Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam Versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies

We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.

Kinetic spectrophotometric determination of certain cephalosporins using iodate/iodide mixture

A simple, precise and accurate kinetic spectro-photometric method for determination of ce-fradine anhydrous, cefaclor monohydrate, ce-fadroxil monohydrate, cefalexin anhydrous and cefixime in bulk and in pharmaceutical formula-tions has been developed. The method based on a kinetic investigation of the reaction of the free carboxylic acid group of the drug with a mixture of potassium iodate and potassium iodide at room temperature to form yellow coloured triiodide ions. The reaction was followed up spectrophotometrically by measuring the increase in absorbance at 352 nm as a function of time. The initial rate, fixed time, variable time and rate-constant methods were adopted for constructing the calibration curves but fixed time method has been found to be more applicable. The analytical performance of the method, in terms of accuracy and precision, was statistically validated;the results were satisfactory. The method has been successfully applied to the determination of the studied drugs in commercial pharmaceutical formulations. Statistical comparison of the results with a well established reported method showed excellent ag- reement and proved that there is no significant difference in the accuracy and precision.

Spectophotometric method for determination of certain cephalosporins using 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl)

A simple, accurate and precise spectrophotometric method has been proposed for the determination of eleven cephalosporins, namely;cefaclor monohydrate, cefadroxil monohydrate, cefalexin anhydrous, cefradine anhydrous, cefotaxime sodium, cefoperazone sodium, ceftriaxone sodium, ceftazidime penthydrate, cefazolin sodium, cefixime and cefpodoxime pro- xetil in bulk drug and in pharmaceutical formulations. The method depends on hydrolysis of the studied drugs using 0.5M NaOH at 100°C and subsequent reaction of the formed sulfide ions with NBD-Cl (4-chloro-7-nitrobenzo-2-oxa-1, 3-diazole) to form a yellow-colored chromogen measured at 390 nm. Different variables affecting the reaction (e.g. NaOH concentration, hydrolysis time, NBD-Cl concentration and diluting solvent) were studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990- 0.9999) were found in the range of 5-160 μg mL-1 for all studied drugs. The limits of assay detection and quantitiation ranged from 0.289 to 5.867 and from 0.878 to 17.778 μg mL-1;respectively. The accuracy and precision of the proposed method were satisfactory. The method was successfully applied for analysis of the studied drugs in their pharmaceutical formulations and the recovery percentages ranged from 96.6 to 103.5%.

Studies on Semisynthesis and Anibacterial Activity of 7 β-(5-Methyl-1-Aryl-1H-1,2,3-Triazoly-4-Carboxamido) Cephalosporins

Nine new derivatives of 7 β - (5- methyl- 1- aryl- 1H-1, 2, 3- triazoly- 4- carboxamido) cephalosporins were synthesized by acylction of 7 β -amino group of 7-ACA, 7-ADCA and 7-ACT with 5 -methsyl- 1 -aryl- 1 H- 1,2,3-triazoly-4-formyl chloride. The structure of the compounds were confirmed by elementray analysis IR, HNMR and FAB-MS. Some of them showed significant antibacterial activity

Variable selection in near infrared spectroscopy for quantitative models of homologous analogs of cephalosporins

Two universal spectral ranges(4550-4100 cm^(-1) and 6190-5510 cm^(-1))for construction of quantitative models of homologous analogs of cephalosporins were proposed by evaluating theperformance of five spectral ranges and their combinations,using three data sets of cephalos-porins for injection,ie.,cefuroxime sodium,cetriaxone sodium and cefoperazone sodium.Subsequently,the proposed ranges were validated by using eight calibration sets of otherhomologous analogs of cephalosporins for injection,namely cefmenoxime hydrochloride,ceftezole sodium,cefmetazole,cefoxitin sodium,cefotaxime sodium,cefradine,cephazolin sodium and ceftizoxime sodium.All the constructed quantitative models for the eight kinds of cephalosporinsusing these universal ranges could fulill the requirements for quick quantification.After that,competitive adaptive reweighted sampling(CARS)algorithm and infrared(IR)-near infrared(NIR)two-dimensional(2D)correlation spectral analysis were used to determine the scientific basis of these two spectral ranges as the universal regions for the construction of quantitativemodels of cephalosporins.The CAR.S algorithm demonstrated that the ranges of 4550-4100 cm^(-1) and 6190-5510 cm^(-1) included some key wavenumbers which could be attributed to content changes of cephalosporins.The IR-NIR 2D spectral analysis showed that certain wavenumbersin these two regions have strong correlations to the structures of those cephalosporins that wereeasy to degrade.

