Antimicrobial Resistance Of Shigella Research Articles

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.

Concordance between Genotypic and Phenotypic Drug-Resistant Profiles of Shigella Isolates from Taiyuan City, Shanxi Province, China, 2005 to 2016.

Antimicrobial resistance in Shigella spp. is a global public health concern. In this study, the AMR phenotypic profiles of 10 kinds of antibiotics were compared with the genotypic profiles using genomic analysis of 218 Shigella isolates from Taiyuan City, Shanxi Province, China, 2005 to 2016. Core genome Multilocus Sequence Typing (cgMLST) based on the EnteroBase Escherichia/Shigella scheme was used to obtain the genetic relatedness of Shigella isolates. Multiple-drug resistance was observed in 96.79% Shigella spp., and the resistance to antimicrobial agents varied between S. flexneri and S. sonnei. The genotypic results correlated well with the phenotypic profiles with concordance rates of 96.42% and 94.50% in S. flexneri and S. sonnei isolates, respectively, from Taiyuan City, Shanxi Province. The sensitivity and specificity of the genotypic antimicrobial susceptibility testing (AST) were 97.56% and 95.34% for S. flexneri, and 95.65% and 93.31% for S. sonnei isolates, respectively. A discrepancy of genotypic and phenotypic AST results existed in some cephalosporin- and azithromycin-resistant Shigella isolates; there were no clear resistance patterns to predict ciprofloxacin resistance. There were major discrepancies between genotypic and phenotypic AST in the genotypically resistant but phenotypically susceptible isolates. The drug-resistance patterns and essential drug-resistance genes to predict the phenotypic drug-resistant profiles were the discrepancies between S. flexneri and S. sonnei isolates. Phylogenetic analysis showed that isolates of the same cluster but with different antibiotic-resistance gene patterns occurred because of the loss or gain of antibiotic-resistance genes located in the plasmids and multidrug-resistance islands. IMPORTANCE Antimicrobial resistance in Shigella spp. has become a global public health concern. In this study, we identified the antimicrobial susceptibility testing (AST) characteristics based on genomic sequences of 218 Shigella isolates and analyzed the correlation between genotypic and phenotypic antibiotic resistance profiles of Shigella spp., especially for fluoroquinolone, macrolides, and third-generation cephalosporins. Our results show that the genotypic results correlated with the phenotypic profiles with concordance rates of 96.42% and 94.50% in S. flexneri and S. sonnei isolates, respectively. The drug-resistance patterns and essential drug-resistance genes to predict the phenotypic drug-resistant profiles of S. flexneri and S. sonnei isolates in Taiyuan city were distinct. The discrepancy between genotypic and phenotypic AST was considerable in the genotypically resistant but phenotypically susceptible isolates. The information on drug resistance and resistance genes in this study can offer more details on the prevalence of drug resistance of Shigella spp.

Increasing trend of antimicrobial resistance in Shigella associated with MSM transmission in Barcelona, 2020-21: outbreak of XRD Shigella sonnei and dissemination of ESBL-producing Shigella flexneri.

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. 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. 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. 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.

Prevalence of Multidrug-Resistant and Extended-Spectrum Beta-Lactamase-Producing Shigella Species in Asia: A Systematic Review and Meta-Analysis.

Shigellosis remains one of the leading causes of morbidity and mortality worldwide and is the second leading cause of diarrheal mortality among all age groups. However, the global emergence of antimicrobial-resistant Shigella strains, limiting the choice of effective drugs for shigellosis, has become the major challenge in the treatment of Shigella infections. The aim of this systematic review and meta-analysis was to provide an updated picture of the prevalence of antimicrobial-resistant Shigella species in Asia. A comprehensive and systematic search was performed on three electronic databases (PubMed, ScienceDirect and Scopus), in which 63 eligible studies published between 2010 and 2022 were identified. From our meta-analysis of proportions using a random-effects model, the overall prevalence of Shigella spp. in Asian patients was estimated to be 8.0% (95% CI: 5.5-10.5). The pooled prevalence rates of multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL)-producing Shigella strains were 68.7% (95% CI: 59.9-77.5) and 23.9% (95% CI: 12.9-34.8), respectively. Concerning recommended antimicrobial drugs for Shigella, the prevalence of resistance was highest for ciprofloxacin (29.8%) and azithromycin (29.2%), followed by ceftriaxone (23.8%), in spite of their importance as first- and second-line treatments for shigellosis. In contrast, resistance to carbapenems, such as ertapenem (0.0%), imipenem (0.1%) and meropenem (0.0%), was almost non-existent among the 49 tested antibiotics. The significantly high prevalence estimation suggests that the multidrug-resistant Shigella is a pressing threat to public health worthy of careful and justified interventions. Effective antibiotic treatment strategies, which may lead to better outcomes for the control and treatment of shigellosis in Asia, are essential.

