Antibiotic Resistance Determinants Research Articles

Antibiotic Susceptibility and Clarithromycin Resistance Determinants in Helicobacter pylori in the Northeast of Spain: A One-Year Prospective Study.

Helicobacter pylori is one of the most widespread infections, and it is reaching alarming resistance levels worldwide. The recommended first-line empirical treatment differs according to the local rate of clarithromycin resistance. Macrolide resistance is mainly associated with three point mutations in the 23S rRNA gene. The aim of this study was to describe the antibiotic susceptibility of H. pylori in our healthcare area and the main mechanisms involved in clarithromycin resistance. Gastric biopsies (n = 641) were collected and cultured in a one-year prospective study. Antibiotic susceptibility testing was performed by gradient diffusion. A multiplex real-time PCR test (AllplexTMH.pylori & ClariR Assay, Seegene) was used to detect the most frequent mutations associated with clarithromycin resistance. Overall, 141 isolates were available for antibiotic susceptibility testing. The highest resistance rates were detected in metronidazole and levofloxacin. The rate of clarithromycin resistance was 12.1%, and the associated mutations were A2143G and A2142G. More than half of the clarithromycin-resistant isolates presented high MIC values (>256 mg/L). Tetracycline resistance was not detected, suggesting that therapies that contain tetracycline could be a suitable option. The low clarithromycin resistance rate coupled with the high rates of metronidazole resistance may support the recovery of the classical triple therapy in our healthcare area.

Molecular characterizations of antibiotic resistance, biofilm formation, and virulence determinants of Pseudomonas aeruginosa isolated from burn wound infection.

Burn injuries result in disruption of the skin barrier against opportunistic infections. Pseudomonas aeruginosa is one of the main infectious agents colonizing burn wounds and making severe infections. Biofilm production and other virulence factors along with antibiotic resistance limit appropriate treatment options and time. Wound samples were collected from hospitalized burn patients. P.aeruginosa isolates and related virulence factors identified by the standard biochemical and molecular methods. Antibiotic resistance patterns were determined by the disc diffusion method and β-lactamase genes were detected by polymerase chain reaction (PCR) assay. To determine the genetic relatedness amongst the isolates, enterobacterial repetitive intergenic consensus (ERIC)-PCR was also performed. Forty P.aeruginosa isolates were identified. All of these isolates were biofilm producers. Carbapenem resistance was detected in 40% of the isolates, and blaTEM (37/5%), blaVIM (30%), and blaCTX-M (20%) were the most common β-lactamase genes. The highest resistance was detected to cefotaxime, ceftazidime, meropenem, imipenem and piperacillin, and 16 (40%) isolates were resistant to these antibiotics. The minimum inhibitory concentrations (MIC) of colistin was lower than 2μg/mL and no resistance was observed. Isolates were categorized to 17 MDR, 13 mono-drug resistance, and 10 susceptible isolates. High genetic diversity was also observed among the isolates (28 ERIC types) and most carbapenem-resistant isolates were classified into four main types. Antibiotic resistance, particularly carbapenem resistance was considerable among the P.aeruginosa isolates colonizing burn wounds. Combining carbapenem resistance with biofilm production and virulence factors would result in severe and difficult-to-treat infections.

Identification of Novel Mobile Genetic Elements Associated with Resistance to Macrolide and Lincosamide in Streptococcus dysgalactiae subsp. equisimilis

Background: Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an important human pathogen. Recently, several studies have described the incidence of antibiotic resistance for SDSE worldwide, however, the data on the presence of corresponding genes and their possible association with mobile genetic elements are still limited. Objective: The objective of this research was to analyze the macrolide resistance in SDSE and to identify genetic determinants, mechanisms of resistance, and association with mobile genetic elements. Methods: A total of 9 SDSE strains from the collection of Joint Russian-Vietnamese Tropical Research and Technological Center (Hanoi, Vietnam) were used. These strains were previously isolated from throat swabs of children with pharyngotonsillitis in 6 provinces in Vietnam from 2012 to 2015. Antimicrobial resistance was tested by disk diffusion method. The presence of antibiotic resistance genes (ARG) was analyzed by PCR. The strains were characterized by emm typing and multilocus sequence typing (MLST). Illumina sequencing was employed for genome analysis of 4 representative SDSE isolates. Analysis of genetic elements with antibiotic resistance determinants was done using PubMed database and BLAST-searches. Artemis was used for comparative analysis of genetic elements. Results: In our study, we identified emm types that were similar to those reported in other studies. All SDSE isolates remained susceptible to penicillin, but presented alarming level of resistance to macrolides, tetracyclines, and fluoroquinolones. Most of the erythromycin-resistant strains were also characterized by clindamycin-resistance (MLSB phenotype). Both erm and different alleles of mef genes widely distributed among streptococcus pyogenes and Streptococcus pneumoniae were detected, except erm (TR) gene. The genetic elements carrying resistance determinants showed significant interspecies similarities, indicating conjugative transfer of antibiotic resistance genes between streptococcal species. Conclusion: Identification of the novel antibiotic resistance genes in SDSE indicates the necessity of monitoring of antibiotic resistance spreading and gene transfer in this bacterium.

