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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 -
AAPS PharmSciTech Nov 2023Fatty acids, including medium-chain saturated and polyunsaturated fatty acids, are known for their broad health benefits, including antimicrobial activity. Through their...
Fatty acids, including medium-chain saturated and polyunsaturated fatty acids, are known for their broad health benefits, including antimicrobial activity. Through their green properties, deep eutectic systems have been heralded as having the potential to be at the forefront of pharmaceutical applications. In this work, capric acid and geranic acid, two examples of medium-chain saturated and polyunsaturated fatty acids, were employed to enhance the pharmaceutical properties and the antibacterial activity of levofloxacin. To this end, levofloxacin formulations with either capric or geranic acid were prepared and characterized using appropriate techniques. Levofloxacin was utilized to create innovative deep eutectic systems in conjunction with capric acid at three different molar ratios: 1:9, 2:8 and 3:7. This was confirmed through a rigorous analysis involving nuclear magnetic resonance, infrared spectroscopy and differential scanning calorimetry. Furthermore, it is noteworthy that geranic acid demonstrated an impressive threefold improvement in levofloxacin's solubility compared to its solubility in aqueous solutions. The antibacterial activity of the novel combinations of levofloxacin with either fatty acid was evaluated using a checkerboard titration assay. Gratifyingly, both formulations exhibited synergistic effects against a panel of levofloxacin-sensitive and resistant Gram-negative bacteria. In conclusion, the observed superior antibacterial activity of levofloxacin illuminates the potential use of fatty acid-based formulations and deep eutectic systems as green and innovative strategies to combat the global antimicrobial resistance problem.
Topics: Levofloxacin; Fatty Acids; Anti-Bacterial Agents; Decanoic Acids; Fatty Acids, Unsaturated; Pharmaceutical Preparations; Solvents
PubMed: 38030950
DOI: 10.1208/s12249-023-02701-w -
Journal of Oncology Pharmacy Practice :... Oct 2016Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated... (Review)
Review
INTRODUCTION
Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated guideline on the use of antimicrobial agents in neutropenic patients with cancer indicates that patients who have completed an appropriate treatment course of broad-spectrum antibiotics, with resolution of signs and symptoms of infection but persistent neutropenia, can be de-escalated to oral fluoroquinolone prophylaxis until ANC recovery.
METHODS
The primary objective of this retrospective investigation was to evaluate the safety and efficacy of de-escalating broad-spectrum antibiotics in patients remaining neutropenic after at least 14 days of empiric broadspectrum antibiotics for febrile neutropenia compared to patients continuing broad-spectrum antibiotics until ANC recovery.
RESULTS
There were 16 patients (61.5%) in the comparator group who met the primary endpoint of remaining afebrile and without escalation of antibiotics for at least 72 hours after 14 days of broad-spectrum antibiotics and 21 patients (80.7%) in the de-escalation group who met the primary endpoint of remaining afebrile and without reinitiation of broad-spectrum antibiotics for at least 72 hours after de-escalation to levofloxacin therapy (p = 0.11). Mean total duration of broad-spectrum antibiotic therapy was 23.5 ± 1.5 days in the comparator group versus 22.2 ± 1.43 days in the de-escalation group (p = 0.39).
CONCLUSIONS
Results of this investigation indicate that broad-spectrum antibiotics can be safely de-escalated to levofloxacin prophylaxis prior to ANC recovery in select patients. This practice may decrease the duration of broad-spectrum antibiotic exposure and associated complications.
Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Febrile Neutropenia; Female; Humans; Leukocyte Count; Levofloxacin; Male; Middle Aged; Retrospective Studies
PubMed: 26227319
DOI: 10.1177/1078155215597558 -
Colloids and Surfaces. B, Biointerfaces Jul 2022Levofloxacin is the levo-enantiomer of ofloxacin (a fluoroquinolone class of antibacterial drug). Cyclodextrins (CDs) including hydroxypropyl-β-cyclodextrin (HPβCD)...
