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United European Gastroenterology Journal Feb 2024Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful...
BACKGROUND
Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication.
AIM
To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg).
METHODS
Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022.
RESULTS
Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness.
CONCLUSIONS
We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.
Topics: Adult; Humans; Proton Pump Inhibitors; Helicobacter pylori; Metronidazole; Clarithromycin; Levofloxacin; Bismuth; Prospective Studies; Drug Therapy, Combination; Anti-Bacterial Agents; Helicobacter Infections; Amoxicillin; Tetracycline; Registries
PubMed: 38050339
DOI: 10.1002/ueg2.12476 -
American Journal of Veterinary Research Oct 2019To determine the pharmacokinetics of levofloxacin following oral administration of a generic levofloxacin tablet and IV administration to dogs and whether the achieved...
OBJECTIVE
To determine the pharmacokinetics of levofloxacin following oral administration of a generic levofloxacin tablet and IV administration to dogs and whether the achieved plasma levofloxacin concentration would be sufficient to treat susceptible bacterial infections.
ANIMALS
6 healthy adult Beagles.
PROCEDURES
Levofloxacin was administered orally as a generic 250-mg tablet (mean dose, 23.7 mg/kg) or IV as a solution (15 mg/kg) to each dog in a crossover study design, with treatments separated by a minimum 2-day washout period. Blood samples were collected at various points for measurement of plasma levofloxacin concentration via high-pressure liquid chromatography. Pharmacokinetic analysis was performed with compartmental modeling.
RESULTS
After oral administration of the levofloxacin tablet, mean (coefficient of variation) peak plasma concentration was 15.5 μg/mL (23.8%), mean elimination half-life was 5.84 hours (20.0%), and mean bioavailability was 104% (29.0%). After IV administration, mean elimination half-life (coefficient of variation) was 6.23 hours (14.7%), systemic clearance was 145.0 mL/kg/h (22.2%), and volume of distribution was 1.19 L/kg (17.1%).
CONCLUSIONS AND CLINICAL RELEVANCE
In these dogs, levofloxacin was well absorbed when administered orally, and a dose of approximately 25 mg/kg was sufficient to reach pharmacokinetic-pharmacodynamic targets for treating infections with susceptible Enterobacteriaceae (ie, ≤ 0.5 μg/mL) or (ie, ≤ 1 μg/mL) according to clinical breakpoints established by the Clinical and Laboratory Standards Institute.
Topics: Administration, Intravenous; Administration, Oral; Animals; Anti-Bacterial Agents; Area Under Curve; Biological Availability; Chromatography, High Pressure Liquid; Cross-Over Studies; Dogs; Female; Half-Life; Levofloxacin; Male; Tablets
PubMed: 31556716
DOI: 10.2460/ajvr.80.10.957 -
Hong Kong Medical Journal = Xianggang... Dec 2021In 2018, the World Health Organization recommended a 6-month treatment regimen that included levofloxacin and pyrazinamide for isoniazid-resistant without rifampicin...
INTRODUCTION
In 2018, the World Health Organization recommended a 6-month treatment regimen that included levofloxacin and pyrazinamide for isoniazid-resistant without rifampicin resistance (Hr-TB). Susceptibility testing for both drugs is not routinely performed for Hr-TB in Hong Kong. This study examined the prevalences of levofloxacin and pyrazinamide resistances in Hr-TB and explored associated risk factors.
METHODS
All Hr-TB isolates archived during 2018 were retrieved. Isolates were de-duplicated to identify unique cases. Levofloxacin susceptibility testing was performed using the MGIT 960 System; pncA gene sequencing was used as a surrogate indicator of pyrazinamide susceptibility. Previous laboratory records for each case were analysed.
RESULTS
In total, 160 phenotypic Hr-TB cases were identified from among 3411 patients with tuberculosis (4.7%). Among these, 157 were analysed, revealing 0.6% (n=1) levofloxacin resistance and 4.5% (n=7) pyrazinamide resistance, respectively. Independent risk factors associated with mutations included history of tuberculosis in the affected patient and isoniazid poly-resistance (ie, double and triple resistances), but not mono-resistance.
