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PloS One 2023The negative consequences of Substandard and falsified (SF) medicines are widely documented nowadays and there is still an urgent need to find them in more efficient...
The negative consequences of Substandard and falsified (SF) medicines are widely documented nowadays and there is still an urgent need to find them in more efficient ways. Several screening tools have been developed for this purpose recently. In this study, three screening tools were used on 292 samples of ciprofloxacin and metronidazole collected in Cameroon. Each sample was then analyzed by HPLC and disintegration tests. Seven additional samples from the nitro-imidazole (secnidazole, ornidazole, tinidazole) and the fluoroquinolone (levofloxacin, ofloxacin, norfloxacin, moxifloxacin) families were analyzed to mimic falsified medicines. Placebo samples that contained only inert excipients were also tested to mimic falsified samples without active pharmaceutical ingredient (API). The three screening tools implemented were: a simplified visual inspection checklist, a low-cost handheld near infrared (NIR) spectrophotometer and paper analytical devices (PADs). Overall, 61.1% of the samples that failed disintegration and assay tests also failed the visual inspection checklist test. For the handheld NIR, one-class classifier models were built to detect the presence of ciprofloxacin and metronidazole, respectively. The APIs were correctly identified in all the samples with sensitivities and specificities of 100%. However, the importance of a representative and up-to-date spectral database was underlined by comparing models built with different calibration set spanning different variability spaces. The PADs were used only on ciprofloxacin samples and detected the API in all samples in which the presence of ciprofloxacin was confirmed by HPLC. However, these PADs were not specific to ciprofloxacin since they reacted like ciprofloxacin to other fluoroquinolone compounds. The advantages and drawbacks of each screening tool were highlighted. They are promising means in the frame of early detection of SF medicines and they can increase the speed of decision about SF medicines in the context of pharmaceutical post-marketing surveillance.
Topics: Humans; Metronidazole; Counterfeit Drugs; Substandard Drugs; Ciprofloxacin; Levofloxacin; Product Surveillance, Postmarketing
PubMed: 37566594
DOI: 10.1371/journal.pone.0289865 -
Frontiers in Cellular and Infection... 2020antibiotic resistance is increasing worldwide, emphasizing the urgent need for more rapid resistance detection prior to the administration of eradication regimens....
antibiotic resistance is increasing worldwide, emphasizing the urgent need for more rapid resistance detection prior to the administration of eradication regimens. Macrolides and fluoroquinolones are widely used to treat . In this study, we aimed to compare the diagnostic performance of A) 23SrDNA qPCR (with melting curve analysis) and an in-house developed qPCR followed by Sanger sequencing with a commercial IVD-marked hybridization probe assay (for 23SrDNA and ) using 142 gastric biopsies (skipping culturing) and B) the same two qPCR for 23SrDNA and (including Sanger sequencing) with whole-genome sequencing (WGS) and phenotypic characterization of clarithromycin and levofloxacin resistance using 76 cultured isolates. The sensitivity of both qPCRs was 100% compared to that of the commercial IVD-marked hybridization probe assay for the detection of in gastric biopsies (without resistance testing). The specificity of the qPCR followed by Sanger sequencing was 100%, indicating that the best sequence identity was always . The results show good agreement between molecular tests, especially between qPCR (inclusive Sanger sequencing) and WGS. Discrepancies (concerning mutated or wild type of positive gastric biopsies) were observed between Sanger sequencing of the gene and the corresponding commercial hybridization probe assay, mostly because the high sequence diversity of the gene even at positions adjacent to the relevant codons of 87 and 91 interfered with obtaining correct results from the hybridization probe assay. Interestingly, we found several mixed sequences, indicating mixed populations in the gastric biopsies (direct detection without culturing). There was a high percentage of both levofloxacin and clarithromycin resistance in gastric biopsies (both between 22% and 29%, direct detection in gastric biopsies). Therefore, we recommend analyzing both targets in parallel. We confirmed that phenotypic resistance is highly correlated with the associated mutations. We concluded that the two qPCR followed by Sanger sequencing of the gene is a fast, cost-effective and comprehensive method for resistance testing of directly in gastric biopsies.
