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1.
BMC Microbiol ; 24(1): 360, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39306662

RESUMEN

BACKGROUND: Urinary tract infections (UTIs) are the second most common infection, affecting 150 million people each year worldwide. Enterobacteriaceae species expressing extended-spectrum ß-lactamases (ESBLs) are on the rise across the globe and are becoming a severe problem in the therapeutic management of clinical cases of urinary tract infection. Knowledge of the prevalence and antibiogram profile of such isolates is essential to develop an appropriate treatment methodology. This study aimed to investigate the prevalence of Enterobacteriaceae isolates exhibiting ESBL and their selective oral antibiogram profile at the district general hospital, Polonnaruwa. RESULTS: A total of 4386 urine specimens received to the Microbiology Laboratory during the study period. Among them, 1081 (24.6%) showed positive results for urine culture while 200/1081 specimens showed ESBL isolates. Out of the selected 200 specimen's majority (67.5%) of samples received from the In-Patient Department. There were 200 patients and reported that 115 (57.5%) were females and 85 (42.5%) were males. The majority (51%) of the patients belong to the age group of 55-74 years. Among the ESBLs positive specimens, the majority 74.5% (n = 149) identified organisms were E. coli followed by Klebsiella spp.17.5% (n = 35), Enterobacteriaceae 7% (n = 14) and only1% (n = 2) isolate of Proteus spp. Mecillinam (87.92%) and Nitrofurantoin (83.2%) showed higher effectiveness against E. coli. Nitrofurantoin showed the highest effectiveness against Klebsiella spp. (40%), other Enterobacteriaceae spp. (100%). Proteus spp. showed 100% effectiveness and resistance respectively against Ciprofloxacin, Cotrimoxazole and Nitrofurantoin. CONCLUSION: The most predominant ESBLs producing uro-pathogen was the E. coli in the study setting and E. coli had higher sensitivity rate against Mecillinam. Among currently used oral antibiotics Nitrofurantoin was the best choice for UTIs caused by ESBL producers.


Asunto(s)
Antibacterianos , Infecciones por Enterobacteriaceae , Enterobacteriaceae , Pruebas de Sensibilidad Microbiana , Infecciones Urinarias , beta-Lactamasas , Humanos , Infecciones Urinarias/microbiología , Infecciones Urinarias/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Masculino , beta-Lactamasas/metabolismo , Anciano , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/enzimología , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Adulto , Adulto Joven , Anciano de 80 o más Años , Adolescente , Nitrofurantoína/farmacología , Nitrofurantoína/uso terapéutico , Prevalencia , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Escherichia coli/enzimología
2.
J Mater Chem B ; 12(36): 9005-9017, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39149933

RESUMEN

In the current era of rapid population growth, there has been an increase in resource consumption and the subsequent release of organic pollutants into water bodies by various industries. To address this issue, we have developed a nanocomposite material, Bi2S3-TiO2/HNTs, for electrochemical sensors capable of simultaneously detecting nitrofurantoin (NFT) and 4-nitrophenol (4-NP) contaminants. The nanocomposite material was synthesized using a novel one-pot sol-gel method, and its structural morphology was characterized using techniques such as FE-SEM, FT-IR, HR-TEM, and XRD. The electrochemical sensor exhibited a remarkably low limit of detection (3.2 nM for NFT and 3.5 nM for 4-NP) and a wide concentration range from 0 µM to 260 µM for both NFT and 4-NP, demonstrating their high sensitivity and accuracy for pollutant detection, and furthermore its potential for real-world application was assessed considering pond and tap water as real samples.


Asunto(s)
Técnicas Electroquímicas , Nanocompuestos , Nitrofurantoína , Nitrofenoles , Titanio , Contaminantes Químicos del Agua , Titanio/química , Nanocompuestos/química , Nitrofenoles/análisis , Nitrofenoles/química , Contaminantes Químicos del Agua/análisis , Nitrofurantoína/análisis , Nitrofurantoína/química , Sulfuros/química
3.
Talanta ; 280: 126726, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39173246

