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American Journal of Therapeutics
Topics: Humans; Levofloxacin; Anti-Bacterial Agents; Ofloxacin; Brain Diseases
PubMed: 36848632
DOI: 10.1097/MJT.0000000000001615 -
The American Journal of Gastroenterology Apr 2024Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the...
INTRODUCTION
Antibiotic resistance is one of the main factors that determine the efficacy of treatments to eradicate Helicobacter pylori infection. Our aim was to evaluate the effectiveness of first-line and rescue treatments against H. pylori in Europe according to antibiotics resistance.
METHODS
Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included.
RESULTS
A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results.
DISCUSSION
In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.
Topics: Adult; Humans; Anti-Bacterial Agents; Bismuth; Clarithromycin; Drug Resistance, Microbial; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Levofloxacin; Metronidazole; Prospective Studies; Tinidazole
PubMed: 37983769
DOI: 10.14309/ajg.0000000000002600 -
Antibiotics (Basel, Switzerland) Jul 2023The extensive use of fluoroquinolones has been consequently accompanied by the emergence of bacterial resistance, which triggers the necessity to discover new compounds.... (Review)
Review
The extensive use of fluoroquinolones has been consequently accompanied by the emergence of bacterial resistance, which triggers the necessity to discover new compounds. Delafloxacin is a brand-new anionic non-zwitterionic fluoroquinolone with some structural particularities that give it attractive proprieties: high activity under acidic conditions, greater in vitro activity against Gram-positive bacteria-even those showing resistance to currently-used fluoroquinolones-and nearly equivalent affinity for both type-II topoisomerases (i.e., DNA gyrase and topoisomerase IV). During phases II and III clinical trials, delafloxacin showed non-inferiority compared to standard-of-care therapy in the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia, which resulted in its approval in 2017 by the Food and Drug Administration for indications. Thanks to its overall good tolerance, its broad-spectrum in vitro activity, and its ease of use, it could represent a promising molecule for the treatment of bacterial infections.
PubMed: 37627661
DOI: 10.3390/antibiotics12081241 -
The Lancet. Gastroenterology &... Jan 2024We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic resistance continues to rise is unknown. Therefore, we aimed to assess the latest prevalence of H pylori antibiotic resistance in this region.
METHODS
We did an updated systematic review and meta-analysis of observational studies and randomised controlled trials published in PubMed, Embase, and Cochrane Library between Jan 1, 1990, and July 12, 2023. Studies investigating primary H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline in individuals naive to eradication therapy in the Asia-Pacific region (as defined by the UN geoscheme) were eligible for inclusion. There were no language restrictions. Studies that focused on specific subpopulations (eg, children) were excluded. Using a standardised extraction form, two authors independently reviewed and extracted summary data from all eligible articles. The updated prevalence of antibiotic resistance was generated by meta-analysis under a random-effects model and subgroup analyses were done by countries and periods of study. Between-study variability was assessed by use of I. The study is registered in PROSPERO, CRD42022339956.
FINDINGS
A total of 351 studies, including 175 new studies and 176 studies from our previous analysis, were included in this meta-analysis. The overall prevalence of primary antibiotic resistance of H pylori between 1990 and 2022 was 22% (95% CI 20-23; I=96%) for clarithromycin, 52% (49-55; I=99%) for metronidazole, 26% (24-29; I=96%) for levofloxacin, 4% (3-5; I=95%) for tetracycline, and 4% (3-5; I=95%) for amoxicillin. Prevalence varied considerably between countries and across study periods. From 1990 to 2022, the prevalence of primary resistance increased for clarithromycin, metronidazole, and levofloxacin but remained stable for amoxicillin and tetracycline. The latest primary resistance prevalences were 30% (95% CI 28-33; I=93%) for clarithromycin, 61% (55-66; I=99%) for metronidazole, 35% (31-39; I=95%) for levofloxacin, 4% (2-6; I=96%) for tetracycline, and 6% (4-8; I=96%) for amoxicillin in the Asia-Pacific region.
INTERPRETATION
Treatment guidelines should be adapted in response to the rising primary resistance of key antibiotics for H pylori eradication. A global policy to control and monitor the antibiotic resistance of H pylori is urgently needed.
FUNDING
Ministry of Health and Welfare of Taiwan, National Science and Technology Council of Taiwan, and National Taiwan University.
