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The Journal of Antimicrobial... Aug 2023Infection with ESBL-producing Enterobacteriaceae infection is ubiquitous in some neonatal ICUs and increasing levels of antibiotic resistance are a cause for urgent...
BACKGROUND
Infection with ESBL-producing Enterobacteriaceae infection is ubiquitous in some neonatal ICUs and increasing levels of antibiotic resistance are a cause for urgent concern. Delineation of bacterial and viral sepsis can be challenging, often leading to patients receiving empirical antibiotics without or whilst waiting for a definitive causal diagnosis. Empirical therapy is often dependent on broad-spectrum 'Watch' antibiotics, contributing to further resistance.
METHODS
ESBL-producing Enterobacteriaceae clinical isolates found to have caused neonatal sepsis and meningitis underwent a detailed in vitro screening including susceptibility testing, chequerboard combination analysis and hollow-fibre infection model dynamic analyses using combinations of cefotaxime, ampicillin and gentamicin in combination with β-lactamase inhibitors.
RESULTS
Additivity or synergy was found for all antibiotic combinations against seven Escherichia coli and three Klebsiella pneumoniae clinical isolates. Cefotaxime or ampicillin plus sulbactam combined with gentamicin was able to consistently inhibit the growth of ESBL-producing isolates at typical neonatal doses, and the combination cleared the hollow-fibre infection model system of organisms resistant to each agent alone. The combination of cefotaxime/sulbactam and gentamicin was consistently bactericidal at clinically achievable concentrations (Cmax of 180, 60 and 20 mg/L for cefotaxime, sulbactam and gentamicin, respectively).
CONCLUSIONS
The addition of sulbactam to cefotaxime or ampicillin to the typical first-line empirical therapy could obviate the need for carbapenems and amikacin in settings with high ESBL-infection prevalence.
Topics: Infant, Newborn; Humans; Amikacin; Carbapenems; Sulbactam; Gentamicins; Neonatal Sepsis; Prevalence; Anti-Bacterial Agents; Cefotaxime; Ampicillin; Escherichia coli; beta-Lactamases; Microbial Sensitivity Tests
PubMed: 37283195
DOI: 10.1093/jac/dkad177 -
The Journal of Antimicrobial... Jul 2022To describe the population pharmacokinetics of cefotaxime and desacetylcefotaxime in critically ill paediatric patients and provide dosing recommendations. We also...
OBJECTIVES
To describe the population pharmacokinetics of cefotaxime and desacetylcefotaxime in critically ill paediatric patients and provide dosing recommendations. We also sought to evaluate the use of capillary microsampling to facilitate data-rich blood sampling.
METHODS
Patients were recruited into a pharmacokinetic study, with cefotaxime and desacetylcefotaxime concentrations from plasma samples collected at 0, 0.5, 2, 4 and 6 h used to develop a population pharmacokinetic model using Pmetrics. Monte Carlo dosing simulations were tested using a range of estimated glomerular filtration rates (60, 100, 170 and 200 mL/min/1.73 m2) and body weights (4, 10, 15, 20 and 40 kg) to achieve pharmacokinetic/pharmacodynamic (PK/PD) targets, including 100% ƒT>MIC with an MIC breakpoint of 1 mg/L.
RESULTS
Thirty-six patients (0.2-12 years) provided 160 conventional samples for inclusion in the model. The pharmacokinetics of cefotaxime and desacetylcefotaxime were best described using one-compartmental model with first-order elimination. The clearance and volume of distribution for cefotaxime were 12.8 L/h and 39.4 L, respectively. The clearance for desacetylcefotaxime was 10.5 L/h. Standard dosing of 50 mg/kg q6h was only able to achieve the PK/PD target of 100% ƒT>MIC in patients >10 kg and with impaired renal function or patients of 40 kg with normal renal function.
CONCLUSIONS
Dosing recommendations support the use of extended or continuous infusion to achieve cefotaxime exposure suitable for bacterial killing in critically ill paediatric patients, including those with severe or deep-seated infection. An external validation of capillary microsampling demonstrated skin-prick sampling can facilitate data-rich pharmacokinetic studies.
