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1.
BMC Pediatr ; 24(1): 311, 2024 May 06.
Article En | MEDLINE | ID: mdl-38711011

BACKGROUND: Diarrhea caused by Salmonella and Shigella species are the leading cause of illness especially in developing countries. These infections are considered as the main public health problems in children, including Ethiopia. This study aimed to assess the prevalence, associated factors, and antimicrobial susceptibility patterns of Salmonella and Shigella species in Sheik Hassan Yabere Referral Hospital Jigjiga, Eastern Ethiopia from August 05 to November 15, 2022. METHOD: A cross-sectional study was conducted among 239 under-five children with diarrhea selected through a convenient sampling technique. A structured questionnaire was used to collect associated factors. A stool sample was collected and processed for the identification of Salmonella and Shigella species using MacConkey adar, Xylose Lysine Deoxycholate agar (Oxoid Ltd) and Biochemical tests. The antimicrobial susceptibility pattern of isolates was performed using the Kirby-Bauer disc diffusion technique. The data was entered into Epi-data version 4.6 and exported to the statistical package of social science version 22 for analysis. The association between outcome and independent variables was assessed using bivariate, multivariable, and chi-square and P-value < 0.05 was considered as statistical significance. RESULT: Overall prevalence of Salmonella and Shigella species was 6.3% (95% CI, 5.7-6.9%), of which 3.8% (95 CI, 3.2-4.4%) were Salmonella species and 2.5% (95% CI, 1.95-3%) were Shigella species. Unimproved water source (AOR = 5.08, 95% CI = 1.45, 17.25), open field (AOR = 2.3, 95% CI = 1.3, 5.03), rural residence (AOR = 1.8, 95% CI = 1.4, 7.5), Hand-washing practice (p = 0.001), and raw meat consumption (p = 0.002) were associated with occurrence of Salmonella and Shigella species. Salmonella and Shigella isolates were resistant to Ampicilin (100%). However, Salmonella isolates was sensitive to Norfloxacin (100%). About 22.2% and 16.7% of Salmonella and Shigella isolates were multi-drug resistant, respectively. CONCLUSION: Prevalence of Salmonella and Shigella species were lower than most studies done in Ethiopia. Hand-washing habit, water source type, Open field waste disposal habit, raw meat consumption and rural residence were associated with Salmonellosis and shigellosis. All isolated Salmonella were sensitive to norfloxacin. The evidence from this study underscores the need for improved water, sanitation and hygiene (WASH) system and the imperative to implement drug susceptibility tests for the treatment of Salmonella and Shigella infection.


Diarrhea , Dysentery, Bacillary , Microbial Sensitivity Tests , Salmonella , Shigella , Humans , Ethiopia/epidemiology , Cross-Sectional Studies , Child, Preschool , Female , Salmonella/isolation & purification , Salmonella/drug effects , Male , Prevalence , Shigella/drug effects , Shigella/isolation & purification , Infant , Diarrhea/microbiology , Diarrhea/epidemiology , Dysentery, Bacillary/epidemiology , Dysentery, Bacillary/microbiology , Dysentery, Bacillary/drug therapy , Salmonella Infections/epidemiology , Salmonella Infections/microbiology , Salmonella Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Risk Factors , Feces/microbiology , Drug Resistance, Bacterial
2.
Biomed Res Int ; 2024: 5554208, 2024.
Article En | MEDLINE | ID: mdl-38595330

