Concentrations Of Ceftriaxone Research Articles

Influences of protein levels on the cerebrospinal fluid distribution of ceftazidime & ceftriaxone in the cerebrospinal fluid of patients with inflamed meningitis

IntroductionCeftazidime and ceftriaxone are used to treat various gram-negative pathogens, such as Streptococcus pneumoniae and Pseudomonas aeruginosa, and have shown excellent therapeutic efficacy against bacterial meningitis. However, there is insufficient information on the pharmacokinetic characteristics of their cerebrospinal distribution. Here, we investigated the association of clinical laboratory data in cerebrospinal fluid with ceftazidime and ceftriaxone concentration in the cerebrospinal fluid of patients with inflamed meningitis. MethodsCerebrospinal fluid samples were collected from eight adult patients with inflamed meningitis who intravenously received either ceftazidime or ceftriaxone (ceftazidime: a total of 25 samples from three patients, ceftriaxone: a total of 12 samples from five patients). Total cell number, protein concentration, and glucose concentration in the cerebrospinal fluid were retrospectively collected from electronic medical charts. All ceftazidime and ceftriaxone concentrations in the cerebrospinal fluid were determined using high-performance liquid chromatography. ResultsBoth ceftazidime and ceftriaxone concentrations in cerebrospinal fluid correlated with protein concentration in cerebrospinal fluid; however, no significant correlation was observed in total cell number and glucose concentration in cerebrospinal fluid. ConclusionsThis is the first report on the relationship between the cerebrospinal distribution of these antibiotics and clinical laboratory data in cerebrospinal fluid of adult patients with meningitis.

In Vitro Comparison of Brand-name and Generic Ceftriaxone: Potency Versus Price

Background Ceftriaxone is a broad-spectrum third-generation cephalosporin antibiotic used to treat many significant infections due to its high antibacterial potential, a broad spectrum of activity, and low toxicity. These antibiotics are prescribed for various infections every day, especially in developing countries. The difference in the price of generic and brand-name ceftriaxone impressed that brand-name drug has better quality than generic. This study aimed to compare brand-name ceftriaxone's quality over generics that have a notable price difference. Methods: We presumed all ceftriaxone injections had a similar quality. Escherichia coli ATCC? 25922 with MIC of 0.03-0.12 ug/ml against ceftriaxone was used as the evaluation standard. Using Mueller Hinton agar with serial ceftriaxone concentration double diluted from 0.48 until 0.0075 ug/ml. There were three groups of ceftriaxone, brand-name, generic name, and control (SIGMA Aldrich). A drop of suspension of Escherichia coli ATCC-25922 in 20 ?l of 104CFU was applied on the surface medium. After incubation at 37?C overnight, the MIC of the three groups was noted. MIC, as shown in the concentration of 0.03-0.12 ug/ml, was confirmed as good quality ceftriaxone. Results A total of 11 brand names and 14 generic ceftriaxone injections shared identical MIC at 0.06 ?g/ml. Brand-name ceftriaxone overpriced generic with average price 234,400 ($16,32) and 16,686 ($1,16) respectively. Conclusion: While being sold at a higher price, brand-name ceftriaxone has equivalent in vitro potency to generic.

Pharmacokinetics of ceftriaxone-tazobactam (8:1) combination in healthy and Escherichia coli induced diarrhoeic birds.

Antibiotic-resistant Escherichia coli infection of poultry causes significant economic losses. Extended spectrum β lactamases (ESBL) producing E. coli was inoculated in a broiler, Rhode Island Red and Haringhata Black birds orally at 56×108 c.f.u. mL-1 for induction of diarrhoea. Pharmacokinetics of ceftriaxone-tazobactam combination (8:1) was studied following a single intramuscular injection at 28.125 mg kg-1 and the combination was administered twice daily to treat such infection. Plasma concentration of both ceftriaxone persisted up to 8 h in experimental birds and maintained an approximate ratio of 8:1 with tazobactam for a period of 2 h, 0.25 h and 0.75 h, respectively in a broiler, Rhode Island Red and Haringhata Black birds. The Kel was significantly lower in all experimental birds compared to healthy birds. Efficacy study was conducted in diarrhoeic birds by administration of ceftriaxone-tazobactam combination at 28.125 mg kg-1 body weight twice daily intramuscularly for three days which caused an increase in specific antibody titre in the broiler on 5th day and in Rhode Island Red birds 10th day. However, Haringhata black birds were inherently showed more resistance towards the infection. The combination of ceftriaxone and tazobactam in the ratio of 8:1 can be an effective treatment to combat ESBL producing E. coli infections.

