Cefixime loaded bare and functionalized halloysite nanocarriers and their biomedical applications.

Effective drug delivery for is the foremost requirement for the complete recovery of the disease. Nanomedicine and nanoengineering has provided so many spaces and ideas for the drug delivery design, whether controlled, targeted, or sustained. Different types of nanocarriers or nanoparticles are aggressively designed for the drug delivery applications. Clay minerals are identified as a one of the potential nanocarrier for the drug delivery. Owing to their biocompatibility and very low cytotoxicity, clay minerals showing effective therapeutic applications. In the present investigation, clay mineral, i.e., Halloysite nano tubes are utilized as a nanocarrier for the delivery of antibiotic cefixime (CFX), a third-generation cephalosporin. The HNT was first functionalized with the sulfuric acid and then further treated with the 3-(aminopropyl)triethoxysilane (APTES). The drug is loaded on three different classifications of HNTs, i.e., Bare-CFX-HNT, Acid-CFX-HNT, and APTES-CFX-HNT and their comparative analysis is established. Different characterization techniques such as X-ray diffractometry (XRD), Fourier transform infra-red (FT-IR), Transmission electron microscopy TEM), Brunauer-Emmett-Teller (BET), adsorption studies, and Thermogravimetric analysis (TGA) were performed to evaluate their chemical, structural, morphological, and thermal properties. TGA confirmed the encapsulation efficiency of Bare-CFX-HNT, Acid-CFX-HNT, and APTES-CFX-HNT as 42.65, 52.19, and 53.43%, respectively. Disk diffusion and MTT assay confirmed that the drug loaded HNTs have potential antibacterial activities and less cytotoxicity. The adsorption capacity of CFX with different HNTs are evaluated and Different adsorption and kinetic models have been discussed. Drug release studies shows that APTES-CFX-HNT showing sustained release of cefixime as compared to Bare-CFX-HNT and Acid-CFX-HNT.

Degradation of cefixime by photocatalysis via Ba-doped BiFeO3 nanomaterial using RSM analysis under LED light source.

In the current work, Response Surface Methodology (RSM)-a statistical method-is used to optimize procedures like photocatalysis with the least amount of laboratory testing. However, to determine the most effective model for achieving the maximum rate of removal efficiency, the Response Surface Methodology was employed. The Ba-doped BiFeO3 photocatalyst was synthesized by the co-precipitation method, and its intrinsic properties were investigated by utilizing a range of spectroscopic techniques, such as FESEM, EDX, XRD, FTIR, and UV-vis. Herein, four independent factors such as, pH, contact time, pollutant concentration, and catalyst dosage were chosen. The results revealed that under acidic conditions with a contact duration of 2 min, a moderate catalyst dosage, and higher pollutant concentration, a degradation rate of 89.8% was achieved. The regression coefficient (R2) and probability value (P) were determined to be 0.99551 and 0.0301, respectively, therefore confirming the excellent fit of the RSM model. Furthermore, this research investigated the potential photocatalytic degradation mechanisms of cefixime, demonstrating that the removal efficiency of cefixime is greatly influenced by the functional parameters.

Mechanistic insight into the synergistic antimicrobial potential of Fagonia indica Burm.f. extracts with cefixime.

