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Microbiology Spectrum Aug 2023Cutibacterium avidum is an emerging causative agent of orthopedic device-related infections (ODRIs). There are no guidelines for the antimicrobial treatment of ODRI,...
Cutibacterium avidum is an emerging causative agent of orthopedic device-related infections (ODRIs). There are no guidelines for the antimicrobial treatment of ODRI, but oral rifampin is frequently used in combination with a fluoroquinolone following intravenous antibiotics. We describe the emergence of combined resistance to rifampin and levofloxacin in a strain isolated from a patient with early-onset ODRI treated with debridement, antibiotic treatment, and implant retention (DAIR) using rifampin combined with levofloxacin as the oral treatment. Whole-genome sequencing of isolates before and after antibiotic exposure confirmed strain identity and identified new mutations in and , leading to amino acid substitutions previously reported to be associated with resistance to rifampin (S446P) and fluoroquinolones (S101L), respectively, in other microbial agents, in the posttherapy isolate. Aside from the molecular insights reported here, this study highlights potential limitations of the combination of oral rifampin and levofloxacin in patients undergoing a DAIR procedure for ODRI and the potential need to evaluate specific optimal therapy for emerging ODRI pathogens. In this study, we report for the first time the emergence of dual resistance to levofloxacin and rifampin in isolated from a patient who received both antibiotics orally in the setting of a salvage debridement and implant retention of an ODRI. Aside from the molecular insights reported here, this study highlights potential limitations of the combination of oral rifampin and levofloxacin in patients undergoing these surgical procedures and the potential need to evaluate specific optimal therapy for emerging ODRI pathogens.
Topics: Humans; Levofloxacin; Rifampin; Anti-Bacterial Agents; Propionibacteriaceae; Fluoroquinolones; Microbial Sensitivity Tests
PubMed: 37289061
DOI: 10.1128/spectrum.03687-22 -
Journal of Clinical Pharmacology Mar 2020Women are associated with longer electrocardiographic QT intervals and increased proarrhythmic risks of QT-prolonging drugs. The purpose of this study was to... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Women are associated with longer electrocardiographic QT intervals and increased proarrhythmic risks of QT-prolonging drugs. The purpose of this study was to characterize the differences in cardiac electrophysiology between moxifloxacin and levofloxacin in men and women and to assess the balance of inward and outward currents through the analysis of QT subintervals. Data from 2 TQT studies were used to investigate the impact of moxifloxacin (400 mg) and levofloxacin (1000 and 1500 mg) on QT subintervals using algorithms for measurement of J-T and T -T intervals. Concentration-effect analyses were performed to establish potential relationships between the ECG effects and the concentrations of the 2 fluoroquinolones. Moxifloxacin was shown to be a more potent prolonger of QT interval corrected by Fredericia (QTcF) and had a pronounced effect on J-T c. Levofloxacin had little effect on J-T c. For moxifloxacin, the concentration-effect modeling showed a greater effect for women on QTcF and J-T c, whereas for levofloxacin the inverse was true: women had smaller QTcF and J-T c effects. The different patterns in repolarization after administration of both drugs suggested a sex difference, which may be related to the combined I and I inhibitory properties of moxifloxacin versus I suppression only of levofloxacin. The equipotent inhibition of I and I appears to affect women more than men. Sex hormones are known to influence cardiac ion channel expression and differences in QT duration. Differences in I and I balances, influenced by sex hormones, may explain the results. These results support the impact of sex differences on the cardiac safety assessment of drugs.
Topics: Action Potentials; Adult; Algorithms; Anti-Bacterial Agents; Calcium Channels; Cross-Over Studies; Double-Blind Method; Electrocardiography; Female; Gonadal Steroid Hormones; Healthy Volunteers; Heart; Humans; Levofloxacin; Long QT Syndrome; Male; Moxifloxacin; Potassium Channels; Retrospective Studies; Sex Characteristics
PubMed: 31637733
DOI: 10.1002/jcph.1534 -
Chemosphere Dec 2021Here, the antibiotic levofloxacin (LFX) widely used and detected in the environment was degraded by photoelectrolysis using a new electrode based on zinc oxide (ZnO) and...
Here, the antibiotic levofloxacin (LFX) widely used and detected in the environment was degraded by photoelectrolysis using a new electrode based on zinc oxide (ZnO) and a mixture of mixed oxides of ruthenium and titanium (MMO). The influence of the potential and irradiation of UV light was investigated in the photostability of the Ti/MMO/ZnO electrode and in the degradation of the antibiotic. The experiments were conducted at different pH values (5.0, 7.0 and 9.0) in sodium sulfate solution in a glass reactor with central lighting. It was observed that the new Ti/MMO/ZnO electrode has good stability under light irradiation and potential, presenting excellent photocurrent and high photoactivity in LFX photoelectrolysis. The removal efficiency of the compound was directly related to the formation of oxidizing species in solution, the photo-generated charges on the electrode and the electrostatic characteristics of the molecule. The mineralization rate, the formation of reaction intermediates and short chain carboxylic acids (acetic, maleic, oxalic and oxamic acid), in addition to the formation of N-mineral species (NO and NH) was dependent on the pH of the solution and the investigated processes: photoelectrolysis was more efficient than photolysis, which, in turn, was more efficient than electrolysis. The synergistic effect and the high rate of degradation of LFX after 4.0 h of treatment (100%) observed in photoelectrolysis at alkaline pH, was associated with the high stability of the Ti/MMO/ZnO electrode at this pH, the photoactivation of sulfate ions and the ease generation of oxidizing radicals, such as OH.
