Rapid Changes in Nasopharyngeal Antibiotic Resistance Gene Profiles After Short Courses of Antibiotics in a Pilot Study of Ambulatory Young Children. - Related Documents




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491701.0000Rapid Changes in Nasopharyngeal Antibiotic Resistance Gene Profiles After Short Courses of Antibiotics in a Pilot Study of Ambulatory Young Children. We quantified antibiotic resistance genes before and after short antibiotic courses in nasopharyngeal specimens from ambulatory children. Carriage of certain bacteria and resistance genes was common before antibiotics. After antibiotics, we observed substantial reductions in pneumococcal and Staphylococcus aureus carriage and rapid expansion in the abundance of certain resistance genes.202135350815
465310.9998Modelling the effectiveness of surveillance based on metagenomics in detecting, monitoring, and forecasting antimicrobial resistance in livestock production under economic constraints. Current surveillance of antimicrobial resistance (AMR) is mostly based on testing indicator bacteria using minimum inhibitory concentration (MIC) panels. Metagenomics has the potential to identify all known antimicrobial resistant genes (ARGs) in complex samples and thereby detect changes in the occurrence earlier. Here, we simulate the results of an AMR surveillance program based on metagenomics in the Danish pig population. We modelled both an increase in the occurrence of ARGs and an introduction of a new ARG in a few farms and the subsequent spread to the entire population. To make the simulation realistic, the total cost of the surveillance was constrained, and the sampling schedule was set at one pool per month with 5, 20, 50, or 100 samples. Our simulations demonstrate that a pool of 20-50 samples and a sequencing depth of 250 million fragments resulted in the shortest time to detection in both scenarios, with a time delay to detection of change of [Formula: see text]15 months in all scenarios. Compared with culture-based surveillance, our simulation indicates that there are neither significant reductions nor increases in time to detect a change using metagenomics. The benefit of metagenomics is that it is possible to monitor all known resistance in one sampling and laboratory procedure in contrast to the current monitoring that is based on the phenotypic characterisation of selected indicator bacterial species. Therefore, overall changes in AMR in a population will be detected earlier using metagenomics due to the fact that the resistance gene does not have to be transferred to and expressed by an indicator bacteria before it is possible to detect.202337990114
465420.9998Early Bacterial Colonization and Antibiotic Resistance Gene Acquisition in Newborns. Several studies have recently identified the main factors contributing to the bacterial colonization of newborns and the dynamics of the infant microbiome development. However, most of these studies address large time periods of weeks or months after birth, thereby missing on important aspects of the early microbiome maturation, such as the acquisition of antibiotic resistance determinants during postpartum hospitalization. The pioneer bacterial colonization and the extent of its associated antibiotic resistance gene (ARG) dissemination during this early phase of life are largely unknown. Studies addressing resistant bacteria or ARGs in neonates often focus only on the presence of particular bacteria or genes from a specific group of antibiotics. In the present study, we investigated the gut-, the oral-, and the skin-microbiota of neonates within the first 72 h after birth using 16S rDNA sequencing approaches. In addition, we screened the neonates and their mothers for the presence of 20 different ARGs by directed TaqMan qPCR assays. The taxonomic analysis of the newborn samples revealed an important shift of the microbiota during the first 72 h after birth, showing a clear site-specific colonization pattern in this very early time frame. Moreover, we report a substantial acquisition of ARGs during postpartum hospitalization, with a very high incidence of macrolide resistance determinants and mecA detection across different body sites of the newborns. This study highlights the importance of antibiotic resistance determinant dissemination in neonates during hospitalization, and the need to investigate the implication of the mothers and the hospital environment as potential sources of ARGs.202032754449
