scholarly journals Microbiome Compositions and Resistome Levels after Antibiotic Treatment of Critically Ill Patients: An Observational Cohort Study

2021 ◽  
Vol 9 (12) ◽  
pp. 2542
Author(s):  
Karen Leth Nielsen ◽  
Markus Harboe Olsen ◽  
Albert Pallejá ◽  
Søren Røddik Ebdrup ◽  
Nikolaj Sørensen ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Broad Spectrum ◽  
Selection Pressure ◽  
Shannon Index ◽  
Post Treatment ◽  
Neurointensive Care ◽  
Resistant Bacteria ◽  
Metagenomic Sequencing ◽  
Narrow Spectrum ◽  
Broad Spectrum Treatment

Hospitalization and treatment with antibiotics increase the risk of acquiring multidrug-resistant bacteria due to antibiotic-mediated changes in patient microbiota. This study aimed to investigate how broad- and narrow-spectrum antibiotics affect the gut microbiome and the resistome in antibiotic naïve patients during neurointensive care. Patients admitted to the neurointensive care unit were treated with broad-spectrum (meropenem or piperacillin/tazobactam) or narrow-spectrum antibiotic treatment (including ciprofloxacin, cefuroxime, vancomycin and dicloxacillin) according to clinical indications. A rectal swab was collected from each patient before and after 5–7 days of antibiotic therapy (N = 34), respectively. Shotgun metagenomic sequencing was performed and the composition of metagenomic species (MGS) was determined. The resistome was characterized with CARD RGI software and the CARD database. As a measure for selection pressure in the patient, we used the sum of the number of days with each antibiotic (antibiotic days). We observed a significant increase in richness and a tendency for an increase in the Shannon index after narrow-spectrum treatment. For broad-spectrum treatment the effect was more diverse, with some patients increasing and some decreasing in richness and Shannon index. This was studied further by comparison of patients who had gained or lost >10 MGS, respectively. Selection pressure was significantly higher in patients with decreased richness and a decreased Shannon index who received the broad treatment. A decrease in MGS richness was significantly correlated to the number of drugs administered and the selection pressure in the patient. Bray–Curtis dissimilarities were significant between the pre- and post-treatment of samples in the narrow group, indicating that the longer the narrow-spectrum treatment, the higher the differences between the pre- and the post-treatment microbial composition. We did not find significant differences between pre- and post-treatment for both antibiotic spectrum treatments; however, we observed that most of the antibiotic class resistance genes were higher in abundance in post-treatment after broad-spectrum treatment.

scholarly journals Ridinilazole, a narrow spectrum antibiotic for treatment of Clostridioides difficile infection, enhances preservation of microbiota-dependent bile acids

2020 ◽  
Vol 319 (2) ◽  
pp. G227-G237 ◽  
Author(s):  
Xi Qian ◽  
Karin Yanagi ◽  
Anne V. Kane ◽  
Nicholas Alden ◽  
Ming Lei ◽  
...  
Keyword(s):  
Bile Acid ◽  
Antibiotic Treatment ◽  
Broad Spectrum ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Treatment Cessation ◽  
Broad Spectrum Antibiotic ◽  
Narrow Spectrum ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection

This is the first study to demonstrate in humans the relationships between Clostridioides difficile antibiotic treatment choice and bile acid metabolism both during therapy and after treatment cessation. The results show a microbiota- and metabolome-preserving property of a novel narrow-spectrum agent that correlates with the agent’s favorable sustained clinical response rates compared with broad-spectrum antibiotic treatment.

scholarly journals Impact of narrow spectrum Penicillin V on the oral and fecal resistome in a young child treated for otitis media

2019 ◽  
Author(s):  
Kjersti Sturød ◽  
Achal Dhariwal ◽  
Ulf R Dahle ◽  
Didrik F Vestrheim ◽  
Fernanda C Petersen
Keyword(s):  
Otitis Media ◽  
Acute Otitis Media ◽  
Resistant Bacteria ◽  
Metagenomic Sequencing ◽  
Sequencing Data ◽  
Fecal Samples ◽  
Narrow Spectrum ◽  
Penicillin V ◽  
Antimicrobial Resistance Genes ◽  
The Impact

