scholarly journals Impact of Phage Therapy on Multidrug-Resistant Escherichia coli Intestinal Carriage in a Murine Model

2021 ◽  
Vol 9 (12) ◽  
pp. 2580
Author(s):  
François Javaudin ◽  
Pascale Bémer ◽  
Eric Batard ◽  
Emmanuel Montassier

Introduction: The growing resistance of bacteria to antibiotics is a major global public health concern. An important reservoir of this resistance is the gut microbiota. However, limited data are available on the ability of phage therapy to reduce the digestive carriage of multidrug-resistant bacteria. Materials and methods: Four novel lytic phages were isolated in vitro for efficacy against an extended-spectrum beta-lactamase-producing (ESBL) Escherichia coli strain also resistant to carbapenems through a carbapenemase OXA-48. The first step was to develop models of ESBL E. coli digestive carriage in mice. The second step was to test the efficacy of an oral and rectal phage therapy (a cocktail of four phages or microencapsulated phage) to reduce this carriage. Results: The two most intense models of digestive carriage were obtained by administering amoxicillin (0.5 g·L−1) continuously in the drinking water (Model 1) or pantoprazole (0.1 g·L−1) continuously in the drinking water, combined with amoxicillin (0.5 g·L−1), for the first 8 days (Model 2). Oral administration of the phage cocktail to Model 1 resulted in a transient reduction in the concentration of ESBL E. coli in the faeces 9 days after the bacterial challenge (median = 5.33 × 108 versus 2.76 × 109 CFU·g−1, p = 0.02). In contrast, in Model 2, oral or oral + rectal administration of this cocktail did not alter the bacterial titre compared to the control (area under the curve, AUC, 3.49 × 109; 3.41 × 109 and 3.82 × 109 for the control, oral and oral + rectal groups, respectively; p-value > 0.8 for each two-by-two group comparison), as well as the administration of an oral microencapsulated phage in Model 1 (AUC = 8.93 × 109 versus 9.04 × 109, p = 0.81). Conclusions: Oral treatment with amoxicillin promoted digestive carriage in mice, which was also the case for the addition of pantoprazole. However, our study confirms the difficulty of achieving efficacy with phage therapy to reduce multidrug-resistant bacterial digestive carriage in vivo.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaitlin S. Witherell ◽  
Jason Price ◽  
Ashok D. Bandaranayake ◽  
James Olson ◽  
Douglas R. Call

AbstractMultidrug-resistant bacteria are a growing global concern, and with increasingly prevalent resistance to last line antibiotics such as colistin, it is imperative that alternative treatment options are identified. Herein we investigated the mechanism of action of a novel antimicrobial peptide (CDP-B11) and its effectiveness against multidrug-resistant bacteria including Escherichia coli #0346, which harbors multiple antibiotic-resistance genes, including mobilized colistin resistance gene (mcr-1). Bacterial membrane potential and membrane integrity assays, measured by flow cytometry, were used to test membrane disruption. Bacterial growth inhibition assays and time to kill assays measured the effectiveness of CDP-B11 alone and in combination with colistin against E. coli #0346 and other bacteria. Hemolysis assays were used to quantify the hemolytic effects of CDP-B11 alone and in combination with colistin. Findings show CDP-B11 disrupts the outer membrane of E. coli #0346. CDP-B11 with colistin inhibits the growth of E. coli #0346 at ≥ 10× lower colistin concentrations compared to colistin alone in Mueller–Hinton media and M9 media. Growth is significantly inhibited in other clinically relevant strains, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. In rich media and minimal media, the drug combination kills bacteria at a lower colistin concentration (1.25 μg/mL) compared to colistin alone (2.5 μg/mL). In minimal media, the combination is bactericidal with killing accelerated by up to 2 h compared to colistin alone. Importantly, no significant red blood hemolysis is evident for CDP-B11 alone or in combination with colistin. The characteristics of CDP-B11 presented here indicate that it can be used as a potential monotherapy or as combination therapy with colistin for the treatment of multidrug-resistant infections, including colistin-resistant infections.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Akihisa Hata ◽  
Noboru Fujitani ◽  
Fumiko Ono ◽  
Yasuhiro Yoshikawa