RESUMEN

More and more attention has been paid to food safety. Due to the overuse and misuse of antibiotics, the problem of antibiotic residues in animal food is one of the important challenges to ensure food safety. The development of a feasible strategy to detect antibiotic residues in animal food has become desirable. In this paper, we creatively synthesize a water-stable fluorescence sensing material, namely, Co(Ⅱ)-Coordination polymer [Co2(CA) (L)0.5 (H2O)3] n (L = 1,4-bis(imidazole-1-ylmethyl) benzene, CA= Citric acid). The single crystal X-ray diffraction shows that it crystallizes in tetragonal space group I-4. It is worth mentioning that there exists the rare Co4(µ3-O)4 cubane cluster structure and Co8 cluster units. Those adjacent Co8 cluster units are connected into an infinite two-dimensional net structure by four flexible bridged L ligands. Finally, the Co(Ⅱ)-Coordination polymer (CP) further develops into the three-dimensional supramolecular structure via the hydrogen bonds of O-H⋯O and C-H⋯O. It could selectively detect the antibiotic-nitrofurantoin (NFT) residue by way of fluorescence quenching, Co-CP for the detection of NFT shows broad linearity from 0 to 200 µM, with a detection limit of 0.13 µM and strong anti-interference ability. It is used to detect the NFT residual of tap water and milk with a spiked recovery of 86.35-112.47 %.


Asunto(s)
Antibacterianos , Cobalto , Complejos de Coordinación , Colorantes Fluorescentes , Nitrofurantoína , Polímeros , Cobalto/química , Cobalto/análisis , Antibacterianos/análisis , Antibacterianos/química , Polímeros/química , Nitrofurantoína/análisis , Nitrofurantoína/química , Colorantes Fluorescentes/química , Complejos de Coordinación/química , Espectrometría de Fluorescencia/métodos , Animales , Leche/química , Modelos Moleculares , Contaminación de Alimentos/análisis , Fluorescencia
4.
Food Chem ; 461: 140915, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39181055

RESUMEN

The excessive use of nitrofurantoin (NFT) represents a threat to ecosystems and food safety, making it necessary to develop efficient and accurate detection methods. Herein, the Ru/NiFe-LDH-MXene/SPCE electrode was successfully synthesized by one-step electrodeposition and employed to the NFT electrochemical sensing. Combining 2D MXenes with multifunctional 2D layered double hydroxides (LDHs) creates synergistic interactions within the MXene-LDH heterostructures, modifying the electrochemical performance. Furthermore, the incorporation of noble metal nanoparticles and nanoclusters can significantly enhance electrochemical performance by promoting favorable interactions at the metal-carrier interface and optimizing the rearrangement of electronic structure. Based on this, the developed Ru/NiFe-LDH-MXene/SPCE sensor demonstrates remarkable sensitivity (152.44 µA µM-1 cm-2) and an ultralow detection limit (2.2 nM). Notably, the sensor was employed for NFT detection in food samples with satisfactory recoveries, making it a promising electrochemical sensor for the detection of NFT.


Asunto(s)
Técnicas Electroquímicas , Contaminación de Alimentos , Nanopartículas del Metal , Nitrofurantoína , Rutenio , Técnicas Electroquímicas/instrumentación , Contaminación de Alimentos/análisis , Nitrofurantoína/análisis , Nitrofurantoína/química , Nanopartículas del Metal/química , Rutenio/química , Límite de Detección , Hidróxidos/química , Electrodos , Níquel/química
6.
JAMA ; 332(9): 730-737, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39115856

RESUMEN

Importance: Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes. Objectives: To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them. Design, Setting, and Participants: Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not. Exposure: Various classes of oral antibiotics. Main Outcomes and Measures: Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group. Results: During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital. Conclusion and Relevance: Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.


Asunto(s)
Antibacterianos , Erupciones por Medicamentos , Macrólidos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Administración Oral , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Estudios de Casos y Controles , Cefalosporinas/efectos adversos , Cefalosporinas/administración & dosificación , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/efectos adversos , Hospitalización/estadística & datos numéricos , Macrólidos/administración & dosificación , Macrólidos/efectos adversos , Nitrofurantoína/administración & dosificación , Nitrofurantoína/efectos adversos , Ontario/epidemiología , Penicilinas/administración & dosificación , Penicilinas/efectos adversos , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Medición de Riesgo/estadística & datos numéricos
7.
Int J Antimicrob Agents ; 64(3): 107277, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39032672