Topics: Anti-Bacterial Agents; Bacteria; Cefotaxime; Child; Critical Illness; Humans; Microbial Sensitivity Tests; Monte Carlo Method
PubMed: 35678266
DOI: 10.1093/jac/dkac168 -
Archives of Razi Institute Jun 2022Dexamethasone (DEX), which is a corticosteroid hormone (glucocorticoid), has been used to treat different conditions, such as immune system disorders,...
Dexamethasone (DEX), which is a corticosteroid hormone (glucocorticoid), has been used to treat different conditions, such as immune system disorders, certain skin and eye disorders, as well as breathing problems. Cefotaxime sodium, also called Claforan, is synthesized from a naturally occurring material (semisynthetic). It is a broad-spectrum cephalosporin antibiotic that could be utilized for parenteral administration. The present study aimed to investigate histological changes occurring in the tissues and cells of the rats' ovary (primordial, primary, secondary, antral, and mature follicle) treated with Cefotaxime sodium, as well as DEX, and evaluate the impacts of these medications on animals' fertility. In total, 40 female adult Wistar rats were divided into four groups (n=10). The control group received 0.5 ml/kg of distilled water daily for five days as a placebo. The second group was injected with 0.5 mg/kg of DEX daily for five days. The same amount of Claforan (0.5 mg/kg) was injected into the third group daily for five days, and the fourth group received 0.5 mg/kg of both Claforan and DEX daily for five days. Afterward, the ovaries were prepared for histological examination. The ImageJ image analysis system was used to detect morphometric parameters and calculate the area of these organs. The findings of the present study showed that the DEX and Claforan brought changes to the ovarian area and the number of follicles. The ovarian area significantly increased (<0.007) in the DEX-treated group (mean±SEM=7.3±0.5 mm), compared to the control group (mean±SEM=4.6±0.20 mm). However, DEX was found to decrease body weight. Furthermore, the ovarian area significantly increased in the Claforan-treated group (mean±SEM=8.6±0.6 mm); however, their body weight significantly decreased (<0.008), in comparison with the control and DEX-treated groups. The combination treatment (i.e., DEX + Cefotaxime sodium) significantly increased (<0.009) the area of ovaries even more, compared to single treatments (mean±SEM=9.6±0.4 mm). Overall, both DEX and Claforan brought histological changes to ovaries. However, the effect of DEX on ovaries was less than that of Claforan. The concurrent administration of both medications was found to have more significant effects on rats' ovaries.
Topics: Rats; Female; Animals; Ovary; Cefotaxime; Rats, Wistar; Ovarian Follicle; Dexamethasone
PubMed: 36618313
DOI: 10.22092/ARI.2022.357511.2050 -
Therapeutic Drug Monitoring Oct 2023Recently, several studies have assessed the effects of therapeutic drug monitoring of frequently prescribed beta-lactam antibiotics, for which they were quantified in...
BACKGROUND
Recently, several studies have assessed the effects of therapeutic drug monitoring of frequently prescribed beta-lactam antibiotics, for which they were quantified in human plasma samples. Beta-lactams are considered unstable, leading to extra challenges in quantification. Therefore, to ensure sample stability and minimize sample degradation before analysis, stability studies are crucial. This study investigated the stability of 10 frequently used beta-lactam antibiotics in human plasma at relevant storage conditions for clinical use.
METHODS
Amoxicillin, benzylpenicillin, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, imipenem, meropenem, and piperacillin were analyzed using ultraperformance convergence chromatography tandem mass spectrometry and liquid chromatography tandem mass spectrometry. Their short-term and long-term stabilities were investigated by measuring quality control samples at low and high concentrations against freshly prepared calibration standards. Measured concentrations at each time point were compared with the concentrations at T = 0. Antibiotics were considered stable if recovery results were between 85% and 115%.
RESULTS
Short-term stability results indicated ceftriaxone, cefuroxime, and meropenem to be stable up to 24 hours at room temperature. All evaluated antibiotics, except imipenem, were stable on ice in a cool box for 24 hours. Amoxicillin, benzylpenicillin, and piperacillin were stable for 24 hours at 4-6°C. Cefotaxime, ceftazidime, cefuroxime, and meropenem were stable at 4-6°C up to 72 hours. Ceftriaxone and flucloxacillin were stable for 1 week at 4-6°C. Long-term stability results showed that all antibiotics were stable up to 1 year at -80°C, except imipenem and piperacillin, which were stable for 6 months at -80°C.
