Cefadroxil and cephalexin pharmacokinetics and pharmacodynamics in children with musculoskeletal infections.

Cephalexin, a first-generation cephalosporin, is the first-line oral therapy for children with musculoskeletal infections due to methicillin-susceptible Staphylococcus aureus (MSSA). Cefadroxil, a similar first-generation cephalosporin, is an attractive alternative to cephalexin given its longer half-life. In this study, we describe the comparative pharmacokinetics (PK) and pharmacodynamics (PD) of cephalexin and cefadroxil in children with musculoskeletal infections. Children aged 6 months to 18 years with a musculoskeletal infection were enrolled in a prospective, open-label, crossover PK study and given single oral doses of cefadroxil (50-75 mg/kg up to 2,000 mg) and cephalexin (50 mg/kg up to 1,375 mg). Population PK models were developed and used for dosing simulations. Our primary PD target was the achievement of free antibiotic concentrations above the minimum inhibitory concentration (fT >MIC) for 40% of the day for MICs ≤ 4 mg/L. PK of cephalexin (n = 15) and cefadroxil (n = 14) were best described using a one-compartment, first-order absorption model, with a lag time component for cefadroxil. PK parameters were notable for cefadroxil's longer half-life (1.61 h) than cephalexin's (1.10 h). For pediatric weight bands, our primary PD target was achieved by cephalexin 25 mg/kg/dose, maximum 750 mg/dose, administered three times daily and cefadroxil 40 mg/kg/dose, maximum 1,500 mg/dose, administered twice daily. More aggressive dosing was required to achieve higher PD targets. Among children with musculoskeletal infections, oral cephalexin and cefadroxil achieved PD targets for efficacy against MSSA. Given less frequent dosing, twice-daily cefadroxil should be further considered as an alternative to cephalexin for oral step-down therapy for serious infections due to MSSA.

Environmental risk assessment of pharmaceutical pollutants in the Oro River Sub-basin (Colombia).

Pharmaceuticals and Personal Care Compounds (PPCPs) are contaminants present in wastewater and in the receiving surface waters, which have no regulations and can bring on environmental risks. In this study, we evaluated the presence of six PPCPs in the Oro River Sub-basin (Colombia) and the environmental risk associated with them. We have verified that the monitored rivers show the presence of Ibuprofen, Cephalexin and Carbamazepine; the first ones (Ibuprofen and cephalexin) were those that presented higher concentrations since they are widely prescribed in Colombia. Pharmaceutical compound concentrations in the rivers downstream of the wastewater treatment plants from Floridablanca were higher than in other monitoring sites being a significant point source of contamination. This wastewater treatment plant receives hospital discharges from the city, including internationally recognized clinics accepting patients from different parts of the country. The environmental risk assessment showed that ibuprofen and Cephalexin have a higher impact on aquatic organisms.

Quantitative analysis of cephalexin in solid dosage form by Raman spectroscopy and chemometric tools.

OBJECTIVE: To use Raman Spectroscopy for qualitative and quantitative evaluation of pharmaceutical formulations of active pharmaceutical ingredient (API) of Cephalexin. SIGNIFICANCE: Raman Spectroscopy is a noninvasive, nondestructive, reliable and rapid detection technique used for various pharmaceutical drugs quantification. The present study explores the potential of Raman Spectroscopy for quantitative analysis of pharmaceutical drugs. METHOD: For qualitative and quantitative analysis of Cephalexin API, various standard samples containing less and more concentration of API than commercial tablet was prepared. To study spectral differences, the mean plot of all the samples was prepared. For qualitative analysis, Principal Component Analysis (PCA) and for quantitative analysis Partial Least Square Regression analysis (PLSR) was used. Both of these are Multivariate data analysis techniques and give reliable results as published in previous literature. RESULTS: PCA model distinguished all the Raman Spectral data related to the various Cephalexin solid dosage formulations whereas the PLSR model was used to calculate the concentration of different unknown formulations. For the PLSR model, RMSEC and RMSEP were determined to be 3.3953 and 3.8972, respectively. The prediction efficiency of this built PLSR model was found to be very good with a goodness of the model value (R2) of 0.98. The PLSR model also predicted the concentrations of Cephalexin formulations in the blind or unknown sample. CONCLUSION: These findings demonstrate that the Raman spectroscopy coupled to PLSR analysis could be regarded as a fast and effectively reliable tool for quantitative analysis of pharmaceutical drugs.

