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1.
Iran J Microbiol ; 16(4): 477-483, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39267930

RESUMEN

Background and Objectives: Urinary tract infections (UTIs), one of the most prevalent bacterial infections, are facing limited treatment options due to escalating concern of antibiotic resistance. Urine cultures significantly help in identification of etiological agents responsible for these infections. Assessment of antibiotic susceptibility patterns of these bacteria aids in tackling the emerging concern of antibiotic resistance and establishment of empirical therapy guidelines. Our aim was to determine various agents responsible for urinary tract infections and to assess their antibiotic susceptibility patterns. Materials and Methods: This cross-sectional study was performed over a period of six months from January 2023 to July 2023 in Department of Microbiology of Pakistan Institute of Medical Sciences (PIMS). Results: Out of 2957 positive samples, Gram negative bacteria were the most prevalent in 1939 (65.6%) samples followed by Gram positive bacteria in 418 (14.1%) and Candida spp. in 269 (9.1%) samples. In gram negative bacteria, Escherichia coli (E. coli) was the most prevalent bacteria isolated from 1070 samples (55.2%) followed by Klebsiella pneumoniae in 397 samples (20.5%). In Gram positive bacteria, Enterococcus spp. was the most common bacteria in 213 samples (51%) followed by Staphylococcus aureus in 120 samples (28.7%). Amikacin was the most sensitive drug (91%) for Gram negative bacteria. Gram positive bacteria were most susceptible to linezolid (97%-100%). Conclusion: The generation of a hospital tailored antibiogram is essential for the effective management of infections and countering antibiotic resistance. By adopting antimicrobial stewardship strategies by deeper understanding of sensitivity patterns, we can effectively combat antibiotic resistance.

2.
BMC Microbiol ; 24(1): 344, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39271999

RESUMEN

BACKGROUND: In the present study, we aimed to determine the frequency of the csgA, fimH, mrkD, foc, papaGI, papGII and papGIII genes, to provide and to design fimbrial adhesin gene (FAG) patterns and profiles for the isolated uropathogenic Escherichia coli (UPEC) strains. METHODS: The enrollment of 108 positive urine samples was performed during seven months, between January 2022 and July 2022. The UPEC strains were confirmed through the standard microbiological and biochemical tests. The antimicrobial susceptibility test was performed through the Kirby-Bauer disc diffusion method. Molecular screening of FAGs was done through the polymerase chain reaction technology. The statistical analyses including chi square and Fisher's exact tests were performed to interpret the obtained results in the present study. RESULTS: As the main results, the antimicrobial resistance (AMR) patterns, multi- (MDR) and extensively drug-resistance (XDR) patterns and FAG patterns were designed and provided. fimH (93.3%), csgA (90.4%) and papG (37.5%) (papGII (30.8%)) genes were recognized as the top three FAGs, respectively. Moreover, the frequency of csgA-fimH gene profile was identified as the top FAG pattern (46.2%) among the others. The isolates bearing csgA-fimH gene profile were armed with a versatile of phenotypic AMR patterns. In the current study, 27.8%, 69.4% and 1.9% of the UPEC isolates were detected as extended-spectrum ß-lactamases (ESBLs) producers, MDR and XDR strains, respectively. CONCLUSIONS: In conclusion, detection, providing and designing of patterns and profiles in association with FAGs, AMR feature in UPEC strains give us an effective option to have a successful and influential prevention for both of UTIs initiation and AMR feature.


Asunto(s)
Infecciones por Escherichia coli , Proteínas de Escherichia coli , Proteínas Fimbrias , Fimbrias Bacterianas , Infecciones Urinarias , Escherichia coli Uropatógena , Escherichia coli Uropatógena/genética , Escherichia coli Uropatógena/efectos de los fármacos , Humanos , Proteínas de Escherichia coli/genética , Infecciones por Escherichia coli/microbiología , Infecciones Urinarias/microbiología , Proteínas Fimbrias/genética , Proteínas Fimbrias/metabolismo , Fimbrias Bacterianas/genética , Fimbrias Bacterianas/metabolismo , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Adhesinas de Escherichia coli/genética , Adhesinas de Escherichia coli/metabolismo , Femenino , Adulto , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Masculino , Farmacorresistencia Bacteriana Múltiple/genética , Persona de Mediana Edad , Adulto Joven , Adolescente , Proteínas Bacterianas
3.
Sci Rep ; 14(1): 20598, 2024 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232037