CONCLUSIONS
Plasma samples for amoxicillin, benzylpenicillin, cefotaxime, ceftazidime, flucloxacillin, and piperacillin may be stored for a maximum of 24 hours in a cool box. Refrigeration is suitable for plasma samples of amoxicillin, benzylpenicillin, meropenem, and piperacillin for up to 24 hours and cefotaxime, ceftriaxone, ceftazidime and cefuroxime for 72 hours. Plasma samples for imipenem should be frozen directly at -80°C. For long-term storage, plasma samples can be stored at -80°C for a maximum of 6 months for imipenem and piperacillin and 12 months for all other evaluated antibiotics.
Topics: Humans; Meropenem; Ceftazidime; Floxacillin; Cefuroxime; Ceftriaxone; Anti-Bacterial Agents; Piperacillin; Monobactams; Tandem Mass Spectrometry; Imipenem; Cefotaxime; Amoxicillin
PubMed: 37199408
DOI: 10.1097/FTD.0000000000001100 -
Scientific Reports Dec 2020Bio/chemoinformatics tools can be deployed to compare antimicrobial agents aiming to select an efficient nose-to-brain formulation targeting the meningitis disease by...
Bio/chemoinformatics tools can be deployed to compare antimicrobial agents aiming to select an efficient nose-to-brain formulation targeting the meningitis disease by utilizing the differences in the main structural, topological and electronic descriptors of the drugs. Cefotaxime and ceftriaxone were compared at the formulation level (by comparing the loading in gelatin and tripalmitin matrices as bases for the formation of nanoparticulate systems), at the biopharmaceutical level (through the interaction with mucin and the P-gp efflux pumps) and at the therapeutic level (through studying the interaction with S. pneumoniae bacterial receptors). GROMACS v4.6.5 software package was used to carry-out all-atom molecular dynamics simulations. Higher affinity of ceftriaxone was observed compared to cefotaxime on the investigated biopharmaceutical and therapeutic macromolecules. Both drugs showed successful docking on mucin, P-gp efflux pump and S. pneumoniae PBP1a and 2b; but ceftriaxone showed higher affinity to the P-gp efflux pump proteins and higher docking on mucin. Ceftriaxone showed less out-of-matrix diffusion and higher entrapment on the gelatin and the tripalmitin matrices. Accordingly, Ceftriaxone gelatin nanospheres or tripalmitin solid lipid nanoparticles may pose a more feasible and efficient nose-to-brain formulation targeting the meningitis disease compared to the cefotaxime counterparts.
Topics: Anti-Bacterial Agents; Brain; Cefotaxime; Ceftriaxone; Cheminformatics; Gelatin; Molecular Dynamics Simulation; Mucins; Software; Triglycerides
PubMed: 33277611
DOI: 10.1038/s41598-020-78327-w -
Journal of Infection and Public Health Dec 2021Worldwide, multi-drug resistant Klebsiella pneumoniae (K. pneumonia) and their virulence's were contributed more in the multi-drug resistant effect. According to the...
BACKGROUND
Worldwide, multi-drug resistant Klebsiella pneumoniae (K. pneumonia) and their virulence's were contributed more in the multi-drug resistant effect. According to the World Health organization report, it is an emerging thread in developing countries and also comes under first ever critical list. In this context, the current study was concentrated on detection of extended spectrum beta lactamase (ESBL) producing strain and their antimicrobial susceptibility study of K. pneumoniae.
MATERIALS AND METHODS
Firstly, the multi-drug resistant effect of the K. pneumoniae was identified from specific CLSI guidelines recommended antibiotics by disc diffusion method. Consecutively, the primary ESBL identification test was performed using ceftazidime and cefotaxime, followed by double disc combination and phenotypic confirmation tests using ceftazidime/clavulanic acid and cefotaxime/clavulanic acid. Finally, the minimum inhibition concentration of some important sensitive antibiotics were performed against selected K. pneumoniae was confirmed by micro broth dilution method.