Effectiveness of oral cephalexin in antibiotic-course completion for methicillin-susceptible Staphylococcus aureus-induced bacteremic vertebral osteomyelitis.

BACKGROUND: Methicillin-susceptible Staphylococcus aureus (MSSA) is the most common causative microorganism of pyogenic vertebral osteomyelitis (PVO). Although oral antimicrobial therapy with first-generation cephalosporins can treat MSSA infection, data on PVO are scarce. This study evaluated the treatment efficacy of cephalexin as oral antibiotic therapy for MSSA-induced PVO. METHODS: This retrospective study included adult patients treated with oral cephalexin as the completing treatment for PVO with MSSA bacteremia from 2012 to 2020. Treatment effectiveness of cephalexin was evaluated by comparing improvement (5-point scale; score ≥ 4/5 indicates treatment success) in symptoms and laboratory and imaging results between intravenous antimicrobial and oral cephalexin treatment. RESULTS: Among 15 participants (8 [53%] women; median [interquartile range, IQR], age 75 [67.5-80.5] years; Charlson Comorbidity Index 2 [0-4]), 10 (67%) had lumbar spine lesions, 12 (80%) had spinal abscesses, and 4 (27%) had remote abscesses; no patients had concomitant endocarditis. In 11 patients with normal renal function, cephalexin 1,500-2,000 mg/day was administered. Five patients (33%) underwent surgery. Median (IQR; range) duration (days) of intravenous antibiotics, cephalexin, and total treatment was 36 (32-61; 21-86), 29 (19-82; 8-251), and 86 (59-125; 37-337), respectively. Cephalexin had an 87% treatment success rate without recurrence during a median follow-up of 119 (IQR, 48.5-350) days. CONCLUSIONS: In patients with MSSA bacteremia and PVO, antibiotic treatment completion with cephalexin is a reasonable option, even in cases with spinal abscess, if at least 3 weeks of effective intravenous antimicrobial therapy is provided.

Irinotecan-induced gastrointestinal damage alters the expression of peptide transporter 1 and absorption of cephalexin in rats.

Irinotecan causes severe gastrointestinal damage, which may affect the expression of intestinal transporters. However, neither the expression of peptide transporter 1 (Pept1) nor the pharmacokinetics of Pept1 substrate drugs has been investigated under irinotecan-induced gastrointestinal damage. Therefore, the present study quantitatively investigated the effects of irinotecan-induced gastrointestinal damage on the intestinal expression of Pept1 and absorption of cephalexin (CEX), a typical Pept1 substrate, in rats. Irinotecan was administered intravenously to rats for 4 days to induce gastrointestinal damage. The expression of Pept1 mRNA and the Pept1 protein in the upper, middle, and lower segments of the small intestine of irinotecan-treated rats was assessed by quantitative real-time polymerase chain reaction (PCR) and western blotting, respectively. The pharmacokinetic profile of CEX was examined after its oral or intravenous administration (10 mg/kg). In irinotecan-treated rats, ∼2-fold increases in Pept1 protein levels were observed in all three segments, whereas mRNA levels remained unchanged. The oral bioavailability of CEX significantly decreased to 76% of that in control rats. The decrease in passive diffusion caused by intestinal damage may have overcome the increase in Pept1-mediated uptake. In conclusion, irinotecan may decrease the intestinal absorption of Pept1 substrate drugs; however, it increased the expression of intestinal Pept1.