332530.9998Long-term beneficial effect of faecal microbiota transplantation on colonisation of multidrug-resistant bacteria and resistome abundance in patients with recurrent Clostridioides difficile infection. BACKGROUND: Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of Clostridioides difficile infections and can also be useful for other microbiota-related diseases. METHODS: We study the effect of FMT in patients with multiple recurrent C. difficile infections on colonisation with MDR bacteria and antibiotic resistance genes (ARG) on the short (3 weeks) and long term (1-3 years), combining culture methods and faecal metagenomics. RESULTS: Based on MDR culture (n = 87 patients), we notice a decrease of 11.5% in the colonisation rate of MDR bacteria after FMT (20/87 before FMT = 23%, 10/87 3 weeks after FMT). Metagenomic sequencing of patient stool samples (n = 63) shows a reduction in relative abundances of ARGs in faeces, while the number of different resistance genes in patients remained higher compared to stools of their corresponding healthy donors (n = 11). Furthermore, plasmid predictions in metagenomic data indicate that patients harboured increased levels of resistance plasmids, which appear unaffected by FMT. In the long term (n = 22 patients), the recipients' resistomes are still donor-like, suggesting the effect of FMT may last for years. CONCLUSIONS: Taken together, we hypothesise that FMT restores the gut microbiota to a composition that is closer to the composition of healthy donors, and potential pathogens are either lost or decreased to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, a notable part of which on plasmids, FMT decreases the total load of resistance genes.202438419010
314440.9998Impact of florfenicol dosing regimen on the phenotypic and genotypic resistance of enteric bacteria in steers. The food animal sector's use of antimicrobials is heavily critiqued for its role in allowing resistance to develop against critically important antimicrobials in human health. The WHO recommends using lower tier antimicrobials such as florfenicol for disease treatment. The primary objective of this study was to assess the differences in resistance profiles of enteric microbes following administration of florfenicol to steers using both FDA-approved dosing regimens and two different detection methods. Our hypothesis was that we would identify an increased prevalence of resistance in the steers administered the repeated, lower dose of florfenicol; additionally, we hypothesized resistance profiles would be similar between both detection methods. Twelve steers were administered either two intramuscular (20 mg/kg q 48 h; n = 6) or a single subcutaneous dose (40 mg/kg, n = 6). Fecal samples were collected for 38 days, and E. coli and Enterococcus were isolated and tested for resistance. Fecal samples were submitted for metagenomic sequencing analysis. Metagenomics revealed genes conferring resistance to aminoglycosides as the most abundant drug class. Most multidrug resistance genes contained phenicols. The genotypic and phenotypic patterns of resistance were not similar between drug classes. Observed increases in resistant isolates and relative abundance of resistance genes peaked after drug administration and returned to baseline by the end of the sampling period. The use of a "lower tier" antimicrobial, such as florfenicol, may cause an increased amount of resistance to critically important antimicrobials for a brief period, but these changes largely resolve by the end of the drug withdrawal period.202438418677
491850.9998Time trends for bacterial species and resistance patterns in semen in patients undergoing evaluation for male infertility. Semen from asymptomatic men who are being evaluated as male partners in interfile couples have been reported to contain a variety of bacteria. Longitudinal studies of the variation of these bacteria over time and their resistance patterns have not been commonly reported. At our institution, residues from semen samples are routinely evaluated for bacteria, including antibiotic sensitivity profiles. We set out to profile the changes in semen bacteria and antibiotic resistance at our institution over time. A total of 72 semen isolates were examined for type of bacteria and sensitivity to a panel of antibiotics. The results were divided into two separate 5-year intervals (the first beginning in 2006, the second in 2011) and compared. The majority of bacteria were skin flora, with Streptococcus and Staphylococcus being the most prevalent. The resistance data for these two pathogens showed minimal statistically significant difference between the two time periods, although the Staphylococcus species did show a trend toward increasing resistance, suggesting that antibiotics currently used in sperm cell preparations may need to be varied.201829706808
