Cefonicid Research Articles

Virtual screening of inhibitors against Envelope glycoprotein of Chikungunya Virus: a drug repositioning approach.

Chikungunya virus (CHIKV) a re-emerging mosquito-borne alpha virus causes significant distress which is further accentuated in the lack of specific therapeutics or a preventive vaccine, mandating accelerated research for anti-CHIKV therapeutics. In recent years, drug repositioning has gained recognition for the curative interventions for its cost and time efficacy. CHIKV envelope proteins are considered to be the promising targets for drug discovery because of their essential role in viral attachment and entry in the host cells. In the current study, we propose structure-based virtual screening of drug molecule on the crystal structure of mature Chikungunya envelope protein (PDB 3N41) using a library of FDA approved drug molecules. Several cephalosporin drugs docked successfully within two binding sites prepared at E1-E2 interface of CHIKV envelop protein complex with significantly low binding energies. Cefmenoxime, ceforanide, cefotetan, cefonicid sodium and cefpiramide were identified as top leads with a cumulative score of -67.67, -64.90, -63.78, -61.99, and - 61.77, forming electrostatic, hydrogen and hydrophobic bonds within both the binding sites. These shortlisted leads could be potential inhibitors of E1-E2 hetero dimer in CHIKV, hence might disrupt the integrity of envelope glycoprotein leading to loss of its ability to form mature viral particles and gain entry into the host.

Study on the effect of protein on drug efficacy: cefonicid sodium–pepsin binding mechanism

The mechanism of interaction between cefonicid sodium and pepsin was investigated by various spectroscopic methods and molecular docking. Cefoncid sodium quenched the intrinsic fluorescence of pepsin at pH of 2.0 to form a new complex in a 1:1 binding mode driven by Van der Waals and hydrogen bonds. The mechanism of quenching was static. The results of molecular docking indicated that the cefonicid sodium-binding site was located in the active site of pepsin. The protein binding rates of cefonicid sodium in gastric juice was calculated and the binding model was established. It is concluded that cefonicid sodium is not suitable for oral administration.

Interactions and Molecular Docking Studies of Cefonicid Sodium with Papain Amino Acid Residues

This study aims to investigate the interaction between cefonicid sodium (CFS) and papain (PAPA) using fluorescence spectroscopy, synchronous fluorescence spectroscopy and molecular docking methods. The results indicated that the fluorescence intensity of PAPA was decreased considerably upon the addition of CFS through a static quenching mechanism. Synchronous fluorescence spectroscopy studies showed that the combination of CFS and PAPA could change the conformation of PAPA. At the temperature of 293 K, there was a good linear relationship between the fluorescence intensity of the system and the concentration of CFS in the range of 6.0×10-6 to 1.0×10-4 mol/L and the detection limit of the method was 3.05×10-6 mol/L (n=10). From the results of the thermodynamic constant and molecular model analysis, it could be inferred that the CFS and PAPA molecules mainly combine by electrostatic attraction and hydrogen bonding. The binding model was established based on the experimental data, and the binding rate data of CFS and PAPA was obtained. The results showed that taking PAPA while taking CFS was safe.

Separation and characterization of unknown impurities in cefonicid sodium by trap-free two-dimensional liquid chromatography combined with ion trap time-of-flight mass spectrometry.

Seven unknown antibiotic impurities in cefonicid sodium were separated and characterized by a trap-free two-dimensional liquid chromatography coupled to high-resolution ion-trap time-of-flight mass spectrometry (2D-LC/IT-TOF MS) using both positive and negative modes of electrospray ionization. Trap-free 2D-LC and an online demineralization technique made it possible to characterize cefonicid sodium under the conditions of the official standard, and the TIC chromatogram obtained by LC/MS was in conformity with the LC chromatogram obtained by the official analytical method in the peak sequence of impurities. In the first dimension, the column was a GRACE Alltima C18 (250mm×4.6mm, 5μm), and the gradient elution used 0.02mol·L-1 ammonium dihydrogen phosphate solution and methanol as mobile phase. In the second dimension, the analytical column was a Shimadzu Shim-pack GISS C18 (50mm×2.1mm, 1.9μm) with 10mmol·L-1 ammonium formate solution and methanol as mobile phase. Full scan LC/MS was first executed to obtain the exact m/z values of the molecules. Then LC/MS2 and LC-MS3 experiments were performed on the compounds of interest. The structures of seven unknown degradation products in cefonicid sodium were deduced based on the high-resolution MSn data using both positive and negative mode. The problem of incompatibility between the non-volatile salt mobile phase and mass spectrometry was solved completely by multidimensional heart-cutting approaches and an online demineralization technique, which is worthy of widespread use and application for the advantages of stability and repeatability.