CONCLUSION
For Hr-TB in Hong Kong, levofloxacin resistance is rare and pyrazinamide resistance-associated mutations are uncommon. Routine susceptibility testing for these drugs is not indicated unless related risk factors are identified.
Topics: Amidohydrolases; Antitubercular Agents; Hong Kong; Humans; Isoniazid; Levofloxacin; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis; Prevalence; Tuberculosis, Multidrug-Resistant
PubMed: 34949730
DOI: 10.12809/hkmj208553 -
Clinical Microbiology and Infection :... Feb 2021The first objective of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) subcommittee for antimycobacterial susceptibility testing (AMST), launched...
OBJECTIVES
The first objective of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) subcommittee for antimycobacterial susceptibility testing (AMST), launched in 2016, was to set a reference method for determining the MICs of antituberculous agents, since many protocols are used worldwide and a consensus one is needed for the determination of microbiological breakpoints.
METHODS
During 2017 and 2018, MIC determination protocols were evaluated prospectively in a multicentre study within the four AMST laboratories. MIC results were obtained for isoniazid, levofloxacin and amikacin on the reference strain Mycobacterium tuberculosis H37Rv ATCC 27294. Broth microdilution (BMD) in Middlebrook 7H9 and solid medium dilution (SMD) in Middlebrook 7H10 were performed using two inoculum concentrations. MICs were interpreted with regard to visual and 99% inhibition after 7, 14 or 21 days of incubation for BMD and 21 days for SMD.
RESULTS
Following the EUCAST reference protocol, intra- and inter-assay agreements were within ±1 MIC dilution for >95% of the observations for the three drugs in both methods. MIC values, presented as MIC mode (range) for BMD and SMD respectively, were: 0.03 (0.015-0.06) mg/L and 0.12 (0.06-0.25) mg/L for isoniazid, 0.25 mg/L (0.25-0.5) and 0.5 mg/L (0.12-0.5) for levofloxacin, and 0.5 mg/L (0.5-1.0) and 0.5 mg/L (0.5-1.0) for amikacin.
CONCLUSIONS
Both SMD and BMD were reproducible and eligible as a reference method for MIC determination of the Mycobacterium tuberculosis complex (MTBC). BMD was finally selected as the EUCAST reference method. From now on it will be used to set epidemiological cut-off values and clinical breakpoints of new and old antituberculous agents.
Topics: Amikacin; Antitubercular Agents; Bacteriological Techniques; Humans; Isoniazid; Levofloxacin; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Reproducibility of Results
PubMed: 33198949
DOI: 10.1016/j.cmi.2020.10.019 -
PloS One 2020The DNA topoisomerase complement of Streptococcus pneumoniae is constituted by two type II enzymes (topoisomerase IV and gyrase), and a single type I enzyme...
The DNA topoisomerase complement of Streptococcus pneumoniae is constituted by two type II enzymes (topoisomerase IV and gyrase), and a single type I enzyme (topoisomerase I). These enzymes maintain the DNA topology, which is essential for replication and transcription. While fluoroquinolones target the type II enzymes, seconeolitsine, a new antimicrobial agent, targets topoisomerase I. We compared for the first time the in vitro effect of inhibition of topoisomerase I by seconeolitsine and of the type II topoisomerases by the fluoroquinolones levofloxacin and moxifloxacin. We used three isogenic non-encapsulated strains and five non-vaccine serotypes isolates belonging to two circulating pneumococcal clones, ST638 (2 strains) and ST1569V (3 strains). Each group contained strains with diverse susceptibility to fluoroquinolones. Minimal inhibitory concentrations, killing curves and postantibiotic effects were determined. Seconeolitsine demonstrated the fastest and highest bactericidal activity against planktonic bacteria and biofilms. When fluoroquinolone-susceptible planktonic bacteria were considered, seconeolitsine induced postantibiotic effects (1.00-1.87 h) similar than levofloxacin (1.00-2.22 h), but longer than moxifloxacin (0.39-1.71 h). The same effect was observed in sessile bacteria forming biofilms. Seconeolitsine induced postantibiotic effects (0.84-2.31 h) that were similar to those of levofloxacin (0.99-3.32 h) but longer than those of moxifloxacin (0.89-1.91 h). The greatest effect was observed in the viability and adherence of bacteria in the postantibiotic phase. Seconeolitsine greatly reduced the thickness of the biofilms formed in comparison with fluoroquinolones: 2.91 ± 0.43 μm (seconeolitsine), 7.18 ± 0.58 μm (levofloxacin), 17.08 ± 1.02 μm (moxifloxacin). When fluoroquinolone-resistant bacteria were considered, postantibiotic effects induced by levofloxacin and moxifloxacin, but not by seconeolitsine, were shorter, decreasing up to 5-fold (levofloxacin) or 2-fold (moxifloxacin) in planktonic cells, and up to 1.7 (levofloxacin) or 1.4-fold (moxifloxacin) during biofilm formation. Therefore, topoisomerase I inhibitors could be an alternative for the treatment of pneumococcal diseases, including those caused by fluoroquinolone-resistant isolates.
