Pantoprazole promotes sustained intestinal carriage of multidrug-resistant Escherichia coli in amoxicillin-treated mice.

AIMS: The main objective of this study was to compare extended-spectrum ß-lactamase (ESBL) Escherichia coli fecal titers during 12 days between two groups: mice who received proton pump inhibitors (PPIs) and those that did not. METHODS AND RESULTS: We tested three different in vivo models: model 1, high inoculum (106 CFU ml-1); model 2, low inoculum (102 CFU ml-1); and model 3, low inoculum and 2-day amoxicillin wash-out. There was no significant difference between the two groups in fecal ESBL E. coli titers in models 1 and 2. The fecal titers of ESBL E. coli were probably too high to show differences in colonization related to PPI treatment. By introducing a 2-day wash-out period after stopping amoxicillin (model 3), the fecal ESBL E. coli titers were higher in the PPI-treated mice during 12 days (3 log versus 11 log day CFU g-1; P < 0.05). This result highlighted that PPIs promote stable ESBL E. coli digestive carriage in mice. Fecal quantitative PCR showed that mice with low ESBL E. coli fecal titers had a much higher concentration of equol-producing bacteria, Muribaculum sp., and Adlercreutzia caecimuris. CONCLUSIONS: Pantoprazole treatment promotes sustained digestive carriage of ESBL E. coli in amoxicillin-treated mice.

Systematic screening for digestive carriage of extended-spectrum ß-lactamase-producing Enterobacterales (E-ESBL) at hospital readmission among patients with past history of E-ESBL colonization or infection.

BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacterales (E-ESBL) are commensal multidrug-resistant (MDR) bacteria of the digestive tract whose prevalence has risen sharply worldwide and in Europe over the past two decades. AIM: To assess digestive carriage at hospital readmission of a large cohort of 2509 patients with E-ESBL carriage over a five-year survey; 833 (33%) patients were readmitted at least once. METHODS: A retrospective, single-centre survey conducted at a tertiary care hospital in France. FINDINGS: Among patients with several hospital readmissions (range: 2-13), the proportion of patients still E-ESBL-colonized at hospital readmission, detected by systematic screening for E-ESBL colonization, was >80% within an 18-month period after prior hospitalization with the first E-ESBL isolation. CONCLUSION: There is a need to reconsider the continuation of systematic screening for E-ESBL colonization because of a high rate of patients still colonized at hospital readmission over a long period of time.

Prevalence, Risk Factors, and Genetic Characterization of Extended-Spectrum Beta-Lactamase Escherichia coli Isolated From Healthy Pregnant Women in Madagascar.

Antimicrobial resistance is a major public health concern worldwide affecting humans, animals and the environment. However, data is lacking especially in developing countries. Thus, the World Health Organization developed a One-Health surveillance project called Tricycle focusing on the prevalence of ESBL-producing Escherichia coli in humans, animals, and the environment. Here we present the first results of the human community component of Tricycle in Madagascar. From July 2018 to April 2019, rectal swabs from 492 pregnant women from Antananarivo, Mahajanga, Ambatondrazaka, and Toamasina were tested for ESBL-E. coli carriage. Demographic, sociological and environmental risk factors were investigated, and E. coli isolates were characterized (antibiotic susceptibility, resistance and virulence genes, plasmids, and genomic diversity). ESBL-E. coli prevalence carriage in pregnant women was 34% varying from 12% (Toamasina) to 65% (Ambatondrazaka). The main risk factor associated with ESBL-E. coli carriage was the rainy season (OR = 2.9, 95% CI 1.3-5.6, p = 0.009). Whole genome sequencing was performed on 168 isolates from 144 participants. bla CTX-M-15 was the most frequent ESBL gene (86%). One isolate was resistant to carbapenems and carried the bla NDM-5 gene. Most isolates belonged to commensalism associated phylogenetic groups A, B1, and C (90%) and marginally to extra-intestinal virulence associated phylogenetic groups B2, D and F (10%). Multi locus sequence typing showed 67 different sequence types gathered in 17 clonal complexes (STc), the most frequent being STc10/phylogroup A (35%), followed distantly by the emerging STc155/phylogroup B1 (7%), STc38/phylogroup D (4%) and STc131/phylogroup B2 (3%). While a wide diversity of clones has been observed, SNP analysis revealed several genetically close isolates (n = 34/168) which suggests human-to-human transmissions. IncY plasmids were found with an unusual prevalence (23%), all carrying a bla CTX-M-15. Most of them (85%) showed substantial homology (≥85%) suggesting a dissemination of IncY ESBL plasmids in Madagascar. This large-scale study reveals a high prevalence of ESBL-E. coli among pregnant women in four cities in Madagascar associated with warmth and rainfall. It shows the great diversity of E. coli disseminating throughout the country but also transmission of specific clones and spread of plasmids. This highlights the urgent need of public-health interventions to control antibiotic resistance in the country.