Analysis of Whole-Genome Sequences of Pathogenic Gram-Positive and Gram-Negative Isolates from the Same Hospital Environment to Investigate Common Evolutionary Trends Associated with Horizontal Gene Exchange, Mutations and DNA Methylation Patterning

Hospital-acquired infections are a generally recognized problem for healthcare professionals. Clinical variants of Gram-negative and Gram-positive pathogens are characterized with enhanced antibiotic resistance and virulence due to mutations and the horizontal acquisition of respective genetic determinants. In this study, two Escherichia coli, two Klebsiella pneumoniae, three Pseudomonas aeruginosa, two Staphylococcus aureus, one Staphylococcus epidermidis and one Streptococcus pneumoniae showing broad spectra of antibiotic resistance were isolated from patients suffering from nosocomial infections in a local hospital in Almaty, Kazakhstan. The aim of the study was to compare general and species-specific pathways of the development of virulence and antibiotic resistance through opportunistic pathogens causing hospital-acquired infections. The whole-genome PacBio sequencing of the isolates allowed for the genotyping and identification of antibiotic resistance and virulence genetic determinants located in the chromosomes, plasmids and genomic islands. It was concluded that long-read sequencing is a useful tool for monitoring the epidemiological situation in hospitals. Marker antibiotic resistance mutations common for different microorganisms were identified, which were acquired due to antibiotic-selective pressure in the same clinical environment. The genotyping and identification of strain-specific DNA methylation motifs were found to be promising in estimating the risks associated with hospital infection outbreaks and monitoring the distribution and evolution of nosocomial pathogens.

Class 1 and 2 Integrons in Escherichia coli Strains Isolated from Diarrhea and Bacteremia in Children Less Than 2 Years of Age from Peru.

Class 1 and Class 2 integrons are mobilizable elements able to carry a variety of antibiotic resistance determinants. In the present study, Class 1 and 2 integrons present in 355 pathogenic Escherichia coli (285 diarrheagenic, of these 129 were enteropathogenic, 90 enteroaggregative, 66 enterotoxigenic, and 70 bacteremic) isolated from healthy and ill children under age 5 from periurban areas of Lima, Peru, were characterized. The presence of integrase 1 and 2 was established by polymerase chain reaction (PCR), and variable regions were grouped by PCR-restriction fragment length polymorphism and subsequent sequencing. Antimicrobial resistance was established by disk diffusion. Ninety-seven isolates (27.3%) presented integrase 1, and 16 (4.5%) presented integrase 2 (P < 0.0001); in addition, seven (2.0%) isolates, six diarrheagenic and one bacteremic, presented both integrase genes. The presence of integrase 1 was more frequent among bacteremic isolates (P = 0.0004). Variable regions were amplified in 76/120 (63.3%) isolates with up to 14 gene arrangements. The most prevalent gene cassettes were those encoding dihydrofolate reductases as well as aminoglycoside modifying enzymes. Of note, Class 1 integrons tended to be associated with the presence of extended-spectrum β-lactamases (ESBLs). A variety of Class 1 and 2 integrons were detected in diarrheagenic and bacteremic E. coli, demonstrating the heterogeneity of variable regions circulating in the area. The association of integrons with ESBLs is worrisome and has an impact on the development of multidrug resistance.

