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Background Managing drug–food interactions may help to achieve the optimal action and safety profile of β-lactam antibiotics. Methods We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 β-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD) indices. Results Eighteen of 25 β-lactams for which data on food impact were available had clinically important interactions. We observed the highest negative influence of food (AUC or C max decreased by >40%) for ampicillin, cefaclor (immediate-release formulations), cefroxadine, cefradine, cloxacillin, oxacillin, penicillin V (liquid formulations and tablets) and sultamicillin, whereas the highest positive influence (AUC or C max increased by >45%) for cefditoren pivoxil, cefuroxime and tebipenem pivoxil (extended-release tablets). Significantly lower bioavailability in the presence of antacids or mineral supplements occurred for 4 of 13 analysed β-lactams, with the highest negative impact for cefdinir (with iron salts) and moderate for cefpodoxime proxetil (with antacids). Data on beverage impact were limited to 11 antibiotics. With milk, the extent of absorption was decreased by >40% for cefalexin, cefradine, penicillin G and penicillin V, whereas it was moderately increased for cefuroxime. No significant interaction occurred with cranberry juice for two tested drugs (amoxicillin and cefaclor). Conclusions Factors such as physicochemical features of antibiotics, drug formulation, type of intervention, and patient's health state may influence interactions. Due to the poor actuality and diverse methodology of included studies and unproportionate data availability for individual drugs, we judged the quality of evidence as low. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 β-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 β-lactamase, overexpression of AcrABTolC 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 β-lactams and improving the therapeutic efficacy of Glässer's disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

Cephalexin and Cefaclor, are widely prescribed antibiotics known for their characteristic bitter taste. This bitterness is attributed to the specific chemical composition of these substances. The sensory experience of bitterness is influenced by distinct functional groups present in various foods and chemicals. Researchers have developed diverse techniques and strategies to modify these antibiotics' chemical structure while preserving their therapeutic efficacy to overcome this taste challenge. This study examines the role of the primary amine functional group in generating the bitter taste associated with Cephalexin andCefaclor. Methods: Schiff base reaction used to make Imines of Cephalexin and Cefaclor on their Primary amine functional group by reacting with Aldehydes (Citral, Vanillin, and Benzaldehyde). The Schiff bases bitternesselation evaluated through gustatory volunteers. Results: Formation of imines on the primary amine functional group in both Cephalexin and Cefaclor was achieved through the creation of Schiff bases with aldehydes, specifically Citral, Vanillin, and b enzaldehyde. This chemical transformation led to a slight alteration in the bitterness intensity measurement. Conclusions: The bitterness of Cephalexin and Cefaclor could be attributed to their Primary amine to a considerable extent, but not solely to the primary amine. Since the bitterness would not be obliterated evenafter manipulating it. The bitterness of the Cephalosporins is multifactorial involving other functional groupshappen to be found in their chemical structure. Further investigations should be carried out for each functional group of Cephalexin and Cefaclor evaluating the contribution of each of the

Root canal infection in primary teeth is polymicrobial in nature. Most resistant micro-organisms, such as E.faecalis survive in chronic infection of the root canal at the periapical area and are difficult to remove by various root canal irrigants. C.albicans has been found in chronic infections of root canals of primary teeth due to its ability to invade dentinal tubules. The multiple bacteria strains which cause endodontic infections, make it difficult to clean root canals with a single effective antibiotic. Hence Triple Antibiotic Paste (TAP) has been previously introduced, consisting of ciprofloxacin, metronidazole, and minocycline. Although this mixture aids in pulp regeneration and has been used to disinfect root canal systems, it is linked to tooth discolouration. The aim of this study is to evaluate and compare the antimicrobial efficacy of a newly formulated 3C antibiotic paste (consisting of Ciprofloxacin, Clindamycin, and Cefaclor) with conventional TAP against E. faecalis and C. albicans. In this in-vitro laboratory study, pure culture of C. albicans and E. faecalis will be grown on Sabouraud’s dextrose agar (SD) agar and Brain heart infusion agar (BHI) agar respectively and will be suspended for 24 hours at 37°C. For comparison of antimicrobial efficacy, the zone of inhibition will be for the 3C antibiotic paste against conventional TAP (control) for E. faecalis and C. albicans, and will be determined using digital calliper in millimetre after every 24 and 72 hours. We hypothesise that the newly formulated 3C paste will have better antimicrobial efficacy when compared with conventional TAP. It is expected that a newly formulated 3C paste will prove to be the successful as root canal filling material for primary teeth.

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.

