Effect of Chestnut (Castanea Mollissima Blume) Bur Polyphenol Extract on Shigella dysenteriae: Antibacterial Activity and the Mechanism.

Shigella dysenteriae is a highly pathogenic microorganism that can cause human bacillary dysentery by contaminating food and drinking water. This study investigated the antibacterial activity of chestnut bur polyphenol extract (CBPE) on S. dysenteriae and the underlying mechanism. The results showed that the minimum inhibitory concentration (MIC) of CBPE for S. dysenteriae was 0.4 mg/mL, and the minimum bactericidal concentration (MBC) was 1.6 mg/mL. CBPE treatment irreversibly disrupted cell morphology, decreased cell activity, and increased cell membrane permeability, cell membrane depolarization, and cell content leakage of S. dysenteriae, indicating that CBPE has obvious destructive effects on the cell membrane and cell wall of S. dysenteriae. Combined transcriptomic and metabolomics analysis revealed that CBPE inhibits S. dysenteriae by interfering with ABC protein transport, sulfur metabolism, purine metabolism, amino acid metabolism, glycerophospholipid metabolism, and some other pathways. These findings provide a theoretical basis for the prevention and treatment of S. dysenteriae infection with extract from chestnut burs.

Foodborne Outbreak of Extended Spectrum Beta-lactamase Producing Shigella sonnei Associated with Contaminated Spring Onions in the United Kingdom.

Globalization of the food supply chain has created conditions favorable for emergence and spread of multidrug-resistant (MDR) foodborne pathogens. In November 2021, the UK Health Security Agency detected an outbreak of 17 cases infected with the same strain of MDR extended spectrum beta-lactamase (ESBL)-producing Shigella sonnei. Phylogenetic analysis of whole-genome sequencing data revealed the outbreak was closely related to strains of S. sonnei isolated from travelers returning to the UK from Egypt. None of the outbreak cases reported travel and all 17 cases reported eating food from a restaurant/food outlet in the week prior to symptom onset, of which 11/17 (64.7%) ate at branches of the same national restaurant franchise. All 17 cases were adults and 14/17 (82.4%) were female. Ingredient-level analyses of the meals consumed by the cases identified spring onions as the common ingredient. Food chain investigations revealed that the spring onions served at the implicated restaurants could be traced back to a single Egyptian producer. The foodborne transmission of ESBL-producing bacteria is an emerging global health concern, and concerted action from all stakeholders is required to ensure an effective response to mitigate the risks to public health.

Toxicity and Activity of Ethanolic Leaf Extract of Paullinia pinnata Linn (Sapindaceae) in Shigella flexneri-Induced Diarrhea in Wistar Rats.

Herbal products from Paullinia pinnata Linn are widely used in African folk medicine to treat several infectious diseases. Although the extracts from this plant has been shown to possess antimicrobial potential, their activity in infectious diarrhea is less reported. Diarrhea was induced by oral administration of 1.2 × 109 CFU/mL of Shigella flexneri to the rats. The infected rats were treated for 5 days with the doses of 111.42, 222.84, and 445.68 mg/kg of P pinnata. The level of biochemical parameters was assessed and histology of organs examined by 14 days subacute toxicity. S flexneri stool load was considerably reduced after 4 days of treatment with the dose of 445.68 mg/kg, 5 days at the dose of 222.84 mg/kg for the extract, and 2 days with ciprofloxacin. The dose of 111.42 mg/kg appeared efficient after 5 days of treatment. The creatinine level increased at the dose of 445.68 mg/kg in both male and female rats and decrease at the dose of 222.84 mg/mL in female rats while an increase was noted in the male rats. Liver and kidney histology were modified at the dose of 445.68 mg/kg while no change was observed at the doses of 111.42 and 222.84 mg/kg. P pinnata leaf extract is efficient against infectious diarrhea at 111.42 mg/kg without side effect.

Anti-Shigellosis Activity of Cola anomala Water/Ethanol Pods Extract on Shigella flexneri-Induced Diarrhea in Rats.