Detection of rifampicin resistance in methicillin-resistant Staphylococcus aureus isolates from the medical centers at Ahmadu Bello University

Objective: The aim of this study was to evaluate the prevalence of rifampicin resistance among methicillin-resistant Staphylococcus (S.) aureus (MRSA) isolates obtained from patients in two health facilities at Ahmadu Bello University, Zaria. Methods: A total of 200 non-duplicate presumptive Staphylococcal isolates were collected from the health facilities. The isolates were confirmed using mannitol salt agar, and biochemical tests were performed to identify S. aureus. The confirmed S. aureus isolates underwent antibiotic susceptibility tests, and the results were interpreted according to the guidelines provided by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Polymerase chain reaction (PCR) was used to investigate virulence and antibiotic resistance determinant, such as Spa, mecA, and rpoB. Results: This study revealed a S. aureus isolation rate of 22 (11.0%), and 18.2% of these S. aureus isolates were methicillin-resistant, with the highest prevalence of resistance (9.1%) found in wound swab. The results further showed that 75.0% of the MRSA isolates were resistant to rifampicin. The molecular analysis showed that all the isolates carried the virulence gene (Spa), with a prevalence of 10.0% for mecA and 20.0% for rpoB genes, respectively. Conclusions: This study underscores the prevalence of rifampicin resistance among MRSA isolates in medical centers, advocating for the development of alternative strategies to combat the current trends in antibiotic resistance and control of rifampicin-resistant MRSA.

Investigation of Salmonella types and its antibiotic resistance profile and determination of parasite carrier in free-living hedgehogs in Istanbul, Türkiye

Hedgehogs, which are kept as pets worldwide, are prohibited from being sold or kept as pets in Türkiye. The aim of the study was to investigate Salmonella and endo-parasite carriage in hedgehogs and to determine the antibacterial resistance profiles of isolated Salmonella agents. Free-range hedgehogs living in parks and gardens of Istanbul that were brought to veterinary clinics by animal lovers for check-up and treatment were used for sampling. Thirty faecal samples were taken from the animals. For bacteriological examinations, samples were seeded on selective media, and then the isolates were identified by conventional methods as Salmonella spp. Identification and antibiotic susceptibilities of the isolates were determined by the BD Phoenix Automated Microbiology System. All faecal samples were also investigated by PCR for Salmonella spp. specific gene regions. The aminoglycoside and quinolone resistance profiles of the strains were analysed by PCR. On parasitological examination, samples were analysed for parasites’ eggs, oocysts, and larvae. Two Salmonella isolates were determined as Salmonella enterica serovar Typhimurium (S. Typhimurium), whose antigenic formula was 4,5,12:i:1,2. The isolates were phenotypically resistant to ciprofloxacin but did not harbour any of the genes examined. Out of 30 faecal samples, 19 (63.3%) were positive for one or more genera of parasites. The hedgehogs were infected with the species of Capillaria spp. (60%), Crenosoma spp. (13.3%), Eimeria spp. (10%) and Acanthocephala spp. (6.6%). This study is the first report of Salmonella carrier and internal parasite fauna of hedgehogs in Istanbul, Türkiye.

Uncovering Genetic Determinants of Antibiotic Resistance in Helicobacter pylori through Next-Generation Sequencing and Genome-Wide Association Study

Uncovering Genetic Determinants of Antibiotic Resistance in Helicobacter pylori through Next-Generation Sequencing and Genome-Wide Association Study

Colonization Rate and Associated Factors of Non-Pathogenic Neisseria Species, and Moraxella catarrhalis Among Healthy School Children in Gondar, Northwest Ethiopia.

Although commensal Neisseria species inhabiting mucosal surfaces in the upper respiratory tract (URT) are rarely associated with infections, their presence in the area has been linked to the development of immunity against N. meningitidis and the source of antibiotic resistance determinants in pathogenic species. M. catarrhalis in the oropharynx of children is also a predisposing factor for otitis media. As a result, determining the oropharyngeal carriage rate of these commensal species and associated factors among healthy schoolchildren is substantial. This community-based cross-sectional study was conducted in Gondar, Northwest Ethiopia, from January to April 2019. A multi-stage and simple random sampling technique were used to select schools and participants, respectively. A total of 524 oropharyngeal swabs were collected using cotton swabs. Modified Thayer-Martin media was used for primary bacterial isolation, and battery of biochemical tests was performed to identify species. For frequencies, descriptive statistics were computed and the logistic regression model was used to see the relationship between dependent and independent variables. A total of 524 healthy schoolchildren with a mean age of 12.2 ± 2.74 years participated in this study. The overall oropharyngeal carriage rate was 21.8% (114/524). Of these, N. meningitidis, N. lactamica, N. sicca, and M. catarrhalis were identified in 53 (46.5%), 14 (12.3%), 11 (9.6%), and 36 (31.6%) children, respectively. The culture positivity rate was higher at a younger age, which was 8.1%, 11.3%, and 14.9% in ages between 15-18, 11-14, and 7-10, respectively. The oropharyngeal carriage was significantly associated with the number of students per class (>40). There is a higher proportion of carriers of commensal N. lactamica and M. catarrhalis in Gondar town schoolchildren. The oropharyngeal carriage rate was associated with a crowded classroom. The characterization of non-pathogenic Neisseria species and M. catarrhalis in the study area can support the diagnosis of patients suspected of having N. meningitis infections.