Sexually transmitted outbreaks and genomic surveillance

Sexually transmitted outbreaks and genomic surveillance

Evolutionary histories and antimicrobial resistance inShigella flexneri and Shigella sonnei in Southeast Asia

Conventional disease surveillance for shigellosis in developing country settingsrelies on serotyping and low-resolution molecular typing, which fails to contextualise the evolutionary history of the genus. Here, we interrogated a collection of 1,804 Shigella whole genome sequences from organisms isolated in four continental Southeast Asian countries (Thailand, Vietnam, Laos, and Cambodia) over three decades to characterise the evolution of both S. flexneri and S. sonnei. We show that S. sonnei and each major S. flexneri serotype are comprised of genetically diverse populations, the majority of which were likely introduced into Southeast Asia in the 1970s-1990s. Intranational and regional dissemination allowed widespread propagation of both species across the region. Our data indicate that the epidemiology of S. sonnei and the major S. flexneri serotypes were characterised by frequent clonal replacement events, coinciding with changing susceptibility patterns against contemporaneous antimicrobials. We conclude that adaptation to antimicrobial pressure was pivotal to the recent evolutionary trajectory of Shigella in Southeast Asia.

The repurposing of Tebipenem pivoxil as alternative therapy for severe gastrointestinal infections caused by extensively drug-resistant Shigella spp.

Diarrhoea remains one of the leading causes of childhood mortality globally. Recent epidemiological studies conducted in low-middle income countries (LMICs) identified Shigella spp. as the first and second most predominant agent of dysentery and moderate diarrhoea, respectively. Antimicrobial therapy is often necessary for Shigella infections; however, we are reaching a crisis point with efficacious antimicrobials. The rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem. Aiming to identify alternative antimicrobial chemicals with activity against antimicrobial resistant Shigella, we initiated a collaborative academia-industry drug discovery project, applying high-throughput phenotypic screening across broad chemical diversity and followed a lead compound through in vitro and in vivo characterisation. We identified several known antimicrobial compound classes with antibacterial activity against Shigella. These compounds included the oral carbapenem Tebipenem, which was found to be highly potent against broadly susceptible Shigella and contemporary MDR variants for which we perform detailed pre-clinical testing. Additional in vitro screening demonstrated that Tebipenem had activity against a wide range of other non-Shigella enteric bacteria. Cognisant of the risk for the development of resistance against monotherapy, we identified synergistic behaviour of two different drug combinations incorporating Tebipenem. We found the orally bioavailable prodrug (Tebipenem pivoxil) had ideal pharmacokinetic properties for treating enteric pathogens and was effective in clearing the gut of infecting organisms when administered to Shigella-infected mice and gnotobiotic piglets. Our data highlight the emerging antimicrobial resistance crisis and shows that Tebipenem pivoxil (licenced for paediatric respiratory tract infections in Japan) should be accelerated into human trials and could be repurposed as an effective treatment for severe diarrhoea caused by MDR Shigella and other enteric pathogens in LMICs. Tres Cantos Open Lab Foundation (projects TC239 and TC246), the Bill and Melinda Gates Foundation (grant OPP1172483) and Wellcome (215515/Z/19/Z).