RESUMEN

The use of antimicrobial drugs in food-producing animals contributes to the selection pressure on pathogenic and commensal bacteria to become resistant. This study aims to evaluate the existence of trade-offs between treatment effectiveness, cost, and the dynamics of resistance in gut commensal bacteria. We developed a within-host ordinary differential equation model to track the dynamics of antimicrobial drug concentrations and bacterial populations in the site of infection (lung) and the gut. The model was parameterized to represent enrofloxacin treatment for bovine respiratory disease (BRD) caused by Pastereulla multocida in cattle. Three approved enrofloxacin dosing regimens were compared for their effects on resistance on P. multocida and commensal E. coli: 12.5 mg/kg and 7.5 mg/kg as a single dose, and 5 mg/kg as three doses. Additionally, we explored non-FDA-approved regimes. Our results indicated that both 12.5 mg/kg and 7.5 mg/kg as a single dose scenario increased the most the treatment costs and prevalence of P. multocida resistance in the lungs, while 5 mg/kg as three doses increased resistance in commensal E. coli bacteria in the gut the most out of the approved scenarios. A proposed non-FDA-approved scenario (7.5 mg/kg, two doses 24 h apart) showed low economic costs, minimal P. multocida, and moderate effects on resistant E. coli. Overall, the scenarios that decrease P. multocida, including resistant P. multocida did not coincide with those that decrease resistant E. coli the most, suggesting a trade-off between both outcomes. The sensitivity analysis suggests that bacterial populations were the most sensitive to drug conversion factors into plasma ( ß ), elimination of the drug from the colon ( ϑ ), fifty percent sensitive bacteria (P. multocida) killing effect ( L s50 ), fifty percent of bacteria (E. coli) above ECOFF killing effect ( C r50 ), and net drug transfer rate in the lung ( γ ) parameters.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana , Enrofloxacina , Escherichia coli , Animales , Enrofloxacina/farmacología , Enrofloxacina/administración & dosificación , Enrofloxacina/uso terapéutico , Bovinos , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Farmacorresistencia Bacteriana/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Pasteurella multocida/efectos de los fármacos , Enfermedades de los Bovinos/tratamiento farmacológico , Enfermedades de los Bovinos/microbiología , Pruebas de Sensibilidad Microbiana , Resultado del Tratamiento , Pulmón/microbiología , Pulmón/efectos de los fármacos
4.
Eur J Med Chem ; 278: 116790, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39236497

RESUMEN

New antibacterial compounds are urgently needed, especially for infections caused by the top-priority Gram-negative bacteria that are increasingly difficult to treat. Lipid A is a key component of the Gram-negative outer membrane and the LpxH enzyme plays an important role in its biosynthesis, making it a promising antibacterial target. Inspired by previously reported ortho-N-methyl-sulfonamidobenzamide-based LpxH inhibitors, novel benzamide substitutions were explored in this work to assess their in vitro activity. Our findings reveal that maintaining wild-type antibacterial activity necessitates removal of the N-methyl group when shifting the ortho-N-methyl-sulfonamide to the meta-position. This discovery led to the synthesis of meta-sulfonamidobenzamide analogs with potent antibacterial activity and enzyme inhibition. Moreover, we demonstrate that modifying the benzamide scaffold can alter blocking of the cardiac voltage-gated potassium ion channel hERG. Furthermore, two LpxH-bound X-ray structures show how the enzyme-ligand interactions of the meta-sulfonamidobenzamide analogs differ from those of the previously reported ortho analogs. Overall, our study has identified meta-sulfonamidobenzamide derivatives as promising LpxH inhibitors with the potential for optimization in future antibacterial hit-to-lead programs.


Asunto(s)
Antibacterianos , Benzamidas , Diseño de Fármacos , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Benzamidas/farmacología , Benzamidas/química , Benzamidas/síntesis química , Relación Estructura-Actividad , Humanos , Sulfonamidas/química , Sulfonamidas/farmacología , Sulfonamidas/síntesis química , Estructura Molecular , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Relación Dosis-Respuesta a Droga , Amidohidrolasas/antagonistas & inhibidores , Amidohidrolasas/metabolismo , Modelos Moleculares
5.
Front Cell Infect Microbiol ; 14: 1444031, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39282498

