Structure-Based Analysis of Cefaclor Pharmacokinetic Diversity According to Human Peptide Transporter-1 Genetic Polymorphism.

Cefaclor is a substrate of human-peptide-transporter-1 (PEPT1), and the impact of inter-individual pharmacokinetic variation due to genetic polymorphisms of solute-carrier-family-15-member-1 (SLC15A1) has been a topic of great debate. The main objective of this study was to analyze and interpret cefaclor pharmacokinetic variations according to genetic polymorphisms in SLC15A1 exons 5 and 16. The previous cefaclor bioequivalence results were integrated with additional SLC15A1 exons 5 and 16 genotyping results. An analysis of the structure-based functional impact of SLC15A1 exons 5 and 16 genetic polymorphisms was recently performed using a PEPT1 molecular modeling approach. In cefaclor pharmacokinetic analysis results according to SLC15A1 exons 5 and 16 genetic polymorphisms, no significant differences were identified between genotype groups. Furthermore, in the population pharmacokinetic modeling, genetic polymorphisms in SLC15A1 exons 5 and 16 were not established as effective covariates. PEPT1 molecular modeling results also confirmed that SLC15A1 exons 5 and 16 genetic polymorphisms did not have a significant effect on substrate interaction with cefaclor and did not have a major effect in terms of structural stability. This was determined by comprehensively considering the insignificant change in energy values related to cefaclor docking due to point mutations in SLC15A1 exons 5 and 16, the structural change in conformations confirmed to be less than 0.05 Å, and the relative stabilization of molecular dynamic simulation energy values. As a result, molecular structure-based analysis recently suggested that SLC15A1 exons 5 and 16 genetic polymorphisms of PEPT1 were limited to being the main focus in interpreting the pharmacokinetic diversity of cefaclor.

HLA-DRB1 is associated with cefaclor-induced immediate hypersensitivity.

Background: Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity. Methods: Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site. Results: Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10-8 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 [95% CI 1.51-14.09], P < 0.002) and HLA-DRB1∗14:54 (OR 3.86 [95% CI 1.09-13.67], P < 0.002). Conclusion: LIMD1, HLA-DRB1∗04:03 and HLA-DRB1∗14:54 may affect susceptibility to cefaclor induced type I hypersensitivity. Further confirmative studies with a larger patient population should be performed to ascertain the role of HLA-DRB1 and LIMD1 in the development of cefaclor induced hypersensitivity.

Matrine reverses the resistance of Haemophilus parasuis to cefaclor by inhibiting the mutations in penicillin-binding protein genes (ftsI and mrcA).

Introduction: Matrine (MT) is a potential resistance reversal agent. However, it remains unclear whether MT can reverse the resistance of Haemophilus parasuis (H. parasuis) to ß-lactams, and, if so, by what mechanism MT works. Methods: We screened one cefaclor (CEC)-resistant strain (clinical strain C7) from eight clinical (H. parasuis) strains and determined the underlying resistance mechanism. Then, we investigated the reversal effect of MTon the resistance of this strain to CEC. Results and Discussion: The production of ß-lactamase, overexpression of AcrAB-TolC system, and formation of biofilm might not be responsible for the resistance of clinical strain C7 to CEC. Fourteen mutation sites were found in four PBP genes (ftsI, pbp1B, mrcA, and prcS) of clinical strain C7, among which the mutation sites located in ftsI (Y103D and L517R) and mrcA (A639V) genes triggered the resistance to CEC. The minimum inhibitory concentration (MIC) of CEC against clinical strain C7 was reduced by two to eight folds after MT treatment, accompanied by the significant down-regulated expression of mutated ftsI and mrcA genes. Based on such results, we believed that MT could reverse the resistance of H. parasuis to CEC by inhibiting the mutations in ftsI and mrcA genes. Our research would provide useful information for restoring the antimicrobial activity of ß-lactams and improving the therapeutic efficacy of Glässer's disease.

The Efficacy of Different Antibiotic Compounds in Regenerative Treatment of Immature Necrotic Teeth.