AbstractThere is a lack of an established antimicrobial resistance (AMR) surveillance system in animal welfare centers. Therefore, the AMR prevalence in shelter dogs is rarely known. Herein, we conducted a survey in animal shelters in Chiba and Kanagawa prefectures, in the Kanto Region, Japan, to ascertain the AMR status of Escherichia coli  (E. coli) prevalent in shelter dogs. E. coli was detected in the fecal samples of all 61 and 77 shelter dogs tested in Chiba and Kanagawa, respectively. The AMR was tested against 20 antibiotics. E. coli isolates derived from 16.4% and 26.0% of samples from Chiba and Kanagawa exhibited resistance to at least one antibiotic, respectively. E. coli in samples from Chiba and Kanagawa prefectures were commonly resistant to ampicillin, piperacillin, streptomycin, kanamycin, tetracycline, and nalidixic acid; that from the Kanagawa Prefecture to cefazolin, cefotaxime, aztreonam, ciprofloxacin, and levofloxacin and that from Chiba Prefecture to chloramphenicol and imipenem. Multidrug-resistant bacteria were detected in 18 dogs from both regions; β-lactamase genes (blaTEM, blaDHA-1, blaCTX-M-9 group CTX-M-14), quinolone-resistance protein genes (qnrB and qnrS), and mutations in quinolone-resistance-determining regions (gyrA and parC) were detected. These results could partially represent the AMR data in shelter dogs in the Kanto Region of Japan.


Author(s):  
Nahla Omer Eltai ◽  
Hadi M. Yassine ◽  
Sara H. Al-Hadidi ◽  
Tahra ElObied ◽  
Asmaa A. Al Thani ◽  
...  

The dissemination of antimicrobial resistance (AMR) bacteria has been associated with the inappropriate use of antibiotics in both humans and animals and with the consumption of food contaminated with resistant bacteria. In particular, the use of antibiotics as prophylactic and growth promotion purposes in food-producing animals has rendered many of the antibiotics ineffective. The increased global prevalence of AMR poses a significant threat to the safety of the world’s food supply. Objectives: This study aims at determining the prevalence of antibiotic-resistant Escherichia coli (E. coli) isolated from local and imported retail chicken meat in Qatar. Methodology: A total of 270 whole chicken carcasses were obtained from three different hypermarket stores in Qatar. A total of 216 E. coli were isolated and subjected to antibiotic susceptibility testing against 18 relevant antibiotics using disc diffusion and micro- dilution methods. Furthermore, extended-spectrum β-lactamase (ESBL) production was determined via a double-disc synergetic test. Isolates harboring colistin resistance were confirmed using multiplex-PCR and DNA sequencing. Results: Nearly 89% (192/216) of the isolates were resistant to at least one antibiotics. In general, isolates showed relatively higher resistance to sulfamethoxazole (62%), tetracycline (59.7%), ampicillin and trimethoprim (52.3%), ciprofloxacin (47.7%), cephalothin, and colistin (31.9%). On the other hand, less resistance was recorded against amoxicillin/clavulanic acid (6%), ceftriaxone (5.1%), nitrofurantoin (4.2%) and piperacillin/tazobactam (4.2%), cefepime (2.3%), meropenem (1.4%), ertapenem (0.9%), and amikacin (0.9%). Nine isolates (4.2%) were ESBL producers. Furthermore, 63.4% were multidrug-resistant (MDR). The percentage of MDR, ESBL producers, and colistin-resistant isolates was significantly higher among local isolates compared to imported chicken samples. Conclusion: We reported a remarkably high percentage of the antibiotic-resistant E. coli in chicken meat sold at retail in Qatar. The high percentage of MDR and colistin isolates is troublesome to the food safety of raw chicken meat and the potential of antibiotic resistance spread to public health. Our findings support the need for the implementation of one health approach to address the spread of antimicrobial resistance and the need for a collaborative solution.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Neha Giri ◽  
Anchal Lodhi ◽  
Devendra Singh Bisht ◽  
Suvarna Bhoj ◽  
Deepak Kumar Arya

