scholarly journals Metagenomic Characterization of Gut Microbiota of Carriers of Extended-Spectrum Beta-Lactamase or Carbapenemase-Producing Enterobacteriaceae Following Treatment with Oral Antibiotics and Fecal Microbiota Transplantation: Results from a Multicenter Randomized Trial

2020 ◽  
Vol 8 (6) ◽  
pp. 941
Author(s):  
Stefano Leo ◽  
Vladimir Lazarevic ◽  
Myriam Girard ◽  
Nadia Gaïa ◽  
Jacques Schrenzel ◽  
...  

Background: The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) WP3 study was the first multicenter randomized clinical trial systematically investigating fecal microbiota transplantation (FMT) for intestinal decolonization of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Here, we characterized the temporal dynamics of fecal microbiota changes in a sub-cohort of the R-GNOSIS WP3 participants before and after antibiotics/FMT using whole metagenome shotgun sequencing. Methods: We sequenced fecal DNA obtained from 16 ESBL-E/CPE carriers having received oral colistin/neomycin followed by FMT and their corresponding seven donors. Ten treatment-naïve controls from the same trial were included. Fecal samples were collected at baseline (V0), after antibiotics but before FMT (V2) and three times after FMT (V3, V4 and V5). Results: Antibiotic treatment transiently decreased species richness and diversity and increased the abundance of antibiotic resistance determinants (ARDs). Bifidobacterium species, together with butyrate- and propionate-producing species from Lachnospiraceae and Ruminococcaceae families were significantly enriched in post-FMT microbiota of treated carriers. After FMT, the proportion of Enterobacteriaceae was lower compared to baseline but without statistical significance. Conclusions: Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE.

2020 ◽  
Author(s):  
Kanika Kuwelker ◽  
Nina Langeland ◽  
Iren Löhr ◽  
Joshua Gidion ◽  
Joel Manyahi ◽  
...  

Abstract Background: Extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) has emerged as an urgent global health threat, and is by World Health Organization ranked as priority 1 among pathogens in need of new treatment. Studies have shown high mortality in Tanzanian children with ESBL-E infections. Gut colonization of ESBL-E, which is a potential risk factor of ESBL-E infections, is reported to be very high among children in Tanzania. Probiotics may potentially reduce gut colonization of multidrug-resistant bacteria. However, there is limited data on whether probiotics may reduce ESBL-E carriage in infants. The ProRIDE Trial aims to evaluate whether the use of probiotics can reduce morbidity and mortality among infants in Haydom, Tanzania, and whether this effect is mediated through prevention of ESBL-E carriage. Methods/Design: This large randomized double-blinded placebo-controlled trial aims to recruit 2000 newborn infants at Haydom Lutheran Hospital and the surrounding area in the period of November 2020 to November 2021. Participants will be enrolled from day 0-3 after birth, and randomized to receive probiotics or placebo for four weeks. Participants will be followed up for six months, during which three visits will be made to collect clinical and demographic information, as well as rectal swabs and fecal samples which will be subjected to laboratory analysis. The primary composite outcome is the prevalence of death and/or hospitalization at six months of age. Discussion: As the use of probiotics may give a more favorable gut composition, and thereby improve health and reduce morbidity and mortality, the results may have implications for future therapy guidelines in Africa and internationally. Trial Registration: www.clinicaltrials.gov , Trial identifier NCT04172012, Registered 21 November 2019


Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Christophe Le Terrier ◽  
Marco Vinetti ◽  
Paul Bonjean ◽  
Régine Richard ◽  
Bruno Jarrige ◽  
...  

Abstract Background High-level antibiotic consumption plays a critical role in the selection and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in the ICU. Implementation of a stewardship program including a restrictive antibiotic policy was evaluated with respect to ESBL-E acquisition (carriage and infection). Methods We implemented a 2-year, before-and-after intervention study including all consecutive adult patients admitted for > 48 h in the medical-surgical 26-bed ICU of Guadeloupe University Hospital (French West Indies). A conventional strategy period (CSP) including a broad-spectrum antibiotic as initial empirical treatment, followed by de-escalation (period before), was compared to a restrictive strategy period (RSP) limiting broad-spectrum antibiotics and shortening their duration. Antibiotic therapy was delayed and initiated only after microbiological identification, except for septic shock, severe acute respiratory distress syndrome and meningitis (period after). A multivariate Cox proportional hazard regression model adjusted on propensity score values was performed. The main outcome was the median time of being ESBL-E-free in the ICU. Secondary outcome included all-cause ICU mortality. Results The study included 1541 patients: 738 in the CSP and 803 in the RSP. During the RSP, less patients were treated with antibiotics (46.8% vs. 57.9%; p < 0.01), treatment duration was shorter (5 vs. 6 days; p < 0.01), and administration of antibiotics targeting anaerobic pathogens significantly decreased (65.3% vs. 33.5%; p < 0.01) compared to the CSP. The incidence of ICU-acquired ESBL-E was lower (12.1% vs. 19%; p < 0.01) during the RSP. The median time of being ESBL-E-free was 22 days (95% CI 16-NA) in the RSP and 18 days (95% CI 16–21) in the CSP. After propensity score weighting and adjusted analysis, the median time of being ESBL-E-free was independently associated with the RSP (hazard ratio, 0.746 [95% CI 0.575–0.968]; p = 0.02, and hazard ratio 0.751 [95% CI 0.578–0.977]; p = 0.03, respectively). All-cause ICU mortality was lower in the RSP than in the CSP (22.5% vs. 28.6%; p < 0.01). Conclusions Implementation of a program including a restrictive antibiotic strategy is feasible and is associated with less ESBL-E acquisition in the ICU without any worsening of patient outcome.