Objectives: Endodontic treatment of immature teeth poses a significant challenge, especially in achieving a proper seal using traditional obturation methods. Revascularization presents itself as an alternative approach to this problem, and the application of triple antibiotic paste (TAP) has been suggested as a means to achieve disinfection during the procedure. This study aims to compare the antibacterial properties of three different antibiotic combinations to assess their effectiveness on root canal disinfection. Materials and Methods: Eighty samples were employed to assess the impact of three antibiotic combinations on Enterococcus faecalis, Escherichia coli, Streptococcus mutans, and a combination thereof. The antibiotics included metronidazole, ciprofloxacin, and cefaclor (CCM), the commonly used TAP, and a double antibiotic paste (DAP) composed of metronidazole and ciprofloxacin. Dentin shavings collected using Gates-Glidden drills were placed in microtubes containing a 2ml standard bacterial suspension. Microtube contents were diluted and cultured on BHI agar plates, with colony counts calculated based on dentine shavings' weight in CFU/mg. Kruskal-Wallis and Dunn's post-hoc tests were used for statistical analysis and P<0.05 was considered significant. Results: A significant difference in mean CFU was observed among all bacterial groups (P<0.05). Dunn's post-hoc analysis showed a significant difference only between the control group (methylcellulose) and the other antibiotic groups. There was no significant difference between the other antibiotic groups in two-by-two comparisons. Conclusion: There was no significant difference in the antimicrobial properties of DAP, TAP and CCM. Therefore, DAP and CCM may be used during regenerative treatment.

Exploring the pharmacokinetics of second-generation cephalosporin, cefaclor: a systematic review in healthy and diseased populations.

Cefaclor is a bactericidal antibiotic recommended for treating diverse types of infections. This review aims to comprehensively assess the pharmacokinetic (PK) data on cefaclor in humans.Google Scholar, PubMed, Cochrane Library, and EBSCO databases were systematically performed to identify all the relevant studies containing at least one reported PK parameter of cefaclor.Cefaclor shows the linear PK profile as the area under the plasma concentration-time curve from 0 to t (AUC0-t) and maximum plasma concentration (Cmax) increase in a dose-dependent manner. The AUC0-t of cefaclor in the rice diet was found to be higher than that of bread food, i.e. 19.9 ± 2.6 ug/ml.hr vs 15.4 ± 4 ug/ml.hr. The AUC in paediatrics during the fed state was significantly higher compared to that in adults. Patients with renal impairments showed a Cmax 2.2 times higher than that of normal subjects. A significant increase in Cmax was depicted among individuals following a vegetarian diet in comparison with the non-vegetarian diet. Moreover, cefaclor exhibits time-dependent killing above the minimum inhibitory concentration (MIC < 2 ug), favouring its use in treating infections caused by specific pathogens.This systematic review summarises all the reported PK parameters of cefaclor in healthy and diseased subjects in the literature. This data can help practitioners in adjusting cefaclor doses among different diseases and populations to avoid drug interactions and adverse effects.

Activated carbon fiber as an efficient co-catalyst toward accelerating Fe2+/Fe3+ cycling for improved removal of antibiotic cefaclor via electro-Fenton process using a gas diffusion electrode.

The electro-Fenton (EF) based on gas-diffusion electrodes (GDEs) reveals promising application prospective towards recalcitrant organics degradation because such GDEs often yields superior H2O2 generation efficiency and selectivity. However, the low efficiency of Fe2+/Fe3+ cycle with GDEs is always considered to be the limiting step for the EF process. In this study, activated carbon fiber (ACF) was firstly employed as co-catalyst to facilitate the performance of antibiotic cefaclor (CEC) decomposition in EF process. It was found that the addition of ACF co-catalyst achieved a rapid Fe2+/Fe3+ cycling, which significantly enhanced Fenton's reaction and hydroxyl radicals (•OH) generation. X-ray photoelectron spectroscopy (XPS) results indicated that the functional groups on ACF surface are related to the conversion of Fe3+ into Fe2+. Moreover, DMSO probing experiment confirmed the enhanced •OH production in EF + ACF system compared to conventional EF system. When inactive BDD and Ti4O7/Ti anodes were paired to EF system, the addition of ACF could significantly improve mineralization degree. However, a large amount of toxic byproducts, including chlorate (ClO3-) and perchlorate (ClO4-), were generated in these EF processes, especially for BDD anode, due to their robust oxidation capacity. Higher mineralization efficiency and less toxic ClO4- generation were obtained in the EF + ACF process with Ti4O7/Ti anode. This presents a novel alternative for efficient chloride-containing organic removal during wastewater remediation.

