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Environmental Pollution (Barking, Essex... Dec 2022Antibiotics play an essential role in the medical healthcare world, but their widespread usage and high prevalence have posed negative environmental consequences. During... (Review)
Review
Antibiotics play an essential role in the medical healthcare world, but their widespread usage and high prevalence have posed negative environmental consequences. During the past few decades, various antibiotic drugs have been detected in aquatic and terrestrial ecosystems. Among them, the Fluoroquinolones (FQ) group is ubiquitous in the environment and has emerged as a major environmental pollutant. FQs are very significant, broad-spectrum antibiotics used in treating various pathogenic diseases of humans and animals. The most known and used FQs are ciprofloxacin, norfloxacin, ofloxacin, levofloxacin, enrofloxacin, danofloxacin, and moxifloxacin. After human and animal administration, about 70% of these drugs are excreted out in unaltered form into the environment. Besides, wastewater discharge from pharmaceutical industries, hospitals, and agriculture runoff is the major contributor to the accumulation of FQs into the ecosystem. Their long-term presence in the environment creates selection pressure on microorganisms and contributes to the emergence of multi-drug-resistant bacteria. In addition to the resistance, these antibiotics also impose ecotoxicological effects on various animals and plant species. The presence of the fluorine atom in Fluoroquinolones makes them highly electronegative, strong, recalcitrant, and less compatible with microbial degradation. Many biological and chemical processes have been invented and successfully implemented during the past few decades for the elimination of these pollutants from the environment. This review provides a detailed overview of the classification, occurrence, distribution, and ecotoxicological effects of Fluoroquinolones. Their modes of action, resistance mechanism, detection and analysis methods, and remediation strategies have also been discussed in detail.
Topics: Animals; Humans; Ecosystem; Fluoroquinolones; Ciprofloxacin; Anti-Bacterial Agents; Levofloxacin
PubMed: 36265724
DOI: 10.1016/j.envpol.2022.120440 -
American Journal of Therapeutics
Topics: Humans; Levofloxacin; Anti-Bacterial Agents; Ofloxacin; Brain Diseases
PubMed: 36848632
DOI: 10.1097/MJT.0000000000001615 -
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 -
Tuberculosis (Edinburgh, Scotland) May 2015The fluoroquinolones are key components of current multidrug-resistant tuberculosis (MDR-TB) treatment regimens and are being evaluated in shortened treatment regimens... (Review)
Review
The fluoroquinolones are key components of current multidrug-resistant tuberculosis (MDR-TB) treatment regimens and are being evaluated in shortened treatment regimens as well as in the prevention of drug-resistant TB. The objective of this review was to identify existing evidence for the use of the fluoroquinolones ofloxacin, levofloxacin and moxifloxacin in the treatment of TB in children. Existing data from in vitro, animal and human studies consistently demonstrate the efficacy of the fluoroquinolones against Mycobacterium tuberculosis, with superiority of levofloxacin and moxifloxacin compared to ofloxacin. In vitro and murine studies demonstrated the potential of moxifloxacin to shorten drug-susceptible TB treatment, but in multiple randomized controlled trials shortened fluoroquinolone-containing regimens have not been non-inferior compared to standard therapy. Resistance occurs frequently via mutations in the gyrA gene, and emerges rapidly depending on the fluoroquinolone concentration, with newer more potent fluoroquinolones less likely to develop resistance. Emerging data from paediatric studies underlines the importance of fluoroquinolones in the treatment of MDR-TB in children. There is a paucity of pharmacokinetic data especially in children <5 years of age and HIV-infected children; existing studies show substantially lower serum concentrations in children compared to adults at currently recommended doses, probably due to faster elimination. This has implications for optimizing paediatric treatment and for the development of resistance. Fluoroquinolone use has been restricted in children due to concerns about drug-induced arthropathy. The available data does not demonstrate any serious arthropathy or other severe toxicity in children. Although there is limited paediatric safety data for the prolonged treatment of MDR-TB, extended administration of fluoroquinolones in adults with MDR-TB does not show serious adverse effects and there is no evidence suggesting less tolerability of fluoroquinolones in children. Additional study of moxifloxacin and levofloxacin for TB treatment and prevention in children is an urgent priority.
Topics: Age Factors; Antitubercular Agents; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Fluoroquinolones; Humans; Levofloxacin; Moxifloxacin; Ofloxacin; Risk Factors; Treatment Outcome; Tuberculosis, Multidrug-Resistant
PubMed: 25797610
DOI: 10.1016/j.tube.2015.02.037 -
Deutsche Medizinische Wochenschrift... Aug 2019Diagnosed and reported Legionella pneumonias are slightly increasing during recent years. This might at least partially be due to more frequently used diagnostic...