AbstractBackgroundAntibiotic overuse has led to a global emergence of resistant bacteria, and children are among the frequent users. Most studies with broad-spectrum antibiotics show severe impact on the resistome development of patients. Although narrow-spectrum antibiotics are believed to have less side-effects, their impact on the microbiome and resistome is mostly unknown. The aim of this study was to investigate the impact of the narrow-spectrum antibiotic phenoxymethylpenicillin (Penicillin V) on the microbiome and resistome of a child treated for acute otitis media (OM).MethodsOral and fecal samples were collected from a one-year child before (day 0) and after (day 5 and 30) receiving Penicillin V against OM. Metagenomic sequencing data was analysed to determine taxonomic profiling, using Kraken and Bracken software, and resistance profiling, using KMA in combination with the ResFinder database.ResultsIn the oral samples, 11 antimicrobial resistance genes (ARGs), belonging to four classes, were identified at baseline. At day 5, the abundance of some ARGs was increased, some remained unchanged, while others disappeared. At day 30, most ARGs had returned to baseline levels, or lower. In the fecal samples we observed seven ARGs at baseline and five at day 5, with only one gene observed at day 5 being present at baseline. At day 30 the number of ARGs increased to 21 ARGs from 7 different classes.ConclusionsPenicillin V had a remarkable impact on the fecal resistome indicating that even narrow-pectrum antibiotics may have important consequences in selecting for a more resistant microbiome.

A de-escalated treatment strategy in the management of paediatric cervicofacial actinomycosis

2021 ◽  
Vol 14 (11) ◽  
pp. e245950
Author(s):  
Justin Jui Yuan Yeo ◽  
Michael Edward Hopkins ◽  
Aidah Isa
Keyword(s):  
Antibiotic Treatment ◽  
Adjuvant Treatment ◽  
Treatment Strategy ◽  
Surgical Intervention ◽  
Granulomatous Inflammation ◽  
Post Treatment ◽  
Bacterial Disease

Actinomycosis is a rare invasive bacterial disease that is characterised by granulomatous inflammation often mistaken as malignancy. Traditionally, this has been managed with prolonged courses of antibiotics with durations up to 6–12 months. Surgical intervention as an adjuvant treatment has been shown to reduce the length of antibiotic treatment significantly to 4 weeks. We report a case of cervicofacial actinomycosis in a 12-year-old girl who was adequately treated with an 11-day course of antibiotics without surgical intervention and shows no signs of recurrence at 6 months post-treatment.

scholarly journals A Degradation Product from Hydrolysate of Imipenem with Imis Broad-Spectrum Inhibits Metallo-β-Lactamases

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Ying Ge ◽  
Li-Wei Xu ◽  
Jian-Bin Zhen ◽  
Cheng Chen ◽  
Miao Lv ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Degradation Product ◽  
Substrate Inhibition ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Leaving Group ◽  
Ic50 Values ◽  
Hydrolysis Of

Background: Infections caused by metallo-β-lactamases (MβLs)-producing antibiotic-resistant bacteria pose a severe threat to public health. The synergistic use of current antibiotics in combination with MβL inhibitors is a promising therapeutic mode against these antibiotic-resistant bacteria. Objectives: The study aimed to probe the inhibition of MβLs and obtain the active component, P1, in the degradation product after imipenem was hydrolyzed by ImiS. Methods: The hydrolysis of two carbapenems with MβL ImiS was monitored by UV-Vis in real-time, and the degradation product from the leaving group produced after imipenem was hydrolyzed (but not for faropenem) was purified by HPLC to give one component, P1. Results: Kinetic assays revealed that P1 exhibited a broad-spectrum inhibition against VIM-2, NDM-1, ImiS, and L1, from three sub-classes of MβLs, with IC50 values of 8 - 32, 13.8 - 29.3, and 14.2 - 19.2 µM, using imipenem, cefazolin, and nitrocefin as substrates, respectively. Also, P1 showed synergistic antibacterial efficacy against drug-resistant Escherichia coli producing VIM-2, NDM-1, ImiS, and L1, in combination with antibiotics, restoring 16 to 32-fold and 32 to 128-fold efficacies of imipenem and cefazolin, respectively. Spectroscopic and Ellman's reagent analyses suggested that P1, a mercaptoethyl-form imidamide, is a mechanism-based inhibitor, while faropenem has no substrate inhibition, due to the lack of a leaving group. Conclusions: This work reveals that the hydrolysate of imipenem, a carbapenem with a good leaving group, can be used in screening for broad-spectrum inhibitors of MβLs.