Antimicrobial resistant Shigella in North India since the turn of the 21st century

PurposeThe ubiquitous presence and rampant spread of antibiotic resistant strains of Shigella spp is a major public health concern. Therefore, monitoring the trends of antimicrobial resistance in them is essential. MethodsA total of 15440 stool samples were inoculated on MacConkey agar, lysine deoxycholate agar and Selenite F enrichment broth from 2001 to 2015.Out of 491 shigellae isolated, 250 isolates were recovered from our culture collection. Antimicrobial susceptibility was performed by Kirby Bauer disc diffusion method, E-test and phenotypic resistance screening for ESBL and AmpC production was performed. For the detection of beta-lactamase genes, PCR for blaTEM, blaSHV, blaOXA, blaCTX-M-15, CMY-2 and mphA PCR in isolates with decreased susceptibility to azithromycin(DSA) was performed. ResultsS. flexneri (n ​= ​173) was most common, followed by S.dysenteriae (n ​= ​24), S.sonnei (n ​= ​23), S.boydii (n ​= ​10) and Non agglutinating Shigella (NAG, n ​= ​20). A see-saw pattern in the prevalence of S. flexneri and S. dysenteriae and rising prevalence of S. sonnei and NAG was seen. Majority (77%) of the isolates had MICs >4 ​mg/L for ciprofloxacin and >50% had high MIC90 (12 ​mg/L) for ceftriaxone and cefepime (8 ​mg/L). Nearly 20% of S.flexneri were resistant to third generation cephalosporin by disc diffusion and 33.7% had MIC ≥1 ​μg/mL. Among the ceftriaxone resistant isolates (n ​= ​29) the blaTEM beta-lactamase resistance gene was seen in all, blaCTX-M-15 in 37%, blaCMY-2 in 45.6% and blaOXA in 52%. The first report of DSA at our institute was in 2001 (n ​= ​1, 2.5%) which increased to 35.1% (n ​= ​40) in 2011–15. The isolates with DSA included S. flexneri (n ​= ​40), S. boydii (n ​= ​4) and S. sonnei (n ​= ​1) and plasmid mediated resistance to azithromycin by mphA gene was detected in 19 out of 40 isolates of S. flexneri. ConclusionGlobal emergence of resistance Shigella is a matter of concern and calls for systematic monitoring and periodic updates of countrywide and local antibiogram.

Epidemic and molecular characterization of fluoroquinolone-resistant Shigella dysenteriae 1 isolates from calves with diarrhea

BackgroundThe widespread distribution of antimicrobial-resistant Shigella has become a recurrent challenge in many parts of the developing world. Previous studies indicate that the host of Shigella has expanded from humans to animals. This study aimed to investigate the prevalence of fluoroquinolone resistance and associated molecular characterization of S. dysenteriae 1 isolated from calves.ResultsAll 38 unduplicated S. dysenteriae 1 isolates were collected from calves in Gansu Province from October 2014 to December 2016. According to MLST and PFGE analysis, these isolates were separated into 4 and 28 genotypes, respectively. The most common STs identified were ST228 (34.21%, 13/38) and ST229 (39.47%, 15/38), which were first found in the present study. All isolates harbored virulence genes, and the incidence of the seven virulence genes were ipaH (100%), ipaBCD (92.11%), stx (73.68%), ial (57.89%), sen (28.95%), set1A and set1B (0%). According to the results of antimicrobial susceptibilities, 76.32% (29/38) were resistant to fluoroquinolone and showed multidrug resistance. In a study on the polymorphism of quinolone resistance–determining region (QRDR) of gyrA/B and parC/E genes, we identified two mutations in gyrA (Ser83 → Leu and Asp87 → Asn) and parC (Ser80 → Ile and Ser83 → Leu), respectively. Among them, 55.17% (16/29) of resistant strains had the gyrA point mutations (Ser83 → Leu) and parC point mutation (Ser83 → Leu). Moreover, 41.38% (12/29) of isolates had all five point mutations of gyrA and parC. In addition, the prevalence of the plasmid-mediated quinolone resistance (PMQR) determinant genes was also investigated. All 29 fluoroquinolone-resistant isolates were positive for the aac (6′)-Ib-cr gene but negative for qepA, except for SD001. In addition, only 6 (20.69%, 6/29) isolates harbored the qnr gene, including two with qnrB (6.90%, 2/29) and four with qnrS (13.79%, 4/29).ConclusionGiven the increased common emergence of multidrug resistant isolates, uninterrupted surveillance will be necessary to understand the actual epidemic burden and control this infection.