Topics: Catalysis; Electrodes; Electrolysis; Levofloxacin; Titanium; Water Pollutants, Chemical; Zinc Oxide
PubMed: 34182289
DOI: 10.1016/j.chemosphere.2021.131303 -
Journal of Global Antimicrobial... Sep 2023The aim of the study was to update the classification of drugs used in multidrug-resistant tuberculosis (MDR-TB) regimens. Group A drugs (fluoroquinolones, bedaquiline... (Meta-Analysis)
Meta-Analysis Review
Evaluation of genetic mutations associated with phenotypic resistance to fluoroquinolones, bedaquiline, and linezolid in clinical Mycobacterium tuberculosis: A systematic review and meta-analysis.
OBJECTIVES
The aim of the study was to update the classification of drugs used in multidrug-resistant tuberculosis (MDR-TB) regimens. Group A drugs (fluoroquinolones, bedaquiline (BDQ), and linezolid (LZD)) are crucial drugs for the control of MDR-TB. Molecular drug resistance assays could facilitate the effective use of Group A drugs.
METHODS
We summarised the evidence implicating specific genetic mutations in resistance to Group A drugs. We searched PubMed, Embase, MEDLINE, and the Cochrane Library for studies published from the inception of each database until July 1, 2022. Using a random-effects model, we calculated the odds ratios and 95% confidence intervals as our measures of association.
RESULTS
A total of 5001 clinical isolates were included in 47 studies. Mutations in gyrA A90V, D94G, D94N, and D94Y were significantly associated with an increased risk of a levofloxacin (LFX)-resistant phenotype. In addition, mutations in gyrA G88C, A90V, D94G, D94H, D94N, and D94Y were significantly associated with an increased risk of a moxifloxacin (MFX)-resistant phenotype. In only one study, the majority of gene loci (n = 126, 90.65%) in BDQ-resistant isolates were observed to have unique mutations in atpE, Rv0678, mmpL5, pepQ, and Rv1979c. The most common mutations occurred at four sites in the rrl gene (g2061t, g2270c, g2270t, and g2814t) and at one site in rplC (C154R) in LZD-resistant isolates. Our meta-analysis demonstrated that there were no mutations associated with BDQ- or LZD-resistant phenotypes.
CONCLUSION
The mutations detected by rapid molecular assay were correlated with phenotypic resistance to LFX and MFX. The absence of mutation-phenotype associations for BDQ and LZD hindered the development of a rapid molecular assay.
Topics: Humans; Mycobacterium tuberculosis; Linezolid; Fluoroquinolones; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Levofloxacin; Phenotype
PubMed: 37172764
DOI: 10.1016/j.jgar.2023.05.001 -
The International Journal of... Dec 2020
Topics: Adolescent; Child; Humans; Anti-Bacterial Agents; Aza Compounds; Fluoroquinolones; Levofloxacin; Linezolid; Microbial Sensitivity Tests; Moxifloxacin; Ofloxacin; Tuberculosis
PubMed: 33317680
DOI: 10.5588/ijtld.20.0544 -
Antimicrobial Agents and Chemotherapy May 2017The pharmacodynamics of finafloxacin, ciprofloxacin, and levofloxacin against extended-spectrum-β-lactamase (ESBL)-producing isolates were compared. Since quinolones...
Pharmacodynamics of Finafloxacin, Ciprofloxacin, and Levofloxacin in Serum and Urine against TEM- and SHV-Type Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae Isolates from Patients with Urinary Tract Infections.
The pharmacodynamics of finafloxacin, ciprofloxacin, and levofloxacin against extended-spectrum-β-lactamase (ESBL)-producing isolates were compared. Since quinolones lose activity in acidic media, and particularly in urine, their activities were tested in parallel under conventional conditions and in acidic artificial urine. For this purpose, TEM- and SHV-type ESBL-producing and strains and their wild-type counterparts were exposed in a modified Grasso model to simulated concentrations of drugs in serum and urine following oral doses of either finafloxacin at 800 mg once a day (q.d.), immediate-release ciprofloxacin at 500 mg twice a day (b.i.d.), extended-release ciprofloxacin at 1,000 mg q.d., or levofloxacin at 500 or 750 mg q.d. The concentrations of the drugs in urine were fitted by compartmental modeling. Bacteria were cultivated in Mueller-Hinton broth (MHB) at pH 7.2 or 5.8 or in artificial urine at pH 5.8. Bacteria were counted every 2 h until 10 h and at 24 h; the areas under the bacterial-count-versus-time curves were calculated. It was found that finafloxacin eliminated all strains within 2 h under all the conditions studied. At all doses studied, ciprofloxacin and levofloxacin were highly active against wild-type strains in MHB at pH 7.2 but lost activity in MHB, and particularly in urine, at pH 5.8. Viable counts of ESBL producers were reduced for 6 to 8 h by 3 log titers, but the bacteria regrew thereafter. Ciprofloxacin and levofloxacin were almost inactive against the SHV producer grown in artificial urine. We conclude that pharmacodynamic models using artificial urine may mirror the physiology of urinary tract infections more closely than those using conventional media. In contrast to ciprofloxacin and levofloxacin, finafloxacin gained activity in this model at an acidic pH, maintained activity in artificial urine, and was active against TEM and SHV producers.
