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Iranian Journal of Microbiology Apr 2024is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the...
BACKGROUND AND OBJECTIVES
is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the antibacterial and antibiofilm effects of diclofenac and levofloxacin/diclofenac combination against levofloxacin resistant isolates.
MATERIALS AND METHODS
Minimum inhibitory concentration was determined using broth microdilution method for levofloxacin, diclofenac, and levofloxacin/diclofenac combination. Biofilm forming capacity and biofilm inhibition assay were determined. Relative gene expression was measured for efflux pump genes; , and genes and biofilm related genes , and without and with diclofenac and the combination.
RESULTS
Diclofenac demonstrated MIC of 1 mg/ml. The combination-with ½ MIC diclofenac-showed synergism where levofloxacin MIC undergone 16-32 fold decrease. All the isolates that overexpressed and showed a significant decrease in gene expression in presence of diclofenac or the combination. The mean percentage inhibition of biofilm formation with diclofenac and the combination was 40.59% and 46.49%, respectively. This agreed with biofilm related genes expression investigations.
CONCLUSION
Diclofenac showed an antibacterial effect against The combination showed synergism, significant reduction in biofilm formation and in the relative level of gene expression. Furthermore, it can potentiate the levofloxacin activity or revert its resistance.
PubMed: 38854979
DOI: 10.18502/ijm.v16i2.15349 -
Iranian Journal of Microbiology Apr 2024Antibiotic resistance within the poultry sector presents a considerable health concern due to treatment inefficacy and resistance transmission to humans and the...
BACKGROUND AND OBJECTIVES
Antibiotic resistance within the poultry sector presents a considerable health concern due to treatment inefficacy and resistance transmission to humans and the environment. The investigation of plasmid-mediated quinolone resistance (PMQR) in acknowledged for its role in advancing resistance, remains inadequately studied in Iranian poultry. This study aimed to evaluate PMQR gene prevalence as well as to determine correlation between resistance phenotype and genotype in obtained from poultry colibacillosis.
MATERIALS AND METHODS
A collection of 100 isolates from the viscera of broilers suspected to colibacillosis was assessed. Using the Kirby-Bauer disk diffusion method, antimicrobial susceptibility tests were conducted for ofloxacin, nalidixic acid, levofloxacin, ciprofloxacin, and ampicillin. Additionally, PCR was employed to screen for and genes.
RESULTS
Among the analyzed isolates, 51% demonstrated resistance to at least one of the tested antibiotics, with 17% exhibiting resistance to four different antibiotics. Nalidixic acid displayed the highest resistance rate at 48%, while ampicillin had the lowest at 16%. PMQR genes were detected in 28% of the isolates, with being the most prevalent at 14%, followed by in 13%, and in 7%.
CONCLUSION
The study underscores the vital need for careful antibiotic usage in poultry to curb the emergence of antibiotic-resistant bacteria. The results illuminate the prevalence of PMQR genes and their association with resistance trends in Iranian poultry, forming a pivotal basis for forthcoming approaches to combat antibiotic resistance within the poultry sector.
PubMed: 38854977
DOI: 10.18502/ijm.v16i2.15352 -
RSC Advances Jun 2024[This corrects the article DOI: 10.1039/D4RA02144D.].
Correction: Characterization of chitosan- and β-cyclodextrin-modified forms of magnesium-doped hydroxyapatites as enhanced carriers for levofloxacin: loading, release, and anti-inflammatory properties.
[This corrects the article DOI: 10.1039/D4RA02144D.].
PubMed: 38854835
DOI: 10.1039/d4ra90068e -
Langmuir : the ACS Journal of Surfaces... Jun 2024The design of single-atom nanozymes with dual active sites to increase their activity and for the detection and degradation of contaminants is rare and challenging. In...
The design of single-atom nanozymes with dual active sites to increase their activity and for the detection and degradation of contaminants is rare and challenging. In this work, a single-atom nanozyme (FeCu-NC) based on a three-dimensional porous Fe/Cu dual active site was developed as a colorimetric sensor for both the quantitative analysis of isoniazid (INH) and the efficient degradation of levofloxacin (LEV). FeCu-NC was synthesized using a salt template and freeze-drying method with a three-dimensional hollow porous structure and dual active sites (Fe-N and Cu-N). In terms of morphology and structure, FeCu-NC exhibits excellent peroxidase-like activity and catalytic properties. Therefore, a colorimetric sensor was constructed around FeCu-NC for sensitive and rapid quantitative analysis of INH with a linear range of 0.9-10 μM and a detection limit as low as 0.3 μM, and the sensor was successfully applied to the analysis of INH in human urine. In addition, FeCu-NC promoted the efficient degradation of LEV by peroxymonosulfate activation, with a degradation rate of 90.4% for LEV at 30 min. This work sheds new light on the application of single-atom nanozymes to antibiotics for colorimetric sensing and degradation.
