RESUMEN
AIMS: This study aimed to assess the antimicrobial potential of Bp1-AdE, produced by Bacillus pumilus 64-1, and to investigate its mode of action against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). METHODS AND RESULTS: Bp-1AdE, derived from sponge-associated B. pumilus, exhibited bactericidal activity at 1 550 µg ml-1 against S. aureus ATCC29213 and MRSA strains. Light and fluorescence microscopy revealed drastic cell lysis of S. aureus treated with Bp-1AdE. Scanning and transmission electron microscopy suggested that Bp-1AdE disrupts the cytoplasmic membrane. Toxicity assays showed that Bp-1AdE was non-toxic to Tenebrio molitor larvae. Liquid chromatography-mass spectrometry and Global Natural Product Social spectral libraries identified four substances within Bp-1AdE, including aliphatic alcohols [3,4-dipentylhexane-2,5-diol and 1,1'-(4,5-dibutyl-3,6-dimethylcyclohexane-1,2-diyl)bis(ethan-1-one)] and terpenoids (cholic acid and canrenone). CONCLUSIONS: Bp-1AdE demonstrated selective toxicity and bactericidal activity, highlighting its potential for controlling infections caused by multidrug-resistant S. aureus strains.
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Antibacterianos , Bacillus pumilus , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Bacillus pumilus/efectos de los fármacos , Antibacterianos/farmacología , Staphylococcus aureus/efectos de los fármacos , Animales , Farmacorresistencia Bacteriana Múltiple , Poríferos/microbiologíaRESUMEN
Methicillin-resistant Staphylococci (MRS) cause infections at various sites and exhibit multidrug resistance. Despite their importance in veterinary medicine, only little is known about Staphylococcus spp. colonizing and infecting cats. Therefore, in this study, we aimed to isolate and identify Staphylococcus spp. colonizing hospitalized and non-hospitalized domestic cats and analyze their antimicrobial resistance profiles, genetic diversity, and risk factors associated with MRS colonization. A total of 218 oral and axillary swabs were obtained from 109 cats, including 77 non-hospitalized and 32 hospitalized cats. After plating on selective media, the isolates were identified via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and rpoB and 16S rRNA gene sequencing. Subsequently, antimicrobial sensitivity of the strains was assessed, and they were screened for mecA gene. Methicillin-resistant S. haemolyticus (MRSH) isolates were subjected to multilocus sequence typing, whereas methicillin-resistant S. pseudintermedius (MRSP) and S. felis isolates were subjected to whole genome sequencing. S. felis was most commonly isolated from non-hospitalized cats (28.1%), whereas S. pseudintermedius and MRS were commonly isolated from hospitalized cats (25%). MRSH isolates from hospitalized animals were classified as ST3. The identified MRSP strains belonged to two well-known sequence types, ST551 and ST71. Moreover, antimicrobial use (p = 0.0001), hospitalization (p = 0.0141), and comorbidities (p = 0.002) were associated with increased MRS prevalence in cats.
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Enfermedades de los Gatos , Variación Genética , Infecciones Estafilocócicas , Animales , Gatos/microbiología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/veterinaria , Infecciones Estafilocócicas/epidemiología , Brasil , Enfermedades de los Gatos/microbiología , Antibacterianos/farmacología , Staphylococcus/genética , Staphylococcus/efectos de los fármacos , Staphylococcus/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Femenino , Pruebas de Sensibilidad Microbiana , Masculino , ARN Ribosómico 16S/genética , Resistencia a la Meticilina/genética , Hospitalización , Proteínas Bacterianas/genética , Tipificación de Secuencias MultilocusRESUMEN
BACKGROUND: In the pediatric population, Staphylococcus aureus infections are responsible for increased morbidity and mortality, length of hospitalization and the cost of inpatient treatment. The aim of this study is to describe the antimicrobial resistance profile of S. aureus isolated in clinical specimens from pediatric patients admitted to a tertiary hospital in Rio de Janeiro, Brazil. METHODS: Culture reports and medical records of hospitalized patients under 18 years of age with S. aureus infections between January 2015 and December 2022 were retrospectively analyzed. Information was collected on recent antibiotic use, previous hospital admission, inpatient unit, clinical specimen, time of infection (community or nosocomial), classification according to susceptibility to methicillin (methicillin sensitive - MSSA or methicillin resistant - MRSA) and sensitivity to other antimicrobials. We analyzed the distribution of the sensitivity profile of S. aureus infections over the 7 years evaluated in the study. RESULTS: Were included 255 unique clinical episodes, among which the frequencies of MSSA and MRSA were 164 (64%) and 91 (36%), respectively. Over the 7 years evaluated, there was stability in the prevalence percentage, with a predominance of MSSA in the range of 60 to 73.3%, except in 2020, when there was a drop in the prevalence of MSSA (from 73.3% in 2019 to 52.5%) with an increase in MRSA (from 26.7% in 2019 to 47.5%). Ninety-seven (38%) infections were community-acquired and 158 (62%) were healthcare-associated. The main clinical specimens collected were blood cultures (35.2%) and wound secretions (17%). The MRSA isolates presented percentages of sensitivity to trimethoprim-sulfamethoxazole from 90.4 to 100%, and to clindamycin from 77 to 89.8% in MRSA healthcare associated and MRSA community respectively. CONCLUSION: There was a constant predominance in the prevalence of MSSA with percentage values ââmaintained from 2015 to 2022, except in 2020, in which there was a specific drop in the prevalence of MSSA with an increase in MRSA. MSSA infections are still predominant in the pediatric population, but MRSA rates also present significant values, including in community infections, and should be considered in initial empiric therapy.