Fagonia indica Burm.f. is known for its anti-infective character and has been studied in the present work as a synergistic remedy against resistant bacterial strains. Initially, phytochemicals were quantified in n-Hexane (n-Hex), ethyl acetate (E.A), methanol (MeOH), and aqueous (Aq.) extracts by Total Phenolic Content (TPC), Total Flavonoid Content (TFC) and Reverse Phase High Performance Liquid Chromatography (RP-HPLC) analysis. Later, after establishing an antibacterial resistance profile for extracts and antibiotics against gram-positive and gram-negative strains, synergism was evaluated in combination with cefixime through time-kill kinetics and bacterial protein estimation studies. Topographic images depicting synergism were obtained by scanning electron microscopy for Methicilin-resistant Staphylococcus aureus (MRSA) and Resistant Escherichia coli (R.E. coli). Results showed the presence of maximum phenolic (28.4 ± 0.67 µg GAE/mg extract) and flavonoid (11 ± 0.42 µg QE/mg extract) contents in MeOH extract. RP-HPLC results also displayed maximum polyphenols in MeOH extract followed by E.A extract. Clinical strains were resistant to cefixime whereas these were moderately inhibited by all extracts (MIC 150-300 µg/ml) except Aq. extract. E.A and n-Hex extracts demonstrated maximum synergism (Fractional inhibitory concentration index (FICI) 0.31) against R.E. coli. The n-Hex extract displayed total synergism against R.P. a with a 4-fold reduction in cefixime dose. Time-kill kinetics showed maximum inhibition of gram-negative bacterial growth from 3 to 12 h when treated at FICI and 2FICI values with > 10-fold reduction of the extracts' dose. All combinations demonstrate > 70 % protein content inhibition with bacterial cell wall disruption in SEM images. Fortunately, FICI concentrations have low hemolytic potential (<5%). Conclusively, F. indica extracts can mitigate antimicrobial resistance against cefixime and can be investigated in detail by in vivo and mechanistic studies.

Antibacterial and anti-biofilm properties of carvacrol alone and in combination with cefixime against Escherichia coli.

BACKGROUND: Plant-derived compounds can be used as antimicrobial agents in medicines and as food preservatives. These compounds can be applied along with other antimicrobial agents to strengthen the effect and/or reduce the required treatment dose. RESULTS: In the present study, the antibacterial, anti-biofilm and quorum sensing inhibitory activity of carvacrol alone and in combination with the antibiotic cefixime against Escherichia coli was investigated. The MIC and MBC values for carvacrol were 250 µg/mL. In the checkerboard test, carvacrol showed a synergistic interaction with cefixime against E. coli (FIC index = 0.5). Carvacrol and cefixime significantly inhibited biofilm formation at MIC/2 (125 and 62.5 µg/mL), MIC/4 (62.5 and 31.25 µg/mL) and MIC/8 (31.25 and 15.625 µg/mL) for carvacrol and cefixime, respectively. The antibacterial and anti-biofilm potential effect of carvacrol confirmed by the scanning electron microscopy. Real-time quantitative reverse transcription PCR revealed significant down-regulation of the luxS and pfs genes following treatment with a MIC/2 (125 µg/mL) concentration of carvacrol alone and of only pfs gene following treatment with MIC/2 of carvacrol in combination with MIC/2 of cefixime (p < 0.05). CONCLUSIONS: Because of the significant antibacterial and anti-biofilm activity of carvacrol, the present study examines this agent as an antibacterial drug of natural origin. The results indicate that in this study the best antibacterial and anti-biofilm properties are for the combined use of cefixime and carvacrol.

Antimicrobial susceptibilities and genomic epidemiology of Neisseria gonorrhoeae in Stockholm, Sweden.

The aim of this study was to investigate the genomic epidemiology and antimicrobial susceptibilities of N. gonorrhoeae isolates in Stockholm, Sweden. In total, 6723 isolates detected in Stockholm, Sweden, from January 2016 to September 2022, were examined for antimicrobial susceptibilities by using E-test. Whole-genome sequencing (WGS) was applied to isolates in sentinel surveillance and isolates resistant to extended-spectrum cephalosporins (ESCs) or high-level azithromycin (HLAzi-R, MIC ≥ 256 mg/L). As sentinel surveillance, consecutive clinical isolates (n = 396) detected every 4th week from January 2021 to September 2022 were enrolled in the study. Of the 6723 isolates investigated, 33 isolates (< 1%) were found to be resistant to cefixime, one of which was co-resistant to ceftriaxone and ciprofloxacin and was detected in September 2022. Ten isolates presented a high level of azithromycin resistance. Resistant rates to ciprofloxacin varied from 32 in 2017 to 68-69% in 2021-2022. Elevated MIC50 and MIC90 of azithromycin were observed over the years. No resistance to spectinomycin was identified. The most frequently occurring MLST in the sentinel surveillance was ST9362 (23%), followed by ST11706 (9%), ST7359 (8%), ST10314 (7%), and ST11422 (6%). The ceftriaxone-resistant isolate belonged to ST8130 and the novel NG-STAR ST4859. Genomic resistance traits found in this strain included mutations in genes mtrR (A39T), parC (S87N), and gyrA (S91F and D95A), as well as the presence of blaTEM-135 and tetM genes. A predominance of ST9362 was observed in Stockholm. The high number of azithromycin and ciprofloxacin-resistant isolates and the emergence of a strain with a novel NG-STAR are of great concern.