340460.9997Association between antibiotic residues, antibiotic resistant bacteria and antibiotic resistance genes in anthropogenic wastewater - An evaluation of clinical influences. The high use of antibiotics in human and veterinary medicine has led to a wide spread of antibiotics and antimicrobial resistance into the environment. In recent years, various studies have shown that antibiotic residues, resistant bacteria and resistance genes, occur in aquatic environments and that clinical wastewater seems to be a hot spot for the environmental spread of antibiotic resistance. Here a representative statistical analysis of various sampling points is presented, containing different proportions of clinically influenced wastewater. The statistical analysis contains the calculation of the odds ratios for any combination of antibiotics with resistant bacteria or resistance genes, respectively. The results were screened for an increased probability of detecting resistant bacteria, or resistance genes, with the simultaneous presence of antibiotic residues. Positive associated sets were then compared, with regards to the detected median concentration, at the investigated sampling points. All results show that the sampling points with the highest proportion of clinical wastewater always form a distinct cluster concerning resistance. The results shown in this study lead to the assumption that ciprofloxacin is a good indicator of the presence of multidrug resistant P. aeruginosa and extended spectrum β-lactamase (ESBL)-producing Klebsiella spec., Enterobacter spec. and Citrobacter spec., as it positively relates with both parameters. Furthermore, a precise relationship between carbapenemase genes and meropenem, regarding the respective sampling sites, could be obtained. These results highlight the role of clinical wastewater for the dissemination and development of multidrug resistance.202031622887
393270.9997Acquired antibiotic resistance: are we born with it? The rapid emergence of antibiotic resistance (AR) is a major public health concern. Recent findings on the prevalence of food-borne antibiotic-resistant (ART) commensal bacteria in ready-to-consume food products suggested that daily food consumption likely serves as a major avenue for dissemination of ART bacteria from the food chain to human hosts. To properly assess the impact of various factors, including the food chain, on AR development in hosts, it is important to determine the baseline of ART bacteria in the human gastrointestinal (GI) tract. We thus examined the gut microbiota of 16 infant subjects, from the newborn stage to 1 year of age, who fed on breast milk and/or infant formula during the early stages of development and had no prior exposure to antibiotics. Predominant bacterial populations resistant to several antibiotics and multiple resistance genes were found in the infant GI tracts within the first week of age. Several ART population transitions were also observed in the absence of antibiotic exposure and dietary changes. Representative AR gene pools including tet(M), ermB, sul2, and bla(TEM) were detected in infant subjects. Enterococcus spp., Staphylococcus spp., Klebsiella spp., Streptococcus spp., and Escherichia coli/Shigella spp. were among the identified AR gene carriers. ART bacteria were not detected in the infant formula and infant foods examined, but small numbers of skin-associated ART bacteria were found in certain breast milk samples. The data suggest that the early development of AR in the human gut microbiota is independent of infants' exposure to antibiotics but is likely impacted by exposure to maternal and environmental microbes during and after delivery and that the ART population is significantly amplified within the host even in the absence of antibiotic selective pressure.201121821748
332880.9997The gastrointestinal antibiotic resistome in pediatric leukemia and lymphoma patients. INTRODUCTION: Most children with leukemia and lymphoma experience febrile neutropenia. These are treated with empiric antibiotics that include β-lactams and/or vancomycin. These are often administered for extended periods, and the effect on the resistome is unknown. METHODS: We examined the impact of repeated courses and duration of antibiotic use on the resistome of 39 pediatric leukemia and lymphoma patients. Shotgun metagenome sequences from 127 stool samples of pediatric oncology patients were examined for abundance of antibiotic resistance genes (ARGs) in each sample. Abundances were grouped by repeated courses (no antibiotics, 1-2 courses, 3+ courses) and duration (no use, short duration, long and/or mixed durationg) of β-lactams, vancomycin and "any antibiotic" use. We assessed changes in both taxonomic composition and prevalence of ARGs among these groups. RESULTS: We found that Bacteroidetes taxa and β-lactam resistance genes decreased, while opportunistic Firmicutes and Proteobacteria taxa, along with multidrug resistance genes, increased with repeated courses and/or duration of antibiotics. Efflux pump related genes predominated (92%) among the increased multidrug genes. While we found β-lactam ARGs present in the resistome, the taxa that appear to contain them were kept in check by antibiotic treatment. Multidrug ARGs, mostly efflux pumps or regulators of efflux pump genes, were associated with opportunistic pathogens, and both increased in the resistome with repeated antibiotic use and/or increased duration. CONCLUSIONS: Given the strong association between opportunistic pathogens and multidrug-related efflux pumps, we suggest that drug efflux capacity might allow the opportunistic pathogens to persist or increase despite repeated courses and/or duration of antibiotics. While drug efflux is the most direct explanation, other mechanisms that enhance the ability of opportunistic pathogens to handle environmental stress, or other aspects of the treatment environment, could also contribute to their ability to flourish within the gut during treatment. Persistence of opportunistic pathogens in an already dysbiotic and weakened gastrointestinal tract could increase the likelihood of life-threatening blood borne infections. Of the 39 patients, 59% experienced at least one gastrointestinal or blood infection and 60% of bacteremia's were bacteria found in stool samples. Antimicrobial stewardship and appropriate use and duration of antibiotics could help reduce morbidity and mortality in this vulnerable population.202336909730
