Concentrations Of Ceftriaxone Research Articles

Influence of ceftriaxone on human bone cell viability and in vitro mineralization potential is concentration- and time-dependent.

AimsIn orthopaedic and trauma surgery, implant-associated infections are increasingly treated with local application of antibiotics, which allows a high local drug concentration to be reached without eliciting systematic adverse effects. While ceftriaxone is a widely used antibiotic agent that has been shown to be effective against musculoskeletal infections, high local concentrations may harm the surrounding tissue. This study investigates the acute and subacute cytotoxicity of increasing ceftriaxone concentrations as well as their influence on the osteogenic differentiation of human bone progenitor cells.MethodsHuman preosteoblasts were cultured in presence of different concentrations of ceftriaxone for up to 28 days and potential cytotoxic effects, cell death, metabolic activity, cell proliferation, and osteogenic differentiation were studied.ResultsCeftriaxone showed a cytotoxic effect on human bone progenitor cells at 24 h and 48 h at concentrations above 15,000 mg/l. With a longer incubation time of ten days, subtoxic effects could be observed at concentrations above 500 mg/l. Gene and protein expression of collagen, as well as mineralization levels of human bone progenitor cells, showed a continuous decrease with increasing ceftriaxone concentrations by days 14 and 28, respectively. Notably, mineralization was negatively affected already at concentrations above 250 mg/l.ConclusionThis study demonstrates a concentration-dependent influence of ceftriaxone on the viability and mineralization potential of primary human bone progenitor cells. While local application of ceftriaxone is highly established in orthopaedic and trauma surgery, a therapeutic threshold of 250 mg/l or lower should diminish the risk of reduced osseointegration of prosthetic implants.Cite this article: Bone Joint Res 2021;10(3):218–225.

Pharmacological evaluation of prophylactic anti-microbial use in laparoscopic cholecystectomy; an open labelled study evaluating theconcentrations of single dose intravenous ceftriaxone at serum and tissue level.

The goal of administering preoperative systemic prophylactic antibiotics is to have the concentration in the tissues at its optimum level at the start and throughout the surgery. The rationale for the use of antibiotics is not well accepted; possible side effects and development of microbial resistance patterns are potential risks along with the financial burden. Therefore, the present study was conducted with the aim to clinically evaluate the serum and tissue concentration of single-dose prophylactic ceftriaxone during an ongoing laparoscopic cholecystectomy (LC) and to find out risk factors for post operative surgical site infections (SSI). It was an open labelled prospective study in 50 consecutive patients who underwent elective laparoscopic cholecystectomy under prophylactic cover of ceftriaxone. Serum and tissue concentration were estimated by HighPerformanceLiquidChromatography during the ongoing surgery. Subjects were observed for any post-operative complications including SSI. Serum and tissue concentrations of ceftriaxone were significant at test value of 4milligrams/Litre. Body mass index was significantly correlated with the tissue concentration of ceftriaxone at the time of incision. The rate of SSI was 2%. It significantly correlated with age more than 60years, diabetes and infected bile. A single prophylactic intra-venous dose of 1g ceftriaxone immediately prior to skin incision in LC is good enough for prevention of SSI in Indian patients.

Minimum inhibitory concentration (MIC) of ceftriaxone for blood culture isolates of nalidixic acid resistant Salmonella (NARS) – A 9 year study

Minimum inhibitory concentration (MIC) of ceftriaxone for blood culture isolates of nalidixic acid resistant Salmonella (NARS) – A 9 year study

Molecular Typing of Neisseria gonorrhoeae Clinical Isolates in Russia, 2018-2019: A Link Between penA Alleles and NG-MAST Types.

This work aimed to study penA gene polymorphisms in clinical isolates of Neisseria gonorrhoeae collected in Russia in 2018–2019 and the contribution of the penA allele type to susceptibility to β-lactam antibiotics. A total of 182 isolates were analyzed. penA allele types were determined by sequencing, and the minimum inhibitory concentrations (MICs) of benzylpenicillin and ceftriaxone were measured. The influence of genetic factors on MICs was evaluated by regression analysis. All isolates were susceptible to ceftriaxone, and 40.1% of isolates were susceptible to penicillin. Eleven penA allele types were identified. The mosaic type XXXIV penA allele and the Gly120Lys substitution in PorB made the greatest contributions to increasing the ceftriaxone MIC; the presence of the blaTEM plasmid, Gly120Asp, Ala121Gly/Asn substitutions in PorB, and the adenine deletion in the promoter region of the mtrR gene caused an increase in the penicillin MIC. Among 61 NG-MAST types identified, the most frequent were types 228, 807, 9486, 1993, and 6226. A link between penA alleles and Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST) types was established. Resistance to two groups of β-lactam antibiotics was associated with non-identical changes in penA alleles. To prevent the emergence of ceftriaxone resistance in Russia, NG-MAST genotyping must be supplemented with penA allele analysis.