RESUMEN

Tigecycline is a last-resort drug used to treat serious infections caused by multidrug-resistant bacteria. tet(X4) is a recently discovered plasmid-mediated tigecycline resistance gene that confers high-level resistance to tigecycline and other tetracyclines. Since the first discovery of tet(X4) in 2019, it has spread rapidly worldwide, and as a consequence, tigecycline has become increasingly ineffective in the clinical treatment of multidrug-resistant infections. In this study, we identified and analyzed tet(X4)-positive Escherichia coli isolates from duck farms in Hunan Province, China. In total, 976 samples were collected from nine duck farms. Antimicrobial susceptibility testing and whole-genome sequencing (WGS) were performed to establish the phenotypes and genotypes of tet(X4)-positive isolates. In addition, the genomic characteristics and transferability of tet(X4) were determined based on bioinformatics analysis and conjugation. We accordingly detected an E. coli strain harboring tet(X4) and seven other resistance genes in duck feces. Multi-locus sequence typing analysis revealed that this isolate belonged to a new clone, and subsequent genetic analysis indicated that tet(X4) was carried in a 4608-bp circular intermediate, flanked by ISVsa3-ORF2-abh elements. Moreover, it exhibited transferability to E. coli C600 with a frequency of 10-5. The detection of tet(X4)-harboring E, coli strains on duck farms enhances our understanding of tigecycline resistance dynamics. The transferable nature of the circular intermediate of tet(X4) contributing to the spread of tigecycline resistance genes poses a substantial threat to healthcare. Consequently, vigilant monitoring and proactive measures are necessary to prevent their spread.


Asunto(s)
Antibacterianos , Patos , Infecciones por Escherichia coli , Escherichia coli , Granjas , Tigeciclina , Secuenciación Completa del Genoma , Animales , Antibacterianos/farmacología , China , Farmacorresistencia Bacteriana/genética , Farmacorresistencia Bacteriana Múltiple/genética , Patos/microbiología , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/genética , Heces/microbiología , Transferencia de Gen Horizontal , Genotipo , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Plásmidos/genética , Enfermedades de las Aves de Corral/microbiología , Tigeciclina/farmacología
6.
Sci Rep ; 14(1): 22598, 2024 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-39349568

RESUMEN

Antimicrobial resistance (AMR) leads to a decrease in the adequacy of antimicrobial agents and an increase in the rate of adverse effects and mortality. The main objective of this project is to investigate the synergistic effect of BiAu@NCLin-T1 and its substructures as an antimicrobial photodynamic therapy (aPDT) agent to combat microbial resistance. In addition, the effect of photothermal therapy (PTT) on some of the designed nanostructures at a temperature of 40 °C was also tested. The antimicrobial test was carried out using the growth curve method against Escherichia coli and Staphylococcus aureus. Computational methods were used to investigate the stability and entropy of oligonucleotide sequence structures. Various analyses were performed to identify the nanostructures, including Ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDS) and fluorescence analysis. The BiAu@NCLin-T1 appeared the significant aPDT impact against the gram-negative E.coli strain at two distinctive oligonucleotide concentrations (1, and 1.5 micromolar (µM)). Based on the results, the outlined nanostructures can act as a photosensitizer (PS), a photothermal treatment (PTT) agent, and an antimicrobial agent to combat resistant bacteria.


Asunto(s)
Bismuto , Escherichia coli , Oro , Fotoquimioterapia , Fármacos Fotosensibilizantes , Staphylococcus aureus , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Escherichia coli/efectos de los fármacos , Oro/química , Oro/farmacología , Staphylococcus aureus/efectos de los fármacos , Bismuto/química , Bismuto/farmacología , Fotoquimioterapia/métodos , Antibacterianos/farmacología , Antibacterianos/química , Nanopartículas del Metal/química , Pruebas de Sensibilidad Microbiana , Espectroscopía Infrarroja por Transformada de Fourier , Farmacorresistencia Bacteriana/efectos de los fármacos , Terapia Fototérmica/métodos
7.
Adv Healthc Mater ; : e2401289, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978439

RESUMEN

Infectious wounds occur when harmful microorganisms such as bacteria or viruses invade a wound site. Its problems associated include delayed healing, increased pain, swelling, and the potential for systemic infections. Therefore, developing new wound dressing materials with antibacterial effects is crucial for improving the healing process. Here a redox-degradable hydrogel loaded with an antibacterial peptide (vancomycin) in a straightforward gram-scale synthesis, is developed. The hydrogel structure consists of a disulfide bond-containing hyperbranched polyglycerol (SS-hPG) that is cross-linked by 4-arm polyethylene glycol-thiol (4-arm PEG-SH). The polymerization mechanism and full characterization of SS-hPG are described as this synthesis is reported for the first time. Rheology is used to ascertain the hydrogel's mechanical characteristics, such as stiffness, and self-healing, determining these properties for different ratios and concentrations of both gel components. The incorporation of disulfide bonds in the hydrogel is proved by conducting degradation experiments in reductive environments. Fluorescein isothiocyanate-albumin (FITC-BSA) and vancomycin both are loaded into the gel, and the guest release kinetics is assessed for both slow and on-demand releases. Finally, the in vitro and in vivo experiments prove that the vancomycin-loaded hydrogel acts as an antibacterial barrier for wound dressing and accelerates the healing of infectious wounds in a mouse model.

