Nanoparticles combined with cefixime as an effective synergistic strategy against Salmonella enterica typhi.

Enteric fever caused by Salmonella typhi has been the most crucial health issue in rural people, especially in Southeast Asia and Africa. Another disease, Salmonellosis, caused by a large group of bacteria of the genus Salmonella, cause substantial economic loss resulting from mortality and morbidity. Higher concentration and repeated use of antibiotics to treat these diseases will likely develop antibiotic resistance among the microbes. The nanoparticle has good penetration power and can kill microbes. Combining two strategies by using nanoparticles with antibiotics kills microbes and reduces the chances of the development of antibiotics resistance. Silver, Nickel, Copper, and Zinc oxide Nanoparticles were chemically synthesized and characterized in this study. Silver nanoparticles at a concentration of 10 µg/ml inhibit all the strains under study. In comparison, silver nanoparticles (16.90 µg/ml), Nickel nanoparticles (83 µg ml-1), Copper nanoparticles (249 µg ml-1), and Zinc oxide (1614 µg ml-1) along with 50 µg/ml cefixime gave maximum zone of inhibition of 35 mm, 19 mm, 31 mm and 23 mm respectively. The antimicrobial assay showed that silver nanoparticles presented good antibacterial performance against all multi-drug-resistant pathogenic Salmonella sp alone as well as in combinations. The present study proved that silver nanoparticles at the lowest concentration along with cefixime could be a possible alternative to control the multi-drug-resistant pathogens.

Susceptibilidad a la ciprofloxacina en Salmonella enterica serotipo Typhi, no multidrogorresistente, 2017 a 2020 / Susceptibility to ciprofloxacin in Salmonella enterica serotype Typhi, no multidrug resistant, 2017 to 2020

Introducción. Los patrones de susceptibilidad antimicrobiana de Salmonella enterica serotipo Typhi se han modificado globalmente durante las últimas tres décadas. Objetivo. Describir los patrones de susceptibilidad antimicrobiana de las cepas de Salmonella enterica Typhi, aisladas en El Salvador de enero 2017 a junio 2020. Metodología. Evaluación secundaria de las bases de datos del Laboratorio Nacional de Salud Pública, de los aislamientos de Salmonella enterica Typhi con sus respectivos antibiogramas, de muestras de pacientes que adolecieron de fiebre tifoidea en El Salvador, de enero 2017 a junio 2020. Resultados. 1406 aislamientos de Salmonella enterica Typhi fueron reportados. El 100 % de los aislamientos analizados presentó susceptibilidad a la ceftriaxona y a la azitromicina. El 99,9 % de los aislamientos analizados presentó susceptibilidad a la ampicilina, al cloranfenicol, a la tetraciclina y al trimetoprim-sulfametoxazol. Para ciprofloxacina, se detectó susceptibilidad en el 8,5% de las cepas analizadas, susceptibilidad intermedia en el 91,5% y resistencia en el 0,08 %. Conclusión. Los hallazgos son compatibles con lo reportado a nivel mundial: el desarrollo rápido de susceptibilidad intermedia o resistencia a la ciprofloxacina, una vez esta es adoptada como el tratamiento de elección para la fiebre tifoidea. En El Salvador, los antibióticos antes considerados como de primera línea contra Salmonella enterica Typhi, deben ser reciclados

Introduction. The antimicrobial susceptibility patterns of Salmonella enterica serotype Typhi have been modified globally for the past three decades. Target. Describe the antimicrobial susceptibility patterns of Salmonella enterica Typhi strains, isolated in El Salvador from January 2017 to June 2020. Methodology. Secondary assessment from the databases of the National Public Health Laboratory, of the isolates of Salmonella enterica Typhi with their respective antibiograms, of samples of patients who suffered from typhoid fever in El Salvador, from January 2017 to June 2020. Results. 1406 isolates of Salmonella enterica Typhi were reported. 100% of the isolations analyzed showed susceptibility to ceftriaxone and azithromycin. 99.9% of the isolates analyzed presented susceptibility to ampicillin, chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole. For ciprofloxacin, detected susceptibility in 8.5% of the strains analyzed, intermediate susceptibility in 91.5% and resistance in the 0.08%. Conclution. The findings are consistent with what has been reported worldwide: the rapid development of susceptibility intermediate or resistance to ciprofloxacin, once it is adopted as the treatment of choice for typhoid fever. In El Salvador, antibiotics previously considered first-line against Salmonella enterica Typhi, must be recycled

Antimicrobial Susceptibility Pattern of Salmonella spp. Isolated from Enteric Fever Patients in Nepal.