Pharmacodynamics of Ceftriaxone, Ertapenem, Fosfomycin and Gentamicin in Neisseria gonorrhoeae.

Objectives: To assess the in vitro effect of select antimicrobials on the growth of N. gonorrhoeae and its pharmacodynamic parameters. Methods: Time–kill assays were performed on two reference N. gonorrhoeae strains (ceftriaxone-resistant WHO X and ceftriaxone-susceptible WHO F) and one clinical N. gonorrhoeae strain (ceftriaxone-susceptible CS03307). Time–kill curves were constructed for each strain by measuring bacterial growth rates at doubling antimicrobial concentrations of ceftriaxone, ertapenem, fosfomycin and gentamicin. Inputs from these curves were used to estimate minimal bacterial growth rates at high antimicrobial concentrations (ψmin), maximum bacterial growth rates in the absence of antimicrobials (ψmax), pharmacodynamic minimum inhibitory concentrations (zMIC), and Hill’s coefficients (κ). Results: Ceftriaxone, ertapenem and fosfomycin showed gradual death overtime at higher antimicrobial concentrations with a relatively high ψmin, demonstrating time-dependent activity. Compared to WHO F, the ψmin for WHO X was significantly increased, reflecting decreased killing activity for ceftriaxone, ertapenem and fosfomycin. At high ceftriaxone concentrations, WHO X was still efficiently killed. CS03307 also showed a high ψmin for ceftriaxone in spite of a low MIC and no difference in ψmin for fosfomycin in spite of significant MIC and zMIC differences. Gentamicin showed rapid killing for all three strains at high concentrations, demonstrating concentration-dependent activity. Conclusions: Based on time–kill assays, high-dosage ceftriaxone could be used to treat N. gonorrhoeae strains with MIC above breakpoint, with gentamicin as a potential alternative. Whether ertapenem or fosfomycin would be effective to treat strains with a high MIC to ceftriaxone is questionable.

Genome-wide association, prediction and heritability in bacteria with application to Streptococcus pneumoniae.

Whole-genome sequencing has facilitated genome-wide analyses of association, prediction and heritability in many organisms. However, such analyses in bacteria are still in their infancy, being limited by difficulties including genome plasticity and strong population structure. Here we propose a suite of methods including linear mixed models, elastic net and LD-score regression, adapted to bacterial traits using innovations such as frequency-based allele coding, both insertion/deletion and nucleotide testing and heritability partitioning. We compare and validate our methods against the current state-of-art using simulations, and analyse three phenotypes of the major human pathogen Streptococcus pneumoniae, including the first analyses of minimum inhibitory concentrations (MIC) for penicillin and ceftriaxone. We show that the MIC traits are highly heritable with high prediction accuracy, explained by many genetic associations under good population structure control. In ceftriaxone MIC, this is surprising because none of the isolates are resistant as per the inhibition zone criteria. We estimate that half of the heritability of penicillin MIC is explained by a known drug-resistance region, which also contributes a quarter of the ceftriaxone MIC heritability. For the within-host carriage duration phenotype, no associations were observed, but the moderate heritability and prediction accuracy indicate a moderately polygenic trait.