Streptococcus suis Meningitis in Humans: the Cause of Emerging Bacterial Infectious Diseases in Brazil? Case Report

Over the past few years, the number of reported human infections caused by ingestion of contaminated food has increased. S. suis infections caused by porcine products in humans present a wide variety of clinical manifestations after they invade the host, such as arthritis, septic shock, polyserositis, meningitis, and endocarditis. This article presents a rare case of meningitis in a Brazilian elderly male after consumption of porcine meat. Bacterial identification was performed with MALDI-TOF, a quick and accurate technique to identify this agent. The minimal inhibitory concentration of ceftriaxone was < 0.12 μg/ml, and the patient underwent a satisfactory course of treatment with ceftriaxone for 14 days. This case shows the importance of adopting sanitary inspection measures in order to avoid potentially lethal events associated with it, during handling, transportation and consumption of porcine meat in a developing country.

Pathogenic Escherichia coli Possess Elevated Growth Rates under Exposure to Sub-Inhibitory Concentrations of Azithromycin.

Antimicrobial resistance (AMR) has been identified by the World Health Organization (WHO) as one of the ten major threats to global health. Advances in technology, including whole-genome sequencing, have provided new insights into the origin and mechanisms of AMR. However, our understanding of the short-term impact of antimicrobial pressure and resistance on the physiology of bacterial populations is limited. We aimed to investigate morphological and physiological responses of clinical isolates of E. coli under short-term exposure to key antimicrobials. We performed whole-genome sequencing on twenty-seven E. coli isolates isolated from children with sepsis to evaluate their AMR gene content. We assessed their antimicrobial susceptibility profile and measured their growth dynamics and morphological characteristics under exposure to varying concentrations of ciprofloxacin, ceftriaxone, tetracycline, gentamicin, and azithromycin. AMR was common, with all organisms resistant to at least one antimicrobial; a total of 81.5% were multi-drug-resistant (MDR). We observed an association between resistance profile and morphological characteristics of the E. coli over a three-hour exposure to antimicrobials. Growth dynamics experiments demonstrated that resistance to tetracycline promoted the growth of E. coli under antimicrobial-free conditions, while resistance to the other antimicrobials incurred a fitness cost. Notably, antimicrobial exposure heterogeneously suppressed bacterial growth, but sub-MIC concentrations of azithromycin increased the maximum growth rate of the clinical isolates. Our results outline complex interactions between organism and antimicrobials and raise clinical concerns regarding exposure of sub-MIC concentrations of specific antimicrobials.

Plasma and Peritoneal Ceftriaxone Concentrations After Intraperitoneal Administration in Horses With Septic Peritonitis

Intraperitoneal ceftriaxone administration in healthy horses results in high and prolonged peritoneal concentrations. Recent findings suggest that intraperitoneal ceftriaxone might increase survival rates in horses affected by peritonitis. The present study aimed to evaluate plasma and peritoneal concentrations of ceftriaxone after intraperitoneal administration in horses with septic peritonitis. Twenty-six horses presenting clinical, laboratorial, and sonographic findings compatible with the disease were included. All horses received daily intraperitoneal ceftriaxone (25 mg/kg bwt) in addition or not with other antibiotics and support therapies. High-performance liquid chromatography was used to determine plasma and peritoneal ceftriaxone concentrations before and after 12 and 24 hours of ceftriaxone administration. Mean plasma concentrations 12 and 24 hours after administration were, respectively, 1.84 ± 0.43 and 0.37 ± 0.07 μg/mL, and mean peritoneal concentrations were 5.7 ± 2.84 and 0.42 ± 0.13 μg/mL. Ceftriaxone concentration was lower in comparison with previous studies in healthy horses and presented under the minimal inhibitory concentration for enterobacteria (≤1 μg/mL) and for gram-positive isolates (≤0.5 μg/mL) at 24 hours. The variation of the results obtained between healthy horses and with septic peritonitis demonstrated that pharmacokinetics/dynamics are different between these patients and suggests the use of an interval of dose of 12 hours.