Effect of Excessive Serotonin on Pharmacokinetics of Cephalexin after Oral Administration: Studies with Serotonin-Excessive Model Rats.

PURPOSE: Serotonin (5-HT) is important for gastrointestinal functions, but its role in drug absorption remains to be clarified. Therefore, the pharmacokinetics and oral absorption of cephalexin (CEX) were examined under 5-HT-excessive condition to understand the role of 5-HT. METHODS: 5-HT-excessive rats were prepared by multiple intraperitoneal dosing of 5-HT and clorgyline, an inhibitor for 5-HT metabolism, and utilized to examine the pharmacokinetics, absorption behavior and the intestinal permeability for CEX. RESULTS: Higher levels of 5-HT in brain, plasma and small intestines were recognized in 5-HT-excessive rats, where the oral bioavailability of CEX was significantly enhanced. The intestinal mucosal transport via passive diffusion of CEX was significantly increased, while its transport via PEPT1 was markedly decreased specifically in the jejunal segment, which was supported by the decrease in PEPT1 expression on brush border membrane (BBM) of intestinal epithelial cells. Since no change in antipyrine permeability and significant increase in FITC dextran-4 permeability were observed in 5-HT-excessive rats, the enhanced permeability for CEX would be attributed to the opening of tight junction, which was supported by the significant decrease in transmucosal electrical resistance. In 5-HT-excessive rats, furthermore, total body clearance of CEX tended to be larger and the decrease in PEPT2 expression on BBM in kidneys was suggested to be one of the reasons for it. CONCLUSIONS: 5-HT-excessive condition enhanced the oral bioavailability of CEX in rats, which would be attributed to the enhanced permeability across the intestinal mucosa via passive diffusion through the paracellular route even though the transport via PEPT1 was decreased.

A new NiS nanoparticle-enhanced chemiluminescence method for determination of cephalexin in pharmaceuticals and spiked human serum.

It has been reported that NiS nanoparticles (NPs) can markedly enhance light emission from the chemiluminescence (CL) reaction of luminol-O2 (λmax = 425 nm). Additionally, it was shown that cephalexin (CEF) could further increase the intensity of light emitted from the NiS NPs-luminol-O2 CL reaction. Inspired by these findings, we aimed to develop a new and straightforward CL method for the determination of CEF. A calibration graph over the range 1.00 × 10-6 to 4.00 × 10-5  mol L-1 was established. The limit of detection of the CL method was 8.00 × 10-7  mol L-1 . The coefficient of variation of the CL method was 2.20% (n = 6) for the measurement of 6.00 × 10-6  mol L-1 CEF. NiS NPs were produced by exploiting the precipitation method and identified using several spectroscopic approaches. The proposed CL method was successfully used to measure CEF in some pharmaceutical products and in spiked human serum. The chemical mechanism governing the CL reaction was briefly explained.

Dynamic interactions between cephalexin and macrophages on different Staphylococcus aureus inoculum sizes: a tripartite in vitro model.

BACKGROUND: The bactericidal activity of an antimicrobial drug is generally assessed by in vitro bacterial time-kill experiments which do not include any components of the immune system, even though the innate immunity, the primary host defence, is probably able to kill a large proportion of pathogenic bacteria in immunocompetent patients. We developed an in vitro tripartite model to investigate the joint action of C57Bl/6 murine bone-marrow-derived macrophages and cephalexin on the killing of Staphylococcus aureus. RESULTS: By assessing the bactericidal effects on four bacterial inoculum sizes, we showed that macrophages can cooperate with cephalexin on inoculum sizes lower than 106 CFU/mL and conversely, protect S. aureus from cephalexin killing activity at the highest inoculum size. Cell analysis by flow cytometry revealed that macrophages were rapidly overwhelmed when exposed to large inoculums. Increasing the initial inoculum size from 105 to 107 CFU/mL increased macrophage death and decreased their ability to kill bacteria from six hours after exposure to bacteria. The addition of cephalexin at 16-fold MIC to 105 and 106 CFU/mL inoculums allowed the macrophages to survive and to maintain their bactericidal activity as if they were exposed to a small bacterial inoculum. However, with the highest inoculum size of 107 CFU/mL, the final bacterial counts in the supernatant were higher with macrophages plus cephalexin than with cephalexin alone. CONCLUSIONS: These results suggest that if the bacterial population at the infectious site is low, as potentially encountered in the early stage of infection or at the end of an antimicrobial treatment, the observed cooperation between macrophages and cephalexin could facilitate its control.

