in november 2015 , public health england ( phe ) identified a cluster of s. sonnei isolates by analyzing whole - genome sequencing data from specimens collected during september and october from 4 adult men residing in london and having no known travel history . the isolates were later found to exhibit high levels of antimicrobial drug resistance to amoxicillin , ceftriaxone , tetracycline , sulfonamides , trimethoprim , and azithromycin and to produce extended - spectrum -lactamase ( esbl ) ( table 1 ) . phe convened an outbreak control team to identify additional cases , characterize cases , capture exposure information , rule out a point source for the outbreak , and provide evidence for additional targeted public health efforts . amc , amoxicillin / clavulanate ; amp , ampicillin ; atm , aztreonam ; azt , azithromycin ; caz , ceftazidime ; cfp , cefepime ; cip , ciprofloxacin ; col , colistin ; cro , ceftriaxone ; ctx , cefotaxime ; ert , ertapenem ; fos , fosfomycin ; gen , gentamicin ; i d , identification ; mer , meropenem ; sep , trimethoprim / sulfamethoxazole ; tem , temocillin ; tmp , trimethoprim ; tob , tobramycin . phenotypic antimicrobial drug susceptibility testing was performed by using etest ( biomrieux , marcy letoile , france ) and interpreted by using breakpoints for enterobacteriaceae established by the european committee on antimicrobial susceptibility testing ( http://www.eucast.org/ ) . production of extended - spectrum -lactamase was confirmed by using ctx + clavulunic acid and caz + clavalunic acid in combination ( biomrieux ) . since august 2015 , phe has conducted whole - genome sequencing of 70% of s. sonnei isolates ( those voluntarily referred from hospital laboratories ) ( technical appendix ) . single nucleotide polymorphism ( snp ) clustering is performed , as previously described ( 3 ) . readings ( in fastq format ) from all sequences in this study can be found at the phe pathogens bioproject ( national center for biotechnology information project no . the multidrug - resistance phenotype was explained by the presence of an 89,000-bp incfii plasmid designated p183660 ( genbank accession no . this plasmid had > 95% nt identity to pksr100 , a multidrug - resistance plasmid from an msm case of s. flexneri 3a infection ( genbank accession no . ln624486 ) that had acquired the previously described pksr100 integron ( blatem-1 , dfra17 , dfra1 , sul1 , aada5 ) ( 4 ) and a novel mobile element harboring blactx - m-27 ( figure 1 ) . genomic plot of multidrug - resistance plasmid p183660 ( inner ring , blue ) from a man in england infected with shigella sonnei compared with pksr100 ( outer ring , purple ) , a multidrug - resistance plasmid from a case of s. flexneri 3a infection occurring among men who have sex in men ( 4 ) . , we defined a case - patient as a resident of england with laboratory - confirmed s. sonnei infection belonging to a 5 snp cluster with the snp address 1.3.3.9.207.212.% , a resistance profile characterized by the presence of the plasmid p183660 , and a specimen collected during september 1 , 2015february 29 , 2016 . we identified 9 case - patients ( figure 2 ) from fecal specimens ; all had no known travel history in the 2 weeks before illness . treatment failure was reported for 2 patients ; both were hospitalized and 1 died , although shigella was not recorded as a cause of death . diagnoses occurred in general practice ( n = 5 ) , sexual health clinics ( n = 2 ) , and hospitals ( n = 2 ) . seven patients resided in london ; 2 resided elsewhere in england , 1 of whom reported recent travel to london . maximum - likelihood phylogeny showing isolates from a cluster of 9 cases ( gray shading ) of shigella sonnei infection among men who have sex with men in england , 2015 . for context , 246 s. sonnei isolates that are representatives from each t25 cluster were included in the comparison . depth questionnaires administered by telephone interviews collected information on sexual history , food exposures , and travel history ; 8 patients completed the interviews . seven answered detailed sexual history questions ( including the 2 patients identified as msm from clinical reporting data ) ; all 7 reported having male partners . six reported exposures considered to be high risk for shigella transmission during the incubation period ( e.g. , fisting , sex under the influence of recreational drugs , oral - anal contact , attendance at sex parties , or use of sex toys with a partner ) ( table 2 ) . reported number of sexual partners during the 2 weeks before illness was 05 . the 7 patients who completed the sexual history questions reported previous high - risk sexual exposures ; 6 of these patients and 1 patient who partially completed the questionnaire reported a history of other sexually transmitted infections , including gonorrhea , chlamydia , syphilis , nonspecific urethritis , hepatitis c , and pubic lice . five reported using mobile apps to meet partners at some time in the past ; none reported a prior shigellosis diagnosis . all had visited sexual health services ( table 2 ) . some patients were hiv positive ( * esbl , extended - spectrum -lactamase ; scat play , sexual  arousal or activity linked to feces . unknowns were not included in percentage calculations ; 7 of 9 patients completed and 1 partially completed interviews about sexual behavior . no epidemiologic links were identified among patients , and no point sources were identified , although food exposure data was collected for 5 patients only . two reported attending the same sex - on - premises venue in london 3 months apart ( 1 reported no sexual contact at the venue ) . none reported awareness of possible infection with shigella spp . or of contact with others with gastrointestinal symptoms . patients reported that they accessed health promotion messages at sexual health clinics and on the internet . we describe a phylogenetic cluster of esbl - producing s. sonnei infections in msm in england that raises concerns about the ability to manage the spread of resistant shigella infection in this population . whole - genome sequencing revealed that the multidrug - resistance phenotype is conferred by acquisition of an incfii plasmid ( p183660 ) known to be circulating in s. flexneriaffected msm ( 4 ) ; this plasmid has acquired blactx - m-27 . patient - reported behaviors were similar to those reported in an earlier s. flexneri epidemic among msm : high numbers of sexual partners , high levels of condomless sex , attendance at sex parties , sex under the influence of recreational drugs , and prior hiv infection ( 6 ) . we identified no point source , further indicating that sexual contact was the dominant mode of transmission . although s. sonnei causes self - limiting diarrhea in most patients , life - threatening invasive infections in patients co - infected with hiv have occurred ( 7 ) . quinolone and azithromycin resistance have been observed in recent outbreaks of s. sonnei infections in msm ; cepaholsporins are recognized as a suitable therapeutic choice for invasive or prolonged infections ( 8,9 ) . primary public health concerns include possible treatment failure for severe shigellosis in immunocompromised patients ; further spread of the multidrug - resistant incfii plasmid to other enteric pathogens in msm , with possible implications for treatment among the immunocompromised ; rapid spread of drug - resistant s. sonnei infections among msm , including outside the united kingdom , as happened with s. flexneri 3a ( 4 ) , especially among the hiv infected ; and transmission through food handling and childcare centers , with potential to cause outbreaks of drug - resistant s. sonnei infections in other populations . low awareness of shigella infections among patients in our study suggests that prior awareness campaigns targeting high - risk msm in england ( 10 ) have not been fully successful . future campaigns being planned to improve awareness of shigella infection and transmission routes will target social media , sexual health clinics , and primary care workers to increase awareness among msm and healthcare staff . frontline sexual health clinicians and microbiologists in england have been made aware of emerging drug resistance in shigella spp . among this vulnerable group and of the need to perform antimicrobial drug susceptibility testing if treatment is considered necessary .
in england in 2015 , shigella sonnei isolates from men who have sex with men produced extended - spectrum -lactamases and exhibited macrolide resistance . 
 whole - genome sequencing showed a close relationship among the isolates , which harbored a plasmid that was previously identified in a shigellosis outbreak among this population but has acquired a mobile element .