The role of international travellers in the spread of CTX-M-15-producing Shigella sonnei in the Republic of Korea.

Multidrug-resistant Shigella isolates have recently emerged as a serious public health threat worldwide. In particular, overseas travel is a risk factor for acquisition of antimicrobial-resistant Shigella strains. To explore the role of travel in the spread of cefotaxime-resistant Shigella sonnei in Korea, we screened 751 Shigella spp. isolates from 2007 to 2016 through the National Surveillance system, and 28 cephalosporin-resistant S. sonnei isolates were identified. For cephalosporin-resistant S. sonnei isolates, epidemiological and molecular analyses (plasmid structure analysis, pulsed-field gel electrophoresis (PFGE) and high-quality single-nucleotide polymorphisms (hqSNPs) based on whole-genome sequencing (WGS)) were conducted to investigate the source of infection and transmission route. Among the 28 cefotaxime-resistant S. sonnei strains, 18 were isolated from travellers returning from Asia, including Vietnam (n=11). Molecular analysis of 18 blaCTX-M-type isolates revealed that 15 contain CTX-M-15; 50% of isolates from domestic patients contain CTX-M-14. Analysis of the genetic environments of the blaCTX-M-14 and blaCTX-M-15 genes revealed different genetic organization surrounding the blaCTX-M genes. Additionally, PFGE and hqSNP results suggested a large phylogenetic distance between the S. sonnei isolates related to overseas travel and those acquired domestically in Korea. Our study data demonstrates that two prevalent blaCTX-M genes, blaCTX-M-14 and blaCTX-M-15, have been circulating in S. sonnei in Korea over the last 10 years. Recently, international travellers are at a high risk for acquisition of CTX-M-15-producing S. sonnei in Korea.

Prevalence and molecular characterization of multidrug-resistant Shigella species of food origins and their inactivation by specific lytic bacteriophages

Shigella spp. can be isolated from various food sources and is responsible for many outbreaks and sporadic cases of foodborne diseases worldwide. Although Shigella species are known as one of the major foodborne pathogens, a few studies have characterized the prevalence and molecular basis of antibiotic resistance of Shigella spp. isolated from food origins. This study investigated the prevalence of Shigella spp. in a wide range of food samples (1400 samples), and the phenotypic and genotypic basis of antimicrobial resistance of the isolates. In addition, the potential of two Shigella specific phages (vB_SflS-ISF001 and vB_SsoS-ISF002) to control the growth of the isolates in food was tested. Shigella sonnei and Shigella flexneri were detected in 11 (0.8%) and 8 (0.6%) samples, respectively. The highest prevalence of Shigella spp. was observed in vegetables. Multidrug resistance phenotypes were noticeably frequent and observed in 17 isolates (89.5%) out of 19 isolates. Moreover, 13 (68.4%), 9 (47.4%) and 17 (89.5%) isolates were positive for β-lactamase-encoding, plasmid-mediated quinolone resistance and tetracycline resistance genes, respectively. Treatment with the phages reduced bacterial counts up to 3 and 4 log when used individually or in cocktail form, respectively. The findings of this study indicate the prevalence of Shigella spp. in food sources and also provide useful information for a better understanding of the molecular aspects of antimicrobial resistance in Shigella spp.. The results also suggest that the combination of vB_SflS-ISF001 and vB_SsoS-ISF002 phages can effectively reduce contamination of two important species of Shigella in food.

Use of whole genome sequencing in surveillance for antimicrobial-resistant Shigella sonnei infections acquired from domestic and international sources.

Shigella species are a major cause of gastroenteritis worldwide, and Shigella sonnei is the most common species isolated within the United States. Previous surveillance work in Pennsylvania documented increased antimicrobial resistance (AMR) in S. sonnei associated with reported illnesses. The present study examined a subset of these isolates by whole genome sequencing (WGS) to determine the relationship between domestic and international isolates, to identify genes that may be useful for identifying specific Global Lineages of S. sonnei and to test the accuracy of WGS for predicting AMR phenotype. A collection of 22 antimicrobial-resistant isolates from patients infected within the United States or while travelling internationally between 2009 and 2014 was chosen for WGS. Phylogenetic analysis revealed both international and domestic isolates were one of two previously defined Global Lineages of S. sonnei, designated Lineage II and Lineage III. Twelve of 17 alleles tested distinguish these two lineages. Lastly, genome analysis was used to identify AMR determinants. Genotypic analysis was concordant with phenotypic resistance for six of eight antibiotic classes. For aminoglycosides and trimethoprim, resistance genes were identified in two and three phenotypically sensitive isolates, respectively. This article contains data hosted by Microreact.