Occurrence of virulent Serratia marcescens with co-existing antibiotic resistance determinants in ready-to-eat food samples

Background: Foodborne illness is a global concern and identification of pathogens that cause foodborne disease is a public health priority. Serratia marcescens is an opportunistic pathogen responsible for food poisoning due to its ability to colonize the gastrointestinal surfaces. S. marcescens is also responsible for causing a wide range of extraintestinal infections like pneumonia, urinary tract infection, keratitis, etc. Aim: The current study investigated the presence of antibiotic resistant virulent S. marcescens from street food samples. Methods: Two pigmented S. marcescens were recovered from Panipuri samples which were then identified using VITEK® GN cards. The virulence genes and the antibiotic resistance genes harboured by the S. marcescens isolates were investigated and further transformation assay was conducted to check the horizontal transferability of the plasmid carrying the antimicrobial resistance genes. Incompatibility typing of the transformants were also assessed and ERIC PCR was performed to check the heterogeneity of the S. marcescens isolates. Results: Two S. marcescens isolates harbouring virulence genes as well as antibiotic resistance genes were detected in this study and it was observed that Inc FIB type plasmid was carrying the resistance genes. Conclusion: The co-existence of both the virulence and antibiotic resistance genes in the two S. marcescens isolates warrants proper surveillance in order to prevent the spread of such pathogenic strains in environment as well as community through food samples.

Determination of antibiotic resistance and biofilm formation in Klebsiella strains isolated from bovine mastitis cases

Mastitis is diseases of dairy cows with a high economic impact. Bovine mastitis is caused by a wide range of bacterial pathogens. As one of the major environmental pathogens Klebsiella ssp. was investigated in this study by some phenotypic characteristics like antibiotic resistance patterns and biofilm formation properties. A number of 483 cows by dairy farms around the Konya were examined by California Mastitis Test (CMT) producing 36 positive in terms of subclinical mastitis. A further 19 samples from clinical mastitic udders were also collected. Samples were inoculated onto Trypticase Soy Agar medium enriched with sheep blood and incubated aerobicaly for 24-48 hours at 37 °C. By morphological, biochemical and cultural charcateristics 14 isolates out of 37 coliform were identified as Klebsiella ssp. The double disc synergy method and Congo Red Agar test were used to perform antibiotic susceptibility and in vitro slime forming properties, respectively. Resistances to the antibiotics Ampicillin, Carbenicillin, Cephotaxime, Chloramphenicol, Erythromycin, Gentamicin, Neomycin, Oxytetracycline, Sulphamethoxazole/Trimpethoprim, Amoxicillin-Clavulanate and Imipenem were 78.5%, 78.5%, 35.7%, 42.8%, 100%, 7%, 7%, 50%, 14%, 21% and 7%, respectively. Three of the total isolets produced biofilm only. This appears to the first report on ESBL producing Klebsiella ssp from subclinical cases of bovine mastitis in Konya, Türkiye. Presently, two numbers of antimicrobial combinations to treat bovine cases are recommended by this work. In conclusion, because of costly challange nature of Klebsiella caused bovine mastitis implemantation of an effective mastitis control program should be used in local farms from Konya.