Computational Calculations of Molecular Properties and Molecular Docking of New and Reference Cephalosporins on Penicillin Binding Proteins and Various β-Lactamases

An approach of using molinspiration calculations and molecular docking on PBPs （penicillin-binding proteins） and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of newer and reference cephalosporins. The previously synthesized cephalosporins 1-8 and reference cephalosporins were subjected to extensive evaluations by calculating the molecular properties, drug-likeness scores on the bases of Lipinski＇s rule and bioactivity prediction using the method of molinspiration web-based software. The TPSA （topological polar surface area）, OH-NH interactions, n-violation and the molinspiration Log partition coefficient （miLogP） values were also calculated. The investigated cephalosporins were subjected to molecular docking study on PBPs （lpyy） and on β-lactamases produced by S. aureus, K. pneumonia, E. coil and P. auroginosa using 1-click-docking website. Molecular properties of 1-8 recorded higher ＂FPSA than cephalexin and were lower than the reference cephalosporins and do not fulfill the requirements for Lipinski＇s rule. Bioactivities of 1-8 were predicted to be less and their docking scores on PBPs were comparable to those of the reference cephalosporins, particularly ceftobiprole. The references recorded various docking scores on the above β-lactamases and as expected, cefiobiprole recorded the lowest scores on all β-lactarnases. Cephalosporins 1-8 recorded various docking scores on β-lactamases. Molecular docking studies on PBPs and β-lactamases are considered as very useful, reliable and practical approach for predicting the bioactivity scores and to afford some information about the stability and selectivity of the newly proposed cephalosporins against β-lactamases of certain pathogenic microbes, such as P. auroginosa and MRSA, by recording the relative docking scores in comparison with those of reference cephalosporins.

Dissimilarity of different cephalosporins on volatile fatty acids production and antibiotic resistance genes fates during sludge fermentation and underlying mechanisms

The distinct influences of cephalosporins(CEPs, i.e., cefamandole nafate and cefpirome sulfate) affiliated to different generations on the volatile fatty acids(VFAs) production and antibiotic resistance genes(ARGs) fates during waste activated sludge(WAS) fermentation were unveiled. The presence of CEPs mainly exhibited negative effects on the total VFAs production(5%–15% reduction), especially the cefamandole nafate, which is quite different to previous understanding. Further investigation revealed that the CEPs contributed to the solubilization and hydrolysis but inhibited the acidification process by affecting the functional microbial populations(i.e., Tissierella) and general microbial metabolic activities(i.e., pyruvate metabolism and VFAs biosynthesis). In addition, CEPs(especially the cefpirome sulfate)caused the propagation of ARGs(i.e., bla TEM, tet X and mex F) during WAS fermentation. CEPs enhanced the cell membrane permeability to promote the antibiotics mechanism of efflux pump and the horizontal transfer of ARGs. Also, the CEPs altered the regulatory systems(i.e., two component system) and microbial populations associated with ARGs, resulting in the proliferation of specific ARGs. Overall, the dissimilarity of different CEPs impacts on the WAS fermentation for VFAs production and ARGs variations enlightened the diverse environmental behaviors of anthropogenic pollutants and evoked the caution of ecological risks.