This study was undertaken to evaluate the activities of water/ethanol Cola anomala pods extract. In vitro antimicrobial susceptibility was determined by the disk diffusion method; the minimum inhibitory concentration and minimum bactericidal concentration were determined by agar dilution technique. In vivo, shigellosis was induced in healthy Wistar albino rats by oral administration of Shigella flexneri inoculum, 12 × 108 CFU/mL. At the onset of diarrhea, infected and normal control animals were subdivided into various groups treated with distilled water, with water/ethanol Cola anomala pods extract at 25, 50, or 100 mg/kg, or with ciprofloxacin, 2.5 mg/kg. After one-week treatment, rats were sacrificed, and blood and colon were collected. Blood was used for blood cell count. A portion of the colon served for histological studies while homogenate from the remaining part was centrifuged and the supernatant was collected for the determination of NO, PGE2, IL-1ß, and TNF-α levels. In vitro, water/ethanol Cola anomala pods extract showed to be bactericidal, with a minimum inhibitory concentration of 2.0 mg/mL and a minimum bactericidal concentration of 3.0 mg/mL. In diarrheic rats, the extract significantly (P < 0.01) increased the white blood cells and significantly (P < 0.01) decreased stool Shigella density from the first to the seventh day of treatment. It partially restored the structure of eroded intestine epithelium and prevented weight loss; the dose dependently and significantly (P < 0.001) decreased NO, IL-1ß, and TNF-α production in the colon and was found to have no significant effect on PGE2 production. These results support the use of this plant in traditional medicine in the treatment of gastrointestinal ailments.

Testing the efficacy of kitasamycin for use in the control and treatment of swine dysentery in experimentally infected pigs.

BACKGROUND: Swine dysentery (SD) caused by Brachyspira hyodysenteriae is an important disease in Australia. AIM: The aim of this study is to evaluate the macrolide antibiotic kitasamycin for use in SD control. METHODS: The minimum inhibitory concentrations (MICs) of kitasamycin, tylosin and lincomycin for 32 Australian isolates of B. hyodysenteriae were evaluated. Mutations in the 23S rRNA gene were examined. Isolate '13' with a low kitasamycin MIC was used to challenge weaner pigs. Sixty pigs were housed in 20 pens each containing three pigs: pigs in four pens received 2 kg/tonne of a product containing kitasamycin (3.1% active) prophylactically in their food starting 4 days before B. hyodysenteriae challenge (group 1); pigs in four pens were challenged and received the same dose therapeutically once one pig in a pen showed diarrhoea (group 2); four pens were challenged and received 4 kg/tonne of the product therapeutically (group 3); four pens were challenged but not medicated (group 4); two pens were unmedicated and unchallenged (group 5) and two pens received 2 kg/tonne and were unchallenged (group 6). Pigs were monitored for B. hyodysenteriae excretion and disease. RESULTS: Macrolide resistance was widespread, and mutations in the 23S rRNA gene were identified in 23 isolates. Four isolates with kitasamycin MICs < 5 µg/mL were considered susceptible. Following experimental challenge, 10 of 12 unmedicated pigs developed SD. No pigs receiving kitasamycin prophylactical or therapeutically developed SD. Medicated pigs shed low numbers of B. hyodysenteriae in their faeces. CONCLUSIONS: Kitasamycin can help control SD in pigs infected with susceptible isolates of B. hyodysenteriae.

A murine model of diarrhea, growth impairment and metabolic disturbances with Shigella flexneri infection and the role of zinc deficiency.

Shigella is one of the major enteric pathogens worldwide. We present a murine model of S. flexneri infection and investigate the role of zinc deficiency (ZD). C57BL/6 mice fed either standard chow (HC) or ZD diets were pretreated with an antibiotic cocktail and received S. flexneri strain 2457T orally. Antibiotic pre-treated ZD mice showed higher S. flexneri colonization than non-treated mice. ZD mice showed persistent colonization for at least 50 days post-infection (pi). S. flexneri-infected mice showed significant weight loss, diarrhea and increased levels of fecal MPO and LCN in both HC and ZD fed mice. S. flexneri preferentially colonized the colon, caused epithelial disruption and inflammatory cell infiltrate, and promoted cytokine production which correlated with weight loss and histopathological changes. Infection with S. flexneri ΔmxiG (critical for type 3 secretion system) did not cause weight loss or diarrhea, and had decreased stool shedding duration and tissue burden. Several biochemical changes related to energy, inflammation and gut-microbial metabolism were observed. Zinc supplementation increased weight gains and reduced intestinal inflammation and stool shedding in ZD infected mice. In conclusion, young antibiotic-treated mice provide a new model of oral S. flexneri infection, with ZD promoting prolonged infection outcomes.