Researchers have encountered new challenges with the discovery of multiple drug resistance in microbes. Currently, multidrug resistant bacteria are considered a major public health concern and an emerging global epidemic. Presence of Escherichia coli in water is used as a faecal pollution measure. In this study E. coli isolates were collected from 20 sample collection sites at Lake Nainital. 20 E. coli isolates, 1 from each sample collection sites, were examined for their antibiotic response patterns against a panel of widely used 15 antibiotics. The result of this study showed 100% resistance to Penicillin G followed by Erythromycin (80%). All isolates (100%) were found susceptible for Gentamycin. The susceptibilities for Chloramphenicol and Co-trimoxazaole were found next to Gentamycin as 90 and 85% respectively. Multiple antibiotic resistance (MAR) index was also determined. 0.73 MAR index was observed as highest in 1 isolate. 13 out of 20 isolates had more than 0.2 MAR indices. The result reveals the origin of E. coli isolates from an area of high antibiotics use.


2019 ◽  
Vol 18 (1) ◽  
pp. 67-76 ◽  
Author(s):  
David Ortega-Paredes ◽  
Pedro Barba ◽  
Santiago Mena-López ◽  
Nathaly Espinel ◽  
Verónica Crespo ◽  
...  

Abstract Urban river pollution by multidrug-resistant (MDR) bacteria constitutes an important public health concern. Epidemiologically important strains of MDR Escherichia coli transmissible at the human–animal–environment interfaces are especially worrying. Quantifying and characterizing MDR E. coli at a molecular level is thus imperative for understanding its epidemiology in natural environments and its role in the spread of resistance in precise geographical areas. Cefotaxime-resistant E. coli was characterized along the watercourse of the major urban river in Quito. Our results showed high quantities of cefotaxime-resistant E. coli (2.7 × 103–5.4 × 105 CFU/100 mL). The antimicrobial resistance index (ARI) revealed the exposure of the river to antibiotic contamination, and the multiple antibiotic resistance index indicated a high risk of contamination. The blaCTX-M-15 gene was the most prevalent in our samples. Isolates also had class 1 integrons carrying aminoglycoside-modifying enzymes and folate pathway inhibitors. The isolates belonged to phylogroups A, B1 and D. Clonal complex 10 was found to be the most prevalent (ST10, ST44 and ST 167), followed by ST162, ST394 and ST46. Our study provides a warning about the high potential of the major urban river in Quito for spreading the epidemiologically important MDR E. coli.


Author(s):  
Taniya Bardhan ◽  
Madhurima Chakraborty ◽  
Bornali Bhattacharjee

Indiscriminate use of antibiotics has resulted in a catastrophic increase in the levels of antibiotic resistance in India. Hospitals treat critical bacterial infections and thus can serve as reservoirs of multidrug resistant (MDR) bacteria. Hence, this study was conducted to gauge the prevalence patterns of MDR bacteria in hospital wastewater. Water samples collected from 11 hospitals and 4 environmental sources belonging to 5 most-densely populated districts of West Bengal, India were grown on MacConkey and Eosin Methylene Blue agar. A total of 84 (hospital-associated = 70, environmental water sources = 14) isolates were characterized. The predominant species found in water from hospital-associated areas (HAA) were Acinetobacter baumannii (22.9%), Escherichia coli (28.6 %), and Klebsiella pneumoniae (25.7%). Greater than 75% of the HAA isolates were found to be mcr-1 gene negative and colistinresistant. Meropenem non-susceptibility was also high among the HAA isolates at 58.6%, with the presence of the carbapenemase gene and blaNDM in 67.1% of the non-susceptible isolates. Among the three predominant species, significantly higher numbers of E. coli isolates were found to be non-susceptible to meropenem ((80%), p-value = 0.00432) and amikacin (AK (90%), p-value = 0.00037). This study provides evidence for the presence of high numbers of colistin-resistant and carbapenem-hydrolyzing Proteobacteriain hospital wastewater.