Molecular genetic characteristics of &lt;i&gt;Vibrio cholerae&lt;/i&gt; nono1/nono139 strain, the causative agent of a new case of acute intestinal infection in Rostov-on-Don

During more than 50 years, a heterogeneous population of Vibrio cholerae non-O1/non-O139 (NAGs) exists in Rostov region of Russia, whose representatives periodically cause acute human intestinal infections; the last case was registered in 2018. In 2022, a sick child was again revealed in Rostov, from whom 2 NAG subcultures were isolated. Aim of the study: bioinformatics analysis of whole genome sequences (WGSs) of the 2022 clinical NAG isolates, genetic determinants of pathogenicity factors and relevant products. Materials and methods. Isolation, identification of cultures, as well as antibiotic sensitivity were carried out according to the MUK 4.2.3745-22. SNP analysis of WGSs obtained on the MiSeq Illumina platform were analyzed by means of designed software; BioEdit 7.2.5, Vector NTI Advance 11 package, CARD database were used to identify and analyze genes and relevant deduced products. Results. The isolated cultures with identical phenotypic features, PCR-genotypes and results of SNP analysis, were identified as a non-toxigenic NAG. The agent showed sensitivity to chloramphenicol, ceftriaxone, streptomycin, gentamicin, nalidixic acid, ciprofloxacin, ampicillin, amikacin and intermediate resistance to tetracycline, doxycycline, furazolidon and co-trimoxazole. WGSs lacked CTX and preCTX prophages, pathogenicity island VPI, thermostable and cholix toxin genes, pandemic islands VSP-I and VSP-II. The determinants of the type 6 secretion system (T6SS) were not presented completely, which evidenced in favor of the loss of its functionality. An intact T3SS cluster was revealed, which was adjacent to the nan-nag region of the VPI-2 pathogenicity island in the absence of the proximal and distal parts of the latter. Other determinants of pathogenicity factors were revealed: RTX cluster responsible for synthesis of MARTX cytotoxin, genes for hemolysin HlyA, cytotonic toxin Cef, several serine and metalloproteases. The nucleotide compositions of most determinants differed from the prototypes, but their putative products preserved characteristic active domains. The adhesive activity might be provided by mannose-insensitive MSHA-like pili, since the msh-cluster included all the genes necessary for their production, as well as flagella, as both clusters responsible for their assembling were 99% identical to the prototype. From antibiotic resistance determinants only -lactamase VarG gene was found. Conclusion. The NAG strain examined here contains a sufficient set of intact virulence-associated genetic determinants, expression of which could contribute to the development of the disease.

Comparative analysis of Methicillin-resistant Staphylococcus aureus through whole genome sequencing in the largest tertiary care hospital in Peshawar, Pakistan.

Methicillin-resistant Staphylococcus aureus (MRSA) is a globally disseminated antibiotic-resistant pathogen and causes mild to severe infections. The population structure of MRSA is highly clonal and individual genetic clones harbor specific plasmid, and determinants for antibiotic resistance and virulence, therefore, whole genome sequencing (WGS) of five MRSA isolates of the predominant genetic lineage was performed to gain insight into the most prevalent endemic strains. Sequencing libraries were arranged in accordance with the Nextera XT DNA Library Prep Guide (Illumina). WGS was performed on Illumina NextSeq 500 platform with 2×151bp using a NextSeq Mid-Output Kit. The sequenced genome was characterized for spa type, MLST type, SCCmec type, plasmid, antibiotic resistance gene, and virulence gene by publicly available bioinformatics tools on the website of the Center for Genomic Epidemiology. All the isolates were characterized as ST8/t064-SCCmecIVa(2B) clones of MRSA and, A total of 13 resistance genes, 11 virulence genes, and 6 types of plasmids were identified in the sequenced isolates of MRSA, furthermore, the sequenced isolates showed a similar pattern of distribution for antibiotic resistance genes and virulence genes. WGS revealed that the isolates are genetically closely related and showed a similar pattern of distribution for different genetic markers, therefore, these strains could be an accidental case cluster or cluster of an outbreak.

Diversity, Resistance Pattern and Level of Antibiotic Resistance Determinants Associated with Bacteria Isolated from Different Water Sources in Southwest Nigeria