458190.9997Development of aminoglycoside and β-lactamase resistance among intestinal microbiota of swine treated with lincomycin, chlortetracycline, and amoxicillin. Lincomycin, chlortetracycline, and amoxicillin are commonly used antimicrobials for growth promotion and infectious disease prophylaxis in swine production. In this study, we investigated the shifts and resistance development among intestinal microbiota in pregnant sows before and after lincomycin, chlortetracycline, and amoxicillin treatment by using phylogenetic analysis, bacterial enumeration, and PCR. After the antimicrobial treatment, shifts in microbial community, an increased proportion of resistant bacteria, and genes related to antimicrobial resistance as compared to the day before antimicrobial administration (day 0) were observed. Importantly, a positive correlation between antimicrobial resistance gene expression in different categories, especially those encoding aminoglycoside and β-lactamase and antimicrobial resistance, was observed. These findings demonstrate an important role of antimicrobial usage in animals in the development of antimicrobial resistance, and support the notion that prudent use of antimicrobials in swine is needed to reduce the risk of the emergence of multi-drug resistant zoonotic pathogens.201425408688
3405100.9997Practical implications of erythromycin resistance gene diversity on surveillance and monitoring of resistance. Use of antibiotics in human and animal medicine has applied selective pressure for the global dissemination of antibiotic-resistant bacteria. Therefore, it is of interest to develop strategies to mitigate the continued amplification and transmission of resistance genes in environmental reservoirs such as farms, hospitals and watersheds. However, the efficacy of mitigation strategies is difficult to evaluate because it is unclear which resistance genes are important to monitor, and which primers to use to detect those genes. Here, we evaluated the diversity of one type of macrolide antibiotic resistance gene (erm) in one type of environment (manure) to determine which primers would be most informative to use in a mitigation study of that environment. We analyzed all known erm genes and assessed the ability of previously published erm primers to detect the diversity. The results showed that all known erm resistance genes group into 66 clusters, and 25 of these clusters (40%) can be targeted with primers found in the literature. These primers can target 74%-85% of the erm gene diversity in the manures analyzed.201829346541
4647110.9997Development of Antibiotic Resistance during Simulated Treatment of Pseudomonas aeruginosa in Chemostats. During treatment of infections with antibiotics in critically ill patients in the intensive care resistance often develops. This study aims to establish whether under those conditions this resistance can develop de novo or that genetic exchange between bacteria is by necessity involved. Chemostat cultures of Pseudomonas aeruginosa were exposed to treatment regimes with ceftazidime and meropenem that simulated conditions expected in patient plasma. Development of antibiotic resistance was monitored and mutations in resistance genes were searched for by sequencing PCR products. Even at the highest concentrations that can be expected in patients, sufficient bacteria survived in clumps of filamentous cells to recover and grow out after 3 to 5 days. At the end of a 7 days simulated treatment, the minimal inhibitory concentration (MIC) had increased by a factor between 10 and 10,000 depending on the antibiotic and the treatment protocol. The fitness costs of resistance were minimal. In the resistant strains, only three mutations were observed in genes associated with beta-lactam resistance. The development of resistance often observed during patient treatment can be explained by de novo acquisition of resistance and genetic exchange of resistance genes is not by necessity involved. As far as conclusions based on an in vitro study using P. aeruginosa and only two antibiotics can be generalized, it seems that development of resistance can be minimized by treating with antibiotics in the highest concentration the patient can endure for the shortest time needed to eliminate the infection.201626872140