Shigella stands as a major contributor to bacterial dysentery worldwide scale, particularly in developing countries with inadequate sanitation and hygiene. The emergence of multidrug-resistant strains exacerbates the challenge of treating Shigella infections, particularly in regions where access to healthcare and alternative antibiotics is limited. Therefore, investigations on how bacteria evade antibiotics and eventually develop resistance could open new avenues for research to develop novel therapeutics. The aim of this study was to analyze whole genome sequence (WGS) of human pathogenic Shigella spp. to elucidate the antibiotic resistance genes (ARGs) and their mechanism of resistance, gene-drug interactions, protein-protein interactions, and functional pathways to screen potential therapeutic candidate(s). We comprehensively analyzed 45 WGS of Shigella, including S. flexneri (n = 17), S. dysenteriae (n = 14), S. boydii (n = 11), and S. sonnei (n = 13), through different bioinformatics tools. Evolutionary phylogenetic analysis showed three distinct clades among the circulating strains of Shigella worldwide, with less genomic diversity. In this study, 2,146 ARGs were predicted in 45 genomes (average 47.69 ARGs/genome), of which only 91 ARGs were found to be shared across the genomes. Majority of these ARGs conferred their resistance through antibiotic efflux pump (51.0%) followed by antibiotic target alteration (23%) and antibiotic target replacement (18%). We identified 13 hub proteins, of which four proteins (e.g., tolC, acrR, mdtA, and gyrA) were detected as potential hub proteins to be associated with antibiotic efflux pump and target alteration mechanisms. These hub proteins were significantly (p < 0.05) enriched in biological process, molecular function, and cellular components. Therefore, the finding of this study suggests that human pathogenic Shigella strains harbored a wide range of ARGs that confer resistance through antibiotic efflux pumps and antibiotic target modification mechanisms, which must be taken into account to devise and formulate treatment strategy against this pathogen. Moreover, the identified hub proteins could be exploited to design and develop novel therapeutics against MDR pathogens like Shigella.


Dysentery, Bacillary , Shigella , Humans , Phylogeny , Drug Resistance, Bacterial/genetics , Microbial Sensitivity Tests , Shigella/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/genetics , Dysentery, Bacillary/microbiology , Shigella flexneri
4.
Sci Rep ; 14(1): 6947, 2024 03 23.
Article En | MEDLINE | ID: mdl-38521802

Shigellosis remains a common gastrointestinal disease mostly in children < 5 years of age in developing countries. Azithromycin (AZM), a macrolide, is currently the first-line treatment for shigellosis in Bangladesh; ciprofloxacin (CIP) and ceftriaxone (CRO) are also used frequently. We aimed to evaluate the current epidemiology of antimicrobial resistance (AMR) and mechanism(s) of increasing macrolide resistance in Shigella in Bangladesh. A total of 2407 clinical isolates of Shigella from 2009 to 2016 were studied. Over the study period, Shigella sonnei was gradually increasing and become predominant (55%) over Shigella flexneri (36%) by 2016. We used CLSI-guided epidemiological cut-off value (ECV) for AZM in Shigella to set resistance breakpoints (zone-diameter ≤ 15 mm for S. flexneri and ≤ 11 mm for S. sonnei). Between 2009 and 2016, AZM resistance increased from 22% to approximately 60%, CIP resistance increased by 40%, and CRO resistance increased from zero to 15%. The mphA gene was the key macrolide resistance factor in Shigella; a 63MDa conjugative middle-range plasmid was harboring AZM and CRO resistance factors. Our findings show that, especially after 2014, there has been a rapid increase in resistance to the three most effective antibiotics. The rapid spread of macrolide (AZM) resistance genes among Shigella are driven by horizontal gene transfer rather than direct lineage.


Dysentery, Bacillary , Shigella , Child , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/epidemiology , Macrolides/pharmacology , Macrolides/therapeutic use , Drug Resistance, Bacterial/genetics , Azithromycin/pharmacology , Azithromycin/therapeutic use , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Ceftriaxone/pharmacology , Microbial Sensitivity Tests , Protein Synthesis Inhibitors/pharmacology , Plasmids/genetics
5.
Infect Disord Drug Targets ; 24(1): e110823219657, 2024.
Article En | MEDLINE | ID: mdl-37723953

Shigella infection is commonly related to diarrhea and has been a noteworthy source of morbidity and mortality worldwide. There is a wide range of symptoms associated with these contagious microorganisms, from watery diarrhea to fulminant dysentery manifesting with recurrent bloody stools, fever, and prostration. While the mortality rate from Shigellosis has decreased significantly during the past three decades, it remains a principal cause of death in the world. The use of antibiotics in Shigella treatment remarkably lowers the mortality rates and even the prevalence of the infection. However, strains are becoming increasingly resistant, while antibiotics are becoming increasingly ineffective. Shigella species, which were previously susceptible to common antibiotics such as nalidixic acid, co-trimoxazole, chloramphenicol, and ampicillin, have become resistant to cephalosporins, fluoroquinolones and macrolides like azithromycin. These strains have caused many Shigellosis outbreaks. Men who have had sex with men (MSM) and travelers have contributed to the spreading of multiresistant Shigella strains across continents, which has prompted new antibiotic recommendations. People should be informed about the threat of antimicrobial-resistant bacteria, so a periodic report of antibiotic susceptibility after analysis is essential for antibiotic treatment guidance. The present study provides a brief overview of the pathogenicity of Shigella spp., and the antibiotic resistance patterns of two common Shigella species during the last seven years in Iran were evaluated.