RESULTS AND CONCLUSIONS
The current result was most favorable to selected K. pneumoniae with more multi drug resistant characteristic nature. All the performed antibiotics were almost more sensitive to selected K. pneumoniae. The effective antibiotics of piperacillin was also exhibited more resistant effect against tested bacteria and it cleaved the bacterial enzyme clearly. The present result of primary ESBL identification test result was exhibited with ≤22 mm and ≤27 mm against ceftazidime and cefotaxime were observed respectively. Followed result of double disc combination and phenotypic confirmation experiments results were clearly stated that the selected K. pneumoniae was ESBL producer. The ceftazidime, cefotaxime and ceftazidime/clavulanic acid and cefotaxime/clavulanic acid were exhibited with merged zones and ≥5 mm zones around the combination disc when compared with disc alone were observed. All the ESBL detection test results were clearly indicated that the selected K. pneumoniae strain was ESBL producer.
Topics: Anti-Bacterial Agents; Cefotaxime; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pharmaceutical Preparations; Piperacillin; beta-Lactamases
PubMed: 34772638
DOI: 10.1016/j.jiph.2021.10.017 -
Antimicrobial Agents and Chemotherapy Apr 2018Cefotaxime is the first-line treatment for meningitis in neonates and young infants. However, limited data on cefotaxime cerebrospinal fluid (CSF) concentrations in...
Cefotaxime is the first-line treatment for meningitis in neonates and young infants. However, limited data on cefotaxime cerebrospinal fluid (CSF) concentrations in neonates and young infants were available. The aim of the present study was to evaluate the penetration of cefotaxime into CSF in neonates and young infants. Blood and CSF samples were collected from neonates and young infants treated with cefotaxime using an opportunistic pharmacokinetic sampling strategy, and concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The analysis was performed using NONMEM and R software. Thirty neonates and young infants (postmenstrual age range, 25.4 to 47.4 weeks) were included. A total of 67 plasma samples and 30 CSF samples were available for analysis. Cefotaxime plasma and CSF concentrations ranged from 2.30 to 175.42 mg/liter and from 0.39 to 25.38 mg/liter, respectively. The median ratio of the CSF concentration to the plasma concentration was 0.28 (range, 0.06 to 0.76). Monte Carlo simulation demonstrated that 88.4% and 63.9% of hypothetical neonates treated with 50 mg/kg of body weight three times a day (TID) would reach the pharmacodynamic target (the percentage of the dosing interval that the free antimicrobial drug concentration remains above the MIC, 70%) using the standard EUCAST MIC susceptibility breakpoints of 2 mg/liter and 4 mg/liter, respectively. The penetration of cefotaxime into the CSF of neonates and young infants was evaluated using an opportunistic sampling approach. A dosage regimen of 50 mg/kg TID could cover the most causative pathogens with MICs of <2 mg/liter. Individual dosage adaptation was required for more resistant bacterial strains, such as .
Topics: Cefotaxime; Chromatography, High Pressure Liquid; Humans; Infant; Infant, Newborn; Models, Theoretical
PubMed: 29437625
DOI: 10.1128/AAC.02448-17 -
International Journal of Infectious... Mar 2021Ceftriaxone and cefotaxime share a similar antibacterial spectrum and similar indications but have different pharmacokinetic characteristics. Ceftriaxone is administered... (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND
Ceftriaxone and cefotaxime share a similar antibacterial spectrum and similar indications but have different pharmacokinetic characteristics. Ceftriaxone is administered once daily and 40% of its clearance is by biliary elimination, whereas cefotaxime requires three administrations per day and shows less than 10% biliary elimination. The high biliary elimination of ceftriaxone suggests a greater impact of this antibiotic on the gut microbiota than cefotaxime. The objective of this study was to compare the impact of ceftriaxone and cefotaxime on the gut microbiota.
METHODS
A prospective clinical trial was performed that included 55 patients treated with intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for at least 3 days. Three fresh stool samples were collected from each patient (days 0, 3, and 7 or at the end of intravenous treatment) to assess the emergence of third-generation cephalosporin (3GC)-resistant Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa, toxigenic Clostridioides difficile, and vancomycin-resistant enterococci.
