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Antimicrobial resistance is a major issue in the Shigellae, particularly as a specific multidrug-resistant (MDR) lineage of Shigella sonnei (lineage III) is becoming globally dominant. Ciprofloxacin is a recommended treatment for Shigella infections. However, ciprofloxacin-resistant S. sonnei are being increasingly isolated in Asia and sporadically reported on other continents. We hypothesized that Asia is a primary hub for the recent international spread of ciprofloxacin-resistant S. sonnei. We performed whole-genome sequencing on a collection of 60 contemporaneous ciprofloxacin-resistant S. sonnei isolated in four countries within Asia (Vietnam, n = 11; Bhutan, n = 12; Thailand, n = 1; Cambodia, n = 1) and two outside of Asia (Australia, n = 19; Ireland, n = 16). We reconstructed the recent evolutionary history of these organisms and combined these data with their geographical location of isolation. Placing these sequences into a global phylogeny, we found that all ciprofloxacin-resistant S. sonnei formed a single clade within a Central Asian expansion of lineage III. Furthermore, our data show that resistance to ciprofloxacin within S. sonnei may be globally attributed to a single clonal emergence event, encompassing sequential gyrA-S83L, parC-S80I, and gyrA-D87G mutations. Geographical data predict that South Asia is the likely primary source of these organisms, which are being regularly exported across Asia and intercontinentally into Australia, the United States and Europe. Our analysis was limited by the number of S. sonnei sequences available from diverse geographical areas and time periods, and we cannot discount the potential existence of other unsampled reservoir populations of antimicrobial-resistant S. sonnei. This study suggests that a single clone, which is widespread in South Asia, is likely driving the current intercontinental surge of ciprofloxacin-resistant S. sonnei and is capable of establishing endemic transmission in new locations. Despite being limited in geographical scope, our work has major implications for understanding the international transfer of antimicrobial-resistant pathogens, with S. sonnei acting as a tractable model for studying how antimicrobial-resistant Gram-negative bacteria spread globally.

Shigella sonnei increasingly dominates the international epidemiological landscape of shigellosis. Treatment options for S. sonnei are dwindling due to resistance to several key antimicrobials, including the fluoroquinolones. Here we analyse nearly 400  S. sonnei whole genome sequences from both endemic and non-endemic regions to delineate the evolutionary history of the recently emergent fluoroquinolone-resistant S. sonnei . We reaffirm that extant resistant organisms belong to a single clonal expansion event. Our results indicate that sequential accumulation of defining mutations ( gyrA -S83L, parC -S80I, and gyrA -D87G) led to the emergence of the fluoroquinolone-resistant S. sonnei population around 2007 in South Asia. This clone was then transmitted globally, resulting in establishments in Southeast Asia and Europe. Mutation analysis suggests that the clone became dominant through enhanced adaptation to oxidative stress. Experimental evolution reveals that under fluoroquinolone exposure in vitro, resistant S. sonnei develops further intolerance to the antimicrobial while the susceptible counterpart fails to attain complete resistance. Shigella sonnei is one of the main species causing shigellosis worldwide. Here the authors analyse nearly 400  S. sonnei genome sequences and carry out experimental evolution experiments to shed light into the evolutionary processes underlying the recent emergence of fluoroquinolone resistance in this pathogen.

The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several treatment failures and isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. Typhi isolates were genome sequenced and clinical observations, treatment failures and fever clearance times (FCTs) were stratified by lineage. Most fluoroquinolone-resistant S. Typhi belonged to a specific H58 subclade. Treatment failure with S. Typhi-H58 was significantly less frequent with ceftriaxone (3/31; 9.7%) than gatifloxacin (15/34; 44.1%)(Hazard Ratio 0.19, p=0.002). Further, for gatifloxacin-treated patients, those infected with fluoroquinolone-resistant organisms had significantly higher median FCTs (8.2 days) than those infected with susceptible (2.96) or intermediately resistant organisms (4.01)(p<0.001). H58 is the dominant S. Typhi clade internationally, but there are no data regarding disease outcome with this organism. We report an emergent new subclade of S. Typhi-H58 that is associated with fluoroquinolone treatment failure. Clinical trial registration: ISRCTN63006567. People who ingest a type of bacteria called Salmonella Typhi can develop the symptoms of typhoid fever. This disease is common in low-income settings in Asia and Africa, and causes a high rate of death in people who are not treated with antimicrobial drugs. During a study in Nepal, Thanh et al. tried to evaluate which of two antimicrobials was better for treating typhoid fever. One of the drugs – called gatifloxacin – did not work in some of the patients. To understand why this treatment failed, Thanh et al. decoded the entire DNA sequences of all the Salmonella Typhi bacteria isolated during the study. Comparing this genetic data to the clinical data of the patients identified a new variant of Salmonella Typhi. These bacteria have a specific combination of genetic mutations that render them resistant to the family of drugs that gatifloxacin belongs to – the fluoroquinolones. Patients infected with the variant bacteria and treated with gatifloxacin were highly likely to completely fail treatment and have longer-lasting fevers. On further investigation Thanh et al. found these organisms were likely recently introduced into Nepal from India. Fluoroquinolones are amongst the most effective and common antimicrobials used to treat typhoid fever and other bacterial infections. However, the presence of bacteria that are resistant to these compounds in South Asia means that they should no longer be the first choice of drug to treat typhoid fever in this location.