3935120.9997Removal of antimicrobial prophylaxis and its effect on swine carriage of antimicrobial-resistant coliforms. The use of antimicrobials in the food animal industry has caused an increased prevalence of antimicrobial-resistant bacteria and antimicrobial resistance genes, which can be transferred to the microbiota of humans through the food chain or the environment. To reduce the development and spread of antimicrobial resistance, restrictions on antimicrobial use in food animals have been implemented in different countries. We investigated the impact of an antimicrobial restriction intervention during two generations of pigs. Fecal samples were collected in five growth phases. The frequency of antimicrobial-resistant coliforms and antimicrobial-resistant bacteria or antimicrobial resistance genes was analyzed. No differences in the richness or abundance of antimicrobial-resistant coliforms or antimicrobial resistance genes were found when animals fed with or without prophylactic antimicrobials were compared. Withholding antimicrobial supplementation did not negatively affect weight gain in pigs. Withdrawal of prophylactic antimicrobial consumption during two generations of pigs was not enough to reduce the prevalence of antimicrobial resistance genes, as measured by richness and abundance markers. This study indicates that the fitness costs associated with bacterial carriage of some antimicrobial resistance genes are low.202134872396
2549130.9997Effects of selective digestive decontamination (SDD) on the gut resistome. OBJECTIVES: Selective digestive decontamination (SDD) is an infection prevention measure for critically ill patients in intensive care units (ICUs) that aims to eradicate opportunistic pathogens from the oropharynx and intestines, while sparing the anaerobic flora, by the application of non-absorbable antibiotics. Selection for antibiotic-resistant bacteria is still a major concern for SDD. We therefore studied the impact of SDD on the reservoir of antibiotic resistance genes (i.e. the resistome) by culture-independent approaches. METHODS: We evaluated the impact of SDD on the gut microbiota and resistome in a single ICU patient during and after an ICU stay by several metagenomic approaches. We also determined by quantitative PCR the relative abundance of two common aminoglycoside resistance genes in longitudinally collected samples from 12 additional ICU patients who received SDD. RESULTS: The patient microbiota was highly dynamic during the hospital stay. The abundance of antibiotic resistance genes more than doubled during SDD use, mainly due to a 6.7-fold increase in aminoglycoside resistance genes, in particular aph(2″)-Ib and an aadE-like gene. We show that aph(2″)-Ib is harboured by anaerobic gut commensals and is associated with mobile genetic elements. In longitudinal samples of 12 ICU patients, the dynamics of these two genes ranged from a ∼10(4) fold increase to a ∼10(-10) fold decrease in relative abundance during SDD. CONCLUSIONS: ICU hospitalization and the simultaneous application of SDD has large, but highly individualized, effects on the gut resistome of ICU patients. Selection for transferable antibiotic resistance genes in anaerobic commensal bacteria could impact the risk of transfer of antibiotic resistance genes to opportunistic pathogens.201424710024
3400140.9997Chicken liver is a potential reservoir of bacteriophages and phage-derived particles containing antibiotic resistance genes. Poultry meat production is one of the most important agri-food industries in the world. The selective pressure exerted by widespread prophylactic or therapeutic use of antibiotics in intensive chicken farming favours the development of drug resistance in bacterial populations. Chicken liver, closely connected with the intestinal tract, has been directly involved in food-borne infections and found to be contaminated with pathogenic bacteria, including Campylobacter and Salmonella. In this study, 74 chicken livers, divided into sterile and non-sterile groups, were analysed, not only for microbial indicators but also for the presence of phages and phage particles containing antibiotic resistance genes (ARGs). Both bacteria and phages were detected in liver tissues, including those dissected under sterile conditions. The phages were able to infect Escherichia coli and showed a Siphovirus morphology. The chicken livers contained from 10(3) to 10(6) phage particles per g, which carried a range of ARGs (bla(TEM) , bla(CTx-M-1) , sul1, qnrA, armA and tetW) detected by qPCR. The presence of phages in chicken liver, mostly infecting E. coli, was confirmed by metagenomic analysis, although this technique was not sufficiently sensitive to identify ARGs. In addition, ARG-carrying phages were detected in chicken faeces by qPCR in a previous study of the group. Comparison of the viromes of faeces and liver showed a strong coincidence of species, which suggests that the phages found in the liver originate in faeces. These findings suggests that phages, like bacteria, can translocate from the gut to the liver, which may therefore constitute a potential reservoir of antibiotic resistance genes.202235485188