Antibiotic Resistance Acquisition in the First Week of Life.

Objectives: The fetus is considered sterile but recent studies have suggested that gut colonization could start before birth. Scarce data are available for the acquisition of resistant Gram-negative bacteria (GNB) during the first days of life. Several studies have shown that integrons play a major role in antibiotic resistance acquisition. In this work, we studied the dynamics of human intestinal acquisition of GNB and integrons during the first days of life. Methods: Meconium was collected at birth and a stool sample before hospital discharge (days 2 or 3) on 185 term neonates. GNB were searched by culture on each sample and class 1, 2, and 3 integrons from each GNB or directly from samples. Eight risk factors for integron and GNB acquisition were studied. Results: We isolated 228 GNB, 46 from meconium and the remainder from stools. No link was found between GNB isolation and antibiotic exposure during delivery, but antibiotic exposure during labor significantly selected blaTEM-positive amoxicillin-resistant Enterobacteria. Two-thirds of GNB were antibiotic-susceptible and most of the resistant isolates were acquired after birth. Integrons were detected in 18 of the 228 GNB isolates from 3 meconium and 20 stools. Antibiotic administration during delivery and vaginal carriage of Streptococcus agalactiae appeared as risk factors for integron acquisition. Conclusion: Gram-negative bacteria and integrons are mostly acquired after birth during the first days of life even if for some term neonates, meconium was not sterile. Antibiotic administration during delivery is a major risk for integron acquisition and for selection of amoxicillin-resistant Enterobacteria.

Integron Digestive Carriage in Human and Cattle: A "One Health" Cultivation-Independent Approach.

Objectives: Dissemination of antimicrobial resistance (AMR) is a global issue that requires the adoption of a "One-Health" approach promoting integration of human and animal health. Besides culture-dependent techniques frequently used for AMR surveillance, cultivation-independent methods can give additional insights into the diversity and reservoir of AMR genetic determinants. Integrons are molecular markers that can provide overall and reliable estimation of AMR dissemination. In this study, considering the "One-Health" approach, we have analyzed the integron digestive carriage from stools of humans and cattle living in a same area and exposed to different antibiotic selection pressures. Methods: Three collections of human [general population (GP) and intensive care unit patients (ICUs)] and bovine (BOV) stool samples were analyzed. The three main classes of integrons were detected using a multiplex qPCR both from total DNA extracted from stools, and from Gram-negative bacteria obtained by culture after an enrichment step. Results: With the cultivation-independent approach, integron carriage was 43.8, 52.7, and 65.6% for GP, ICU, and BOV respectively, percentages being at least twofold higher to those obtained with the cultivation-dependent approach. Class 1 integrons were the most prevalent; class 2 integrons seemed more associated to cattle than to humans; no class 3 integron was detected. The integron carriage was not significantly different between GP and ICU populations according to the antibiotic consumption, whatever the approach. Conclusion: The cultivation-independent approach constitutes a complementary exploratory method to investigate the integron digestive carriage of humans and bovines, notably within subjects under antibiotic treatment. The high frequency of carriage of integrons in the gut is of clinical significance, integrons being able to easily acquire and exchange resistant genes under antibiotic selective pressure and so leading to the dissemination of resistant bacteria.