Topics: Anti-Bacterial Agents; Benzodioxoles; DNA Gyrase; DNA Topoisomerase IV; Fluoroquinolones; Levofloxacin; Moxifloxacin; Phenanthrenes; Streptococcus pneumoniae; Topoisomerase I Inhibitors
PubMed: 33141832
DOI: 10.1371/journal.pone.0241780 -
Microbiology Spectrum Oct 2022Pseudomonas aeruginosa (PA) biofilm infection is clinically prevalent and difficult to eradicate. In the present work, we aimed to evaluate the and efficacy of...
Pseudomonas aeruginosa (PA) biofilm infection is clinically prevalent and difficult to eradicate. In the present work, we aimed to evaluate the and efficacy of colistin (COL)-based combinations against PA biofilm. MICs and fractional inhibitory concentration indexes (FICIs) of four antibiotics (COL, amikacin, levofloxacin, and meropenem) to bioluminescent strain PAO1, carbapenem-resistant PAO1 (CRPAO1), and clinically isolated strains were assessed. Minimal biofilm eradication concentrations (MBECs) of monotherapy and combinations were examined by counting the live bacteria in biofilm, accompanied by visual confirmation using confocal laser-scanning microscopy. An animal biofilm infection model was established by implanting biofilm subcutaneously, and the therapeutic effect was evaluated according to the change in luminescence through a live animal bio-photonic imaging system. , even combined with 4 or 8 mg/L COL, meropenem needed to reach 128 or 256 mg/L to eradicate the biofilm. Moreover, 2 mg/L COL combined with 32 mg/L amikacin or 4-8 mg/L levofloxacin could kill the PAO1 and CRPAO1 in biofilm within 24 h. , COL combined with amikacin or levofloxacin could shorten the eradication time of biofilm than monotherapy. For PAO1 biofilm, combination therapy could eradicate the biofilm in all mice on the 5th day, whereas monotherapy only eradicated biofilms in almost half of the mice. For CRPAO1 biofilm, the biofilm eradication rate on the 6th day in the COL+ amikacin, amikacin, or COL alone regimen was 90%, 10%, or 40%, respectively. COL combined with levofloxacin did not show a better effect than each individual antibiotic. COL-based combinations containing levofloxacin or amikacin were promising choices for treating PA biofilm infection. Infections associated with PA biofilm formation are extremely challenging. When monotherapy fails to achieve optimal efficacy, combination therapy becomes the last option. After evaluating multiple drug combinations through a series of experiments and , we confirmed that colistin-based combinations containing levofloxacin or amikacin were promising choices for treating PA biofilm infection. The efficacy of these combinations derives from the different bactericidal mechanisms and the bacterial susceptibility to each antibiotic. This study provided a new regimen to solve the incurable problem of biofilm by using COL combined with other antibiotics.
Topics: Mice; Animals; Colistin; Amikacin; Levofloxacin; Pseudomonas aeruginosa; Meropenem; Drug Resistance, Multiple, Bacterial; Pseudomonas Infections; Biofilms; Anti-Bacterial Agents; Microbial Sensitivity Tests; Carbapenems; Drug Combinations
PubMed: 36102678
DOI: 10.1128/spectrum.01468-22 -
PloS One 2020Pakistan is among top five high burden countries for tuberculosis and drug resistant TB. Among rifampicin sensitive new pulmonary TB (PTB), prevalence of isoniazid...
