a plasmid previously identified in Proteus mirabilis in the same hospital. Moreover, 99% of the isolates remained susceptible to the veterinary-approved drug apramycin, currently under clinical development for human medicine. CONCLUSION: Such findings in geographically and temporally related isolates suggest a combination of vertical clonal spread as well as horizontal interspecies and intraspecies plasmid transfer. This broad rmtB dissemination in an endemic setting for KPC-producing clones is worrisome since it provides resistance to most clinically available aminoglycosides, including the novel aminoglycoside-modifying enzyme-resistant plazomicin.
Assuntos
Klebsiella pneumoniae , beta-Lactamases , Proteínas de Bactérias/genética , Brasil , Humanos , Interleucinas , Klebsiella pneumoniae/genética , Metiltransferases , Testes de Sensibilidade Microbiana , Plasmídeos/genética , RNA Ribossômico 16S/genética , Sisomicina/análogos & derivados , beta-Lactamases/genéticaRESUMO
Resumen Los antimicrobianos son los medicamentos más utilizados en los neonatos durante su primer mes de vida cuando se encuentran en unidades neonatales, principalmente por el alto riesgo que presentan de adquirir infecciones graves como la sepsis. La mayoría de estos antimicrobianos se utilizan con dosis extrapoladas en base a las recomendaciones en población adulta y niños mayores, a pesar de que la fisiopatología en los recién nacidos es absolutamente diferente. Lo anterior lleva a un mayor riesgo a que ocurran más efectos adversos los que pueden conducir a una mayor toxicidad y a fallas terapéuticas, entre otros. En la última década se han realizado mayores estudios farmacocinéticos de antimicrobianos en neonatos; esta reciente evidencia ha permitido nuevas recomendaciones de dosificación considerando el peso y la edad gestacional del recién nacido, entre otras variables, de acuerdo al antimicrobiano estudiado. En base a una mayor evidencia sobre el comportamiento farmacocinético de los antimicrobianos en neonatos, se ha elaborado este documento para así facilitar y promover su correcto uso en las unidades neonatales.
Abstract Antibiotics are the most widely used medications in neonates during their first month of life in neonatal units, mainly due to the high risk they present of acquiring serious infections such as sepsis. Most of these antibiotics are used with extrapolated doses based on the suggestions in the adult population and older children, despite the fact that the pathophysiology in newborns is absolutely different. This leads to a higher risk of more adverse effects occurring, which can lead to greater toxicity and therapeutic failures, among others. In the last decade more and more pharmacokinetic studies of antibiotics have been carried out in neonates, this recent evidence has led to new dosage recommendations taking into account the weight and gestational age of the newborn, among other variables, in agreement to the antibiotic studied. Therefore, based on the need to order and summarize the most up-to-date and most evidence-based information on antibiotics in neonates, this document was prepared to facilitate and promote its correct use in neonatal units.
Assuntos
Humanos , Recém-Nascido , Doenças Transmissíveis , Antibacterianos/uso terapêutico , Neonatologia , Chile , Comitês ConsultivosRESUMO
Aminoglycosides and ß-lactams are the most commonly used antimicrobial agents in clinical practice. This occurs because they are capable of acting in the treatment of acute bacterial infections. However, the effectiveness of antibiotics has been constantly threatened due to bacterial pathogens producing resistance enzymes. Among them, the aminoglycoside-modifying enzymes (AMEs) and ß-lactamase enzymes are the most frequently reported resistance mechanisms. AMEs can inactivate aminoglycosides by adding specific chemical molecules in the compound, whereas ß-lactamases hydrolyze the ß-lactams ring, preventing drug-target interaction. Thus, these enzymes provide a scenario of multidrug-resistance and a significant threat to public health at a global level. In response to this challenge, in recent decades, several studies have focused on the development of inhibitors that can restore aminoglycosides and ß-lactams activity. In this context, peptides appear as a promising approach in the field of inhibitors for future antibacterial therapies, as multiresistant bacteria may be susceptible to these molecules. Therefore, this review focused on the most recent findings related to peptide-based inhibitors that act on AMEs and ß-lactamases, and how these molecules could be used for future treatment strategies.