Dysentery, Bacillary , Sexual and Gender Minorities , Shigella , Humans , Male , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/epidemiology , Dysentery, Bacillary/microbiology , Homosexuality, Male , Iran/epidemiology , Drug Resistance, Microbial , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Diarrhea/microbiology , Microbial Sensitivity Tests
6.
BMC Prim Care ; 24(1): 267, 2023 12 13.
Article En | MEDLINE | ID: mdl-38087210

BACKGROUND: Shigellosis is an acute diarrheal disease transmitted through contaminated food, water, objects, poor hand hygiene, or sexual activity. Healthcare providers (HCP) may not be aware of the multiple routes of Shigella transmission, populations at increased risk, or importance of antibiotic susceptibility testing (AST). This study assessed HCP knowledge and clinical practices regarding shigellosis and antibiotic resistance. METHODS: Porter Novelli Public Services administered a web-based survey (Fall DocStyles 2020) to HCP in the United States. Pediatricians, primary care physicians, nurse practitioners, and physician assistants completed questions about knowledge and clinical practice of acute diarrhea and shigellosis. RESULTS: Of 2196 HCP contacted, 1503 responded (68% response rate). Most identified contaminated food (85%) and water (79%) as routes of Shigella transmission; fewer recognized person-to-person contact (40%) and sexual activity (18%). Men who have sex with men (MSM) were identified as being at risk for shigellosis by 35% of respondents. Most reported counseling patients to wash hands (86%) and avoid food preparation (77%) when ill with shigellosis; 29% reported recommending avoiding sex. Many HCP reported treating shigellosis empirically with ciprofloxacin (62%) and azithromycin (32%), and 29% reported using AST to guide treatment. CONCLUSIONS: We identified several gaps in shigellosis knowledge among HCP including MSM as a risk group, person-to-person transmission, and appropriate antibiotic use. Improving HCP education could prevent the spread of shigellosis, including drug-resistant infections, among vulnerable populations.


Anti-Infective Agents , Dysentery, Bacillary , Sexual and Gender Minorities , Shigella , Male , Humans , United States/epidemiology , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/epidemiology , Dysentery, Bacillary/prevention & control , Homosexuality, Male , Anti-Bacterial Agents/therapeutic use , Diarrhea/complications , Diarrhea/drug therapy , Anti-Infective Agents/therapeutic use , Water
7.
Appl Environ Microbiol ; 89(12): e0107423, 2023 12 21.
Article En | MEDLINE | ID: mdl-38032177

IMPORTANCE: Shigella sonnei is a major human enteric pathogen that causes bacillary dysentery. The increasing spread of drug-resistant S. sonnei strains has caused an emergent need for the development of new antimicrobial agents against this pathogenic bacterium. In this study, we demonstrate that Stattic employs two antibacterial mechanisms against S. sonnei. It exerted both anti-virulence activity and bactericidal activity against S. sonnei, suggesting that it shows advantages over traditional antibiotics. Moreover, Stattic showed excellent synergistic effects with kanamycin, ampicillin, chloramphenicol, and gentamicin against S. sonnei. Our findings suggest that Stattic has promising potential for development as a new antibiotic or as an adjuvant to antibiotics for infections caused by S. sonnei.


