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Applied and Environmental Microbiology Jun 2022Bacterial species in the polymicrobial community evolve interspecific interaction relationships to adapt to the survival stresses imposed by neighbors or environmental...
Bacterial species in the polymicrobial community evolve interspecific interaction relationships to adapt to the survival stresses imposed by neighbors or environmental cues. Pseudomonas aeruginosa and Staphylococcus aureus are two common bacterial pathogens frequently coisolated from patients with burns and respiratory disease. Whether the application of commonly used antibiotics influences the interaction dynamics of the two species still remains largely unexplored. By performing a series of on-plate competition assays and RNA sequencing-based transcriptional profiling, we showed that the presence of the cephalosporin antibiotic cefotaxime or the quinolone antibiotic levofloxacin at subinhibitory concentration contributes to selecting P. aeruginosa from the coculture with S. aureus by modulating the quorum-sensing (QS) system of P. aeruginosa. Specifically, a subinhibitory concentration of cefotaxime promotes the growth suppression of S. aureus by P. aeruginosa in coculture. This process may be related to the increased production of the antistaphylococcal molecule pyocyanin and the expression of , which is the central regulatory gene of the P. aeruginosa QS hierarchy. On the other hand, subinhibitory concentrations of levofloxacin decrease the competitive advantage of P. aeruginosa over S. aureus by inhibiting the growth and the QS system of P. aeruginosa. However, signaling of P. aeruginosa can be activated instead to overcome S. aureus. Therefore, this study contributes to understanding the interaction dynamics of P. aeruginosa and S. aureus during antibiotic treatment and provides an important basis for studying the pathogenesis of polymicrobial infections. Increasing evidence has demonstrated the polymicrobial characteristics of most chronic infections, and the frequent communications among bacterial pathogens result in many difficulties for clinical therapy. Exploring bacterial interspecific interaction during antibiotic treatment is an emerging endeavor that may facilitate the understanding of polymicrobial infections and the optimization of clinical therapies. Here, we investigated the interaction of cocultured P. aeruginosa and S. aureus with the intervention of commonly used antibiotics in clinic. We found that the application of subinhibitory concentrations of cefotaxime and levofloxacin can select P. aeruginosa in coculture with S. aureus by modulating P. aeruginosa QS regulation to enhance the production of antistaphylococcal metabolites in different ways. This study emphasizes the role of the QS system in the interaction of P. aeruginosa with other bacterial species and provides an explanation for the persistence and enrichment of P. aeruginosa in patients after antibiotic treatment and a reference for further clinical therapy.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Cefotaxime; Coculture Techniques; Coinfection; Humans; Levofloxacin; Pseudomonas Infections; Pseudomonas aeruginosa; Quorum Sensing; Staphylococcal Infections; Staphylococcus aureus
PubMed: 35638844
DOI: 10.1128/aem.00592-22 -
Journal of Ayub Medical College,... 2023Helicobacter pylori (H. pylori) is a gram-negative bacterium which usually resides in the mucoid lining of the stomach and may cause different gastric pathologies e.g.,... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy And Cost-Effectiveness, Comparison Of 7-Days Vonoprazan Versus 14-Days Esomeprazole Based Triple Therapies For Treating Helicobacter Pylori Infection In Pakistani Population: A Randomized Clinical Trial.
BACKGROUND
Helicobacter pylori (H. pylori) is a gram-negative bacterium which usually resides in the mucoid lining of the stomach and may cause different gastric pathologies e.g., Gastritis, peptic ulcer disease, adenocarcinoma of the gastric system and mucoid associated lymphoma (MALT). The Objective was to compare the effect of 7-days Vonoprazan based triple therapy and 14-days Esomeprazole based triple therapy on eradication rate, compliance and cost effectiveness in Helicobacter pylori infected patients.