3723150.9997Hospital Antibiotics Usage: Environmental Hazard and Promotion of Antibiotic Resistant Bacteria. INTRODUCTION: Hospitals constitute a particular source of drug residues emission, especially antibiotics considered as the most critical therapeutic classes used in hospitals. Thus, the hospital wastewater can widely spread both types of emerging pollutants, antibiotic residues and antibiotic resistance bacteria. For this reason, antibiotics usage must be monitored. This study was conducted to investigate potential antibiotic compounds which can present potential environmental hazard and promote antibiotic resistance. METHODS: The consumption-based approach was adopted to calculate predicted antibiotic concentrations in hospital wastewaters. In the process, we assessed the antibiotics potential environmental hazard, with the hazard quotient between predicted concentrations and predicted no effect concentrations intended to be protective of ecological species. In order to evaluate the hospital contribution to antibiotic resistance bacteria promotion, we also compared predicted concentrations with predicted no effect concentrations as theoretical selective resistance bacteria. RESULTS: The highest expected concentrations in hospital wastewater were found for Penicillins and Cephalosporins being the most prescribed antibiotics in our context. We noted that among this class, Ampicillin is the most hazardous compound followed by Imipenem and Gentamicin as exclusive hospital use antibiotics, in spite of their low consumption. The results showed also that Ampicillin, Amoxicillin, and Ceftriaxone had a high ratio of potential antibiotic resistance bacteria promotion, confirming the correlation found previously between abundance of resistant bacteria and the corresponding effluent antibiotic concentrations. Nevertheless, the promotion of resistance selection can also be attributed to Imipenem and Ciprofloxacin as little-used antibiotics and occur at low to moderate levels in hospital wastewater. CONCLUSION: This study identified the profile antibiotics consumption and their potential environmental hazard contribution and antibiotic resistant bacteria promotion. It can help decision-makers make appropriate management decisions, especially preventive measures related to antibiotic use pattern, as neither dilution nor treatment can eliminate antibiotic residues and antibiotic resistance genes.202234113952
4649160.9997Factors affecting the measurement of antibiotic resistance in bacteria isolated from lake water. It is more difficult to obtain a reliable assessment of antibiotic resistance in populations of aquatic bacteria than in those populations which are well characterized (e.g. bacteria of medical and veterinary significance). Factors which influence the results include the bacterial taxa involved, their site of origin and the methods and media used to isolate and subculture the bacteria, and to perform the sensitivity tests. Examples of these effects are provided. The resistance profiles obtained with populations of aquatic pseudomonads depend on the species composition of the population. Resistance patterns in aquatic bacteria varied with the site from which they were isolated; a higher incidence of resistance was recorded along shorelines and in sheltered bays than in the open water. The inclusion of antibiotics in the media employed for primary isolation increased the number of individual and multiple resistances recorded. A similar effect was observed with increased inoculum size in the sensitivity disc method but this could be reversed by raising the incubation temperature. The medium used to conduct the test also affected the results and many aquatic bacteria failed to grow on media such as Iso-Sensitest Agar. It is recommended that the sensitivity disc method is adopted for aquatic bacteria because it permits interpretation of a wider range of response. Comparison of the incidence of antibiotic resistance in different habitats will remain meaningless, however, until comprehensive methods for the identification of bacteria are developed and the techniques used for sensitivity testing are standardized.19863636321
3721170.9997Contribution of Time, Taxonomy, and Selective Antimicrobials to Antibiotic and Multidrug Resistance in Wastewater Bacteria. The use of nontherapeutic broad-spectrum antimicrobial agents triclosan (TCS) and benzalkonium chloride (BC) can contribute to bacterial resistance to clinically relevant antibiotics. Antimicrobial-resistant bacteria within wastewater may reflect the resistance burden within the human microbiome, as antibiotics and pathogens in wastewater can track with clinically relevant parameters during perturbations to the community. In this study, we monitored culturable and resistant wastewater bacteria and cross-resistance to clinically relevant antibiotics to gauge the impact of each antimicrobial and identify factors influencing cross-resistance profiles. Bacteria resistant to TCS and BC were