Safe water is an essential resource for the existence and sustenance of life. The unavailability of safe water is a significant cause of water-related diseases, especially in developing countries like Nigeria. A spike in the incidence of waterborne diseases has become a public health concern. Hence, this study was designed to evaluate the diversity of bacteria, resistance pattern and level of antibiotic resistance determinants associated with bacteria isolated from different water sources in South-West Nigeria. A total of 120 water samples were collected across South-Western Nigeria from which bacteria were isolated, and identification was achieved by sequencing its partial 16S rRNA. Disc diffusion and multiplex PCR were used to determine antibiotic susceptibility and resistance determinants. A total of 50 bacterial isolates were identified, consisting of Proteus spp. (2), Bacillus spp. (8), Enterobacter spp. (8), Klebsiella spp. (9), Escherichia coli (7), Citrobacter spp. (6), Pseudomonas spp. (4), and Serratia marcescens (6). All the isolates were resistant to ceftazidime, cefuroxime, cefixime and amoxicillin/clavulanate, whereas 72%, 60%, 54% and 44% were resistant to nitrofurantoin, gentamicin, ciprofloxacin and ofloxacin respectively. Quinolone-resistant genes (qnrB, qnrA and qnrS), and tetracycline-resistant genes (tetA and tetB) were found in the isolates. The beta-lactamase gene and class 1 integron were also detected in the isolates, with the class 1 integron genes occurring the least. The results revealed that isolates were highly resistant to antibiotics used, as evident in the presence of antibiotic genes. This reveals the unsanitary states of water consumed by the general public, and the ingestion of these antibiotic-resistant bacteria is responsible for the birth of untreatable diseases. Keywords: Diversity, Antibiotic resistance, Resistance pattern, Resistance genes.

A review of antibiotic resistance among Campylobacter species in human, animal, and water sources in South Africa: a One Health Approach.

Campylobacter species are among the aetiological agents responsible for 400-500 million human diarrhoea cases per annum. The risk of dissemination of antibiotic-resistant Campylobacter species between humans, animals, and the environment is anticipated, given its transmissibility through these sources. The objective of this paper is to present a situation analysis that reports the current patterns and determinants of Campylobacter antibiotic resistance in South Africa. This review applies the One Health (OH) Approach to systematically review and collate the current antibiotic resistance status among Campylobacter spp. in South Africa. The highest level of resistance of Campylobacter in humans is to azithromycin (69.7%), whereas the lowest level of resistance of Campylobacter is to gatifloxacin (8.3%). In animals, high resistance to common antibiotics erythromycin (95.06%), clindamycin (95.68%), doxycycline (87.65%), erythromycin (90%), tetracycline (84.3%), streptomycin (88%), and ampicillin (73%) while 100% resistance of Campylobacter from water samples to tetracycline, imipenem, is recorded. Furthermore, resistance to clarithromycin (95%), azithromycin (92%), clindamycin (84.2%), doxycycline (80%), and ciprofloxacin (77.8%) is reported among Campylobacter spp. from water samples. The genetic similarity results suggest the movement of antibiotic-resistant Campylobacter spp. between humans and the environment. More research on antibiotic resistance among Campylobacter from other sources, outside clinical isolates, is recommended.

Mapping the evidence of the effects of environmental factors on the prevalence of antibiotic resistance in the non-built environment: Protocol for a systematic evidence map

BackgroundHuman, animal, and environmental health are increasingly threatened by the emergence and spread of antibiotic resistance. Inappropriate use of antibiotic treatments commonly contributes to this threat, but it is also becoming apparent that multiple, interconnected environmental factors can play a significant role. Thus, a One Health approach is required for a comprehensive understanding of the environmental dimensions of antibiotic resistance and inform science-based decisions and actions. The broad and multidisciplinary nature of the problem poses several open questions drawing upon a wide heterogeneous range of studies. ObjectiveThis study seeks to collect and catalogue the evidence of the potential effects of environmental factors on the abundance or detection of antibiotic resistance determinants in the outdoor environment, i.e., antibiotic resistant bacteria and mobile genetic elements carrying antibiotic resistance genes, and the effect on those caused by local environmental conditions of either natural or anthropogenic origin. MethodsHere, we describe the protocol for a systematic evidence map to address this, which will be performed in adherence to best practice guidelines. We will search the literature from 1990 to present, using the following electronic databases: MEDLINE, Embase, and the Web of Science Core Collection as well as the grey literature. We shall include full-text, scientific articles published in English. Reviewers will work in pairs to screen title, abstract and keywords first and then full-text documents. Data extraction will adhere to a code book purposely designed. Risk of bias assessment will not be conducted as part of this SEM.We will combine tables, graphs, and other suitable visualisation techniques to compile a database i) of studies investigating the factors associated with the prevalence of antibiotic resistance in the environment and ii) map the distribution, network, cross-disciplinarity, impact and trends in the literature.