Molecular analysis of integrons and antimicrobial resistance profile in Shigella spp. isolated from acute pediatric diarrhea patients.

Introduction: Shigella spp. is a growing global health concern due to increasing multiple drug resistance, commonly resulting in therapeutic failure. Integrons are gene expression systems run by integrase genes. The aims of this study were detection of class I, II and III integrons and assessment of antimicrobial resistance in Shigella spp. isolated from acute pediatric diarrhea patients.Materials and methods: From January to December 2015, 16 Shigella spp. were isolated from 310 non-duplicative diarrheal stool samples in Children’s Medical Center, Tehran, Iran. The isolates were analyzed for their antibiotic susceptibility using CLSI guidelines M100-S14. Multiplex PCR was used for amplification of I, II and III integron-associated integrase (intl) genes.Results: Of 310 stool samples, 16 (5.2%) were positive for Shigella spp., in 7 of them S. sonnei and in 9 of them S. flexneri were identified. Results of the antimicrobial susceptibility test showed that 6.2%, 50%, 31.2%, 6.2%, 81.2%, 56.2% and 31.2% of the isolates were resistant to gentamicin, chloramphenicol, nalidixic acid, ciprofloxacin, tetracycline, ampicillin and trimethoprim-sulfamethoxazole, respectively. Multiplex PCR results revealed that 6.2% (1/16), 31.2% (5/16), 50% (8/16) of Shigella isolates carried intlI, intlII and both intlI/intllI genes. No class 3 integrons were detected.Discussion: In this study, multidrug resistance was seen in Shigella isolates similar to that in isolates from other geographical areas. This is possible due to inappropriate use of antimicrobials. Furthermore, prevalence of multidrug resistance was significantly linked to the presence of integrin genes. Conclusion: A class 2 integron plays a role in presence of multidrug resistance in Shigella spp. It is vital to prevent the spread of antibiotic resistance through continuous monitoring.

Patterns of Acute Non Amebiasis Dysentery in Adults

iarrhea is still a major cause of death in many People all over the world. Acute diarrhea causes 3 million people death annually. Etiologic agents for bacterial dysentery are: Shigella (dysenteria, flexneri, boydii, sonnei), Salmonella (Typhi and para typhi), Campylobacter (jejuni) and Yersinia (entero colitica). The most common agent in developing countries is shigella Dysenteria and in developed countries is campylobacter jejuni [1]. While dysentery is a self limited disease, the antibiotic treatment not only reduces the symptomatic time, but also the excretion of the microbes, preventing its infection exposing other people [2]. The present study was aimed to determine patterns of acute non amebiasis dysentery in adult. This cross-sectional study performs in 2012. Patients with acute invasive diarrhea (bloody or mucoid diarrhea) for shorter than 3 days duration or watery diarrhea with fever or chill or tenesmus enrolled. Exclusion criteria were lactating and pregnant women, antibiotic therapy in 72 h past, patients with high toxicity and poor general condition and complications. In first, we get from all patients a sample of stool for direct examination and culture and antibiogram. Dysentery confirmed by positivity stool for WBC and RBC without amebiasis, then some of patients received azithromycin and other group received tab ciprofloxacin 500 mg/12 h for 5 days. After 48 h patients were examined for fever, general condition, decreased diarrhea and tenesmus. For patients with good clinical response, duration of treatment completed for 5 days but in groups without good clinical response, with use of results of culture and antibiogram, treatment changed. Stool culture was done from all patients in 5th day after treatment. Also patients evaluate for drug reactions in two groups. Data was analyzed using SPSS-11 software and χ test was used p<0.05 was set as the significant level. From 84 patients, 52 (61.9%) patients were male and 32 patients (38.9%) were female. In 29 (34.5%) patients culture result was negative. Shigella dysenteria cultured from 41 (48.8%) patients and other organisms (E. coli, Salmonella paratyphi A, Campylobacter jejuni cultured in 14 (16.6%) patients. Bloody diarrhea was seen at 38.1% patients and 27.3% had watery diarrhea and 32% mucoid and mixed diarrhea. From 55 patients that had antibiogram, 32 (58.1%) were sensitive to ciprofloxacin and 41 (74.4%) to azithromycin. Clinical response in azithromycin was more than ciprofloxacin 93.5% versus 88.6%. Stool cultures were negative in 100% patients at the end of treatment. In our study in patients with dysenteria, Shigella dysenteria is the most common etiologic agent but is not only bacterial etiology and other Gram negative bacillus example Salmonella paratyphi A, Campylobacter jejuni and E. coli. This may be to Shigella dysenteria low tolerance to hard environment conditions that it difficult Shigella dysenteria diagnosis or early antibiotic use by patients with dysenteria. Other studies showed quinolone resistance in Shigella (all species) has increased at an alarming speed, reinforcing the importance of continuous monitoring of antimicrobial resistance in Shigella (all species) [3]. In our study microbiological resistance for azithromycin was 19.3% and for ciprofloxacin was 23.8%, that indicated Shigella dysenteria resistant to new antibiotics example macrolides and quinolones is increased but clinical response to azithromycin and ciprofloxacin were good.