Antimicrobial susceptibility of Neisseria gonorrhoeae in Barcelona during a five-year period, 2013 to 2017.

IntroductionIncreasing rates of antimicrobial resistance in Neisseria gonorrhoeae cause problems for treating gonorrhoea.AimThis observational study aimed to describe isolates from all patients found infected with N. gonorrhoeae, in Barcelona, Spain, between 2013 and 2017, and with available antimicrobial susceptibility data.MethodsMinimum inhibitory concentrations (MICs) of penicillin (PEN), cefixime (CFM), ceftriaxone (CRO), azithromycin (AZM), ciprofloxacin (CIP), spectinomycin (SPT), fosfomycin (FOF) and gentamicin (GEN) were determined by E-test. Susceptibility was assessed using clinical breakpoints from the European Committee on Antimicrobial Susceptibility Testing. Time trends for PEN, CFM, AZM and CIP were investigated using logistic regression.ResultsOf 1,979 patients with infection (2,036 isolates), 1,888 (95.4%) were men. Patient median age was 32 years. The proportions of isolates resistant to extended-spectrum cephalosporins were low, with 0.3% (5/1,982) resistant to CRO and 4.9% (98/1,985) to CFM. AZM resistance prevalence was 2.7% (52/1,981), including 16 isolates detected in 2016 and 2017, with high-level resistance. For CIP, 51.3% (1,018/1,986) of isolates were resistant, and for PEN, 20.1% (399/1,985). All isolates were susceptible to SPT. MIC50 and MIC90 values of GEN were 4 and 6 mg/L and of FOF 12 and 24 mg/L, respectively. Between 2013 and 2017, PEN and CFM resistance rates each decreased from 28.1% (92/327) to 12.2% (70/572) and from 8.3% (27/327) to 4.4% (25/572) (p ≤ 0.0073). In contrast, AZM resistance prevalence appeared to increase from 1.5% in 2014 (5/340) to 3.0% (17/572) in 2017. No trend was identified for CIP.ConclusionAntimicrobial susceptibility surveillance is important to timely detect new phenotypes and trends.

Assessment of phage-mediated inhibition of Salmonella Typhimurium treated with sublethal concentrations of ceftriaxone and ciprofloxacin.

This study was designed to evaluate the synergistic effect of phage (P22) and antibiotic on the inhibition of Salmonella Typhimurium exposed to ceftriaxone (CEF) and ciprofloxacin (CIP). The effect of phage and antibiotic treatments was evaluated by plaque size, disk diffusion, antibiotic susceptibility and phage multiplication assays. The sequential treatment effect of phage and antibiotic was carried out in different treatment order and time for 12h at 37°C.P22 plaque sizes were increased by 28 and 71%, respectively, in the presence of CEF and CIP. The clear zone sizes in disk diffusion assay were significantly increased to >37mm in the presence of CEF and CIP compared to the control (28-31mm). Pre-treatment with P22 enhanced the antimicrobial effect of CIP, showing >2 log reduction after a 12h incubation. Phage P22 combined with antibiotics (CEF and CIP) effectively inhibited the growth of S. Typhimurium depending on the treatment order and time. These results provide useful information for understanding the synergistic effect of phage and antibiotic treatment which can be an effective option to control antibiotic resistant pathogens.

Prediction of Unbound Ceftriaxone Concentration in Children: Simple Bioanalysis Method and Basic Mathematical Equation.