735. Contribution of the Oral Cavity and Gastrointestinal Microbiome on Bloodstream Infections inLeukemia Patients

BackgroundBlood stream infections (BSI) are a common cause of morbidity and mortality in immunocompromised patients. It was previously reported that intestinal domination (defined as occupation of ≥ 30% of the microbiota by a single bacterial taxon) byEnterococcus and Proteobacteria often preceded enterococcal and gram-negative BSI.Methods16s rRNA sequencing was used to analyze the saliva and stool of 73 acute leukemia patients with BSIs to determine the correlation between the taxa present ( > 0% relative abundance), colonizing ( > 3%) or dominating ( > 30%) a patient’s microbiome and the BSI agent. Species level confirmation of these findings was performed via digital droplet PCR (ddPCR) and LEfSe analysis was used to determine enrichment of infectious taxa at either collection site. Whole genome sequencing and antimicrobial susceptibilities on all BSI isolates.ResultsWe collected simultaneous patient stool and blood isolates from 11 Pseudomonas aeruginosa, 14 Escherichia coli, 4 Klebsiella sp., 8 Enterococcus sp., 18 viridans group streptococci (VGS), 13 Staphylococcus epidermidis, and 5 Staphylococcus aureus BSIs. Mann-Whitney testing confirmed that individuals with P. aeruginosa (oral P =.004, stool P < .001), E. coli (stool P < .001), and VGS infections (oral P =.001) had significantly higher relative abundance of those respective genera compared to other BSI patients, and this appeared to be site specific. LEfSe analysis confirmed enrichment of Pseudomonas in the saliva and stool, Escherichia in the stool, and Streptococcus in the saliva of respective infections. However, while 64 patients showed presence of the infectious genera in the stool and/or saliva at time of BSI, only 7 exhibited domination. ddPCR was used to confirm not only species specificity, but the detection of those antibiotic resistance determinants (CTX-14, CTX-15, Van A and CfrA) found in the BSI isolates within concurrent stool samples.ConclusionIt appears that GI domination by the infecting organism was not present at the time of most BSIs. However, in scenarios where the etiological agent was detectable in the saliva or stool, so were the antibiotic resistant determinants. Furthermore, certain infections exhibited a significant difference in oral or stool presence by the same bacteria they were infected with.DisclosuresAll Authors: No reported disclosures.

1737. Xeruborbactam (QPX) Potentiates the Activity of β-Lactam (BL) Antibiotics Against a Diverse Group of Highly Drug-Resistant Enterobacterales (ENT)

Abstract Background Antibiotic resistant ENT are a growing threat worldwide. QPX is an ultra-broad-spectrum β-lactamase inhibitor (BLI) with potent inhibition of classes A and D, and many metallo-β-lactamases, which has potential to fill the void of currently available BL-BLIs. Methods We evaluated QPX (fixed concentration of 8 µg/mL) in combination with meropenem (MEM), cefepime (FEP) and aztreonam (ATM) against a diverse group of ENT clinical isolates selected from a worldwide repository. Antibiotic resistance determinants were assessed by mining whole-genome sequencing data generated using Illumina MiSeq. Results Klebsiella spp, Enterobacter spp, and Escherichia coli were most common among the 90 isolates tested (Fig. 1). 71% (64) produced carbapenemases (Fig. 2): 3 isolates produced both class A and B carbapenemases. 11% of isolates harbored mutations in ompK 36/ompC genes. 57% (51) were resistant to MEM, 31% to imipenem-relebactam, 17% (15) to ceftazidime-avibactam (CZA), and 9% to MEM-vaborbactam (MVB). ENT-resistant to CZA were due to production of class B, D or KPC-3 variants, or ompC mutation in a K. aerogenes isolate. ENT-resistant to MVB were due to class B or D enzymes, or class A with ompK36 or ompC mutations. MIC distributions of BL with or without QPX against all isolates tested are presented in Fig. 3. Addition of QPX to MEM, FEP and AMT reduced MIC50s and MIC90s of these agents (Fig. 3; p&amp;lt; 0.0001). Of note, addition of QPX reduced MEM MICs more than did vaborbactam (median 533- versus 24-fold; p=0.0006). QPX reduced MICs of MEM, FEP and ATM to levels below respective breakpoints for non-susceptibility (Fig. 3). MIC distribution of ENT isolates stratified by the types of carbapenemases are presented in Fig. 4. QPX potentiated activity of MEM, FEP or ATM against ENT, regardless of whether they produced class A, B or D carbapenemases. Conclusion QPX enhanced activity of MEM, FEP and ATM against carbapenemase-producing or other carbapenem-resistant ENT (CRE), regardless of species or other resistance determinants. Most remarkably, QPX rendered each BL equally active against CRE. The expanded spectrum of QPX against class B and D carbapenemases addresses a major unmet need against CRE. Disclosures Cornelius J. Clancy, MD, receives research funding paid to his institution from Astellas and Merck: Grant/Research Support|serves as an advisory Board member for Astellas, Cidara, and Scynexis, served on the advisory board for Merck, Qpex Biopharma, and Shionogi: Advisor/Consultant|Venatorx and Needham &amp; Associates: Advisor/Consultant.