Shigella flexneri serotype 3a: the rise of a superbug

Shigellosis is a highly contagious acute gastrointestinal infection conferred by faeco-oral transmission of the pathogen Shigella spp. 1 Musher DM Musher BL Contagious acute gastrointestinal infections. N Engl J Med. 2004; 351: 2417-2427 Crossref PubMed Scopus (129) Google Scholar In low-income countries and high-risk regions, poor sanitation is responsible for about 165 million cases of shigellosis annually, with at least 1 million of these resulting in death. 2 Kotloff KL Winickoff JP Ivanoff B et al. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull World Health Organ. 1999; 77: 651-666 PubMed Google Scholar In high-income countries and low-risk regions, shigellosis is typically associated with travel to high-risk regions (Africa, Asia, and Latin America). 3 Borg ML Modi A Tostmann A et al. Ongoing outbreak of Shigella flexneri serotype 3a in men who have sex with men in England and Wales, data from 2009–2011. Euro Surveill. 2012; 17: 1-5 Google Scholar Since 2000, shigellosis has also been reported as a sexually transmitted infection (STI) among men who have sex with men (MSM). 4 CDCShigella sonnei outbreak among men who have sex with men San Francisco, California, 2000–2001. MMWR Morb Mortal Wkly Rep. 2001; 50: 922-926 PubMed Google Scholar In most cases of shigellosis, treatment relies on replacement of fluids and salts lost due to severe diarrhoea, which usually lasts for less than a week. 5 US National Library of MedicineNational Institutes of Health http://www.nlm.nih.gov/medlineplus/ency/article/000295.htm Google Scholar However, severe infections in young children and old adults, or immunocompromised people, might require antibiotic treatment. 6 DuPont HL Approach to the patient with infectious colitis. Curr Opin Gastroenterol. 2012; 28: 39-46 Crossref PubMed Scopus (25) Google Scholar The emergence of Shigella spp strains with decreased antibiotic susceptibility is a growing public health concern. 7 Gu B Cao Y Pan S et al. Comparison of the prevalence and changing resistance to nalidixic acid and ciprofloxacin of Shigella between Europe-America and Asia-Africa from 1998 to 2009. Int J Antimicrob Agents. 2012; 40: 9-17 Summary Full Text Full Text PDF PubMed Scopus (106) Google Scholar Intercontinental dissemination of azithromycin-resistant shigellosis through sexual transmission: a cross-sectional studyWe identified transmission-facilitating behaviours and atypical course(s) of infection as precipitating factors in shigellosis-affected MSM. The intercontinental spread of antimicrobial-resistant shigella through established transmission routes emphasises the need for new approaches to tackle the public health challenge of sexually transmitted infections in MSM. Full-Text PDF

