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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 -
Molecules (Basel, Switzerland) Aug 2021In this study, broilers were fed with heavy-metal-containing diets (Zn, Cu, Pb, Cr, As, Hg) at three rates (T1: 5 kg premix/ton feed, T2: 10 kg premix/ton feed and T3:...
In this study, broilers were fed with heavy-metal-containing diets (Zn, Cu, Pb, Cr, As, Hg) at three rates (T1: 5 kg premix/ton feed, T2: 10 kg premix/ton feed and T3: 15 kg premix/ton feed) and Doxycycline (DOX) and Gatifloxacin (GAT) at low or high doses (T4: 31.2 mg DOX/bird/day and 78 mg GAT/bird/day, T5: 15.6 mg DOX/bird/day and 48 mg GAT/bird/day) to assess the accumulation of various heavy metals and the fate of two antibiotics in broiler manure after 35 days of aerobic composting. The results indicated that the two antibiotics changed quite differently during aerobic composting. About 14.96-15.84% of Doxycycline still remained at the end of composting, while Gatifloxacin was almost completely removed within 10 days of composting. The half-lives of Doxycycline were 13.75 and 15.86 days, while the half-lives of Gatifloxacin were only 1.32 and 1.38 days. Based on the Redundancy analysis (RDA), the concentration of antibiotics was significantly influenced by physico-chemical properties (mainly temperature and pH) throughout the composting process. Throughout the composting process, all heavy metal elements remained concentrated in organic fertilizer. In this study the Cr content reached 160.16 mg/kg, 223.98 mg/kg and 248.02 mg/kg with increasing premix feed rates, similar to Zn, which reached 258.2 mg/kg, 312.21 mg/kg and 333.68 mg/kg. Zn and Cr concentrations well exceeded the United States and the European soil requirements. This experiment showed that antibiotic residues and the accumulation of heavy metals may lead to soil contamination and pose a risk to the soil ecosystem.
Topics: Animals; Composting; Doxycycline; Gatifloxacin; Manure; Metals, Heavy
PubMed: 34500659
DOI: 10.3390/molecules26175225 -
Medicines (Basel, Switzerland) May 2023Fluoroquinolones (FQNs) are related to several central nervous system side effects. This review aims to evaluate the clinical-epidemiological profile, pathophysiological... (Review)
Review
BACKGROUND
Fluoroquinolones (FQNs) are related to several central nervous system side effects. This review aims to evaluate the clinical-epidemiological profile, pathophysiological mechanisms, and management of FQNs-associated movement disorders (MDs).
METHODS
Two reviewers identified and assessed relevant reports in six databases without language restriction between 1988 and 2022.
RESULTS
A total of 45 reports containing 51 cases who developed MDs secondary to FQNs were reported. The MDs included 25 myoclonus, 13 dyskinesias, 7 dystonias, 2 cerebellar syndromes, 1 ataxia, 1 tic, and 2 undefined cases. The FQNs reported were ciprofloxacin, ofloxacin, gatifloxacin, moxifloxacin, levofloxacin, gemifloxacin, and pefloxacin. The mean and median age were 64.54 (SD: 15.45) and 67 years (range: 25-87 years). The predominant sex was male (54.16%). The mean and median time of MD onset were 6.02 (SD: 10.87) and 3 days (range: 1-68 days). The mean and median recovery time after MD treatment was 5.71 (SD: 9.01) and 3 days (range: 1-56 days). A complete recovery was achieved within one week of drug withdrawal in 80.95% of the patients. Overall, 95.83% of the individuals fully recovered after management.
CONCLUSIONS
Future cases need to describe the long-term follow-up of the individuals. Additionally, FQN-induced myoclonus should include electrodiagnostic studies.
PubMed: 37367728
DOI: 10.3390/medicines10060033 -
American Family Physician Feb 2002With the recent introduction of agents such as gatifloxacin and moxifloxacin, the traditional gram-negative coverage of fluoroquinolones has been expanded to include... (Review)
Review
With the recent introduction of agents such as gatifloxacin and moxifloxacin, the traditional gram-negative coverage of fluoroquinolones has been expanded to include specific gram-positive organisms. Clinical applications beyond genitourinary tract infections include upper and lower respiratory infections, gastrointestinal infections, gynecologic infections, sexually transmitted diseases, and some skin and soft tissue infections. Most quinolones have excellent oral bioavailability, with serum drug concentrations equivalent to intravenous administration. Quinolones have few adverse effects, most notably nausea, headache, dizziness, and confusion. Less common but more serious adverse events include prolongation of the corrected QT interval, phototoxicity, liver enzyme abnormalities, arthropathy, and cartilage and tendon abnormalities. The new fluoroquinolones are rarely first-line agents and should be employed judiciously. Inappropriate use of agents from this important class of antibiotics will likely worsen current problems with antibiotic resistance. Applications of fluoroquinolones in biologic warfare are also discussed.