8.
Antibiotics (Basel) ; 13(7)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-39061271

RESUMEN

Yokenella regensburgei is a Gram-negative rod part of the Enterobacteriaceae family (order Enterobacterales) and a rare cause of human infections. Although improved diagnostic methods have led to an increase in reports of this elusive pathogen, information remains limited. In order to provide a better understanding of this bacterium, we developed the first comprehensive review of its biology, biochemical profile, antimicrobial resistance pattern, virulence factors, natural reservoir and involvement in various veterinary and human infections. Human infections with this bacterium are scarcely reported, most probably due to constraints regarding its identification and biochemical similarities to Hafnia alvei. Multiple systematic searches revealed 23 cases of human infection, with a seemingly worldwide distribution, mostly in middle-aged or elderly male patients, often associated with immunosuppression. To date, Y. regensburgei has been reported in skin and soft tissue infections, bacteremia and sepsis, osteoarticular infections and in others such as urinary tract and digestive infections. The unique ability of Y. regensburgei to degrade polystyrene presents a novel and promising avenue for addressing plastic pollution in the near future. However, large-scale applications of this bacterium will undoubtedly increase human exposure, highlighting the necessity for comprehensive research into its role in human and veterinary infections, pathogenicity and antibiotic resistance.

9.
Mycoses ; 67(7): e13768, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39036952

RESUMEN

BACKGROUND: There is a concerning rise in antifungal-resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene. OBJECTIVES: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States. METHODS: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18-month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real-time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His). RESULTS: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution. CONCLUSION: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk.


Asunto(s)
Antifúngicos , Arthrodermataceae , Farmacorresistencia Fúngica , Onicomicosis , Escualeno-Monooxigenasa , Terbinafina , Humanos , Onicomicosis/microbiología , Onicomicosis/epidemiología , Onicomicosis/tratamiento farmacológico , Escualeno-Monooxigenasa/genética , Femenino , Persona de Mediana Edad , Masculino , Terbinafina/farmacología , Terbinafina/uso terapéutico , Farmacorresistencia Fúngica/genética , Estados Unidos/epidemiología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Estudios Longitudinales , Anciano , Arthrodermataceae/genética , Arthrodermataceae/efectos de los fármacos , Adulto , Mutación , Estudios de Cohortes , Trichophyton/genética , Trichophyton/efectos de los fármacos , Adulto Joven , Prevalencia , Mutación Puntual , Anciano de 80 o más Años , Adolescente , Uñas/microbiología
10.
Front Pharmacol ; 15: 1397602, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38910882

RESUMEN

Drug repurposing (repositioning) is a dynamically-developing area in the search for effective therapy of infectious diseases. Repositioning existing drugs with a well-known pharmacological and toxicological profile is an attractive method for quickly discovering new therapeutic indications. The off-label use of drugs for infectious diseases requires much less capital and time, and can hasten progress in the development of new antimicrobial drugs, including antibiotics. The use of drug repositioning in searching for new therapeutic options has brought promising results for many viral infectious diseases, such as Ebola, ZIKA, Dengue, and HCV. This review describes the most favorable results for repositioned drugs for the treatment of bacterial infections. It comprises publications from various databases including PubMed and Web of Science published from 2015 to 2023. The following search keywords/strings were used: drug repositioning and/or repurposing and/or antibacterial activity and/or infectious diseases. Treatment options for infections caused by multidrug-resistant bacteria were taken into account, including methicillin-resistant staphylococci, multidrug-resistant Mycobacterium tuberculosis, or carbapenem-resistant bacteria from the Enterobacteriaceae family. It analyses the safety profiles of the included drugs and their synergistic combinations with antibiotics and discusses the potential of antibacterial drugs with antiparasitic, anticancer, antipsychotic effects, and those used in metabolic diseases. Drug repositioning may be an effective response to public health threats related to the spread of multidrug-resistant bacterial strains and the growing antibiotic resistance of microorganisms.