RESUMEN

OBJECTIVES: Nitrofurantoin is recommended as first-line therapy for the optimal treatment of uncomplicated urinary tract infections (UTIs) caused by enterococci and Escherichia coli. However, the mechanisms of nitrofurantoin resistance in enterococci have not been elucidated. This study aimed to investigate the mechanisms of nitrofurantoin resistance in E. faecium, focusing on the role of the nitroreductase NrmA. METHODS: Enterococcus strains isolated from the urinary tract samples were collected and were tested for nitrofurantoin susceptibility. Potential genes associated with nitrofurantoin resistance were screened in the NCBI nucleotide database and by polymerase chain reaction (PCR). Complementation assays and enzyme kinetic tests were performed to assess the impact of the Q48K mutation in NrmA on nitrofurantoin resistance. RESULTS: Of the 128 E. faecium isolates tested, 59 (46.1%) were resistant to nitrofurantoin. Analysis revealed the presence of a type IB nitroreductase, designated NrmA, in all E. faecium strains studied, shared 18.7% sequence identity with nitroreductase NfsB in E. coli. Different from NrmA in nitrofurantoin-susceptible E. faecium, nitrofurantoin-resistant strains had a single amino acid substitution, i.e., a lysine instead of a glutamine at position 48 (Q48K mutation). Complementation assays of nitrofurantoin-resistant E. faecium HS17-112 showed that the nitrofurantoin minimal inhibitory concentration of the complemented strain HS17-112: pIB166-nrmA (wild type [WT]) decreased from 128 mg/L to 4 mg/L. Compared with NrmA (WT), NrmA (Q48K) showed significantly reduced catalytic efficiency, with a kcat/Km value decreasing from 0.122 µM-1 s-1 to 0.000042 µM-1 s-1. CONCLUSION: The Q48K mutation in nitroreductase NrmA is responsible for nitrofurantoin resistance in E. faecium.


Asunto(s)
Farmacorresistencia Bacteriana , Enterococcus faecium , Nitrofurantoína , Nitrorreductasas , Humanos , Antibacterianos/farmacología , Antiinfecciosos Urinarios/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Farmacorresistencia Bacteriana/genética , Enterococcus faecium/genética , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/enzimología , Proteínas de Escherichia coli , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Mutación , Nitrofurantoína/farmacología , Nitrorreductasas/genética , Nitrorreductasas/metabolismo , Infecciones Urinarias/microbiología
8.
Ann Afr Med ; 23(3): 514-517, 2024 Jul 01.
Artículo en Francés, Inglés | MEDLINE | ID: mdl-39034584

RESUMEN

Nitrofurantoin is the antibiotic of choice for treatment and prophylaxis of recurrent episodes of lower urinary tract infections. Although adverse effects such as anorexia, vomiting, and pulmonary hypersensitivity are commonly reported with nitrofurantoin use, studies have demonstrated that rarely nitrofurantoin can also induce diverse forms of liver injury, spanning from mild hepatitis to severe and potentially fatal fulminant liver failure. These occur especially in elderly females with preexisting liver or renal impairment. Here, we present a case of a 62-year-old female in good health who exhibited symptoms of fatigue, abdominal pain, and dark-colored urine. Through investigation, she was diagnosed with a case of drug-induced liver injury associated with the prolonged use of nitrofurantoin.


RésuméLa nitrofurantoïne est l'antibiotique de choix pour le traitement de la prophylaxie d'épisodes récurrents d'infections des voies urinaires intérieures. Bien que des effets indésirables tels que l'anorexie, des vomissements et une hypersensibilité pulmonaire soient fréquemments rapportés lors de l'utilisation de la nitrofuratoïne, des études ont demontré que dans de rares cas, la nitrofurantoïne peut également induire diverses formes de lésions hépatiques, allant d'une hépatite légère à une incapacité hépatique fulminante grave et potentiellement mortelle. Celle-ci surviennent particulièrement chez des femmes âgées ayant une insuffisance hépatique ou rénale préexistante.Nous présentons ici l'étude d'une femme de 62 ans en bonne santé qui manifestait des symptômes de fatigue, de douleurs abdominales et d'urine de couleur foncée. À travers une enquête, on lui a diagnostiquée un cas de lésion hépatique d'origine médicamenteuse associée à l'utilisation prolongée de la nitrofurantoïne.


Asunto(s)
Antiinfecciosos Urinarios , Enfermedad Hepática Inducida por Sustancias y Drogas , Nitrofurantoína , Infecciones Urinarias , Humanos , Nitrofurantoína/efectos adversos , Femenino , Persona de Mediana Edad , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Antiinfecciosos Urinarios/efectos adversos , Infecciones Urinarias/tratamiento farmacológico , Resultado del Tratamiento
9.
Ann Intern Med ; 177(6): JC67, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38830223

RESUMEN

SOURCE CITATION: Wagenlehner F, Perry CR, Hooton TM, et al. Oral gepotidacin versus nitrofurantoin in patients with uncomplicated urinary tract infection (EAGLE-2 and EAGLE-3): two randomised, controlled, double-blind, double-dummy, phase 3, non-inferiority trials. Lancet. 2024;403:741-755. 38342126.