Isoniazid resistance profile and associated levofloxacin and pyrazinamide resistance in rifampicin resistant and sensitive isolates/from pulmonary and extrapulmonary tuberculosis patients in Pakistan: A laboratory based surveillance study 2015-19.
BACKGROUND
Pakistan is among top five high burden countries for tuberculosis and drug resistant TB. Among rifampicin sensitive new pulmonary TB (PTB), prevalence of isoniazid resistance is 8.3% (95%CI: 7.0-10.7) and resistance to fluoroquinolone is higher (11·1%, 95%CI: 7·8-14·3) than isoniazid resistance.
METHOD
Five year retrospective data (2015-2019) of drug susceptibility testing (DST) for Mycobacterium tuberculosis isolates, performed using recommended phenotypic (pDST) and/or genotypic (gDST) methods was analyzed stratified by rifampicin results for isoniazid resistance profiles and associated levofloxacin and pyrazinamide resistance.
FINDINGS
DST data was analyzed from 11045 TB patients. Isolates were tested using pDST (87%), gDST (92%) and both methods (79.5%). For both rifampicin and isoniazid, a significant difference (P < .001) was noted between resistance detected by pDST and gDST. Among isolates, tested by both methods (8787), 49% were resistant to rifampicin and 51.7% to isoniazid with discordance in resistant results of 15.8% for each, with 13.2% (570) of rifampicin resistance reported sensitive by pDST and 14.2% (660) of isoniazid resistance missed by gDST. Estimated isoniazid resistance among rifampicin sensitive new PTB, extrapulmonary TB and previously treated PTB was 9.8% (95%CI: 8.7-11.1), 6.8% (95%CI: 5.4-8.5) and 14.6% (95%CI: 11.8-17.9) respectively. Significant differences were reported between the genotypic profile of isoniazid resistance associated with rifampicin-resistant and sensitive isolates including detectable mutations (87% vs 71.6%), frequency of inhA (7.6% and 30.2%) and katG mutations (76.1% vs 41.2%) respectively. Among rifampicin resistant and sensitive isolates, a significantly higher level of resistance to levofloxacin and pyrazinamide was seen associated with isoniazid resistance.
CONCLUSION
There are risks and many challenges in implementing WHO recommended treatment for isoniazid resistant tuberculosis. The laboratory based surveillance can complement random surveys in country specific planning for TB diagnostics and appropriate treatment regimens.
Topics: Adolescent; Adult; Antitubercular Agents; Child; Child, Preschool; Drug Resistance, Bacterial; Epidemiological Monitoring; Female; Genotype; Humans; Infant; Isoniazid; Laboratories; Levofloxacin; Male; Microbial Sensitivity Tests; Pakistan; Phenotype; Pyrazinamide; Retrospective Studies; Rifampin; Tuberculosis, Multidrug-Resistant; Young Adult
PubMed: 32966321
DOI: 10.1371/journal.pone.0239328 -
Archives of Medical Research Jul 2021Treatments for Helicobacter pylori (H. pylori) eradication include the use of antibiotics and a proton-pump inhibitor. Antibiotic resistance is a major concern for two...
BACKGROUND
Treatments for Helicobacter pylori (H. pylori) eradication include the use of antibiotics and a proton-pump inhibitor. Antibiotic resistance is a major concern for two drugs: levofloxacin and clarithromycin. The aim was to determine the prevalence of levofloxacin resistance (LevoR) and clarithromycin resistance (ClaR) in an urban population in Santiago, Chile.
METHODS
Gastric mucosa biopsies were obtained for DNA isolation from 143 H. pylori-positive individuals aged 18-80 years. Direct sequencing of the quinolone-resistance determining region (QRDR) of the gyrA gene was used to determine LevoR. ClaR was determined using restriction-fragment length polymorphism or 5'exonuclease assay.
RESULTS
The prevalences of LevoR and ClaR were 29 and 27%, respectively. LevoR was higher in women than in men (39 vs. 13%, p <0.001), while no sex difference was observed for ClaR (p = 0.123). The prevalence of LevoR increased with age (p-trend = 0.004) but not for ClaR (p-trend = 0.054). In sex-stratified analyses, both LevoR and ClaR increased with age only among women. Older women (>50 years) had a higher probability to carry LevoR strains as compared to men. The prevalence of dual LevoR and ClaR was 12.6%.