Topics: Ciprofloxacin; Drug Interactions; Humans; Male; Prostatitis; Quinolones; Respiratory Tract Diseases; Sexually Transmitted Diseases; Urinary Tract Infections
PubMed: 11858629
DOI: No ID Found -
Ecotoxicology and Environmental Safety Jul 2022The novel fourth-generation fluoroquinolones (FQs) were developed to improve the antimicrobial activity and their utilization has rapidly increased in recent years....
The novel fourth-generation fluoroquinolones (FQs) were developed to improve the antimicrobial activity and their utilization has rapidly increased in recent years. However, knowledge of the ecotoxicity and microalgae-mediated biodegradation of these novel FQs is limited. In this research, the toxic effects of moxifloxacin (MOX) and gatifloxacin (GAT) on Chlamydomonas reinhardtii as well as their biodegradation and metabolic fate were investigated. The results showed that the toxicity of MOX to C. reinhardtii was higher than that of GAT, and increased with culture time. Chlorophyll fluorescence and pigment content analyses suggested that the decrease in photosynthetic efficiency was primarily caused by the inhibition of electron transport after Q in PSII complex. These FQs induced oxidative damage in cells, and the antioxidation mechanisms of C. reinhardtii were analyzed. The maximum MOX removal of 77.67% by C. reinhardtii was achieved at 1 mg/L MOX, whereas the maximum GAT removal of 34.04% was attained at 20 mg/L GAT. The different hydrophilicity and lipophilicity of these FQs resulted in distinct findings in biodegradation experiments. Identification of the transformation products suggested that the likely biodegradation pathways of FQs by C. reinhardtii were hydroxylation, demethylation, and ring cleavage.
Topics: Biodegradation, Environmental; Chlamydomonas reinhardtii; Fluoroquinolones; Gatifloxacin; Moxifloxacin; Photosynthesis
PubMed: 35653971
DOI: 10.1016/j.ecoenv.2022.113711 -
Antibiotics (Basel, Switzerland) Oct 2022Stenotrophomonas maltophilia (S. maltophilia) is a Gram-negative, opportunistic pathogen that can lead to ocular infections, such as keratitis and endophthalmitis. The...
Stenotrophomonas maltophilia (S. maltophilia) is a Gram-negative, opportunistic pathogen that can lead to ocular infections, such as keratitis and endophthalmitis. The purpose of this study was to determine the antibiotic susceptibility and minimum inhibitory concentrations (MICs) of S. maltophilia isolates from ocular infections and to evaluate the differences in antibiotic MICs between keratitis and endophthalmitis isolates. The disc diffusion method revealed that S. maltophilia isolates exhibited 91% susceptibility to levofloxacin and moxifloxacin and 61% susceptibility to trimethoprim−sulfamethoxazole (TMP−SMX). The E-test indicated that S. maltophilia isolates exhibited 40%, 100%, 72%, 91%, 91%, and 93% susceptibility to ceftazidime, tigecycline, TMP−SMX, levofloxacin, gatifloxacin, and moxifloxacin, respectively. The MIC90 values of amikacin, ceftazidime, cefuroxime, tigecycline, TMP−SMX, levofloxacin, gatifloxacin, and moxifloxacin were >256, >256, >256, 3, >32, 1, 2, and 0.75 µg/mL, respectively. The geometric mean MICs of ceftazidime, TMP−SMX, levofloxacin, gatifloxacin, and moxifloxacin were significantly lower for the keratitis isolates than for the endophthalmitis isolates (p = 0.0047, 0.003, 0.0029, 0.0003, and 0.0004, respectively). Fluoroquinolones showed higher susceptibility and lower MICs for the S. maltophilia isolates when compared with other antibiotics. Fluoroquinolones can be recommended for treating S. maltophilia ocular infections. Tigecycline and TMP−SMX could be alternative antibiotics for S. maltophilia ocular infections.
PubMed: 36358112
DOI: 10.3390/antibiotics11111457 -
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 -
JAMA Ophthalmology Feb 2021Off-label treatment was common for ophthalmia neonatorum because only erythromycin ointment had been approved by the US Food and Drug Administration (FDA) for this... (Review)
Review
IMPORTANCE
Off-label treatment was common for ophthalmia neonatorum because only erythromycin ointment had been approved by the US Food and Drug Administration (FDA) for this indication. Ophthalmia neonatorum was previously considered a different indication from bacterial conjunctivitis in older children and adults because of uncertain similarities in the cause of disease and the treatment course between the 2 populations. Prospective therapeutic clinical studies were required to demonstrate the effectiveness of treatment for ophthalmia neonatorum.