Asunto(s)
Nitrofurantoína , Infecciones Urinarias , Adulto , Femenino , Humanos , Persona de Mediana Edad , Acenaftenos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Antiinfecciosos Urinarios/uso terapéutico , Método Doble Ciego , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Nitrofurantoína/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Fase III como Asunto
10.
Food Chem ; 456: 140036, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-38878538

RESUMEN

1-Aminohydantoin (AHD), the residual marker of nitrofurantoin, is usually detected after derivatisation using the derivatisation reagent 2-nitrobenzaldehyde. Avoiding the antibody recognition of the derivatisation reagent is essential for the accurate detection of AHD residues. In this paper, a novel hapten called hapten D was designed, and then, a monoclonal antibody that did not recognise 2-nitrobenzaldehyde was prepared based on this novel hapten. An ultra-sensitive indirect competitive enzyme linked-immunosorbent assay (icELISA) was established under optimal conditions. The 50% inhibition concentration and limit of detection of AHD were 0.056 and 0.0060 ng/mL, respectively, which improved the sensitivity by 9-37-fold compared with the previously reported icELISA methods. The average recovery rates were 88.1%-97.3%, and the coefficient of variation was <8.6%. The accuracy and reliability of the icELISA were verified using liquid chromatography-tandem mass spectrometry. These results demonstrated that the developed icELISA is a useful and reliable tool.


Asunto(s)
Anticuerpos Monoclonales , Ensayo de Inmunoadsorción Enzimática , Hidantoínas , Nitrofurantoína , Anticuerpos Monoclonales/química , Ensayo de Inmunoadsorción Enzimática/métodos , Nitrofurantoína/química , Nitrofurantoína/análisis , Hidantoínas/química , Hidantoínas/análisis , Animales , Límite de Detección , Contaminación de Alimentos/análisis , Ratones , Haptenos/química , Haptenos/inmunología , Femenino , Ratones Endogámicos BALB C
11.
Virulence ; 15(1): 2356692, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38797966

RESUMEN

The increasing antibiotic resistance poses a significant global health challenge, threatening our ability to combat infectious diseases. The phenomenon of collateral sensitivity, whereby resistance to one antibiotic is accompanied by increased sensitivity to another, offers potential avenues for novel therapeutic interventions against infections unresponsive to classical treatments. In this study, we elucidate the emergence of tobramycin (TOB)-resistant small colony variants (SCVs) due to mutations in the hemL gene, which render S. Typhimurium more susceptible to nitrofurantoin (NIT). Mechanistic studies demonstrate that the collateral sensitivity in TOB-resistant S. Typhimurium SCVs primarily stems from disruptions in haem biosynthesis. This leads to dysfunction in the electron transport chain (ETC) and redox imbalance, ultimately inducing lethal accumulation of reactive oxygen species (ROS). Additionally, the upregulation of nfsA/B expressions facilitates the conversion of NIT prodrug into its active form, promoting ROS-mediated bacterial killing and contributing to this collateral sensitivity pattern. Importantly, alternative NIT therapy demonstrates a significant reduction of bacterial load by more than 2.24-log10 cfu/g in the murine thigh infection and colitis models. Our findings corroborate the collateral sensitivity of S. Typhimurium to nitrofurans as a consequence of evolving resistance to aminoglycosides. This provides a promising approach for treating infections due to aminoglycoside-resistant strains.


Asunto(s)
Antibacterianos , Nitrofurantoína , Salmonella typhimurium , Tobramicina , Nitrofurantoína/farmacología , Animales , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Tobramicina/farmacología , Ratones , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana/genética , Mutación , Femenino , Especies Reactivas de Oxígeno/metabolismo , Infecciones por Salmonella/microbiología , Infecciones por Salmonella/tratamiento farmacológico , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo
12.
Comput Biol Chem ; 111: 108093, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38772047

RESUMEN

Malaria is one of most widespread infectious disease in world. The antimalarial therapy presents a series of limitations, such as toxicity and the emergence of resistance, which makes the search for new drugs urgent. Thus, it becomes necessary to explore essential and exclusive therapeutic targets of the parasite to achieve selective inhibition. Enoyl-ACP reductase is an enzyme of the type II fatty acid biosynthetic pathway and is responsible for the rate-limiting step in the fatty acid elongation cycle. In this work, we use hierarchical virtual screening and drug repositioning strategies to prioritize compounds for phenotypic assays and molecular dynamics studies. The molecules were tested against chloroquine-resistant W2 strain of Plasmodium falciparum (EC50 between 330.05 and 13.92 µM). Nitrofurantoin was the best antimalarial activity at low micromolar range (EC50 = 13.92 µM). However, a hit compound against malaria must have a biological activity value below 1 µM. A large number of molecules present problems with permeability in biological membranes and reaching an effective concentration in their target's microenvironment. Nitrofurantoin derivatives with inclusions of groups which confer increased lipid solubility (methyl groups, halogens and substituted and unsubstituted aromatic rings) have been proposed. These derivatives were pulled through the lipid bilayer in molecular dynamics simulations. Molecules 14, 18 and 21 presented lower free energy values than nitrofurantoin when crossing the lipid bilayer.