WHO consultation on ETEC and Shigella burden of disease, Geneva, 6-7th April 2017: Meeting report.

According to the 2015 Global Burden of Disease Study, diarrhea ranked ninth among causes of death for all ages, and fourth among children under 5 years old, accounting for an estimated 499,000 deaths in this young age group. It was also the second most common cause of years lived with disability (2.39 billion YLDs). The goal of the WHO/UNICEF Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhea (GAPPD) is to reduce deaths from diarrhea in children under 5 years of age to less than 1 per 1000 live births, by 2025. Development of new and improved vaccines against diarrheal infections is a fundamental element of the strategy towards achieving this goal. Enterotoxigenic Escherichia coli (ETEC) and Shigella are enteropathogens that cause significant global mortality and morbidity, particularly in low- and middle-income countries. In 2016, WHO's Product Development for Vaccines Advisory Committee (PDVAC) recommended that the WHO's Initiative for Vaccine Research (IVR) engage in this area, based on PDVAC's criteria of prioritizing the development of vaccines against pathogens that will address a major unmet public health need, and for which clinical candidates with a good probability of technical success are in the pipeline. As a first step, WHO's IVR convened global subject matter experts to discuss the current global ETEC and Shigella disease burden estimates, including the current understanding of the long-term indirect effects of ETEC and Shigella infection, and how these data may affect future decision making on vaccine development for both pathogens. The available global burden estimates for ETEC and Shigella differ with respect to the relative importance of these two pathogens. The mortality estimates vary between iterations published by the same group, as well as between estimates of different groups, although the uncertainty intervals are broad and overlapping. These variances are attributable to differences in the data available and incorporated in the models; the methods used to detect the pathogens; the modelling methodologies; and, to actual changes in the total number of diarrheal deaths over time. The changes in the most recently reported mortality estimates for these pathogens, as compared to previous iterations, has led to debate as to whether investment in development of stand-alone vaccines, rather than combined vaccines, is warranted from cost-effectiveness and vaccine impact perspectives. Further work will be needed to understand better the variances and uncertainties in the reported mortality estimates to support investment decision making, and ultimately policy recommendations for vaccine use. In addition, a comprehensive assessment of the value proposition for vaccines against these pathogens is needed and will be strengthened if the long-term health consequences associated with diarrhea and dysentery due to these pathogens are better defined.

Prevalence and antibiotic susceptibility patterns of Shigella and Salmonella among children aged below five years with Diarrhoea attending Nigist Eleni Mohammed memorial hospital, South Ethiopia.

BACKGROUND: Diarrhoeal disease is the second leading cause of death among children aged below 5 years. Even though, both preventable and treatable diseases, globally there are nearly 1.7 billion cases of childhood diarrhoeal disease and responsible for killing around 525,000 children every year. Shigella and Salmonella species were the leading cause of etiologic agents for diarrhoea associated deaths. The aim of this study was to determine the prevalence and antibiotic susceptibility patterns of Shigella and Salmonella isolated from children aged below 5 years with diarrhoea attending Nigist Eleni Mohammed Memorial Hospital, Hossana, South Ethiopia. METHODS: A cross sectional study was conducted from June 02 to September 24, 2017. Two hundred four children aged below 5 years with diarrhoea were enrolled consecutively using convenience sampling technique. Stool specimens were processed in accordance with the standard bacteriological methods and antibiotic susceptibility pattern of the isolates was determined using disc diffusion method. Data were analyzed using SPSS version 20. RESULTS: Out of the 204 children aged below 5 years with diarrhoeal disease 19/204 (9.3%, [95%CI, 5.7-13.7%]) of them were positive for bacterial growth, of which 17/204(8.3%) were Shigella species and 2/204(1%) were Salmonella species. Both Shigella and Salmonella isolates were 100% susceptible to norfloxacin, nalidixic acid and kanamycin. However, isolates of Shigella showed 100, 76.5 and 64.7% resistance to ampicillin, gentamicin and cotrimoxazole respectively while Salmonella species were highly resistant to ampicillin and gentamicin (100% each). CONCLUSIONS: Salmonella and Shigella species is prevalent in the current study area. Among the tested antibiotics, norfloxacin, nalidixic acid and kanamycin were found to be most effective for both isolates. Both species are developing resistance to the commonly prescribed antibiotic. Therefore, culture based bacterial species identification and antimicrobial susceptibility testing services are strongly recommended to avoid empirical treatment in the study area.