Topics: Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Microbial Sensitivity Tests
PubMed: 33392106
DOI: 10.3389/fcimb.2020.596371 -
European Journal of Hospital Pharmacy :... Sep 2022Oral antimicrobials, including ciprofloxacin, levofloxacin and doxycycline, are susceptible to binding with enteral therapies such as calcium and iron therapies.... (Observational Study)
Observational Study
INTRODUCTION
Oral antimicrobials, including ciprofloxacin, levofloxacin and doxycycline, are susceptible to binding with enteral therapies such as calcium and iron therapies. Administered together, the bioavailability of these antimicrobials is expected to be reduced.
METHODS
A retrospective case series of patients receiving oral antimicrobials (ciprofloxacin, levofloxacin and doxycycline) was analysed at a single-centre NHS acute hospital (April 2016-September 2019). Patient demographics, including concurrent enteral therapies, were recorded using medical records. Clinically important interactions were defined as doses administered within 2 hours of antimicrobial therapy.
RESULTS
A total of 4067 prescriptions for the study antimicrobials (ciprofloxacin, n=1905; levofloxacin, n=538; and doxycycline, n=1624) were prescribed for 3584 patients. 1918/3583 (53.5%) of the patients were female, and the median age was 67 years (range 0.5-105.0 years). 810/4067 (19.3%) prescriptions reviewed had an interacting enteral therapy (calcium or iron salt) administered within 2 hours of the study medication.
CONCLUSION
The concomitant administration of enteral calcium and iron with oral antimicrobials is common within the acute care hospital setting. Approximately one in five patients has a clinically important interaction which may impair oral bioavailability and limit treatment efficacy. As antimicrobial stewardship teams strive for increased intravenous-to-oral de-escalation, it is important that optimum dosing administration is followed to optimise patient outcomes.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Calcium; Child; Child, Preschool; Ciprofloxacin; Doxycycline; Female; Humans; Infant; Iron; Levofloxacin; Male; Middle Aged; Retrospective Studies; Young Adult
PubMed: 33414257
DOI: 10.1136/ejhpharm-2020-002445 -
Antimicrobial Agents and Chemotherapy Mar 2017A retrospective study was conducted in a large sample of acutely hospitalized older patients who underwent therapeutic drug monitoring during levofloxacin treatment. The...
A retrospective study was conducted in a large sample of acutely hospitalized older patients who underwent therapeutic drug monitoring during levofloxacin treatment. The aim was to assess the population pharmacokinetics (popPK) and pharmacodynamics of levofloxacin among older patients. PopPK and Monte Carlo simulation were performed to define the permissible doses in older patients according to various degrees of renal function. Classification and regression tree (CART) analysis was used to detect the cutoff 24-hour area under the concentration-time curve (AUC)/MIC ratio that best correlated with the clinical outcome. The probability of target attainment (PTA) of this value was calculated against different pathogens. A total of 168 patients were included, and 330 trough and 239 peak concentrations were used for the popPK analysis. Creatinine clearance (CrCL) was the only covariate that improved the model fit (levofloxacin CL = 0.399 + 0.051 × CrCL [creatinine clearance estimated by means of the chronic kidney disease epidemiology]). Drug doses ranged between 500 mg every 48 h and 500 mg every 12 h in relation to different renal functions. The identified cutoff AUC/MIC ratio (≥95.7) was the only covariate that correlated with a favorable clinical outcome in multivariate regression analysis (odds ratio [OR], 20.85; 95% confidence interval [CI], 1.56 to 186.73). PTAs were optimal (>80%) against and , borderline against , and suboptimal against The levofloxacin doses defined in our study may be effective for the treatment of infections due to bacterial pathogens, with an MIC of ≤0.5 mg/liter in older patients with various degrees of renal function, while minimizing the toxicity risk. Conversely, the addition of another active antimicrobial should be considered whenever treating infections caused by less susceptible pathogens.
Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Area Under Curve; Bacterial Infections; Biological Availability; Body Mass Index; Creatinine; Drug Administration Schedule; Drug Dosage Calculations; Drug Monitoring; Escherichia coli; Female; Haemophilus influenzae; Hospitalization; Humans; Kidney Function Tests; Levofloxacin; Male; Microbial Sensitivity Tests; Models, Statistical; Pseudomonas aeruginosa; Retrospective Studies; Staphylococcus aureus
PubMed: 28031199
DOI: 10.1128/AAC.02134-16 -
Revista Espanola de Enfermedades... Jun 2020According to some series, 0.3-1.5% of all cases of acute pancreatitis are drug induced. Acute pancreatitis due to levofloxacin is included in its safety data sheet as an...
According to some series, 0.3-1.5% of all cases of acute pancreatitis are drug induced. Acute pancreatitis due to levofloxacin is included in its safety data sheet as an adverse effect.
Topics: Acute Disease; Humans; Levofloxacin; Pancreatitis
PubMed: 32496110
DOI: 10.17235/reed.2020.6652/2019 -
Journal of Controlled Release :... Aug 2022Melanin binding of drugs is known to increase drug concentrations and retention in pigmented eye tissues. Even though the correlation between melanin binding in vitro...
Melanin binding of drugs is known to increase drug concentrations and retention in pigmented eye tissues. Even though the correlation between melanin binding in vitro and exposure to pigmented eye in vivo has been shown, there is a discrepancy between rapid drug release from melanin particles in vitro and the long in vivo retention in the pigmented tissues. We investigated mechanisms and kinetics of pigment-related drug retention experimentally using isolated melanin particles from porcine retinal pigment epithelium and choroid, isolated porcine eye melanosomes, and re-pigmented ARPE-19 cells in a dynamic flow system. The experimental studies were supplemented with kinetic simulations. Affinity and capacity of levofloxacin, terazosin, papaverine, and timolol binding to melanin revealed K values of ≈ 50-150 μM and B ≈ 40-112 nmol.mg. The drugs were released from melanin in <1 h (timolol) or in 6-12 h (other drugs). The drugs were released slower from the melanosomes than from melanin; the experimental differences ranged from 1.2-fold (papaverine) to 7.4-fold (timolol). Kinetic simulations supported the role of the melanosomal membrane in slowing down the release of melanin binders. In release studies from the pigmented ARPE-19 cells, drugs were released from the cellular melanin to the extracellular space in ≈ 1 day (timolol) and ≈ 11 days (levofloxacin), i.e., much slower than the release from melanin or melanosomes. Simulations of drug release from pigmented cells in the flow system matched the experimental data and enabled further sensitivity analyses. The simulations demonstrated a significant prolongation of drug retention in the cells as a function of decreasing drug permeability in the melanosomal membranes and increasing melanin content in the cells. Overall, we report the impact of cellular factors in prolonging drug retention and release from melanin-containing cells. These data and simulations will facilitate the design of melanin binding drugs with prolonged ocular actions.
Topics: Animals; Computer Simulation; Levofloxacin; Melanins; Papaverine; Retinal Pigment Epithelium; Swine; Timolol
PubMed: 35738465
DOI: 10.1016/j.jconrel.2022.05.059 -
Alimentary Pharmacology & Therapeutics Sep 2016Levofloxacin triple therapy has been used for the first-line and second-line treatment of Helicobacter pylori infection for more than 10 years. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Levofloxacin triple therapy has been used for the first-line and second-line treatment of Helicobacter pylori infection for more than 10 years.
AIMS
To systematically review the efficacy of levofloxacin triple therapy in the first- and second-line treatment, and to assess the time trend and factors that might affect its efficacy.