Study of the Interaction of Cefonicid Sodium with Bovine Serum Albumin by Fluorescence Spectroscopy

The reaction mechanism of cefonicid sodium with bovine serum albumin was investigated by traditional fluorescence spectroscopy and synchronous fluorescence spectroscopy. The results demonstrated that cefonicid sodium caused a strong fluorescence quenching of bovine serum albumin through a static quenching mechanism, during which the electrostatic force played the dominant role in this system, and the number of binding sites in the system was close to 1. It also showed that the primary binding site for cefonicid sodium was closer to tryptophan residues located in sub-hydrophobic domain IIA. Moreover, circular dichroism spectroscopy showed that the secondary structure of bovine serum albumin changed. The donor-to-acceptor distance r < 8 nm indicated that the static fluorescence quenching of bovine serum albumin was a nonradiation energy transfer process. The data obtained from Δλ = 60 nm and λex = 295 nm indicated that synchronous fluorescence spectroscopy had higher sensitivity and accuracy compared to traditional fluorescence spectroscopy.

Evaluation of Outpatient Antibiotic Use in Beijing General Hospitals in 2015.

Background:Medical misuse of antibiotics is associated with the acquisition and spread of antibiotic resistance, resulting in a lack of effective drugs and increased health-care cost. Nevertheless, inappropriate antibiotic use in China remains common and the situation requires urgent improvement. Here, we analyzed the prescriptions of antibiotics and evaluated the rationality of antibiotic use among outpatients in Beijing general hospitals during 2015.Methods:We collected basic medical insurance claim data from January 1, 2015 to December 31, 2015 in 507 general hospitals of Beijing. A descriptive analysis of outpatient antibiotic prescribing was performed. The Anatomical Therapeutic Chemical Classification/defined daily doses system was used to evaluate the rationality of antibiotic use.Results:Over the study, an estimated 721,930, 613,520, and 822,480 antibiotics were dispensed in primary, secondary, and tertiary general hospitals corresponding to 5.09%, 5.06%, and 2.53% of all prescriptions, respectively. Antibiotic combinations represented 2.95%, 7.74%, and 10.18% of the total antibiotic prescriptions, respectively. Expenditure for the top twenty antibiotics in primary, secondary, and tertiary general hospitals was RMB 42.92, 65.89, and 83.26 million Yuan, respectively. Cephalosporins were the most frequently prescribed class of antibiotic in clinical practice. The antibiotics used inappropriately included azithromycin enteric-coated capsules, compound cefaclor tablets and nifuratel nysfungin vaginal soft capsules in primary hospitals, amoxicillin and clavulanate potassium dispersible tablets (7:1) and cefonicid sodium for injection in secondary hospitals, cefminox sodium for injection and amoxicillin sodium and sulbactam sodium for injection in tertiary hospitals.Conclusions:Antibiotic use in Beijing general hospitals is generally low; however, inappropriate antibiotic use still exists. Inappropriately used antibiotics should be subject to rigorous control and management, and public policy initiatives are required to promote the judicious use of antibiotics.

Mechanism of Interaction Between Cefonicid Sodium and Trypsin by Spectroscopic and Molecular Docking Methods

The binding of cefonicid sodium (CFS) with trypsin was investigated by spectroscopic and molecular docking methods under different temperatures conditions (303, 310 and 318 K). The results demonstrated that the interaction between CFS and trypsin was taking place via static quenching with 1:1 binding ratio. The fluorescence datas were treated by using the double logarithmic equation, and the binding constants K a of the interaction of CFS-trypsin systems and the number of binding sites n were obtained. The thermodynamic parameters of CFS-trypsin systems under different temperatures were obtained by the thermodynamic equation. The experimental data show that the interactions between them were mainly hydrophobic interaction and hydrogen bonding interaction, and with the molecular docking results are consistent.