Antibiotic resistance and molecular characterization of shigella isolates recovered from children aged less than 5 years in Manhiça, Southern Mozambique.

The objective of this study was to assess antibiotic resistance and the molecular epidemiology of shigella isolates from a case-control study of diarrhoea, conducted from 2007 to 2012 in children aged less than 5 years in Manhiça district, southern Mozambique. All isolates were tested for antimicrobial susceptibility using the disc diffusion method. Polymerase chain reaction was used to detect different molecular mechanisms of antibiotic resistance. Serotyping was performed using specific antisera. The clonal relationship of Shigella flexneri and Shigella sonnei was assessed by pulsed-field gel electrophoresis (PFGE). Of the 67 shigella isolates analysed, 59 were diarrhoeal cases and eight were controls. S. flexneri (70.1%; 47/67) was the most common species, followed by S. sonnei (23.9%; 16/67). The most prevalent S. flexneri serotypes were 2a (38.3%; 18/47), 6 (19.2%; 9/47) and 1b (14.9%; 7/47). High rates of antimicrobial resistance were observed for trimethoprim-sulfametoxazole (92.5%; 62/67), tetracycline (68.7%; 46/67), chloramphenicol (53.7%; 36/67) and ampicillin (50.7%; 34/67). Multi-drug resistance (MDR) was present in 55.2% (37/67) of the isolates and was associated with a case fatality rate of 8.1% (3/37). PFGE revealed 22 clones (16 S. flexneri and 6 S. sonnei), among which P1 (31.9%; 15/47), P9 (17%; 8/47) and P2 (10.6%; 5/47) were the most prevalent clones of S. flexneri. In conclusion, S. flexneri was the most prevalent species, with MDR isolates mainly belonging to three specific clones (P1, P9 and P2). The case fatality rate observed among MDR isolates is a matter of concern, indicating the need for appropriate treatment.

Azithromycin Resistance in Shigella spp. in Southeast Asia.

Infection by Shigella spp. is a common cause of dysentery in Southeast Asia. Antimicrobials are thought to be beneficial for treatment; however, antimicrobial resistance in Shigella spp. is becoming widespread. We aimed to assess the frequency and mechanisms associated with decreased susceptibility to azithromycin in Southeast Asian Shigella isolates and use these data to assess appropriate susceptibility breakpoints. Shigella isolates recovered in Vietnam and Laos were screened for susceptibility to azithromycin (15 µg) by disc diffusion and MIC. Phenotypic resistance was confirmed by PCR amplification of macrolide resistance loci. We compared the genetic relationships and plasmid contents of azithromycin-resistant Shigella sonnei isolates using whole-genome sequences. From 475 available Shigella spp. isolated in Vietnam and Laos between 1994 and 2012, 6/181 S. flexneri isolates (3.3%, MIC ≥ 16 g/liter) and 16/294 S. sonnei isolates (5.4%, MIC ≥ 32 g/liter) were phenotypically resistant to azithromycin. PCR amplification confirmed a resistance mechanism in 22/475 (4.6%) isolates (mphA in 19 isolates and ermB in 3 isolates). The susceptibility data demonstrated the acceptability of the S. flexneri (MIC ≥ 16 g/liter, zone diameter ≤ 15 mm) and S. sonnei (MIC ≥ 32 g/liter, zone diameter ≤ 11 mm) breakpoints with a <3% discrepancy. Phylogenetic analysis demonstrated that decreased susceptibility has arisen sporadically in Vietnamese S. sonnei isolates on at least seven occasions between 2000 and 2009 but failed to become established. While the proposed susceptibility breakpoints may allow better recognition of resistant isolates, additional studies are required to assess the impact on the clinical outcome. The potential emergence of azithromycin resistance highlights the need for alternative options for management of Shigella infections in countries where Shigella is endemic.