The pharmacological activity of ceftriaxone depends on the unbound concentration. However, direct measurement of unbound concentrations is obstructive, and high individual variability of the unbound fraction of ceftriaxone was shown in children. We aim to evaluate and validate a method to predict unbound ceftriaxone concentrations in pediatric patients. Ninety-five pairs of concentrations (total and unbound) from 92 patients were measured by the bioanalysis method that we developed. The predictive performance of the three equations (empirical in vivo equation, disease-adapted equation, and multiple linear regression equation) was assessed by the mean absolute prediction error (MAPE), the mean prediction error (MPE), the proportions of the prediction error within ±30% (P30) and ±50% (P50), and linear regression of predicted versus actual unbound levels (R2). The average total and unbound ceftriaxone concentrations were 126.18 ± 81.46 μg/ml and 18.82 ± 21.75 μg/ml, and the unbound fraction varied greatly from 4.75% to 39.97%. The MPE, MAPE, P30, P50, and R2 of the empirical in vivo equation, disease equation, and multiple linear equation were 0.17 versus 0.00 versus 0.06, 0.24 versus 0.15 versus 0.27, 63.2% versus 89.5% versus 74.7%, 96.8% versus 97.9% versus 86.3%, and 0.8730 versus 0.9342 versus 0.9315, respectively. The disease-adapted equation showed the best predictive performance. We have developed and validated a bioanalysis method with one-step extraction pretreatment for the determination of total ceftriaxone concentrations, and a prediction equation of the unbound concentration is recommended. The proposed method can facilitate clinical practice and research on unbound ceftriaxone in children. (This study has been registered at ClinicalTrials.gov under identifier NCT03113344.).

Ceftriaxone dosing in patients admitted from the emergency department with sepsis.

Unbound ceftriaxone pharmacokinetics in adult patients have been poorly characterised. The objective of this study is to determine the ceftriaxone dose that achieves an unbound trough concentration ≥ 0.5 mg/L in > 90% of adult patients receiving once-daily dosing presenting to the emergency department (ED) with sepsis. We performed a prospective single-centre pharmacokinetic study. A single unbound plasma ceftriaxone concentration was obtained from each patient using blood collected as part of routine clinical practice within the first dosing interval. Samples were analysed using a validated ultra-high pressure liquid chromatography method. Population pharmacokinetic analysis and Monte Carlo simulations (n = 1000) were performed using Pmetrics for R. A ceftriaxone concentration obtained throughout the first dosing interval was available for fifty adult patients meeting sepsis criteria. Using this concentration time-curve data, a pharmacokinetic model was developed with acceptable predictive performance per the visual predictive check. Simulations show that a 1-g once-daily dose is unlikely to achieve the minimum therapeutic ceftriaxone exposure in > 90% patients with a creatinine clearance ≥ 60 mL/min. However, a 2-g once-daily dose will provide a therapeutic exposure for target pathogens infecting patients with a creatinine clearance ≤ 140 mL/min. Ceftriaxone administered as a 1-g once-daily dose is unlikely to achieve a therapeutic exposure in > 90% of patients presenting to the ED with sepsis. Increasing the ceftriaxone dose to 2 g once daily will likely achieve the desired exposure against target pathogens. Future clinical trials are required to determine any potential clinical benefit of optimised ceftriaxone dosing.

Population Pharmacokinetic Study of Ceftriaxone in Elderly Patients, Using Cystatin C-Based Estimates of Renal Function To Account for Frailty.

Ceftriaxone is widely used for respiratory and urinary infections in elderly and frail patients, but there are few pharmacokinetic studies. A prospective population pharmacokinetic study of ceftriaxone in adults over 65 years old was undertaken. Dried blood spots collected at baseline (predose) and 0.5, 1, 4, 8, and 24 h after administration of 1 g of ceftriaxone were assayed using a validated liquid chromatography-mass spectroscopy analytical method. Frailty was classified using the Edmonton frailty scale and grip strength via a hand dynamometer. Estimates of glomerular filtration rate were determined using creatinine-based and cystatin C-based equations. Of 26 patients recruited, 23 (88%) were vulnerable or very frail. Estimates of drug clearance improved significantly with a cystatin C-based estimate of renal function that accounted for frailty. Simulations indicate that the combined effects of ranges of size and renal function resulted in a 6-fold range in peak ceftriaxone concentrations and 9-fold range in total exposure (area under the concentration-time curve [AUC]). For elderly patients with moderate or severe renal impairment, 48-h dosing results in greater trough concentrations and total exposure than the trough concentrations and total exposure in patients with normal renal function receiving 24-h dosing. Cystatin C-based measures of renal function improved predictions of ceftriaxone clearance in elderly patients.