In situ preparation of MOF-199 into the carrageenan-grafted-polyacrylamide@Fe3O4 matrix for enhanced adsorption of levofloxacin and cefixime antibiotics from water.

In this research study, a novel method, an in-situ growth approach, to incorporate metal-organic framework (MOF) into carrageenan-grafted- polyacrylamide-Fe3O4 substrate was introduced. Carrageenan-grafted-polyacrylamide-Fe3O4/MOF nanocomposite (kC-g-PAAm@Fe3O4-MOF-199) was fabricated utilizing three stages. In this way, the polyacrylamide (PAAm) was grafted onto the carrageenan (kC) backbone via free radical polymerization in the presence of methylene bisacrylamide (MBA) as cross-linker and Fe3O4 magnetic nanoparticles. Next, the kC-g-PAAm@Fe3O4 was modified by MOF-199 via an in-situ solvothermal approach. Several analyses such as Fourier transform infrared spectroscopy (FT-IR), X-Ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy-Dispersive X-ray Spectroscopy (EDX), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), Brunauer-Emmett-Teller (BET) demonstrated the successful synthesis of kC-g-PAAm@Fe3O4-MOF-199 magnetic hydrogel nanocomposite. The XRD pattern of magnetic hydrogel nanocomposite illustrated characteristic peaks of Fe3O4, neat kC, and MOF-199 with enhanced crystallinity in comparison with kC-g-PAAm@Fe3O4. TGA showed it has a char yield of 24 wt% at 800 °C. VSM confirmed its superparamagnetic behavior (with Ms of 8.04 emu g-1), and the BET surface area of kC-g-PAAm@Fe3O4-MOF-199 was measured at 64.864 m2 g-1, which was higher than that of kC-g-PAAm@Fe3O4 due to the highly porous MOF-199 incorporation with a BET surface area of 905.12 m2 g-1). The adsorption effectiveness of kC-g-PAAm@Fe3O4-MOF-199 for eliminating cephalosporin and quinolones antibiotics, i.e., Cefixime (CFX) and Levofloxacin (LEV) from the aquatic area was considered. Several experimental setups were used to evaluate the efficacy of adsorption, such as solution pH, amount of adsorbent, contact duration, and initial concentration. The maximum adsorption capacity (Qmax) of the prepared magnetic hydrogel nanocomposite was found to be 2000 and 1666.667 mg-1 for LEV and CFX using employing 0.0025 g of adsorbent. The Freundlich isotherm model well described the experimental adsorption data with R2CFX = 0.9986, and R2LEV = 0.9939. And the adsorption kinetic data were successfully represented by the pseudo-second-order model with R2LEV = 0.9949 and R2CFX = 0.9906. Hydrogen bonding, π-π interaction, diffusion, and entrapment in the hydrogel network all contributed to the successful adsorption of both antibiotics onto the kC-g-PAAm@Fe3O4-MOF-199 adsorbent. Other notable physicochemical properties include the three-dimensional structure and availability of the reactive adsorption sites. Moreover, the adsorption/desorption efficacy of magnetic hydrogel nanocomposites was not significantly diminished after four cycles of recovery.

Clinical pharmacokinetics of cefixime: a systematic review.