Shigella species epidemiology and antimicrobial susceptibility: the implications of emerging azithromycin resistance for guiding treatment, guidelines and breakpoints.

OBJECTIVES: To examine antimicrobial susceptibility patterns and predictors of resistance among Shigella isolates in New South Wales (NSW), Australia during 2013-14 with emphasis on azithromycin. METHODS: Cross-sectional analysis of all shigellosis cases (160) notified to public health authorities in NSW, Australia was performed. RESULTS: Among 160 Shigella isolates tested, 139 (86.9%) were susceptible to azithromycin, 104 (65.0%) to ciprofloxacin and 38 (23.7%) to co-trimoxazole. Ciprofloxacin resistance was 1.9 times more common in infections acquired in Australia compared with those acquired overseas, while azithromycin resistance was 8.5 times more common in males. CONCLUSIONS: We recommend ongoing reconsideration of guidelines for the treatment of shigellosis based on emerging resistance patterns. First-line therapy may need to be reconsidered based on local resistance rates due to common resistance to co-trimoxazole and ciprofloxacin. We recommend culture and susceptibility testing for suspected and proven shigellosis. Azithromycin susceptibility breakpoints for Shigella species may need to be species specific.

Improving chances for successful clinical outcomes with better preclinical models.

In order to avoid expensive clinical failures, better and more predictive animal models of vaccine efficacy are needed to screen Shigella and ETEC vaccine candidates for protective efficacy. The 2016 Vaccines Against Shigella and ETEC (VASE) Conference included a workshop focused on the strengths and weaknesses of current models, particularly in terms of the correlation to vaccine efficacy in human clinical trials. Workshop presenters shared information on existing preclinical animal models for assessing the immunogenicity and protective efficacy of Shigella and ETEC vaccines. The presentations were followed by a discussion about how to best utilize these models, how the models can be improved, and best practices for Shigella and ETEC vaccine developers. The workshop concluded with three major recommendations for the field: (1) develop better and more consistent reagents for animal studies and make them widely available, (2) prioritize harmonization of animal models and immunology assays, and (3) develop preclinical correlates of protection, which will be key in selecting the best vaccine candidates for further clinical development.

Antimicrobial susceptibility pattern of Shigella spp. isolated from children under 5 years of age attending tertiary care hospitals, Nepal along with first finding of ESBL-production.

BACKGROUND: Shigella is an important cause of bacterial gastroenteritis in resource-poor countries. The treatment of shigellosis mostly requires antibiotics. However, the increase of multidrug resistance along with emergence of extended-spectrum ß-lactamase and ciprofloxacin resistance among Shigella spp. has challenged the situation. This study was conducted to determine the distribution of species and antibiotic susceptibility pattern of Shigella species isolated from stool specimen among children less than 5 years of age in Nepal. RESULTS: Out of total 717 stool samples collected, 15 cases of Shigella spp. was isolated which includes 12 S. flexneri and 3 S. sonnei. Multidrug resistance was found among 13(86%) of the isolates. One of the isolates of S. flexneri was found to be ESBL-producer with MIC >256 mg/L for cefixime. CONCLUSION: The high occurrence of multidrug resistance among Shigella spp. along with a case of ESBL-production for the first time in Nepal alarms the concerns about dissemination of the resistant isolates. So, systemic monitoring of the antimicrobial susceptibility pattern of Shigella spp. is becoming crucial to guide therapy.

Identification and antimicrobial resistance patterns of bacterial enteropathogens from children aged 0-59 months at the University Teaching Hospital, Lusaka, Zambia: a prospective cross sectional study.