Topics: Anti-Bacterial Agents; Blood; Ciprofloxacin; Escherichia coli; Fluoroquinolones; Humans; Klebsiella pneumoniae; Levofloxacin; Microbial Sensitivity Tests; Urinary Tract Infections; Urine; beta-Lactamases
PubMed: 28193648
DOI: 10.1128/AAC.02446-16 -
PloS One 2022Potential association between oral levofloxacin use and hypoglycemic emergency (HE) have been established. However, a large epidemiological study is required to verify...
Potential association between oral levofloxacin use and hypoglycemic emergency (HE) have been established. However, a large epidemiological study is required to verify this observation. This study aimed to determine if use of oral levofloxacin increased the risk of HE. The nationwide database between 1999 and 2013, including 1.6 million patients with type 2 diabetes (T2D), was used to conduct a nested case-control study. Cases and controls comprised of patients with and without HE, respectively. To avoid indication bias the control subjects were chosen through propensity score matching with cases in a 10-fold ratio. T2D severity was classified based on the adjusted diabetic complication severity index score. 26,695 and 266,950 matched patients with T2D, were finally used as cases and controls, respectively, for the analysis. Multivariate logistic regression analysis showed that antibiotic use was associated with an increased risk for HE (adjusted odds ratio (aOR) = 6.08, 95% confidence interval (95% CI): 5.79-6.38). When compared with antibiotic non-users, those who used fluoroquinolones and sulfonamides displayed the highest (aOR = 12.05, 95% CI: 10.66-13.61) and second highest (aOR = 7.20, 95% CI: 6.29-8.24) risks of HE, respectively. The associated risk for HE was significantly higher with levofloxacin than that with cephalosporins (aOR = 5.13, 95% CI: 2.28-11.52) and penicillin (aOR = 9.40, 95% CI: 2.25-39.24). In the joint effect analyses, the risk for HE increased with the combination of levofloxacin with insulin (aOR = 8.42, 95% CI: 1.91-37.00) or sulfonylurea (aOR = 3.56, 95% CI: 1.12-11.33). Use of oral levofloxacin, compared to that of other antibiotics, was found to be significantly associated with HE in T2D patients. Clinicians should exercise caution while prescribing levofloxacin, especially when combined with insulin or sulfonylurea.
Topics: Anti-Bacterial Agents; Case-Control Studies; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Levofloxacin; Propensity Score; Risk Factors; Sulfonylurea Compounds
PubMed: 35377912
DOI: 10.1371/journal.pone.0266471 -
Medical Archives (Sarajevo, Bosnia and... Apr 2021infections induce chronic gastric mucosal inflammation and peptic ulcer disease, and eradication is recommended. (Comparative Study)
Comparative Study
BACKGROUND
infections induce chronic gastric mucosal inflammation and peptic ulcer disease, and eradication is recommended.
OBJECTIVE
To investigate antibiotic resistance and eradication rates in children with gastroduodenal ulcers in Vietnam.
METHODS
We performed gastroduodenal endoscopies, cultures, and antimicrobial susceptibility testing (clarithromycin, amoxicillin, metronidazole, tetracycline, and levofloxacin) In children with gastroduodenal ulcers at Children's Hospital 2 from November 1, 2019, to June 30, 2020.
RESULTS
A total of 76 participants were studied, with an average age of 9.3 ± 2.8 years (range: 4-15 years), including 52.6% males and 47.4% females. The antibiotic resistance rates were clarithromycin, 92.1%; amoxicillin, 50%; levofloxacin, 31.6%; metronidazole, 14.5%; and tetracycline, 0%. The successful eradication rate was 44.7%. Bismuth increased the eradication rate by 3.69-fold that without bismuth (p = 0.030). The eradication rate of levofloxacin was high (100%, p = 0.038) compared with other antibiotics. The effectiveness of high-dose amoxicillin in cases with >50% amoxicillin resistance was only 32.6% (p = 0.015).
CONCLUSION
Increased antibiotic resistance among resulted in decreased eradication efficacy, which was 44.7% in this study. Drug combinations, such as levofloxacin and bismuth, can increase the eradication efficacy in children.
Topics: Adolescent; Amoxicillin; Anti-Bacterial Agents; Asian People; Child; Child, Preschool; Clarithromycin; Disease Eradication; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Helicobacter Infections; Humans; Levofloxacin; Male; Metronidazole; Microbial Sensitivity Tests; Peptic Ulcer; Tetracycline
PubMed: 34219870
DOI: 10.5455/medarh.2021.75.112-115 -
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