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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 -
International Journal of Infectious... Sep 2022To evaluate the pharmacokinetic parameters of the 2020 World Health Organization (WHO)-recommended pediatric dosage of levofloxacin and the higher-than-WHO dosage.
OBJECTIVES
To evaluate the pharmacokinetic parameters of the 2020 World Health Organization (WHO)-recommended pediatric dosage of levofloxacin and the higher-than-WHO dosage.
METHODS
Children aged 1-15 years with tuberculosis who received levofloxacin-based treatment for at least 7 days were enrolled. First, five children were enrolled to receive the WHO-recommended dosage (15-20 mg/kg/day), then an additional five children received a dosage higher than the WHO-recommended dosage (20-30 mg/kg/day). Blood samples were collected at predose and postdose 1, 2, 4, 6, 8, and 12 hours. A target of the ratio of the free area under the concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was 100.
RESULTS
The median (interquartile range) age was 9.6 (4.9-10.5) and 12.0 (10.1-12.3) years in the WHO dosage and higher-than-WHO dosage groups, respectively. The median (interquartile range) duration of antituberculosis treatment was 24 (8-24) weeks. The geometric mean (95% confidence interval) of fAUC/MIC was 60.4 (43.5-84.0) and 103.2 (70.1-151.8) in the WHO and higher-than-WHO dosage groups, respectively. There was no adverse event of QT prolongation or any other grade 3 or 4 adverse events.
CONCLUSION
Levofloxacin at a higher dose of 20-30 mg/kg/day could achieve the fAUC/MIC target in children.
Topics: Antitubercular Agents; Child; Humans; Levofloxacin; Pilot Projects; Tuberculosis; World Health Organization
PubMed: 35842213
DOI: 10.1016/j.ijid.2022.07.029 -
Journal of Global Antimicrobial... Sep 2023The incidence of Helicobacter pylori (HP) is 25-50% in developed countries and 80% in developing countries, including 56.2% in China. However, antibiotic resistance of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The incidence of Helicobacter pylori (HP) is 25-50% in developed countries and 80% in developing countries, including 56.2% in China. However, antibiotic resistance of HP is a threat to HP control. The purpose of this study was to comprehensively evaluate primary drug resistance of HP in China.
METHODS
The full text of reports of the primary antibiotic resistance prevalence of HP was obtained from multiple databases (PubMed, Web of Science, Evimed, Cochrane Library, and China National Knowledge Internet). Review Manager 5.2 was adopted for meta-analysis, sensitivity analysis, and bias analysis. The Newcastle-Ottawa Scale was used to assess the article quality.
RESULTS
In total, 38804 HP samples from 22 trials were extracted. The results suggested that the overall prevalence of amoxicillin, clarithromycin, metronidazole, and levofloxacin resistance among HP in adults was as follows: mean difference (MD) = 1.35%, 95% confidence interval (CI) [1.03%, 1.68%]; MD = 23.76%, 95% CI [20.23%, 27.3%]; MD = 69.32%, 95% CI [64.85%, 73.8%]; and MD = 29.45%, 95% CI [4.90, 176.96], respectively. From the results of sensitivity and publication bias, we find that these results are robust and had little publication bias.
CONCLUSION
Our research showed that in China, the prevalence of HP resistance to primary antibiotics warrants attention, especially with regard to metronidazole, levofloxacin, and clarithromycin.
Topics: Adult; Humans; Metronidazole; Clarithromycin; Levofloxacin; Helicobacter pylori; Helicobacter Infections; Drug Resistance, Bacterial; Anti-Bacterial Agents; China
PubMed: 37315738
DOI: 10.1016/j.jgar.2023.05.014 -
Comparative Study on the Efficacy of Two Perioperative Chemotherapy Regimens for Lumbar Brucellosis.Drug Design, Development and Therapy 2023The clinical efficacy of perioperative chemotherapy regimen (rifampicin, doxycycline, levofloxacin, ceftriaxone) was evaluated for lumbar brucellosis spondylitis...
OBJECTIVE
The clinical efficacy of perioperative chemotherapy regimen (rifampicin, doxycycline, levofloxacin, ceftriaxone) was evaluated for lumbar brucellosis spondylitis patients with neurological injury.