Antimicrobial susceptibility of commensal Neisseria in a general population and men who have sex with men in Belgium

Non-pathogenic Neisseria are a reservoir of antimicrobial resistance genes for pathogenic Neisseria meningitidis and Neisseria gonorrhoeae. Men who have sex with men (MSM) are at risk of co-colonization with resistant non-pathogenic and pathogenic Neisseria. We assessed if the antimicrobial susceptibility of non-pathogenic Neisseria among MSM differs from a general population and if antimicrobial exposure impacts susceptibility. We recruited 96 participants at our center in Belgium: 32 employees, 32 MSM who did not use antibiotics in the previous 6 months, and 32 MSM who did. Oropharyngeal Neisseria were cultured and identified with MALDI-TOF–MS. Minimum inhibitory concentrations for azithromycin, ceftriaxone and ciprofloxacin were determined using E-tests® and compared between groups with non-parametric tests. Non-pathogenic Neisseria from employees as well as MSM were remarkably resistant. Those from MSM were significantly less susceptible than employees to azithromycin and ciprofloxacin (p < 0.0001, p < 0.001), but not ceftriaxone (p = 0.3). Susceptibility did not differ significantly according to recent antimicrobial exposure in MSM. Surveilling antimicrobial susceptibility of non-pathogenic Neisseria may be a sensitive way to assess impact of antimicrobial exposure in a population. The high levels of antimicrobial resistance in this survey indicate that novel resistance determinants may be readily available for future transfer from non-pathogenic to pathogenic Neisseria.

Variability in the serum and tissue concentrations of pre-incisional ceftriaxone for surgery in paediatric population and outcome of surgical-site infections; An open labelled, prospective, non-randomized, analytical study

Studies have determined the serum concentration of ceftriaxone in the adult population, but there are only a few studies that measured the tissue concentrations. However, no studies have concurrently evaluated the serum and tissue concentrations of ceftrixaone in elective pediatric surgery patients. Therefore, our study was planned to evaluate the serum and tissue concentrations of single dose intravenous prophylactic ceftriaxone intra-operatively during an ongoing pediatric surgery and the outcome of surgical-site infections (SSIs). We did a correlation analysis to determine the relationship of various concentrations and surgery related risk factors with the outcome of SSIs. It was an open label prospective study in 50 patients who underwent elective pediatric surgery under prophylactic cover of ceftriaxone. Serum and tissue concentration were estimated by High Pressure Liquid Chromatography (HPLC). Subjects were observed for post operative complications including SSI. Serum and tissue concentrations of ceftriaxone were significant at test value of 4 ​mg/L. Tissue concentrations of ceftriaxone at incision (p ​= ​0.02) and closure (p ​= ​0.04) were significantly correlated with SSI but there was no significant association. The measured serum ceftriaxone concentrations were more than 20 times the susceptible minimum inhibitory concentration (MIC) at any given point of the surgery. On the other hand, this target level was achieved at the tissue levels in the majority of the patient. The factors associated with SSI were duration of surgery, wound category of contaminated clean type, the use of urinary catheter and implants in the surgery. An intra-operative re-dose, extension of dose or addition of another antibiotic may be considered for such patients.

Верификация цефтриаксона и определение его концентрации в сыворотке крови методом капиллярного электрофореза у больных хирургического профиля

Objective: to develop a method for verifying ceftriaxone and determining its concentration in blood serum by means of capillary electrophoresis. Materials and methods. The study used ceftriaxone sodium salt (CJSC Pharmaceutical Company "Lekko"), model mixtures of biological fluids (whole blood, serum and blood plasma) with different concentrations of ceftriaxone; clinical biological blood samples taken during breast surgery against the background of perioperative antibiotic prophylaxis. The concentration of ceftriaxone was determined by using a Capel-105M capillary electrophoresis system (CJSC Lumex, St. Petersburg, Russia). Results. An express method has been developed for the determination of ceftriaxone in blood serum (sample volume - 0.1 ml), which involves the use of a precipitant of protein substances - crystalline ammonium sulfate, extraction of the organic system chloroform - isobutanol in a ratio of 3: 1, re-extraction of the substance into a working electrolyte diluted with water, and subsequent electrophoresis on the device "Capel-105M". Method validation indicates its linearity, correctness, precision and specificity; the lower limit of quantitation is 0.1 µg/0.1 ml biological medium. The effectiveness of the technique was confirmed in a clinical trial by determining the concentration of ceftriaxone in the blood serum 30 minutes after intravenous administration of 1 g of the drug for the purpose of perioperative antibiotic prophylaxis. Conclusion. The method for the quantitative determination of ceftriaxone in blood serum, performed by using a capillary electrophoresis system (“Kapel-105M”), meets the established validation criteria. At the same time, the identification of the antibiotic is carried out under selective conditions and requires a minimum amount of the object, thereby reducing the amount of co-extractive substances in the samples, which, in combination with the method of stacking during electrophoresis, provides a high sensitivity of the technique. It can be recommended for analysis in clinical diagnostic laboratories.

