FeS2 nanosheets-luminol-O2 chemiluminescence method for determination of venlafaxine hydrochloride, imipramine hydrochloride, and cefazolin sodium.

This study introduces a novel chemiluminescence (CL) approach utilizing FeS2 nanosheets (NSs) catalyzed luminol-O2 CL reaction for the measurement of three pharmaceuticals, namely venlafaxine hydrochloride (VFX), imipramine hydrochloride (IPM), and cefazolin sodium (CEF). The CL method involved the phenomenon of quenching induced by the pharmaceuticals in the CL reaction. To achieve the most quenching efficacy of the pharmaceuticals in the CL reaction, the concentrations of reactants comprising luminol, NaOH, and FeS2 NSs were optimized accordingly. The calibration curves demonstrated exceptional linearity within the concentration range spanning from 4.00 × 10-7 to 1.00 × 10-3 mol L-1, 1.00 × 10-7 to 1.00 × 10-4 mol L-1, and 4.00 × 10-6 to 2.00 × 10-4 mol L-1 with detection limits (3σ) of 3.54 × 10-7, 1.08 × 10-8, and 2.63 × 10-6 mol L-1 for VFX, IPM, and CEF, respectively. This study synthesized FeS2 NSs using a facile hydrothermal approach, and then the synthesized FeS2 NSs were subjected to a comprehensive characterization using a range of spectroscopic methods. The proposed CL method was effective in measuring the aforementioned pharmaceuticals in pharmaceutical formulations as well as different water samples. The mechanism of the CL system has been elucidated.

Exploring the Role of L10 Loop in New Delhi Metallo-ß-lactamase (NDM-1): Kinetic and Dynamic Studies.

Four NDM-1 mutants (L218T, L221T, L269H and L221T/Y229W) were generated in order to investigate the role of leucines positioned in L10 loop. A detailed kinetic analysis stated that these amino acid substitutions modified the hydrolytic profile of NDM-1 against some ß-lactams. Significant reduction of kcat values of L218T and L221T for carbapenems, cefazolin, cefoxitin and cefepime was observed. The stability of the NDM-1 and its mutants was explored by thermofluor assay in real-time PCR. The determination of TmB and TmD demonstrated that NDM-1 and L218T were the most stable enzymes. Molecular dynamic studies were performed to justify the differences observed in the kinetic behavior of the mutants. In particular, L218T fluctuated more than NDM-1 in L10, whereas L221T would seem to cause a drift between residues 75 and 125. L221T/Y229W double mutant exhibited a decrease in the flexibility with respect to L221T, explaining enzyme activity improvement towards some ß-lactams. Distances between Zn1-Zn2 and Zn1-OH- or Zn2-OH- remained unaffected in all systems analysed. Significant changes were found between Zn1/Zn2 and first sphere coordination residues.

Effects of cefazolin-containing niosome nanoparticles against methicillin-resistant Staphylococcus aureus biofilm formed on chronic wounds.

The ability of biofilm formation in methicillin-resistant Staphylococcus aureus (MRSA) causes significant mortality and morbidity in wound infections. Nanoparticles because of the drug concentration increment at the point of contact of nanoparticles and bacteria, and slower release of the drug at the desired location are considered as proper tools to overcome the therapeutic problem of antimicrobial-resistant infections. This study was aimed to evaluate the anti-biofilm activity of cefazolin-loaded nanoparticles against MRSA isolates. The 27 clinical isolates of MRSA were collected from patients with pressure sores and diabetic ulcers referred to Loghman Hospital in Tehran-Iran. MRSA isolates were detected by polymerase chain reaction (PCR) and biochemical tests. Cefazolin-loaded niosome was synthesized using the thin-film hydration method and were characterized by zeta potential measurement and transmission electron microscopy (TEM). The round-shaped cefazolin-loaded niosomes had a diameter of 100 nm and a -63 mV zeta potential. The cefazolin-containing niosomes removed 1, 3, and 5 d old biofilms at the concentration of 128 µg ml-1, 128 µg ml-1, and 256 µg ml-1, respectively. Histological results indicated that BALB/c mice receiving cefazolin-loaded niosomes were treated effectively faster than those treated by cefazolin or untreated group. In conclusion, the cefazolin-loaded niosome could be considered as a promising candidate for the treatment of biofilm-mediated infections of MRSA.

Fabrication and characterization of mucoadhesive bioplastic patch via coaxial polylactic acid (PLA) based electrospun nanofibers with antimicrobial and wound healing application.

Polylactic acid (PLA) is the second-highest consumed bioplastic in the world. PVP/PLA-PEO complex nanofibers encapsulating collagen and cefazolin dressing scaffold were fabricated using a coaxial electrospinning method to target the release of the encapsulated compounds. It was observed that in collagen doses of 10 and 20%, the speed of healing showed a significant difference with the control sample, but the dose of 40% caused a decrease in wound healing rate in mice. The nanofibers' morphology and surface roughness were investigated by scanning electron microscopy (SEM) and atomic force microscopy (AFM), respectively. The mechanical properties and adhesion strength of the scaffolds were investigated. The scaffolds' antimicrobial activity was evaluated by disk diffusion method against the E. coli, S. aureus, and P. aeruginosa. The results indicated a positive effect on the antimicrobial activity of the samples. In this study, we were able to prolong the effect of scaffolds by changing the pattern of release of cefazolin from inside the nanofibers. Possible interactions between the polymers and the encapsulated compounds were investigated using Fourier-transform infrared spectroscopy (FTIR). Finally, in-vivo and histological tests were performed to evaluate the efficacy of the scaffolds in accelerating wound healing.