isolated from wastewater influent over 21 months, and cross-resistance, taxonomy, and monthly changes were characterized under both antimicrobial selection regimes. Cross-resistance profiles from each antimicrobial differed within and between taxa. BC-isolated bacteria had a significantly higher prevalence of resistance to "last-resort antibiotic" colistin, while isolates resistant to TCS exhibited higher rates of multidrug resistance. Prevalence of culturable TCS-resistant bacteria decreased over time following Food and Drug Administration (FDA) TCS bans. Cross-resistance patterns varied according to sampling date, including among the most clinically important antibiotics. Correlations between strain-specific resistance profiles were largely influenced by taxonomy, with some variations associated with sampling date. The results reveal that time, taxonomy, and selection by TCS and BC impact features of cross-resistance patterns among diverse wastewater microorganisms, which could reflect the variety of factors influencing resistance patterns relevant to a community microbiome.202033258596
3327180.9997Ribaxamase, an Orally Administered β-Lactamase, Diminishes Changes to Acquired Antimicrobial Resistance of the Gut Resistome in Patients Treated with Ceftriaxone. INTRODUCTION: Intravenous (IV) β-lactam antibiotics, excreted through bile into the gastrointestinal (GI) tract, may disrupt the gut microbiome by eliminating the colonization resistance from beneficial bacteria. This increases the risk for Clostridium difficile infection (CDI) and can promote antimicrobial resistance by selecting resistant organisms and eliminating competition by non-resistant organisms. Ribaxamase is an orally administered β-lactamase for use with IV β-lactam antibiotics (penicillins and cephalosporins) and is intended to degrade excess antibiotics in the upper GI before they can disrupt the gut microbiome and alter the resistome. METHODS: Longitudinal fecal samples (349) were collected from patients who participated in a previous Phase 2b clinical study with ribaxamase for prevention of CDI. In that previous study, patients were treated with ceftriaxone for a lower respiratory tract infection and received concurrent ribaxamase or placebo. Extracted fecal DNA from the samples was subjected to whole-genome shotgun sequencing and analyzed for the presence of antimicrobial resistance (AMR) genes by alignment of sequences against the Comprehensive Antibiotic Resistance Database. A qPCR assay was also used to confirm some of the results. RESULTS: Database alignment identified ~1300 acquired AMR genes and gene variants, including those encoding β-lactamases and vancomycin resistance which were significantly increased in placebo vs ribaxamase-treated patients following antibiotic exposure. qPCR corroborated the presence of these genes and supported both new acquisition and expansion of existing gene pools based on no detectable copy number or a low copy number in pre-antibiotic samples which increased post-antibiotics. Additional statistical analyses demonstrated significant correlations between changes in the gut resistome and clinical study parameters including study drug assignment and β-lactamase and vancomycin resistance gene frequency. DISCUSSION: These findings demonstrated that ribaxamase reduced changes to the gut resistome subsequent to ceftriaxone administration and may help limit the emergence of AMR.202032801790
4621190.9997High Prophage Count in Staphylococcus Periprosthetic Joint Infection Is Associated With an Increase in Antibiotic Resistance Genes. BACKGROUND: Periprosthetic joint infections (PJI) caused by Staphylococcus species present a significant clinical challenge, especially in the context of rising antibiotic resistance. Lysogenic phages (viruses that infect bacteria and can integrate into the bacteria's genome in the form of a prophage) have the potential to contribute to antibiotic resistance and treatment failure through the transport of genetic material between bacteria. We hypothesized that prophage presence may be associated with the presence of antimicrobial resistance genes and phenotypic resistance in Staphylococcus species associated with PJI. METHODS: We examined the relationship between the presence of prophage and antibiotic resistance in Staphylococcus isolates collected from synovial fluid samples from 15 PJI patients. Bacterial isolates were assessed for antibiotic resistance and sequenced to identify prophages and antibiotic resistance genes. RESULTS: We observed that a higher prophage count was associated with a higher number of antibiotic resistance genes, but not with phenotypic antibiotic resistance. In addition, none of the prophages identified were significantly associated with phenotypic resistance. CONCLUSIONS: These findings suggest that prophages may contribute to the spread of antibiotic resistance genes, but the impact on phenotypic resistance may be more complex, highlighting the need for further research to explore prophage profiling in PJI biofilms.202540436077