2017 ◽  
Vol 81 (2) ◽  
pp. 302-307 ◽  
Author(s):  
Nahla O. Eltai ◽  
Elmoubasher A. Abdfarag ◽  
Hamad Al-Romaihi ◽  
Eman Wehedy ◽  
Mahmoud H. Mahmoud ◽  
...  

ABSTRACT Antibiotic resistance (AR) is a growing public health concern worldwide, and it is a top health challenge in the 21st century. AR among Enterobacteriaceae is rapidly increasing, especially in third-generation cephalosporins and carbapenems. Further, strains carrying mobilized colistin resistance (mcr) genes 1 and 2 have been isolated from humans, food-producing animals, and the environment. The uncontrolled use of antibiotics in food-producing animals is a major factor in the generation and spread of AR. No studies have been done to evaluate AR in the veterinary sector of Qatar. This study aimed at establishing primary baseline data for the prevalence of AR among food-producing animals in Qatar. Fecal samples (172) were obtained from two broiler farms and one live bird market in Qatar, and 90 commensal Escherichia coli bacteria were isolated and subjected to susceptibility testing against 16 clinically relevant antibiotics by using the E-test method. The results found that 81 (90%) of 90 isolates were resistant to at least one antibiotic, 14 (15.5%) of 90 isolates were colistin resistant, 2 (2.2%) of 90 isolates were extended-spectrum β-lactamase producers, and 2 (2.2%) of 90 isolates were multidrug resistant to four antibiotic classes. Extended-spectrum β-lactamase–producing E. coli and colistin-resistant isolates were confirmed by using double-disc susceptibility testing and PCR, respectively. Such a high prevalence of antibiotic-resistant E. coli could be the result of a long application of antibiotic treatment, and it is an indicator of the antibiotic load in food-producing animals in Qatar. Pathogens carrying AR can be easily transmitted to humans through consumption of undercooked food or noncompliance with hygiene practices, mandating prompt development and implementation of a stewardship program to control and monitor the use of antibiotics in the community and agriculture.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Mourouge Saadi Alwash ◽  
Hawraa Mohammed Al-Rafyai

Surface water contamination remains a major worldwide public health concern and may contribute to the dissemination of antibiotic-resistant bacteria. The Al-Hillah River in the city of Babylon Province, Iraq, diverts flows from the Euphrates River. Because of its importance in irrigation and population density, it faces several forced and unforced changes due to anthropogenic activities. To evaluate water quality, water samples were collected from three sites with different anthropogenic pressures along the Al-Hillah River. These samples were subjected to bacteriological analyses, i.e., total coliforms, Escherichia coli, and faecal enterococci. The phylogenetic groups of the E. coli isolates (n = 61) were typed by rapid PCR-based analyses. Representatives of each isolate were tested phenotypically for resistance to six classes of antibiotics and characterized according to their phylogenetic groups. The results demonstrated the highest resistance levels were to β-lactam antibiotics, followed by fosfomycin and aminoglycosides. Escherichia coli isolates belonging to phylogenetic groups A and B2 were the most common and were characterized by a higher prevalence of antibiotic resistance. This study is important for understanding the current conditions of the Al-Hillah River, as the data reveal a high prevalence of multiresistance among E. coli isolates circulating at the three sampling sites.


2021 ◽  
Vol 8 ◽  
Author(s):  
Joshua Mbanga ◽  
Daniel G. Amoako ◽  
Akebe L. K. Abia ◽  
Mushal Allam ◽  
Arshad Ismail ◽  
...  