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Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Staphylococcus aureus , Centros de Atención Terciaria , Humanos , Centros de Atención Terciaria/estadística & datos numéricos , Niño , Brasil/epidemiología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/tratamiento farmacológico , Preescolar , Femenino , Masculino , Estudios Longitudinales , Lactante , Estudios Retrospectivos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Adolescente , Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/genética , Infección Hospitalaria/microbiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Prevalencia , Recién NacidoRESUMEN
Aim: This work aimed to synthesize a new pyrimidine PYB01 with potential application against antimicrobial resistance.Materials & methods: PYB01 was synthesized through condensation reaction between 3a and 3b. The antimicrobial evaluation was carried out using the microdilution method in Mueller-Hinton Agar and in silico predictions using different software.Results: PYB01 has moderate antibiotic activity and high capacity to efficiently modulate antibiotic resistance in Staphylococcus aureus. In silico evaluations demonstrated that PYB01 is probably an allosteric inhibitor of Protein Binding Penicilin 2a and modulates the action of oxacillin by decreasing the minimum inhibitory concentration by 64-times. PYB01 demonstrate a good pharmacokinetic profile and toxicological.Conclusion: PYB01 has great potential to go further in investigating its use against antimicrobial resistance.
[Box: see text].
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Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Oxacilina , Pirimidinas , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Pirimidinas/química , Pirimidinas/farmacología , Pirimidinas/síntesis química , Oxacilina/farmacología , Estructura Molecular , Sinergismo Farmacológico , Animales , HumanosRESUMEN
The cefazolin inoculum effect (CzIE) has been associated with poor clinical outcomes in patients with methicillin-susceptible Staphylococcus aureus (MSSA) infections. We aimed to investigate the point prevalence of the CzIE among nasal colonizing MSSA isolates from ICU patients in a multicenter study in Colombia (2019-2023). Patients underwent nasal swabs to assess for S. aureus colonization on admission to the ICU, and some individuals had follow-up swabs. We performed cefazolin MIC by broth microdilution using standard and high inoculum and developed a modified nitrocefin-based rapid test to detect the CzIE. Whole-genome sequencing was carried out to characterize BlaZ types and allotypes, phylogenomics, and Agr-typing. A total of 352 patients were included; 46/352 (13%) patients were colonized with S. aureus and 22% (10/46) and 78% (36/46) with MRSA and MSSA, respectively. Among 36 patients who contributed with 43 MSSA colonizing isolates, 21/36 (58%) had MSSA exhibiting the CzIE. BlaZ type A and BlaZ-2 were the predominant type and allotype in 56% and 52%, respectively. MSSA belonging to CC30 were highly associated with the CzIE, and single-nucleotide polymorphism (SNP) analyses supported possible transmission of MSSA exhibiting the CzIE among some patients of the same unit. The modified nitrocefin rapid test had 100%, 94.4%, and 97.7% sensitivity, specificity, and accuracy, respectively. We found a high point prevalence of the CzIE in MSSA colonizing the nares of critically ill patients in Colombia. A modified rapid test was highly accurate in detecting the CzIE in this patient population.
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Antibacterianos , Cefazolina , Unidades de Cuidados Intensivos , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Humanos , Colombia/epidemiología , Cefazolina/farmacología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Antibacterianos/farmacología , Femenino , Masculino , Persona de Mediana Edad , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Prevalencia , Nariz/microbiología , Anciano , Secuenciación Completa del Genoma , AdultoRESUMEN
Staphylococcus aureus is a bacterial pathogen that causes bloodstream infections, pneumonia, and skin abscesses and is the primary pathogen responsible for medical devices associated with biofilm infections, accounting for approximately 70 % of cases. Therefore, the World Health Organization (WHO) has designated this microorganism as a top priority due to its role in causing over 20,000 bacteremia-related deaths in the US each year. The issue of pathogen resistance to antibiotics, mainly by a biofilm, further complicates these infections since biofilms render the bacterial colony impervious to antibiotics. However, many natural and synthetic substances also induce bacterial biofilm formation. Therefore, we investigated whether the most common active pharmaceutical ingredients (APIs) could induce biofilm formation in two clinical isolates of extended-spectrum beta-lactamase Staphylococcus aureus, one of them also methicillin-resistant (A2M) and two medical devices. We detected biofilm inducers, inhibitors, and destabilizers. Microbial strain, medical devices, API structure, and concentration influenced the modulatory effects of biofilm. In all devices tested, including microplates, FR18 duodenal probe, and respiratory probe, the clinic isolate methicillin-resistant S. aureus A2M exhibited lower susceptibility to biofilm formation than S. aureus A1. The anti-inflammatory acetaminophen, the hypocholesterolemic lovastatin, and the diuretic hydrochlorothiazide all induced biofilm. However, verapamil, an antihypertensive, and cetirizine, an antihistamine, inhibited biofilm on S. aureus A2M, while propranolol, another antihypertensive, inhibited biofilm on S. aureus A1. Additionally, diclofenac, an analgesic, and cetirizine destabilized the biofilm, resulting in more free bacteria and possibly making them more susceptible to external agents such as antibiotics. Nonetheless, further epidemiologic analyses and in vivo assays are needed to confirm these findings and to establish a correlation between drug use, the onset of bacterial infections in patients, and the use of medical devices. This work provides information about the probable clinical implications of drugs in patients using medical devices or undergoing surgical procedures. Inhibitory APIs could also be used as drug repurposing or templates to design new, more potent biofilm inhibitors.