Theoretical Analysis of Structural Characteristics of Morin Rearrangement for Cephalosporins Prepared from Penicillin Sulfoxide

The structure of penicillin sulfoxide is rearranged to cephalosporins by the Morin rearrangement. It is a unit reaction for the preparation of various types of cephalosporins. In order to make better use of the reaction and in view of the shortage of the reaction theory, this study used m062x/6-311++G(d, p) to explore the possible ring-opening reaction of the penicillin sulfoxide. It is found that the isomer of(S)-sulfoxide is a necessary structure. At the same time, the intramolecular hydrogen bonding effect between the side-chain amide proton(-CONH-) and the sulfinyl oxygen(-SO) is the decisive structure factor for the formation of alkenyl in ring-opening reaction, and the best reaction path is S0-> TS2-> IN1 channel. The main effect of acid catalysis is to catalyze the dehydration reaction of sulfenic acid to form sulfur cations for subsequently ring closing reaction.

Investigation of the pharmacokinetics and determination of certain cephalosporins in rabbit plasma by a kinetic spectrophotometric method with the aid of chemometrics

This paper describes a kinetic spectrophotometric method for simultaneous determination of three cephalosporin antibiotics,cephradine,cefaclor and cefixime,with the aid of chemometrics. The method relies on their oxidation with KMnO4 to produce green manganate with different kinetic rates in alkaline medium. The proposed method was successfully applied to a pharmacokinetic study of three cephalosporin antibiotics in rabbit plasma via intravenous injections. The results indicated that the amount of cephradine,cefaclor and cefixime were reduced rapidly in rabbit blood,showing clear dose-dependency and the half-life of cefixime (160 min) was longer than those of cephradine (60 min) and cefaclor (60 min).

Decreasing susceptibility of bacteria to ampicillin/sulbactam and third generation cephalosporins in urinary tract infections

Background:Urinary tract infections(UTIs)are among the most common bacterial infections worldwide and have become more difficult to treat over the years.Inappropriate antibiotic use has led to increased antibiotic resistance.Materials and methods:We examined 1921 urine culture samples from a single hospital and analyzed them for bacterial spectrum and antibiotic susceptibility.We further analyzed changes in the rates of detected bacteria and of the sensitivity of these uropathogens to antibiotics over the years.Results:In our hospital-based analysis,cystitis was the most frequently diagnosed UTI in women(76%)and men(79%).Escherichia coli(48%)was the most commonly identified uropathogen.Samples demonstrated an increase in the proportion of E.coli(p<0.001)and a decrease in Enterococcus faecalis(p<0.001)over the study time period.Antimicrobial susceptibility analysis showed an increase over time in the number of isolates with resistance to ampicillin/sulbactam(p<0.001)and to third-generation cephalosporins cefotaxime(p=0.043)and ceftazidime(p<0.001).Conclusions:Ampicillin/sulbactam and third-generation cephalosporins are antibiotics frequently used in the treatment of UTIs.When selecting an optimal antimicrobial treatment regimen for patients with UTIs,it is imperative to understand regional and timedependent differences in the prevalence of various uropathogens and antimicrobial resistance patterns.Therefore,continuous surveillance of local pathogen and antimicrobial susceptibility patterns for frequently used antibiotics should be prioritized.

Prevalence and antimicrobial susceptibility patterns of bacteria in ICU patients with lower respiratory tract infection: A cross-sectional study