Dysentery, Bacillary , Shigella , Humans , Shigella sonnei , Anti-Bacterial Agents/pharmacology , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/microbiology , Ampicillin/pharmacology , Microbial Sensitivity Tests
8.
Sci Rep ; 13(1): 16582, 2023 10 03.
Article En | MEDLINE | ID: mdl-37789081

Azithromycin (AZM) resistance among Shigella is a major public health concern. Here, we investigated the epidemiology of Shigella flexneri serotype 1b recovered during 2016-2018 in Ontario, to describe the prevalence and spread of AZM resistance. We found that 72.3% (47/65) of cases were AZM-resistant (AZMR), of which 95.7% (45/47) were among males (P < 0.001). Whole-genome based phylogenetic analysis showed three major clusters, and 56.9% of isolates grouped within a single closely-related cluster (0-10 ∆SNP). A single AZMR clonal population was persistent over 3 years and involved 67.9% (36/53) of all male cases, and none reported international travel. In 2018, a different AZMR cluster appeared among adult males not reporting travel. A proportion of isolates (10.7%) with reduced susceptibility to ciprofloxacin (CIP) due to S83L mutation in gyrA were AZM susceptible, and 71.4% reported international travel. Resistance to AZM was due to the acquisition of mph gene-bearing incFII plasmids having > 95% nucleotide similarity to pKSR100. Plasmid-borne resistance limiting treatment options to AZM, ceftriaxone (CRO) and CIP was noted in a single isolate. We characterized AZMR isolates circulating locally among males and found that genomic analysis can support targeted prevention and mitigation strategies against antimicrobial-resistance.


Azithromycin , Dysentery, Bacillary , Male , Humans , Azithromycin/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Shigella flexneri/genetics , Ontario/epidemiology , Phylogeny , Neisseria gonorrhoeae/genetics , Ciprofloxacin/pharmacology , Whole Genome Sequencing , Microbial Sensitivity Tests , Drug Resistance, Bacterial/genetics , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/epidemiology
9.
mSphere ; 8(5): e0015423, 2023 10 24.
Article En | MEDLINE | ID: mdl-37565760

Shigella flexneri is a facultative intracellular pathogen that causes shigellosis, a human diarrheal disease characterized by the destruction of the colonic epithelium. Novel antimicrobial compounds to treat infections are urgently needed due to the proliferation of bacterial antibiotic resistance and lack of new effective antimicrobials in the market. Our approach to find compounds that block the Shigella virulence pathway has three potential advantages: (i) resistance development should be minimized due to the lack of growth selection pressure, (ii) no resistance due to environmental antibiotic exposure should be developed since the virulence pathways are not activated outside of host infection, and (iii) the normal intestinal microbiota, which do not have the targeted virulence pathways, should be unharmed. We chose to utilize two phenotypic assays, inhibition of Shigella survival in macrophages and Shigella growth inhibition (minimum inhibitory concentration), to interrogate the 1.7 M compound screening collection subset of the GlaxoSmithKline drug discovery chemical library. A number of secondary assays on the hit compounds resulting from the primary screens were conducted, which, in combination with chemical, structural, and physical property analyses, narrowed the final hit list to 44 promising compounds for further drug discovery efforts. The rapid development of antibiotic resistance is a critical problem that has the potential of returning the world to a "pre-antibiotic" type of environment, where millions of people will die from previously treatable infections. One relatively newer approach to minimize the selection pressures for the development of resistance is to target virulence pathways. This is anticipated to eliminate any resistance selection pressure in environmental exposure to virulence-targeted antibiotics and will have the added benefit of not affecting the non-virulent microbiome. This paper describes the development and application of a simple, reproducible, and sensitive assay to interrogate an extensive chemical library in high-throughput screening format for activity against the survival of Shigella flexneri 2457T-nl in THP-1 macrophages. The ability to screen very large numbers of compounds in a reasonable time frame (~1.7 M compounds in ~8 months) distinguishes this assay as a powerful tool in further exploring new compounds with intracellular effect on S. flexneri or other pathogens with similar pathways of pathogenesis. The assay utilizes a luciferase reporter which is extremely rapid, simple, relatively inexpensive, and sensitive and possesses a broad linear range. The assay also utilized THP-1 cells that resemble primary monocytes and macrophages in morphology and differentiation properties. THP-1 cells have advantages over human primary monocytes or macrophages because they are highly plastic and their homogeneous genetic background minimizes the degree of variability in the cell phenotype (1). The intracellular and virulence-targeted selectivity of our methodology, determined via secondary screening, is an enormous advantage. Our main interest focuses on hits that are targeting virulence, and the most promising compounds with adequate physicochemical and drug metabolism and pharmacokinetic (DMPK) properties will be progressed to a suitable in vivo shigellosis model to evaluate the therapeutic potential of this approach. Additionally, compounds that act via a host-directed mechanism could be a promising source for further research given that it would allow a whole new, specific, and controlled approach to the treatment of diseases caused by some pathogenic bacteria.