Efficient enzymatic synthesis of cephalexin in suspension aqueous solution system.

An efficient method for the enzymatic synthesis of cephalexin (CEX) from 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and d-phenylglycine methyl ester (PGME) using immobilized penicillin G acylase (IPGA) as catalyst in a suspension aqueous solution system was developed, where the reactant 7-ADCA and product CEX are mainly present as solid particles. The effects of key factors on the enzymatic synthesis were investigated. Results showed that continuous feeding of PGME was more efficient for the synthesis of CEX than the batch mode. Under the optimized conditions, the maximum 7-ADCA conversion ratio of 99.3% and productivity of 200 mmol/L/H were achieved, both of which are much superior to the homogeneous aqueous solution system. Besides, IPGA still retained 95.4% of its initial activity after 10 cycles of enzymatic synthesis, indicating the excellent stability of this approach. The developed approach shows great potential for the industrial production of CEX via an enzyme-based route.

Efficacy of Panax ginseng extract combined with cephalexin as a dry cow therapy.

Our objective was to evaluate the efficacy of intramammary administration, at drying-off, of a Panax ginseng extract (PGe) combined with cephalexin (Ceph) on the post-calving bacteriological cure rate of pre-existing intramammary infections (IMI) and on the occurrence of new IMI during the dry period. In addition, milk yield and somatic cell count (SCC) in the post-treatment lactation were evaluated. One hundred and eight late-lactation cows were randomly divided into two experimental groups and were treated at drying-off with Ceph alone or PGe combined with Ceph.Cure rates for IMI present at drying-off were similar for both treatments (OR = 0.95, 95% CI = 0.33-2.74). Cure rates for Staphylococcus aureus were lower (OR = 15.4, 95% CI = 1.66-142.52) in quarters treated with PGe + Ceph than in those treated with Ceph alone. Intramammary infusion of PGe + Ceph at drying-off had no effect on preventing new dry period IMI (OR = 0.75, 95% CI = 0.38-1.51), compared with infusion of Ceph alone. Milk production and SCC in the ensuing lactation were not affected by PGe + Ceph treatment. In conclusion, addition of PGe to dry cow therapy did not show any advantage over the use of dry cow therapy alone.

Evaluating the Removal of the Antibiotic Cephalexin from Aqueous Solutions Using an Adsorbent Obtained from Palm Oil Fiber.

This study aimed to understand the adsorption process of cephalexin (CPX) from aqueous solution by a biochar produced from the fiber residue of palm oil. Scanning electron microscopy, Fourier transform infrared spectroscopy, Boehm titration, and the point of zero charge were used to characterize the morphology and surface functional groups of the adsorbent. Batch tests were carried out to evaluate the effects of the solution pH, temperature, and antibiotic structure. The adsorption behavior followed the Langmuir model and pseudo-second-order model with a maximum CPX adsorption capacity of 57.47 mg g-1. Tests on the thermodynamic behavior suggested that chemisorption occurs with an activation energy of 91.6 kJ mol-1 through a spontaneous endothermic process. Electrostatic interactions and hydrogen bonding represent the most likely adsorption mechanisms, although π-π interactions also appear to contribute. Finally, the CPX removal efficiency of the adsorbent was evaluated for synthetic matrices of municipal wastewater and urine. Promising results were obtained, indicating that this adsorbent can potentially be applied to purifying wastewater that contains trace antibiotics.