Topics: Isoniazid; Levofloxacin; Iron; Copper; Humans; Peroxidase; Colorimetry; Nanostructures; Catalysis
PubMed: 38853520
DOI: 10.1021/acs.langmuir.4c01166 -
Journal of Global Antimicrobial... Jun 2024Despite the increasing reports of bla in Enterobacterales in Brazil, comprehensive whole genome sequencing (WGS) data remains scarce. To address this knowledge gap, our...
OBJECTIVE
Despite the increasing reports of bla in Enterobacterales in Brazil, comprehensive whole genome sequencing (WGS) data remains scarce. To address this knowledge gap, our study focuses on the characterization of the genome of an NDM-1-producing Klebsiella quasipneumoniae subsp. quasipneumoniae (KQPN) clinical strain isolated in Brazil.
METHODS
The antimicrobial susceptibility profile of the A-73.113 strain was performed by agar dilution or broth microdilution following the BrCAST/EUCAST recommendations. WGS was performed using the Illumina® NextSeq platform and the generated reads were assembled using the SPAdes software. The sequences obtained were submitted to the bioinformatics pipelines to determine the sequence type, resistome, plasmidome, and virulome.
RESULTS
The A-73.113 strain was identified as KQPN and was susceptible to polymyxins (MICs, ≤0.25 µg/mL), tigecycline (MIC, 0.5 µg/mL), ciprofloxacin (MIC, 0.5 µg/mL), and levofloxacin (MIC, 1 µg/mL). WGS analysis revealed the presence of genes conferring resistance to β-lactams (bla, bla, bla, bla, bla), aminoglycosides [aph(3')-VI, aadA1, aac(6')-Ib], and fluoroquinolones (oqxAB, qnrS1, aac(6')-Ib-cr]. Additionally, it was verified the presence of the plasmid replicons Col(pHAD28), IncFIA(HI1), IncFIB(K) (pCAV1099-114), IncFIB(pQil), and IncFII(K), as well as virulence-encoding genes: fimABCDEFGHIK (type 1 fimbria), pilW (type IV pili), iutA (aerobactin), entABCDEFS/fepABCDG/fes (Ent siderophores), iroE (salmochelin), and allABCDRS (allantoin utilization). Furthermore, we found that A-73.113 strain belongs to ST1040.
CONCLUSION
Here we report the genomic characteristics of an NDM-1-producing KQPN ST1040 strain isolated from blood culture in Brazil. These data will enhance our comprehension of how this species contributes to the acquisition and dissemination of bla in Brazilian nosocomial settings.
PubMed: 38852850
DOI: 10.1016/j.jgar.2024.05.022 -
International Journal of Biological... Jun 2024Human serum albumin (HSA) effectively binds to compounds having different molecular weight and thus facilitates their distribution in the living organisms. Thus, the...
Human serum albumin (HSA) effectively binds to compounds having different molecular weight and thus facilitates their distribution in the living organisms. Thus, the binding interactions between a potential antibacterial drug (levofloxacin) and synthesized choline based levofloxacinate conjugates with HSA have been explored. The binding efficacy and mechanism were explored by utilizing different spectroscopic techniques; UV-Visible, steady state fluorescence, time resolved fluorescence and esterase-like activity. The interactions between the ligands and protein were electrostatic as well as hydrophobic in nature. The influence of different ligands having different alkyl chain shows quenching of the fluorescence emission of HSA. The spontaneous binding/quenching of HSA with ligands was static in nature, validated by steady state and time resolved fluorescence spectroscopy. Also, the impact of these ligands on the conformation of the native HSA structure was evaluated by using circular dichroism spectroscopy. In combination to the structural change study, the native protein functionality was observed (in terms of 'esterase-like activity') which has been found to be on lower side due to ligand binding. Further, we have performed the reverse study to check the impact of HSA on the fluorescent fluoroquinolone drug. The current study may prove helpful in elucidating the chemico-biological interactions which may prove useful in the pharmaceuticals, pharmacology, and different biochemistry fields.
PubMed: 38852730
DOI: 10.1016/j.ijbiomac.2024.133011 -
International Journal of Antimicrobial... Jun 2024Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3 multicentre, randomised, double-blind, double-dummy,...
A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate versus levofloxacin for community-acquired pneumonia in adult patients.
BACKGROUND
Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3 multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin versus levofloxacin for treatment of community-acquired pneumonia (CAP) in adult patients.
METHODS
The eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at test of cure (TOC) visit in the modified intent-to-treat (mITT) population. The efficacy and safety were also compared between nemonoxacin and levofloxacin in terms of secondary efficacy and safety endpoints.
RESULTS
Overall, 525 patients were randomised and treated with nemonoxacin (n=349) or levofloxacin (n=176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P> 0.05). The clinical efficacy of nemonoxacin was noninferior to levofloxacin in treatment of CAP. Nemonoxacin achieved microbiological success rate of 88.8% (95/107), while levofloxacin achieved 87.8% (43/49) (P > 0.05) at TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in nemonoxacin group and 22.2% in levofloxacin group, mostly local reactions at the infusion site, nausea, elevated ALT/AST, and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin.