OBJECTIVE
To review the therapeutic clinical trials for patients with bacterial conjunctivitis to evaluate the similarity in the cause of disease and the treatment response between neonates and older children and adults.
DESIGN, SETTING, AND PARTICIPANTS
In this comparative effectiveness research review of pooled data from the most recent 30 bacterial conjunctivitis trials (N = 2018) submitted to the FDA to support the approval of topical ophthalmic solutions for older children and adults, 95% CIs were constructed from clinical cure rates. Cure rates in 3 neonatal randomized clinical trials (N = 392) of patients treated with ophthalmic anti-infective solutions of ciprofloxacin, gatifloxacin, and moxifloxacin were constructed and compared. The baseline ocular swab cultures were analyzed.
MAIN OUTCOMES AND MEASURES
Cure rates of neonatal trials were compared with the 95% CIs among older children and adults. The bacterial organisms isolated from these 2 populations were compared.
RESULTS
The 3 neonatal trials enrolled a total of 392 patients, and the 30 trials of older children and adults enrolled a total of 2018 patients. Neonatal clinical cure rates for moxifloxacin (day 4, 48%), ciprofloxacin (day 4, 49%; day 5, 61%), and gatifloxacin (day 7, 79%) were within the 95% CI for products approved to treat older children and adults with bacterial conjunctivitis. Bacterial organisms were consistent between these 2 populations.
CONCLUSIONS AND RELEVANCE
Comparison of the pooled analysis of these historical trial data suggests similarity in the cause of disease and the treatment response between neonates and older children and adults with bacterial conjunctivitis. Therefore, it was appropriate to extrapolate the effectiveness from older children and adults to neonates to support the approval of therapies for ophthalmia neonatorum. Based on this analysis, ophthalmic solutions of ciprofloxacin, gatifloxacin, and moxifloxacin are now approved for all age groups. This analysis presents an approach of using pooled data from previously underpowered individual trials to establish the similarities in the cause of disease and in treatment response between children and adults, which are the fundamental elements used to evaluate whether extrapolation of effectiveness can be used to support drug approval.
Topics: Administration, Ophthalmic; Age Factors; Anti-Bacterial Agents; Comparative Effectiveness Research; Conjunctivitis, Bacterial; Drug Approval; Evidence-Based Medicine; Humans; Infant, Newborn; Ophthalmia Neonatorum; Ophthalmic Solutions; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 33331874
DOI: 10.1001/jamaophthalmol.2020.5558 -
Translational Vision Science &... May 2023Although a comprehensive knowledge of antibiotic/corticosteroid combinations is essential for the appropriate treatment of eye infections, the impact of their...
PURPOSE
Although a comprehensive knowledge of antibiotic/corticosteroid combinations is essential for the appropriate treatment of eye infections, the impact of their co-administration has not been well studied to date. A systematic pharmacodynamic/pharmacokinetic study to determine the effects of cotreatment with various antibiotics and corticosteroids was conducted.
METHODS
Four bacterial strains, seven antibiotics, and four corticosteroids were used in the analyses. Drug interactions were evaluated by considering antibacterial effects with a checkerboard assay and intracellular concentrations in human corneal epithelial cells.
RESULTS
The drug combinations that showed the most stable effects against Pseudomonas aeruginosa was levofloxacin-prednisolone. Stable combinations against the three types of Gram-positive bacteria were neomycin-prednisolone, ofloxacin-dexamethasone, ofloxacin-prednisolone, and polymyxin-dexamethasone. The cellular concentrations were changed for the gatifloxacin-fluorometholone, moxifloxacin-fluorometholone, tobramycin-dexamethasone, and tobramycin-prednisolone combinations.
CONCLUSIONS
Loteprednol and fluorometholone reduced the antibacterial effects of all of the tested antibiotics in this study. Dexamethasone and prednisolone showed various effects in this regard, depending on the co-administered antibiotic. Prior knowledge of specific antibiotic/corticosteroid interactions provides valuable information to clinical practitioners by combining data on the antibacterial and intracellular uptake effects of their co-administration.
TRANSLATIONAL RELEVANCE
When using antibiotics and corticosteroids, drug combinations can be selected by referring to the results of this study.
Topics: Humans; Adrenal Cortex Hormones; Anti-Bacterial Agents; Bacteria; Eye Infections, Bacterial; Drug Interactions; Epithelium, Corneal; Cell Line; Drug Therapy, Combination; Corneal Diseases
PubMed: 37184498
DOI: 10.1167/tvst.12.5.16