Simultaneous Quantification of Cephalexin and Sodium Benzoate in their Dosage forms by high analytical technique. Application of Lean Six Sigma and In-Vitro Dissolution studies.

OBJECTIVES: The aim of the present work is to develop and validate a novel and simple Chromatographic and MCR methods for simultaneous quantification of cephalexin (CPH) and sodium benzoate (SDM) in their dosage form and application of Lean Six Sigma (LSS) to reduce variation and improve quality. METHODS: Isocratic separation is performed using Agilent XDB-C8 (4.6mm×250mm) 5µm, with a mobile phase consisting of acetonitrile: water (30: 70, v/v) containing 0.1% orthophosphoric acid (OPA) at flow rate of 1.5mL/min and wavelength 254nm with injection volume of 20µL for HPLC and Agilent ZORBAX SB-C18 column (50mm×2.1mm, 1.8µm particle size) at flow rate 0.25mL/min, injection volume 0.8µL for UPLC. MCR spectrophotometric method is successfully applied for resolving spectral overlap of drugs at 240nm and 250nm for CPH and SDM, respectively. Comparative invitro dissolution studies are established on Generic product; Rivalexin and Lexin 250mg/5mL, consequently it had been considered equivalent and like the innovator product; Cephalexin USP 250mg/5mL using different USP media. RESULTS: Good Linearity and recovery are achieved over the concentration range of 10-300, and 5-50µg/mL for the studied drugs. Process Capability Index (Cpk) is >1.33 and still capable during all stages of the product release. CONCLUSION: The proposed method is accurate and could be applied to dosage form and LSS to interpret the data of quality attributes.

Joint effect of surfactants and cephalexin on the formation of Escherichia coli filament.

Both antibiotics and surfactants commonly exist in natural environment and have generated great concerns due to their biological influence on the ecosystem. A major concern lies in the capacity of antibiotics to induce bacterial filaments formation, which has potential health risks. However, their joint effect is not clear so far. Here, we studied the joint effect of cephalexin (Cex), a typical antibiotic, and differently charged surfactants on the formation of E. coli filaments. Three kinds of surfactants characterized by different charges were used: cationic surfactant (CTAB), anionic surfactant (SDS) and nonionic surfactant (Tween). Data showed that Cex alone caused the formation of E. coli filaments, elongating their maximum profile from ca. 2 µm (a single E. coli cell) to tens of micrometers (an E. coli filament). A joint use of surfactants with Cex could produce even longer E. coli filaments, elongating the maximum length of the bacteria to larger than 100 µm. The capacity order of different surfactants under their optimum concentrations to produce elongated E. coli filaments was Tween > SDS > CTAB. The E. coli filaments were characterized with a normal DNA distribution and a good cell membrane integrity. We measured the stiffness of bacterial cell wall by atomic force microscopy and correlated the elongation capacity of the E. coli filaments to the stiffness of cell wall. Zeta potential measurement indicated that inserting into or being bound to the cell surface in a large quantity was tested not to be the major way that surfactants interacted with bacteria.

Insight into effect of high-level cephalexin on fate and driver mechanism of antibiotics resistance genes in antibiotic wastewater treatment system.