scholarly journals Nanoparticles Enable Efficient Delivery of Antimicrobial Peptides for the Treatment of Deep Infections

2021 ◽  
Author(s):  
Yingxue Deng ◽  
Rui Huang ◽  
Songyin Huang ◽  
Menghua Xiong
Keyword(s):  
Antimicrobial Peptides ◽  
Broad Spectrum ◽  
Antimicrobial Properties ◽  
Therapeutic Index ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Efficient Delivery ◽  
Delivery Vehicles

Antimicrobial peptides (AMPs) have emerged as promising alternatives of traditional antibiotics against drug-resistant bacteria owing to their broad-spectrum antimicrobial properties and low tendency to drugresistance. However, their therapeutic efficacy in vivo, especially for infections in deep organs, is limited owing to their systemic toxicity and low bioavailability. Nanoparticles-based delivery systems offer a strategy to increase the therapeutic index of AMPs by preventing proteolysis, increasing the accumulation at infection sites, and reducing toxicity. Herein, we will discuss the current progress of using nanoparticles as delivery vehicles for AMPs for the treatment of deep infections.

Microbiological pattern of prosthetic hip and knee infections: a high-volume, single-centre experience in China

2021 ◽  
Author(s):  
Yali Yu ◽  
Yiyi Kong ◽  
Jing Ye ◽  
Aiguo Wang ◽  
Wenteng Si
Keyword(s):  
Antibiotic Treatment ◽  
Prolonged Treatment ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Musculoskeletal Infection ◽  
Gram Negative ◽  
Content Type ◽  
Empirical Antibiotic Treatment ◽  
Link Type

Introduction. Prosthetic joint infection (PJI) is a serious complication after arthroplasty, which results in high morbidity, prolonged treatment and considerable healthcare expenses in the absence of accurate diagnosis. In China, microbiological data on PJIs are still scarce. Hypothesis/Gap Statement. The incidence of PJI is increasing year by year, and the proportion of drug-resistant bacteria infection is nicreasing, which brings severe challenges to the treatment of infection. Aim. This study aimed to identify the pathogens in PJIs, multi-drug resistance, and evaluate the effect of the treatment regimen in patients with PJI. Methodology. A total of 366 consecutive cases of PJI in the hip or knee joint were admitted at the Orthopedic Surgery Center in Zhengzhou, China from January 2012 to December 2018. Infections were confirmed in accordance with the Infectious Diseases Society of America and the Musculoskeletal Infection Society (MSIS) criteria. Concurrently, patient demographic data, incidence and antibiotic resistance were investigated. Statistical differences were analysed using Fisher’s exact test or chi-square test. Results. Altogether, 318 PJI cases satisfying the inclusion criteria were enrolled in this study, including 148 with hip PJIs and 170 with knee PJIs. The average age of patients with hip PJIs was lesser than that of patients with knee PJIs (56.4 vs. 68.6 years). Meanwhile, coagulase-negative staphylococcus (CNS, n=81, 25.5 %) was the predominant causative pathogen, followed by Staphylococcus aureus (n=67, 21.1 %). Methicillin-resistant Staphylococcus (MRS) was identified in 28.9 % of PJI patients. In addition, fungus accounted for 4.8 % (n=15), non-tuberculosis mycobacterium accounted for 1.6 % (n=5), polymicrobial pathogens accounted for 21.7 % (n=69), and Gram-negative bacteria accounted for 7.9 % (n=25) of the total infections. The results of antibiotic susceptibility testing showed that gentamicin and clindamycin β-lactam antibiotics were poorly susceptible to Gram-positive isolates, but they were sensitive to rifampicin, linezolid and vancomycin. While antibiotics such as amikacin and imipenem were effective against Gram-negative bacteria, there was a high resistance rate of other pathogens to gentamicin, clindamycin and some quinolone antibacterial drugs. Empirical antibiotic treatment should combine vancomycin and cephalosporin, levofloxacin or clindamycin. When the pathogen is confirmed, the treatment should be individualized. Conclusions. The prevalence of culture-negative PJIs is still very high. Gram-positive bacteria are still the main type of pathogens that cause PJIs. Attention should be paid to the high incidence of MRS, such as MRSA and MR-CNS, among PJI patients. Empirical antibiotic treatment should cover Gram-positive isolates, especially Staphylococcus .