Interaction between bovine transferrin and cefonicid sodium by multi-spectroscopy

ABSTRACTIn the Tris-HCl buffer solution with pH = 7.4, the reaction mechanism of cefonicid sodium with bovine transferrin was investigated by multi-spectroscopic methods at different temperatures (298, 303, and 310 K). The results demonstrated that non-radiative energy transfer occurred between cefonicid sodium and bovine transferrin, which gradually quenched the fluorescence of bovine transferrin, and the quenching mechanism was a static quenching progress. During the quenching progress, the electrostatic force played a dominant role in this system, and the number of binding sites in the system was close to 1. Moreover, ultraviolet visible absorption spectroscopy and synchronous fluorescence spectroscopy showed that the structure of bovine transferrin was changed. The polarity around amino acid residues increased and the hydrophobicity decreased. Circular dichroism spectroscopy also showed that cefonicid sodium changed the secondary structure of bovine transferrin. However, the structure of the bovine transferrin was also predominantly α-helical even after binding to cefonicid sodium. The values of Hill’s coefficients were less than 1, indicating that drugs had negative cooperativity for subsequent ligands in the system.

Microcalorimetric studies on the antimicrobial actions of different cephalosporins

Microcalorimetry was applied to study the effect of cephalosporins (cefazolin sodium and cefonicid sodium) on the E. coli growth. The microbial activity was recorded as power-time curves through an ampoule method with a TAM Air Isothermal Microcalorimeter at 37°C. The parameters such as the growth rate constant (k), inhibitory ratio (I), the maximum power output (Pm) and the time corresponding to the maximum power output (tm) were calculated. The change tendencies of k, with the increasing of concentration (C) of the two cephalosporins, are similar which show that cefazolin sodium and cefonicid sodium have the same inhibitory mechanism. The experimental results reveal that cefonicid sodium has a stronger antibacterial activity towards E. coli than that of cefazolin sodium and this was coincide with the clinical manifestations.

Acinetobacter baumannii bloodstream infection: clinical features and antimicrobial susceptibilities of isolates.

The number of nosocomial infections caused by Acinetobacter baumannii has increased in recent years. The purposes of this study are to discover the risk factors of transmission to prevent the nosocomial infection of A. baumannii. We retrospectively studied 36 patients with A. baumannii bacteremia at China Medical College Hospital from January 1996 to December 1997. There were 23 males and 13 females. All bacteremia were acquired nosocomially. Malignancy (n = 8) and intracranial hemorrhage (n = 6) were the most common underlying diseases. Only one patient on arterial line disclosed intraarterial catheter-related A. baumannii bacteremia and 3 patients had evidence of A. baumannii pneumonia. Twenty-one patients (58%) had central venous catheters in place at the onset of bacteremia, but none was proven to be catheter-related infection. There were 32 patients (89%) with unknown portal of entry. Multivariate logistic regression analysis revealed that potential risk factors related to A. baumannii bacteremia were prior antimicrobial therapy (P < 0.05). The most common clinical features of A. baumannii bacteremia were, in descending order, fever, leukocytosis, thrombocytopenia and hypotension. Eleven patients (30.6%) died directly from A. baumannii bacteremia. All isolates were resistant to ampicillin, cephalothin, cefonicid and moxalactam. The most alarming evidence was that 19% of isolates showed resistance to imipenem. Our findings emphasized that A. baumannii bacteremia had the following characteristics: usually acquired nosocomially, unknown portal of entry, and high multiresistance, especially the increasing resistance rate to imipenem. Imipenem must be reserved as a last-line agent to treat A. baumannii infections, so we want to suggest that the treatment of choice for A. baumannii is gentamicin, amikacin or ceftazidime.

Compatibility of Clindamycin Phosphate with Aztreonam in Polypropylene Syringes and with Cefoperazone Sodium, Cefonicid Sodium, and Cefuroxime Sodium in Partial-Fill Glass Bottles

The stability and compatibility of clindamycin phosphate admixed with four beta-lactams, an experimental monobactam (aztreonam), and three cephalosporins (cefoperazone sodium, cefonicid sodium, and cefuroxime sodium), were studied. Aztreonam alone and the combination of clindamycin phosphate-aztreonam were prepared in duplicate polypropylene syringes. Each cephalosporin antibiotic as well as the three clindamycin phosphate-cephalosporin combinations were admixed in duplicate 100 ml partial-fill glass bottles containing either dextrose 5% in water or NaCl 0.9%. All solutions were examined, antibiotic concentrations were determined, and pH was measured at the time of admixture and 1, 4, 8, 12, 24, and 48 hours later. The solutions were maintained at room temperature under fluorescent lighting for the length of the study. Antibiotic concentrations were determined by drug-specific high performance liquid chromatographic assays. Significant instability or incompatibility was defined as a decrease in concentration of greater than ten percent relative to the initial concentration measured at the time of admixture. All antibiotics were stable for 48 hours. In the combination studies, clindamycin was stable for 48 hours, both in partial-fill glass bottles and syringes. Aztreonam, cefoperazone, cefonicid, and cefuroxime were also stable for 48 hours.