Diagnosed and reported Legionella pneumonias are slightly increasing during recent years. This might at least partially be due to more frequently used diagnostic tests.In severe pneumonia, nucleic acid amplification based methods should supplement the L. pneumophila serogroup-1 urinary antigen test because of their improved spectrum and sensitivity.Recent in vitro data suggest enhanced efficacy of levofloxacin when compared to macrolides. This complements recent clinical cohort data. Thus levofloxacin (750-1000 mg/d) is regarded the treatment of choice for confirmed legionellosis. Second line options are azithromycin or moxifloxacin. Treatment duration of 7 days should be sufficient in most cases.Development of resistance is rare and no routine resistance testing is necessary.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Legionella; Legionellosis; Levofloxacin
PubMed: 31350743
DOI: 10.1055/a-0662-9330 -
Pharmacotherapy Jun 2016Fluoroquinolone antibiotics recently have gained increased national attention due to safety concerns. A well-described and serious adverse event associated with receipt... (Review)
Review
Fluoroquinolone antibiotics recently have gained increased national attention due to safety concerns. A well-described and serious adverse event associated with receipt of fluoroquinolones is tendinitis and tendon rupture. These tendon injuries can result in long-term sequelae, including chronic pain and mobility restrictions, and may warrant surgery. Due to the severity of these adverse events, a black box warning is included in the product labeling of all fluoroquinolones. In light of the mounting concerns surrounding fluoroquinolone-associated toxicities, the purpose of this clinical review is to provide a comprehensive summary of the risk of tendinopathy associated with levofloxacin, one of the most widely prescribed antibiotics in the United States, across in vitro, animal, and clinical studies, relative to other antibiotics. As part of this review, clinical presentation and onset, proposed mechanisms, patient-specific risk factors, and management of fluoroquinolone-induced tendon injury are summarized. Data were obtained from a comprehensive PubMed literature search and a review of U.S. Food and Drug Administration documents. Although tendinopathy is considered a fluoroquinolone class-wide toxicity, data from in vitro studies, animal studies, patient-level analyses, and large national and international surveillance reports suggest that levofloxacin, as well as its parent compound ofloxacin, possess higher propensities to cause tendon damage relative to other fluoroquinolones. Risk with ofloxacin and levofloxacin appears to be exposure dependent, with higher doses and longer durations being most commonly associated with tendinopathy. Other well-described patient risk factors for fluoroquinolone-associated tendinopathy include older age (older than 60 yrs), receipt of concomitant corticosteroid therapy, presence of renal dysfunction, and history of solid organ transplantation. Given widespread use of levofloxacin across patient care settings, knowledge of both patient- and drug-specific characteristics associated with increased risk of tendinitis and tendon rupture can promote safe use of levofloxacin and other fluoroquinolones.
Topics: Animals; Anti-Bacterial Agents; Disease Management; Fluoroquinolones; Humans; Levofloxacin; Ofloxacin; Risk Factors; Tendinopathy
PubMed: 27138564
DOI: 10.1002/phar.1761 -
Journal of Hazardous Materials Mar 2024Intraparticle domains are the critical locations for storing contaminants and retarding contaminant transport in subsurface environments. While the kinetics and extent...
Intraparticle domains are the critical locations for storing contaminants and retarding contaminant transport in subsurface environments. While the kinetics and extent of antibiotics sorption and desorption in subsurface materials have been extensively studied, their behaviors in intraparticle domains have not been well understood. This study investigated the sorption and desorption of antibiotics (ATs) in the intraparticle domains using quartz grains and clay, and antibiotic tetracycline (TC) and levofloxacin (LEV) as examples that are commonly present in groundwater systems. Batch experiments coupled with the analyses using various microscopic and spectroscopic techniques were performed to investigate the sorption and desorption kinetics, and to provide insights into the intraparticle sorption and desorption of TC and LEV. Results indicated that both TC and LEV with different physiochemical properties can migrate into intraparticle domains that were consistent with sorptive diffusion. The rate and extent of the sorption are a function of intraparticle surface area and properties, pore volume and connectivity, and ionic properties of the ATs. The sorptive diffusion led to the slow desorption of both TC and LEV after their sorption, apparently showing an irreversible desorption behavior (with desorption percentage about 1.86-20.51%). These results implied that intraparticle domains can be important locations for storing ATs, retarding ATs transport, and may serve as a long-term secondary source for groundwater contamination.