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

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. [ABSTRACT FROM AUTHOR]

Root canal infection in primary teeth is polymicrobial in nature. Most resistant micro-organisms, such as E.faecalis survive in chronic infection of the root canal at the periapical area and are difficult to remove by various root canal irrigants. C.albicans has been found in chronic infections of root canals of primary teeth due to its ability to invade dentinal tubules. The multiple bacteria strains which cause endodontic infections, make it difficult to clean root canals with a single effective antibiotic. Hence Triple Antibiotic Paste (TAP) has been previously introduced, consisting of ciprofloxacin, metronidazole, and minocycline. Although this mixture aids in pulp regeneration and has been used to disinfect root canal systems, it is linked to tooth discolouration. The aim of this study is to evaluate and compare the antimicrobial efficacy of a newly formulated 3C antibiotic paste (consisting of Ciprofloxacin, Clindamycin, and Cefaclor) with conventional TAP against E. faecalis and C. albicans. In this in-vitro laboratory study, pure culture of C. albicans and E. faecalis will be grown on Sabouraud’s dextrose agar (SD) agar and Brain heart infusion agar (BHI) agar respectively and will be suspended for 24 hours at 37°C. For comparison of antimicrobial efficacy, the zone of inhibition will be for the 3C antibiotic paste against conventional TAP (control) for E. faecalis and C. albicans, and will be determined using digital calliper in millimetre after every 24 and 72 hours. We hypothesise that the newly formulated 3C paste will have better antimicrobial efficacy when compared with conventional TAP. It is expected that a newly formulated 3C paste will prove to be the successful as root canal filling material for primary teeth.

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. [ABSTRACT FROM AUTHOR]

In present study, eleven cephalosporin drugs were selected to explore their new medically important enzyme targets with inherited safety advantage. To this end, selected drugs with active ingredient, cefpodoxime proxetil, ceftazidime, cefepime, ceftriaxone sodium, cefaclor, cefotaxime sodium, cefixime trihydrate, cephalexin, cefadroxil, cephradine, and cefuroxime, were evaluated and found to have significant activity against urease (IC 50 = 0.06 ± 0.004 to 0.37 ± 0.046 mM) and tyrosinase (IC 50 = 0.01 ± 0.0005 to 0.12 ± 0.017 mM) enzymes. Urease activity was lower than standard thiourea; however, tyrosinase activity of all drugs outperforms (ranging 6 to 18 times) the positive control: hydroquinone (IC 50 = 0.18 ± 0.02 mM). Moreover, the kinetic analysis of the most active drugs, ceftriaxone sodium and cefotaxime sodium, revealed that they bind irreversibly with both the enzymes; however, their mode of action was competitive for urease and mixed-type, preferentially competitive for tyrosinase enzyme. Like in vitro activity, ceftriaxone sodium and cefotaxime sodium docking analysis showed their considerable binding affinity and significant interactions with both urease and tyrosinase enzymes sufficient for downstream signaling responsible for observed enzyme inhibition in vitro, purposing them as potent candidates to control enzyme-rooted obstructions in future. [ABSTRACT FROM AUTHOR]

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%.

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Abstract 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

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.

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. [ABSTRACT FROM AUTHOR]

Abstract Background Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC. Methods We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy. Results Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n = 160; 68.6%), followed by Klebsiella species and E. coli-extended spectrum β-lactamase (ESBL) (n = 19; 8.1% and n = 18; 7.7%). Overall success rate was 94.0% (n = 219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P

Abstract 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.

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.

Over past 30 years as the expanse and complication involved in marketing new drug entities have increased, with concomitant recognition of the therapeutic advantages of controlled drug delivery, greater attention has been focused on development of extended or controlled release drug delivery systems. In the present research work an attempt has been made to optimize, formulate and characterize extended-release tablet of Cefaclor. The preformulation studies were performed for the drug (e.g., physico-chemical properties, melting point, solubility etc.). The drug had shown the results under standard specifications. UV spectroscopic analytical method was also performed for quantitative determinations by plotting standard curve. Before this the pure drug was also scanned for the λ max value at different concentrations. The pre-compressions parameters and the post compression parameters for the nine formulated tablets were performed. The drug release study of the selected formulations EF3, EF6 and EF9 was performed as those formulations has shown the results within pharmacopoeia limits. The Formulation EF9 was then taken for release kinetic study as it has shown best results among the other three formulations. So, it confirms the drug release by Higuchi diffusion mechanism. From the results, conclusion can be drawn that the formulation consisting 10-12% concentration of hydroxypropyl methyl cellulose K4-M with 1% microcrystalline cellulose and 25% of lactose are considered as ideal for the optimized extended-release tablet formulation for Cefaclor. [ABSTRACT FROM AUTHOR]