Intercontinental dissemination of azithromycin-resistant shigellosis through sexual transmission: a cross-sectional study

Shigellosis is an acute, severe bacterial colitis that, in high-income countries, is typically associated with travel to high-risk regions (Africa, Asia, and Latin America). Since the 1970s, shigellosis has also been reported as a sexually transmitted infection in men who have sex with men (MSM), in whom transmission is an important component of shigellosis epidemiology in high-income nations. We aimed to use sophisticated subtyping and international sampling to determine factors driving shigellosis emergence in MSM linked to an outbreak in the UK. We did a large-scale, cross-sectional genomic epidemiological study of shigellosis cases collected from 29 countries between December, 1995, and June 8, 2014. Focusing on an ongoing epidemic in the UK, we collected and whole-genome sequenced clinical isolates of Shigella flexneri serotype 3a from high-risk and low-risk regions, including cases associated with travel and sex between men. We examined relationships between geographical, demographic, and clinical patient data with the isolate antimicrobial susceptibility, genetic data, and inferred evolutionary relationships. We obtained 331 clinical isolates of S flexneri serotype 3a, including 275 from low-risk regions (44 from individuals who travelled to high-risk regions), 52 from high-risk regions, and four outgroup samples (ie, closely related, but genetically distinct isolates used to determine the root of the phylogenetic tree). We identified a recently emerged lineage of S flexneri 3a that has spread intercontinentally in less than 20 years throughout regions traditionally at low risk for shigellosis via sexual transmission in MSM. The lineage had acquired multiple antimicrobial resistance determinants, and prevailing sublineages were strongly associated with resistance to the macrolide azithromycin. Eight (4%) of 206 isolates from the MSM-associated lineage were obtained from patients who had previously provided an isolate; these serial isolations indicated atypical infection patterns (eg, reinfection). We identified transmission-facilitating behaviours and atypical course(s) of infection as precipitating factors in shigellosis-affected MSM. The intercontinental spread of antimicrobial-resistant shigella through established transmission routes emphasises the need for new approaches to tackle the public health challenge of sexually transmitted infections in MSM. Wellcome Trust (grant number 098051).

Antimicrobial Resistance of Shigella Isolates in Alanya, Turkey

Shigella spp. were isolated from stool samples and stored at −80 °C for antimicrobial susceptibility. Antimicrobial susceptibility was determined according to the Clinical and Laboratory Standards Institute criteria. The antimicrobials tested against Shigella spp. included ampicillin, trimethoprim–sulfamethoxazole, tetracycline, chloramphenicol, ciprofloxacin, ceftriaxone and azithromycin. Minimum inhibitory concentration of ceftriaxone and azithromycin were determined by E-test. Quality control was ensured by testing Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213. A total of 33 Shigella isolates (17 S. sonnei, 9 S. flexneri, 5 S. dysenteriae and 2 S. boydii) were assessed for their antimicrobial susceptibility patterns. The resistance to trimethoprim–sulfamethoxazole, ampicillin, tetracycline, chloramphenicol, ceftriaxone and azithromycin were found to be 66.7, 45.5, 57.6, 9.1, 9.1 and 3 %, respectively. S. sonnei showed higher resistance than S. flexneri to trimethoprim–sulfamethoxazole, but resistance to ampicillin was more common in S. flexneri than S. sonnei. Minimum inhibitory concentration values were in the following ranges: azithromycin 0.75–16 μg/mL and ceftriaxone 0.002 to >32 μg/mL. Minimum inhibitory concentration that inhibit 90 % of the strains for azithromycin and ceftriaxone were 6 and 0.47 μg/mL, respectively. The resistance to ceftriaxone and azithromycin may be a cause for concern.