BACKGROUND: Bacterial diarrhoeal disease is among the most common causes of mortality and morbidity in children 0-59 months at the University Teaching Hospital in Lusaka, Zambia. However, most cases are treated empirically without the knowledge of aetiological agents or antimicrobial susceptibility patterns. The aim of this study was, therefore, to identify bacterial causes of diarrhoea and determine their antimicrobial susceptibility patterns in stool specimens obtained from the children at the hospital. METHODS: This hospital-based cross-sectional study involved children aged 0-59 months presenting with diarrhoea at paediatrics wards at the University Teaching Hospital in Lusaka, Zambia, from January to May 2016. Stool samples were cultured on standard media for enteropathogenic bacteria, and identified further by biochemical tests. Multiplex polymerase chain reaction was used for characterization of diarrhoeagenic Escherichia coli strains. Antimicrobial susceptibility testing was performed on antibiotics that are commonly prescribed at the hospital using the Kirby-Bauer disc diffusion method, which was performed using the Clinical Laboratory Standards International guidelines. RESULTS: Of the 271 stool samples analysed Vibrio cholerae 01 subtype and Ogawa serotype was the most commonly detected pathogen (40.8%), followed by Salmonella species (25.5%), diarrhoeagenic Escherichia coli (18%), Shigella species (14.4%) and Campylobacter species (3.5%). The majority of the bacterial pathogens were resistant to two or more drugs tested, with ampicillin and co-trimoxazole being the most ineffective drugs. All diarrhoeagenic Escherichia coli isolates were extended spectrum ß-lactamase producers. CONCLUSION: Five different groups of bacterial pathogens were isolated from the stool specimens, and the majority of these organisms were multidrug resistant. These data calls for urgent revision of the current empiric treatment of diarrhoea in children using ampicillin and co-trimoxazole, and emphasizes the need for continuous antimicrobial surveillance as well as the implementation of prevention programmes for childhood diarrhoea.

Aloe vera (Aloe barbadensis Miller) supplemented probiotic lassi prevents Shigella infiltration from epithelial barrier into systemic blood flow in mice model.

The aim of present work was to investigate preventive role of orally administered Aloe vera supplemented probiotic lassi (APL) on Shigella dysenteriae infection in mice. At the end of experimental period (2, 5 and 7 days of challenging), different organs such as spleen, liver, small intestine, large intestine, and peritoneal fluid were collected and assessed for Shigella colonization. Secretary IgA was estimated in intestinal fluid. Blood was collected in heparinized tubes for various haematological studies. Oral administration of APL showed a significant (p < 0.05) reduction in the Shigella counts (log cfu/mL) in all organs as compared to other treatment groups at different intervals after post feeding. Similarly, secretary IgA antibody levels (µg/mL) in intestinal fluid were significantly (p < 0.05) increased in case of APL fed mice. Further, feeding of APL also demonstrated a positive effect on different haematological parameters viz. Hb (gm %), RBC and WBC count. The results indicated the immunoprotective effects of APL against Shigella dysenteriae induced infection in mice.

South Asia as a Reservoir for the Global Spread of Ciprofloxacin-Resistant Shigella sonnei: A Cross-Sectional Study.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections.

OBJECTIVES: We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally. METHODS: Clinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis. Time-kill experiments were performed to evaluate the impact of MIC on the in vitro growth of Shigella and Cox regression modelling was used to compare clinical outcome between treatments and Shigella species. RESULTS: Shigella flexneri patients treated with gatifloxacin had significantly worse outcomes than those treated with ciprofloxacin. However, the MICs of fluoroquinolones were not significantly associated with poorer outcome. The presence of S83L and A87T mutations in the gyrA gene significantly increased MICs of fluoroquinolones. Finally, elevated MICs and the presence of the qnrS gene allowed Shigella to replicate efficiently in vitro in high concentrations of ciprofloxacin. CONCLUSIONS: We found that below the CLSI breakpoint, there was no association between MIC and clinical outcome in paediatric shigellosis infections. However, S. flexneri patients had worse clinical outcomes when treated with gatifloxacin in this study regardless of MIC. Additionally, Shigella harbouring the qnrS gene are able to replicate efficiently in high concentrations of ciprofloxacin and we hypothesize that such strains possess a competitive advantage against fluoroquinolone-susceptible strains due to enhanced shedding and transmission.