Background: Conventional drug mixtures used in regenerative endodontic procedures have a toxic effect and no consensus has been reached about their best composition and concentration. Therefore, the aim of this study was to determine minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum biofilm inhibitory concentration (MBIC) of the antimicrobial preparations and to compare their antimicrobial efficacy on bovine dentin infected by Enterococcus faecalis. Materials and Methods: For this original ex vivo investigation, prepared concentrations (MIC, MBC, and MBIC) of triple antibiotic paste (TAP), double antibiotic paste (DAP), modified triple antibiotic paste (MTAP)-1, MTAP2, co-amoxiclav, and calcium hydroxide (CH) were added to the prepared bovine dentin blocks (which incubated in E. faecalis suspension previously) and incubated for 3 days. The samples were subsequently prepared for culture and CFU counts. Statistical analysis of data was carried out using one-way analysis of variance and post hoc tests. The statistical power was set at P < 0.05. Results: All medicament groups significantly showed an antimicrobial efficacy compared with negative control (without antibiotic) (P < 0.001). TAP, DAP, co-amoxiclav, and CH (at its MBC value) were significantly capable of eliminating E. faecalis biofilm and showed no significant difference in comparison with positive control (complete biofilm removal) (P < 0.05). Conclusion: TAP, DAP, co-amoxiclav, and CH (at its MBC value) could effectively eliminate biofilm bacteria on the dentin surface. Antimicrobial efficacy of other medicaments containing cefaclor or clindamycin was limited. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors have no conflict of interest relevant to this article to disclose., (© 2024 The Authors.)

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 β-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 β-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 (Y 103 D and L 517 R) and mrcA (A 639 V) 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 β-lactams and improving the therapeutic efficacy of Glässer's disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Yang, Deng, Li, Wang, Yi, Kuang, Xu, Li, Li, Yu and Yang.)

ObjectiveAntibiotic use rates have declined dramatically since the 1990s. We aimed to determine if, when, and at what level the decline in antibiotic-dispensing rates ended and which diagnoses contributed to the trends.MethodsAntibiotic dispensings and diagnoses were obtained from 2 health insurers for 3- to

Background: Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC.Methods: We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy.Results: Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n = 160; 68.6%), followed by Klebsiella species and E. coli-extended spectrum β-lactamase (ESBL) (n = 19; 8.1% and n = 18; 7.7%). Overall success rate was 94.0% (n = 219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P < 0.001). In the subgroup analysis, the success rate in patients with resistance to levofloxacin or cefazolin was 100% (n = 24) or 93.3% (n = 14). The rate in patients with resistance to both antibiotics was 60.0% (n = 9), and the pathogens in the other 40.0% (n = 6) of patients with treatment failure were E. coli-ESBL.Conclusion: Cefaclor showed excellent efficacy in AUC patients, even in those with in vitro resistance to cefazolin or levofloxacin. Cefaclor may be considered as a first-line option in patients with AUC and a second-line option for those with levofloxacin treatment failure. [ABSTRACT FROM AUTHOR]

Diabetic foot ulceration is a common and severe complication of diabetes, causing substantial social, medical, and economic burdens. Treatment of foot ulcers remains challenging, thus requiring increasing awareness and more efficient management. This study investigates the efficacy of ointments, containing as main active ingredient the olive oil extract of the marine isopod Ceratothoa oestroides, in the treatment of patients with diabetic foot ulcers. Fifty‐two patients were allocated into four treatment groups either receiving therapy with an ointment containing extract of C. oestroides or extract of C. oestroides and eosin or extract of C. oestroides and cefaclor or no treatment. Patients were monitored for a period of 135 days by evaluation of transepidermal water loss, skin hydration, planimetry, photo‐documentation, and clinical condition. Treatment with the extract of C. oestroides demonstrated significant healing properties that became evident after 45 days of treatment and resulted in complete ulcer healing in 61% of the patients. A significant improvement in transepidermal water loss (p < 0.001), skin hydration levels (p < 0.001), and wound area (p < 0.001) was observed in all patients. Similar efficacy was demonstrated for the combination of C. oestroides extract with eosin treatment (p < 0.001). On the contrary, the combination of C. oestroides extract with cefaclor antibiotic agent completely inhibited the healing properties of the isopod extract and did not improve water loss, skin hydration, or wound area. An important factor for C. oestroides extract healing properties is its selective activity against Gram negative bacteria. Ointments containing C. oestroides extract alone or combined with the antimicrobial agent eosin emerges as an effective regimen for the treatment of diabetic foot ulcers. [ABSTRACT FROM AUTHOR]