Mesoporous silica pellets as bifunctional bone drug delivery system for cefazolin.

For decades, bone drug delivery systems dedicated for osteomyelitis treatment have been investigated as bifunctional materials that exhibit prolonged drug release and mineralization potential. Herein, composite-type pellets based on cefazolin-loaded amino-modified mesoporous silica SBA-15 and microwave-assisted hydroxyapatite were investigated as potential bone drug delivery system in vitro. Pellets were obtained by granulation, extrusion and spheronization methods in laboratory scale and studied in terms of physical properties, drug release, mineralization potential, antimicrobial activity and cytotoxicity towards human osteoblasts. The obtained pellets were characterized for hardness and friability which indicated the pellets durability during further investigations. Prolonged (5-day) release of cefazolin from pellets was observed. The pellets exhibited mineralization potential in simulated body fluid, i.e., a continuous layer of bone-like apatite was formed on the surface of pellets after 28 days of incubation. An antimicrobial assay of pellets revealed an antibacterial effect against Staphylococcus aureus strain during 6 days. No cytotoxic effects of pellets towards human osteoblasts were observed. The obtained results proved that proposed pellets appear to have potential applications as bone drug delivery systems.

The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor.

A continuing quest for specific inhibitors of proinflammatory cytokines brings promise for effective therapies designed for inflammatory and autoimmune disorders. Cefazolin, a safe, first-generation cephalosporin antibiotic, has been recently shown to specifically interact with interleukin 15 (IL-15) receptor subunit α (IL-15Rα) and to inhibit IL-15-dependent TNF-α and IL-17 synthesis. The aim of this study was to elucidate cefazolin activity against IL-2, IL-4, IL-15 and IL-21, i.e. four cytokines sharing the common cytokine receptor γ chain (γc). In silico, molecular docking unveiled two potential cefazolin binding sites within the IL-2/IL-15Rß subunit and two within the γc subunit. In vitro, cefazolin decreased proliferation of PBMC (peripheral blood mononuclear cells) following IL-2, IL-4 and IL-15 stimulation, reduced production of IFN-γ, IL-17 and TNF-α in IL-2- and IL-15-treated PBMC and in IL-15 stimulated natural killer (NK) cells, attenuated IL-4-dependent expression of CD11c in monocyte-derived dendritic cells and suppressed phosphorylation of JAK3 in response to IL-2 and IL-15 in PBMC, to IL-4 in TF-1 (erythroleukemic cell line) and to IL-21 in NK-92 (NK cell line). The results of the study suggest that cefazolin may exert inhibitory activity against all of the γc receptor-dependent cytokines, i.e. IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.

Facile hydrothermal synthesis of novel Fe-Cu layered double hydroxide/biochar nanocomposite with enhanced sonocatalytic activity for degradation of cefazolin sodium.

This study reports the successful synthesis of Fe-Cu layered double hydroxide (Fe-Cu-LDH) /biochar (BC) nanocomposite by a hydrothermal method. The sonocatalytic performance of Fe-Cu-LDH/BC nanocomposite was investigated for the degradation of cefazolin sodium (CFZ), as a model emerging contaminant, from the solution. The physico-chemical properties of the synthesized samples were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDX), Brunauer-Emmett-Teller (BET), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR), and UV-Vis diffuse reflectance spectroscopy (DRS) analyses. The best sonocatalytic efficiency of 97.6% was achieved by using 1.0 g/L sonocatalyst, 0.1 mM CFZ, and an ultrasonic power of 300 W at pH = 6.5 (natural) within 80 min. Additionally, the effects of the addition of various oxidants, dissolved gases, and organic and inorganic scavengers on the degradation of CFZ were studied. Moreover, the possible sonocatalytic mechanism of the sonochemical degradation of CFZ in the presence of Fe-Cu-LDH/BC sonocatalyst was proposed based on the results of GC-MS analysis. The mineralization of CFZ solution was evaluated using COD and IC analyses. Finally, the reusability test of Fe-Cu-LDH/BC nanocomposite in the CFZ degradation revealed that almost 9% drop occurred after five successive cycles.

Determination of total or free cefazolin and metronidazole in human plasma or interstitial fluid by HPLC-UV for pharmacokinetic studies in man.

