Detection of OXA-181 Carbapenemase in Shigella flexneri.

We report the detection of OXA-181 carbapenemase in an azithromycin-resistant Shigella spp. bacteria in an immunocompromised patient. The emergence of OXA-181 in Shigella spp. bacteria raises concerns about the global dissemination of carbapenem resistance in Enterobacterales and its implications for the treatment of infections caused by Shigella bacteria.

Genome-Wide Investigation Reveals Potential Therapeutic Targets in Shigella spp.

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.

Multidrug-resistant conjugative plasmid carrying mphA confers increased antimicrobial resistance in Shigella.

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.

A Review on the Antibiotic Resistance of Shigella Strains in Iran.

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.

Healthcare providers' knowledge and clinical practice surrounding shigellosis - DocStyles Survey, 2020.

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-virulence and bactericidal activities of Stattic against Shigella sonnei.

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.

Whole genome sequencing of increased number of azithromycin-resistant Shigella flexneri 1b isolates in Ontario.

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.

Novel inhibitors that target bacterial virulence identified via HTS against intra-macrophage survival of Shigella flexneri.

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.

Case of Extensively Drug-Resistant Shigella sonnei Infection, United States.

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.

Multidrug-Resistant Shigella sonnei Bacteremia among Persons Experiencing Homelessness, Vancouver, British Columbia, Canada.

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.

An automated microscopy workflow to study Shigella-neutrophil interactions and antibiotic efficacy in vivo.

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.

Extensively Drug-Resistant Shigella flexneri 2a, California, USA, 2022.

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.

Whole-genome sequencing of Shigella for surveillance purposes shows (inter)national relatedness and multidrug resistance in isolates from men who have sex with men.

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.

Biogenic Preparation and Characterization of Silver Nanoparticles from Seed Kernel of Mangifera indica and Their Antibacterial Potential against Shigella spp.

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.

[Shigellosis attended in the emergency department of a regional hospital in southeastern Spain: from their presence to multiresistance]. / Shigelosis atendidas en el servicio de urgencias de un hospital regional del sudeste de España: Desde su presencia a la multirresistencia.

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.

Monitoring Longitudinal Trends and Assessment of the Health Risk of Shigella flexneri Antimicrobial Resistance.

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.

Discovery of a novel sub-lineage of multi-drug resistant Shigella flexneri in Southern California.

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.

Genomic reconstruction and directed interventions in a multidrug-resistant Shigellosis outbreak in Seattle, WA, USA: a genomic surveillance study.

BACKGROUND: Shigella spp have been associated with community-wide outbreaks in urban settings. We analysed a sustained shigellosis outbreak in Seattle, WA, USA, to understand its origins and mechanisms of antimicrobial resistance, define ongoing transmission patterns, and optimise strategies for treatment and infection control. METHODS: We did a retrospective study of all Shigella isolates identified from stool samples at the clinical laboratories at Harborview Medical Center and University of Washington Medical Center (Seattle, WA, USA) from May 1, 2017, to Feb 28, 2022. We characterised isolates by species identification, phenotypic susceptibility testing, and whole-genome sequencing. Demographic characteristics and clinical outcomes of the patients were retrospectively examined. FINDINGS: 171 cases of shigellosis were included. 78 (46%) patients were men who have sex with men (MSM), and 88 (52%) were people experiencing homelessness (PEH). Although 84 (51%) isolates were multidrug resistant, 100 (70%) of 143 patients with data on antimicrobial therapy received appropriate empirical therapy. Phylogenomic analysis identified sequential outbreaks of multiple distinct lineages of Shigella flexneri and Shigella sonnei. Discrete clonal lineages (ten in S flexneri and nine in S sonnei) and resistance traits were responsible for infection in different at-risk populations (ie, MSM, PEH), enabling development of effective guidelines for empirical treatment. The most prevalent lineage in Seattle was probably introduced to Washington State via international travel, with subsequent domestic transmission between at-risk groups. INTERPRETATION: An outbreak in Seattle was driven by parallel emergence of multidrug-resistant strains involving international transmission networks and domestic transmission between at-risk populations. Genomic analysis elucidated not only outbreak origin, but directed optimal approaches to testing, treatment, and public health response. Rapid diagnostics combined with detailed knowledge of local epidemiology can enable high rates of appropriate empirical therapy even in multidrug-resistant infection. FUNDING: None.