METHODS
This clinical trial was performed in the Department of Pharmacology Army Medical College, National University of Medical Sciences (NUMS) in collaboration with the Gastroenterology Department, Pak Emirates Military Hospital (PEMH) Rawalpindi from December 2022 to March 2023. A total of one hundred and twenty-two patients with dyspepsia symptoms and yielding lab results positive for Helicobacter pylori by stool antigen test were enrolled in the study. They were randomly allocated into two groups. The Esomeprazole group received 14 days of triple therapy orally with Esomeprazole 20 mg twice a day; Amoxicillin 1000 mg twice a day; and Levofloxacin 500 mg one time a day. The comparative Vonoprazan group was given 7-days triple therapy orally with Vonoprazan 20 mg twice a day; Amoxicillin 1000 mg twice a day; and Levofloxacin 500 mg one time a day. Eradication success was evaluated by stool antigen test four weeks later, as counted from the start of treatment. compliance and cost-effectiveness of both therapies were also assessed.
RESULTS
The eradication rate was (95.1%) in the Vonoprazan group with 58 out of 61 patients negative for H. pylori and (93.1%) in Esomeprazole group with 54 patients out of 58 yielding a negative result demonstrating p-value of 0.64. Compliance was 95.0% in the Esomeprazole group with p-value of 0.07. Cost effective ratio for Vonoprazan triple therapy was lower (731.8PKR) than the Esomeprazole group.
CONCLUSION
One two-week Vonoprazan regimen demonstrated improved eradication rate, good compliance, and better tolerability in patients with less cost and a half duration of treatment in comparison with two weeks Esomeprazole regimen, attesting that one week Vonoprazan therapy is more cost efficacious in producing better results.
Topics: Humans; Amoxicillin; Anti-Bacterial Agents; Cost-Benefit Analysis; Cost-Effectiveness Analysis; Drug Therapy, Combination; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Levofloxacin; Pakistan; Pyrroles; Sulfonamides; Treatment Outcome
PubMed: 38406904
DOI: 10.55519/JAMC-S4-12110 -
International Journal of Molecular... Sep 2023Point mutations in the , , and genes can confer resistance to clarithromycin (CAM) and levofloxacin (LVX) by altering target sites or protein structure, thereby...
Point mutations in the , , and genes can confer resistance to clarithromycin (CAM) and levofloxacin (LVX) by altering target sites or protein structure, thereby reducing the efficacy of standard antibiotics in the treatment of infections. Considering the confirmed primary CAM and LVX resistance in infected patients from southern Croatia, we performed a molecular genetic analysis of three target genes (, and ) by PCR and sequencing, together with computational molecular docking analysis. In the CAM-resistant isolates, the mutation sites in the gene were A2142C, A2142G, and A2143G. In addition, the mutations D91G and D91N in GyrA and N481E and R484K in GyrB were associated with resistance to LVX. Molecular docking analyses revealed that mutant strains with resistance-related mutations exhibited a lower susceptibility to CAM and LVX compared with wild-type strains due to significant differences in non-covalent interactions (e.g., hydrogen bonds, ionic interactions) leading to destabilized antibiotic-protein binding, ultimately resulting in antibiotic resistance. Dual resistance to CAM and LVX was found, indicating the successful evolution of resistance to unrelated antimicrobials and thus an increased risk to human health.
Topics: Humans; Clarithromycin; Levofloxacin; Helicobacter pylori; Helicobacter Infections; RNA, Ribosomal, 23S; Molecular Docking Simulation; Croatia; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Anti-Bacterial Agents; Biopsy
PubMed: 37834008
DOI: 10.3390/ijms241914560 -
Alimentary Pharmacology & Therapeutics Feb 2016Helicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and... (Review)
Review
BACKGROUND
Helicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma.
AIM
To review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms.
METHODS
A PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing.
RESULTS
The prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced.
CONCLUSIONS
Since the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; China; Clarithromycin; Drug Resistance, Microbial; Female; Global Health; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Metronidazole; Microbial Sensitivity Tests; Prevalence; Treatment Failure; Treatment Outcome
PubMed: 26694080
DOI: 10.1111/apt.13497 -
PloS One 2023To analyze the effect of levofloxacin-induced intestinal microbiota modifications on intestinal, joint, and systemic inflammation in the DBA/1 mice with spontaneous...
Levofloxacin induces differential effects in the transcriptome between the gut, peripheral and axial joints in the Spondyloarthritis DBA/1 mice: Improvement of intestinal dysbiosis and the overall inflammatory process.