Asunto(s)
Antimaláricos , Simulación de Dinámica Molecular , Plasmodium falciparum , Antimaláricos/farmacología , Antimaláricos/química , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/enzimología , Pruebas de Sensibilidad Parasitaria , Estructura Molecular , Humanos , Desarrollo de Medicamentos , Enoil-ACP Reductasa (NADH)/antagonistas & inhibidores , Enoil-ACP Reductasa (NADH)/metabolismo , Nitrofurantoína/química , Nitrofurantoína/farmacología , Relación Estructura-Actividad
13.
Antimicrob Agents Chemother ; 68(7): e0024224, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38767379

RESUMEN

Nitrofurantoin resistance in Escherichia coli is primarily caused by mutations damaging two enzymes, NfsA and NfsB. Studies based on small isolate collections with defined nitrofurantoin MICs have found significant random genetic drift in nfsA and nfsB, making it extremely difficult to predict nitrofurantoin resistance from whole-genome sequence (WGS) where both genes are not obviously disrupted by nonsense or frameshift mutations or insertional inactivation. Here, we report a WGS survey of 200 oqxAB-negative E. coli from community urine samples, of which 34 were nitrofurantoin resistant. We characterized individual non-synonymous mutations seen in nfsA and nfsB among this collection using complementation cloning and NfsA/B enzyme assays in cell extracts. We definitively identified R203C, H11Y, W212R, A112E, and A112T in NfsA and R121C, Q142H, F84S, P163H, W46R, K57E, and V191G in NfsB as amino acid substitutions that reduce enzyme activity sufficiently to cause resistance. In contrast, E58D, I117T, K141E, L157F, A172S, G187D, and A188V in NfsA and G66D, M75I, V93A, and A174E in NfsB are functionally silent in this context. We identified that 9/166 (5.4%) nitrofurantoin-susceptible isolates were "pre-resistant," defined as having loss of function mutations in nfsA or nfsB. Finally, using NfsA/B enzyme assays and proteomics, we demonstrated that 9/34 (26.5%) ribE wild-type nitrofurantoin-resistant isolates also carried functionally wild-type nfsB or nfsB/nfsA. In these cases, NfsA/B activity was reduced through downregulated gene expression. Our biological understanding of nitrofurantoin resistance is greatly improved by this analysis but is still insufficient to allow its reliable prediction from WGS data.


Asunto(s)
Farmacorresistencia Bacteriana , Proteínas de Escherichia coli , Escherichia coli , Nitrofurantoína , Nitrorreductasas , Humanos , Antibacterianos/farmacología , Antiinfecciosos Urinarios/farmacología , Farmacorresistencia Bacteriana/genética , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Proteínas de Escherichia coli/genética , Genoma Bacteriano/genética , Pruebas de Sensibilidad Microbiana , Mutación , Nitrofurantoína/farmacología , Nitrorreductasas/genética , Nitrorreductasas/metabolismo , Secuenciación Completa del Genoma/métodos
14.
ACS Appl Bio Mater ; 7(5): 2924-2935, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38637912

RESUMEN

Herein, a facile and highly effective nonenzymatic electrochemical sensing system is designed for the detection of the antibacterial drug nitrofurantoin (NFT). This electrocatalyst is a combination of a trimetallic Prussian blue analogue and conductive polyaniline coated onto a three-dimensional porous nickel foam substrate. A comprehensive set of physicochemical analyses have verified the successful synthesis. The fabricated electrochemical sensor exhibits an impressively low limit of detection (0.096 nM) and quantification (0.338 nM, S/N = 3.3), coupled with a wide linear range spanning from 0.1 nM to 5 mM and a sensitivity of 13.9 µA nM-1 cm-2. This excellent performance is attributed to the collaborative effects of conducting properties of polyaniline (PANI) and the remarkable redox behavior of the Prussian blue analogue (PBA). When both are integrated into the nickel foam, they create a significantly enlarged surface area with numerous catalytic active sites, enhancing the sensor's efficiency. The sensor demonstrates a high degree of specificity for NFT, while effectively minimizing responses to potential interferences such as flutamide, ascorbic acid, glucose, dopamine, uric acid, and nitrophenol, even when present in 2-3-fold higher concentrations. Moreover, to validate its practical utility, the sensor underwent real sample analysis using synthetic urine, achieving outstanding recovery rates of 118 and 101%.