Cefixime is an antibiotic from the cephalosporin class used to treat various bacterial infections. The purpose of performing this review is to thoroughly evaluate the pharmacokinetic (PK) data on cefiximeFive databases were systematically searched to identify studies on the PK of cefixime.A total of 38 articles meeting the eligibility criteria were included that provide data on concentration-time profiles or PK parameters such as peak plasma and serum concentration (Cmax), area under the curve (AUC), clearance (CL), and time to reach Cmax (tmax). A dose-dependent increase in AUC and Cmax of cefixime was depicted in healthy volunteers. The clearance of cefixime decreased according to the degree of renal insufficiency among haemodialysis patients. A significant difference in CL was found in comparing fasted and fed states. A biphasic decline in serum concentrations of cefixime was reported when it was taken without probenecid.This review compiles all the reports on the PK of cefixime in healthy and really impaired patients; the summarised information can be used to optimise cefixime dosing in different disease states. Moreover, cefixime has increased time above MIC value suggesting that it may be an effective treatment for infections caused by certain pathogens.

Improved catalytic performance of ZnO via coupling with CoFe2O4 and carbon nanotubes: A new, photocatalysis-mediated peroxymonosulfate activation system, applied towards Cefixime degradation.

In this study, a ternary ZnO@spinel cobalt ferrite@carbon nanotube magnetic photocatalyst (ZSCF@CNT) was successfully synthesized and used to activate peroxymonosulfate (PMS) for Cefixime (CFX) antibiotic degradation under UVC irradiation. The morphology, optical, structural, and physicochemical properties of ZSCF@CNT were characterized and analyzed by XPS, XRD, FESEM-EDX, TEM, BET, VSM, UV-vis DRS and PL analysis. The results indicated that the ternary ZSCF@CNT photocatalyst exhibited superior catalytic activity on CFX elimination than that of individual components and binary composite catalysts, in which CFX with was rapidly removed under UVC irradiation and PMS. The effect of operational parameters including initial PMS, catalyst, and CFX concentrations and solution pH on the catalytic activity was investigated in detail; the optimal conditions were: pH: 7.0, catalyst: 0.3 g/L, PMS: 3.0 mM, leading to total CFX (10 mg/L) elimination in ∼20 min. Based on the radical scavenger tests, various radicals and non-radical species including sulfate, hydroxyl and superoxide radicals, singlet oxygen and electrons were involved in the ZSCF@CNT/PMS/UVC system. The high surface area, reduced agglomeration formation and excellent separation of photogenerated electron-hole pairs embodied in ZSCF@CNT photocatalyst conferred its superior catalytic activity and stability. The results from the tests in real water matrices revealed that ZSCF@CNT could be a promising photocatalyst to activate PMS for actual aqueous matrices' treatment.

Enhanced Intestinal Permeability of Cefixime by Self-Emulsifying Drug Delivery System: In-Vitro and Ex-Vivo Characterization.

BACKGROUND: Cefixime (CFX) belongs to a group of third-generation cephalosporin antibiotics with low water solubility and low intestinal permeability, which ultimately leads to significantly low bioavailability. AIM: This study aimed to increase solubility, improve drug release, and intestinal permeability of CFX by loading into SEDDS. METHODS: Suitable excipients were selected based on drug solubility, percent transmittance, and emulsification efficiency. Pseudo-ternary phase diagram was fabricated for the identification of effective self-emulsification region. The best probably optimized formulations were further assessed for encumbered drug contents, emulsification time, cloud point measurement, robustness to dilution, mean droplet size, zeta potential, polydispersity index (PDI), and thermodynamic and chemical stability. Moreover, in vitro drug release studies and ex vivo permeation studies were carried out and apparent drug permeability Papp of different formulations was compared with the marketed brands of CFX. RESULTS: Amongst the four tested SEDDS formulations, F-2 formulation exhibited the highest drug loading of 96.32%, emulsification time of 40.37 ± 3 s, mean droplet size of 19.01 ± 1.12 nm, and demonstrated improved long-term thermodynamic and chemical stability when stored at 4 °C. Release studies revealed a drug release of 97.32 ± 4.82% within 60 min in simulated gastric fluid. Similarly, 97.12 ± 5.02% release of CFX was observed in simulated intestinal fluid within 120 min; however, 85.13 ± 3.23% release of CFX was observed from the marketed product. Ex vivo permeation studies displayed a 2.7-fold increase apparent permeability compared to the marketed product in 5 h. CONCLUSION: Owing to the significantly improved drug solubility, in vitro release and better antibacterial activity, it can be assumed that CFX-loaded SEDDS might lead to an increased bioavailability and antibacterial activity, possibly leading to improved therapeutic effectiveness.