1289. The Challenge of Treating Community-Associated Enterobacterales Infections in a Middle-Income Country: Data from SMART 2018-2019

BackgroundAntimicrobial stewardship programs have been used widely in hospital settings due to the rise of resistant bacteria, antibiotic toxicities, and costs. Nevertheless, few efforts are done to prevent the rising antimicrobial resistance in community settings. The aim of our study was to evaluate the antimicrobial resistance from Enterobacterales community- and hospital-acquired infections in Southern Brazil.MethodsA total of 272 Enterobacterales isolates (i.e., Escherichia coli, Klebsiella spp., Citrobacter spp., Enterobacter spp., Serratia spp., Proteus spp., and Providencia) were collected from 2018 and 2019. Broth microdilution method was used to determine minimum inhibitory concentrations for ceftriaxone, cefepime, levofloxacin, amikacin and ertapenem. Molecular evaluation of beta-lactamases (ESBLs, AmpC, and KPC) was also performed.ResultsNinety-three, and a hundred and seventy-nine isolates were from community- and hospital-acquired infections, respectively. Similar MIC distribution was found between community and hospital settings (Table 1). Levofloxacin MIC of 8mg/L occurred in 38.7% (n=36) and 30.7% (n=55) of isolates from community- and hospital-acquired infections, respectively (Figure 1). Ceftriaxone MIC of 16mg/L occurred in 39.7%(n=37) and 39.1% (n=70) of isolates from community- and hospital-acquired infections, respectively (Figure 1). At last, cefepime MIC of 32mg/L occurred in 22% (n=21) and 25% (n=46) of isolates from community- and hospital-acquired infections, respectively. The following beta-lactamases were found in isolates from community-acquired group, ACT-MIR, CTX-M, SHV and TEM; while beta-lactamases from the hospital-acquired group were ACT-MIR, CMY II, KPC-2, CTX-M, SHV and TEM. Table 1. Enterobacterales ceftriaxone, cefepime, levofloxacin, amikacin and ertapenem minimum inhibitory concentrations (mg/L) distribution from community- and hospital-settings. Figure 1. Enterobacterales ceftriaxone and levofloxacin minimum inhibitory concentrations (mg/L) distribution from community- and hospital-settings.ConclusionSimilar antimicrobials resistances were found in Enterobacterales from community- and hospital-acquired infections. New anti-infective agents are needed urgently to treat pathogens from the community-acquired infections and hospitals that have resistance to the first line regimen. Additionally, community antimicrobial stewardship programs are required.Disclosures All Authors: No reported disclosures

Gentamicin Susceptibility in Neisseria gonorrhoeae and Treatment Outcomes for Urogenital Gonorrhea After 25 Years of Sustained Gentamicin Use in Malawi.

