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Therapeutic Advances in Respiratory... 2022Duration of antibiotic treatment in acute exacerbation of COPD (AECOPD) is most commonly based on expert opinion. Typical administration periods range from 5 to... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Duration of antibiotic treatment in acute exacerbation of COPD (AECOPD) is most commonly based on expert opinion. Typical administration periods range from 5 to 7 days. A 2-day course with levofloxacin was not previously assessed. We performed a randomized clinical trial to evaluate the efficacy of 2-day 7-day treatment with levofloxacin in patients with AECOPD.
METHODS AND ANALYSIS
Patients with AECOPD were randomized to receive levofloxacin for 2 days and 5 days placebo ( = 155) or levofloxacin for 7 days ( = 155). All patients received a common dose of intravenous prednisone daily for 5 days. The primary outcome measure was cure rate, and secondary outcomes included need for additional antibiotics, ICU admission rate, re-exacerbation rate, death rate, and exacerbation-free interval (EFI) within 1-year follow-up. The study protocol has been prepared in accordance with the revised Helsinki Declaration for Biomedical Research Involving Human Subjects and Guidelines for Good Clinical Practice. The study was approved by ethics committees of all participating centers prior to implementation (Monastir and Sousse Universities).
RESULTS
310 patients were randomized to receive 2-day course of levofloxacin ( = 155) or 7-day course ( = 155). Cure rate was 79.3% ( = 123) and 74.2% ( = 115), respectively, in 2-day and 7-day groups [OR 1.3; 95% CI 0.78-2.2 ( = 0.28)]. Need for additional antibiotics rate was 3.2% and 1.9% in the 2-day group and 7-day group, respectively; ( = 0.43). ICU admission rate was not significantly different between both groups. One-year re-exacerbation rate was 34.8% ( = 54) in 2-day group 29% ( = 45) in 7-day group ( = 0.19); the EFI was 121 days (interquartile range, 99-149) 110 days (interquartile range, 89-132) in 2-day and 7-day treatment groups, respectively; ( = 0.73). One-year death rate was not significantly different between the 2 groups, 5.2% 7.1% in the 2-day group and 7-day group, respectively; ( = 0.26). No difference in adverse effects was detected.
CONCLUSION
Levofloxacin once daily for 2 days is not inferior to 7 days with respect to cure rate, need for additional antibiotics and hospital readmission in AECOPD. Our findings would improve patient compliance and reduce the incidence of bacterial resistance and adverse effects.
Topics: Administration, Intravenous; Anti-Bacterial Agents; Humans; Levofloxacin; Patient Readmission; Pulmonary Disease, Chronic Obstructive
PubMed: 35657073
DOI: 10.1177/17534666221099729 -
American Journal of Therapeutics
Topics: Humans; Levofloxacin; Anti-Bacterial Agents; Ofloxacin; Brain Diseases
PubMed: 36848632
DOI: 10.1097/MJT.0000000000001615 -
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 -
Actas Dermo-sifiliograficas Oct 2019
Topics: Aged; Anti-Bacterial Agents; Humans; Hyperpigmentation; Leg Dermatoses; Levofloxacin; Male
PubMed: 31133294
DOI: 10.1016/j.ad.2018.04.010 -
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 -
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 -
The Journal of Antimicrobial... Apr 2022This study aimed at characterizing the pharmacokinetics (PK) of oral levofloxacin in adult patients in order to optimize dosing scheme and explore the...
OBJECTIVES
This study aimed at characterizing the pharmacokinetics (PK) of oral levofloxacin in adult patients in order to optimize dosing scheme and explore the PK/pharmacodynamics (PD) of levofloxacin in bone and joint infections (BJIs).
METHODS
From November 2015 to December 2019, all patients hospitalized in Cochin Hospital, treated with levofloxacin and who had at least one dosage for therapeutic drug monitoring were included. PK was described using non-linear mixed-effect modelling. In a subgroup of patients with BJIs, the association between PK, MIC for the isolated pathogen and clinical outcome was investigated. Monte Carlo simulations investigated dosing regimens to achieve the PK/PD target (AUC/MIC ratio >100).
RESULTS
One hundred and two patients were included (199 measurements), including 32 treated for BJI. A one-compartment model with first-order absorption and elimination best described the data. Effects of estimated creatinine clearance (eCLCR) and age were significant on levofloxacin clearance. In BJI patients, no significant association was found between levofloxacin PK/microbiological parameters and either clinical outcome or adverse events. Based on our model, we proposed optimized oral levofloxacin dosing regimens according to renal function, to reach the PK/PD target AUC/MIC ratio >100 for three frequent causative pathogens (Staphylococcus aureus, Enterobacterales and Pseudomonas aeruginosa).
CONCLUSIONS
Our results reinforce the need of determining the MIC and using therapeutic drug monitoring in complex infections caused by P. aeruginosa.