Multidrug‐resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic diversity of K. pneumoniae in resource‐poor hospital settings. Through whole‐genome sequencing (WGS), we reconstructed an outbreak of MDR K. pneumoniae occurring on high‐dependency wards in a hospital in Kathmandu during 2012 with a case‐fatality rate of 75%. The WGS analysis permitted the identification of two MDR K. pneumoniae lineages causing distinct outbreaks within the complex endemic K. pneumoniae . Using phylogenetic reconstruction and lineage‐specific PCR, our data predicted a scenario in which K. pneumoniae , circulating for 6 months before the outbreak, underwent a series of ward‐specific clonal expansions after the acquisition of genes facilitating virulence and MDR. We suggest that the early detection of a specific NDM‐1 containing lineage in 2011 would have alerted the high‐dependency ward staff to intervene. We argue that some form of real‐time genetic characterisation, alongside clade‐specific PCR during an outbreak, should be factored into future healthcare infection control practices in both high‐ and low‐income settings. Synopsis Whole‐genome sequencing and further data analysis allowed for a comprehensive understanding of the emergence and spread of two highly virulent clones of drug‐resistant Klebsiella pneumonia bloodstream infections from one hospital in Kathmandu, Nepal. MDR Klebsiella pneumoniae (Kp) can cause serious hospital outbreaks and can be associated with high mortality in hospitals in developing countries. Whole‐genome sequencing (WGS) of Kp bloodstream infections was used to study localized transmission and genetic adaptation during a hospital outbreak in Nepal. Genetic material specific to outbreak lineages permitted a retrospective temporal reconstruction of two Kp outbreak lineages across the hospital. The added benefit of Kp WGS in this study was to dissect these outbreaks with extremely fine detail. Genetic characterization of Kp causing bloodstream infections in hospitals in developing countries should be performed routinely to identify and isolate outbreaks early. Graphical Abstract Whole‐genome sequencing and further data analysis allowed for a comprehensive understanding of the emergence and spread of two highly virulent clones of drug‐resistant Klebsiella pneumonia bloodstream infections from one hospital in Kathmandu, Nepal.

Non-typhoidal Salmonella (NTS) serovars, sequences types and antimicrobial susceptibility profiles have specific associations with animal and human infections in Vietnam. Antimicrobial resistance may have an effect on the manifestation of human NTS infections, with isolates from asymptomatic individuals being more susceptible to antimicrobials than those associated with animals and human diarrhoea.

The host–pathogen interactions induced by Salmonella Typhi and Salmonella Paratyphi A during enteric fever are poorly understood. This knowledge gap, and the human restricted nature of these bacteria, limit our understanding of the disease and impede the development of new diagnostic approaches. To investigate metabolite signals associated with enteric fever we performed two dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC/TOFMS) on plasma from patients with S. Typhi and S. Paratyphi A infections and asymptomatic controls, identifying 695 individual metabolite peaks. Applying supervised pattern recognition, we found highly significant and reproducible metabolite profiles separating S. Typhi cases, S. Paratyphi A cases, and controls, calculating that a combination of six metabolites could accurately define the etiological agent. For the first time we show that reproducible and serovar specific systemic biomarkers can be detected during enteric fever. Our work defines several biologically plausible metabolites that can be used to detect enteric fever, and unlocks the potential of this method in diagnosing other systemic bacterial infections. Enteric fever is estimated to affect over 37 million people every year. Although treatable with antimicrobial drugs, a slow and/or incorrect diagnosis can result in serious and often life-threatening complications. Enteric fever is the combined name for typhoid fever and paratyphoid fever. While the symptoms of these diseases are indistinguishable, the strains of Salmonella bacteria that cause them are genetically distinct. Moreover, the two organisms that cause the disease exhibit different propensities to develop resistance to antimicrobials. It is important, therefore, to be able to distinguish between typhoid fever and paratyphoid fever so that the correct treatment can be prescribed. However, the diagnostic tools available today struggle to discriminate between Salmonella Typhi (which causes typhoid fever) and Salmonella Paratyphi A (which causes paratyphoid fever). Now, Näsström et al. have developed a methodology that can determine if an individual is infected by Salmonella Typhi or Salmonella Paratyphi A, or neither. Rather than trying to detect the bacteria themselves, the test relies on measuring the levels of various metabolites—molecules produced during metabolism—in the blood. Näsström et al. discovered a set of six metabolites that are affected in different ways by typhoid and paratyphoid fever. The next challenge is to develop this approach so it can be used in endemic settings.