Modified planar sensors for determination of some cephalosporin antibiotics in biological and medicinal media

Pluripotential cephalosporin antibiotics of different generations active against Gram-negative bacteria are used when treating urinary tract infections, mild and moderate pyelonephritis, acute otitis in children, etc. Rapid determination of cephalosporin antibiotics in the biological fluids is important to evaluate physiological and biochemical processes resulting from their metabolism in a human organism. Planar potentiometric sensors of different types — unmodified and modified with polyaniline (0.3 – 1%), NiZnFeO nanoparticles, and their binary mixes — are developed on the basis of associates of tetradecylammonium (TDA) with complex compounds silver (I) — β -lactam [Ag (I) – ( β -lac) 2 ] which are sensitive to some cephalosporin antibiotics, i.e., cefazoline (Cef), cefuroksime (Cefur) and ceftriaksone (Ceftr). In the sensors of type I, electrode-active components (EAC) and modifiers were added to carbon-containing ink, whereas in type II sensors the polyvinylchloride plasticized unmodified and modified membranes based on [Ag 2 (Ceftr) 2 ] 2 · 2TDA were used. Electroanalytic and operational characteristics of unmodified and modified planar sensors in aqueous solutions of cefazoline, cefuroxime, ceftriaxone and against the background of oral fluid were estimated. It is shown that introduction of the modifiers into sensor membranes leads to stabilization of their potential, increases angular coefficients of electrode functions, decreases the antibiotic detection limit to 1.7 Ч 10 –5 M, reduces the response time and potential drift. Nanoparticles of NiZnFeO appeared to be the most effective modifier. For the sensors of type II linearity of electrode functions is observed in the range of ceftriaxone concentrations of 3.1 Ч 10 –5 – 0.1 Ч 10 –1 M. Depending on the content of the electrode active components in the membrane phase of the unmodified planar sensors, the values of the angular coefficients of the electrode functions vary within 25 – 27 mV/p C and correspond to the values of the non-static value for doubly-charged ions. The linearity intervals of sensor electrode functions are identical at all EAC concentrations under study; as Ceas increases, potential drift and response time decreases. The developed planar sensors were used for determination of cephalosporin antibiotics in model aqueous solutions, medicinal preparations and oral fluid.

Degradation of Ceftriaxone from aquatic solution using a heterogeneous and reusable O3/UV/ Fe3O4@TiO2 systems: operational factors, kinetics and mineralisation

ABSTRACT The present study was developed to evaluate and optimise catalytic oxidative degradation of Ceftriaxone (CTX) from aqueous solution using heterogeneous O3/UV/Fe3O4@TiO2 systems. The performance of combined system O3/UV/Fe3O4@TiO2 was examined as a function of operational parameters including catalyst dosage, solution pH, initial concentration and ozone concentration in a batch system. Physical and chemical properties of the catalyst composite materials were characterised using scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectra and vibrating sample magnetometer. A high removal efficiency of CTX (92.40%) and total organic carbon (TOC) reduction (72.5%) were obtained under optimum conditions, i.e. (time: 30 min, photocatalyst dosage: 2 g/L, pH: 9, initial CTX concentration: 10 mg/L and ozone dosage: 0.2 g/h). The high removal efficiency of CTX and TOC after six consecutive catalyst uses proved the excellent reusing potential of Fe3O4@TiO2. Quenching experiments confirmed that OH° played major roles compared with h+ and O2 − in photocatalytic degradation of CTX. Integration of O3/UV/Fe3O4@TiO2exhibited an excellent performance into CTX removal over 30 min reaction, which can be considered as a promising and effective technique for the decontamination of polluted waters.

Optimal Dosing of Ceftriaxone in Infants Based on a Developmental Population Pharmacokinetic-Pharmacodynamic Analysis.

Ceftriaxone is a third-generation cephalosporin used to treat infants with community-acquired pneumonia. Currently, there is a large variability in the amount of ceftriaxone used for this purpose in this particular age group, and an evidence-based optimal dose is still unavailable. Therefore, we investigated the population pharmacokinetics of ceftriaxone in infants and performed a developmental pharmacokinetic-pharmacodynamic analysis to determine the optimal dose of ceftriaxone for the treatment of infants with community-acquired pneumonia. A prospective, open-label pharmacokinetic study of ceftriaxone was conducted in infants (between 1 month and 2 years of age), adopting an opportunistic sampling strategy to collect blood samples and applying high-performance liquid chromatography to quantify ceftriaxone concentrations. Developmental population pharmacokinetic-pharmacodynamic analysis was conducted using nonlinear mixed effects modeling (NONMEM) software. Sixty-six infants were included, and 169 samples were available for pharmacokinetic analysis. A one-compartment model with first-order elimination matched the data best. Covariate analysis elucidated that age and weight significantly affected ceftriaxone pharmacokinetics. According to the results of a Monte Carlo simulation, with a pharmacokinetic-pharmacodynamic target of a free drug concentration above the MIC during 70% of the dosing interval (70% fT>MIC), regimens of 20 mg/kg of body weight twice daily for infants under 1 year of age and 30 mg/kg twice daily for those older than 1 year of age were suggested. The population pharmacokinetics of ceftriaxone were established in infants, and evidence-based dosing regimens for community-acquired pneumonia were suggested based on developmental pharmacokinetics-pharmacodynamics.