Resistance-Guided Therapy for Neisseria gonorrhoeae.

Antimicrobial-resistant Neisseria gonorrhoeae infections are a threat to public health. Novel strategies for combating such resistance include the development of molecular assays to facilitate real-time prediction of antimicrobial susceptibility. Resistance to ciprofloxacin is determined by the presence of a single mutation at codon 91 of the gyrase A gene; molecular assays to guide therapy are commercially available. Resistance to cefixime is conferred via 1 of 6 critical mutations in either the mosaic penA gene or specific loci in the nonmosaic region. Resistance to ceftriaxone is conferred through mutations in 1 of 4 genes: penA, ponA, penB, and mtr; however, the ability to predict reduced susceptibility based on those genes varies by geographic region. Here, we highlight the work done toward the development of 3 such assays for ciprofloxacin, cefixime, and ceftriaxone, discuss the status of our current understanding and ongoing challenges, and suggest future directions.

Randomized controlled trial of the relative efficacy of high-dose intravenous ceftriaxone and oral cefixime combined with doxycycline for the treatment of Chlamydia trachomatis and Neisseria gonorrhoeae co-infection.

OBJECTIVES: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the commonest bacterial causes of sexually transmitted infections in humans with high incidence of co-infection. Treatment with high doses of ceftriaxone (CRO) and cefixime (CFM) is strongly recommended due to the reduced drug susceptibility of NG. However, their safety and efficacy have not been confirmed. We compared the safety and efficacy of a single 1 g intravenous (IV) dose of ceftriaxone (CRO) plus doxycycline (DOX) versus a single 800 mg oral dose of cefixime (CFM) plus DOX for the treatment of NG-CT co-infection. METHODS: An open-label randomized controlled trial was conducted on 125 individuals aged > 18 years with untreated gonorrhea and chlamydia to compare a single 1 g intravenous dose of CRO + DOX and a single 800 mg oral dose of CFM + DOX. The primary outcome was the clearance of NG from all the initially infected sites. Secondary outcomes included symptom resolution, changes in the serum clearance levels, glomerular filtration rate, and antibiotic minimum inhibitory concentrations. RESULTS: Both regimens were highly effective in treating gonorrhea with success rates of 96.7% (95% confidence interval [CI] 88.8-99.1%) for CRO and 95.3% (95% CI 87.1-98.4%) for CFM. However, CRO + DOX was superior to CFM + DOX for the treatment of NG-CT co-infection (odds ratio 4.41, 95% CI 1.11-25.7). The safety profiles of the two regimens were similar. CONCLUSIONS: CRO + DOX was superior to CFM + DOX for the treatment of NG-CT co-infection. CFM + DOX may be indicated in patients with CRO allergy and in settings where CRO is unavailable. Trial registration ClinicalTrials.gov (NCT05216744) on 31/01/22.

Cefixime and cefixime-clavulanate for screening and confirmation of extended-spectrum beta-lactamases in Escherichia coli.