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Antibacterianos , Biopelículas , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Staphylococcus aureus , beta-Lactamasas , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Antibacterianos/farmacología , Humanos , Staphylococcus aureus/efectos de los fármacos , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , beta-Lactamasas/metabolismo , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacosRESUMEN
INTRODUCTION: intravenous antibiotic prophylaxis has significantly reduced the incidence of periprosthetic joint infection (PJI) in knee surgeries. However, for patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) or those at risk of colonization, prophylaxis should include vancomycin. Intraosseous (IO) administration of vancomycin could enhance its effectiveness in total knee arthroplasty (TKA). MATERIAL AND METHODS: a retrospective review was conducted, including 143 patients at risk of PJI scheduled for TKA who received IO vancomycin along with intravenous (IV) cefazolin, referred to as group I (GI), between May 2021 and December 2022. The occurrence of complications in the first three postoperative months was evaluated. Results were compared with 140 patients without risk factors who received standard IV prophylaxis, designated as group II (GII). RESULTS: in GI, 500 mg of IO vancomycin was administered, injected into the proximal tibia, in addition to standard IV prophylaxis. In GII, patients received only IV cefazolin. The incidence of complications was 1.64% in GI and 1.4% in GII. The PJI rate at 90 postoperative days was 0.69% in GI and 0.71% in GII. CONCLUSIONS: IO vancomycin administration, along with standard IV prophylaxis, provides a safe and effective alternative for patients at risk of MRSA colonization. This approach minimizes complications associated with IV vancomycin use and addresses logistical challenges of timely administration.
INTRODUCCIÓN: la profilaxis antibiótica intravenosa ha reducido significativamente la incidencia de infección articular periprotésica (IAP) en cirugías de rodilla. No obstante, para pacientes colonizados con Staphylococcus aureus resistente a meticilina (SARM) o aquellos con riesgo de colonización, la profilaxis debe incluir vancomicina. La administración intraósea de vancomicina podría potenciar su efectividad en la artroplastía total de rodilla. MATERIAL Y MÉTODOS: se realizó una revisión retrospectiva que incluyó a 143 pacientes en riesgo de IAP programados para artroplastía total de rodilla que recibieron vancomicina intraósea junto a cefazolina intravenosa (IV), a quienes denominamos grupo I (GI), entre mayo de 2021 y diciembre de 2022. Se evaluó la aparición de complicaciones en los primeros tres meses postoperatorios. Los resultados se compararon con 140 pacientes sin factores de riesgo que recibieron profilaxis intravenosa estándar, denominados grupo II (GII). RESULTADOS: en el GI, se administraron 500 mg de vancomicina intraósea, inyectados en la tibia proximal, además de la profilaxis intravenosa estándar. En el GII, los pacientes recibieron sólo cefazolina intravenosa. La incidencia de complicaciones fue de 1.64% en el GI y de 1.4% en el GII. La tasa de IAP a los 90 días postoperatorios fue de 0.69% en el GI y de 0.71% en el GII. CONCLUSIONES: la administración de vancomicina intraósea, junto con la profilaxis intravenosa estándar, ofrece una alternativa segura y eficaz para pacientes con riesgo de colonización por SARM. Este enfoque minimiza las complicaciones asociadas con el uso intravenoso de vancomicina y soluciona los desafíos logísticos de la administración oportuna.