Ceftriaxone pharmacokinetics by a sensitive and simple LC–MS/MS method: Development and application

Ceftriaxone is a third-generation cephalosporin, worldwide use as a first-line treatment for several infections, including life-threatening infections as meningitis or endocarditis. Nowadays, ceftriaxone use is changing, embracing high-dose schemes, new populations treated and requirement of dose individualization and optimization. These reasons warranted the development of new sensitive assays. This study aimed to develop and validate a fast and handy bioanalytical method for the quantification of ceftriaxone in human plasma covering a broad range of concentrations. The analysis was performed using high-performance liquid chromatography coupled to tandem mass spectrometry. Sample preparation was based on protein precipitation with acetonitrile followed by centrifugation. Chromatography separation was performed on Phenomenex Luna C18 column (5 μm, 150 × 2.0 mm) and a mobile phase consisting of 70 % of mobile phase A (10 mM of ammonium acetate and 1% formic acid in purified water) and 30 % mobile phase B (0.1 % formic acid in acetonitrile) at a flow rate of 500 μl/min on an isocratic program. Both the analyte and the internal standard were quantified using the positive electrospray ionization (ESI) mode within a single runtime of 5.00 min. The method was validated following the U.S. Food and Drug Administration guidelines over the concentration range of 3−1000 μg/mL. The within-run and between-run precision and accuracy were <15 %, and therefore met the standard regulatory acceptance criterion. In conclusion, a sensitive and robust LC–MS/MS method was developed for a fast quantitation of ceftriaxone concentrations in plasma samples with multiples applications in research and clinical therapeutic drug monitoring.

Comparative study on the pharmacokinetic bioequivalence of two intravascular Ceftriaxone preparations

The pharmacokinetics and bioequivalence of two Ceftriaxone preparations, Cefin(R) 'Panbiotic' for I.M injection and Rocephin(R) 'Roche,' were compared in twelve healthy male volunteers. A 1g dose of Ceftriaxone disodium hemiheptahydrate was given intramuscularly in a balanced two-way cross-over study for Cefin(R) and Rocephin(R) groups. Blood samples were obtained at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2,0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0 and 24.0 hours after the dosing. Ceftriaxone concentration in plasma was assayed by a high performance liquid chromatographic method using an UV detector. All the data was processed by SigmaPlot(R) and SigmaStat(R) computer software and the pharmacokinetic parameters were calculated, based on one-compartment model. The results revealed that the maximal concentration (Cmax) of Cefin(R) and Rocephin(R) was 118.89 ± 15.59 and 120.02 ± 15.04 μg/ml; the time to reach maximal concentration (Tmax) was 1.83 ± 0.33 and 1.75 ± 0.26 hr; the elimination rate constant (Ke) was 0.11 ± 0.02 hr-1 for both; the elimination half life (T( 1/4 ), β) was 6.54 ± 0.93 and 6.25 ± 0.90 hr; the absorption rate constant (Ka) was 1.83 ± 0.38 and 1.81 ± 0.28 hr-1; the area under curve (from 0 to 1 hou-rs) (AUC0-1) was 1263.45 ± 106.69 and 1218.86 ± 118.30 μg hr/ml; the area under curve (from 0 hour to infinity) (AUC(0-∞)) was 1405.97 ± 138.87 and 1356.27 ± 166.90 μg hr/ml; C1/F was 0.71 ± 0.07 and 0.75 ± 0.09 (L/hr); Vdβ was 8.49 ± 1.21 and 8.11 ± 1.17(L), respectively. In order to strengthen the statistical evidence, the power of the test (1-β) was also calculated. According to the statically pharmacokinetic results, statistical power value and the natural logarithmic transformation of Cmax and AUC, we conclude that Cefin(R) manufactured by Panbiotic and Rocephin(R) manufactured by Roche are bioequivalent.