METHODS
Prospective trials reporting the efficacy of levofloxacin triple therapy in either the first-line or second-line treatment of H. pylori infection in adults were searched from the PubMed and Cochrane database from January 2000 to September 2015. Meta-analysis was performed to calculate the cumulative eradication rate and the efficacies in subgroups.
RESULTS
Of the 322 articles identified, a total of 4574 patients from 41 trials, including 16 trials in the first-line treatment and 25 trials in the second-line treatment were eligible for analysis. The cumulative eradication rate was 77.3% (95% confidence intervals, CI: 74.7-79.6) and was 80.7% (95% CI 77.1-83.7) in the first-line treatment and 74.5% (95% CI: 70.9-77.8) in the second-line treatment. The efficacies of levofloxacin triple therapy before 2008, between 2009 and 2011, and after 2012 were 77.4%, 79.6% and 74.8% respectively. The eradication rate was higher when levofloxacin was given once daily (80.6%, 95% CI: 77.1-83.7) than twice daily (73.6%, 95% CI: 69.7-77.2). The efficacy was significantly higher in levofloxacin-susceptible strains than resistant strains (81.1% vs. 36.3%, risk ratio 2.18, 95% CI: 1.6-3, P < 0.001).
CONCLUSION
The efficacy of levofloxacin triple therapy has been lower than 80% in many countries and it is not recommended when the levofloxacin resistance is higher than 5-10%.
Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Clinical Trials as Topic; Databases, Factual; Drug Resistance, Bacterial; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Prospective Studies; Treatment Outcome
PubMed: 27363687
DOI: 10.1111/apt.13712 -
Asia-Pacific Journal of Ophthalmology... 2017To investigate various regimens of prophylactic antibiotic therapy for vitreoretinal surgery. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To investigate various regimens of prophylactic antibiotic therapy for vitreoretinal surgery.
DESIGN
This study compared different prophylactic therapies with 0.5% levofloxacin eye drops.
METHODS
Two hundred nine patients from 7 hospitals scheduled to undergo vitreoretinal surgery were randomized into 3 groups to receive 0.5% levofloxacin eye drops for 1 day (6 times/d), 2 days (3 times/d), or 3 days (3 times/d) before surgery (groups 1D, 2D, and 3D, respectively). all patients received 3 applications of levofloxacin eye drops at 15-minute intervals beginning 1 hour before surgery and conjunctival sac disinfection with 5.0% povidone-iodine 15 minutes before surgery. conjunctival swabs were cultured before levofloxacin therapy (T0), on the morning of surgery (T1), after povidone-iodine disinfection (T2), immediately after surgery (T3), 1 day postoperatively (T4), and 1 week postoperatively (T5).
RESULTS
The positive bacterial culture rates in groups 1D, 2D, and 3D fell, respectively, from 37.33%, 30.77%, and 31.88% at t0 to 10.67%, 12.31%, and 11.59% at t1 and 1.33%, 0%, and 0% at T2. at each time point (T0-T5), there were no significant differences among the groups in positive bacterial culture rate. the bacterial eradication rates in groups 1D, 2D, and 3D were, respectively, 100%, 94.74%, and 90.00% at T1 (after levofloxacin) and 100% in all groups at T2 (after povidone-iodine).
CONCLUSIONS
The efficacy of levofloxacin in preventing postoperative infection was similar in the 3 treatment groups. it is recommended that 0.5% levofloxacin be used for only 1 day before vitreoretinal sur-gery (6 times/d) to minimize the use of prophylactic antibiotics.
Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteria; Conjunctiva; Eye Infections, Bacterial; Female; Humans; Levofloxacin; Male; Middle Aged; Ophthalmic Solutions; Postoperative Complications; Time Factors; Vitreoretinal Surgery
PubMed: 28161927
DOI: 10.22608/APO.2015197 -
International Journal of... 2020Levofloxacin is a preferred drug for multidrug-resistant (MDR)-tuberculosis (TB) with bactericidal activity that correlates with the pharmacokinetic exposures of serum...