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Antibacterianos , Profilaxis Antibiótica , Artroplastia de Reemplazo de Rodilla , Cefazolina , Infecciones Relacionadas con Prótesis , Vancomicina , Humanos , Vancomicina/administración & dosificación , Vancomicina/uso terapéutico , Estudios Retrospectivos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Masculino , Femenino , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Profilaxis Antibiótica/métodos , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/prevención & control , Infecciones Relacionadas con Prótesis/etiología , Cefazolina/administración & dosificación , Cefazolina/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infusiones Intraóseas , Anciano de 80 o más Años , Infecciones Estafilocócicas/prevención & controlRESUMEN
Staphylococcus aureus are extremely important microorganisms, either from an epidemiological point of view or as a pathogen, responsible for causing a series of infectious processes, whether simple, restricted to the skin, or invasive infections such as bacteremia. The emergence of Oxacillin Sensitive-Methicillin Resistant S.aureus (OS-MRSA) isolates has imposed difficulties in the treatment of patients with staphylococcal infection, as such isolates can be mistakenly classified as sensitive and lead to failure of the therapy used. Thus, the objective of this study is to evaluate the prevalence, and genotypic and phenotypic characteristics, of OS-MRSA isolates, from bloodstream infections, collected from patients admitted to a hospital in southern Brazil, as well as to evaluate the treatment used. For this, 801 unique isolates of S. aureus, collected from blood cultures, between January 2011 and December 2020 were evaluated. Of these, 96 isolates were classified as sensitive to oxacillin. The isolates were identified and had their sensitivity profile performed by manual and automated methods. The minimum inhibitory concentration for vancomycin, daptomycin, oxacillin, linezolid and teicoplanine was performed by e-test. The mecA, vanA genes, typing of the SCCmec elements, as well as the search for the icaA, tst-1 and pvl virulence genes were performed by PCR. Biofilm formation was performed using the crystal violet technique. The Sequence Type (ST), as well as the Clonal Complex (CC) of the isolates was evaluated by the RTq -PCR. The clinical characteristics of the patients were evaluated through an active search in medical records. After investigating the mecA gene, 27.1% (26/96) of the isolates were considered OS-MRSA, with SCCmec type I being the most prevalent, 46.1% (12/26). Among the evaluated isolates, 41% (9/22) were included in CC5 and ST9. As for virulence, all isolates were positive for the icaA gene and characterized as strong biofilm formers. The pvl gene was found in 92.3% (24/26) of the isolates and the toxic shock syndrome toxin was present in 61.5% of the isolates (16/26). All isolates were negative for the presence of the van A gene. As for the clinical outcome, 73% (19/26) of the patients were discharged from the hospital and 27% (7/26) died. It was possible to observe a high frequency of OS-MRSA isolates causing bloodstream infections. Furthermore, such isolates contain several virulence genes, which may contribute to a worse clinical outcome.
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Antibacterianos , Bacteriemia , Proteínas Bacterianas , Genotipo , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Oxacilina , Proteínas de Unión a las Penicilinas , Infecciones Estafilocócicas , Centros de Atención Terciaria , Humanos , Oxacilina/farmacología , Brasil , Antibacterianos/farmacología , Infecciones Estafilocócicas/microbiología , Centros de Atención Terciaria/estadística & datos numéricos , Bacteriemia/microbiología , Proteínas Bacterianas/genética , Proteínas de Unión a las Penicilinas/genética , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/clasificación , FenotipoRESUMEN
Biofilm-producing methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (MR-CoNS) pose clinical challenges in treating healthcare-associated infections. As alternative antimicrobial options are needed, in this study, we aimed to determine the effect of curcumin-chitosan magnetic nanoparticles (Cur-Chi-MNP) on the biofilms of staphylococcal clinical isolates. MRSA and CoNS clinical isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing was performed using the broth microdilutions. Nanoparticles were synthesized by the co-precipitation of magnetic nanoparticles (MNP) and encapsulated by the ionotropic gelation of curcumin (Cur) and chitosan (Chi). Biofilm inhibition and eradication by nanoparticles, with and without the addition of oxacillin (OXA), were assessed in Staphylococcus strains. Cur-Chi-MNP showed antimicrobial activity against planktonic cells of MRSA and MR-CoNS strains and inhibited MRSA biofilm. The addition of OXA to Cur-Chi-MNP increased the biofilm inhibition and eradication activity against all staphylococcal strains (P = 0.0007), and higher biofilm activity was observed in the early biofilm stages. Cur-Chi-MNP showed antimicrobial and biofilm inhibitory activities against S. aureus. Addition of OXA increased biofilm inhibition and eradication activity against all staphylococcal strains. A combination treatment of Cur-Chi-MNP and OXA could potentially be used to treat staphylococcal biofilm-associated infections in the early stages before the establishment of biofilm bacterial cells.