Insights into antibiotic cefaclor mineralization by electro-Fenton and photoelectro-Fenton processes using a Ti/Ti4O7 anode: Performance, mechanism, and toxic chlorate/perchlorate formation.

A comparative degradation of antibiotic cefaclor (CEC) between Ti/Ti4O7 and Ti/RuO2 anodes, in terms of degradation kinetics, mineralization efficiency, and formation of toxic chlorate (ClO3-) and perchlorate (ClO4-), was performed with electrochemical-oxidation (EO), electro-Fenton (EF), and photoelectro-Fenton (PEF) processes. Besides, CEC degradation by EF with boron-doped diamond (BDD) anode was also tested. Results showed CEC decays always followed pseudo-first-order kinetics, with increasing apparent rate constants in the sequence of EO < EF < PEF. The mineralization efficiency of the processes with Ti/Ti4O7 anode was higher than that of Ti/RuO2 anode, but slightly lower than that of BDD anode. Under the optimal conditions, 94.8% mineralization was obtained in Ti/Ti4O7-PEF, which was much higher than 64.4% in Ti/RuO2-PEF. The use of Ti/RuO2 gave no generation of ClO3- or ClO4-, while the use of Ti/Ti4O7 yielded a small amount of ClO3- and trace amounts of ClO4-. Conversely, the use of BDD led to the highest generation of ClO3- and ClO4-. The reaction mechanism was studied systematically by detecting the generated H2O2 and •OH. The initial N of CEC was released as NH4+ and, in smaller proportion, as NO3-. Four short-chain carboxylic acids and nine aromatic intermediates were also detected, a possible reaction sequence for CEC mineralization was finally proposed.

Vagus nerve-dependent effects of fluoxetine on anxiety- and depression-like behaviors in mice.

The vagus nerve is a major pathway in the body that is responsible for regulating the activity of the parasympathetic nervous system, which plays an important role in mood disorders including anxiety and depression. Fluoxetine, also known as Prozac, is widely used to treat depression. Nevertheless, there are few studies on the vagus nerve-mediated action of fluoxetine. In this study, we aimed to investigate the vagus nerve-dependent actions of fluoxetine in mice with restraint stress-induced or antibiotics-induced anxiety- and depression-like behaviors. Compared to sham operation, vagotomy alone did not exhibit significant effects on behavioral changes and serotonin-related biomarkers in mice not exposed to stress, antibiotics, or fluoxetine. Oral administration of fluoxetine significantly alleviated anxiety- and depression-like behaviors. However, celiac vagotomy significantly attenuated the anti-depressive effects of fluoxetine. The vagotomy also inhibited the effect of fluoxetine to attenuate restraint stress- or cefaclor-induced reduction in serotonin levels and Htr1a mRNA expression in the hippocampus. These findings suggest that the vagus nerve may regulate the efficacy of fluoxetine for depression.

Quantification of cefaclor in human plasma using SIL-IS LC-ESI-MS/MS for pharmacokinetics study in healthy Chinese volunteers.

A steady, high-efficiency, and precise liquid chromatography-electrospray ionization-tandem mass spectrometry method was established and validated using cefaclor-d5 as the stable isotope-labeled internal standard for quantification of cefaclor in human plasma. One-step protein precipitation was applied to extract human plasma samples using methanol as precipitant. An Ultimate XB C18 column (2.1 × 50.0 mm, 5.0 µm) was used to achieve chromatographic separation. Mobile phases of gradient elution were an aqueous solution containing 0.1% formic acid (mobile phase A) and an acetonitrile solution containing 0.1% formic acid (mobile phase B). Electrospray ionization in positive-ion mode was applied to detect under multiple reaction monitoring mode. Target fragment ion pairs of cefaclor and stable isotope-labeled internal standard, respectively, were m/z 368.2 → 191.1 and m/z 373.2 → 196.1. Linear range of this method was between 20.0 and 10,000.0 ng/ml, with coefficient of determination (R2 ) >0.9900. Seven concentrations of quality control samples were used: 20.0 ng/ml (lower limit of quantitation), 60.0 ng/ml (low quality control), 650 ng/ml (middle quality control), 5000 ng/ml (arithmetic average middle quality control [AMQC]), 7500 ng/ml (high quality control), 10,000 ng/ml (upper limit of quantification), and 40,000 ng/ml (dilution quality control [DQC]). The method was validated for selectivity, lower limit of quantitation, linearity, accuracy, precision, recovery, matrix effect, dilution reliability, stability, carryover, and incurred sample reanalysis. This stable isotope-labeled internal standard liquid chromatography-electrospray ionization-tandem mass spectrometry approach has been successfully applied to study the pharmacokinetics of cefaclor dry suspension among healthy Chinese volunteers.