INTRODUCTION: Enteric fever, a systemic infection caused by Salmonella enterica Typhi and S. enterica Paratyphi is one of the most common infections in developing countries such as Nepal. Aside from irrational practices of antibiotic use, mutations in chromosomal genes encoding DNA gyrase and Topoisomerase IV and by plasmid mediated quinolone resistant (PMQR) genes are suggested mechanisms for the development of resistance to nalidixic acid and reduced susceptibility to ciprofloxacin. Regardless of high endemicity of enteric fever in Nepal, there is paucity of studies on prevalence and drug-resistance of the pathogen. Therefore, this study aimed to assess the antibiotic susceptibility pattern of Salmonella isolates and determine the minimum inhibitory concentration of ciprofloxacin. METHODS: A total of 1298 blood samples were obtained from patients with suspected enteric fever, attending Sukraraj Tropical and Infectious Disease Hospital (STIDH) during March-August, 2019. Blood samples were inoculated immediately into BACTEC culture bottles and further processed for isolation and identification of Salmonella Typhi and S. Paratyphi. Axenic cultures of the isolates were further subjected to antimicrobial susceptibility testing (AST) by using the modified Kirby-Bauer disc diffusion method based on the guidelines by CLSI. The minimum inhibitory concentration (MIC) of ciprofloxacin was determined by agar-dilution method. RESULTS: Out of 1298 blood cultures, 40 (3.1%) were positive for Salmonella spp. among which 29 (72.5%) isolates were S. Typhi and 11 (27.5%) isolates were S. Paratyphi A. In AST, 12.5% (5/40), 15% (6/40) and 20% (8/40) of the Salmonella isolates were susceptible to nalidixic acid, ofloxacin and levofloxacin, respectively, whereas none of the isolates were susceptible to ciprofloxacin. The MIC value for ciprofloxacin ranged from 0.06-16 µg/mL in which, respectively, 5% (2/40) and 52.5% (21/40) of the isolates were susceptible and resistant to ciprofloxacin. None of the isolates showed multidrug-resistance (MDR) in this study. CONCLUSION: This study showed high prevalence of quinolone-resistant Salmonella spp., while there was marked re-emergence of susceptibilities to traditional first option drugs. Hence, conventional first-line-drugs and third-generation cephalosporins may find potential usage as the empirical drugs for enteric fever. Although our reporting was free of MDR strains, extensive surveillance, augmentation of diagnostic facilities and treatment protocol aided by AST report are recommended for addressing the escalating drug-resistance in the country.

Anti quorum sensing and anti virulence activity of tannic acid and it's potential to breach resistance in Salmonella enterica Typhi / Paratyphi A clinical isolates.

Salmonella enterica Typhi and Paratyphi A are food borne pathogens causing typhoid, which is one of the most important food borne disease in the developing world. S. Typhi and S. Paratyphi A are of much concern as multi drug resistance has been on the rise. The current study is aimed to screen phytochemicals for anti quorum sensing (QS) activity against S. Typhi and S. Paratyphi A. Upon screening with swarming assay, tannic acid (TA) showed highest anti-QS activity with minimal concentration of 400µg/ml. The anti-QS activity of TA was confirmed with C. violaceum ATCC 12,472. TA showed 38-43% and 35-50% of inhibition in cell surface hydrophobicity and EPS production respectively. Through FTIR analysis, it has been observed that EPS of treated cells has a considerable change in protein and peptide. TA has also exhibited drastic reduction in the surfactant production as high as 85-90%. Blood sensitivity and antibiotic sensitivity assay revealed that TA significantly sensitizes the S. Typhi and S. Paratyphi A cells to immune components in human blood and antibiotics. It has reduced the resistance of S. Typhi and S. Paratyphi A cells against amikacin, ampicillin, ciprofloxacin, azithromycin, chloramphenicol and gentamycin, thus revitalized the usage of these antibiotics against drug resistant S. Typhi and S. Paratyphi A infections. The consistency of anti-QS potential of TA was further evaluated and established with another eight clinical isolates of S. Typhi and S. Paratyphi A. Thus TA has been proved as a promising anti QS agent that can be developed as a therapeutic combination against S. Typhi and S. Paratyphi A.

Salmonella Typhi Bactericidal Antibodies Reduce Disease Severity but Do Not Protect against Typhoid Fever in a Controlled Human Infection Model.

Effective vaccines against Salmonella Typhi, a major cause of febrile illness in tropical regions, can have a significant effect as a disease control measure. Earlier work has shown that immunization with either of two Salmonella Typhi vaccines, licensed Ty21a or candidate M01ZH09, did not provide full immunity in a controlled human infection model. Here, we describe the human humoral immune responses to these oral vaccines and their functional role in protection after challenge with S. Typhi. Serum, obtained from healthy volunteers before and after vaccination with Ty21a or M01ZH09 or placebo and before and after oral challenge with wild-type S. Typhi, was assessed for bactericidal activity. Single-dose vaccination with M01ZH09 induced an increase in serum bactericidal antibodies (p = 0.001) while three doses of Ty21a did not. No association between bactericidal activity and protection against typhoid after challenge was seen in either vaccine arm. Bactericidal activity after vaccination correlated significantly with delayed disease onset (p = 0.013), lower bacterial burden (p = 0.006), and decreased disease severity scores (p = 0.021). Depletion of antibodies directed against lipopolysaccharide significantly reduced bactericidal activity (p = 0.009). We conclude that antibodies induced after ingestion of oral live-attenuated typhoid vaccines or after challenge with wild-type S. Typhi exhibit bactericidal activity. This bactericidal activity is mediated by anti-O:LPS antibodies and significantly reduces clinical symptoms but does not provide sterile immunity. This directs future vaccine studies toward other antigens or mechanisms of protection against typhoid.

Infectious diseases in humanized mice.

Despite many theoretical incompatibilities between mouse and human cells, mice with reconstituted human immune system components contain nearly all human leukocyte populations. Accordingly, several human-tropic pathogens have been investigated in these in vivo models of the human immune system, including viruses such as human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV), as well as bacteria such as Mycobacterium tuberculosis and Salmonella enterica Typhi. While these studies initially aimed to establish similarities in the pathogenesis of infections between these models and the pathobiology in patients, recent investigations have provided new and interesting functional insights into the protective value of certain immune compartments and altered pathology upon mutant pathogen infections. As more tools and methodologies are developed to make these models more versatile to study human immune responses in vivo, such improvements build toward small animal models with human immune components, which could predict immune responses to therapies and vaccination in human patients.