Dysentery, Bacillary , Shigella , Humans , Shigella flexneri , Virulence/genetics , Dysentery, Bacillary/drug therapy , Small Molecule Libraries/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Macrophages
10.
Emerg Infect Dis ; 29(8): 1708-1711, 2023 08.
Article En | MEDLINE | ID: mdl-37486233

We report extensively drug-resistant (XDR) Shigella sonnei infection in an immunocompromised patient in Texas, USA. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry failed to identify XDR Shigella, but whole-genome sequencing accurately characterized the strain. First-line antimicrobials are not effective against emerging XDR Shigella. Fosfomycin, carbapenems, and tigecycline are potential alternatives.


Anti-Infective Agents , Dysentery, Bacillary , Shigella , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/pharmacology , Dysentery, Bacillary/diagnosis , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/epidemiology , Microbial Sensitivity Tests , Shigella sonnei/genetics , United States/epidemiology
11.
Emerg Infect Dis ; 29(8): 1668-1671, 2023 08.
Article En | MEDLINE | ID: mdl-37486309

Increased invasive bloodstream infections caused by multidrug resistant Shigella sonnei were noted in Vancouver, British Columbia, Canada, during 2021-2023. Whole-genome sequencing revealed clonal transmission of genotype 3.6.1.1.2 (CipR.MSM5) among persons experiencing homelessness. Improvements in identifying Shigella species, expanding treatment options for multidrug resistant infections, and developing public health partnerships are needed.


Bacteremia , Dysentery, Bacillary , Ill-Housed Persons , Shigella , Humans , Shigella sonnei/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , British Columbia/epidemiology , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/epidemiology , Drug Resistance, Multiple, Bacterial/genetics , Bacteremia/drug therapy , Bacteremia/epidemiology , Microbial Sensitivity Tests
12.
Dis Model Mech ; 16(6)2023 06 01.
Article En | MEDLINE | ID: mdl-37161932

Shigella are Gram-negative bacterial pathogens responsible for bacillary dysentery (also called shigellosis). The absence of a licensed vaccine and widespread emergence of antibiotic resistance has led the World Health Organisation (WHO) to highlight Shigella as a priority pathogen requiring urgent attention. Several infection models have been useful to explore the Shigella infection process; yet, we still lack information regarding events taking place in vivo. Here, using a Shigella-zebrafish infection model and high-content microscopy, we developed an automated microscopy workflow to non-invasively study fluorescently labelled bacteria and neutrophils in vivo. We applied our workflow to antibiotic-treated zebrafish, and demonstrate that antibiotics reduce bacterial burden and not neutrophil recruitment to the hindbrain ventricle. We discovered that nalidixic acid (a bactericidal antibiotic) can work with leukocytes in an additive manner to control Shigella flexneri infection and can also restrict dissemination of Shigella sonnei from the hindbrain ventricle. We envision that our automated microscopy workflow, applied here to study the interactions between Shigella and neutrophils as well as antibiotic efficacy in zebrafish, can be useful to innovate treatments for infection control in humans.


Dysentery, Bacillary , Shigella , Humans , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Zebrafish , Microscopy , Workflow , Dysentery, Bacillary/drug therapy
13.
Emerg Infect Dis ; 29(7): 1473-1475, 2023 07.
Article En | MEDLINE | ID: mdl-37204919

In Los Angeles, California, USA, persistent, refractory shigellosis was diagnosed in an immunocompetent man who has sex with men. Whole-genome sequencing augmented phenotypic antimicrobial susceptibility testing to comprehensively profile bacterial drug resistance and appropriately guide therapy and clear the infection.