Gentamicin has been used for the treatment of gonorrhea in Malawi since 1993. However, declining clinical cure rates have been suspected. We evaluated current Neisseria gonorrhoeae susceptibility to gentamicin in vitro and clinically. Men with acute urethritis were recruited at the Bwaila District Hospital STI Clinic in Lilongwe, Malawi, between January 2017 and August 2019. All men provided urethral swabs for etiological testing at enrollment and test of cure (TOC), 1 week later, using Gram-stained microscopy and culture. We used Etest to determine minimum inhibitory concentrations (MICs) of gentamicin, azithromycin, cefixime, ceftriaxone, ciprofloxacin, and spectinomycin; disc diffusion for tetracycline susceptibility; and whole-genome sequencing (WGS) to verify/refute treatment failure. Among 183 N. gonorrhoeae culture-positive men enrolled, 151 (82.5%) had a swab taken for TOC. Of these 151 men, 16 (10.6%) had a positive culture at TOC. One hundred forty-one baseline isolates were tested for gentamicin susceptibility using Etest: 2 (1.4%), MIC = 2 μg/mL; 111 (78.7%), MIC = 4 μg/mL; and 28 (19.9%), MIC = 8 μg/mL. All isolates were susceptible to azithromycin, cefixime, ceftriaxone, and spectinomycin, whereas 63.1% had intermediate susceptibility or resistance to ciprofloxacin. Almost all (96.1%) isolates were resistant to tetracycline. All examined isolates cultured at TOC (n = 13) had gentamicin MICs ≤8 μg/mL. Ten men had pretreatment and posttreatment isolates examined by whole-genome sequencing; 2 (20%) were verified new infections (4119 and 1272 single-nucleotide polymorphisms), whereas 8 (80%) were confirmed treatment failures (0-1 single-nucleotide polymorphism). Gentamicin MICs poorly predict gonorrhea treatment outcome with gentamicin, and treatment failures are verified with gonococcal strains with in vitro susceptibility to gentamicin. The first-line treatment of gonorrhea in Malawi should be reassessed.

Effect of P-glycoprotein Inhibition on the Penetration of Ceftriaxone Across the Blood-Brain Barrier.

Recent studies indicate that inhibition of the efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) may represent a putative strategy to increase the BBB penetration of several antibiotics. Therefore, the present study aimed to investigate the effect of P-gp inhibition on the transport of ceftriaxone (CFX) across the BBB. Blood and brain microdialysis in rats was used to monitor blood and brain unbound CFX concentrations following intravenous administration (50mg/kg), with or without pretreatment with one of the P-gp inhibitors, cyclosporin A (6.25, 12.5, 25mg/kg) or verapamil (5, 10, 20mg/kg). An inhibitory effect was demonstrated by an increase in the ratio of unbound brain to unbound blood concentration (Kp.uu.brain) of CFX. The concentrations of CFX in blood and brain from 0 to 180min after intravenous administration (CFX, 50mg/kg) ranged from 3 to 40μg/ml and 1 to 10μg/ml, respectively. The Kp.uu.brain of CFX was 24.74 ± 1.34%. Pretreatment with cyclosporin A increased the brain concentration and the Kp.uu.brain of CFX in a dose-dependent manner. However, pretreatment with verapamil increased the brain concentration of CFX but not the Kp.uu.brain. The present data shows that CFX might be a substrate of P-gp efflux transporter at the BBB and P-gp inhibition might enhance the brain concentration of CFX. Future studies involving more selective P-gp inhibitors or knockout mouse models should be conducted to specifically elucidate the impact of P-gp inhibition on penetration of CFX across the BBB.

Population Pharmacokinetic Modeling of Total and Free Ceftriaxone in Critically Ill Children and Young Adults and Monte Carlo Simulations Support Twice Daily Dosing for Target Attainment.

Critical illness, including sepsis, causes significant pathophysiologic changes that alter the pharmacokinetics (PK) of antibiotics. Ceftriaxone is one of the most prescribed antibiotics in patients admitted to the pediatric intensive care unit (PICU). We sought to develop population PK models of both total ceftriaxone and free ceftriaxone in children admitted to a single-center PICU using a scavenged opportunistic sampling approach. We tested if the presence of sepsis and phase of illness (before or after 48 h of antibiotic treatment) altered ceftriaxone PK parameters. We performed Monte Carlo simulations to evaluate whether dosing regimens commonly used in PICUs in the United States (50 mg/kg of body weight every 12 h versus 24 h) resulted in adequate antimicrobial coverage. We found that a two-compartment model best described both total and free ceftriaxone concentrations. For free concentrations, the population clearance value is 6.54 L/h/70 kg, central volume is 25.4 L/70 kg, and peripheral volume is 19.6 L/70 kg. For both models, we found that allometric weight scaling, postmenstrual age, creatinine clearance, and daily highest temperature had significant effects on clearance. The presence of sepsis or phase of illness did not have a significant effect on clearance or volume of distribution. Monte Carlo simulations demonstrated that to achieve free concentrations above 1 μg/ml for 100% of the dosing intervals, a dosing regimen of 50 mg/kg every 12 h is recommended for most patients. A continuous infusion could be considered if the target is to maintain free concentrations four times above the MICs (4 μg/ml).

