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Actas Espanolas de Psiquiatria May 2020Quinolones are an antibiotic group widely used due to their antimicrobial action and security profile, however, it has been described neuropsychiatric adverse effects,... (Review)
Review
Quinolones are an antibiotic group widely used due to their antimicrobial action and security profile, however, it has been described neuropsychiatric adverse effects, being induced-psychotic episodes one of the most clinically relevant. Nevertheless, this secondary effect has been scarcely studied. A literature search using PRISMA guidelines was performed between 01/01/1962 and 01/31/2019 on PubMed and ScienceDirect, including manuscripts which described substance-induced psychotic disorder according to DSM-5 and in which the symptomatology was not attributable to an acute confusional state (delirium) or to other induced psychiatric disorders. 459 articles were found, but only 27 manuscripts fulfilled inclusion criteria (n=27 patients, median age of 36.15±16.96 years). Ciprofloxacin, levofloxacin and ofloxacin were the main antibiotics implicated. Quinolone- induced psychosis is a clinical relevant issue due to the high prescription of these antibiotics and the severity of this clinical syndrome. In general, this syndrome can remit in a few days with the withdrawal of the quinolone and performing symptomatic support if it is necessary. Finally, it is important to perform further research on this issue. Keywords: Quinolones, Psychosis, Ciprofloxacin, Levofloxacinn, Psychotic Induced.
Topics: Anti-Bacterial Agents; Ciprofloxacin; Delirium; Humans; Levofloxacin; Ofloxacin; Psychoses, Substance-Induced; Quinolones
PubMed: 32905605
DOI: No ID Found -
Biology of Blood and Marrow... Apr 2020Antibiotic-induced gut dysbiosis has been associated with poor outcomes after intensive therapy. We evaluated the effect of levofloxacin (LEVO), the most commonly used...
Antibiotic-induced gut dysbiosis has been associated with poor outcomes after intensive therapy. We evaluated the effect of levofloxacin (LEVO), the most commonly used prophylactic antibacterial antibiotic during intensive chemotherapy and allogeneic hematopoietic cell transplantation (allo-HCT), on the gut microbiota in 2 cohorts of patients, 1 cohort comprising 20 patients with acute leukemia receiving intensive chemotherapy and the other cohort comprising 20 allo-HCT recipients. 16S rRNA gene sequencing of thrice-weekly collected stool samples permitted a comparison between intervals with no antibacterial antibiotic exposure and those with only LEVO exposure. In mixed-effects modeling, the only variables influenced by LEVO were the relative abundances of Parabacteroides (regression coefficient, -.063; 99% confidence interval [CI], -.102 to -.024) and Blautia (regression coefficient, .050; 99% CI, .004 to .095). Other taxa and microbiota diversity were unaffected. Overall, the effect of LEVO on the gut microbiota in these cohorts was mild.
Topics: Dysbiosis; Gastrointestinal Microbiome; Hematopoietic Stem Cell Transplantation; Humans; Levofloxacin; RNA, Ribosomal, 16S
PubMed: 31870930
DOI: 10.1016/j.bbmt.2019.12.722 -
The Cochrane Database of Systematic... Jun 2013Currently the World Health Organization only recommend fluoroquinolones for people with presumed drug-sensitive tuberculosis (TB) who cannot take standard first-line... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Currently the World Health Organization only recommend fluoroquinolones for people with presumed drug-sensitive tuberculosis (TB) who cannot take standard first-line drugs. However, use of fluoroquinolones could shorten the length of treatment and improve other outcomes in these people. This review summarises the effects of fluoroquinolones in first-line regimens in people with presumed drug-sensitive TB.
OBJECTIVES
To assess fluoroquinolones as substitute or additional components in antituberculous drug regimens for drug-sensitive TB.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; CENTRAL (The Cochrane Library 2013, Issue 1); MEDLINE; EMBASE; LILACS; Science Citation Index; Databases of Russian Publications; and metaRegister of Controlled Trials up to 6 March 2013.