Pharmacokinetics and safety of the two oral cefaclor formulations in healthy chinese subjects in the fasting and postprandial states.

We conducted a phase I bioequivalence trial in healthy Chinese subjects in the fasting and postprandial states. The goal of this trial was to compare the pharmacokinetics and safety of the test preparation Cefaclor granule (Disha Pharmaceutical Group Co., Ltd.) and the reference preparation Cefaclor suspension (Ceclor®, Eli Lilly and Company). In this trial, 24 subjects were selected in the fasting and postprandial states, respectively. Enrolled subjects randomly accepted a single dose of 0.125 g Cefaclor granule or Cefaclor suspension. The washout period was set as 2 days. Blood samples were collected within 8 h after administration in the fasting state and within 10 h after administration in the postprandial state. Plasma concentrations were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters (AUC, Cmax) were used to evaluate bioequivalence of the two drugs. In the fasting trial, the geometric mean ratios (90% confidence intervals CIs) for Cmax, AUC0-t, and AUC0-∞ were 93.01% (85.96%-100.63%), 97.92% (96.49%-99.38%) and 97.95% (96.52%-99.41%), respectively. The GMR (90% CIs) for Cmax, AUC0-t, and AUC0-∞ in postprandial state were 89.27% (81.97%-97.22%), 97.31% (95.98%-98.65%) and 97.31% (95.93%-98.71%), respectively. The 90% CIs of AUC and Cmax in the fasting and postprandial states were within the 80-125% bioequivalence range. Therefore, Cefaclor granule and Cefaclor suspension were bioequivalent and displayed similar safety profiles. Furthermore, food intake affected the pharmacokinetic parameters of both drugs.

Dataset of response characteristics of H2-producing bacteria consortium to ß-lactams, aminoglycosides, macrolides, quinolones antibiotics.

Antibiotics on H2 producing bacteria shall be considered as being one of the critical elements in biological H2 production utilizing livestock manure as raw resources. Despite the fact that the manure stands a significance role in bio-fermentation, the possibility of antibiotics being contained in excreta shall not be eliminated. Findings of whether the above saying might threaten the safety of bio-H2 production needs to be further studied. The experiment subjects include: six single and three combined antibiotics were tested and analyzed by the application of the gradient experiment method. Along with the H2 production rate, CHO content, pH and OD600 were used to analyze the effects of various antibiotics introduction on the hydrolysis, fermentation and H2 production. To a further extent, four typical representative samples were selected for biodiversity analysis from the single antibiotic experiment groups. Amounting more than 6000 pieces of data were obtained in a series of experiments. Data suggested that remarkable measure of antibiotics have various degrees of H2 production inhibition, while some antibiotics, Penicillin G, Streptomycin Sulfate, and their compound antibiotics, could promote the growth of Ethanoligenens sp. and improve H2 yield in the contrary. Correspondent to the transition of key metabolic intermediates and end products, the mechanism of each antibiotic type and dose on H2 production were summarized as follows: the main inhibitory mechanisms were: (1) board-spectrum inhibition, (2) partial inhibition, (3) H2 consumption enhancement; and the enhancement mechanisms were: (1) enhance the growth of H2-producing bacteria, (2) enhanced starch hydrolysis, (3) inhibitory H2 consumption or release of acid inhibition. Meanwhile, data analysis found that the effect of antibiotics on H2 producing was not only related to type, but also to dosage. Even one kind of antibiotic may have completely opposite effects on H2-producing bacteria under different dosage conditions. Inhibition of H2 yield was highest with Levofloxacin at 6.15 mg/L, gas production was reduced by 88.77%; and enhancement of H2 yield was highest with Penicillin G at 7.20 mg/L, the gas production increased by 72.90%.

Intradermal testing increases the accuracy of an immediate-type cefaclor hypersensitivity diagnosis.