11.
Iran J Microbiol ; 16(2): 159-165, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38854976

RESUMEN

Background and Objectives: Over the last decade, hospital-acquired infections, particularly in the critical care setting, have become more common, with Gram-negative bacterial infections having the highest prevalence. This study aims to determine the prevalence and antibiotic susceptibility pattern of Pseudomonas species to WHO's, aware class of antibiotics, which are commonly prescribed across various ICU's, medical and surgical wards of our tertiary care teaching hospital. Materials and Methods: This prospective study conducted from January 2021 to June 2022 at a tertiary care centre of central India identified Pseudomonas species from clinical samples using standard procedures and antimicrobial susceptibility testing performed as per Clinical Laboratory Standards Institute (CLSI) guidelines (M100; 32th Edition). Results: A total of 1490 non duplicate Pseudomonas species isolates were grown from 21,019 culture positive clinical samples, of which 1247 were Pseudomonas aeruginosa. Out of these 1247 Pseudomonas aeruginosa 384 were MDR (30.7%). Pseudomonas aeruginosa were most commonly isolated from the pus samples (85%). ICU isolates were significantly more resistant to antibiotics than those from other units. P. aeruginosa strains from ICUs showed the highest rates of resistance to ceftazidime (93.9%). Reserve drug colistin showed good susceptibility (98.2%). All the 18 colistin resistant strains were found to be negative for plasmid mediated mcr-1,2,3 genes. Conclusion: The study shall help to generate and disseminate the data so that proper antibiotic policy can be made for judicious use of Access, Watch and Reserve antibiotics and antibiotic de-escalation plan can be put forth.

12.
J Med Microbiol ; 73(6)2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38922673

RESUMEN

Introduction. Fluoroquinolone prophylaxis during haematopoietic cell transplantation (HCT) can lead to antimicrobial resistance (AMR). Identifying the groups of patients that have the highest likelihood of benefiting from prophylactic antimicrobials is important for antimicrobial stewardship (AMS).Hypothesis. We aimed to identify groups of HCT recipients that have the highest likelihood of benefiting from prophylactic fluroquinolones.Methods. All admissions for HCT in a tertiary centre between January 2020 and December 2022 (N = 400) were retrospectively studied. Allogeneic HCT (allo-HCT) recipients had prophylaxis with ciprofloxacin during the chemotherapy-induced neutropenia, while autologous HCT (auto-HCT) recipients did not. Bacteraemias were recorded when non-contaminant bacterial pathogens were isolated in blood cultures.Results. Allo-HCT was performed for 43.3 % (173/400) of patients and auto-HCT was performed for 56.7 % (227/400). A bacteraemia was documented in 28.3 % (113/400) of cases. Allo-HCT recipients were more likely to have a Gram-positive bacteraemia (20.8%, 36/173, vs 10.1%, 23/227, P = 0.03), while a difference was not observed for Gram-negative bacteraemias (18.5%, 32/173 vs 18.1%, 41/227, P = 0.91). Among auto-HCT recipients not receiving ciprofloxacin prophylaxis, patients with germ cell tumours had the highest probability (P for trend 0.09) of recording any bacteraemia (43.5%, 10/23) followed by patients with lymphomas (32.5%, 13/40), other auto-HCT indications (22.2%, 2/9), multiple myeloma (22.1%, 29/131) and multiple sclerosis (12.5%, 3/24). The higher number of bacteraemias in patients with germ cell tumours was primarily driven by Gram-negative pathogens.Conclusions. Ciprofloxacin prophylaxis was associated with a reduced incidence of Gram-negative bacteraemias in allo-HCT recipients. Auto-HCT recipients due to germ cell tumours, not receiving ciprofloxacin prophylaxis, recorded the highest incidence of bacteraemias and represent a possible target group for this intervention.