INTRODUCTION: Detection of Extended-Spectrum Beta-Lactamases (ESBLs) depends on screening for resistance to certain cephalosporins, confirmation with selective ESBL inhibitors, and ESBL genes detection. New tests are required for accurate ESBL detection. AIMS: To test the ability of cefixime (CFM) and cefixime-amoxicillin/clavulanate (CFM-AMC) as a screening and confirmatory test for ESBL identification. METHODS: 246 clinical isolates of Escherichia coli were tested by an ESBL screening test, a double-disk synergy test (DDST), a disk replacement test, the Vitek 2 ESBL test, and an ESBL genes test by PCR. CFM ESBL Screening was performed by disk diffusion, while CFM-AMC confirmation was performed by DDST and a disk replacement test. RESULTS: 246 E. coli clinical isolates from two referral hospitals were collected over 2 years. The mean age ± standard deviation of patients was 43.8 ± 27.7 years and 76.8% were females. Resistance rates to penicillins, first, second, and third generation cephalosporins, and monobactams were very high at 97%, 84%, 100% and 97%, respectively. ESBL screening was positive in 81.3% of isolates, DDST was positive in 74.8%, disk replacement was positive in 79%, Vitek 2 ESBL test was positive in 67.3%, and ESBL genes were detected in 85.8% of isolates (CTX-M 75%, TEM 42.5%, SHV 4.6%). Compared to genotyping, screening with CFM achieved 87.7% sensitivity and 64.7% specificity. CFM-AMC DDST achieved 75.8% sensitivity and 75.4% specificity, and CFM-AMC disk replacement had 73% sensitivity and 70% specificity. CONCLUSIONS: High prevalence of ESBLs was noted among E. coli isolates, dominated by CTX-M genotype. ESBL screening and confirmation using CFM and CFM-AMC is a new and accurate method for ESBLs detection.

Tungsten disulfide (WS2)/fluorescein ratiometric fluorescent probe for detection of cefixime residues in milk.

In this research work, it has been reported a ratiometric fluorescent sensor based on tungsten disulfide quantum dots (WS2 QDs) and fluorescein for the determination of Cefixime (CEF). When excited by radiation of 400 nm wavelength the probe illustrates dual emissions centered at 460 nm and 510 nm. CEF quenches the fluorescence (FL) intensity of fluorescein (510 nm), while it doesn't affect the FL emission of WS2 QDs at 460 nm. The change in the ratio of the two peaks (F460/F510) of the prepared sensor (WS2 QDs/fluorescein) is linearly proportional to the CEF concentration in the range of 200-2.500 ng/mL with a limit of detection (LOD) of 45 ng/mL. Hence, the proposed probe can be successfully used for CEF quantification in the milk samples.

Restoration of cefixime-induced gut microbiota changes by a prebiotic blend in a mouse model.

Recent studies have provided compelling evidence linking the composition of the gut microbiota, host diet, and host physiology. Prebiotics are substrates that are selectively utilized by host microorganisms, conferring health benefits. Prebiotics, such as prebiotic blends (PB), are commonly used worldwide in food processing. Here, microbiome-metabolomics was used to evaluate how PB affect gut microbes and metabolic functions in C57BL/6 J mice administered cefixime. We found favorable effects of PB on obesity outcomes. PB supplementation significantly increased the abundance of Bifidobacterium, Parabacteroides, Alloprevotella, Alistipes, and Dubosiella, and decreased that of Robinsoniella, Blautia, Lachnoclostridium, Coprobacillus, Hungatella, Erysipelatoclostridium, Helicobacter, Clostridium sensu stricto 1, Enterococcus, and Akkermansia compared to that in the cefixime administration (CEF) group. In particular, PB increased the abundance of Parabacteroides goldsteinii and suppressed that of Robinsoniella peoriensis and Akkermansia muciniphila. In addition, it regulated the levels of microbial metabolites such as unsaturated fatty acids and bile acids. Thus, PB can alleviate metabolic disorders induced by antibiotic intervention, indicating a potential dietary strategy for populations with antibiotic-associated diarrhea. KEY POINTS: • Prebiotic blends significantly increased the Parabacteroides goldsteinii colony. • Prebiotic blends selectivity reversed this increase of Akkermansia muciniphila by antibiotic intervention. • Prebiotic blends relieve cefixime-induced alteration of intestinal flora by regulating metabolites, such as fatty acids and bile acids.

The Development and Evaluation of a Selective Enrichment for the Detection of Escherichia albertii in Food.