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Antibacterianos , Biopelículas , Quitosano , Curcumina , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas , Biopelículas/efectos de los fármacos , Quitosano/farmacología , Quitosano/química , Curcumina/farmacología , Antibacterianos/farmacología , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Nanopartículas de Magnetita/química , Oxacilina/farmacología , Staphylococcus/efectos de los fármacos , Staphylococcus/fisiologíaRESUMEN
Flavonoids are an abundant class of naturally occurring compounds with broad biological activities, but their limited abundance in nature restricts their use in medicines and food additives. Here we present the synthesis and determination of the antibacterial and antioxidant activities of twenty-two structurally related flavonoids (five of which are new) by scientifically validated methods. Flavanones (FV1-FV11) had low inhibitory activity against the bacterial growth of MRSA 97-7. However, FV2 (C5,7,3',4' = OH) and FV6 (C5,7 = OH; C4' = SCH3) had excellent bacterial growth inhibitory activity against Gram-negative E. coli (MIC = 25 µg/mL for both), while Chloramphenicol (MIC = 25 µg/mL) and FV1 (C5,7,3' = OCH3; 4' = OH) showed inhibitory activity against Gram-positive L. monocytogenes (MIC = 25 µg/mL). From the flavone series (FO1-FO11), FO2 (C5,7,3',4' = OH), FO3 (C5,7,4' = OH; 3' = OCH3), and FO5 (C5,7,4' = OH) showed good inhibitory activity against Gram-positive MRSA 97-7 (MIC = 50, 12, and 50 µg/mL, respectively), with FO3 being more active than the positive control Vancomycin (MIC = 25 µg/mL). FO10 (C5,7= OH; 4' = OCH3) showed high inhibitory activity against E. coli and L. monocytogenes (MIC = 25 and 15 µg/mL, respectively). These data add significantly to our knowledge of the structural requirements to combat these human pathogens. The positions and number of hydroxyl groups were key to the antibacterial and antioxidant activities.
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Antibacterianos , Antioxidantes , Flavonoides , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Flavonoides/farmacología , Flavonoides/química , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/crecimiento & desarrollo , Flavanonas/farmacología , Flavanonas/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacosRESUMEN
OBJECTIVE: Increased mupirocin use leads to mupirocin resistance and is associated with persistence of methicillin-resistant Staphylococcus aureus (MRSA) carriers, prolonged hospitalization, and significant economic burdens for health systems. The study aimed to investigate the antimicrobial activity of compounds of Salvia rosmarinus L. ("rosemary", formerly Rosmarinus officinalis), alone or in combination with mupirocin, against multidrug resistant MRSA using isolates obtained from pediatric patients. METHODS: The in vitro antibacterial activity of the monoterpene α-pinene (α-Pi), a rosemary essential oil constituent, alone and in combination with mupirocin, was evaluated by determining the minimum inhibitory concentrations and minimum bactericidal concentrations (MBCs) and the fractional inhibitory concentration indices (FICIs) and fractional bactericidal concentration indices against multidrug-resistant clinical MRSA strains. The in vivo efficacy of α-Pi, alone and in combination with mupirocin, to eradicate MRSA infection was determined using an optimized mouse model of MRSA-infected wounds. Mouse skin samples (obtained via biopsy) were assessed for toxicity, and rabbit skin samples for irritation. RESULTS: Both in vitro and in vivo, α-Pi was active against MRSA strains and acted synergistically with mupirocin against MRSA strains. Mupirocin-monoterpene combinations exhibited FICI values of 0.2 to 0.4, reducing the MBC of topical mupirocin 33-fold. A topical formulation containing α-Pi and mupirocin enhanced the efficacy of mupirocin in an in vivo MRSA-infected mouse skin model without significantly harming the skin of mice and rabbits. CONCLUSIONS: A topical formulation combining mupirocin and α-Pi may aid in the development of innovative agents for treating MRSA infections.
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Antibacterianos , Monoterpenos Bicíclicos , Farmacorresistencia Bacteriana Múltiple , Sinergismo Farmacológico , Quimioterapia Combinada , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Mupirocina , Mupirocina/administración & dosificación , Mupirocina/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Animales , Ratones , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Monoterpenos Bicíclicos/administración & dosificación , Monoterpenos Bicíclicos/farmacología , Humanos , Monoterpenos/farmacología , Monoterpenos/administración & dosificación , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Modelos Animales de Enfermedad , FemeninoRESUMEN
BACKGROUND: CKD patients on hemodialysis (HD) with Staphylococcus aureus (SA) bacteremia present high morbidity, mortality and increased risk of MRSA. Vancomycin is the antibiotic of choice in these cases, it has a narrow therapeutic margin and inadequate dosage generates a risk of toxicity, therefore, the recommendation is to dosage it through serum levels. METHODS: This is a retrospective cohort study in 3 hospitals of third level of complexity in the city of Medellin in which there were differences in the measurement and implementation of vancomycin25 dosage based on trough levels (VL) in patients with chronic kidney disease on hemodialysis (CKD- HD) with uncomplicated bacteremia based infection by methilcillin-resistant Staphyloccocus aureus (MRSA). The primary outcome was the composite of hospital mortality, clinical response (fever, hemodynamic instability and altered consciousness), complications associated with bacteremia, or bacteriological response failure (positive cultures at first week follow-up) at 7 days. The composite variables were analyzed individually as secondary outcomes. RESULTS: The main unadjusted outcome (OR 1.3, CI 0.6 - 2.7) and adjusted for age, Charlson index, loading dose, initial dose, dosing frequency and MIC to vancomycin (OR 1.2, CI 0.5 - 2.7). Regarding adjusted secondary outcomes: clinical response (OR 1.4 CI 0.3 - 5.8), death (OR 1.3 CI 0.3 - 4.6) and complications (OR 0.9, CI 0.37 - 2.2). CONCLUSIONS: We conclude that the measurement of trough levels in patients with HD-CKD does not modify the composite outcome. The main limitation is the sample size and type of study, randomized control trials may be required to confirm the results presented.