Dysentery, Bacillary , Shigella , Male , Humans , Shigella flexneri/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Dysentery, Bacillary/diagnosis , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/epidemiology , Drug Resistance, Bacterial , Los Angeles , Microbial Sensitivity Tests
14.
Microb Genom ; 9(4)2023 04.
Article En | MEDLINE | ID: mdl-37022322

In the Netherlands, more than half of domestic shigellosis cases are among men who have sex with men (MSM), particularly in the Amsterdam region. However, there is limited insight into which Shigella strains circulate in the Netherlands. Our objective was to assess the added value of whole-genome sequencing (WGS)-based surveillance for Shigella. To this end, we determined the relatedness among Shigella spp. isolates from patients in the Amsterdam region, as well as in an international context, including antimicrobial resistance markers, using WGS. The following criteria were used: it should provide insight into (1) clustering of shigellosis cases and the affected population, (2) the extent of admixture of MSM-associated isolates with those from the broader population and (3) the presence of antimicrobial resistance. It should then lead to more opportunities for targeted control measures. For this study, Shigella isolates from three laboratories in the Amsterdam region obtained between February 2019 and October 2021 were subjected to Illumina WGS at the National Institute for Public Health and the Environment (RIVM). Raw data were quality-checked and assembled, the Shigella serotype was determined with ShigaTyper, and antimicrobial resistance markers were detected using ResFinder and PointFinder. For Shigella sonnei, subclades were determined using Mykrobe. Relatedness of isolates, including 21 international reference genomes, was assessed with core genome multilocus sequence typing. In total, 109 isolates were included, of which 27 were from females (25 %) and 66 were from males (61 %), with which the majority (n=48, 73 %) being from MSM. No information on sex was available for the remaining 16 cases. The WGS data for all isolates, comprising 55 S. sonnei, 52 Shigella flexneri, 1 Shigella boydii and 1 Shigella dysenteriae, met the quality criteria. In total, 14 clusters containing 51 isolates (49 %) were identified, with a median cluster size of 2.5 cases (range: 2-15). Nine out of 14 clusters were MSM-associated, and 8 clusters (57 %) were travel-related. Six of the MSM clusters were related to international reference genomes. The prevalence of antimicrobial resistance markers was higher among isolates from MSM than non-MSM patients, particularly for ciprofloxacin (89 vs 33 %) and azithromycin (58 vs 17 %). In conclusion, about half of Shigella spp. patients were part of a cluster, of which a substantial part were related to international reference genomes, particularly among MSM, and a high prevalence of antimicrobial resistance markers was found. These findings indicate widespread international circulation of Shigella spp., particularly among MSM, with multidrug resistance that hampers treatment of patients. Moreover, the results of this study led to the implementation of a national WGS-based laboratory surveillance programme for Shigella spp. that started in April 2022.


Anti-Infective Agents , Dysentery, Bacillary , Sexual and Gender Minorities , Shigella , Female , Humans , Male , Drug Resistance, Multiple , Dysentery, Bacillary/epidemiology , Dysentery, Bacillary/drug therapy , Homosexuality, Male , Shigella/genetics , Travel
15.
Molecules ; 28(6)2023 Mar 08.
Article En | MEDLINE | ID: mdl-36985439

Shigellosis is a serious foodborne diarrheal disease caused by the Shigella species. It is a critical global health issue. In developing countries, shigellosis causes most of the mortality in children below 5 years of age. Globally, around 165 million cases of diarrhea caused by Shigella are reported, which accounts for almost 1 million deaths, in which the majority are recorded in Third World nations. In this study, silver nanoparticles were synthesized using Mangifera indica kernel (MK-AgNPs) seed extracts. The biosynthesized M. indica silver nanoparticles (MK-AgNPs) were characterized using an array of spectroscopic and microscopic tools, such as UV-Vis, scanning electron microscopy, particle size analyzer, Fourier transform infrared spectroscopy, and X-ray diffractometer. The nanoparticles were spherical in shape and the average size was found to be 42.7 nm. The MK-AgNPs exhibited remarkable antibacterial activity against antibiotic-resistant clinical Shigella sp. The minimum inhibitory concentration (MIC) value of the MK-AgNPs was found to be 20 µg/mL against the multi-drug-resistant strain Shigella flexneri. The results clearly demonstrate that MK-AgNPs prepared using M. indica kernel seed extract exhibited significant bactericidal action against pathogenic Shigella species. The biosynthesized nanoparticles from mango kernel could possibly prove therapeutically useful and effective in combating the threat of shigellosis after careful investigation of its toxicity and in vivo efficacy.