Escherichia albertii is an emerging pathogen causing foodborne infections with diarrhea, abdominal pain, and fever. E. albertii has been isolated from various food sources, such as chicken and pork. Although many foodborne outbreaks of E. albertii have been reported, the causative food has not been identified. It is necessary to develop effective detection methods for E. albertii. Because enrichment procedure as the first step of food test is important for growing pathogens, this study aimed to develop a novel effective enrichment for E. albertii detection in food. In this study, we investigated the optimal concentration and combination of cefixime and tellurite for supplementing modified EC broth (mEC) to effectively isolate E. albertii from chicken meat. The results showed that mEC supplemented with 50 µg/L cefixime and 2.5 mg/L tellurite (CT-mEC) inhibited the growth of competitive bacteria in chicken meat but not that of E. albertii. Therefore, it was indicated that CT-mEC had strong potential to selectively grow E. albertii. In an E. albertii foodborne outbreak, CT-mEC was evaluated. E. albertii was successfully isolated from a food sample, a kind of salad, by enrichment with CT-mEC but not buffered peptone water and mEC. In this study, CT-mEC as a selective enrichment broth has been developed to detect E. albertii in chicken meat. It was demonstrated that the selective enrichment broth was effective for the efficient detection of E. albertii in food.

Molecular docking and dynamic simulations of Cefixime, Etoposide and Nebrodenside A against the pathogenic proteins of SARS-CoV-2.

The catastrophe of the coronavirus continues from one part of the world to another, and hardly a country is left without its devastations. Millions of people were infected and several hundred thousand died of the COVID-19 pandemic across the world. There is no clear targeted drug therapy available for the treatment of the patients. The discovery of vaccines is not enough to curtail its spread and disastrous implications. An instantly qualifying approach is needed to utilize the current drugs and isolated compounds. The purpose of this work is to determine potent inhibitors against the target proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, molecular docking study of pathogenic spike glycoproteins (S), nucleocapsid phosphoprotein (N), an envelope protein (E), two drugs i.e., cefixime, etoposide, and a previously isolated compound nebrodenside A is performed. Promising results were obtained via complimentary analysis of molecular dynamics (MD) simulations performed for the complexes of three proteins with etoposide drug. Minimum values were recorded for the docking scores and binding energies of the complexes. These results were further supported by the RMSD, RMSF data for the stability of proteins and ligands. Additionally, ligand properties and ligand-protein contacts were also explained with histograms of every simulation trajectory. The computational studies confirmed that cefixime, etoposide, and nebrodenoside A can be used as potent inhibitors of COVID-19. Nevertheless, additional experimental investigations and validation of the selected candidates are mandatory to confirm their applicability for clinical trials.

Photocatalytic degradation of cefixime using visible light-driven Z-scheme ZnO nanorod/Zn2TiO4/GO heterostructure.

ZnO nanorod along with a Zn2TiO4/GO heterostructure with enhanced charge transfer capability was synthesized by a facile sol-gel method. FT-IR, XRD, XPS, TEM, SEM, EDX, UV-Vis DRS, photocurrent response and PL analyses were applied to characterize the as-prepared photocatalysts. To investigate the photocatalytic activity of the composite, Cefixime (CEF) removal under visible light was evaluated. The ZnO nanorod/Zn2TiO4/GO, including 65 wt% ZnO and 3 wt% graphene oxide, showed the highest CEF degradation and was selected as the optimal ternary composite. Reduction of electron-hole pair recombination rate, successful interfacial charge transfers, and more visible light reception in the Z-scheme system were the important reasons for improving the photocatalytic properties of ZnO nanorod/Zn2TiO4/GO. Effective operating parameters in the CEF photocatalytic removal process were optimized employing the response surface method and were as follows: photocatalyst dosage = 0.88 g/L, pH = 5, radiation time = 115 min, and CEF concentration = 10 ppm. The photocatalytic degradation% of CEF and total organic carbon (TOC) removal% under the optimal conditions were 71.4 and 57.5%, respectively, for the three-component composite indicating the production of intermediate species during the process. This photocatalytic reaction confirmed the first-order kinetic and using the ZnO nanorod/Zn2TiO4/GO composite was able to improve the reaction rate by about 2.7 and 6.2 times more than ZnO nanorod/Zn2TiO4 and ZnO, respectively. The effects of radiation intensity and temperature were investigated and 175 W/m2 and 35 °C were obtained as optimum values. Eventually, according to the trapping test, h+, superoxide radical, and hydroxyl radical are the most effective active species in this photocatalytic reaction, respectively.