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Antibacterianos , Bacteriemia , Staphylococcus aureus Resistente a Meticilina , Diálisis Renal , Insuficiencia Renal Crónica , Infecciones Estafilocócicas , Vancomicina , Humanos , Vancomicina/uso terapéutico , Estudios Retrospectivos , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Masculino , Diálisis Renal/efectos adversos , Femenino , Insuficiencia Renal Crónica/complicaciones , Anciano , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Anciano de 80 o más Años , Pruebas de Sensibilidad MicrobianaRESUMEN
Aim: The present study investigated the antimicrobial effectiveness of a rhamnolipid complexed with arginine (RLMIX_Arg) against planktonic cells and biofilms of methicillin-resistant Staphylococcus aureus (MRSA). Methodology: Susceptibility testing was performed using the Clinical & Laboratory Standards Institute protocol: M07-A10, checkerboard test, biofilm in plates and catheters and flow cytometry were used. Result: RLMIX_Arg has bactericidal and synergistic activity with oxacillin. RLMIX_Arg inhibits the formation of MRSA biofilms on plates at sub-inhibitory concentrations and has antibiofilm action against MRSA in peripheral venous catheters. Catheters impregnated with RLMIX_Arg reduce the formation of MRSA biofilms. Conclusion: RLMIX_Arg exhibits potential for application in preventing infections related to methicillin-resistant S. aureus biofilms.
[Box: see text].
Asunto(s)
Antibacterianos , Arginina , Biopelículas , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Tensoactivos , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Arginina/farmacología , Arginina/química , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Tensoactivos/farmacología , Tensoactivos/química , Glucolípidos/farmacología , Glucolípidos/química , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/prevención & control , Infecciones Estafilocócicas/tratamiento farmacológico , Oxacilina/farmacología , Sinergismo FarmacológicoRESUMEN
Methicillin-resistant Staphylococcus (MRS) has been associated with neonatal infections, with colonization of the anovaginal tract being the main source of vertical transmission. The COVID-19 pandemic has altered the frequency of antibiotic usage, potentially contributing to changes in the dynamics of bacterial agents colonizing humans. Here we determined MRS colonization rates among pregnant individuals attending a single maternity in Rio de Janeiro, Brazil before (January 2019-March 2020) and during (May 2020-March 2021) the COVID-19 pandemic. Anovaginal samples (n = 806 [521 samples before and 285 during the pandemic]) were streaked onto chromogenic media. Colonies were identified by MALDI-TOF MS. Detection of mecA gene and SCCmec typing were assessed by PCR and antimicrobial susceptibility testing was done according to CLSI guidelines. After the onset of the pandemic, MRS colonization rates increased significantly (p < 0.05) from 8.6% (45) to 54.7% (156). Overall, 215 (26.6%) MRS isolates were detected, of which S. haemolyticus was the most prevalent species (MRSH, 84.2%; 181 isolates). SCCmec type V was the most frequent among MRS (63.3%; 136), and 31.6% (68) of MRS strains had a non-typeable SCCmec, due to new combinations of ccr and mecA complexes. Among MRS strains, 41.9% (90) were resistant to at least 3 different classes of antimicrobial agents, and 60% (54) of them were S. haemolyticus harboring SCCmec V. MRS colonization rates and the emergence of multidrug-resistant variants detected in this study indicate the need for continuing surveillance of this important pathogen within maternal and child populations.