To analyze the effect of levofloxacin-induced intestinal microbiota modifications on intestinal, joint, and systemic inflammation in the DBA/1 mice with spontaneous arthritis. The study included two groups of mice, one of which received levofloxacin. The composition and structure of the microbiota were determined in the mice's stool using 16S rRNA sequencing; the differential taxa and metabolic pathway between mice treated with levofloxacin and control mice were also defied. The effect of levofloxacin was evaluated in the intestines, hind paws, and spines of mice through DNA microarray transcriptome and histopathological analyses; systemic inflammation was measured by flow cytometry. Levofloxacin decreased the pro-inflammatory bacteria, including Prevotellaceae, Odoribacter, and Blautia, and increased the anti-inflammatory Muribaculaceae in mice's stool. Histological analysis confirmed the intestinal inflammation in control mice, while in levofloxacin-treated mice, inflammation was reduced; in the hind paws and spines, levofloxacin also decreased the inflammation. Microarray showed the downregulation of genes and signaling pathways relevant in spondyloarthritis, including several cytokines and chemokines. Levofloxacin-treated mice showed differential transcriptomic profiles between peripheral and axial joints and intestines. Levofloxacin decreased the expression of TNF-α, IL-23a, and JAK3 in the three tissues, but IL-17 behaved differently in the intestine and the joints. Serum TNF-α was also reduced in levofloxacin-treated mice. Our results suggest that the microbiota modification aimed at reducing pro-inflammatory and increasing anti-inflammatory bacteria could potentially be a coadjuvant in treating inflammatory arthropathies.
Topics: Mice; Animals; Levofloxacin; Transcriptome; Tumor Necrosis Factor-alpha; Dysbiosis; RNA, Ribosomal, 16S; Mice, Inbred DBA; Spondylarthritis; Inflammation; Mice, Inbred C57BL
PubMed: 36730179
DOI: 10.1371/journal.pone.0281265 -
MBio Oct 2023Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is...
Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics.
Topics: Humans; Fosfomycin; Levofloxacin; Urinary Tract Infections; Anti-Bacterial Agents; Cystitis
PubMed: 37698412
DOI: 10.1128/mbio.01677-23 -
BMC Infectious Diseases Jun 2022The role of Helicobacter pylori (H. pylori) virulence factors of such as vacA s1m1 and cagA in designating clinical outcomes and eradication rate has been deeply... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of Helicobacter pylori (H. pylori) virulence factors of such as vacA s1m1 and cagA in designating clinical outcomes and eradication rate has been deeply challenged in the last decade. The goal of this analysis was to identify the potential relevance between cagA and vacA genotypes with reported antibiotic resistance observed in clinical H. pylori isolates.
METHODS
This literature search was conducted in databases such as Clarivate analytics, PubMed, Scopus, EMBASE, DOAJ, and Google Scholar by April 2022, regardless of language restrictions and publication date. Quality of the included studies was assessed by the Newcastle-Ottawa scale. Statistical analysis of retrieved studies was fulfilled using Comprehensive Meta-Analysis software version 2.2. Following quality appraisal of eligible studies, potential association between the status of cagA and vacA genes with resistance to clarithromycin, metronidazole, amoxicillin, tetracycline, and levofloxacin was measured using odds ratio with 95% confidence interval. We also used sensitivity analyses and meta-regression to eliminate the source of heterogeneity from the overall estimates. Publication bias was assessed using funnel plot, Egger's test, Begg's test with the trim and fill procedure to assess the presence and magnitude of publication bias in the included studies.
RESULTS
Our findings suggested that a significant relationship between cagA status and increase resistance to metronidazole (OR: 2.69; 95% CI: 1.24-5.83). In subgroup analysis, we found that in the Western population, infection with cagA-positive strains could be led to increase in the resistance to metronidazole (OR: 1.59; 95% CI: 0.78-3.21), amoxicillin (OR: 19.68; 95% CI: 2.74-141.18), and levofloxacin (OR: 11.33; 95% CI: 1.39-91.85). After implementation of trim and fill method, the adjusted OR was not significantly differed from original estimates which in turn represented our subgroup analysis was statistically robust. On the other hand, vacA genotypes usually reduce the antibiotic resistance of this bacterium, so that vacA s1m1 significantly reduces the resistance to metronidazole (OR: 0.41; 95% CI: 0.20-0.86). Surprisingly, resistance of vacA s2m2 strains to antibiotics was low, the reason may be due to the non-inflammatory properties of strains containing vacA s2m2. The meta-regression and sensitivity analyses successfully reduced the effect of heterogeneity from the overall estimates. In addition, although the pooled OR is reduced after trim and fill adjustment but results do not change the conclusion regarding vacA genotypes and antibiotic resistance.