Dysentery, Bacillary , Mangifera , Metal Nanoparticles , Shigella , Child , Humans , Mangifera/chemistry , Metal Nanoparticles/chemistry , Silver/pharmacology , Silver/chemistry , Dysentery, Bacillary/drug therapy , Plant Extracts/pharmacology , Plant Extracts/chemistry , Microbial Sensitivity Tests , Spectroscopy, Fourier Transform Infrared , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Seeds
16.
Int J Infect Dis ; 132: 1-3, 2023 Jul.
Article En | MEDLINE | ID: mdl-36990199

Clustered outbreaks of multi-drug resistant (MDR) Shigella are on the rise among men who have sex with men (MSM). Identification of MDR sub-lineages is critical for clinical management and public health interventions. Here, we describe a novel MDR sub-lineage of Shigella flexneri isolated from an MSM patient without a travel history in Southern California. Detailed genomic characterization of this novel strain would serve as a reference to aid monitoring and future outbreak investigation of MDR Shigella among MSM.


Dysentery, Bacillary , Sexual and Gender Minorities , Shigella , Male , Humans , Shigella flexneri/genetics , Homosexuality, Male , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/epidemiology , California/epidemiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
17.
Environ Sci Technol ; 57(12): 4971-4983, 2023 03 28.
Article En | MEDLINE | ID: mdl-36929874

Shigella flexneri infection is the main cause of diarrhea in humans worldwide. The emergence of antimicrobial resistance (AMR) of S. flexneri is a growing public health threat worldwide, while large-scale studies monitoring the longitudinal AMR trends of isolates remain scarce. Here, the AMR gene (ARG) profiles of 717 S. flexneri isolates from 1920 to 2020 worldwide were determined. The results showed that the average number of ARGs in isolates has increased significantly, from 19.2 ± 2.4 before 1970 to 29.6 ± 5.3 after 2010. In addition, mobile genetic elements were important contributors to ARGs in S. flexneri isolates. The results of the structural equation model showed that the human development index drove the consumption of antibiotics and indirectly promoted the antibiotic resistance. Finally, a machine learning algorithm was used to predict the antibiotic resistance risk of global terrestrial S. flexneri isolates and successfully map the antibiotic resistance threats in global land habitats with over 80% accuracy. Collectively, this study monitored the longitudinal AMR trends, quantitatively surveilled the health risk of S. flexneri AMR, and provided a theoretical basis for mitigating the threat of antibiotic resistance.


Anti-Bacterial Agents , Dysentery, Bacillary , Humans , Anti-Bacterial Agents/pharmacology , Shigella flexneri/genetics , Drug Resistance, Bacterial/genetics , Microbial Sensitivity Tests , Dysentery, Bacillary/epidemiology , Dysentery, Bacillary/drug therapy
18.
Rev Esp Quimioter ; 36(3): 282-290, 2023 Jun.
Article Es | MEDLINE | ID: mdl-36942425

OBJECTIVE: In the bacterial etiology of severe acute infectious diarrhea, except that caused by Clostridioides difficile, most of them have an invasive character and antibiotic treatment will be necessary in specific situations. Shigella is a classic pathogen, in which it is crucial to know the sensitivity to different classic and alternative antimicrobials. The objective of this work was to analyze the presence of shigellosis and the rate of antibiotic resistance. METHODS: A descriptive-retrospective study of the reports of shigellosis of stool cultures issued between January 2016 and April 2022 was conducted. RESULTS: A total of 34 episodes (16 -47.1%- by Shigella sonnei) were observed, as of 2018. There were only 2 pediatric cases. The overall resistance rate to azithromycin, trimethoprim-sulfamethoxazole and ciprofloxacin was 52.9%, 64.7% and 44.1%, respectively. 26.5% were resistant to the 3 groups of antibiotics. There was a higher rate of resistance for S. sonnei. The emergence of resistance to cephalosporins in recent years stands out. Episodes of multidrug-resistant shigellosis were detected between 2020 (1 by S. flexneri) and 2022 (4 by S. sonnei). CONCLUSIONS: The episodes of shigellosis are emerging in our environment with a higher rate of multi-resistance. In this context, current empirical treatments for acute enteroinvasive enteritis are at risk of failure, if necessary.