Conventional disease surveillance for shigellosis in developing country settings relies 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.Hao Chung The et al. analyze 1,804 Shigella genome sequences from organisms isolated in four Southeast Asian countries over three decades to study the evolution of both S. flexneri and S. sonnei. This study suggests that adaptation to antimicrobial pressure may have played a pivotal role in the recent evolutionary trajectory of Shigella in Southeast Asia.

•Shigella sonnei is an emergent and highly drug resistant diarrheal pathogen.•The half-life of maternal S. sonnei IgG in infants is 43 days.•Maternal titer, antibody transfer ratio and gestational age influence birth titer.•Incidence of seroconversion in infants in southern Vietnam is 4/100 infant years.•Children should be vaccinated after 5 months of age if a candidate is licensed. Shigella sonnei is an emergent and major diarrheal pathogen for which there is currently no vaccine. We aimed to quantify duration of maternal antibody against S. sonnei and investigate transplacental IgG transfer in a birth cohort in southern Vietnam. Over 500-paired maternal/infant plasma samples were evaluated for presence of anti-S. sonnei-O IgG and IgM. Longitudinal plasma samples allowed for the estimation of the median half-life of maternal anti-S. sonnei-O IgG, which was 43 days (95% confidence interval: 41–45 days). Additionally, half of infants lacked a detectable titer by 19 weeks of age. Lower cord titers were associated with greater increases in S. sonnei IgG over the first year of life, and the incidence of S. sonnei seroconversion was estimated to be 4/100 infant years. Maternal IgG titer, the ratio of antibody transfer, the season of birth and gestational age were significantly associated with cord titer. Maternal anti-S. sonnei-O IgG is efficiently transferred across the placenta and anti-S. sonnei-O maternal IgG declines rapidly after birth and is undetectable after 5 months in the majority of children. Preterm neonates and children born to mothers with low IgG titers have lower cord titers and therefore may be at greater risk of seroconversion in infancy.

Maternal disorders are the third leading cause of sepsis globally, accounting for 5.7 million (12%) cases in 2017. There are increasing concerns about the emergence of antimicrobial resistance (AMR) in bacteria commonly causing maternal sepsis. Our aim is to describe the protocol for a clinical and microbiology laboratory study to understand risk factors for and the bacterial etiology of maternal sepsis in a tertiary Obstetrics and Gynaecology Hospital. This case-control study aims to recruit 100 cases and 200 controls at Tu Du Hospital in Ho Chi Minh City, Vietnam, which had approximately 55,000 births in 2022. Women aged ≥ 18 years and ≥ 28 weeks gestation having a singleton birth will be eligible for inclusion as cases or controls, unless they have an uncomplicated localised or chronic infection, or an infection with SARS-CoV-2. Cases will include pregnant or recently pregnant women with sepsis recognised between the onset of labour and/or time of delivery/cessation of pregnancy for up to 42 days post-partum. Sepsis will be defined as suspected or confirmed infection with an obstetrically modified Sequential Organ Failure Assessment score of ≥ 2, treatment with intravenous antimicrobials and requested cultures of any bodily fluid. Controls will be matched by age, location, parity, mode of delivery and gestational age. Primary and secondary outcomes are risk factors associated with the development of maternal sepsis, the frequency of adverse outcomes due to maternal sepsis, bacterial etiology and AMR profiles of cases and controls. This study will improve understanding of the epidemiology and clinical implications of maternal sepsis management including the presence of AMR in women giving birth in Vietnam. It will help us to determine whether women in this setting are receiving optimal care and to identify opportunities for improvement.