Asunto(s)
COVID-19 , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Femenino , Embarazo , COVID-19/epidemiología , COVID-19/virología , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Adulto , Brasil/epidemiología , Complicaciones Infecciosas del Embarazo/microbiología , Complicaciones Infecciosas del Embarazo/epidemiología , Antibacterianos/farmacología , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Pandemias , Vagina/microbiologíaRESUMEN
A growing increase in the number of serious infections caused by multidrug resistant bacteria (MDR) is challenging our society. Despite efforts to discover novel therapeutic options, few antibiotics targeting MDR have been approved by the Food and Drug Administration (FDA). Lactic acid bacteria have emerged as a promising therapeutic alternative due to their demonstrated ability to combat MDR pathogens in vitro. Our previous co-culture studies showed Lacticaseibacillus rhamnosus CRL 2244 as having a potent killing effect against carbapenem-resistant Acinetobacter baumannii (CRAB) strains. Here we report that cell-free conditioned media (CFCM) samples obtained from Lcb. rhamnosus CRL 2244 cultures incubated at different times display antimicrobial activity against 43 different pathogens, including CRAB, methicillin-resistant Staphylococcus aureus (MRSA) and carbapenemase Klebsiella pneumoniae (KPC)-positive strains. Furthermore, transwell and ultrafiltration analyses together with physical and chemical/biochemical tests showed that Lcb. rhamnosus CRL 2244 secretes a <3 kDa metabolite(s) whose antimicrobial activity is not significantly impaired by mild changes in pH, temperature and various enzymatic treatments. Furthermore, sensitivity and time-kill assays showed that the bactericidal activity of the Lcb. rhamnosus CRL 2244 metabolite(s) enhances the activity of some current FDA approved antibiotics. We hypothesize that this observation could be due to the effects of Lcb. rhamnosus CRL 2244 metabolite(s) on cell morphology and the enhanced transcriptional expression of genes coding for the phenylacetate (PAA) and histidine catabolic Hut pathways, metal acquisition and biofilm formation, all of which are associated with bacterial virulence. Interestingly, the extracellular presence of Lcb. rhamnosus CRL 2244 induced the transcription of the gene coding for the CidA/LgrA protein, which is involved in programmed cell death in some bacteria. Overall, the findings presented in this report underscore the promising potential of the compound(s) released by Lcb. rhamnosus CRL2244 as an alternative and/or complementary option to treat infections caused by A. baumannii as well as other MDR bacterial pathogens.
Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Lacticaseibacillus rhamnosus , Lacticaseibacillus rhamnosus/metabolismo , Lacticaseibacillus rhamnosus/genética , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Acinetobacter baumannii/efectos de los fármacos , Sinergismo Farmacológico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genéticaRESUMEN
Aim: Compare two vancomycin dosing strategies in critical patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, considering the heterogeneity of the dosing regimens administered and their implications for toxicity and efficacy. Materials & methods: Longitudinal retrospective observational study in two patient cohorts (standard dosing vs dosing via Bayesian algorithms). Results: The group of Bayesian algorithms received substantially higher and significantly heterogeneous doses, with an absence of nephrotoxicity. The speed of decrease observed in CRP and PCT was greater for the Bayesian strategy (p = 0.045 and 0.0009, respectively). Conclusion: Applying Bayesian algorithms to vancomycin dosage individualization allows for administering much higher doses than with standard regimens, facilitating a quicker clinical response in the absence of nephrotoxicity.
[Box: see text].
Asunto(s)
Algoritmos , Antibacterianos , Teorema de Bayes , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Vancomicina , Humanos , Vancomicina/administración & dosificación , Estudios Retrospectivos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Estudios Longitudinales , Anciano , Medicina de Precisión/métodos , Enfermedad Crítica , AdultoRESUMEN
This work aimed to evaluate the effects of 4 selected essential oils on planktonic cells and microbial biofilms of the Staphylococcus aureus strain (MRSA ATCC 33591). The antibacterial activities of the four essential oils Geranium (Pelargonium graveolens), PgEO, Tea Tree (Melaleuca alternifolia) MaEO, Lemon peel (Citrus limon) ClEO and Peppermint (Mentha piperita) MpEO had MICs ranging from 1.56 to 12.5 µl/ml. The evaluation of the antibiofilm activities of the 4 EOs revealed that they had antiadhesive activities against S. aureus MRSA biofilms; the activity reached 60% (the EO of MpEO peppermint at a concentration of 3.12 µl/ml), and the eradication activity was 80% (the EO of PgEO and MpEO at 3.12 µl/ml). The antibiofilm activity of S. aureus has been explained by the binding of several essential oil bioactive molecules to the SarA protein, the main target protein involved in biofilm formation. The synthesis of the virulence factor staphyloxanthin by S. aureus MRSA ATCC 33591 was significantly inhibited in the presence of PgEO at a concentration of MIC/2. This inhibition was explained by the binding of the main PgEO molecules (ß-citronellol and geraniol) to the CrTM protein involved in the staphyloxanthin synthesis pathway. There is evidence that these essential oils could be used as potential anti-virulents to control Staphylococcus biofilm formation.