In the study, antibiotic resistance genes (ARGs) were examined in wastewater and sludge samples to explore the effect of cephalexin (CFX) on the spreading and removal of ARGs in the Expanded Granular Sludge Bed (EGSB) reactor treating antibiotics wastewater. The result showed that the addition of CFX in the wastewater affected the removal amount of ß-lactam ARGs and other types ARGs. Besides, the addition of CFX in the wastewater had no obviously effect on total concentration of targeted ARGs in the sludge, but it was related to the accumulation of some typical ARGs. Based on gene cassette array libraries analysis, the diversity of gene cassettes carried by intI1 gene was increased by the addition of CFX in the wastewater. Furthermore, the co-occurrence patterns between ARGs and bacterial genus were also investigated. The results showed the CFX in the wastewater not only affected the number of potential host bacteria of ARGs, but also changed the types of potential host bacteria of ARGs. The correlation analysis of ARG in influent, effluent and sludge showed that, for blaCTX-M, sul2, qnrS and AmpC genes, their removal amount in EGSB reactor treating antibiotic wastewater system might be enhanced by reducing their concentration in the sludge.

Desirability function approach for development of a thermosensitive and bioadhesive nanotransfersome-hydrogel hybrid system for enhanced skin bioavailability and antibacterial activity of cephalexin.

Cellulitis is a common bacterial infection of the skin and soft tissues immediately beneath the skin. Despite the successful use of antibiotics in the treatment of infectious diseases, bacterial infections continue to impose significant global health challenges because of the rapid emergence of antibiotic resistance. The aim of this work was to develop an in situ hydrogel forming system containing highly permeable cephalexin-loaded nanotransfersomes (NTs), suitable for antibacterial drug delivery. Response surface design was applied for the optimization of NTs. Cephalexin NTs were prepared using thin-film hydration method and then embedded into a 3D hydrogel network. The in vitro antibacterial activity of the optimized NTs was assayed against indicator bacteria of Staphylococcus aureus (S. aureus). The drug permeation was evaluated using an ex vivo rat skin model. The in vivo efficacy of the cephalexin NT hydrogel was also determined against rat skin infection. The resulting data verified the formation of NTs, the size of which was approximately 192 nm. The cephalexin NTs exhibited higher antibacterial activity against S. aureus as compared to the untreated drug. The NT hydrogel improved drug penetration through the skin after 8 h. When applied on the rat skin for 10 days, the cephalexin NT hydrogel exhibited superior antibacterial activity with normal hair growth and skin appearance as compared with the plain drug hydrogel. These findings suggest that the cephalexin NT-hydrogel system can serve as a valuable drug delivery platform against bacterial infections.

Therapy and Outcome of Staphylococcus aureus Infections of Intracorporeal Ventricular Assist Devices.

Infection of the driveline or pump pocket is a common complication in patients with ventricular assist devices (VADs) and Staphylococcus aureus is the main pathogen causing such infections. Limited evidence is currently available to guide the choice of antibiotic therapy and the duration of treatment in these patients. Patients at the University Medical Center Utrecht who developed a VAD-related S. aureus infection between 2007 and 2016 were retrospectively assessed. Blood culture isolates were typed by whole genome sequencing to differentiate between relapses and reinfections, and to determine whether antibiotic therapy had led to acquisition of resistance mutations. Twenty-eight patients had S. aureus VAD infections. Ten of these patients also suffered S. aureus bacteremia. Discontinuation of antibiotic therapy was followed by relapse in 50% of the patients without prior S. aureus bacteremia and in 80% of patients with bacteremia. Oral cephalexin could ultimately suppress the infection for the duration of follow-up in 8/8 patients without S. aureus bacteremia and in 3/6 patients with S. aureus bacteremia. Clindamycin failed as suppressive therapy in 4/4 patients. Cephalexin appears an adequate choice for antibiotic suppression of VAD infections with methicillin-susceptible S. aureus. In patients without systemic symptoms, it may be justified to attempt to stop therapy after treatment of the acute infection, but antibiotic suppression until heart transplant seems indicated in patients with S. aureus bacteremia.

Intravenous cefazolin plus oral probenecid versus oral cephalexin for the treatment of skin and soft tissue infections: a double-blind, non-inferiority, randomised controlled trial.