There is limited information on the comparative genomic diversity of antibiotic-resistant Escherichia coli from wastewater. We sought to characterize environmental E. coli isolates belonging to various pathotypes obtained from a wastewater treatment plant (WWTP) and its receiving waters using whole-genome sequencing (WGS) and an array of bioinformatics tools to elucidate the resistomes, virulomes, mobilomes, clonality, and phylogenies. Twelve multidrug-resistant (MDR) diarrheagenic E. coli isolates were obtained from the final effluent of a WWTP, and the receiving river upstream and downstream of the WWTP were sequenced on an Illumina MiSeq machine. The multilocus sequence typing (MLST) analysis revealed that multiple sequence types (STs), the most common of which was ST69 (n = 4) and ST10 (n = 2), followed by singletons belonging to ST372, ST101, ST569, ST218, and ST200. One isolate was assigned to a novel ST ST11351. A total of 66.7% isolates were positive for β-lactamase genes with 58.3% harboring the blaTEM1B gene and a single isolate the blaCTX−M−14 and blaCTX−M−55 extended-spectrum β-lactamase (ESBL) genes. One isolate was positive for the mcr-9 mobilized colistin resistance gene. Most antibiotic resistance genes (ARGs) were associated with mobile genetic support: class 1 integrons (In22, In54, In191, and In369), insertion sequences (ISs), and/or transposons (Tn402 or Tn21). A total of 31 virulence genes were identified across the study isolates, including those responsible for adhesion (lpfA, iha, and aggR), immunity (air, gad, and iss), and toxins (senB, vat, astA, and sat). The virulence genes were mostly associated with IS (IS1, IS3, IS91, IS66, IS630, and IS481) or prophages. Co-resistance to heavy metal/biocide, antibiotics were evident in several isolates. The phylogenomic analysis with South African E. coli isolates from different sources (animals, birds, and humans) revealed that isolates from this study mostly clustered with clinical isolates. Phylogenetics linked with metadata revealed that isolates did not cluster according to source but according to ST. The occurrence of pathogenic and MDR isolates in the WWTP effluent and the associated river is a public health concern.


2020 ◽  
Author(s):  
Dan Wu ◽  
Yijun Ding ◽  
Jinjing Zhang ◽  
Kaihu Yao ◽  
Wei Gao ◽  
...  

Abstract Background Escherichia coli (E.coli) rank one of the most common pathogens that can cause neonatal infections. The emergence of antibiotic-resistant bacteria is a major cause of treatment failure in newborn with infection. The purpose of this study was to describe the antibiotic resistance and multidrug-resistance of E.coli isolated from neonates with infection.Methods The antimicrobial susceptibility testing of the E. coli strains to selected antibiotics was assessed with the E-test technique on the Mueller-Hinton agar. The antimicrobials tests were included ceftazidime, cefuroxime, cefatriaxone, amoxicillin, amoxicillin-clavulanic acid, cefoperazone - sulbactam, meropenem, gentamicin, ciprofloxacin and sulfonamides. The minimal inhibitory concerntration (MIC) values of the antimicrobial agents selected for this study was determined by an agar dilution technique on Mueller-Hinton agar according to the Clinical and Laboratory Standards Institute recommendations. Results A total of 100 E. coli strains was isolated from phlegm (n = 78), blood (n = 10), cerebrospinal fluid (n = 5), and umbilical discharge (n = 7) of neonates hospitalized at Beijing Children’s Hospital. The highest resistance rate of E.coli was found in amoxicillin at 85%, followed by cefuroxime 65%, and cefatriaxone 60%, respectively. 6% and 5% of all isolates were resistant to amoxicillin/clavulanic acid and cefoperazone -sulbactam merely. The resistance rates to ceftazidime, gentamicin, ciprofloxacin and sulfonamides were 31%, 20%, 33%, 47%, respectively. All the isolates were susceptible to meropenem. Multidrug resistance was defined in E.coli as resistance to at least three antibiotic families. About 26% (26/100) of all the E.coli isolates were multidrug-resistant. The detection rate of ESBL-Producing E. coli was 55%. The rate in E. coli isolates from phlegm was higher than aseptic humoral. The difference was statistically significant (P < 0.05). It is worth noting that the majority of the isolates were also resistant to non-β-lactam antimicrobial agents, but the resistant rates were significantly lower than extended-spectrum β-lactamases.Conclusions: Multi-drug-resistant E.coli has become a thorny problem in clinical treatment. It is necessary to monitor E. coli resistance.


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