METHODS
In Beijing Ditan Hospital affiliated with Capital Medical University, 32 patients with lumbar brucellosis spondylitis underwent surgery and triple perioperative chemotherapy (rifampicin, doxycycline, levofloxacin) between 2011 and 2021 due to neurological injury, and 34 patients matched up with the triple group underwent rifampicin, doxycycline, levofloxacin, and ceftriaxone. Both groups were compared in terms of changes in inflammation index, low back/leg pain, lumbar function, neurological function, and adverse drug reactions.
RESULTS
There was no significant difference in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), low back pain visual analogue scale (VAS), leg pain VAS, lumbar Oswestry disability index (ODI) and nerve function injury rate between the two groups before chemotherapy (>0.05). The ESR, CRP at 1 week and 2 weeks after chemotherapy and 1 week, 2 weeks, 1 month postoperatively in the quadruple group were significantly lower than those in the triple group, which is the same to ESR 3 months postoperatively (<0.05). The low back pain VAS, leg pain VAS and lumbar ODI in the quadruple group were significantly lower than those in the triple group at 1 month and 3 months postoperatively (<0.05). The recovery rate of neurological function in the quadruple group was significantly higher than that in the triple group at 3 and 6 months postoperatively (<0.05). Both groups did not experience significantly different perioperative and postoperative adverse reactions (0.05).
CONCLUSION
For lumbar brucellosis spondylitis with neurological injury, quadruple perioperative chemotherapy of rifampicin, doxycycline, levofloxacin and ceftriaxone can significantly reduce perioperative inflammation, and improve low back/leg pain, as well as promoting neurological function recovery in the short term.
Topics: Humans; Low Back Pain; Doxycycline; Rifampin; Levofloxacin; Ceftriaxone; Lumbar Vertebrae; Treatment Outcome; Brucellosis; Inflammation; Spondylitis; Retrospective Studies
PubMed: 38046280
DOI: 10.2147/DDDT.S427477 -
The Turkish Journal of Gastroenterology... Mar 2021It is known that clarithromycin resistance has increased over the years (success rate 60%). The aim of the study was to investigate the importance of regional...
BACKGROUND
It is known that clarithromycin resistance has increased over the years (success rate 60%). The aim of the study was to investigate the importance of regional antimicrobial resistance rates for full accuracy of both diagnosis and treatment of Helicobacter pylori infection.
METHODS
This study was carried out in the University Hospital Department of Gastroenterology. A total of 116 patients were evaluated with upper gastrointestinal endoscopy. Gastric antrum and corpus biopsy samples were taken for the rapid urease test (RUT), culture, and antimicrobial susceptibility testing for the presence of H. pylori. Antimicrobial susceptibilities of isolated H. pylori strains for clarithromycin and levofloxacin were determined by the epsilometer test (E-test). Minimal inhibitory concentration values for clarithromycin and levofloxacin were ≥1 and >1 μg/mL, respectively.
RESULTS
H. pylori infection was considered clinically positive in 93 (80.2%) patients with either the RUT, culture, or histopathological examination. Seventy (60.3%) of the patients had RUT positivity. Sixty (85.7%) of these 70 patients had RUT positivity within the first 20 min. Among the 90 patients, who had a histopathological examination, HLO was positive in 76 (84.4%) patients. Fifty-two (44.8%) out of 116 patients were culture positive. Resistance rates for both clarithromycin and levofloxacin were high. In these 52 culture-positive patients, resistance rates determined for clarithromycin and levofloxacin were 26.9% and 25.5%, respectively.
CONCLUSION
Clarithromycin or levofloxacin-based treatment regimen may not be an ideal alternative therapy for Turkish patients regardless of culture.
Topics: Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Microbial; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Turkey; Urease
PubMed: 34160356
DOI: 10.5152/tjg.2021.20210 -
Journal of Global Antimicrobial... Jun 2023Generic medications are widely used because of their low cost. However, some generic medications show lower quality and clinical efficacy compared with brand-name...
OBJECTIVE
Generic medications are widely used because of their low cost. However, some generic medications show lower quality and clinical efficacy compared with brand-name medications, especially for antimicrobial drugs. Levofloxacin is a fluoroquinolone antimicrobial drug with excellent antimicrobial activity and wide antimicrobial spectrum, while it is susceptible to drug resistance. Our study aims to evaluate the bioequivalence of generic and brand-name levofloxacin.
METHODS
The pharmacokinetic (PK) parameters (C, AUC, T, and t), pharmacodynamic (PD) parameters (in vitro antibacterial activity and the inhibition of resistant mutation), and PK/PD analysis (the probability of target attainment; the cumulative fraction of response) calculated by Monte Carlo simulation were investigated.