Background: Hypersensitivity reactions to cefaclor have increased in accordance with its frequent use. However, only limited data are available on the diagnostic value of skin tests for these conditions, particularly intradermal tests (IDTs). Objective: To evaluate the clinical usefulness of IDT compared to the ImmunoCAP test in patients with cefaclor-induced immediate-type hypersensitivity. Methods: We conducted a retrospective chart review from January 2010 to June 2020 of adult subjects from 2 tertiary hospitals in Korea with a history of suspected immediate-type hypersensitivity to cefaclor, and who had undergone ImmunoCAP and IDT. Results: Overall, 131 subjects diagnosed with cefaclor hypersensitivity were included in the analysis. Fifty-nine patients (59/131, 45.04%) were positive in both IDT and ImmunoCAP. Fifty-four (54/131, 41.22%) and 6 (6/131, 4.58%) subjects showed positive results only with IDT or the ImmunoCAP test, respectively. Twelve subjects (12/131, 9.16%) were negative by both tests but reacted positively in a drug provocation test. The frequency of IDT positivity was similar regardless of the severity of reactions. However, positivity of ImmunoCAP was lower in subjects with mild reactions compared to those with anaphylaxis. Regarding the diagnosis of cefaclor hypersensitivity, the overall sensitivity of IDT and ImmunoCAP was 0.863 and 0.496, respectively while the specificity was 1. The combination of IDT and ImmunoCAP further increased this sensitivity to 0.908. Conclusion: IDT was more sensitive than ImmunoCAP for the diagnosis of cefaclor allergy, regardless of the severity of the hypersensitivity reaction. Therefore, we recommend a combination of IDT and ImmunoCAP for the diagnosis of cefaclor hypersensitivity.

[Suppurative Thrombophlebitis of the Posterior Neck Caused by Streptococcus constellatus: A Case Report and Literature Review].

We report a rare case of suppurative thrombophlebitis of the posterior neck caused by Streptococcus constellatus. A 69-year-old female patient was admitted to the hospital with neck pain and fever, which had persisted for 16 days prior to hospitalization. On day 1 (day of admission), blood cultures (later identifying S. constellatus) were performed, and ceftriaxone (CTRX) IV (2 g SID) was started. On day 3, suppurative thrombophlebitis of the posterior neck was diagnosed by CT scan. The antimicrobials were changed from CTRX to ampicillin/sulbactam IV (12 g QID) to guard against the possibility of complicated infection with Fusobacterium spp. or Prevotella spp. On day 17, a CT scan revealed that the thrombus remained. Therefore, oral edoxaban (30 mg SID) was started. On day 27, the patient was discharged after her medication was changed to oral amoxicillin/clavulanate (1500 mg/375 mg TID). On day 33, the amoxicillin/clavulanate was changed to oral cefaclor (1500 mg TID) and edoxaban was discontinued due to itching. On day 45, the course of cefaclor was completed. The patient went on to follow an uneventful course with no relapses or complications for two years since the conclusion of treatment. These results suggest that when a patient presents with persistent neck pain accompanied by fever, suppurative thrombophlebitis of the posterior neck should be considered. In antimicrobial therapy, the treatment could be switched from intravenous to oral. In addition, direct-acting oral anticoagulants may be an alternative to other forms of anticoagulants.

Case: Unexpected development of severe penicillin allergy and review of literature.

A 54-year-old man developed a severe anaphylactic penicillin allergy after 16 years and 5 standard erysipelas treatments by intravenous benzylpenicillin and/or oral phenoxymethylpenicillin without any symptoms of allergy. It is recommended to analyze specific IgE antibodies for phenoxymethylpenicillin, benzylpenicillin, amoxicillin, and cefaclor to select an appropriate antibiotic.

Population-Based Incidence of New Ampicillin, Cephalexin, Cefaclor, and Sulfonamide Antibiotic "Allergies" in Exposed Individuals with and without Preexisting Ampicillin, Cephalexin, or Cefaclor "Allergies".

