Characterization of Clostridioides difficile Isolates Available through the CDC & FDA Antibiotic Resistance Isolate Bank.
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SUBMITTER: Paulick A
PROVIDER: S-EPMC8407687 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
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Characterization of Clostridioides difficile Isolates Available through the CDC & FDA Antibiotic Resistance Isolate Bank.
Paulick Ashley A Adamczyk Michelle M Anderson Karen K Vlachos Nick N Machado María-José MJ McAllister Gillian G Korhonen Lauren L Guh Alice Y AY Halpin Alison Laufer AL Rasheed J Kamile JK Karlsson Maria M Lutgring Joseph D JD Gargis Amy S AS
Microbiology resource announcements 20210107 1
Thirty <i>Clostridioides difficile</i> isolates collected in 2016 through the Centers for Disease Control and Prevention Emerging Infections Program were selected for reference antimicrobial susceptibility testing and whole-genome sequencing. Here, we present the genetic characteristics of these isolates and announce their availability in the CDC & FDA Antibiotic Resistance Isolate Bank. ...[more]
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Project description:FDA-CDC Antimicrobial Resistance Bank
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Project description:Clostridioides difficile (CD) is one of the top five urgent antibiotic resistance threats in USA. There is a worldwide increase in MDR of CD, with emergence of novel strains which are often more virulent and MDR. Antibiotic resistance in CD is constantly evolving with acquisition of novel resistance mechanisms, which can be transferred between different species of bacteria and among different CD strains present in the clinical setting, community, and environment. Therefore, understanding the antibiotic resistance mechanisms of CD is important to guide optimal antibiotic stewardship policies and to identify novel therapeutic targets to combat CD as well as other bacteria. Epidemiology of CD is driven by the evolution of antibiotic resistance. Prevalence of different CD strains and their characteristic resistomes show distinct global geographical patterns. Understanding epidemiologically driven and strain-specific characteristics of antibiotic resistance is important for effective epidemiological surveillance of antibiotic resistance and to curb the inter-strain and -species spread of the CD resistome. CD has developed resistance to antibiotics with diverse mechanisms such as drug alteration, modification of the antibiotic target site and extrusion of drugs via efflux pumps. In this review, we summarized the most recent advancements in the understanding of mechanisms of antibiotic resistance in CD and analysed the antibiotic resistance factors present in genomes of a few representative well known, epidemic and MDR CD strains found predominantly in different regions of the world.
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Project description:FDA/CDC Isolate Bank Genome Sequencing
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Project description:BackgroundClostridioides difficile (C. difficile) is one of the primary pathogens responsible for infectious diarrhea. Antibiotic treatment failure, occurring in about 30% of patients, and elevated rates of antibiotic resistance pose a major challenge for therapy. Reinfection often occurs by isolates that produce biofilm, a protective barrier impermeable to antibiotics. We explored the association between antibiotic resistance (in planktonic form) and biofilm-production in 123 C. difficile clinical isolates.ResultsOverall, 66 (53.6%) out of 123 isolates produced a biofilm, with most of them being either a strong (44%) or moderate (34.8%) biofilm producers. When compared to susceptible isolates, a statistically higher percentage of isolates with reduced susceptibility to metronidazole or vancomycin were biofilm producers (p < 0.0001, for both antibiotics). Biofilm production intensity was higher among tolerant isolates; 53.1% of the metronidazole-susceptible isolates were not able to produce biofilms, and only 12.5% were strong biofilm-producers. In contrast, 63% of the isolates with reduced susceptibility had a strong biofilm-production capability, while 22.2% were non-producers. Among the vancomycin-susceptible isolates, 51% were unable to produce biofilms, while all the isolates with reduced vancomycin susceptibility were biofilm-producers. Additionally, strong biofilm production capacity was more common among the isolates with reduced vancomycin susceptibility, compared to susceptible isolates (72.7% vs. 18.8%, respectively). The distribution of biofilm capacity groups was statistically different between different Sequence-types (ST) strains (p =0.001). For example, while most of ST2 (66.7%), ST13 (60%), ST42 (80%) isolates were non-producers, most (75%) ST6 isolates were moderate producers and most of ST104 (57.1%) were strong producers.ConclusionsOur results suggest an association between reduced antibiotic susceptibility and biofilm production capacity. This finding reinforces the importance of antibiotic susceptibility testing, mainly in recurrence infections that may be induced by a strain that is both antibiotic tolerant and biofilm producer. Better adjustment of treatment in such cases may reduce recurrences rates and complications. The link of biofilm production and ST should be further validated; if ST can indicate on isolate virulence, then in the future, when strain typing methods will be more available to laboratories, ST determination may aid in indecision between supportive vs. aggressive treatment.
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Project description:Plasmid-mediated polymyxin resistance encoded by mcr-1 has increased public health concerns due to the potential for rapid horizontal transfer. Here, we report the complete genome sequence of colistin-resistant Escherichia coli Antibiotic Resistance Isolate Bank number 0346, harboring a plasmid-borne mcr-1 gene.