Test of Cure Return Rate and Test Positivity, Strengthening the US Response to Resistant Gonorrhea, United States, 2018-2019.

Reduced antibiotic susceptibility (RS) in Neisseria gonorrhoeae (GC) may increase treatment failure. Conducting tests of cure (TOC) for patients with RS-GC may facilitate identification of treatment failures. We examined 2018 to 2019 data from 8 jurisdictions participating in the US Centers for Disease Control and Prevention's Strengthening US Response to Resistant Gonorrhea project. Jurisdictions collected GC isolates and epidemiological data from patients and performed antimicrobial susceptibility testing. Minimum inhibitory concentrations of ceftriaxone, 0.125 μg/mL or greater; cefixime, 0.250 μg/mL or greater; or azithromycin, 2.0 μg/mL or greater were defined as RS. Patients with RS infections were asked to return for a TOC 8 to 10 days posttreatment. We calculated a weighted TOC return rate and described time to TOC and suspected reasons for any positive TOC results. Overall, 1165 patients were diagnosed with RS infections. Over half returned for TOC (weighted TOC, 61%; 95% confidence interval, 50.1%-72.6%; range by jurisdiction, 32%-80%). Test of cure rates were higher among asymptomatic (68%) than symptomatic patients (53%, P = 0.001), and men who have sex with men (62%) compared with men who have sex with women (50%; P < 0.001). Median time between treatment and TOC was 12 days (interquartile range, 9-16). Of the 31 (4.5%) TOC patients with positive results, 13 (42%) were suspected because of reinfection and 11 (36%) because of false-positive results. There were no treatment failures suspected to be due to RS-GC. Most patients with a RS infection returned for a TOC, though return rates varied by jurisdiction and patient characteristics. Test of cure can identify and facilitate treatment of reinfections, but false-positive TOC results may complicate interpretation and clinical management.

In vitro evaluation of antimicrobial resistance selection in Neisseria gonorrhoeae

Gonococcal infections represent an urgent public-health threat as >50% of cases caused by Neisseria gonorrhoeae strains display reduced susceptibility to at least one antimicrobial agent. We evaluated the pharmacodynamics of a number of antimicrobials against N. gonorrhoeae in order to assess the likelihood of mutant selection by these agents. The mutant prevention concentration (MPC) and mutant selection window (MSW) were determined for azithromycin, ceftriaxone, doxycycline, ertapenem, gentamicin, ciprofloxacin, levofloxacin and moxifloxacin against a wild-type strain of N. gonorrhoeae (ATCC 49226) and a gyrA mutant of ATCC 49226. Pharmacokinetic parameters, including peak concentration (Cmax), half-life (t1/2) and area under the plasma concentration-time curve over 24 h (AUC), associated with each agent were used to calculate the time within the MSW (TMSW, percentage of the dosing interval that antimicrobial concentrations fall within the MSW), Cmax/MPC ratio and AUC/MPC ratio for each antimicrobial agent. Concentrations of ceftriaxone (500 mg), ertapenem, ciprofloxacin, levofloxacin and moxifloxacin surpass the MPC for both strains. Results of pharmacodynamic analyses suggest that ertapenem, ciprofloxacin, levofloxacin and moxifloxacin may be most likely to prevent mutant selection in N. gonorrhoeae. Use of ceftriaxone, azithromycin, doxycycline or gentamicin for gonorrhoea is expected to lead to the ongoing emergence of resistance to these agents. There is a clear need to develop novel treatment regimens for gonococcal infections in order to limit the dissemination of resistance in N. gonorrhoeae.