scholarly journals Merging Metagenomics and Spatial Epidemiology To Understand the Distribution of Antimicrobial Resistance Genes from Enterobacteriaceae in Wild Owls

2020 ◽  
Vol 86 (20) ◽  
Author(s):  
Elizabeth A. Miller ◽  
Julia B. Ponder ◽  
Michelle Willette ◽  
Timothy J. Johnson ◽  
Kimberly L. VanderWaal
Keyword(s):  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Spatial Epidemiology ◽  
Anthropogenic Sources ◽  
Resistant Bacteria ◽  
Metagenomic Sequencing ◽  
Wild Animals ◽  
Natural Ecosystems ◽  
Content Type ◽  
Antimicrobial Resistance Genes

ABSTRACT Antimicrobial resistance (AMR) is a well-documented phenomenon in bacteria from many natural ecosystems, including wild animals. However, the specific determinants and spatial distribution of resistant bacteria and antimicrobial resistance genes (ARGs) in the environment remain incompletely understood. In particular, information regarding the importance of anthropogenic sources of AMR relative to that of other biological and ecological influences is lacking. We conducted a cross-sectional study of AMR in great horned owls (Bubo virginianus) and barred owls (Strix varia) admitted to a rehabilitation center in the midwestern United States. A combination of selective culture enrichment and shotgun metagenomic sequencing was used to identify ARGs from Enterobacteriaceae. Overall, the prevalence of AMR was comparable to that in past studies of resistant Enterobacteriaceae in raptors, with acquired ARGs being identified in 23% of samples. Multimodel regression analyses identified seasonality and owl age to be important predictors of the likelihood of the presence of ARGs, with birds sampled during warmer months being more likely to harbor ARGs than those sampled during cooler months and with birds in their hatch year being more likely to harbor β-lactam ARGs than adults. Beyond host-specific determinants, ARG-positive owls were also more likely to be recovered from areas of high agricultural land cover. Spatial clustering analyses identified a significant high-risk cluster of tetracycline resistance gene-positive owls in the southern sampling range, but this could not be explained by any predictor variables. Taken together, these results highlight the complex distribution of AMR in natural environments and suggest that both biological and anthropogenic factors play important roles in determining the emergence and persistence of AMR in wildlife. IMPORTANCE Antimicrobial resistance (AMR) is a multifaceted problem that poses a worldwide threat to human and animal health. Recent reports suggest that wildlife may play an important role in the emergence, dissemination, and persistence of AMR. As such, there have been calls for better integration of wildlife into current research on AMR, including the use of wild animals as biosentinels of AMR contamination in the environment. A One Health approach can be used to gain a better understanding of all AMR sources and pathways, particularly those at the human-animal-environment interface. Our study focuses on this interface in order to assess the effect of human-impacted landscapes on AMR in a wild animal. This work highlights the value of wildlife rehabilitation centers for environmental AMR surveillance and demonstrates how metagenomic sequencing within a spatial epidemiology framework can be used to address questions surrounding AMR complexity in natural ecosystems.

scholarly journals Stochastic Variation in Expression of the Tricarboxylic Acid Cycle Produces Persister Cells