Asunto(s)
Antibacterianos , Biopelículas , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Aceites Volátiles , Aceites de Plantas , Xantófilas , Biopelículas/efectos de los fármacos , Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Aceites Volátiles/farmacología , Xantófilas/farmacología , Aceites de Plantas/farmacología , Aceites de Plantas/química , Melaleuca/química , Mentha piperita/química , Pelargonium/química , Geranium/química , Citrus/químicaRESUMEN
Antimicrobial resistance (AMR) is one of the biggest threats in modern times. It was estimated that in 2019, 1.27 million deaths occurred around the globe due to AMR. Methicillin-resistant Staphylococcus aureus (MRSA) strains, a pathogen considered of high priority by the World Health Organization, have proven to be resistant to most of the actual antimicrobial treatments. Therefore, new treatments are required to be able to manage this increasing threat. Under this perspective, an important metabolic pathway for MRSA survival, and absent in mammals, is the shikimate pathway, which is involved in the biosynthesis of chorismate, an intermediate for the synthesis of aromatic amino acids, folates, and ubiquinone. Therefore, the enzymes of this route have been considered good targets to design novel antibiotics. The fifth step of the route is performed by shikimate kinase (SK). In this study, an in-house chemical library of 170 benzimidazole derivatives was screened against MRSA shikimate kinase (SaSK). This effort led to the identification of the first SaSK inhibitors, and the two inhibitors with the greatest inhibition activity (C1 and C2) were characterized. Kinetic studies showed that both compounds were competitive inhibitors with respect to ATP and non-competitive for shikimate. Structural analysis through molecular docking and molecular dynamics simulations indicated that both inhibitors interacted with ARG113, an important residue involved in ATP binding, and formed stable complexes during the simulation period. Biological activity evaluation showed that both compounds were able to inhibit the growth of a MRSA strain. Mitochondrial assays showed that both compounds modify the activity of electron transport chain complexes. Finally, ADMETox predictions suggested that, in general, C1 and C2 can be considered as potential drug candidates. Therefore, the benzimidazole derivatives reported here are the first SaSK inhibitors, representing a promising scaffold and a guide to design new drugs against MRSA.
Asunto(s)
Bencimidazoles , Staphylococcus aureus Resistente a Meticilina , Simulación del Acoplamiento Molecular , Fosfotransferasas (Aceptor de Grupo Alcohol) , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/enzimología , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/química , Bencimidazoles/farmacología , Bencimidazoles/química , Cinética , Antibacterianos/farmacología , Antibacterianos/química , Simulación de Dinámica Molecular , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Humanos , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/químicaRESUMEN
Antibiotic-resistant bacteria causing nosocomial infections pose a significant global health concern. This study focused on examining the lipid profiles of both non-resistant and clinically resistant strains of Staphylococcus aureus (MRSA 1418), E. coli (ESBL 1384), and Acinetobacter 1379. The main aim was to investigate the relationship between lipid profiles, hydrophobicity, and antibiotic resistance so as to identify the pathogenic potential and resistance factors of strains isolated from patients with sepsis and urinary tract infections (UTIs). The research included various tests, such as antimicrobial susceptibility assays following CLSI guidelines, biochemical tests, biofilm assays, and hydrophobicity assays. Additionally, gas chromatography mass spectrometry (GC-MS) and GC-Flame Ionization Detector (GC-FID) analysis were used for lipid profiling and composition. The clinically isolated resistant strains (MRSA-1418, ESBL-1384, and Acinetobacter 1379) demonstrated resistance phenotypes of 81.80%, 27.6%, and 63.6%, respectively, with a multiple antibiotic resistance index of 0.81, 0.27, and 0.63. Notably, the MRSA-1418 strain, which exhibited resistance, showed significantly higher levels of hemolysin, cell surface hydrophobicity, biofilm index, and a self-aggregative phenotype compared to the non-resistant strains. Gene expression analysis using quantitative real-time PCR (qPCR). Indicated elevated expression levels of intercellular adhesion biofilm-related genes (icaA, icaC, and icaD) in MRSA-1418 (pgaA, pgaC, and pgaB) and Acinetobacter 1379 after 24 h compared to non-resistant strains. Scanning electron microscopy (SEM) was employed for structural investigation. These findings provide valuable insights into the role of biofilms in antibiotic resistance and suggest potential target pathways for combating antibiotic-resistant bacteria.
Asunto(s)
Acinetobacter , Antibacterianos , Biopelículas , Escherichia coli , Pruebas de Sensibilidad Microbiana , Humanos , Antibacterianos/farmacología , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Acinetobacter/genética , Acinetobacter/efectos de los fármacos , Acinetobacter/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Fenotipo , Infecciones Estafilocócicas/microbiología , Infecciones por Acinetobacter/microbiología , Farmacorresistencia Bacteriana Múltiple/genética , Farmacorresistencia BacterianaRESUMEN
Multidrug resistance in bacteria is a major challenge worldwide, increasing both mortality by infections and costs for the health systems. Therefore, it is of utmost importance to find new drugs against resistant bacteria. Beauvericin (BEA) is a mycotoxin produced by entomopathogenic and other fungi of the genus Fusarium. Our work determines the effect of BEA combined with antibiotics, which has not been previously explored. The combination analysis included different antibiotics against non-methicillin-resistant Staphylococcus aureus (NT-MRSA), methicillin-resistant Staphylococcus aureus (MRSA), and Salmonella typhimurium. BEA showed a synergy effect with oxacillin with a fractional inhibitory concentration index (FICI) = 0.373 and an additive effect in combination with lincomycin (FICI = 0.507) against MRSA. In contrast, it was an antagonist when combined with ciprofloxacin against S. typhimurium. We propose BEA as a molecule with the potential for the development of new therapies in combination with current antibiotics against multidrug-resistant bacteria.