BACKGROUND: There is a theoretical concern, unconfirmed by population-based challenge data, that clinically significant, immunologically mediated hypersensitivity occurs among ß-lactams sharing side chains. OBJECTIVE: To determine the population-based allergy incidence associated with the use of ß-lactams sharing exact R1 side chains (ampicillin, cephalexin, and cefaclor [ACC]), with or without a current ACC allergy or a sulfonamide antibiotic allergy for comparison. METHODS: All courses of ACC and trimethoprim-sulfamethoxazole used by any Kaiser Permanente California members in 2017 and 2018, with follow-up through January 2019, were identified along with their preexisting antibiotic allergy status and all new antibiotic-specific allergies reported within 30 days of course initiation. RESULTS: A total of 1,167,713 courses of ACC were administered to individuals with no sulfonamide antibiotic or ACC allergy and 4,771 new ACC allergies (0.41%) were reported. Moreover, 130,032 courses of ACC were administered to individuals with a sulfonamide antibiotic allergy and no ACC allergy, and 904 new ACC allergies (0.70%) were reported. There were 5,958 courses of ACC administered to individuals with an ACC allergy, 2,341 who also had sulfonamide antibiotic allergy, and 52 new ACC allergies (0.87%) were reported. CONCLUSIONS: The incidence of new ACC allergy reports is minimally and non-specifically increased among individuals with a preexisting ACC or sulfonamide antibiotic allergy compared to the baseline incidence in the population. This argues against clinically significant, immunologically mediated cross-reactivity among ß-lactams sharing exact side chains in individuals with preexisting but unconfirmed ß-lactam allergy. Any previously reported, even unrelated antibiotic allergy appears to be a risk factor for reporting a new antibiotic allergy.

Population Pharmacokinetic Analysis of Cefaclor in Healthy Korean Subjects.

The aims of this study were: (1) to perform population pharmacokinetic analysis of cefaclor in healthy Korean subjects, and (2) to investigate possible effects of various covariates on pharmacokinetic parameters of cefaclor. Although cefaclor belongs to the cephalosporin family antibiotic that has been used in various indications, there have been very few population studies on factors affecting its pharmacokinetics. Therefore, this study is very important in that effective therapy could be possible through a population pharmacokinetic study that explores effective covariates related to cefaclor pharmacokinetic diversity between individuals. Pharmacokinetic results of 48 subjects with physical and biochemical parameters were used for the population pharmacokinetic analysis of cefaclor. A one-compartment with lag-time and first-order absorption/elimination was constructed as a base model and extended to include covariates that could influence between-subject variability. Creatinine clearance and body weight significantly influenced systemic clearance and distribution volume of cefaclor. Cefaclor's final population pharmacokinetic model was validated and some of the population's pharmacokinetic diversity could be explained. Herein, we first describe the establishment of a population pharmacokinetic model of cefaclor for healthy Koreans that might be useful for customizing cefaclor or exploring additional covariates in patients.

Cefaclor Monohydrate-Loaded Colon-Targeted Nanoparticles for Use in COVID-19 Dependent Coinfections and Intestinal Symptoms: Formulation, Characterization, Release Kinetics, and Antimicrobial Activity.

Corona virus disease-2019 (COVID-19) emerged in Wuhan, China in December 2019 and was declared as a pandemic by the World Health Organization in March 2020. Although there is no complete treatment protocol for COVID-19, studies on this topic are ongoing, and it is known that broad-spectrum antibiotics such as cephalosporins are used for coinfections and symptoms in COVID-19 patients. Studies have shown that Staphylococcus aureus and Escherichia coli bacteria can cause symptoms such as diarrhea and coinfections accompanying COVID-19. Therefore, in this study, colon-targeted cefaclor monohydrate (CEF)-loaded poly(lactic-co-glycolic acid) (PLGA)-Eudragit S100 nanoparticles (NPs) were prepared using a nanoprecipitation technique. The particle sizes of the CEF-loaded NPs were between 171.4 and 198.8 nm. The encapsulation efficiency was in the range of 58.4%-81.2%. With dissolution studies, it has been concluded that formulations prepared with Eudragit S100 (E-coded) and Eudragit S100+PLGA (EP-coded) are pH-sensitive formulations and they are targetable to the colon, whereas the formulation prepared only with PLGA (P-coded) can release a higher CEF rate in the colon owing to the slow release properties of PLGA. The release kinetics were fitted to the Korsmeyer-Peppas and Weibull models. The antibacterial activity of E-, EP-, and P-coded formulations was 16-fold, 16-fold, and 2-fold higher than CEF, respectively, for S. aureus and E. coli according to the microdilution results. As a result of the time killing experiment, all formulations prepared were found to be more effective than the antibiotic itself for long periods. Consequently, all formulations prepared in this study hope to guide researchers/clinicians in treating both gram-positive and gram-negative bacteria-induced infections, as well as COVID-19 associated coinfections and symptoms.