Asunto(s)
Antibacterianos , Profilaxis Antibiótica , Bacteriemia , Ciprofloxacina , Trasplante de Células Madre Hematopoyéticas , Neoplasias de Células Germinales y Embrionarias , Humanos , Ciprofloxacina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Estudios Retrospectivos , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Persona de Mediana Edad , Femenino , Adulto , Profilaxis Antibiótica/métodos , Antibacterianos/uso terapéutico , Bacteriemia/prevención & control , Bacteriemia/microbiología , Anciano , Adulto Joven , Neutropenia/complicaciones , Programas de Optimización del Uso de los Antimicrobianos , Adolescente
13.
Front Microbiol ; 15: 1341878, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38860217

RESUMEN

Background: Vaginitis is a common infection in women, with approximately 75% of women experiencing at least one episode during their lifetime. Although antimicrobial agents are widely used to treat vaginitis, recurrent vaginitis occurs in some patients. Resistance to these agents is the major cause of recurrent vaginitis. Therefore, there is an urgent need to develop novel drugs. Methods: We investigated the efficacy of a new biological bacteriostatic agent (BBA), composed of lysozyme, phytoalexin, chitosan oligosaccharide, sinensetin, 18ß/20α-glycyrrhizin, and betaine, against vaginitis using in vitro and in vivo studies. First, we evaluated the antibacterial effects of BBA against 13 microbial strains commonly present in aerobic vaginitis, bacterial vaginosis, vulvovaginal candidiasis, and healthy vaginas. Second, we assessed the safety of various doses of BBA administered orally for 4 weeks in female mice. Third, we examined the in vivo anti-proliferative and anti-inflammatory effects of BBA in Candida albicans-, Candida glabrata-, and Gardnerella-induced vaginitis models. Finally, we evaluated the anti-vaginitis effect of a BBA gel prepared with 0.5% (w/v) ammonium acryloyldimethyltaurate/Vp copolymer. Results: BBA effectively suppressed the growth of the main causative pathogens of vaginitis in vitro. BBA, either undiluted or diluted two-fold, inhibited all microorganisms cultured for 8 h. No obvious organ damage was detected when BBA was administered to mice. Both BBA alone and 70% BBA in a gel formulation effectively inhibited the proliferation of C. albicans, C. glabrata, and Gardnerella in vaginal lavage samples and alleviated tissue inflammation in mice with vaginitis. The 70% BBA gel performed better than BBA alone at treating vaginitis in mice infected with Gardnerella vaginalis. Conclusion: BBA alone and a 70% BBA gel inhibited the growth of pathogens and effectively alleviated inflammation caused by C. albicans, C. glabrata, and G. vaginalis.

14.
Expert Rev Anti Infect Ther ; : 1-14, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38922636

RESUMEN

INTRODUCTION: Non-typhoidal Salmonella (NTS) bacteremia is common in sub-Saharan Africa. We examined the prevalence of antibiotic resistance to fluoroquinolones, third-generation cephalosporins, and multi-drug resistance (MDR) in NTS human isolates from sub-Saharan Africa. METHODS: A systematic review was conducted using a search in Ovid Medline, Embase, and African Index Medicus of publications between 2000 and 2021. A random-effects model meta-analysis was performed using data from 66 studies that included 29,039 NTS blood and 1,065 stool isolates. RESULTS: The pooled prevalence proportions of MDR were 0.685 (95% CI 0.574-0.778) and 0.214 (0.020-0.785) in blood vs. stool isolates. The corresponding estimates of fluoroquinolones resistance were 0.014 (0.008-0.025) vs. 0.021 (0.012-0.036) and third-generation cephalosporins resistance 0.019 (0.012-0.031) vs. 0.035 (0.006-0.185). Similar results were found for children and adults. Resistance prevalence to these antibiotics in blood isolates increased between 2000-2010 and 2011-2021. The guidelines employed to determine antimicrobial resistance and epidemiological characteristics (e.g. sample size, study duration) correlated with the resistance prevalence. CONCLUSIONS: The prevalence of MDR and resistance to fluoroquinolones and third-generation cephalosporins in NTS in sub-Saharan Africa is alarming. EXPERT OPINION: Standardized surveillance of antimicrobial drug resistance in NTS in sub-Saharan Africa is warranted to guide healthcare policymaking and antibiotic stewardship programs.


Non-typhoidal Salmonella (NTS) usually causes diarrheal disease, but some patients might develop bloodstream infection. The occurrence and case fatality of bloodstream infections caused by NTS are high in sub-Saharan Africa. However, the information on antibiotic resistance of these bacteria in this region is scarce. We performed a systematic review and meta-analysis to examine the prevalence of multi-drug resistance (MDR) and resistance to antibiotics used to treat NTS bloodstream infection: fluoroquinolones and third-generation cephalosporins in NTS isolates from patients from sub-Saharan Africa.We used data from 66 studies. In NTS blood isolates, the combined prevalence was 1.4% for fluoroquinolones resistance, 1.9% for resistance to third-generation cephalosporins, and 68.5% for MDR. These estimates were 2.1%, 3.5%, and 21.4% in stool isolates. The prevalence of resistance to fluoroquinolones and third-generation cephalosporins in blood isolates has increased in the past 2 decades. The guidelines employed to determine antimicrobial resistance and the study epidemiological characteristics were related to the resistance prevalence.The high prevalence of MDR in NTS raises concerns, and the emergence of resistance to fluoroquinolones and third-generation cephalosporins is worrisome. Strengthening the monitoring of antimicrobial drug resistance in NTS is essential to guide patients' care and policymaking in sub-Saharan Africa.