Asunto(s)
Compuestos de Anilina , Ferrocianuros , Ensayo de Materiales , Níquel , Nitrofurantoína , Compuestos de Anilina/química , Ferrocianuros/química , Níquel/química , Nitrofurantoína/química , Nitrofurantoína/análisis , Porosidad , Humanos , Técnicas Electroquímicas , Tamaño de la Partícula , Materiales Biocompatibles/química , Materiales Biocompatibles/síntesis química , Propiedades de Superficie
15.
APMIS ; 132(7): 492-498, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38558445

RESUMEN

The antimicrobial agent nitrofurantoin is becoming increasingly important for treatment of urinary tract infections (UTIs) due to widespread occurrence of multidrug-resistant Escherichia coli. Despite many years of use, little data on nitrofurantoin pharmacokinetics (PK) or -dynamics (PD) exist. The objective of this study was to (i) evaluate the pharmacokinetics of nitrofurantoin in a mouse model and (ii) use that data to design an in vivo dose fractionation study in an experimental model of UTI with E. coli for determination of the most predictive PK/PD index. Nitrofurantoin concentrations in urine were approximately 100-fold larger than concentrations in plasma after oral administration of 5, 10, and 20 mg/kg nitrofurantoin. The area under the curve over the minimum inhibitory concentration (AUC/MIC) was weakly correlated to bacterial reduction in urine (r2 = 0.24), while no such correlation was found for the time that nitrofurantoin stayed above the MIC (T > MIC). Increasing size of single-dose treatment was significantly correlated to eradication of bacteria in the urine, while this was not apparent when the same doses were divided in 2 or 3 doses 8 or 12 h apart. In conclusion, the results indicate that nitrofurantoin activity against E. coli in urine is driven by AUC/MIC.


Asunto(s)
Modelos Animales de Enfermedad , Infecciones por Escherichia coli , Escherichia coli , Pruebas de Sensibilidad Microbiana , Nitrofurantoína , Infecciones Urinarias , Nitrofurantoína/farmacocinética , Nitrofurantoína/farmacología , Nitrofurantoína/uso terapéutico , Animales , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Escherichia coli/efectos de los fármacos , Ratones , Femenino , Antiinfecciosos Urinarios/farmacocinética , Antiinfecciosos Urinarios/farmacología , Antiinfecciosos Urinarios/uso terapéutico , Antiinfecciosos Urinarios/administración & dosificación , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Administración Oral
16.
Ir J Med Sci ; 193(4): 1891-1900, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38565823

RESUMEN

BACKGROUND: Escherichia coli is the predominant urinary pathogen in children. Irish and international studies have demonstrated increasing antimicrobial resistance (AMR) to antibiotics such as co-amoxiclav. AIMS: We aimed to (1) examine the AMR patterns of paediatric urinary E. coli isolates, from both hospital and community sources, over a 10-year period; (2) assess the effectiveness of Children's Health Ireland (CHI) antimicrobial guidance given local susceptibility data; and (3) review the clinical management of an admitted patient sub-set over a 6-year period. METHODS: Pure growth of urinary E. coli from patients aged ≤ 14 from 2012 to 2021 were analysed for AMR. Differences in susceptibility rates were assessed. A retrospective chart review conducted on inpatients aged ≥ 2 months to ≤ 14 years, 2016-2021. RESULTS: E. coli accounted for 70.8% of likely significant positive pure growth cultures (9314 isolates). Susceptibility to co-amoxiclav significantly increased over time, from 66.7% to 80.4% (2016-2021, p < 0.001). Nitrofurantoin and cefalexin had significantly higher susceptibility rates than trimethoprim (< 70% annually). 85.1% of isolates were susceptible to the combination of co-amoxiclav and gentamicin, recommended for those > 2months and systemically unwell. The additional gain in empiric susceptibility provided by gentamicin above that provided by co-amoxiclav alone has fallen from 16.4% to 6.7% (2016-2021). The 222 clinical cases reviewed showed improved antimicrobial guideline compliance over time. CONCLUSIONS: This study provides important regional AMR data. Co-amoxiclav susceptibility increased significantly over time, contrasting with previous studies. This was temporally associated with stewardship measures reducing co-amoxiclav prescribing. Decreasing utility of gentamicin supports recent CHI guideline updates reducing gentamicin use.