CONCLUSIONS
The prevalence of ClaR and LevoR is high in Santiago, according to International guidelines that recommend avoiding schemes with antibiotic resistance >15%. Our findings provide evidence to re-evaluate current therapies and guide empirical first- and second-line eradication treatments in Chile.
Topics: Aged; Anti-Bacterial Agents; Chile; Clarithromycin; Drug Resistance, Bacterial; Female; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Prevalence
PubMed: 33583603
DOI: 10.1016/j.arcmed.2021.01.011 -
Medicine Sep 2022Tuberculosis (TB) is one of the serious epidemics that highly threaten the global public health. To explore the treatment effect of Levofloxacin, Moxifloxacin, and... (Meta-Analysis)
Meta-Analysis
The treatment effect of Levofloxacin, Moxifloxacin, and Gatifloxacin contained in the conventional therapy regimen for pulmonary tuberculosis: Systematic review and network meta-analysis.
BACKGROUND
Tuberculosis (TB) is one of the serious epidemics that highly threaten the global public health. To explore the treatment effect of Levofloxacin, Moxifloxacin, and Gatifloxacin contained in the conventional therapy regimen for pulmonary tuberculosis.
METHODS
Medline, PubMed, Embase, and Cochrane Library were searched with the keyword such as "Levofloxacin," "Moxifloxacin," "Gatifloxacin," and "tuberculosis", through June 1992 to 2017. According to the inclusion and exclusion criteria, 2 researchers independently screened the literature, extracted the data, and evaluated the quality of the included studies. The Cochrane system was evaluated by RevMan5.2 and the network meta-analysis was performed by Stata 15.
RESULTS
A total of 891 studies were included, with a total of 6565 patients. The results of network meta-analysis showed that Moxifloxacin + conventional therapy (CT) regimen was superior to CT regimen only on the spectrum culture negative. Both Levofloxacin + CT and Moxifloxacin + CT were superior to the CT regimen in treatment success rate. For the adverse events, the Levofloxacin + CT showed much safer results than CT group, while Moxifloxacin + CT had more adverse events than CT group.
CONCLUSION
Levofloxacin, Moxifloxacin, and Gatifloxacin have different superiority, comparing to CT regimen in spectrum culture negative, treatment success rate, and adverse events. Hence, combined utilization of these quinolone is important on the clinical treatment for tuberculosis.
Topics: Antitubercular Agents; Fluoroquinolones; Gatifloxacin; Humans; Levofloxacin; Moxifloxacin; Network Meta-Analysis; Tuberculosis; Tuberculosis, Pulmonary
PubMed: 36197231
DOI: 10.1097/MD.0000000000030412 -
Letters in Applied Microbiology Sep 2022Pseudomonas aeruginosa is one of the most worrisome infectious bacteria due to its intrinsic and acquired resistance against several antibiotics and the recalcitrance of...
Pseudomonas aeruginosa is one of the most worrisome infectious bacteria due to its intrinsic and acquired resistance against several antibiotics and the recalcitrance of its infections; hence, the development of novel antimicrobials effective against multidrug-resistant P. aeruginosa is mandatory. In this work, silver nanoparticles obtained by green synthesis using a leaf extract and fungi were tested against a battery of clinical strains from cystic fibrosis, pneumonia and burnt patients, some of them with multidrug resistance. Both nanoparticles showed a potent antibacterial effect, causing severe damage to the cell wall, membrane and DNA, and inducing the production of reactive oxygen species. Moreover, the nanoparticles derived from fungi showed synergistic antibacterial effects with the antibiotics meropenem and levofloxacin for some clinical strains and both kinds of nanoparticles were nontoxic for larvae of the moth Galleria mellonella, encouraging further research for their implementation in the treatment of P. aeruginosa infections.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Levofloxacin; Meropenem; Metal Nanoparticles; Microbial Sensitivity Tests; Plant Extracts; Pseudomonas Infections; Pseudomonas aeruginosa; Reactive Oxygen Species; Silver
PubMed: 35687297
DOI: 10.1111/lam.13759