Travel Destinations and Sexual Behavior as Indicators of Antibiotic Resistant Shigella Strains--Victoria, Australia.

BACKGROUND: Knowledge of relationships between antibiotic susceptibility of Shigella isolates and travel destination or other risk factors can assist clinicians in determining appropriate antibiotic therapy prior to susceptibility testing. We describe relationships between resistance patterns and risk factors for acquisition in Shigella isolates using routinely collected data for notified cases of shigellosis between 2008 and 2012 in Victoria, Australia. METHODS: We included all shigellosis patients notified during the study period, where Shigella isolates were tested for antimicrobial sensitivity using Clinical and Laboratory Standards Institute breakpoints. Cases were interviewed to collect data on risk factors, including recent travel. Data were analyzed using Stata 13.1 to examine associations between risk factors and resistant strains. RESULTS: Of the 500 cases of shigellosis, 249 were associated with overseas travel and 210 were locally acquired. Forty-six of 51 isolates of Indian origin displayed decreased susceptibility or resistance to ciprofloxacin. All isolates of Indonesian origin were susceptible to ciprofloxacin. Twenty-six travel-related isolates were resistant to all tested oral antimicrobials. Male-to-male sexual contact was the primary risk factor for 80% (120/150) of locally acquired infections among adult males, characterized by distinct periodic Shigella sonnei outbreaks. CONCLUSIONS: Clinicians should consider travel destination as a marker for resistance to common antimicrobials in returning travelers, where severe disease requires empirical treatment prior to receipt of individual sensitivity testing results. Repeated outbreaks of locally acquired shigellosis among men who have sex with men highlight the importance of prevention and control measures in this high-risk group.

Management of acute infectious diarrhea for children living in resource-limited settings.

Acute infectious gastroenteritis continues to be a leading cause of morbidity and mortality in children below 5 years of age, with the majority of deaths concentrated in 35 'low income' countries. In these countries the under five years of age mortality rates reach 100 per 1000 live births, of which a significant proportion are associated with acute diarrhea. Rotavirus, cryptosporidium, Shigella spp and enterotoxigenic Escherichia coli are the main pathogens causing disease in these settings, although other bacteria and parasites can cause moderate to severe disease in different regions and situations. Treatment of children in these setting should be focused on appropriate rehydration, early hospitalization of severely malnourished children, zinc supplementation, and in specific situations, antimicrobials should be considered. The rationale for antimicrobial use should be based on the potential benefits based on published literature and the opportunity for use. This review provides a pathogen-specific update on the potential benefits of antimicrobials and suggests an empirical management approach for children suffering an acute watery or bloody diarrhea in a resource-limited region.

Coverage of diarrhoea-associated Escherichia coli isolates from different origins with two types of phage cocktails.

Eighty-nine T4-like phages from our phage collection were tested against four collections of childhood diarrhoea-associated Escherichia coli isolates representing different geographical origins (Mexico versus Bangladesh), serotypes (69 O, 27 H serotypes), pathotypes (ETEC, EPEC, EIEC, EAEC, VTEC, Shigella), epidemiological settings (community and hospitalized diarrhoea) and years of isolation. With a cocktail consisting of 3 to 14 T4-like phages, we achieved 54% to 69% coverage against predominantly EPEC isolates from Mexico, 30% to 53% against mostly ETEC isolates from a prospective survey in Bangladesh, 24% to 61% against a mixture of pathotypes isolated from hospitalized children in Bangladesh, and 60% coverage against Shigella isolates. In comparison a commercial Russian phage cocktail containing a complex mixture of many different genera of coliphages showed 19%, 33%, 50% and 90% coverage, respectively, against the four above-mentioned collections. Few O serotype-specific phages and no broad-host range phages were detected in our T4-like phage collection. Interference phenomena between the phage isolates were observed when constituting larger phage cocktails. Since the coverage of a given T4-like phage cocktail differed with geographical area and epidemiological setting, a phage composition adapted to a local situation is needed for phage therapy approaches against E. coli pathogens.