Выделение и характеристика бактериофагов Klebsiella pneumoniae, кодирующих полисахарид-деполимеразы с уникальной капсульной специфичностью

Bacterial infections caused by antibiotic resistant strains of Klebsiella pneumoniae are among the most dangerous threats for the world's public healthcare. Treatment with bacteriophages and/or their derivatives could become one of the alternative methods for therapy of infections caused by K. pneumoniae. The study was aimed to isolate from the environment and characterize the capsule-specific K. pneumoniae bacteriophages that are useful for therapy and possess the polysaccharide depolymerase genes. Bacteriophages were isolated from the river water samples by enrichment method. The host range of bacteriophages were assessed using the collection of 180 K. pneumoniae clinical strains. Bacteriophage whole genome sequencing was performed on the MiSeq platform (Illumina). Four new bacteriophages from different taxonomic groups were isolated and characterized during the study: vB_KpnM_NDO71 (Vequintavirinae family), vB_KpnS_MAG26fr (Casjensviridae family), vB_KpnS_MDA2066 (Ackermannviridae family), and vB_KpnS_PMM-G3 (Drexlerviridae family). Bacteriophages vB_KpnM_NDO71, vB_KpnS_MAG26fr, and vB_KpnS_PMM-G3 had a narrow lytic spectrum and lysed all strains with the capsular type of the host: KL45, KL19 or KL28, respectively. Bacteriophage vB_KpnS_MDA2066 showed lytic activity against strains with two different capsular types: KL19 and KL107. Bacteriophages were strictly virulent and contained no integrase genes, potentially dangerous toxin genes or antibiotic resistance determinants. This allows them to be used in therapeutic practice. Receptor-binding proteins represented by polysaccharide depolymerases were predicted for each bacteriophage.

A geographic cluster of healthcare-associated carbapenemase-producing hypervirulent Klebsiella pneumoniae sequence type 23.

Hypervirulent Klebsiella pneumoniae has typically been associated with invasive, community-associated infections. This study describes the molecular, epidemiological and clinical characteristics of a cluster of carbapenemase-producing hypervirulent K. pneumoniae in the South-East of Ireland. It highlights the increasing risk that hypervirulent K. pneumoniae poses to healthcare and residential care populations. A retrospective analysis of sequences on K. pneumoniae isolates in the K. pneumoniae database of the National Carbapenemase-Producing Enterobacterales Reference Laboratory Service was performed to identify cases of hypervirulent K. pneumoniae from one hospital network. Hypervirulence scores were assigned based on the presence of recognised hypervirulence genes. A retrospective review of patient records was carried out for all confirmed cases of hypervirulent K. pneumoniae identified and clinical, epidemiological and molecular characteristics described. Twenty-eight cases of hypervirulent OXA-48 producing K. pneumoniae were identified over a 2-year period. All isolates were sequence-type 23 with a hypervirulence score of 5. All isolates carried the blaOXA-48 carbapenemase gene. All cases had a record of current or recent hospitalisation or residence in a long-term residential care facility. This study describes extensive dissemination of hypervirulent K. pneumoniae within healthcare facilities and an ongoing outbreak in our region. It shows the convergence of hypervirulence and antibiotic resistance determinants. Healthcare facilities need to consider their infection prevention, control and surveillance strategies to monitor and prevent further dissemination among a vulnerable population. Diagnostic laboratories need to ensure they have the ability and capacity for testing. Readily deployed laboratory methods for detection of hypervirulence are required.