Levofloxacin is the levo-enantiomer of ofloxacin (a fluoroquinolone class of antibacterial drug). Cyclodextrins (CDs) including hydroxypropyl-β-cyclodextrin (HPβCD) are generally used as a chiral selector for the enantioseparation of some drugs including levofloxacin or as a drug/food nanocarrier for the efficacy improvement of many pharmaceuticals. We hypothesized that the cyclodextrin inclusion is potentially able to further improve the antibacterial activity of levofloxacin. To test this hypothesis, the levofloxacin/HPβCD inclusion complex was prepared by the freeze-drying method and characterized by phase solubility diagram, differential scanning calorimetry (DSC), X-ray diffractometry (XRD), UV-Vis spectrophotometer, and H NMR spectroscopy, confirming the successful HPβCD inclusion of levofloxacin. The in vitro antibacterial effects of HPβCD, levofloxacin, and the levofloxacin/HPβCD inclusion complex against four different bacterial strains in liquid media and on agar plates were determined/compared (an MIC of 0.5-1.0 μg/mL for the inclusion complex compared with that of 1.0-2.0 μg/mL for free levofloxacin in liquid). Moreover, the in vivo antibacterial effects of levofloxacin and levofloxacin/HPβCD inclusion complex were tested by using a skin scald model in mice infected with Staphylococcus aureus, and decreased amounts of both bacteria and leukocytes were detected in scalded skin after the inclusion complex treatment. The data revealed that the levofloxacin/HPβCD inclusion complex had an enhanced antibacterial activity compared with free levofloxacin. It implies that cyclodextrins (e.g. HPβCD) may have a beneficial role when using as a chiral selector or as a drug nanocarrier for levofloxacin and that the levofloxacin/HPβCD inclusion complex has the potential of being developed into a pharmaceutical for antibacterial therapies.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Anti-Bacterial Agents; Calorimetry, Differential Scanning; Cyclodextrins; Levofloxacin; Mice; Solubility
PubMed: 35490541
DOI: 10.1016/j.colsurfb.2022.112514 -
Applied and Environmental Microbiology Jun 2022Bacterial species in the polymicrobial community evolve interspecific interaction relationships to adapt to the survival stresses imposed by neighbors or environmental...
Bacterial species in the polymicrobial community evolve interspecific interaction relationships to adapt to the survival stresses imposed by neighbors or environmental cues. Pseudomonas aeruginosa and Staphylococcus aureus are two common bacterial pathogens frequently coisolated from patients with burns and respiratory disease. Whether the application of commonly used antibiotics influences the interaction dynamics of the two species still remains largely unexplored. By performing a series of on-plate competition assays and RNA sequencing-based transcriptional profiling, we showed that the presence of the cephalosporin antibiotic cefotaxime or the quinolone antibiotic levofloxacin at subinhibitory concentration contributes to selecting P. aeruginosa from the coculture with S. aureus by modulating the quorum-sensing (QS) system of P. aeruginosa. Specifically, a subinhibitory concentration of cefotaxime promotes the growth suppression of S. aureus by P. aeruginosa in coculture. This process may be related to the increased production of the antistaphylococcal molecule pyocyanin and the expression of , which is the central regulatory gene of the P. aeruginosa QS hierarchy. On the other hand, subinhibitory concentrations of levofloxacin decrease the competitive advantage of P. aeruginosa over S. aureus by inhibiting the growth and the QS system of P. aeruginosa. However, signaling of P. aeruginosa can be activated instead to overcome S. aureus. Therefore, this study contributes to understanding the interaction dynamics of P. aeruginosa and S. aureus during antibiotic treatment and provides an important basis for studying the pathogenesis of polymicrobial infections. Increasing evidence has demonstrated the polymicrobial characteristics of most chronic infections, and the frequent communications among bacterial pathogens result in many difficulties for clinical therapy. Exploring bacterial interspecific interaction during antibiotic treatment is an emerging endeavor that may facilitate the understanding of polymicrobial infections and the optimization of clinical therapies. Here, we investigated the interaction of cocultured P. aeruginosa and S. aureus with the intervention of commonly used antibiotics in clinic. We found that the application of subinhibitory concentrations of cefotaxime and levofloxacin can select P. aeruginosa in coculture with S. aureus by modulating P. aeruginosa QS regulation to enhance the production of antistaphylococcal metabolites in different ways. This study emphasizes the role of the QS system in the interaction of P. aeruginosa with other bacterial species and provides an explanation for the persistence and enrichment of P. aeruginosa in patients after antibiotic treatment and a reference for further clinical therapy.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Cefotaxime; Coculture Techniques; Coinfection; Humans; Levofloxacin; Pseudomonas Infections; Pseudomonas aeruginosa; Quorum Sensing; Staphylococcal Infections; Staphylococcus aureus
PubMed: 35638844
DOI: 10.1128/aem.00592-22 -
Journal of Biochemical and Molecular... Jun 2023Levofloxacin, the optical S-(-) isomer of ofloxacin, is a broad-spectrum antibacterial agent widely used to control various infections caused by Gram-positive and...