15.
Sci Rep ; 14(1): 14660, 2024 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918410

RESUMEN

The emergence of drug-resistant Mycobacterium tuberculosis strains is a threat to global health necessitating the discovery of novel chemotherapeutic agents. Natural products drug discovery, which previously led to the discovery of rifamycins, is a valuable approach in this endeavor. Against this backdrop, we set out to investigate the in vitro antimycobacterial properties of medicinal plants from Ghana and South Africa, evaluating 36 extracts and their 252 corresponding solid phase extraction (SPE) generated fractions primarily against the non-pathogenic Mycobacterium smegmatis and Mycobacterium aurum species. The most potent fraction was further evaluated in vitro against infectious M. tuberculosis strain. Crinum asiaticum (bulb) (Amaryllidaceae) emerged as the most potent plant species with specific fractions showing exceptional, near equipotent activity against the non-pathogenic Mycobacterium species (0.39 µg/ml ≤ MIC ≤ 25 µg/ml) with one fraction being moderately active (MIC = 32.6 µg/ml) against M. tuberculosis. Metabolomic analysis led to the identification of eight compounds predicted to be active against M. smegmatis and M. aurum. In conclusion, from our comprehensive study, we generated data which provided an insight into the antimycobacterial properties of Ghanaian and South African plants. Future work will be focused on the isolation and evaluation of the compounds predicted to be active.


Asunto(s)
Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Extractos Vegetales , Plantas Medicinales , Plantas Medicinales/química , Sudáfrica , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ghana , Mycobacterium tuberculosis/efectos de los fármacos , Antituberculosos/farmacología , Antituberculosos/química , Mycobacterium/efectos de los fármacos , Mycobacterium smegmatis/efectos de los fármacos , Humanos , Antibacterianos/farmacología , Antibacterianos/química
17.
Am J Infect Control ; 52(9): 1035-1042, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38692307

RESUMEN

BACKGROUND: Understanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step toward informing better infection prevention and control practices and improving public health response. METHODS: Active, population-based surveillance was conducted for CRAB in 9 U.S. sites from January 1 to December 31, 2019. Medical records were reviewed, isolates were collected and characterized including antimicrobial susceptibility testing and whole genome sequencing. RESULTS: Among 136 incident cases in 2019, 66 isolates were collected and characterized; 56.5% were from cases who were male, 54.5% were from persons of Black or African American race with non-Hispanic ethnicity, and the median age was 63.5 years. Most isolates, 77.2%, were isolated from urine, and 50.0% were collected in the outpatient setting; 72.7% of isolates harbored an acquired carbapenemase gene (aCP), predominantly blaOXA-23 or blaOXA-24/40; however, an isolate with blaNDM was identified. The antimicrobial agent with the most in vitro activity was cefiderocol (96.9% of isolates were susceptible). CONCLUSIONS: Our surveillance found that CRAB isolates in the U.S. commonly harbor an aCP, have an antimicrobial susceptibility profile that is defined as difficult-to-treat resistance, and epidemiologically are similar regardless of the presence of an aCP.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Carbapenémicos , Pruebas de Sensibilidad Microbiana , Humanos , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/genética , Acinetobacter baumannii/aislamiento & purificación , Estados Unidos/epidemiología , Infecciones por Acinetobacter/epidemiología , Infecciones por Acinetobacter/microbiología , Masculino , Carbapenémicos/farmacología , Persona de Mediana Edad , Anciano , Femenino , Antibacterianos/farmacología , Adulto , Anciano de 80 o más Años , Secuenciación Completa del Genoma , beta-Lactamasas/genética , Enfermedades Transmisibles Emergentes/microbiología , Enfermedades Transmisibles Emergentes/epidemiología , Adulto Joven , Proteínas Bacterianas/genética
18.
Surg Infect (Larchmt) ; 25(4): 272-290, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38700753