SELECTION CRITERIA
Randomized controlled trials (RCTs) of antituberculous regimens based on rifampicin and pyrazinamide and containing fluoroquinolones in people with presumed drug-sensitive pulmonary TB.
DATA COLLECTION AND ANALYSIS
Two authors independently applied inclusion criteria, assessed the risk of bias in the trials, and extracted data. We used the risk ratio (RR) for dichotomous data and the fixed-effect model when it was appropriate to combine data and no heterogeneity was present. We assessed the quality of evidence using the GRADE approach.
MAIN RESULTS
We identified five RCTs (1330 participants) that met the inclusion criteria. None of the included trials examined regimens of less than six months duration. Fluoroquinolones added to standard regimensA single trial (174 participants) added levofloxacin to the standard first-line regimen. Relapse and treatment failure were not reported. For death, sputum conversion, and adverse events we are uncertain if there is an effect (one trial, 174 participants, very low quality evidence for all three outcomes). Fluoroquinolones substituted for ethambutol in standard regimens Three trials (723 participants) substituted ethambutol with moxifloxacin, gatifloxacin, and ofloxacin into the standard first-line regimen. For relapse, we are uncertain if there is an effect (one trial, 170 participants, very low quality evidence). No trials reported on treatment failure. For death, sputum culture conversion at eight weeks, or serious adverse events we do not know if there was an effect (three trials, 723 participants, very low quality evidence for all three outcomes). Fluoroquinolones substituted for isoniazid in standard regimens A single trial (433 participants) substituted moxifloxacin for isoniazid. Treatment failure and relapse were not reported. For death, sputum culture conversion, or serious adverse events the substitution may have little or no difference (one trial, 433 participants, low quality evidence for all three outcomes). Fluoroquinolines in four month regimensSix trials are currently in progress testing shorter regimens with fluoroquinolones.
AUTHORS' CONCLUSIONS
Ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin have been tested in RCTs of standard first-line regimens based on rifampicin and pyrazinamide for treating drug-sensitive TB. There is insufficient evidence to be clear whether addition or substitution of fluoroquinolones for ethambutol or isoniazid in the first-line regimen reduces death or relapse, or increases culture conversion at eight weeks. Much larger trials with fluoroquinolones in short course regimens of four months are currently in progress.
Topics: Antitubercular Agents; Ciprofloxacin; Drug Substitution; Fluoroquinolones; Humans; Levofloxacin; Ofloxacin; Randomized Controlled Trials as Topic; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 23744519
DOI: 10.1002/14651858.CD004795.pub4 -
Clinical Microbiology and Infection :... May 2006Following the first outbreaks of legionnaire's disease, erythromycin emerged as the treatment of choice without the foundation of rigorous clinical trials. The number of... (Comparative Study)
Comparative Study Review
Following the first outbreaks of legionnaire's disease, erythromycin emerged as the treatment of choice without the foundation of rigorous clinical trials. The number of therapeutic failures with erythromycin, as well as the side-effects and drug interactions, led to the consideration of other drugs such as the new macrolides and quinolones for the treatment of legionnaire's disease in the 1990s. In this article, 19 studies in in-vitro intracellular models and seven animal studies that compared macrolides to quinolones were reviewed. Quinolones were found to have greater activity in intracellular models and improved efficacy in animal models compared with macrolides. No randomised trials comparing the clinical efficacy of the new macrolides and new quinolones have ever been performed. Three observational studies totalling 458 patients with legionnaire's disease have compared the clinical efficacy of macrolides (not including azithromycin) and quinolones (mainly levofloxacin). The results suggested that quinolones may produce a superior clinical response compared with the macrolides (erythromycin and clarithromycin) with regard to defervescence, complications, and length of hospital stay. Little data exist for direct comparison of quinolones and azithromycin.