Levofloxacin, the optical S-(-) isomer of ofloxacin, is a broad-spectrum antibacterial agent widely used to control various infections caused by Gram-positive and Gram-negative bacteria. While the COOH group is necessary for antibacterial activity, its modification can offer anticancer activity to the fluoroquinolone framework. Therefore, several levofloxacin carboxamides 11a-j and 12 containing 5-substituted-1,3,4-thiadiazole residue were synthesized and screened in vitro for their anticancer activity. The in vitro MTT viability assay revealed that the most compounds had significant activity against cancer cells MCF-7, A549, and SKOV3. In particular, the 3-chloro- and 4-fluoro- benzyl derivatives (11b and 11h), with IC values of 1.69-4.76 μM were as potent as or better than doxorubicin. It should be noted that the mother quinolone levofloxacin showed no activity on the tested cancer cell lines. The SAR analysis demonstrated that the 3-chloro or 4-fluoro substituent on the S-benzyl moiety had positive effect on the activity. Further in vitro evaluations of the most promising compounds 11b and 11h by flow cytometric analysis and comet test revealed the ability of compounds in the induction of apoptosis and blockage of the cell proliferation at the G1-phase by nuclear fragmentation and DNA degradation in cancer cells. The obtained results demonstrated that the alteration of 6-COOH functional group in the levofloxacin structure and conjugation with a proper heterocyclic pharmacophore is a good strategy to obtain new anticancer agents.
Topics: Anti-Bacterial Agents; Levofloxacin; Quinolones; Cytotoxins; Structure-Activity Relationship; Gram-Negative Bacteria; Gram-Positive Bacteria; Cell Proliferation; Antineoplastic Agents; Drug Screening Assays, Antitumor; Molecular Structure
PubMed: 36843476
DOI: 10.1002/jbt.23334 -
Journal of Ayub Medical College,... 2023Helicobacter pylori (H. pylori) is a gram-negative bacterium which usually resides in the mucoid lining of the stomach and may cause different gastric pathologies e.g.,... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy And Cost-Effectiveness, Comparison Of 7-Days Vonoprazan Versus 14-Days Esomeprazole Based Triple Therapies For Treating Helicobacter Pylori Infection In Pakistani Population: A Randomized Clinical Trial.
BACKGROUND
Helicobacter pylori (H. pylori) is a gram-negative bacterium which usually resides in the mucoid lining of the stomach and may cause different gastric pathologies e.g., Gastritis, peptic ulcer disease, adenocarcinoma of the gastric system and mucoid associated lymphoma (MALT). The Objective was to compare the effect of 7-days Vonoprazan based triple therapy and 14-days Esomeprazole based triple therapy on eradication rate, compliance and cost effectiveness in Helicobacter pylori infected patients.
METHODS
This clinical trial was performed in the Department of Pharmacology Army Medical College, National University of Medical Sciences (NUMS) in collaboration with the Gastroenterology Department, Pak Emirates Military Hospital (PEMH) Rawalpindi from December 2022 to March 2023. A total of one hundred and twenty-two patients with dyspepsia symptoms and yielding lab results positive for Helicobacter pylori by stool antigen test were enrolled in the study. They were randomly allocated into two groups. The Esomeprazole group received 14 days of triple therapy orally with Esomeprazole 20 mg twice a day; Amoxicillin 1000 mg twice a day; and Levofloxacin 500 mg one time a day. The comparative Vonoprazan group was given 7-days triple therapy orally with Vonoprazan 20 mg twice a day; Amoxicillin 1000 mg twice a day; and Levofloxacin 500 mg one time a day. Eradication success was evaluated by stool antigen test four weeks later, as counted from the start of treatment. compliance and cost-effectiveness of both therapies were also assessed.
RESULTS
The eradication rate was (95.1%) in the Vonoprazan group with 58 out of 61 patients negative for H. pylori and (93.1%) in Esomeprazole group with 54 patients out of 58 yielding a negative result demonstrating p-value of 0.64. Compliance was 95.0% in the Esomeprazole group with p-value of 0.07. Cost effective ratio for Vonoprazan triple therapy was lower (731.8PKR) than the Esomeprazole group.
CONCLUSION
One two-week Vonoprazan regimen demonstrated improved eradication rate, good compliance, and better tolerability in patients with less cost and a half duration of treatment in comparison with two weeks Esomeprazole regimen, attesting that one week Vonoprazan therapy is more cost efficacious in producing better results.
Topics: Humans; Amoxicillin; Anti-Bacterial Agents; Cost-Benefit Analysis; Cost-Effectiveness Analysis; Drug Therapy, Combination; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Levofloxacin; Pakistan; Pyrroles; Sulfonamides; Treatment Outcome
PubMed: 38406904
DOI: 10.55519/JAMC-S4-12110 -
European Journal of Pharmacology Jan 2024Reperfusion therapy is currently the most effective treatment for acute ischemic stroke, but often results in secondary brain injury. Adipocyte fatty acid-binding...