BACKGROUND
Levofloxacin is a preferred drug for multidrug-resistant (MDR)-tuberculosis (TB) with bactericidal activity that correlates with the pharmacokinetic exposures of serum peak concentration (C) and total area under the concentration time curve (AUC). Pharmacokinetic exposures can be measured to personalize dosing to reach targets, but this practice requires venepuncture, chromatographic or mass spectrometry equipment, and technical expertise. We sought to demonstrate the accuracy of using urine colorimetry as a more feasible estimation of levofloxacin exposure.
METHOD
A colorimetric method using bromocresol green was tested on spiked urine samples with levofloxacin measured using a spectrophotometer. This method was tested in urine samples of healthy volunteers given one 750 mg dose of levofloxacin with urine collected at 0-4 h, 4-8 h, and 8-24 h intervals, and concomitant serum samples were collected and analyzed by high-performance liquid chromatography. Validation of this assay was done in a cohort of people living with human immunodeficiency virus (PLWH), initiating a levofloxacin containing MDR-TB regimen.
RESULTS
Urine colorimetry was reproducible in spiked samples and the calibration was curve linear for levofloxacin concentrations ranging from 7.8 μg/ml to 250 μg/ml, with r = 0.98. In healthy volunteers, correlation between urine absorbance values and serum AUC was highest in urine collected between 4 and 8 h (r = 0.91, P = 0.01), yet in PLWH, urine collected between 0 and 4 h had highest correlation (r = 0.66, P = 0.05). The area under the receiver operating characteristics curve was >0.8 in the derivation, as well as the validation cohort for the urine absorbance values identifying people with total serum exposure below target.
CONCLUSION
Urine colorimetry was highly sensitive in predicting target serum concentrations. Colorimetric methods to determine levofloxacin in urine may improve the feasibility of therapeutic drug monitoring and personalized dose adjustment in TB endemic settings.
Topics: Antitubercular Agents; Colorimetry; Drug Monitoring; Female; Humans; Levofloxacin; ROC Curve; Tuberculosis, Multidrug-Resistant
PubMed: 33323657
DOI: 10.4103/ijmy.ijmy_186_20 -
Biomedica : Revista Del Instituto... May 2019Introduction: The main cause for Helicobacter pylori infection treatment failure is antibiotic resistance, where clarithromycin and metronidazole play the main role. In...
Introduction: The main cause for Helicobacter pylori infection treatment failure is antibiotic resistance, where clarithromycin and metronidazole play the main role. In Colombia, primary resistance as a consequence of the use of these two antibiotics and excessive levofloxacin use is above the accepted limit (13.6%, 83%, and 16%, respectively). Despite this fact, empirical therapies that include the combination of these antibiotics are used in patients with previous therapeutic failure. Objective: To determine antibiotic resistance in patients previously treated for H. pylori in Bogotá, Colombia. Materials and methods: We conducted a descriptive study that included ten isolates obtained from five patients with three or four previous failed treatments for H. pylori. Antibiotic resistance to amoxicillin, clarithromycin, levofloxacin, and metronidazole was investigated by agar dilution and confirmed by DNA sequencing (Magrogen, Korea). Results: Eight isolates were resistant to two or more antibiotics. All isolates were resistant to levofloxacin. Susceptibility patterns in isolates from the gastric antrum and the body of the stomach were different in three patients. Conclusion: As far as we know, this is the first evidence of multiple H. pylori resistance in Colombia in previously treated patients. Results demonstrated the consequences of using an ineffective antibiotic scheme and the need to assess antibiotic susceptibility in different anatomical sites of the stomach. The consequences of multiple resistance decrease possible antibiotic effectiveness to eradicate H. pylori in the future.
Topics: Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Biopsy; Clarithromycin; Colombia; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Gastritis; Gastroscopy; Genes, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Male; Metronidazole; Microbial Sensitivity Tests; Middle Aged
PubMed: 31529855
DOI: 10.7705/biomedica.v39i3.4437