Topics: Animals; Anti-Infective Agents; Azithromycin; Clinical Trials as Topic; Humans; Legionella pneumophila; Legionnaires' Disease; Levofloxacin; Microbial Sensitivity Tests; Ofloxacin; Quinolones
PubMed: 16669926
DOI: 10.1111/j.1469-0691.2006.01394.x -
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... 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 -
Ecotoxicology and Environmental Safety Jul 2023Excessive antibiotics transferred into the aquatic environment may affect the development of amphibians. Previous studies on the aquatic ecological risk of ofloxacin...
Excessive antibiotics transferred into the aquatic environment may affect the development of amphibians. Previous studies on the aquatic ecological risk of ofloxacin generally ignored its enantiomers. The purpose of this study was to compare the effects and mechanisms of ofloxacin (OFL) and levofloxacin (LEV) on the early development of Rana nigromaculata. After 28-day exposure at environmental levels, we found that LEV exerted more severe inhibitory effects on the development of tadpoles than OFL. According to the enrichment results of differentially expressed genes in the LEV and OFL treatments, LEV and OFL had different effects on the thyroid development of tadpoles. dio2 and trh were affected by the regulation of dexofloxacin instead of LEV. At the protein level, LEV was the main component that affected thyroid development-related protein, while dexofloxacin in OFL had little effect on thyroid development. Furthermore, molecular docking results further confirmed that LEV was a major component affecting thyroid development-related proteins, including DIO and TSH. In summary, OFL and LEV regulated the thyroid axis by differential binding to DIO and TSH proteins, thereby exerting differential effects on the thyroid development of tadpoles. Our research is of great significance for comprehensive assessment of chiral antibiotics aquatic ecological risk.
Topics: Animals; Ofloxacin; Levofloxacin; Larva; Thyroid Gland; Molecular Docking Simulation; Anti-Bacterial Agents; Ranidae; Hypothalamus; Thyrotropin
PubMed: 37178612
DOI: 10.1016/j.ecoenv.2023.114985 -
Biomedicine & Pharmacotherapy =... Oct 2021Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the...
Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R adjusted = 91.1% and 95.0%, outliers = 4.8% and 5.0%, respectively). PTA allows choosing the best drug and dosage according to various hypotheses. A simple 3-sample protocol (pre-dose, 1 h after intake and 3 h after intake) to estimate ofloxacin and levofloxacin AUC allows optimal drug dosage for the treatment of osteoarticular infections.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bone Diseases, Infectious; Female; Fluoroquinolones; Humans; Joint Diseases; Levofloxacin; Male; Middle Aged; Models, Biological; Monte Carlo Method; Ofloxacin; Prospective Studies; Staphylococcus; Young Adult
PubMed: 34435591
DOI: 10.1016/j.biopha.2021.112053 -
Antimicrobial Agents and Chemotherapy Aug 1995The susceptibilities of 56 Legionella pneumophila isolates (43 clinical and 15 environmental isolates) to levofloxacin, ofloxacin, erythromycin, and rifampin were...