Reperfusion therapy is currently the most effective treatment for acute ischemic stroke, but often results in secondary brain injury. Adipocyte fatty acid-binding protein (A-FABP, FABP4, or aP2) was shown to critically mediate cerebral ischemia/reperfusion (I/R) injury by exacerbating blood-brain barrier (BBB) disruption. However, no A-FABP inhibitors have been approved for clinical use due to safety issues. Here, we identified the therapeutic effect of levofloxacin, a widely used antibiotic displaying A-FABP inhibitory activity in vitro, on cerebral I/R injury and determined its target specificity and action mechanism in vivo. Using molecular docking and site-directed mutagenesis, we showed that levofloxacin inhibited A-FABP activity through interacting with the amino acid residue Asp76, Gln95, Arg126 of A-FABP. Accordingly, levofloxacin significantly inhibited A-FABP-induced JNK phosphorylation and expressions of proinflammatory factors and matrix metalloproteinase 9 (MMP-9) in mouse primary macrophages. In wild-type mice with transient middle cerebral artery occlusion, levofloxacin substantially mitigated BBB disruption and neuroinflammation, leading to reduced cerebral infarction, alleviated neurological outcomes, and improved survival. Mechanistically, levofloxacin decreased MMP-9 expression and activity, and thus reduced degradation of extracellular matrix and endothelial tight junction proteins. Importantly, the BBB- and neuro-protective effects of levofloxacin were abolished in A-FABP or MMP-9 knockout mice, suggesting that the therapeutic effects of levofloxacin highly depended on specific targeting of the A-FABP-MMP-9 axis. Overall, our study demonstrates that levofloxacin alleviates A-FABP-induced BBB disruption and neural tissue injury following cerebral I/R, and unveils its therapeutic potential for the treatment of ischemic stroke.
Topics: Animals; Mice; Rats; Blood-Brain Barrier; Brain Ischemia; Infarction, Middle Cerebral Artery; Ischemic Stroke; Levofloxacin; Matrix Metalloproteinase 9; Molecular Docking Simulation; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury; Fatty Acid-Binding Proteins
PubMed: 38113968
DOI: 10.1016/j.ejphar.2023.176275 -
Journal of Ethnopharmacology Feb 2024Maxing Shigan Decoction (MXSG) is a traditional Chinese Medicine effectively used in respiratory infections and bacterial pneumonia. However, the mechanism of MXSG...
ETHNOPHARMACOLOGICAL RELEVANCE
Maxing Shigan Decoction (MXSG) is a traditional Chinese Medicine effectively used in respiratory infections and bacterial pneumonia. However, the mechanism of MXSG treating acute Pseudomonas aeruginosa (P. aeruginosa) pneumonia is still unclear.
AIM OF THE STUDY
This study aimed to investigate the therapeutic effects of MXSG on acute P. aeruginosa pneumonia and explore its potential mechanisms.
MATERIALS AND METHODS
HPLC-MS analysis was performed to analyze the chemical composition. Antibacterial effects in vitro were evaluated by minimum inhibitory concentration (MIC). Forty-five male BALB/c mice were divided into control group, model group, levofloxacin group, MXSG-L (7.7 g/kg/d), and MXSG-H group (15.4 g/kg/d). Mice were intranasal instillation with P. aeruginosa to induce acute P. aeruginosa pneumonia model. Levofloxacin and MXSG were administered by oral gavage once a day. After 3 days of treatment, the lung index measurement, micro-CT, arterial blood gas analysis, bacteria load determination, and HE staining were performed. Network pharmacological analysis and transcriptome sequencing were employed to predict the potential mechanisms of MXSG on bacterial pneumonia. The expressions of relating genes were detected by immunofluorescence, Western blot, and RT-PCR.
RESULTS
In vitro, MIC of P. aeruginosa is greater than 500 mg/mL. In the treatment of acute P. aeruginosa pneumonia model, MXSG significantly improved body weight loss, lung index, and pulmonary lesions. MXSG treatment also reduced the bacterial load and ameliorated oxygen saturation significantly. Transcriptomes, immunofluorescence, Western blot, and RT-PCR analysis showed MXSG treating acute P. aeruginosa pneumonia through the IL-17 signaling pathway and HIF-1α/IL-6/STAT3 signaling pathway.
CONCLUSIONS
We demonstrated the efficacy and mechanism of MXSG in the treatment of acute P. aeruginosa pneumonia, which provides a scientific basis for its clinical application.
Topics: Male; Mice; Animals; Pseudomonas aeruginosa; Drugs, Chinese Herbal; Levofloxacin; Lung; Mice, Inbred BALB C; Pneumonia, Bacterial
PubMed: 37984543
DOI: 10.1016/j.jep.2023.117424