Objective: To investigate the prevalence of isolated organisms in patients with lower respiratory tract infections and the antibiotic susceptibilities at a tertiary care center. Methods: In this observational and cross-sectional analysis, 114 patients admitted in the intensive care unit were enrolled. The endotracheal aspirates and bronchoalveolar lavage were collected. The bacteria were isolated and identified, and finally, antimicrobial sensitive pattern of the isolated bacteria was examined. Results: The prevalence of infection was 72.72% in male patients and 27.28% in females. The predominant bacteria were Klebsiella pneumoniae (37.50%) followed by Acinetobacter spp. (36.36%), Pseudomonas aeruginosa (7.95%),Escherichia coli (6.81%), Proteus mirabilis (2.27%), atypical Escherichia coli (1.13%), Enterococcus spp. (1.13%),Elizabethkingia meningoseptica (1.13%),Staphylococcus aureus (1.13%),Proteus vulgaris (1.13%), Citrobacter freundii (1.13%), and Citrobacter koseri (1.13%). High resistance to cephalosporins (82.18%) was demonstrated in all Gram-negative bacteria. Bacteria showed susceptibility to colistin (88.75%) followed by tigecycline (83.11%), gentamycin (36.18%), and amikacin (49.23%). Conclusions: As the most frequent respiratory organisms, Klebsiella pneumoniae and Acinetobacter spp. have increased resistance to cephalosporins and susceptibility to colistin followed by tigecycline.

Detection and Identification of Gonococci Resistance to Cephalosporin and Determination the Most Effective Empirical Treatment for Gonococcal Urethritis in Male Human in Egypt

Introduction: Gonorrhoeae and antimicrobial resistance AMR of gonococci is a major health problem today, because emerged resistance to last line empirical treatment for gonorrhoeae cephalosporins in many countries is predictable to be untreatable disease in near future. WHO GASP, WHO GLASS and WHO’s global action plan on AMR recommends to expand nationally and internationally to collect data to monitor AMR of gonococci for public health policies. Objective: Our aim is to detect resistance of gonococci to Cepha- losporins and determine the most effective empirical treatment for un-com- plicated gonococcal urethritis in males in Egypt. Methods: We depended in our methodology on selected gonococci from male urethral discharge specimens on Thyer Martien medium;collected 33 isolates during three years from 2017 to 2020;used antibiotics with MIC according to international standards and measuring IZD according to antimicrobial susceptibility testing reference ranges in international standards. Results: By statistical studies, resistance to cephalosporins was as follows: Cephradine 97%, Cefaclor 87.9%, Cefoxitin 97%, Ceftriaxone 90.9% and 42.4% to Cefepime, that shows hetero-genecity in resistance inside cephalosporin group;while resistance to Macrolides group represented by Azithromycin and Tetracyclins group represented by Doxycycline was as follows: Azithromycin 39.4%, Doxycycilne 27.3%;finally fluoroquinolones, the most effective group, resistance, was as: Levofloxacin 15.2%, Ciprofloxacin 15.2% and Ofloxacin 24.2%. Conclusion: The most effective empirical treatment for uncomplicated gonococcal urethritis in males in EGYPT is Fluoroquinolone;especially Levofloxacin ranks first susceptibility as 78.8% and 15.2% resistance followed by Ciprofloxacin susceptibility as 69.7% and 15.2% resistance, finally Ofloxacin susceptibility as 66.7% and 24.2% resistance;for Ceftriaxone not more recommended in EGYPT as empirical treatment for uncomplicated gonococcal urethritis, it is susceptibility as 6.1% and 90.9% resistance;in addition, we can use combination therapy of Fluoroquinolones with Azithromycin or Doxycycline, whose susceptibility is 30.3% for Azithromycin and 42.4% for Doxycycycline, while resistance is 39.4% for Azithromycin and 27.3% for Doxycycline. It is worth noting that only Cefepime in Cephalosporins group represents 42.4% susceptibility and 42.4% resistance;in addition to the Carbapenems group, it represents as 42.4% susceptibility for Imipenem and 45.5% resistance, then 42.2% susceptibility for Meropenem and 48.5% resistance, which can play role in combination therapy.