CONCLUSIONS
According to our findings, it was clearly demonstrated that cagA-positive strains are resistance to metronidazole, especially in Western countries. In Western countries, vacA s1m1 increases resistance to amoxicillin and levofloxacin. Based on the present findings, the vacA s1m1 genotype significantly increases resistance to metronidazole, while the vacA s1m2 decreases resistance to clarithromycin and metronidazole. Resistance to antibiotics in less virulent (vacA s2m2) strains is statistically significant lower than others.
Topics: Amoxicillin; Anti-Bacterial Agents; Antigens, Bacterial; Bacterial Proteins; Clarithromycin; Drug Resistance, Microbial; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Metronidazole
PubMed: 35752757
DOI: 10.1186/s12879-022-07546-5 -
PeerJ 2023Efficacy of . ) eradication is related to the local antimicrobial resistance epidemiology. We aimed to investigate the antibiotic resistance of in Fujian, China.
BACKGROUND AND AIM
Efficacy of . ) eradication is related to the local antimicrobial resistance epidemiology. We aimed to investigate the antibiotic resistance of in Fujian, China.
METHODS
-infected patients in four centers were enrolled in the study from Oct 2019 to Jan 2022. The bacteria were isolated, cultured and identified from the biopsy of patients' gastric mucosa samples. Antimicrobial susceptibility testing was performed by a modified broth microdilution method for to seven guideline-recommended antibiotics and seven potential choices for eradication.
RESULTS
A total of 205 strains were isolated. The resistance rates of amoxicillin (AMX), amoxicillin and clavulanate potassium (AMC), cefixime (CFM), gentamicin (GEN), tetracycline (TET), doxycycline (DOX), azithromycin (AZM), clarithromycin (CLR), levofloxacin (LVFX), sparfloxacin (SPFX), metronidazole (MTZ), tinidazole (TID), rifampicin (RFP) and furazolidone (FZD) were 11.22%, 12.20%, 7.32%, 12.20%, 4.88%, 4.39%, 44.39%, 43.90%, 30.24%, 21.46%, 40.98%, 45.85%, 5.37% and 10.24%, respectively. The rates of pan-sensitivity, single, double, triple and multiple resistance for seven guideline-recommended antibiotics were 32.68%, 30.24%, 13.17%, 7.76%, and 14.15%, respectively. The main double-resistance patterns were CLR+MTZ (10/205, 5%) and CLR+LVFX (9/205, 4%). The main triple-resistance pattern was CLR+MTZ+ LVFX (15/205, 7%).
CONCLUSIONS
In Fujian, the prevalence of resistance to AZM, CLR, LVFX, SPFX, MTZ, and TID was high, whereas that to AMX, AMC, GEN, CFM, TET, DOX, RFP and FZD was relatively low. CFM and DOX are promising new choices for eradication.
Topics: Humans; Anti-Bacterial Agents; Helicobacter pylori; Helicobacter Infections; Microbial Sensitivity Tests; Metronidazole; Clarithromycin; Amoxicillin; Tetracycline; Drug Resistance, Bacterial; Furazolidone; Cefixime; Doxycycline; Levofloxacin
PubMed: 37456872
DOI: 10.7717/peerj.15611 -
Pharmacological Reports : PR Dec 2021The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified at the end of 2019. Despite growing understanding of SARS-CoV-2 in virology as well...
The application of in silico experimental model in the assessment of ciprofloxacin and levofloxacin interaction with main SARS-CoV-2 targets: S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLpro)-preliminary molecular docking analysis.
BACKGROUND
The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified at the end of 2019. Despite growing understanding of SARS-CoV-2 in virology as well as many molecular studies, except remdesivir, no specific anti-SARS-CoV-2 drug has been officially approved.