RESULTS
Our results demonstrated that compared with generics, brand-name levofloxacin not only had higher drug content, it also showed higher antimicrobial susceptibility, higher resistance to mutation ability, and higher percentage of each dosage interval wherein plasma concentration of antimicrobial agents exceeded the MPC (mutant prevention concentration to prevent the mutation of 90% strains) against various clinical isolates. Although the differences in AUC between brand-name levofloxacin and generics were not statistically significant (P > 0.05, F test), Monte Carlo simulation results showed cumulative fraction of response values for PK/PD of brand-name medications were higher than generics.
CONCLUSION
Our results indicated that PK or PD equivalence did not imply therapeutic equivalence; thus, we suggest including PK/PD analysis in the bioequivalence evaluation system, which benefits prediction of clinical outcome with high application value.
Topics: Levofloxacin; Monte Carlo Method; Anti-Bacterial Agents; Fluoroquinolones; Anti-Infective Agents
PubMed: 36948495
DOI: 10.1016/j.jgar.2023.03.002 -
Antimicrobial Resistance and Infection... Aug 2020Fluoroquinolone resistance in Pseudomonas aeruginosa typically arises through site-specific mutations and overexpression of efflux pumps. In this study, we investigated...
Fluoroquinolone resistance in Pseudomonas aeruginosa typically arises through site-specific mutations and overexpression of efflux pumps. In this study, we investigated the dynamics of different resistance mechanisms in P. aeruginosa populations that have evolved under fluoroquinolone pressure, as well as the interactions between these mechanisms in evolutionary trajectories. Bacteria of strain ATCC27853 were selected under different concentrations of ciprofloxacin and levofloxacin for six parallel lineages, followed by amplification of four target genes in the quinolone-resistance determining region (QRDR) and Sanger sequencing to identify the mutations. The expression of four efflux pump proteins was evaluated by real-time polymerase chain reaction using the relative quantitation method, with the ATCC27853 strain used as a control. We found that ciprofloxacin killed P. aeruginosa sooner than did levofloxacin. Further, we identified five different mutations in three subunits of QRDRs, with gyrA as the main mutated gene associated with conferring fluoroquinolone resistance. Additionally, we found a larger number of mutations appearing at 2 mg/L and 4 mg/L of ciprofloxacin and levofloxacin, respectively. Moreover, we identified the main efflux pump being expressed as MexCD-OprJ, with initial overexpression observed at 0.25 mg/L and 0.5 mg/L of ciprofloxacin and levofloxacin, respectively. These results demonstrated gyrA mutation and MexCD-OprJ overexpression as the primary mechanism conferring ciprofloxacin and levofloxacin resistance in P. aeruginosa. In addition, we also show that ciprofloxacin exhibited a stronger ability to kill the bacteria while potentially rendering it more susceptible to resistance.
Topics: Anti-Bacterial Agents; Ciprofloxacin; Drug Resistance, Bacterial; Fluoroquinolones; Levofloxacin; Membrane Transport Proteins; Microbial Sensitivity Tests; Mutation; Pseudomonas aeruginosa
PubMed: 32758289
DOI: 10.1186/s13756-020-00793-8 -
Diagnostic Microbiology and Infectious... Jul 2023Gepotidacin is a novel agent in development for treatment of gonorrhea and uncomplicated urinary tract infection. This study determined the effect of urine on the in...
Analysis of the effect of urine on the in vitro activity of gepotidacin and levofloxacin against Escherichia coli, Staphylococcus epidermidis, and Staphylococcus saprophyticus.
Gepotidacin is a novel agent in development for treatment of gonorrhea and uncomplicated urinary tract infection. This study determined the effect of urine on the in vitro activity of gepotidacin and levofloxacin against relevant bacteria. Study strains were tested by Clinical and Laboratory Standards Institute broth microdilution and with method variations: CAMHB with 25%, 50%, 100% urine and pH adjusted 100% urine. Mean dilution difference (DD) of urine minimum inhibitory concentration (MICs) were <1 dilution of CAMHB MICs with some exceptions: Gepotidacin mean DD: Escherichia coli and Staphylococcus saprophyticus 100% urine (1.5 and 1.2, respectively) and S. saprophyticus pH 7.3 and 8.1 adjusted 100% urine (1.5 and 1.4, respectively); Levofloxacin mean DD: S. saprophyticus pH 7.3 adjusted 100% urine (1.5) and all species pH 8.1 adjusted 100% urine (1.2-1.8). Effects of urine on gepotidacin and levofloxacin MICs was minimal and not inclusive of all strains. Further analysis is warranted to fully assess the impact of urine on gepotidacin activity.