Post-appendectomy pelvic abscess with extended-spectrum beta-lactamase producing Escherichia coli : A case report and review of literature

BACKGROUND Appendicitis, the inflammation of the appendix, is the most common abdominal surgical emergency requiring expedient surgical intervention. Extendedspectrum beta-lactamases(ESBLs) are bacterial enzymes that catalyse the degradation of the betalactam ring of penicillins and cephalosporins(but without carbapenemase activity), leading to resistance of these bacteria to beta-lactam antibiotics. Recent increases in incidence of ESBL-producing bacteria have caused alarm worldwide. Proportion estimates of ESBLEnterobacteriaceae hover around 46% in China, 42% in East Africa, 12% in Germany, and 8% in the United States.CASE SUMMARY The impact of ESBL-producing bacteria on appendiceal abscesses and consequent pelvic abscesses are yet to be examined in depth. A literature review using the search words "appendiceal abscesses" and "ESBL Escherichia coli(E. coli)" revealed very few cases involving ESBL E. coli in any capacity in the context of appendiceal abscesses. This report describes the clinical aspects of a patient with appendicitis whodeveloped a postoperative pelvic abscess infected with ESBL-producing E. coli. In this report, we discuss the risk factors for contracting ESBL E. coli infection in appendicitis and post-appendectomy pelvis abscesses. We also discuss our management approach for postappendectomy ESBL E. coli pelvic abscesses, including drainage, pathogen identification, and pathogen characterisation. When ESBL E. coli is confirmed, carbapenem antibiotics should be promptly administered, as was done efficaciously with this patient. Our report is the first one in a developed country involving ESBL E. coli related surgical complications in association with a routine laparoscopic appendectomy.CONCLUSION Our report is the first involving ESBL E. coli and appendiceal abscesses, and that too consequent to laparoscopic appendectomy.

Selective Association between Cephalosporin, Quinolone, Macrolide, and Penicillin Antibiotic Consumption and Childhood Obesity in Europe

The accelerated weight gain in productive animals as a result of feeding antibiotic enriched fodder has been well known for decades. The better energy harvest is the result of modified gut microbiota as a consequence of applied antibiotics. Similar mechanisms might result obesity in humans as well. Objectives: Finding associations between global antibiotic consumption of different classes in EU countries and obesity data in adults and children prove that antibiotics might play a significant role in the development of obesity “epidemics” and related illnesses. Methods: Antibiotic consumption data were compared with obesity figures in adults and children in European countries and statistically analyzed for significance. Results: Significant correlation was found between the average yearly consumption of cephalosporins (p = 0.007), quinolones (p = 0.031), macrolides (p = 0.000083) and childhood obesity data, but no significant association was observed with the average penicillin consumption. No association was observed between adult obesity and any of the antibiotic classes studied. Conclusions: Our results support the hypothesis that different types of antibiotics might influence the development of obesity among children, and this finding can serve as a unified explanation for the development of obesity “epidemics”, similarly to the obesity and gut flora alteration-related diseases (type 2 diabetes mellitus, autism, etc.).

Nano-Coupling of Cephalosporin Antibiotics with Fe<SUB>3</SUB>O<SUB>4</SUB>Nanoparticles: Trojan Horse Approach in Antimicrobial Chemotherapy of Infections Caused by <i>Klebsiella spp</i>.

In the present study we had an aim to develop the methods of functionalizing the surface of magnetite nanoparticles with cefotaxime and ceftriaxone antibiotics. The quantitative analysis of the nanostructured cephalosporins was determined by Atom Absorbance Spectroscopy (AAS) and based on the Lambert-Beer law. The engineered nanostructures were tested on gram-negative microorganisms Klebsiella spp., of Enterobacteriaceae, and gram-positive bacteria Staphylococcus aureus, each having multi-drug resistance properties.

Theoretical Insights Elucidate Novel Active Phosphonate Esters—Cephalosporin Antibiotics’ Intermediate

Theoretical insights elucidate a series of active phosphonate esters application in preparation of Cephalosporin antibiotics’ intermediate. The B3LYP/6-311+G(d,p) method was employed to obtain the stable equilibrium geometries including comparing to the AE-active ester. It was found that the Ethyl-aminothiazoly Loximate (AT) molecule fragment is almost planar sheet, but it is almost perpendicular to the plane of phosphoryl ester. Moreover, the calculated Mulliken atomic charge distribution and frontier molecular orbital analysis of these esters showed that the amino N atom connected to the Thiazole ring of the AT had the maximum negative charge, which suggested that this area had high molecular activity. The value of ΔEL-H was energy gap between EHOMO and ELUMO and indicated that compound 6a had high reaction activity. The theory calculation results can explain the reaction mechanism well and predict that the novel active phosphonate ester has a hopeful application prospect in preparation of Cephalosporin antibiotics’ intermediate.