Assuntos
Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Ácido Clavulânico/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sulbactam/uso terapêutico , Tazobactam/uso terapêutico , Aminoglicosídeos/metabolismo , Aminoglicosídeos/uso terapêutico , Antibacterianos/metabolismo , Antibacterianos/uso terapêutico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Desenho de Fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/enzimologia , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Canamicina Quinase/antagonistas & inibidores , Canamicina Quinase/química , Canamicina Quinase/metabolismo , Nucleotidiltransferases/antagonistas & inibidores , Nucleotidiltransferases/química , Nucleotidiltransferases/metabolismo , beta-Lactamases/química , beta-Lactamases/metabolismo , beta-Lactamas/metabolismo , beta-Lactamas/uso terapêuticoRESUMO
In this study the physicochemical characterization of the pulp and almond fixed oil was carried out; their antibacterial activity and aminoglycoside antibiotic modifying action against standard and multiresistant Gram-positive and -negative bacteria were investigated using the broth microdilution assay. Physical properties such as moisture, pH, acidity, peroxide index, relative density and refractive index indicate stability and chemical quality of the oils. In the GC/MS chemical composition analysis, a high unsaturated fatty acid content and the presence of oleic and palmitic acids were observed in the oils. In the antibacterial assay, more significant results were obtained for Escherichia coli, while other standard and multi-resistant strains presented MIC values ≥ 1024 µg/mL. Furthermore, the fixed oils in association with antibiotics were able to significantly improve antibacterial activity against S. aureus with a reduction in MICs.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Malpighiales/química , Óleos de Plantas/farmacologia , Aminoglicosídeos/farmacologia , Escherichia coli/efeitos dos fármacos , Ácidos Graxos/análise , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Óleos de Plantas/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
Gentamicin is an aminoglycoside antibiotic used to treat infections of various origins. In the last few decades, the constant use of gentamicin has resulted in increased bacterial resistance and nephrotoxicity in some cases. In this study, we examined the ability of Dioclea violacea lectin (DVL) in modulate the antimicrobial activity of gentamicin and reduce the nephrotoxicity induced by this drug. The minimum inhibitory concentration (MIC) obtained for DVL against all strains studied was not clinically relevant (MIC ≥ 1024 µg/mL). However, when DVL was combined with gentamicin, a significant increase in antibiotic action was observed against Staphylococcus aureus and Escherichia coli. DVL also reduced antibiotic tolerance in S. aureus during 10 days of continuous treatment. In addition, DVL presented a nephroprotective effect, reducing sodium excretion, N-Gal expression and urinary protein, that are important markers of glomerular and tubular injuries. Taken together, studies of inhibition of hemagglutinating activity, fluorescence spectroscopy and molecular docking revealed that gentamicin can interact with DVL via the carbohydrate recognition domain (CRD), suggesting that the results obtained in this study may be directly related to the interaction of DVL-gentamicin and with the ability of the lectin to interact with glycans present in the cells of the peritoneum.
Assuntos
Antibacterianos/farmacologia , Dioclea/química , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Gentamicinas/farmacologia , Rim/patologia , Lectinas de Plantas/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antibacterianos/química , Bactérias/efeitos dos fármacos , Gentamicinas/química , Hemaglutinação/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/lesões , Rim/fisiopatologia , Masculino , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Lectinas de Plantas/química , Lectinas de Plantas/isolamento & purificação , Coelhos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de FluorescênciaRESUMO
The present study aimed to evaluate the antibacterial and modulatory activity of the Turnera subulate methyl extract in isolation or in combination with aminoglycoside antibiotics, using the microdilution method. The Turnera subulata methyl extract was used in isolation in the antibacterial assays and in combination with antibiotics in the modulation assays. All tests were performed in triplicates. The Turnera subulata methyl extract presented both antibacterial and antibiotic-modulatory effects in vitro, in isolation and in association with aminoglycosides. The extract activity depends on the bacterial strain and may be associated with the presence of tannins and flavonols. However, further studies are required to characterize the Turnera subulata potential for the development of new drugs against multiresistant bacteria.
Assuntos
Extratos Vegetais/farmacologia , Turnera/química , Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Extratos Vegetais/químicaRESUMO
RESUMO Dentre as infecções causadas por Streptococcus β hemolyticus do grupo A de Lancefield, talvez a síndrome do choque tóxico seja a mais grave, com alto índice de mortalidade. A semelhança clínica com outras formas de choque, principalmente séptico, pode, muitas vezes, confundir o avaliador e interferir na escolha da terapêutica mais adequada. Esse relato tem o objetivo de auxiliar seus leitores quanto à necessidade de adicionar tal síndrome como diagnóstico diferencial, frente a quadros de choque, principalmente aqueles que não apresentam manifestações clínicas bem definidas. Para isso, apresentamos o quadro de um lactente com sintomas gripais comuns, que evoluiu rapidamente com exantema, rebaixamento do nível de consciência, sinais clínicos e laboratoriais de choque, com necessidade de suporte intensivo. Além de culturas indicando o agente etiológico, o aparecimento de exantema e fasciíte necrosante levou ao diagnóstico, mas, em menos de 50% dos casos temos sinais clínicos clássicos dessa entidade. As penicilinas em terapia combinada com aminoglicosídeos ainda são a terapia de escolha e possuem alto nível de evidência. Apesar da gravidade a evolução foi satisfatória.
ABSTRACT Among the infections caused by Streptococcus β hemolyticus from the Lancefield serogroup A, toxic shock syndrome is perhaps the most severe, and its mortality rate is high. Its clinical similarity to other forms of shock, especially septic shock, can often confuse the evaluator and interfere with the selection of the most appropriate therapy. This report aims to inform readers of the need to add this syndrome as a differential diagnosis in cases of shock, especially those with no well-defined clinical manifestations. For this purpose, we present the case of an infant with common flu-like symptoms who progressed rapidly with a rash, a reduced level of consciousness and clinical and laboratory signs of shock that required intensive support. In addition to cultures indicating the etiological agent, the appearance of exanthema and necrotizing fasciitis led to the diagnosis. However, less than 50% of cases present classic clinical signs of this entity. Penicillins combined with aminoglycosides are still the therapy of choice and are supported by a high level of evidence. Despite the severity of this patient's presentation, the progression was satisfactory.