A Rare Pediatric Case of Cefixime Induced Toxic Epidermal Necrolysis.

Cefixime is a third-generation cephalosporin that has been used for the treatment of a wide range of infections in children and adults. The incidence of cefixime induced toxic epidermal necrolysis (TEN) is less than 2% in adults, but it is infrequent among pediatric patients. We report a rare case of cefixime induced TEN in a 7-year-old boy. In this case, the child presented with symptoms of TEN after 2 days of administration of cefixime. This case highlights the need to select structurally different antibiotics in case of antibiotic-induced severe cutaneous adverse reaction (SCAR) to avoid recurrence of SCAR. Furthermore, concluded that irrational use of antibiotics could be disastrous as it can result in TEN as the incidence of antibiotics induced TEN ranges from 29% to 42%.

Clinical Efficacy of Cefixime for the Treatment of Early Syphilis.

Safe and efficacious alternative treatment options for syphilis are necessary. This randomized, 2-arm, noncomparative pilot study evaluated the efficacy of oral cefixime 400 mg in achieving a ≥4-fold rapid plasma reagin titer decrease by 3 or 6 months after treatment. The proportion of cefixime arm participants treated successfully was 87% (95% confidence interval, 69%-100%; 13/15). Clinical Trials Registration. NCT03752112.

Antimicrobial resistance and molecular epidemiological typing of Neisseria gonorrhoeae isolates from Kyrgyzstan in Central Asia, 2012 and 2017.

BACKGROUND: Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are significant public health concerns globally. Nearly no gonococcal AMR data are available from Central Asia, and no data from Kyrgyzstan has been published. We examined, for the first time, AMR and molecular epidemiology of N. gonorrhoeae isolates cultured in Kyrgyzstan in 2012 and 2017, in order to inform refinements of the Kyrgyz national gonorrhoea management guidelines. METHODS: N. gonorrhoeae isolates cultured in 2012 (n = 84) and 2017 (n = 72) in Kyrgyzstan were examined. MICs of nine antimicrobials were determined using Etest and, where available, clinical breakpoints from the EUCAST were applied. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was also performed. RESULTS: The overall resistance levels were high to ciprofloxacin (88.5%), tetracycline (56.9%), benzylpenicillin (39.1%), and kanamycin (4.7%). Resistance to cefixime (0.6%, n = 1 isolate), azithromycin (0.6%, n = 1), and gentamicin (0.6%, n = 1) was rare. No resistance to ceftriaxone or spectinomycin was found. However, the proportion of isolates with decreased susceptibility (MIC = 0.125 mg/L) to ceftriaxone and cefixime was 12.8 and 11.5%, respectively. Gonococcal isolates were assigned 69 sequence types, of which 52 (75.4%) were new. CONCLUSIONS: The gonococcal population in Kyrgyzstan in 2012 and 2017 showed a high genetic diversity. Ceftriaxone, 500-1000 mg, in combination with azithromycin 2 g or doxycycline, particularly when chlamydial infection has not been excluded, should be recommended as empiric first-line treatment. Spectinomycin 2 g could be an alternative treatment, and given with azithromycin 2 g if pharyngeal gonorrhoea has not been excluded. Fluoroquinolones, aminoglycosides, benzylpenicillin, or tetracyclines should not be used for empiric treatment of gonorrhoea in Kyrgyzstan. Timely updating and high compliance to national gonorrhoea treatment guidelines based on quality-assured AMR data is imperative. Expanded and improved gonococcal AMR surveillance in Kyrgyzstan is crucial.