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Eliza A. Zalis ◽  
Austin S. Nuxoll ◽  
Sylvie Manuse ◽  
Geremy Clair ◽  
Lauren C. Radlinski ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Bacterial Infections ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Resistant Bacteria ◽  
Chronic Infections ◽  
Persister Cells ◽  
Stochastic Variation ◽  
Content Type ◽  
Atp Levels

ABSTRACT Chronic bacterial infections are difficult to eradicate, though they are caused primarily by drug-susceptible pathogens. Antibiotic-tolerant persisters largely account for this paradox. In spite of their significance in the recalcitrance of chronic infections, the mechanism of persister formation is poorly understood. We previously reported that a decrease in ATP levels leads to drug tolerance in Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. We reasoned that stochastic fluctuation in the expression of tricarboxylic acid (TCA) cycle enzymes can produce cells with low energy levels. S. aureus knockouts in glutamate dehydrogenase, 2-oxoketoglutarate dehydrogenase, succinyl coenzyme A (CoA) synthetase, and fumarase have low ATP levels and exhibit increased tolerance of fluoroquinolone, aminoglycoside, and β-lactam antibiotics. Fluorescence-activated cell sorter (FACS) analysis of TCA genes shows a broad Gaussian distribution in a population, with differences of over 3 orders of magnitude in the levels of expression between individual cells. Sorted cells with low levels of TCA enzyme expression have an increased tolerance of antibiotic treatment. These findings suggest that fluctuations in the levels of expression of energy-generating components serve as a mechanism of persister formation. IMPORTANCE Persister cells are rare phenotypic variants that are able to survive antibiotic treatment. Unlike resistant bacteria, which have specific mechanisms to prevent antibiotics from binding to their targets, persisters evade antibiotic killing by entering a tolerant nongrowing state. Persisters have been implicated in chronic infections in multiple species, and growing evidence suggests that persister cells are responsible for many cases of antibiotic treatment failure. New antibiotic treatment strategies aim to kill tolerant persister cells more effectively, but the mechanism of tolerance has remained unclear until now.

scholarly journals Engineered Lysins With Customized Lytic Activities Against Enterococci and Staphylococci

2020 ◽  
Vol 11 ◽  
Author(s):  
Hana Sakina Binte Muhammad Jai ◽  
Linh Chi Dam ◽  
Lowella Servito Tay ◽  
Jodi Jia Wei Koh ◽  
Hooi Linn Loo ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Catalytic Domain ◽  
Therapeutic Potential ◽  
Multidrug Resistant ◽  
Species Specificity ◽  
Resistant Bacteria ◽  
Modular Architecture ◽  
Narrow Spectrum ◽  
Cell Wall Binding ◽  
Peptidoglycan Hydrolysis

The emergence of multidrug-resistant bacteria has made minor bacterial infections incurable with many existing antibiotics. Lysins are phage-encoded peptidoglycan hydrolases that have demonstrated therapeutic potential as a novel class of antimicrobials. The modular architecture of lysins enables the functional domains – catalytic domain (CD) and cell wall binding domain (CBD) – to be shuffled to create novel lysins. The CD is classically thought to be only involved in peptidoglycan hydrolysis whereas the CBD dictates the lytic spectrum of a lysin. While there are many studies that extended the lytic spectrum of a lysin by domain swapping, few have managed to introduce species specificity in a chimeric lysin. In this work, we constructed two chimeric lysins by swapping the CBDs of two parent lysins with different lytic spectra against enterococci and staphylococci. We showed that these chimeric lysins exhibited customized lytic spectra distinct from the parent lysins. Notably, the chimeric lysin P10N-V12C, which comprises a narrow-spectrum CD fused with a broad-spectrum CBD, displayed species specificity not lysing Enterococcus faecium while targeting Enterococcus faecalis and staphylococci. Such species specificity can be attributed to the narrow-spectrum CD of the chimeric lysin. Using flow cytometry and confocal microscopy, we found that the E. faecium cells that were treated with P10N-V12C are less viable with compromised membranes yet remained morphologically intact. Our results suggest that while the CBD is a major determinant of the lytic spectrum of a lysin, the CD is also responsible in the composition of the final lytic spectrum, especially when it pertains to species-specificity.

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