Dysentery, Bacillary , Child , Humans , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/epidemiology , Dysentery, Bacillary/microbiology , Retrospective Studies , Spain/epidemiology , Drug Resistance, Bacterial , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Diarrhea/drug therapy , Diarrhea/epidemiology , Emergency Service, Hospital
19.
J Antimicrob Chemother ; 78(4): 975-982, 2023 04 03.
Article En | MEDLINE | ID: mdl-36760088

BACKGROUND: Several countries have recently reported the detection of ESBL-producing Shigella sonnei associated with transmission among MSM. In a previous study by our group, 2.8% of Shigella spp. obtained from MSM in Barcelona between 2015 and 2019 were ESBL producers. OBJECTIVES: To describe and characterize the emerging ESBL-producing Shigella spp. associated with sexual transmission among MSM detected from 2020 to 2021 in Barcelona, elucidating their connectivity with contemporaneous ESBL-producing Shigella spp. from other countries. RESULTS: From 2020 to 2021, we identified that among MSM, 68% of S. sonnei were XDR harbouring blaCTX-M-27 and 14% of Shigella flexneri were MDR harbouring blaCTX-M-27. WGS analysis showed that the ESBL-producing S. sonnei were part of a monophyletic cluster, which included isolates responsible for the prolonged outbreak occurring in the UK. Our data also reveal the first emergence and clonal dissemination of ESBL-producing and fluoroquinolone-resistant S. flexneri 2a among MSM. CONCLUSIONS: We report an increasing trend of antimicrobial resistance in Shigella spp. among MSM in Barcelona since 2021, mainly as a consequence of the dissemination of XDR ESBL-producing S. sonnei, previously reported in the UK. These results highlight the importance of international collaborative surveillance of MDR/XDR S. sonnei and S. flexneri for rapid identification of their emergence and the prevention of the transmission of these pathogens.


Dysentery, Bacillary , Sexual and Gender Minorities , Shigella , Male , Humans , Shigella flexneri , Shigella sonnei , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Dysentery, Bacillary/epidemiology , Dysentery, Bacillary/drug therapy , Homosexuality, Male , Drug Resistance, Bacterial , Microbial Sensitivity Tests , Disease Outbreaks
20.
J Clin Microbiol ; 61(3): e0165222, 2023 03 23.
Article En | MEDLINE | ID: mdl-36853032

Fecal culture for isolation and identification of Shigella may take days. The BioFire FilmArray Gastrointestinal (GI) panel (bioMérieux, France) is a PCR-based assay that detects enteric pathogens including Shigella/enteroinvasive Escherichia coli (EIEC) in about an hour. The aim of this study was to evaluate the impact of GI panel detection of Shigella in a pediatric emergency department (ED) during an outbreak. Stool samples from children with acute gastroenteritis were tested by the GI panel. Test results were either withheld in preintervention (PRE) or reported to clinicians/families in the postintervention (POST) period. The impact of the GI panel testing on patient management and outcomes was measured. Shigella/EIEC was identified by the GI panel in the PRE (n = 30) and POST (n = 21) phase. The GI panel detected more Shigella infections than did culture; six of 31 (19.4%) Shigella GI panel-positive patients who also had stool cultures were missed by culture. Azithromycin therapy was prescribed for 20% of subjects in the PRE phase and 71.4% of subjects in the POST phase (P < 0.001). Time from the clinical encounter until starting azithromycin therapy was shorter in the POST phase (n = 9), 8.25 h (range, 6.37 to 52.37 h), than in the PRE phase (n = 1), 72 h. Six subjects in the PRE phase visited additional providers compared with one in the POST phase. Prompt diagnosis of shigellosis with the GI panel may provide the opportunity for prompt antimicrobial therapy and avoid additional visits to providers due to early definitive diagnosis. Prompt diagnosis of Shigella at an ED visit may optimize patient management and reduce transmission.


Dysentery, Bacillary , Shigella , Humans , Child , Azithromycin , Feces , Dysentery, Bacillary/diagnosis , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/epidemiology , Escherichia coli , Disease Outbreaks
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