Topics: Adult; Anti-Bacterial Agents; Area Under Curve; Communicable Diseases; Humans; Levofloxacin; Microbial Sensitivity Tests; Monte Carlo Method; Pseudomonas aeruginosa; Staphylococcus aureus
PubMed: 35178577
DOI: 10.1093/jac/dkac031 -
The Journal of Antimicrobial... Oct 2016The emergence of MDR-TB and XDR-TB has complicated TB treatment success. Among many factors that contribute to the development of resistance, low drug exposure is not... (Review)
Review
The emergence of MDR-TB and XDR-TB has complicated TB treatment success. Among many factors that contribute to the development of resistance, low drug exposure is not the least important. This review summarizes the available information on pharmacokinetic properties of levofloxacin in relation to microbial susceptibilities, in order to optimize the dose and make general treatment recommendations. A total of 37 studies on adult (32 studies) and paediatric (5 studies) MDR-TB patients were included. Among the 32 adult studies, 19 were on susceptibility of Mycobacterium tuberculosis isolates to levofloxacin by MIC, 1 was on susceptibility of M. tuberculosis isolates to levofloxacin by MBC, 1 was on susceptibility of M. tuberculosis isolates to levofloxacin by mutant prevention concentration and 4 were on pharmacokinetics of levofloxacin, and 7 others were included. Likewise, out of five studies on children, two dealt with levofloxacin pharmacokinetic parameters, one reviewed CSF concentrations and two dealt with background information. In adult MDR-TB patients, standard dosing of once-daily 1000 mg levofloxacin in TB treatment did not consistently attain the target concentration (i.e. fAUC/MIC >100 and fAUC/MBC >100) in 80% of the patients with MIC and MBC of 1 mg/L, leaving them at risk of developing drug resistance. However, with an MIC of 0.5 mg/L, 100% of the patients achieved the target concentration. Similarly, paediatric patients failed consistently in achieving given pharmacokinetic/pharmacodynamic targets due to age-related differences, demanding a shift towards once daily dosing of 15-20 mg/kg. Therefore, we recommend therapeutic drug monitoring for patients with strains having MICs of ≥0.5 mg/L and suggest revising the cut-off value from 2 to 1 mg/L.
Topics: Adult; Anti-Bacterial Agents; Antitubercular Agents; Child; Clinical Trials as Topic; Extensively Drug-Resistant Tuberculosis; Humans; Levofloxacin; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Treatment Outcome; Tuberculosis, Multidrug-Resistant
PubMed: 27231277
DOI: 10.1093/jac/dkw164 -
Molecules (Basel, Switzerland) May 2022Tympanic membrane perforation (TMP), a common disease, often needs a scaffold as the patch to support surgery. Due to the environment of auditory meatus, the patch can...
Tympanic membrane perforation (TMP), a common disease, often needs a scaffold as the patch to support surgery. Due to the environment of auditory meatus, the patch can be infected by bacteria that results in failure; therefore, the ideal scaffold may combine biomimetic and antibacterial features. In this work, gelatin was used as the electrospinning framework, genipin as the crosslinking agent, and levofloxacin as an antibacterial in order to prepare the scaffold for TMP. Different contents of levofloxacin have been added to gelatin/genipin. It was found that, with the addition of levofloxacin, the gelatin/genipin membranes exhibit improved hydrophilia and enhanced tensile strength. The antibacterial and cell-cultured experiments showed that the prepared antibacterial membranes had excellent antibacterial properties and good biocompatibility, respectively. In summary, levofloxacin is a good group for the gelatin/genipin scaffold because it improves the physical properties and antibacterial action. Compared with different amounts of levofloxacin, a gelatin/genipin membrane with 1% levofloxacin is more suitable for a TM.
Topics: Anti-Bacterial Agents; Gelatin; Iridoids; Levofloxacin; Nanofibers; Tissue Scaffolds; Tympanic Membrane
PubMed: 35566258
DOI: 10.3390/molecules27092906 -
Expert Opinion on Drug Safety Feb 2015Azithromycin and levofloxacin have been shown to be efficacious in treating infections. The adverse drug events associated with azithromycin and levofloxacin were... (Review)
Review
INTRODUCTION
Azithromycin and levofloxacin have been shown to be efficacious in treating infections. The adverse drug events associated with azithromycin and levofloxacin were considered rare. However, the US FDA released warnings regarding the possible risk of QT prolongation with azithromycin and levofloxacin.
AREAS COVERED
Case reports/case series, observational studies and clinical trials assessing cardiovascular risks associated with azithromycin and levofloxacin were critically reviewed, including 15 case reports/series, 5 observational studies and 5 clinical trials that investigated the cardiac risks associated azithromycin and levofloxacin.
EXPERT OPINION
Results are discordant. Two retrospective studies utilizing large databases demonstrated an increased risk of cardiovascular death with azithromycin, when azithromycin was compared with amoxicillin. Two other retrospective studies found no difference in cardiovascular death associated with azithromycin and other antibiotics. For levofloxacin, the increased risk of cardiovascular death was only found in one retrospective study. Therefore, the risks and benefits of antibacterial therapies should be considered when making prescription decisions. This study should not preclude clinicians from avoiding azithromycin and levofloxacin. If a patient has an indication to receive an antibiotic and if azithromycin or levofloxacin is needed, it may be used, but the potential risks must be understood.
Topics: Anti-Bacterial Agents; Azithromycin; Death; Humans; Levofloxacin; Long QT Syndrome
PubMed: 25494485
DOI: 10.1517/14740338.2015.989210