Asunto(s)
Antibacterianos , Infecciones por Escherichia coli , Escherichia coli , Infecciones Urinarias , Humanos , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Estudios Retrospectivos , Infecciones por Escherichia coli/tratamiento farmacológico , Niño , Lactante , Antibacterianos/uso terapéutico , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Preescolar , Femenino , Masculino , Adolescente , Pruebas de Sensibilidad Microbiana , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Farmacorresistencia Bacteriana , Irlanda/epidemiología , Nitrofurantoína/uso terapéutico , Trimetoprim/uso terapéutico
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 314: 124194, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38569387

RESUMEN

Here, we demonstrated the synthesis of a zinc based luminescent MOF, 1 (NDC = 2,6- naphthalenedicarboxylate) for the ratiometric detection of biomarker riboflavin (RBF; vitamin B2) in water dispersed medium. Further, this MOF detected two other antibiotic drug molecules, nitrofurantoin (NFT) and nitrofurazone (NZF). The detection of these analytes is very quick (∼seconds), and the limit of detection (LOD) for RBF, NZF and NFT are calculated as 16.58 ppm, 47.63 ppb and 56.96 ppb, respectively. The detection of these analytes was also comprehended by solid, solution, cost-effective paper strip method i.e., triphasic identification capabilities. The sensor is reusable without losing its detection efficacy. The sensor further showed the recognition abilities of these antibiotics in real field samples (river water, urine and tablet) and RBF in vitamin B2 pills and food samples (milk and cold drinks). The sensing merit of 1 urged us to fabricate of 1@cotton fabric composite, which exhibited the colorimetric detection of these analytes. In-depth experimental analysis suggested that the occurrence of photo-induced electron transfer (PET), fluorescence resonance energy transfer (FRET), and the inner filter effect (IFE) are the possible sensing mechanisms for the recognition of the antibiotics drug. The FRET mechanism is responsible for the recognition of RBF. The sensing mechanism is further supported by the theoretical analysis and the excited lifetime measurement.


Asunto(s)
Antibacterianos , Transferencia Resonante de Energía de Fluorescencia , Antibacterianos/análisis , Nitrofurantoína , Colorantes/análisis , Agua , Vitaminas/análisis
18.
J Infect Dev Ctries ; 18(3): 391-398, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38635608

RESUMEN

INTRODUCTION: Urinary tract infection (UTI) is a common bacterial complication in pregnancy. The study aimed to estimate the prevalence, risk factors, and bacterial etiology of UTI during pregnancy and determine the efficacy of antimicrobial drugs in treating UTIs. METHODOLOGY: Urine specimens and clinical data were collected from pregnant women who attended primary health centers in Erbil, Iraq. All specimens were cultured on appropriate media and identified by standard microbiological methods. The pregnant women were grouped into symptomatic UTI group, asymptomatic bacteriuria group, and the control group. The agar dilution method was used to determine antimicrobial susceptibility. RESULTS: Among the 5,042 pregnant women included in this study, significant bacteriuria was found in 625 (12.40%) of the cases, and 198 (31.68%) had symptomatic UTI, of which 43.59% were diagnosed during the third trimester. Out of the 643 bacteria isolated, 33.28% were symptomatic UTI, of which 43.59% developed during the third trimester. There was a significant difference in the bacterial etiology between symptomatic UTI and asymptomatic bacteriuria (p = 0.002), as well as between cystitis and pyelonephritis (p = 0.017). The most common bacterial species isolated was Escherichia coli, which was susceptible to fosfomycin (100%), meropenem (99.45%), and nitrofurantoin (97.8%). CONCLUSIONS: Pregnant women are more likely to develop UTI in the third trimester. Escherichia coli is the predominant pathogen. The study suggests the use of fosfomycin, meropenem, and nitrofurantoin for the treatment of UTI. No Gram-positive isolates were resistant to daptomycin.


Asunto(s)
Antiinfecciosos , Bacteriuria , Fosfomicina , Infecciones Urinarias , Femenino , Humanos , Embarazo , Bacteriuria/tratamiento farmacológico , Bacteriuria/epidemiología , Bacteriuria/microbiología , Nitrofurantoína/farmacología , Nitrofurantoína/uso terapéutico , Fosfomicina/uso terapéutico , Mujeres Embarazadas , Meropenem/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología , Infecciones Urinarias/etiología , Antiinfecciosos/uso terapéutico , Escherichia coli , Antibacterianos/farmacología , Antibacterianos/uso terapéutico
19.
World J Urol ; 42(1): 221, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38587648