TRANSLATION
For the Chinese translation of the abstract see Supplementary Materials section.
Topics: Child; Humans; Clarithromycin; Metronidazole; Levofloxacin; Helicobacter pylori; Helicobacter Infections; Anti-Bacterial Agents; Amoxicillin; Tetracycline; Drug Resistance, Microbial; Asia
PubMed: 37972625
DOI: 10.1016/S2468-1253(23)00281-9 -
Chest Feb 2024Antibiotics with extended anaerobic coverage are used commonly to treat aspiration pneumonia, which is not recommended by current guidelines.
BACKGROUND
Antibiotics with extended anaerobic coverage are used commonly to treat aspiration pneumonia, which is not recommended by current guidelines.
RESEARCH QUESTION
In patients admitted to hospital for community-acquired aspiration pneumonia, does a difference exist between antibiotic therapy with limited anaerobic coverage (LAC) vs antibiotic therapy with extended anaerobic coverage (EAC) in terms of in-hospital mortality and risk of Clostridioides difficile colitis?
STUDY DESIGN AND METHODS
We conducted a multicenter retrospective cohort study across 18 hospitals in Ontario, Canada, from January 1, 2015, to January 1, 2022. Patients were included if the physician diagnosed aspiration pneumonia and prescribed guideline-concordant first-line community-acquired pneumonia parenteral antibiotic therapy to the patient within 48 h of admission. Patients then were categorized into the LAC group if they received ceftriaxone, cefotaxime, or levofloxacin. Patients were categorized into the EAC group if they received amoxicillin-clavulanate, moxifloxacin, or any of ceftriaxone, cefotaxime, or levofloxacin in combination with clindamycin or metronidazole. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included incident C difficile colitis occurring after admission. Overlap weighting of propensity scores was used to balance baseline prognostic factors.
RESULTS
The LAC and EAC groups included 2,683 and 1,316 patients, respectively. In hospital, 814 patients (30.3%) and 422 patients (32.1%) in the LAC and EAC groups died, respectively. C difficile colitis occurred in five or fewer patients (≤ 0.2%) and 11 to 15 patients (0.8%-1.1%) in the LAC and EAC groups, respectively. After overlap weighting of propensity scores, the adjusted risk difference of EAC minus LAC was 1.6% (95% CI, -1.7% to 4.9%) for in-hospital mortality and 1.0% (95% CI, 0.3%-1.7%) for C difficile colitis.
INTERPRETATION
Extended anaerobic coverage likely is unnecessary in aspiration pneumonia because it is associated with no additional mortality benefit, only an increased risk of C difficile colitis.
PubMed: 38387648
DOI: 10.1016/j.chest.2024.02.025 -
The Journal of Infectious Diseases Aug 2023We evaluated the relationship between response to efflux pump inhibition in fluoroquinolone-resistant Mycobacterium tuberculosis (Mtb) isolates and differences in gene...
BACKGROUND
We evaluated the relationship between response to efflux pump inhibition in fluoroquinolone-resistant Mycobacterium tuberculosis (Mtb) isolates and differences in gene expression and expression quantitative trait loci (eQTL).
METHODS
We determined ofloxacin minimum inhibitory concentration (MIC) for ofloxacin-resistant and -susceptible Mtb isolates without and with the efflux pump inhibitor verapamil. We performed RNA sequencing (RNA-seq), whole genome sequencing (WGS), and eQTL analysis, focusing on efflux pump, transport, and secretion-associated genes.
RESULTS
Of 42 ofloxacin-resistant Mtb isolates, 27 had adequate WGS coverage and acceptable RNA-seq quality. Of these 27, 7 had >2-fold reduction in ofloxacin MIC with verapamil; 6 had 2-fold reduction, and 14 had <2-fold reduction. Five genes (including Rv0191) had significantly increased expression in the MIC fold change >2 compared to <2 groups. Among regulated genes, 31 eQTLs (without ofloxacin) and 35 eQTLs (with ofloxacin) had significant allele frequency differences between MIC fold change >2 and <2 groups. Of these, Rv1410c, Rv2459, and Rv3756c (without ofloxacin) and Rv0191 and Rv3756c (with ofloxacin) have previously been associated with antituberculosis drug resistance.