Topics: Humans; Levofloxacin; Anti-Bacterial Agents; Staphylococcus saprophyticus; Staphylococcus epidermidis; Escherichia coli; Microbial Sensitivity Tests
PubMed: 37201401
DOI: 10.1016/j.diagmicrobio.2023.115946 -
The American Journal of Case Reports Mar 2018BACKGROUND Levofloxacin covers a broad spectrum of pathogens and is readily prescribed by clinicians. Hepatotoxicity is a known but unusual complication of...
BACKGROUND Levofloxacin covers a broad spectrum of pathogens and is readily prescribed by clinicians. Hepatotoxicity is a known but unusual complication of levofloxacin use. Here, we present a case of severe transaminitis caused by levofloxacin. CASE REPORT A young man in his thirties with a history of asthma, chronic alcoholism, methamphetamine intravenous drug abuse (IVDA), and non-compliant insulin-dependent diabetes mellitus (IDDM) presented to an emergency department with suicidal ideation. Vital signs were stable and the patient was noted to have cellulitis of the right forearm, for which cultures were drawn, and he received IV clindamycin. He was admitted to behavioral medicine for further care. Blood cultures were positive for gram-negative rods and he was transferred to the medicine ward. Cultures eventually grew Brevundimonas diminuta. Clindamycin was discontinued and he was started on levofloxacin. Transaminase levels measured soon after levofloxacin administration showed aminotransferase levels raised to approximately 50 times baseline within a few days. Levofloxacin was discontinued due to concern about drug-induced hepatotoxicity. After discontinuation, transaminase levels decreased immediately. Work-up for other causes of transaminitis revealed no other etiology. CONCLUSIONS Clinicians should remain mindful that levofloxacin can induce hepatotoxicity in rare cases. In patients presenting with acute liver injury who have recently taken levofloxacin, it would be wise to remain cognizant of the possibility of levofloxacin-induced hepatotoxicity.
Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Humans; Levofloxacin; Liver; Male; Young Adult
PubMed: 29523775
DOI: 10.12659/ajcr.907440 -
International Journal of Molecular... Nov 2021Introducing new drugs for clinical application is a very difficult, long, drawn-out, and costly process, which is why drug repositioning is increasingly gaining in...
INTRODUCTION
Introducing new drugs for clinical application is a very difficult, long, drawn-out, and costly process, which is why drug repositioning is increasingly gaining in importance. The aim of this study was to analyze the cytotoxic properties of ciprofloxacin and levofloxacin on bladder and prostate cell lines in vitro.
METHODS
Bladder and prostate cancer cell lines together with their non-malignant counterparts were used in this study. In order to evaluate the cytotoxic effect of both drugs on tested cell lines, MTT assay, real-time cell growth analysis, apoptosis detection, cell cycle changes, molecular analysis, and 3D cultures were examined.
RESULTS
Both fluoroquinolones exhibited a toxic effect on all of the tested cell lines. In the case of non-malignant cell lines, the cytotoxic effect was weaker, which was especially pronounced in the bladder cell line. A comparison of both fluoroquinolones showed the advantage of ciprofloxacin (lower doses of drug caused a stronger cytotoxic effect). Both fluoroquinolones led to an increase in late apoptotic cells and an inhibition of cell cycle mainly in the S phase. Molecular analysis showed changes in , , , and expression in tested cell lines following incubation with ciprofloxacin and levofloxacin. The downregulation of topoisomerase II genes ( and ) was noticed. Three-dimensional (3D) cell culture analysis confirmed the higher cytotoxic effect of tested fluoroquinolone against cancer cell lines.
CONCLUSIONS
Our results suggest that both ciprofloxacin and levofloxacin may have great potential, especially in the supportive therapy of bladder cancer treatment. Taking into account the low costs of such therapy, fluoroquinolones seem to be ideal candidates for repositioning into bladder cancer therapeutics.
Topics: Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Cell Culture Techniques, Three Dimensional; Cell Cycle; Cell Proliferation; Ciprofloxacin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Levofloxacin; Topoisomerase II Inhibitors; Tumor Cells, Cultured; Urogenital Neoplasms
PubMed: 34769400
DOI: 10.3390/ijms222111970