RESUMEN

PURPOSE: Fosfomycin has been used more frequently in managing uncomplicated urinary tract infections (UTIs) due to decreased compliance and increased multidrug-resistant bacteria. The aim of this network meta-analysis was to assess the efficacy of Fosfomycin compared to Nitrofurantoin, Trimethoprim-Sulfamethoxazole (TMP-SMX), and Ciprofloxacin in terms of clinical and microbiological cure alongside with other measurements. MATERIALS AND METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We included randomized control trials (RCTs) with uncomplicated UTI patients who received Fosfomycin, Nitrofurantoin, TMP-SMX, or Ciprofloxacin and reported the clinical or microbiological cure. We used Cochrane Risk of Bias Assessment Tool to assess the included studies' quality. R-software was used for all statistical analysis. We ranked all antibiotics using the netrank function which yielded P scores. Frequentist network meta-analysis was used to assess the efficacy of all outcomes. RESULTS: We included 13 RCTs with a total number of 3856 patients that showed Fosfomycin ranked the highest among the other antibiotics with respect to clinical cure (P-score = 0.99) and microbiological cure (P-score = 0.99) while Ciprofloxacin ranked the lowest (P-score = 0.11 and 0.02, respectively). Moreover, Ciprofloxacin yielded the highest relapse rate (P-score = 1), whereas TMP-SMX had the lowest relapse rate (P-score = 0.07). As for the adverse events, Ciprofloxacin demonstrated the highest adverse events as opposed to Fosfomycin (P-score = 0.98 and 0.05, respectively). CONCLUSION: The network meta-analysis demonstrated that Fosfomycin is the most effective antibiotic in treating uncomplicated UTIs with respect to clinical cure, microbiological cure, and adverse events profile.


Asunto(s)
Fosfomicina , Infecciones Urinarias , Humanos , Antibacterianos/uso terapéutico , Fosfomicina/uso terapéutico , Nitrofurantoína , Combinación Trimetoprim y Sulfametoxazol , Metaanálisis en Red , Infecciones Urinarias/tratamiento farmacológico , Ciprofloxacina/uso terapéutico , Recurrencia
20.
Urogynecology (Phila) ; 30(3): 272-279, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38484242

RESUMEN

IMPORTANCE: Urinary tract infections (UTIs) occur in 8.6% to 48.1% of patients after intradetrusor onabotulinumtoxinA injections. OBJECTIVE: The objective of this study was to evaluate both choice and duration of antibiotic prophylaxis on the incidence of UTI within 30 days after in-office onabotulinumtoxinA injections. STUDY DESIGN: We included a single-site, retrospective cohort of 305 patients with overactive bladder or bladder pain syndrome receiving postprocedure prophylactic antibiotics for in-office, 100-unit intradetrusor onabotulinumtoxinA injections from 2019 to 2023. Categories of antibiotic prophylaxis compared included (1) nitrofurantoin 100 mg twice daily for 3 days, (2) nitrofurantoin 100 mg twice daily for 5 days, (3) trimethoprim-sulfamethoxazole 160 mg/800 mg twice daily for 3 days, and (4) "other regimens." Primary outcome was incidence of UTI within 30 days. Variables were compared via χ2 test. Crude/adjusted odds were estimated using binary logistic regression. RESULTS: Incidence of UTI was 10.4% for 3-day nitrofurantoin, 20.5% for 5-day nitrofurantoin, 7.4% for 3-day trimethoprim-sulfamethoxazole, and 25.7% among "other regimens" (P = 0.023). Differences among primary regimens were substantial but not statistically significant: 3-day trimethoprim-sulfamethoxazole had 31% lower odds of UTI versus 3-day nitrofurantoin (odds ratio [OR], 0.689; P = 0.518). Compared with 3-day nitrofurantoin regimen, the 5-day nitrofurantoin regimen had twice the odds of UTI (OR, 2.22; P = 0.088). Those receiving "other regimens" had nearly 3 times the odds of UTI (OR, 2.98; P = 0.018). Results were similar adjusting for age and race. Overall urinary retention rate was 1.97%. CONCLUSIONS: Prophylactic antibiotic choice and duration of treatment potentially affect UTI incidence after in-office, intradetrusor onabotulinumtoxinA injections. Nitrofurantoin and trimethoprim-sulfamethoxazole for 3 days have the lowest UTI incidence.


Asunto(s)
Toxinas Botulínicas Tipo A , Infecciones Urinarias , Humanos , Antibacterianos/uso terapéutico , Nitrofurantoína/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Toxinas Botulínicas Tipo A/uso terapéutico , Estudios Retrospectivos , Infecciones Urinarias/epidemiología
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