The increasing antimicrobial resistance of Shigella species among Iranian pediatrics: a systematic review and meta-analysis.

BACKGROUND: Shigellosis remains one of the global causes of morbidity and mortality. However, the global emergence of antibiotic resistance has become the leading cause of treatment failure in shigellosis. This review aimed to provide an updated picture of the antimicrobial resistance rates in Shigella species in Iranian pediatrics. METHODS: A comprehensive systematic search was performed on PubMed, Scopus, Embase, and Web of Science until 28 July 2021. The meta-analysis was performed by computing the pooled using a random-effects model with Stata/SE software, v.17.1. The discrepancy within articles was surveyed by the forest plot in addition to the I2 statistic. All statistical interpretations were reported on a 95% confidence interval (CI) basis. RESULTS: Totally, of 28 eligible studies published between 2008 and 2021. The pooled prevalence rate of multidrug-resistant (MDR) was 63% (95% CI 50-76). Regarding suggested antimicrobial agents for Shigella species, the prevalence of resistance for ciprofloxacin, azithromycin, and ceftriaxone as first- and second-line treatments for shigellosis were 3%, 30%, and 28%, respectively. In contrast, resistance to cefotaxime, cefixime, and ceftazidime was 39%, 35%, and 20%. Importantly, subgroup analyses indicated that an increase in resistance rates during the periods (2008-2014, 2015-2021) was recognized for ciprofloxacin (0 % to 6%) and ceftriaxone (6% to 42%). CONCLUSION: Our findings revealed that ciprofloxacin is an effective drug for shigellosis in Iranian children. The substantially high prevalence estimation proposes that the first- and second-line treatments for shigellosis are the major threat to public health and active antibiotic treatment policies are essential.

Antimicrobial resistance in sexually transmitted Shigella in men who have sex with men: A systematic review.

BACKGROUND: Outbreaks of sexually transmitted Shigella flexneri and Shigella sonnei in men who have sex with men (MSM) are a major public health issue. While most cases can be managed conservatively, a minority require antimicrobial treatment. Recent reports have highlighted increasing antimicrobial resistant (AMR) strains of Shigella spp. in men who have sex with men. We aimed to systematically review antimicrobial resistance (and decreased antimicrobial sensitivity) in sexually transmitted shigella in men who have sex with men, focussing on macrolides, quinolones, and third generation cephalosporins. METHODS: We systematically searched 4 bibliographical databases (EMBASE, medline, EMCARE and CINAHL) from January 2011 to November 2021. We used a 2-stage process to assess eligibility: the primary author conducted an initial screen and then 3 authors conducted independent full-text reviews to determine the final eligible manuscripts. We only included manuscripts in English which included men who have sex with men with sexually transmitted shigella where data on antimicrobial resistance was available. RESULTS: Thirty-nine manuscripts met the inclusion criteria. A majority of the manuscripts (N = 34) described reduced susceptibility or antimicrobial resistant to macrolides, quinolones and third generation cephalosporins in circulating strains of shigella within sexual networks of men who have sex with men. Extensively drug resistant outbreaks of shigella in men who have sex with men have been reported containing genetic markers of ceftriaxone resistance (e.g. BlaCTX-M27) where isolates also contained markers of reduced susceptibility, and antimicrobial resistant to macrolides and quinolones. CONCLUSION: There is little role for macrolides, quinolones or third generation cephalosporins in the management of sexually transmitted shigella in men who have sex with men. More research is needed to develop novel strategies for shigella control in men who have sex with men, as antimicrobial options are diminishing.