Synthesis and Antibacterial Activity of New Cephalosporin Compounds

Five new cephalosporin compounds were designed and synthesized, and the antibacterial activities were evaluated by the standard serial 2-fold agar dilution method in vitro. The results showed that the activities of the compounds Ia and lb against ESBL E. coli and K. pneumoniae are comparable to those of Cefepime.

Beta-Lactam Antibiotic Resistance among <i>Enterobacter</i>spp. Isolated from Infection in Animals

Nosocomial infections are frequent complications of hospitalization, caused by opportunistic pathogens that gain access to hosts undergoing invasive procedures, such as surgery, intubation, and placement of deep vein lines. Nosocomial infections in animal hospitals can infect other animals, as well as be transmitted to human personnel. Enterobacter is a genus of common gram-negative bacteria, which can be associated with antibiotic resistant hospital infections. Because of an outbreak in antibiotic resistance in the genus, we decided to investigate five years of Enterobacter infections in the Large Animal Services of the Lois Bates Acheson Veterinary Teaching Hospital (LBAVTH) at Oregon State University. The demographics from 37 Enterobacter-infected patients of the LBAVTH were obtained from charts and analyzed. The identified clusters of infections suggested possible patient-environment sources of infection. The environment of the hospital was sampled in an attempt to determine the source of infection. Although Enterobacter was not isolated, three of the collected samples contained bacteria with resistance to third-generation cephalosporins. Enterobacter isolates from six of the 37 patients were further analyzed for presence of specific ESBL resistance genes. All six of the isolates harbored multiple extended-spectrum beta-lactamase genes, i.e., CTX-M-15, TEM-80, SHV-2 and AmpC. In summary, Enterobacter infection in the veterinary hospital was caused by beta-lactam-resistant strains, carrying ESBL-resistant genes. Veterinary hospital personnel should be aware of the potential for transmission, to both humans and animals, of ESBL-gene-containing bacteria.

Clinical Pharmacokinetic and Bioequivalence Studies of Two Brands of Cephradine in Healthy Korean Using HPLC Method

The goal of our research was to compare the pharmacokinetics and evaluate the bioequivalence of two brands of cephradine 500 mg capsules in 24 normal Korean volunteers. The plasma samples were acquired at 13 time points for 8 h after administration. The concentrations of cephradine in human plasma were measured by a high-performance liquid chromatography (HPLC). Isocratic mobile phase which consisted of acetonitrile, methanol, and 20 mM potassium phosphate (15/5/80, v/v/v, pH 3.48) was used to separate the analytical column cosmosil cholester (250 × 4.6 mm, 3 μm). Analytes were detected in ultraviolet (260 nm). The novel analytical method was described as simple sample preparation, a short retention time (less than 6 min) and making it suitable for use in clinical trials. Pharmacokinetic parameters, such as AUC0-t (20.54 vs 18.42 μg·h/mL), AUC0-infinity (21.22 vs 19.14 μg·h/mL), Cmax (12.69 vs 12.81 μg/mL), Tmax (1.22 vs 0.92 h), half-life (1.02 vs 1.13 h), extrapolation (3.22% vs 3.75%), and Ke (0.73 vs 0.69 h–1) were determined for the reference and test drugs in plasma. Pharmacokinetic parameters with a 90% confidence interval were 87% - 95% for AUC0-t and 91% - 115% for Cmax. They were satisfied within the bioequivalence range 80% - 125% of the KFDA guidelines. Therefore, our HPLC method was well applied in a bioequivalence and pharmacokinetic study of two formulations in normal subjects.