METHODS
In the present study molecular docking technique was applied to test binding affinity of ciprofloxacin and levofloxacin-two commercially available fluoroquinolones, to SARS-CoV-2 S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PL). Chloroquine and dexamethasone were used as reference positive controls.
RESULTS
When analyzing the molecular docking data it was noticed that ciprofloxacin and levofloxacin possess lower binding energy with S protein as compared to the references. In the case of TMPRSS2 protein and PL protease the best docked ligand was levofloxacin and in the case of E proteins and RNA-dependent RNA polymerase the best docked ligands were levofloxacin and dexamethasone. Moreover, a molecular dynamics study also reveals that ciprofloxacin and levofloxacin form a stable complex with E- and TMPRSS2 proteins, RNA polymerase and papain-like protease (PL).
CONCLUSIONS
The revealed data indicate that ciprofloxacin and levofloxacin could interact and potentially inhibit crucial SARS-CoV-2 proteins.
Topics: Anti-Infective Agents; Binding Sites; Ciprofloxacin; Computer Simulation; Coronavirus Papain-Like Proteases; Humans; Levofloxacin; Molecular Docking Simulation; Molecular Dynamics Simulation; RNA-Dependent RNA Polymerase; SARS-CoV-2; Serine Endopeptidases; Viral Proteins; COVID-19 Drug Treatment
PubMed: 34052981
DOI: 10.1007/s43440-021-00282-8 -
Auris, Nasus, Larynx Aug 2023The present study aimed to evaluate the efficacy and safety of 1.5% levofloxacin (LVFX) otic solution for the treatment of patients with otitis media. (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of 1.5% levofloxacin otic solution for the treatment of otitis media in a multicenter, randomized, double-blind, parallel-group, placebo-controlled, phase III study.
OBJECTIVE
The present study aimed to evaluate the efficacy and safety of 1.5% levofloxacin (LVFX) otic solution for the treatment of patients with otitis media.
METHODS
This multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 trial was conducted at 34 institutions in Japan. A total of 202 patients with chronic suppurative otitis media (CSOM) or acute otitis media (AOM) were randomized into either the LVFX group or placebo group. A total of 6-10 drops of 1.5% otic solution of LVFX or its matching placebo were administered in the diseased ear twice daily, in the morning and evening for up to 10 days. Images corresponding to three clinical findings-purulent otorrhea, hyperemia (redness), and granulation tissue formation in the middle ear and tympanic membrane-for each diseased ear were evaluated using digital endoscopy by a blinded central independent review committee (BICRC) at each visit after treatment administration.
RESULTS
In total, the data of 201 participants (LVFX group, 99; placebo group, 102) were analyzed. The proportion of patients with disappearance (improvement rate) of all three clinical findings at the end of treatment or discontinuation by the BICRC was 46.5% (46/99) in the LVFX group and 23.5% (24/102) in the placebo group, and the difference (95% confidence interval) between the groups was 22.0% (8.7, 34.2), with a significantly higher improvement rate in the LVFX group than in the placebo group (p = 0.001; Cochran-Mantel-Haenszel test), demonstrating the efficacy of LVFX. The bacterial eradication rates were 93.9% (77/82) and 12.5% (11/88) in the LVFX and placebo groups, respectively, and the rate was significantly higher in the LVFX group than in the placebo group (p < 0.001). Treatment-related adverse events (AEs) occurred in 5.1% (5/99) and 7.8% (8/102) of the patients in the LVFX and placebo groups, respectively, and no significant difference was noted in incidence rate between the groups.
CONCLUSION
The clinical efficacy of 1.5% LVFX otic solution for CSOM and AOM was demonstrated by the resolution of inflammation in the middle ear and tympanic membrane as well as through the high bacterial eradication rate observed. No deaths or serious treatment-related AEs were observed. The study provided confirmation that 1.5% LVFX otic solution is a safe, well-tolerated, and effective treatment for CSOM and AOM.
Topics: Humans; Anti-Bacterial Agents; Levofloxacin; Otitis Media; Otitis Media, Suppurative; Ear, Middle
PubMed: 36599786
DOI: 10.1016/j.anl.2022.12.013