Assuntos
Humanos , Feminino , Recém-Nascido , Choque Séptico , Infecções Estreptocócicas/diagnóstico , Streptococcus pyogenes/isolamento & purificação , Choque Séptico/microbiologia , Choque Séptico/terapia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/terapia , Unidades de Terapia Intensiva Pediátrica , Diagnóstico DiferencialRESUMO
Orbignya speciosa (babassu) is an important palm tree in Brazil whose fixed almond oil is used in popular medicine and especially in food, in addition to being a research target for the manufacture of biofuels. The aim of this study was to evaluate the fixed almond oil physicochemical characterization and its antibacterial activity in isolation and in association with aminoglycosides against standard and multidrug-resistant bacteria. Analyses such as water content, pH, acidity, peroxide index, relative density, and refractive index indicate the stability and chemical quality of the oil. In the oil's GC/MS chemical composition analysis, a high saturated fatty acid (76.90%) content was observed. Lauric acid (56.28%) and oleic acid (23.10%) were the major oil components. In the antibacterial test, a more significant oil activity was observed against K. pneumoniae KP-ATCC 10031 (minimal inhibitory concentration (MIC) = 406.37 µg/mL) and Staphylococcus aureus ATCC 6538 (MIC = 812.75 µg/mL), but for the other strains-including standard and multi-resistant strains-the oil presented an MIC ≥ 1024 µg/mL. Furthermore, a synergistic effect was observed when the oil was associated with amikacin and gentamicin against S. aureus (SA-10) and an antagonistic effect was observed with amikacin against Escherichia coli. Data indicate the O. speciosa oil as a valuable nutritional source of lauric, oleic, and myristic fatty acids with an ability to modulate aminoglycoside activity.
RESUMO
Introdução: A Lesão Renal Aguda (LRA) é um evento sistêmico, que acomete em sua maioria pacientes com idade avançada e com um tempo maior de internação, tendo este grupo uma maior probabilidade ao óbito. Objetivo: Caracterizar o perfil do paciente que desenvolveram LRA, determinar a extensão da lesão, identificar quais antibióticos estão relacionados a LRA e relacionar a taxa de mortalidade com a LRA. Materiais e métodos: Estudo observacional transversal, realizado com dados do prontuário eletrônico dos pacientes internados na unidade de terapia intensiva no período de abril a setembro de 2017, sendo posteriormente realizada a análise estatística dos dados coletados. Resultados: Neste estudo 67,27% pacientes desenvolveram LRA, o perfil levantado dos que apresentaram tal lesão é em sua maioria do sexo masculino, com média de 56 anos de idade, período de internação superior a 10 dias, e com risco de mortalidade de 73%. Os antibióticos associados a lesão renal foram os Carbapenêmicos e os Aminoglicosídeos, quanto a extensão da lesão renal houve uma maior prevalência do estágio 3, do score Acute Kidney Injury Network (AKIN), quanto ao desfecho clínico a taxa de óbito dos pacientes com LRA foi de 35,13%. Conclusão: O presente estudo apresentou um perfil de pacientes que desenvolveram lesão renal condizente com o que é encontrado na literatura, ele ainda acrescenta o risco de mortalidade dos mesmos a partir do score Apache II, que vem demonstrar o quanto o risco de mortalidade é aumentado em pacientes que desenvolvem LRA relacionado ao uso de antibióticos.
Introduction: Acute Kidney Injury (AKI) is a systemic event, which mainly affects patients with advanced age and a longer time of hospitalization, with this group being more likely to death. Objective: To characterize the profile of the patient who developed AKI, to determine the extent of the lesion, to identify which antibiotics are related to AKI and to relate the mortality rate to AKI. Materials and methods: A cross-sectional observational study was carried out with data from the electronic medical records of patients admitted to the intensive care unit from April to September 2017, after which a statistical analysis of the data collected was performed. Results: In this study, 67.27% of the patients developed AKI. The majority of the patients who presented AKI were men, with a mean age of 56 years, a period of hospitalization of more than 10 days, and a mortality risk of 73%. The antibiotics associated with renal injury were Carbapenemics and Aminoglycosides. Regarding the extent of renal injury, there was a higher prevalence of stage 3 of the Acute Kidney Injury Network (AKIN) score. Regarding the clinical outcome, the death rate of patients with AKI was of 35.13%. Conclusion: The present study presented a profile of patients who developed renal damage consistent with what is found in the literature, it also adds the risk of mortality from the Apache II score, which shows how much the risk of mortality is increased in patients who develop ARF related to the use of antibiotics.