The susceptibilities of 56 Legionella pneumophila isolates (43 clinical and 15 environmental isolates) to levofloxacin, ofloxacin, erythromycin, and rifampin were studied with buffered charcoal yeast extract (BCYE) agar (inoculum, 10(4) CFU per spot), and the susceptibilities of five isolates were studied with buffered yeast extract (BYE) broth (inoculum, 10(5) CFU/ml). The MICs inhibiting 90% of strains tested on BCYE agar were 0.125, 0.25, 1.0, and < or = 0.004 micrograms/ml for levofloxacin, ofloxacin, erythromycin, and rifampin, respectively. The MICs by the BYE broth dilution method were 1 to 3, 2, 1 to 2, and 1 tube lower than those by the agar dilution method for levofloxacin, ofloxacin, erythromycin, and rifampin, respectively. The MBCs were 1 to 2 tubes higher than the broth dilution MICs for levofloxacin, 1 to 3 tubes higher than the broth dilution MICs for ofloxacin, 1 to 3 tubes higher than the broth dilution MICs for erythromycin, and the same as the broth dilution MICs for rifampin. In kinetic time-kill curve studies, at drug concentrations of 1.0 and 2.0 times the MIC, the most active drugs were levofloxacin and rifampin. At 72 h, concentrations of levofloxacin and rifampin of 2.0 times the MIC demonstrated a bactericidal effect against L. pneumophila. In contrast, at concentrations of 1.0 and 2.0 times the MICs regrowth was observed with ofloxacin and only a gradual decrease in the numbers of CFU per milliliter was observed with erythromycin. Only a minor inhibitory effect was observed with 0.25 or 0.5 time the MICs of all drugs at 24 to 48 h, with regrowth occurring at 72 h. In contrast to erythromycin or ofloxacin plus rifampin at 0.25 time the MICs, only levofloxacin plus rifampin demonstrated synergy. Thus, levofloxacin demonstrated the best inhibitory and bactericidal effects against L. pneumophila when it was studied alone or in a combination with rifampin.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Drug Synergism; Drug Therapy, Combination; Erythromycin; Humans; Legionella pneumophila; Legionnaires' Disease; Levofloxacin; Microbial Sensitivity Tests; Ofloxacin; Rifampin; Time Factors
PubMed: 7486896
DOI: 10.1128/AAC.39.8.1661 -
Microbiology Spectrum Jun 2022The activity of two new fluoroquinolones, delafloxacin and finafloxacin, were evaluated against and spp. The MICs of delafloxacin, finafloxacin, and two classical...
The activity of two new fluoroquinolones, delafloxacin and finafloxacin, were evaluated against and spp. The MICs of delafloxacin, finafloxacin, and two classical fluoroquinolones (moxifloxacin and levofloxacin) were tested against 29 and 67 spp. isolates using the broth microdilution method. The molecular mechanisms underlying fluoroquinolone resistance were also investigated. Delafloxacin exhibited low MICs against and spp., including the levofloxacin-resistant isolates. For , delafloxacin showed low MIC value of 1 μg/mL (MIC range, <0.031 -1 μg/mL) compared to 8 μg/mL for finafloxacin, 16 μg/mL for moxifloxacin, and 32 μg/mL for levofloxacin. For and , delafloxacin had low MIC values (, 2 μg/mL; , 4 μg/mL) compared to 16 -32 μg/mL for finafloxacin, 16 μg/mL for moxifloxacin, and 32 - >32 μg/mL for levofloxacin. The two mutations GyrA S153L and ParC S91I were commonly identified in fluoroquinolone-resistant , and ParC S83L was the most frequent mutation identified in fluoroquinolone-resistant spp. Delafloxacin displayed lower MICs against fluoroquinolone-resistant isolates of both and spp. that have mutations in the quinolone resistance determining regions (QRDRs) than the two classical fluoroquinolones. Delafloxacin is a promising fluoroquinolone with low MICs against fluoroquinolone-resistant and spp. Our study confirms the potential clinical use of delafloxacin in treating antimicrobial-resistant and spp. infections. Fluoroquinolone resistance in Mycoplasma hominis and spp. is on the rise globally, which has compromised the efficacy of the currently available antimicrobial agents. This study evaluated the antimicrobial activity of two new fluoroquinolones, delafloxacin and finafloxacin, for the first time, against and spp. clinical isolates. Delafloxacin and finafloxacin displayed different antimicrobial susceptibility profiles against and spp. . Delafloxacin was found to be more effective against and spp. than three classical fluoroquinolones (finafloxacin, moxifloxacin, and levofloxacin). Finafloxacin displayed activity similar to moxifloxacin but superior to levofloxacin against and spp. Our findings demonstrate that delafloxacin is a promising fluoroquinolone with outstanding activity against fluoroquinolone-resistant and spp.
Topics: Anti-Bacterial Agents; Fluoroquinolones; Humans; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Mycoplasma hominis; Ureaplasma; Ureaplasma Infections
PubMed: 35532225
DOI: 10.1128/spectrum.00099-22