Determination of free ceftriaxone concentration and its application in predicting lung tissue concentration

Determination of free ceftriaxone concentration and its application in predicting lung tissue concentration

Effect of ketoprofen and tolfenamic acid on intravenous pharmacokinetics of ceftriaxone in sheep

In this study, the pharmacokinetics of ceftriaxone (40mg/kg) was determined following a single intravenous (IV) administration of ceftriaxone alone and co-administration with ketoprofen (3mg/kg) or tolfenamic acid (2mg/kg) in sheep. Eight healthy Akkaraman sheep (2.4 ± 0.3years and 44 ± 4kg of body weight) were used. The study was carried out according to the longitudinal design in three periods with a 15-day washout period between administrations. In the first period, sheep received ceftriaxone alone via an IV injection. In the second and third periods, the same sheep received ceftriaxone in combination with ketoprofen and tolfenamic acid, respectively. Plasma concentrations of ceftriaxone were assayed by high-performance liquid chromatography and analyzed using non-compartmental analysis. Following the administration of ceftriaxone alone, the elimination half-life (t1/2ʎz ), area under the plasma concentration-time curve from zero (0) hours to infinity (∞) (AUC0-∞ ), total clearance (ClT ), and volume of distribution at steady state were 1.42h, 182.41h*µg/ml, 0.22 L/h/kg, and 0.17 L/kg, respectively. While ketoprofen and tolfenamic acid significantly increased the t1/2ʎz and AUC0-∞ of ceftriaxone, they significantly reduced the ClT . Ceftriaxone (40mg/kg, IV) in concurrent use with ketoprofen and tolfenamic acid can be administrated at the 12h dosing intervals to maintain T> minimum inhibitory concentration (MIC) values above 60% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 and ≤1μg/mL, respectively, in sheep with an inflammatory condition.

Pharmacokinetic/Pharmacodynamic Target Attainment Based on Measured versus Predicted Unbound Ceftriaxone Concentrations in Critically Ill Patients with Pneumonia: An Observational Cohort Study.

The impact of ceftriaxone pharmacokinetic alterations on protein binding and PK/PD target attainment still remains unclear. We evaluated pharmacokinetic/pharmacodynamic (PK/PD) target attainment of unbound ceftriaxone in critically ill patients with severe community-acquired pneumonia (CAP). Besides, we evaluated the accuracy of predicted vs. measured unbound ceftriaxone concentrations, and its impact on PK/PD target attainment. A prospective observational cohort study was carried out in adult patients admitted to the intensive care unit with severe CAP. Ceftriaxone 2 g q24h intermittent infusion was administered to all patients. Successful PK/PD target attainment was defined as unbound trough concentrations above 1 or 4 mg/L throughout the whole dosing interval. Acceptable overall PK/PD target attainment was defined as successful target attainment in ≥90% of all dosing intervals. Measured unbound ceftriaxone concentrations (CEFu) were compared to unbound concentrations predicted from various protein binding models. Thirty-one patients were included. The 1 mg/L and 4 mg/L targets were reached in 26/32 (81%) and 15/32 (47%) trough samples, respectively. Increased renal function was associated with the failure to attain both PK/PD targets. Unbound ceftriaxone concentrations predicted by the protein binding model developed in the present study showed acceptable bias and precision and had no major impact on PK/PD target attainment. We showed suboptimal (i.e., <90%) unbound ceftriaxone PK/PD target attainment when using a standard 2 g q24h dosing regimen in critically ill patients with severe CAP. Renal function was the major driver for the failure to attain the predefined targets, in accordance with results found in general and septic ICU patients. Interestingly, CEFu was reliably predicted from CEFt without major impact on clinical decisions regarding PK/PD target attainment. This suggests that, when carefully selecting a protein binding model, CEFu does not need to be measured. As a result, the turn-around time and cost for ceftriaxone quantification can be substantially reduced.

Minimum inhibitory concentration (MIC) of Ceftriaxone and Azithromycin for blood culture isolates of Salmonella enterica spp.