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Project description:BackgroundIt has been performed worldwidely to explore the potential of animals that might be a reservoir for community associated human infections of Clostridioides difficile. Several genetically undistinguished PCR ribotypes of C. difficile from animals and human have been reported, illustrating potential transmission of C. difficile between them. Pig and calf were considered as the main origins of C. difficile with predominant RT078 and RT033, respectively. As more investigations involved, great diversity of molecular types from pig and calf were reported in Europe, North American and Australia. However, there were quite limited research on C. difficile isolates from meat animals in China, leading to non-comprehensive understanding of molecular epidemiology of C. difficile in China.ResultsA total of 55 C. difficile were isolated from 953 animal stool samples, within which 51 strains were from newborn dairy calf less than 7?days in Shandong Province. These isolates were divided into 3 STs and 6 RTs, of which ST11/RT126 was predominant type, and responsible for majority antibiotic resistance isolates. All the isolates were resistant to at least one tested antibiotics, however, only two multidrug resistant (MDR) isolates were identified. Furthermore, erythromycin (ERY) and clindamycin (CLI) were the two main resistant antibiotics. None of the isolates were resistant to vancomycin (VAN), metronidazole (MTZ), tetracycline (TET), and rifampin (RIF).ConclusionsIn this study, we analyzed the prevalence, molecular characters and antibiotic resistance of C. difficile from calf, sheep, chicken, and pig in China. Some unique features were found here: first, RT126 not RT078 were the dominant type from baby calf, and none isolates were got from pig; second, on the whole, isolates from animals display relative lower resistant rate to these 11 tested antibiotics, compared with isolates from human in China in our previous report. Our study helps to deep understanding the situation of C. difficile from economic animals in China, and to further study the potential transmission of C. difficile between meat animals and human.
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Project description:Clostridioides difficile has been recognized as a life-threatening pathogen that causes enteric diseases, including antibiotic-associated diarrhea and pseudomembranous colitis. The severity of C. difficile infection (CDI) correlates with toxin production and antibiotic resistance of C. difficile. In Thailand, the data addressing ribotypes, toxigenic, and antimicrobial susceptibility profiles of this pathogen are scarce and some of these data sets are limited. In this study, two groups of C. difficile isolates in Thailand, including 50 isolates collected from 2006 to 2009 (THA group) and 26 isolates collected from 2010 to 2012 (THB group), were compared for toxin genes and ribotyping profiles. The production of toxins A and B were determined on the basis of toxin gene profiles. In addition, minimum inhibitory concentration of eight antibiotics were examined for all 76 C. difficile isolates. The isolates of the THA group were categorized into 27 A-B+CDT- (54%) and 23 A-B-CDT- (46%), while the THB isolates were classified into five toxigenic profiles, including six A+B+CDT+ (23%), two A+B+CDT- (8%), five A-B+CDT+ (19%), seven A-B+CDT- (27%), and six A-B-CDT- (23%). By visually comparing them to the references, only five ribotypes were identified among THA isolates, while 15 ribotypes were identified within THB isolates. Ribotype 017 was the most common in both groups. Interestingly, 18 unknown ribotyping patterns were identified. Among eight tcdA-positive isolates, three isolates showed significantly greater levels of toxin A than the reference strain. The levels of toxin B in 3 of 47 tcdB-positive isolates were significantly higher than that of the reference strain. Based on the antimicrobial susceptibility test, metronidazole showed potent efficiency against most isolates in both groups. However, high MIC values of cefoxitin (MICs 256 μg/mL) and chloramphenicol (MICs ≥ 64 μg/mL) were observed with most of the isolates. The other five antibiotics exhibited diverse MIC values among two groups of isolates. This work provides evidence of temporal changes in both C. difficile strains and patterns of antimicrobial resistance in Thailand.
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Project description:BackgroundUntil recently, metronidazole was the first-line treatment for Clostridioides difficile infection and it is still commonly used. Though resistance has been reported due to the plasmid pCD-METRO, this does not explain all cases.ObjectivesTo identify factors that contribute to plasmid-independent metronidazole resistance of C. difficile.MethodsHere, we investigate resistance to metronidazole in a collection of clinical isolates of C. difficile using a combination of antimicrobial susceptibility testing on different solid agar media and WGS of selected isolates.ResultsWe find that nearly all isolates demonstrate a haem-dependent increase in the MIC of metronidazole, which in some cases leads to isolates qualifying as resistant (MIC >2 mg/L). Moreover, we find an SNP in the haem-responsive gene hsmA, which defines a metronidazole-resistant lineage of PCR ribotype 010/MLST ST15 isolates that also includes pCD-METRO-containing strains.ConclusionsOur data demonstrate that haem is crucial for medium-dependent metronidazole resistance in C. difficile.
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