Ceftriaxone Calcium Crystals Induce Acute Kidney Injury by NLRP3-Mediated Inflammation and Oxidative Stress Injury.

Objective To investigate the role of inflammatory reactions and oxidative stress injury in the mechanisms of ceftriaxone calcium crystal-induced acute kidney injury (AKI) both in vivo and in vitro. Methods Male Sprague Dawley rats were randomly divided into five groups of ten each according to different concentrations of ceftriaxone and calcium. Based on the levels of serum creatinine (Scr) and blood urea nitrogen (BUN), the AKI group was chosen for the subsequent experiments. Kidney histological examination and immunohistochemistry were performed. The expression of NLRP3 and IL-1β protein and the concentrations of oxidative stress markers such as ROS, MDA, and H2O2 in kidney tissues were estimated. In parallel, HK-2 human renal proximal tubule cells were exposed to ceftriaxone calcium crystals. The mRNA expression levels of NLRP3 and IL-1β and the concentrations of oxidative stress markers were evaluated. Finally, cell viability and rat survival were also assessed. Results The results showed that significantly increased Scr and BUN levels, consistent with morphological changes and kidney stones, were found in the rats that received the highest concentration of ceftriaxone (1000 mg/kg) combined with calcium (800 mg/kg). The activation of the NLRP3 inflammasome axis and the marked elevation of MDA, H2O2, and ROS levels were observed both in vivo and in vitro. High expression of Nrf2, HO-1, and NQO1 was also documented. In addition, cell apoptosis and rat mortality were promoted by ceftriaxone calcium crystals. Conclusions Notably, we found that ceftriaxone-induced urolithiasis was associated with a high risk of AKI and NLRP3-mediated inflammasome and oxidative stress injury were of major importance in the pathogenesis.

Antibiotic prophylaxis and surgical site infections; a prospective open label study to clinically evaluate the serum and tissue concentration of single dose prophylactic ceftriaxone in laparoscopic cholecystectomy.

The goal of administering preoperative systemic prophylactic antibiotics is to have the concentration in the tissues at its optimum level at the start and throughout the surgery. The rationale for the use of antibiotics is not well accepted, possible side effects and development of microbial resistance patterns are potential risks along with the financial burden. Therefore, the present study was conducted with the aim to clinically evaluate the serum and tissue concentration of single dose prophylactic ceftriaxone during an ongoing laparoscopic cholecystectomy and to find out risk factors for postoperative surgical site infection. It was an open label prospective study in 50 consecutive patients who underwent elective laparoscopic cholecystectomy under prophylactic cover of ceftriaxone. Serum and tissue concentrations were estimated by HPLC during the ongoing surgery. Subjects were observed for any postoperative complications including SSI. Serum and tissue concentrations of ceftriaxone were significant at test value of 4mg/L. Body mass index was significantly correlated with the tissue concentration of ceftriaxone at the time of incision. The rate of SSI was 2%. It was significantly correlated with age more than 60years, diabetes, and infected bile. A single prophylactic iv dose of 1g ceftriaxone immediately prior to skin incision in LC is good enough for prevention of SSI in Indian patients.

Comparative Plasma Pharmacokinetics of Ceftriaxone and Ertapenem in Normoalbuminemia, Hypoalbuminemia, and Albumin Replacement in a Sheep Model.

Optimal concentrations of unbound antimicrobials are essential for a maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare the effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model. The study design was a prospective, three-phase intervention observational study. The subjects were healthy Merino sheep. Eight sheep were subjected to three experimental phases: normoalbuminemia, hypoalbuminemia using plasmapheresis, and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone at 40 mg/kg of body weight and ertapenem at 15 mg/kg were given intravenously. Blood samples were collected at predefined intervals and analyzed using an ultrahigh-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters such as the area under the curve from 0 to 24 h (AUC0-24), plasma clearance (CL), and apparent volume of distribution in the terminal phase (V) were estimated and compared between the phases. The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC0-24 and higher CL of total and unbound concentrations of ceftriaxone than in the other phases, whereas albumin replacement led to higher AUC0-24 and lower CL than in the other phases for both drugs. The V values for total drug concentrations for both drugs were significantly lower with albumin replacement. For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.