Enteric fever caused by Salmonella enterica continues to be a major public health problem worldwide. In the last decade, ceftriaxone and azithromycin have become the drugs of choice for treating enteric fever caused by Nalidixic acid resistant Salmonella (NARS) enterica. This has led to reports of drug resistance to both drugs. Since enteric fever is endemic in India, accurate drug susceptibility surveillance is crucial to ensure empiric management of enteric fever is appropriate. The aim of this study is to evaluate the minimum inhibitory concentration (MIC) of ceftriaxone and azithromycin for blood culture isolates of NARS isolated at our centre. This is a retrospective study conducted in a tertiary care center in Mumbai for blood culture isolates of NARS from 2016 to 2018. Isolates were tested for antimicrobial susceptibility testing (AST) against ceftriaxone and azithromycin using a manual broth microdilution method (BMD). Of 155 blood culture isolates of NARS: S. Typhi (n = 112) and S. Paratyphi A (n = 43) were included in the study. 81.9% (127 / 155) isolates were susceptible, 6.4% (10 / 155) isolates were intermediate while 11.6% (18 / 155) isolates were resistant to ceftriaxone. 100% susceptibility of NARS was observed to azithromycin. This study documents an alarming increase in resistance to ceftriaxone among NARS in Mumbai while azithromycin continues to be susceptible in vitro. It is essential to know MICs to understand epidemiological trends and choose appropriate treatment regimens for treating enteric fever.

Biosorption of ceftriaxone antibiotic by Pseudomonas putida from aqueous solutions

ABSTRACT In this study, Pseudomonas putida biomass was used to remove ceftriaxone from aqueous solutions. Biosorption was studied by living bacteria to achieve maximum biosorption. In order to investigate the shape, the biomass structure was analysed by SEM and FT-IR analyses. The effect of important parameters such as pH, contact time, adsorbent amount, and initial concentration of ceftriaxone solution, temperature, and the effect of ionic intensity on biosorption were studied. This study is an experimental study 250 ml Erlenmeyer was used as a batch reactor for the experiment. With increasing initial concentration, the removal efficiency increased. The best results were obtained at optimum pH = 7, adsorbent dose of 0.1 g, and initial ceftriaxone concentration of 50 mg/l after contact time of 120 minutes at the temperature of37and more than 50% of ceftriaxone was removed. Various isotherms including Langmuir and Freundlich were used to analyse equilibrium data at 37°C. The maximum adsorption capacity of this adsorbent was 109.5 mg/g. The results showed that the Freundlich isotherm is more consistent with the experimental data. Data fitting in the Freundlich adsorption isotherm model indicates non-uniformity of the absorbent surface.

Enhanced stability of salt-assisted sodium ceftriaxone-loaded chitosan nanoparticles: Formulation and optimization by 32-full factorial design and antibacterial effect study against aerobic and anaerobic bacteria

Uniform stable chitosan nanoparticles (CS NPs) loaded with sodium ceftriaxone (CTX) were prepared using the ionic crosslinking method by applying a monovalent salt. To achieve NPs with a minimum polydispersity index (PDI), minimum size, and maximum entrapment efficiency of the drug (EE %), the effect of NaCl salt concentration and pH of CS solution was investigated using a 32-full factorial design. Then, the stability of CTX-loaded CS NPs over six-month storage was investigated. Surface charge density was calculated using Gouy-Chapman theory. Then, minimum inhibitory concentration and minimum bactericidal concentration of free CTX and salt-assisted CTX-loaded CS NPs were determined against Staphylococcus aureus and Escherichia coli as aerobic bacteria, and Bacteroides fragilis as anaerobic bacteria. Results suggested that optimized NP was 265 nm in size with a PDI value of 0.075, and high drug EE% of 80% with high stability over 6 months. Results of time-kill assays revealed that the salt-assisted CTX-loaded CS NPs could thoroughly kill the E. coli and B.fragilis bacterium after 8 h, and S.aureus bacterium after 10 h, while free CTX could kill all bacteria after 24 h. Finally, the salt-assisted CTX-loaded CS NPs provide uniform and stable NPs with more controlled release and higher antibacterial effect compared to free CTX.