CONCLUSIONS
Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and noninferior to levofloxacin for treating CAP in adult patients.
PubMed: 38851462
DOI: 10.1016/j.ijantimicag.2024.107235 -
European Journal of Pharmaceutics and... Jun 2024Immune rejection remains the major cause of corneal graft failure. Immunosuppressants (such as rapamycin; RAPA) adjunctive to antibiotics (such as levofloxacin...
Immune rejection remains the major cause of corneal graft failure. Immunosuppressants (such as rapamycin; RAPA) adjunctive to antibiotics (such as levofloxacin hydrochloride; Lev) are a clinical mainstay after corneal grafts but suffer from poor ocular bioavailability associated with severe side effects. In this study, we fabricated a Lev@RAPA micelle loaded cationic peptide-based hydrogel (NapFFKK) as a dual-drug delivery system by integrating RAPA micelles with Lev into a cationic NapFFKK hydrogel to potentially reduced the risk of corneal graft rejection. The properties of the resulting hydrogels were characterized using transmission electronmicroscopy and rheometer. Lev@RAPA micelles loaded NapFFKK hydrogel provided sustained in vitro drug release without compromising their inherent pharmacological activities. Topical instillation of Lev@RAPA micelles loaded NapFFKK hydrogel resulted in the great ocular tolerance and extended precorneal retention over 60min, thus significantly enhancing the ocular bioavailability of both Lev and RAPA. Overall, such dual-drug delivery system might be a promising formulation for the suppression of corneal graft failure.
PubMed: 38851460
DOI: 10.1016/j.ejpb.2024.114351 -
Journal of Global Antimicrobial... Jun 2024Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKp) poses a significant threat to public health. This study reports an infection related to hv-CRKp in a...
OBJECTIVES
Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKp) poses a significant threat to public health. This study reports an infection related to hv-CRKp in a premature infant and reveals its colistin resistance and evolutionary mechanisms within the host.
METHODS
Three KPC-producing CRKp strains were isolated from a patient with sepsis and CRKp osteoarthritis who had been receiving colistin antimicrobial therapy. The minimum inhibitory concentrations (MICs) of Ceftazidime,Ceftazidime-Avibactam(CAZ-AVI),Meropenem,Imipenem,Tigecycline,Amikacin,Minocycline,Sulfamethoxazole/Trimethoprim,Ciprofloxacin,Levofloxacin,Aztreonam,Cefepime,Cefoperazone/Sulbactam,Piperacillin/Tazobactam and colistin were determined using the microbroth dilution method.The whole-genome sequencing analysis was conducted to determine the STs, virulence genes, and antibiotic resistance genes of three CRKp strains.
RESULTS
Whole-genome sequencing revealed that all three CRKp strains belonged to the sequence type (ST) 11 clone and carried a plasmid encoding blaKPC-2. The three strains all possessed the iucABCDiutA virulence cluster, peg-344 gene, and rmpA/rmpA2 genes, defining them as hv-CRKp. Further experiments and whole-genome analysis revealed that a strain of Kp has developed resistance to colistin. The mechanism found to be responsible for the colistin resistance was a deletion mutation of approximately 9000 bp including mgrB gene.
CONCLUSION
This study characterizes the colistin resistance of ST11 clone hv-CRKp during colistin treatment and its rapid evolution within the host.
PubMed: 38849114
DOI: 10.1016/j.jgar.2024.05.021 -
International Journal of Pharmaceutics Jun 2024Delivering novel antimycobacterial agents through the pulmonary route using nanoparticle-based systems shows promise for treating diseases like tuberculosis. However,...
Delivering novel antimycobacterial agents through the pulmonary route using nanoparticle-based systems shows promise for treating diseases like tuberculosis. However, creating dry powder inhaler (DPI) with suitable aerodynamic characteristics while preserving nanostructure integrity and maintaining bioactivity until the active ingredient travels deeply into the lungs is a difficult challenge. We developed DPI formulations containing levofloxacin-loaded solid lipid nanoparticles (SLNs) via spray-drying technique with tailored aerosolization characteristics for effective inhalation therapy. A range of biophysical techniques, including transmission electron microscopy, confocal microscopy, and scanning electron microscopy were used to measure the morphologies and sizes of the spray-dried microparticles that explored both the geometric and aerodynamic properties. Spray drying substantially reduced the particle sizes of the SLNs while preserving their nanostructural integrity and enhancing aerosol dispersion with efficient mucus penetration. Despite a slower uptake rate compared to plain SLNs, the polyethylene glycol modified formulations exhibited enhanced cellular uptake in both A549 and NR8383 cell lines. The percent viability of Mycobacterium bovis had dropped to nearly 0 % by day 5 for both types of SLNs. Interestingly, the levofloxacin-loaded SLNs demonstrated a lower minimum bactericidal concentration (0.25 µg/mL) compared with pure levofloxacin (1 µg/mL), which indicated the formulations have potential as effective treatments for tuberculosis.
PubMed: 38848797
DOI: 10.1016/j.ijpharm.2024.124309