Clinical characteristics and risk factors for cefaclor-induced immediate hypersensitivity: a retrospective observation at two university hospitals in Korea.

BACKGROUND: Cefaclor, a second-generation oral cephalosporin, is widely prescribed to treat infectious diseases. Immediate hypersensitivity (HS) reactions to cefaclor have continuously been reported and are expected to increase with its greater use. This study aimed to investigate the clinical characteristics and risk factors of immediate HS to cefaclor over the most recent 5 years. METHODS: This retrospective study investigated 521 adverse drug reactions (ADRs) to cefaclor at pharmacovigilance centers at two tertiary hospitals from January 2014 to December 2018. In total, 459 patients with immediate HS to cefaclor were reviewed. RESULTS: A total of 459 cases of cefaclor immediate HS were included among 521 cefaclor ADRs, and anaphylaxis was recorded in 61.2%. Female sex (odds ratio 2.917, 95% confidence interval 2.397-3.550, P < 0.001), age under 65 years (4.225, 3.017-5.916, P < 0.001), hypertension (2.520, 1.875-3.388, P < 0.001), liver diseases (2.189, 1.208-3.967, P = 0.010), asthma (8.075, 5.301-12.302, P < 0.001), and concomitant use of nonsteroidal anti-inflammatory drugs (1.888, 1.554-2.294, P < 0.001) were significantly associated with cefaclor immediate HS. CONCLUSIONS: Cefaclor was found to elicit high proportions of immediate HS and anaphylaxis. Physicians ought to be cautious with prescribing cefaclor to females, individuals with hypertension, liver diseases, or asthma, and patients taking nonsteroidal anti-inflammatory drugs. TRIAL REGISTRATION: This study was retrospectively registered.

Evaluating Immediate Reactions to Cephalosporins: Time Is of the Essence.

BACKGROUND: Few studies have assessed the diagnostic value of cephalosporin skin tests in patients with immediate reactions to these ß-lactams. OBJECTIVE: To evaluate the usefulness of skin tests and challenges in assessing such subjects. METHODS: We conducted a prospective study of 236 consecutive subjects who had suffered 249 immediate reactions (mostly anaphylaxis) to cephalosporins. Skin tests were performed with penicillin reagents and suspected cephalosporins. Serum specific IgE assays (ImmunoCAP) were also carried out for penicillins and cefaclor. Subjects with negative results underwent challenges with the suspected cephalosporins; patients with negative results who had been assessed more than 6 months after their reactions were reevaluated. RESULTS: In the first allergy workup, an IgE-mediated hypersensitivity to cephalosporins was diagnosed in 164 (69.5%) of the 236 patients on the basis of skin test (162 patients) or cefaclor ImmunoCAP positivity (2 patients). Of the 72 patients with negative results, 55 underwent cephalosporin challenges; 3 reacted. Twenty subjects were reevaluated after cephalosporin negative challenges, with a conversion to cephalosporin skin test positivity occurring in 5 of the 6 subjects who had had anaphylactic reactions and in none of the remaining 14 subjects with other reactions. Overall, an immediate hypersensitivity to cephalosporins was diagnosed in 172 patients (of whom it was diagnosed in 5 after retesting). CONCLUSIONS: Most immediate reactions to cephalosporins are IgE-mediated. Cephalosporin skin testing is a useful tool for evaluating these reactions. IgE-mediated cephalosporin hypersensitivity may be a transient condition; therefore, allergy examinations should be repeated in patients with negative results who experienced anaphylaxis more than 6 months before the allergy workup, including challenges.

HPLC/ESI-MS identification of diastereomers of Impurity E - Degradation products of cefaclor.

A seven years old sample of cefaclor stored in room conditions, as a solid, has been analyzed by using high performence liquid chromatography/electrospray ionization-mass spectrometry. As a result of the sample degradation process, two diastereomers of Impurity E have been found to have formed. It is reasonable to assume that the diastereomers are formed due to the isomerization of C6 carbon atom. They have almost identical fragmentation patterns in both positive and negative ion mode. On the other hand, the diastereomers have different efficiencies of formation of dimer ions, under ESI conditions, especially in negative ion mode.