Antimicrobial resistance of Shigella spp. from humans in Shanghai, China, 2004–2011

A retrospective study conducted on patients with diarrhea in Shanghai, China from 2004–2011, indicated that of 77,600 samples collected, 1,635 (2.1%) tested positive for Shigella. Species isolated included S. sonnei (1,066, 65.1%), S. flexneri (569, 34.7%), and S. boydii (3, 0.2%). Most of the Shigella isolates were found to be resistant to streptomycin (98.7%), trimethoprim (98.0%), ampicillin (92.1%), and nalidixic acid (91.7%). Additionally, many isolates were resistant to tetracycline (86.9%), trimethoprim + sulfamethoxazole (80.1%), sulfisoxazole (76.8%) and gentamicin (55.5%). Approximately 80% of the isolates were resistant to at least eight antimicrobial agents, 14% to at least ten antimicrobials tested and 10 isolates to fourteen antimicrobials, including sulfonamides, fluoroquinolones, tetracyclines, aminoglycosides and β-lactamases. Importantly, co-resistance to fluoroquinolones and the third- and fourth-generation cephalosporins was also identified. The high levels of resistance to antimicrobial agents commonly used in clinical medicine presents a great challenge to treating patients with shigellosis.

Antimicrobial resistance in Shigella spp. causing traveller's diarrhoea (1995–2010): A retrospective analysis

Shigellosis is a global human health problem causing an important morbidity among travellers returning from tropical areas. This study was aimed to describe the evolution of antimicrobial resistance profile in Shigella spp. isolated between the years 1995-2010 in patients with traveller's diarrhoea (TD) returning from tropical areas. The levels of antimicrobial resistance were tested in a total of 191 Shigella spp. isolated during the period from 1995 to 2010. A decrease of cases of diarrhoea caused by Shigella has been observed in recent years. A wide spectrum of antibiotic resistance was observed among Shigella spp. These isolates showed high levels of resistance to tetracycline (84%), co-trimoxazole (75.5%), and ampicillin (45.5%). The resistance was low to ciprofloxacin (2.1%), azithromycin (3.9%) and furazolidone (8.4%). According to the period, in the case of ampicillin, amoxicillin plus clavulanic acid, chloramphenicol, values of resistance were significantly decreasing from 1995-2000 to 2001-2010, (62.5% vs. 28.4%, 19.8% vs. 6.6%, 23.4 vs. 10.4%, respectively). Meanwhile in nalidixic acid and tetracycline the evolution of resistance has increased over time. A decrease in the isolation number of Shigella spp. causing TD has been observed. Differential trends in the evolution of the levels of resistance to the tested antibacterial agents have been observed.

Comparison of the prevalence and changing resistance to nalidixic acid and ciprofloxacin of Shigella between Europe–America and Asia–Africa from 1998 to 2009

Shigella is becoming an increasing public health problem due to development of multiple antimicrobial resistance, frequently resulting in treatment failure. A systematic review was conducted based on a literature search of computerised databases. Random or fixed-effects models were used, based on the P-value considering the possibility of heterogeneity between studies, for meta-analysis. Statistical analyses were performed using STATA 10.0. In the area of Asia–Africa, resistance rates to nalidixic acid and ciprofloxacin were 33.6% [95% confidence interval (CI) 21.8–46.6%] and 5.0% (95% CI 2.8–7.8%), respectively, 10.5 and 16.7 times those of Europe–America. Moreover, resistance to nalidixic acid and ciprofloxacin in Asia–Africa progressively increased each year, reaching 64.5% (95% CI 13.8–99.3%) and 29.1% (95% CI 0.9–74.8%), respectively, in 2007–2009, whilst isolates in Europe–America remained at low levels of resistance (<5.0% and <1.0%, respectively). All Shigella flexneri strains showed higher resistance than Shigella sonnei in Europe–America: overall, 3.5% (95% CI 1.4–6.4%) vs. 2.6% (95% CI 1.0–5.0%) resistant to nalidixic acid and 1.0% (95% CI 0.3–2.2%) vs. 0.1% (95% CI 0.0–0.3%) resistant to ciprofloxacin. In Asia–Africa, a similar trend was found for ciprofloxacin [3.0% (95% CI 1.4–5.3%) vs. 0.5% (95% CI 0.2–0.8%)], whereas the trend was reversed for nalidixic acid [32.6% (95% CI 14.5–53.9%) vs. 44.3% (95% CI 26.9–62.5%). In conclusion, quinolone resistance in Shigella has increased at an alarming speed, reinforcing the importance of continuous monitoring of antimicrobial resistance in Shigella.