CONCLUSIONS
In this first reported eQTL analysis in Mtb, Rv0191 had increased gene expression and significance in eQTL analysis, making it a candidate for functional evaluation of efflux-mediated fluoroquinolone resistance in Mtb.
Topics: Mycobacterium tuberculosis; Antitubercular Agents; Fluoroquinolones; Ofloxacin; Verapamil; Gene Expression; Microbial Sensitivity Tests; Drug Resistance, Bacterial
PubMed: 37079382
DOI: 10.1093/infdis/jiad112 -
Helicobacter Oct 2023Antibiotic resistance is a well-known factor of Helicobacter pylori eradication failure. Heteroresistance indicates the coexistence of resistant and susceptible strains...
BACKGROUND
Antibiotic resistance is a well-known factor of Helicobacter pylori eradication failure. Heteroresistance indicates the coexistence of resistant and susceptible strains and might lead to underestimating antimicrobial resistance. This study aims to evaluate the susceptibility profile, the frequency of heteroresistance of H. pylori strains, and their effect on eradication success in a pediatric population.
MATERIALS AND METHODS
Children aged 2-17 years who underwent an upper gastrointestinal endoscopy from 2011 to 2019 with positive H. pylori status were included. Susceptibility was measured by disk diffusion and E-test. The difference in susceptibility profiles between isolates from the antrum and the corpus was used to detect heteroresistance. For those who received eradication treatment, we evaluated eradication rate and factors affecting treatment success.
RESULTS
Inclusion criteria were met by 565 children. Strains susceptible to all antibiotics were detected in 64.2%. Primary resistance rates for clarithromycin (CLA), metronidazole (MET), levofloxacin (LEV), tetracyclin (TET), and amoxicillin (AMO) were 11%, 22.9%, 6.9%, 0.4%, and 0% and secondary resistance rates were 20.4%, 29.4%, 9.3%, 0%, and 0%. Heteroresistance was present in untreated children in 2%, 7.1%, 0.7%, 0.7%, and 0% for CLA, MET, LEV, TET, and AMO. First-line eradication rates were 78.5% in intention-to-treat (ITT), 88.3% in full-analysis-set (FAS), and 94.1% in per-protocol (PP). Factors affecting eradication success were the duration of treatment when the triple-tailored treatment was used, the number of daily doses of amoxicillin administered, and the patient's adherence to treatment.
CONCLUSIONS
This study shows the presence of relatively low primary resistance rates for H. pylori isolates but demonstrates the presence of heteroresistance in our population. Routine biopsies from the antrum and corpus must be considered for susceptibility testing to allow tailored treatments and increase eradication rates. Treatment success is affected by treatment choice, correct dosing of medications, and adherence. All these factors should be considered when evaluating the efficacy of an eradication regimen.
Topics: Child; Humans; Helicobacter Infections; Helicobacter pylori; Anti-Bacterial Agents; Clarithromycin; Amoxicillin; Metronidazole; Levofloxacin; Drug Resistance, Bacterial; Tetracycline; Drug Therapy, Combination
PubMed: 37402147
DOI: 10.1111/hel.13006 -
ACS Omega Jul 2023This study employs advanced solid-state NMR techniques to investigate the atomic-level structure and dynamics of two enantiomers: ofloxacin and levofloxacin. The...
This study employs advanced solid-state NMR techniques to investigate the atomic-level structure and dynamics of two enantiomers: ofloxacin and levofloxacin. The investigation focuses on critical attributes, such as the principal components of the chemical shift anisotropy (CSA) tensor, the spatial proximity of H and C nuclei, and site-specific C spin-lattice relaxation time, to reveal the local electronic environment surrounding specific nuclei. Levofloxacin, the levo-isomer of ofloxacin, exhibits higher antibiotic efficacy than its counterpart, and the dissimilarities in the CSA parameters indicate significant differences in the local electronic configuration and nuclear spin dynamics between the two enantiomers. Additionally, the study employs the H-C frequency-switched Lee-Goldburg heteronuclear correlation (FSLGHETCOR) experiment to identify the presence of heteronuclear correlations between specific nuclei (C15 and H7 nuclei and C13 and H12 nuclei) in ofloxacin but not in levofloxacin. These observations offer insights into the link between bioavailability and nuclear spin dynamics, underscoring the significance of NMR crystallography approaches in advanced drug design.
PubMed: 37426250
DOI: 10.1021/acsomega.3c03406