OBJECTIVE: The purpose of our study was to determine if cephalexin 500 mg orally four times daily was non-inferior to cefazolin 2 g intravenously daily plus probenecid 1 g orally daily in the management of patients with uncomplicated mild-moderate skin and soft tissue infection (SSTI) presenting to the ED. METHODS: This was a prospective, multicentre, double dummy-blind, randomised controlled non-inferiority trial conducted at two tertiary care teaching hospitals in Canada. Patients were enrolled if they presented to the ED with an uncomplicated SSTI, and randomly assigned in a 1:1 fashion to oral cephalexin or intravenous cefazolin plus oral probenecid for up to 7 days. The primary outcome was failure of therapy at 72 hours. Clinical cure at 7 days, intravenous to oral medication transition admission to hospital and adverse events were also evaluated. RESULTS: 206 patients were randomised with 104 patients in the cephalexin group and 102 in the cefazolin and probenecid group. The proportion of patients failing therapy at 72 hours was similar between the treatment groups (4.2% and 6.1%, risk difference 1.9%, 95% CI -3.7% to 7.6%). Clinical cure at 7 days was not significantly different (100% and 97.7%, risk difference -2.3%, 95% CI -6.7% to 0.8%). CONCLUSION: Cephalexin at appropriate doses appears to be a safe and effective alternative to outpatient parenteral cefazolin in the treatment of uncomplicated mild-moderate SSTIs who present to the ED. TRIAL REGISTRATION NUMBER: NCT01029782; Results.

Valorization of Poly (ethylene) terephthalate (PET) wastes into magnetic carbon for adsorption of antibiotic from water: Characterization and application.

Waste Polyethylene terephthalate (PET) bottles were pyrolyzed in the presence of nitrogen and converted into activated carbon (PETAC) by physical activation in carbon dioxide flow. An ex-situ precipitation and external reduction method were applied for the intercalation of ferromagnetic iron oxides onto the PETAC matrix. The characteristic structural and chemical properties of PETAC and magnetic PETAC (M-PETAC) were studied by Brunauer Emmett Teller (BET) surface area analysis, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FTIR) analysis, Raman spectroscopy, X-Ray Diffraction (XRD) analysis, Energy Dispersive analysis of X-rays (EDAX), Vibrating Sample Magnetometer (VSM), Thermal gravimetric analysis (TGA) and elemental analysis. Characterization results indicated that PETAC exhibited a relatively smooth and microporous texture with a surface area of 659.6 m2g-1 while M-PETAC displayed a rugged morphology with a diminished surface area of 288.8 m2g-1. XRD measurements confirmed the formation of iron oxide nanocrystallites with an average Scherrer crystallite size of 19.2 nm. M-PETAC delivered a quick response to an external magnet and exhibited saturation magnetization value of 35.4 emu g-1. PETAC and M-PETAC were explored as potential adsorbents for the adsorption of a pharmaceutical (cephalexin) from water. Isotherm analysis revealed that M-PETAC exhibited a superior adsorption capacity (71.42 mg g-1) compared to PETAC (21.27 mg g-1). FTIR analysis of the adsorbents after CEX adsorption revealed the role of FeO as the nucleation site for enhanced adsorption of cephalexin by M-PETAC.

Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs.