RESULTS
The emergence of 3GC-resistant gram-negative enteric bacilli (Enterobacteriaceae) (5.9% vs 4.7%, p > 0.99), Enterococcus spp, and non-commensal microorganisms did not differ significantly between the groups. Both antibiotics reduced the counts of total gram-negative enteric bacilli and decreased the cultivable diversity of the microbiota, but the differences between the groups were not significant.
CONCLUSION
No significant difference was observed between ceftriaxone and cefotaxime in terms of the emergence of resistance.
Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Drug Resistance, Bacterial; Feces; Female; Gastrointestinal Microbiome; Gram-Negative Bacteria; Hospitalization; Humans; Male; Microbial Sensitivity Tests; Pilot Projects; Prospective Studies
PubMed: 33453395
DOI: 10.1016/j.ijid.2021.01.025 -
Revista Espanola de Quimioterapia :... Apr 2024We assessed the in vitro activity of delafloxacin and the synergy between cefotaxime and delafloxacin among cefotaxime non-susceptible invasive isolates of Streptococcus...
OBJECTIVE
We assessed the in vitro activity of delafloxacin and the synergy between cefotaxime and delafloxacin among cefotaxime non-susceptible invasive isolates of Streptococcus pneumoniae (CNSSP).
METHODS
A total of 30 CNSSP (cefotaxime MIC > 0.5 mg/L) were studied. Serotyping was performed by the Pneumotest-Latex and Quellung reaction. Minimum inhibitory concentrations (MICs) of delafloxacin, levofloxacin, penicillin, cefotaxime, erythromycin and vancomycin were determined by gradient diffusion strips (GDS). Synergistic activity of delafloxacin plus cefotaxime against clinical S. pneumoniae isolates was evaluated by the GDS cross method.
RESULTS
Delafloxacin showed a higher pneumococcal activity than its comparator levofloxacin (MIC50, 0.004 versus 0.75 mg/L and MIC90, 0.047 versus >32 mg/L). Resistance to delafloxacin was identified in 7/30 (23.3%) isolates, belonging to serotypes 14 and 9V. Synergy between delafloxacin and cefotaxime was detected in 2 strains (serotypes 19A and 9V). Antagonism was not observed. Addition of delafloxacin increased the activity of cefotaxime in all isolates. Delafloxacin susceptibility was restored in 5/7 (71.4%) strains.
CONCLUSIONS
CNSSP showed a susceptibility to delafloxacin of 76.7%. Synergistic interactions between delafloxacin and cefotaxime were observed in vitro among CNSSP by GDS cross method.
Topics: Humans; Cefotaxime; Streptococcus pneumoniae; Anti-Bacterial Agents; Levofloxacin; Microbial Sensitivity Tests; Serotyping; Pneumococcal Infections; Fluoroquinolones
PubMed: 38226580
DOI: 10.37201/req/107.2023 -
Clinical Microbiology and Infection :... Jan 2008CTX-M-type enzymes are a group of class A extended-spectrum beta-lactamases (ESBLs) that are rapidly spreading among Enterobacteriaceae worldwide. More that 50 allotypes... (Review)
Review
CTX-M-type enzymes are a group of class A extended-spectrum beta-lactamases (ESBLs) that are rapidly spreading among Enterobacteriaceae worldwide. More that 50 allotypes are known, clustered into six sub-lineages. The CTX-M-encoding genes have been captured from the chromosome of Kluyvera spp. on conjugative plasmids that mediate their dissemination among pathogenic enterobacteria. CTX-M-type ESBLs exhibit powerful activity against cefotaxime and ceftriaxone but generally not against ceftazidime, which has important implications for laboratory detection. However, several CTX-M variants with enhanced ceftazidimase activity have been detected. The rapid and massive spread of CTX-M-type ESBLs is rapidly changing the ESBL epidemiology and, in some geographical areas, these enzymes are now the most prevalent ESBLs in Enterobacteriaceae.
Topics: Anti-Bacterial Agents; Cefotaxime; Ceftazidime; Ceftriaxone; Cephalosporins; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Models, Molecular; Prevalence; beta-Lactam Resistance; beta-Lactamases
PubMed: 18154526
DOI: 10.1111/j.1469-0691.2007.01867.x