RESUMEN

Background: Improvements in liver transplant (LT) outcomes are attributed to advances in surgical techniques, use of potent immunosuppressants, and rigorous pre-LT testing. Despite these improvements, post-LT infections remain the most common complication in this population. Bacteria constitute the most common infectious agents, while fungal and viral infections are also frequently encountered. Multi-drug-resistant bacterial infections develop because of polymicrobial overuse and prolonged hospital stays. Immediate post-LT infections are commonly caused by viruses. Conclusions: Appropriate vaccination, screening of both donor and recipients before LT and antiviral prophylaxis in high-risk individuals are recommended. Antimicrobial drug resistance is common in high-risk LT and associated with poor outcomes; epidemiology and management of these cases is discussed. Additionally, we also discuss the effect of coronavirus disease 2019 (COVID-19) infection and monkeypox in the LT population.


Asunto(s)
COVID-19 , Trasplante de Hígado , Receptores de Trasplantes , Humanos , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/prevención & control , COVID-19/epidemiología , Trasplante de Hígado/efectos adversos , Micosis/epidemiología , Micosis/tratamiento farmacológico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , SARS-CoV-2 , Virosis/epidemiología , Virosis/prevención & control
19.
Heliyon ; 10(8): e29421, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38660263

RESUMEN

Malassezia globosa, a lipophilic pathogen, is known to be involved in various chronic skin diseases. Unfortunately, the available treatments have unwanted side effects and microbial drug resistance is evolving. As the antimicrobial activity of propolis is outstanding, this study aimed to examine the potential of propolis from the stingless bee Geniotrigona thoracica against the yeast. Anti-M. globosa growth activity was ascertained in agar well diffusion and broth microdilution assays and the inhibitory concentration value at 50 % (IC50) was determined. Since the yeast cannot synthesize its own fatty acids, extracellular lipase is important for its survival. Here, anti-M. globosa extracellular lipase activity was additionally investigated by colorimetric and agar-based methods. Compared to the crude hexane and crude dichloromethane extracts, the crude methanol partitioned extract (CMPE) exhibited the best anti-M. globosa growth activity with an IC50 of 1.22 mg/mL. After CMPE was further enriched by silica gel column chromatography, fraction CMPE1 (IC50 of 0.98 mM or 184.93 µg/mL) presented the highest activity and was later identified as methyl gallate (MG) by nuclear magnetic resonance analysis. Subsequently, MG was successfully synthesized and shown to have a similar activity, and a minimal fungicidal concentration of 43.44 mM or 8.00 mg/mL. However, lipase assay analysis suggested that extracellular lipase might not be the main target mechanism of MG. This is the first report of MG as a new anti-Malassezia compound. It could be a good candidate for further developing alternative therapeutic agents.

20.
Iran J Microbiol ; 16(1): 56-61, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38682051

RESUMEN

Background and Objectives: Antimicrobial resistance has emerged as a significant global health threat. Infections caused by Multi Drug-Resistant (MDR) bacteria pose formidable challenges in terms of treatment options and patient outcomes. Pus cultures serve as crucial diagnostic tools in identifying the agents responsible for various infections, and their antimicrobial susceptibility patterns which help in establishment of empirical therapy guidelines. This study was conducted to determine the pathogen and its susceptibility pattern from pus cultures and to generate antibiogram in our tertiary care setting. Materials and Methods: It was a cross-sectional study, conducted for a period of six months, from July 2022 to December 2022, in the Pathology Department of Pakistan Institute of Medical Sciences (PIMS). Results: Out of total 2507 samples received, 1242 (49.5%) showed positive culture. Among the 1242 positive samples, 364 were Gram positive cocci (GPCs) and 878 were Gram negative rods (GNRs). Methicillin resistant Staphylococcus aureus (MRSA) was the most common isolate (23%) followed by Klebsiella pneumoniae (22.6%), Pseudomonas aeruginosa (16.9%), Enterobacter spp. (15.5%) and Escherichia coli (14.2%). Vancomycin was found to be highly effective (100%) against MRSA. GPCs were highly susceptible to linezolid (98%) while GNRs showed high level of sensitivity to colistin (96%) and tigecycline (92%). Conclusion: The generation of a local antibiogram specific to the hospital setting is essential to effectively manage infections empirically and preserve the efficacy of existing antibiotics. By implementing antimicrobial stewardship practices based on a better understanding of antibiotic susceptibility patterns, we can contribute to the mitigation of antibiotic resistance and improve patient outcomes.

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