Background: Intracanal medicaments can be used in various endodontic conditions including multiple visit endodontics after trauma or in regenerative endodontics. These medicaments should be removed from the root canal before the placement of the filling or repair material. The aim of the present study was to evaluate the effect of prior calcium hydroxide (Ca(OH)2) and modified triple antibiotic paste (mTAP) placement on the push-out bond strength of TotalFill BC fast set putty (BC fast set putty) to root dentin when compared to mineral trioxide aggregate (MTA). Methods: The root canals of 45 extracted mandibular premolars were prepared to a standardized internal diameter (1.5 mm). The specimens were randomly assigned to 3 groups according to the intracanal medicament used: mTAP (a mixture of metronidazole, ciprofloxacin, and cefaclor), Ca(OH)2, and no intracanal medicament. After 1 week, the medicaments were removed, and the middle third of the roots were cut into two transverse sections (2.0 ± 0.05) (n = 90 slices). Thereafter, the specimens were divided into two subgroups (n = 45 each): MTA or BC putty. After 1 week, the push-out test was performed and failure mode was evaluated. The data were statistically analyzed using two-way ANOVA and Tukey's post hoc. Results: The application of the intracanal medicament did not significantly affect the bond strength of BC putty (p >.05). For MTA, the prior application of Ca(OH)2 or mTAP significantly decreased the dislocation resistance (p <.05). Specimens in the MTA subgroups showed an almost equal number of cohesive and mixed types of failure while the majority of the specimens in the BC putty subgroups revealed the cohesive type. Conclusions: Ca(OH)2 and mTAP promoted lower bond strength of MTA to root dentin compared to the control group. However, the BC fast set putty bond strength to dentin was not affected by prior medication with Ca(OH)2 or mTAP. [ABSTRACT FROM AUTHOR]

The over‐use of antibiotics has caused a number of problems such as contamination of antibiotic residues and virus resistance, and therefore has attracted global attention. In this study, spectroscopic techniques and molecular docking were employed to predict conformational changes and binding interaction between two cephalosporins (cefaclor and cefixime) and calf thymus DNA (ctDNA). Fluorescence and UV–vis spectra suggested that static quenching was predominant and cephalosporin bound to the groove region of ctDNA. Binding parameters calculated by the Stern–Volmer and Scatchard equations showed that cephalosporin bound to ctDNA with a binding affinity in the order of 103 L mol−1. Thermodynamic parameters further indicated that the reaction was a spontaneous process driven by enthalpy and entropy, and that the main binding force was an electrostatic force. The effects of iodide, denaturant, thermal denaturation and pH on a cephalosporin–Hoechst–DNA complex were also studied, and the results confirmed that cephalosporin bound to the groove area of DNA. Finally, these results were further confirmed by molecular docking and electrochemical studies. [ABSTRACT FROM AUTHOR]

Two simple spectrophotometric methods were developed and validated for determination of cefaclor in presence of its acid induced degradation product; namely simultaneous equation method using two wavelengths 265 and 235 nm Method (A) and Area under the curve method using two wavelength ranges (230–240) nm and (260–270) nm Method (B). The accuracy, precision and linearity ranges of the proposed methods were determined. The methods were validated and the specificity was assessed by analyzing synthetic mixtures containing the drug and its degradate. The two methods were applied for the determination of the cited drug in its pharmaceutical preparation and the obtained results were statistically compared with those of a reported method. The comparison showed that there is no significant difference between the proposed methods and the reported method regarding both accuracy and precision.

A comparative degradation of antibiotic cefaclor (CEC) between Ti/Ti 4 O 7 and Ti/RuO 2 anodes, in terms of degradation kinetics, mineralization efficiency, and formation of toxic chlorate (ClO 3 −) and perchlorate (ClO 4 −), 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/Ti 4 O 7 anode was higher than that of Ti/RuO 2 anode, but slightly lower than that of BDD anode. Under the optimal conditions, 94.8% mineralization was obtained in Ti/Ti 4 O 7 -PEF, which was much higher than 64.4% in Ti/RuO 2 -PEF. The use of Ti/RuO 2 gave no generation of ClO 3 − or ClO 4 −, while the use of Ti/Ti 4 O 7 yielded a small amount of ClO 3 − and trace amounts of ClO 4 −. Conversely, the use of BDD led to the highest generation of ClO 3 − and ClO 4 −. The reaction mechanism was studied systematically by detecting the generated H 2 O 2 and •OH. The initial N of CEC was released as NH 4 + and, in smaller proportion, as NO 3 −. Four short-chain carboxylic acids and nine aromatic intermediates were also detected, a possible reaction sequence for CEC mineralization was finally proposed. • Influence of anode materials on cefaclor (CEC) mineralization was investigated. • Higher mineralization and fewer perchlorate were achieved with Ti/Ti 4 O 7 anode. • A plausible CEC mineralization pathway involving •OH by EF and PEF was proposed. • Ti/Ti 4 O 7 was suitable for EF and PEF treatment of chlorinated organic wastewater. • The comparation of toxic by-products generation for different anodes. [ABSTRACT FROM AUTHOR]

Abstract Globally, pneumonia is considered to be the biggest killer of infants and young children (aged

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.