Topics: Anti-Bacterial Agents; Adsorption; Clay; Tetracycline; Levofloxacin; Kinetics
PubMed: 38181594
DOI: 10.1016/j.jhazmat.2023.133311 -
Drugs Feb 2019The inability to use powerful antituberculosis drugs in an increasing number of patients seems to be the biggest threat towards global tuberculosis (TB) elimination.... (Review)
Review
The inability to use powerful antituberculosis drugs in an increasing number of patients seems to be the biggest threat towards global tuberculosis (TB) elimination. Simplified, shorter and preferably less toxic drug regimens are being investigated for pulmonary TB to counteract emergence of drug resistance. Intensified regimens with high-dose anti-TB drugs during the first weeks of treatment are being investigated for TB meningitis to increase the survival rate among these patients. Moxifloxacin, gatifloxacin and levofloxacin are seen as core agents in case of resistance or intolerance against first-line anti-TB drugs. However, based on their pharmacokinetics (PK) and pharmacodynamics (PD), these drugs are also promising for TB meningitis and might perhaps have the potential to shorten pulmonary TB treatment if dosing could be optimized. We prepared a comprehensive summary of clinical trials investigating the outcome of TB regimens based on moxifloxacin, gatifloxacin and levofloxacin in recent years. In the majority of clinical trials, treatment success was not in favour of these drugs compared to standard regimens. By discussing these results, we propose that incorporation of extended PK/PD analysis into the armamentarium of drug-development tools is needed to clarify the role of moxifloxacin, gatifloxacin and levofloxacin for TB, using the right dose. In addition, to prevent failure of treatment or emergence of drug-resistance, PK and PD variability advocates for concentration-guided dosing in patients at risk for too low a drug-exposure.
Topics: Antitubercular Agents; Fluoroquinolones; Gatifloxacin; Humans; Levofloxacin; Moxifloxacin; Treatment Outcome; Tuberculosis, Pulmonary
PubMed: 30617959
DOI: 10.1007/s40265-018-1043-y -
Research in Veterinary Science Jul 2021A potent third-generation antimicrobial fluoroquinolone drug, levofloxacin was introduced into human clinical practice in 1993. Levofloxacin is also used in veterinary... (Review)
Review
A potent third-generation antimicrobial fluoroquinolone drug, levofloxacin was introduced into human clinical practice in 1993. Levofloxacin is also used in veterinary medicine, however its use is limited: it is completely banned for veterinary use in the EU, and used extralabel in only companion animals in the USA. Since its introduction to clinical practice, many studies have been published on levofloxacin in animal species, including pharmacokinetic studies, tissue drug depletion, efficacy, and animal microbial isolate susceptibility to levofloxacin. This literature overview highlights the most clinically relevant and scientifically important levofloxacin studies linked to the field of veterinary medicine.
Topics: Animals; Anti-Infective Agents; Humans; Levofloxacin
PubMed: 33964616
DOI: 10.1016/j.rvsc.2021.04.031 -
The Journal of Antimicrobial... Oct 2023Levofloxacin is used for treatment and prevention of rifampicin-resistant (RR)-TB in children. Recent data showed higher exposures with 100 mg dispersible compared with... (Clinical Trial)
Clinical Trial
BACKGROUND
Levofloxacin is used for treatment and prevention of rifampicin-resistant (RR)-TB in children. Recent data showed higher exposures with 100 mg dispersible compared with non-dispersible tablet formulations with potentially important dosing implications in children. We aimed to verify and better characterize this finding.
METHODS
We conducted a crossover pharmacokinetic trial in children aged ≤5 years receiving levofloxacin RR-TB preventive therapy. Pharmacokinetic sampling was done after 15-20 mg/kg doses of levofloxacin with 100 mg dispersible and crushed 250 mg non-dispersible levofloxacin formulations. A population pharmacokinetic model was developed.
RESULTS
Twenty-five children were included, median (IQR) weight and age 12.2 (10.7-15.0) kg and 2.56 (1.58-4.03) years, respectively. A two-compartment model with first-order elimination and transit compartment absorption best described levofloxacin pharmacokinetics. Allometric scaling adjusted for body size, and maturation of clearance with age was characterized. Typical clearance in a 12 kg child was estimated at 4.17 L/h. Non-dispersible tablets had 21.5% reduced bioavailability compared with the dispersible formulation, with no significant differences in other absorption parameters.Dosing simulations showed that current recommended dosing for both formulations result in median exposures below adult-equivalent exposures at a 750 mg daily dose, mainly in children >6 months. Higher levofloxacin doses of 16-30 mg/kg for dispersible and 20-38 mg/kg for crushed non-dispersible tablets may be required in children >6 months.
CONCLUSIONS
The dispersible paediatric levofloxacin formulation has improved bioavailability compared with the crushed non-dispersible adult formulation, but exposures remain below those in adults. We propose optimized age- and weight-based dosing for levofloxacin, which require further evaluation.
Topics: Adult; Child, Preschool; Humans; Biological Availability; Cross-Over Studies; Levofloxacin; Rifampin; Tablets; Infant
PubMed: 37596982
DOI: 10.1093/jac/dkad257