BACKGROUND: Medication effect is the sum of its drug, placebo, and drug*placebo interaction effects. It is conceivable that the interaction effect involves modulating drug bioavailability; it was previously observed that being aware of caffeine ingestion may prolong caffeine plasma half-life. This study was set to evaluate such concept using different drugs. METHODS: Balanced single-dose, two-period, two-group, cross-over design was used to compare the pharmacokinetics of oral cephalexin, ibuprofen, and paracetamol, each described by its name (overt) or as placebo (covert). Volunteers and study coordinators were deceived as to study aim. Drug concentrations were determined blindly by in-house, high performance liquid chromatography assays. Terminal-elimination half-life (t½) (primary outcome), maximum concentration (Cmax), Cmax first time (Tmax), terminal-elimination-rate constant (λ), area-under-the-concentration-time-curve, to last measured concentration (AUCT), extrapolated to infinity (AUCI), or to Tmax of overt drug (AUCOverttmax), and Cmax/AUCI were calculated blindly using standard non-compartmental method. Covert-vs-overt effect on drug pharmacokinetics was evaluated by analysis-of-variance (ANOVA, primary analysis), 90% confidence interval (CI) using the 80.00-125.00% bioequivalence range, and percentage of individual pharmacokinetic covert/overt ratios that are outside the +25% range. RESULTS: Fifty, 30, and 50 healthy volunteers (18%, 10%, and 6% females, mean (SD) age 30.8 (6.2), 31.4 (6.6), and 31.2 (5.4) years) participated in 3 studies on cephalexin, ibuprofen, and paracetamol, respectively. Withdrawal rate was 4%, 0%, and 4%, respectively. Eighteen blood samples were obtained over 6, 10, and 14 h in each study period of the three drugs, respectively. ANOVA showed no significant difference in any pharmacokinetic parameter for any of the drugs. The 90% CIs for AUCT, AUCI, Cmax, AUCOverttmax, and Cmax/AUCI were within the bioequivalence range, except for ibuprofen Cmax (76.66-98.99), ibuprofen Cmax/AUCI (77.19-98.39), and ibuprofen (45.32-91.62) and paracetamol (51.45-98.96) AUCOverttmax. Out of the 126 individual covert/overt ratios, 2.0-16.7% were outside the +25% range for AUCT, 2.0-4.2% for AUCI, 25.0-44.9% for Cmax, 67.3-76.7% for AUCOverttmax, and 45.8-71.4% for Tmax. CONCLUSIONS: This study couldn't confirm that awareness of drug ingestion modulates its bioavailability. However, it demonstrates the trivial effect of blinding in bioequivalence studies and the extent of bio-variability that would be expected when comparing a drug product to itself. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01501747 (registered Dec 26, 2011).

Evaluation of cephalexin failure rates in morbidly obese patients with cellulitis.

WHAT IS KNOWN AND OBJECTIVE: Identification of adequate antimicrobial dosing regimens for morbidly obese patients is essential given the simultaneous increase in morbid obesity and cellulitis prevalence in recent years. Insufficient data currently exist to describe the effectiveness of extrapolating traditional antibiotic dosing strategies to morbidly obese patients with cellulitis. The primary objective of this study was to compare therapeutic failure rates in non-obese and morbidly obese patients with cellulitis when treated with cephalexin at standard dosing. METHODS: This was a single-centre, retrospective cohort analysis. Adult patients hospitalized or under inpatient observation at a 1265-bed academic medical centre who received cephalexin monotherapy for non-purulent cellulitis from 2005 to 2015 were evaluated for inclusion. Patients were divided into two cohorts based on body mass index (BMI), where BMI <30 kg/m(2) was defined as non-obese and BMI ≥40 kg/m(2) as morbidly obese. Patients with critical risk factors for purulent or polymicrobial cellulitis were excluded. The primary outcome, therapeutic failure, was defined as a need for extended or additional antimicrobial therapy, surgical intervention, emergency department visit, or re-hospitalization within two to thirty days after cephalexin initiation. RESULTS AND DISCUSSION: A total of 94 patients (69 non-obese and 25 morbidly obese) met inclusion and exclusion criteria, which was below the estimated sample size needed to reach desired power. The rate of therapeutic failure in the morbidly obese group was similar to the non-obese group (20% vs. 14·5%, P = 0·53). Patients most commonly had extended or additional antibiotics prescribed in response to therapeutic failure with cephalexin. WHAT IS NEW AND CONCLUSION: Cephalexin failure rates for cellulitis did not differ statistically between morbidly obese and non-obese patients. The underpowered nature of this study is a limitation. Until further study with a larger sample size is completed, empiric adjustment of cephalexin dosing based solely on BMI may not be necessary.