Outpatient Antibiotic Therapy for Osteomyelitis

To the Editor.— The March 28, 1986, issue ofJAMAcontained an article offering an economic analysis of outpatient therapy for osteomyelitis.1This article is now being distributed by representatives of the Smith Klein & French pharmaceutical company for the purpose of encouraging the use of the cephalosporin antibiotic cefonicid (Monocid) in this In their introduction, the authors justify their analysis by noting that new... cephalosporin antibiotic, cefonicid sodium, has been shown to be effective in treating osteomyelitis in the outpatient setting. This statement is supported by reference to a clinical trial published in a supplement toReviews of Infectious Diseasesunderwritten by Smith Klein & French.2This clinical trial examined (in an uncontrolled fashion) cefonicid therapy for osteomyelitis in 15 patients, 12 of whom completed therapy. The investigators in this clinical trial appropriately noted the limitations of their study: small numbers, no comparison group, lack

Stability of cefonicid sodium in infusion fluids

The chemical stability of cefonicid sodium in infusion fluids was analyzed. Cefonicid sodium vials were reconstituted and diluted with sterile water for injection and other commonly used intravenous fluids to concentrations of 325, 220, 40, 20, and 5 mg/mL. Cefonicid concentration was analyzed by high-performance liquid chromatography initially and after storage at room temperature and 5 degrees C. Reconstituted vials were frozen as long as eight weeks, thawed, and kept at room temperature and 5 degrees C and then analyzed. Cefonicid sodium reconstituted in each of the diluents studied exhibited no change in clarity and very little change in potency after 24 hours at room temperature and after 72 hours at 5 degrees C. Some vials with high concentrations became turbid between 72 and 96 hours at 5 degrees C. The thawed vials were chemically stable for 24 hours at room temperature and for 96 hours at 5 degrees C. When reconstituted with sterile water for injection and other commonly used intravenous fluids, cefonicid sodium vials and small-volume infusions are chemically stable for 24 hours at room temperature and for 72 hours at 5 degrees C. Reconstituted cefonicid sodium vials can be frozen and stored for as long as eight weeks, thawed, and then kept at room temperature for 24 hours or at 5 degrees C for 72 hours.

Azlocillin and cefonicid penetration into bone enhanced by probenecid.

Azlocillin (AZL) and cefonicid (CFD) penetration into rabbit humerus and scapula was evaluated with and without concomitantly administered probenecid. Groups of animals received either 70 mg of AZL intravenously or 20 mg of CFD intramuscularly per kg of body weight; other groups were pretreated with 40 mg of probenecid per kg before the administration of antibiotics. Peak levels of AZL in the sera of animals not receiving probenecid were 76.0 micrograms/ml at 30 min and declined to 7.7 micrograms/ml by 2.0 h. Maximum concentrations in bone were 2.7 micrograms/g in the humerus and 7.1 micrograms/g in the scapula at 1 h. Pretreatment with probenecid significantly elevated levels of AZL in both serum and bone while increasing the half-life in serum from 0.44 to 0.65 h. Maximum drug concentrations in bones of probenecid-pretreated animals were 3.9 and 11.7 micrograms/g in the humerus and scapula, respectively, with detectable levels persisting in bone for up to 4 h. The peak level of CFD alone in serum was 36.7 micrograms/ml at 30 min and declined to 0.86 micrograms/ml at 8 h. Maximum concentrations in bone were 0.66 micrograms/g in the humerus at 1 h and 1.8 micrograms/g in the scapula at 2 h. Pretreatment with probenecid significantly elevated levels of CFD in both serum and bone while increasing the half-life in serum from 1.4 to 2.94 h. Pretreatment with probenecid achieved maximum concentrations of 1.7 and 2.8 micrograms/g in the humerus and scapula, respectively. Detectable levels of CFD persisted in the humerus for up to 4 h and in the scapula for 8 h.

Cefonicid concentrations in human aqueous humor.

One-gram doses of cefonicid sodium were given intravenously to patients prior to cataract surgery. Although serum levels were high, cefonicid levels in aqueous humor were low: mean peak concentrations of 0.25 and 0.27 mg/L were observed two and four hours after administration, respectively. The unusually high protein binding of cefonicid may explain these observations. The observed concentrations were not above the minimum inhibitory concentrations of cefonicid for those pathogens commonly involved in bacterial endophthalmitis.