2020 ◽  
Vol 89 (3) ◽  
pp. 217-223
Author(s):  
Jan Vašek ◽  
Jonáš Vaňhara ◽  
Monika Dolejská ◽  
Martina Masaříková ◽  
Alois Čížek ◽  
...  

The aim of the present study was to monitor the presence of extended-spectrum beta-lactamase (ESBL) producing E. coli on farm A with the history of previous use of ceftiofur in suckling pigletsand to analyse the risk factors of selection and dissemination of ESBL producers in the production herd. In the year of 2014, a total of 411 samples (rectal swabs or faeces)from pigs of various age categories (sows, gilts and suckling piglets) were collected. The sampling was performed more than 24 months after the ban of ceftiofur on the farm.The sows and gilts were sampled repeatedly before and after farrowing. All collected samples were directly cultivated on MacConkey agar (MCA) containing cefotaxime (2 mg/l) and obtained sub-cultures were tested for ESBL production by double disc synergy test. According to our results, all gilts were negative for ESBL-producing E. coli in the introduction period, however, the excretion of ESBL-producing E. coli was observed before and after delivery. Most of the new-born piglets from positive sows and gilts shed ESBL-producing E. coli early after birth. All tested ESBL-producing isolates were resistant to multiple antimicrobials, suggesting that antibiotics from other groups used for therapy co-select for ESBL producers in pigs on the studied farm. Intestinal colonization of lactating sows and their offspring as well as survival of ESBL-producing E. coli in the farm environment should be recognised as important risk factors of circulation and long-time persistence of ESBL producers in the herd.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kanika Kuwelker ◽  
Nina Langeland ◽  
Iren Høyland Löhr ◽  
Joshua Gidion ◽  
Joel Manyahi ◽  
...  

Abstract Background Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) has emerged as an urgent global health threat and is by the World Health Organization ranked as priority 1 among pathogens in need of new treatment. Studies have shown high mortality in Tanzanian children with ESBL-E infections. Gut colonization of ESBL-E, which is a potential risk factor of ESBL-E infections, is reported to be very high among children in Tanzania. Probiotics may potentially reduce gut colonization of multidrug-resistant bacteria. However, there is limited data on whether probiotics may reduce ESBL-E carriage in infants. The ProRIDE Trial aims to evaluate whether the use of probiotics can reduce morbidity and mortality among infants in Haydom, Tanzania, and whether this effect is associated with a reduction in ESBL-E colonization and/or infections. Methods/design This large randomized double-blinded placebo-controlled trial aims to recruit 2000 newborn infants at Haydom Lutheran Hospital and the surrounding area in the period of November 2020 to November 2021. Participants will be enrolled from days 0 to 3 after birth and randomized to receive probiotics or placebo for 4 weeks. Participants will be followed-up for 6 months, during which three visits will be made to collect clinical and demographic information, as well as rectal swabs and fecal samples which will be subjected to laboratory analysis. The primary composite outcome is the prevalence of death and/or hospitalization at 6 months of age. Discussion As the use of probiotics may give a more favorable gut composition, and thereby improve health and reduce morbidity and mortality, the results may have implications for future therapy guidelines in Africa and internationally. Trial registration ClinicalTrials.gov NCT04172012. Registered on November 21, 2019


2019 ◽  
pp. 1-14
Author(s):  
O. O. Bello ◽  
M. O. Oni ◽  
J. O. Bello ◽  
T. K. Bello

Aim: This study was carried out to determine the occurrence of extended-spectrum beta-lactamase (ESBL) producing bacteria in salad vegetables in Ondo City, Nigeria. Study Design: An experimental study design with randomized sampling. Place and Duration of the Study: The research was carried out in the Department of Biological Sciences of Wesley University, Ondo State, Nigeria. Methodology: Samples of cucumber, carrot, green pea, green beans, sweet corn and cabbage were analysed on appropriate agar medium. Pure isolates were identified by biochemical tests and confirmation was done by the use of API 20 E and API 20 NE in accordance with standard procedures. ESBLs screening was carried out using the double disk synergy test. Data were statistically analyzed using MedCalc statistical software (version 17.2). Results: Total viable bacterial counts (TVBCs) ranged from 1.1 × 103 to 7.1 x 105 cfu/ml; total coliform counts (TCC) ranged from 1.2 x 102 to 3.9 x 103 cfu/ml while total faecal counts (TFC) ranged from 0 to 2.9 × 102 cfu/ml. There were statistical differences in mean TVBCs of the samples (P < 0.05).  The mean TCCs of cabbage, carrot and cucumber showed no statistical significance; green beans, green pea and sweet corn also showed no statistical significance (P > 0.05). One hundred and sixty (166) isolates obtained from the samples were identified as Bacillus cereus, Citrobacter freundii, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, Serratia marcesens and Staphylococcus saprophyticus. At least one member of all bacterial species, except S. saprophyticus, produced ESBL.  Conclusion: This study revealed that salad vegetables could be a vehicle for the spread of extended-spectrum beta-lactamase-producing bacteria which translates to a threat to public health around the world as salads are loved and consumed by all categories of people globally.


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