Cefazolin (CFZ) plus metronidazole (MTZ) is commonly used for perioperative antibiotic prophylaxis. An HPLC-UV method is described for the simultaneous determination of total or free cefazolin and metronidazole in human plasma or in microdialysate of subcutaneous tissue. Separation was performed isocratically using a reversed phase column and phosphate buffer/acetonitrile as mobile phase. The validation characteristics were similar for both drugs. Linearity has been shown down to 0.1 mg/L (R > 0.9990). Intra- and inter-assay precision (CV) and in-accuracy were < 5%. The method was applied to the determination of cefazolin and metronidazole in plasma and microdialysate of surgical patients following 30-min intravenous infusion of cefazolin/metronidazole 2.0/0.5 g.

Electrochemical sensing of 2-methyl-4, 6-dinitrophenol by nanomagnetic core shell linked to carbon nanotube modified glassy carbon electrode.

Electrochemical behavior and sensing of 2-methyl-4, 6-dinitrophenol as an herbicide has been investigated by cyclic voltammetry (CV) and square wave voltammetry (SWV). We have synthesized a cefazolin (CEF) immobilized nanomagnetic core-shell (Fe3O4@SiO2-(CH2)3-CEF) and attached it on the modified glassy carbon electrode (GCE/MWCNT) through electrostatic adsorption (GCE/MWCNT/CEF-SiO2@Fe3O4). 2-Methyl-4, 6-dinitrophenol has an oxidation peak that is related to the formation of nitrosamine from hydroxylamine species. This peak was applied for quantifying determination of 2-methyl-4, 6-dinitrophenol. The electrochemical oxidation involves two electron transfers accompanied by two protons. The electrochemical process was controlled by adsorption. The good agreement between the obtained computational studies and the experimental results has demonstrated that outer sphere electron transfer occurred on modified electrode. The new electrochemical sensor was applied to determination of 2-methyl-4, 6-dinitrophenol by SWV in the range of 1.0 × 10-10 to 1.5 × 10-7 M with a detection limit of 0.1 nM. The proposed sensor was applied for determination of 2-methyl-4, 6-dinitrophenol in water samples.

Formulation development and characterization of cefazolin nanoparticles-loaded cross-linked films of sodium alginate and pectin as wound dressings.

The present study focuses on the preparation of nanoparticles-loaded ionic cross-linked films for the topical delivery of cefazolin. The aim of the study was to prepare a dosage form which can provide local effect of cefazolin along with sustained delivery at the site of application. Cefazolin was loaded into chitosan nanoparticles to mask the burst release of the drug and they were optimized based on particle size, PDI, % EE and zeta potential. Finally, the prepared nanoparticles were loaded into the films comprising of sodium alginate and pectin which were then subjected to cross-linking via calcium chloride to improve the mechanical strength of the hydrogel films upon exposure to wound fluid. The films were assessed for physical and mechanical properties, swelling behavior, water transmission rate, mucoadhesion, FTIR, DSC, percent inhibition assay and in vitro release profile. Optimized formulation with Cefazolin nanoparticles in the size range of 227 nm and 0.5% CL films showed significantly better results (p < 0.05) as compared to the films with increased cross-linker concentration. Therefore, 0.5% CL films were considered more suitable for the treatment of infections when applied as wound dressing.

Quantitative analysis of cefazolin sodium in lyophilized powder by infrared spectrophotometry: Green, low cost, fast and effective.

Cefazolin sodium is a broad-spectrum antibiotic used in the treatment of infectious diseases in humans and in the surgical prophylaxis. Thus, since a considerable number of people have access to this drug, it is of great interest of quality control. The aim of this study was development and validation of a green method by Fourier-Transform Infrared (FT-IR) transmission spectrophotometry for the quantification of cefazolin sodium in lyophilized powder. This technique is widely used in the pharmaceutical industry due to its ease of execution, low cost, safety and high precision and accuracy. It has been employed in the quality control routine of numerous pharmaceuticals in order to identify them and quantify their active principles. The proposed method was completely validated according ICH guidelines, showing selectivity, accuracy, precision, robustness and linearity. It was linear over the concentration range of 0.4-1.7 mg with correlation coefficient 0.999, limits of detection and quantification of 0.017 mg and 0.052 mg, respectively, precise, accurate and robust when changes in the time, pressure and mark of potassium bromide were carried out during the preparation of the pellets. The proposed method was successfully applied to the qualitative and quantitative quality control of cefazolin sodium in lyophilized powder. In addition, the method is considered green, clean and sustainable since it uses only a single reagent; it is a fast, low-cost and environmentally friendly method.

Enzymatic synthesis of cefazolin using immobilized recombinant cephalosporin-acid synthetase as the biocatalyst.

A method for the synthesis of ß-lactam antibiotic cefazolin (CEZ) by enzymatic acylation of 7-amino-3-(5-methyl-l,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (TDA) using immobilized cephalosporin-acid synthetase (IECASA) from recombinant E. coli strain VKPM B-12316 has been developed. A stepwise pH gradient designed on the basis of investigations on the solubility of components was applied for synthesis. This helped in avoiding the precipitation of TDA in the reaction when its initial concentration was high (150-200 mM). Thus, under optimal conditions a high yield of CEZ (relative to TDA) of 92-95% was obtained. Where the final reaction mixture contained 65-85 mg/mL of CEZ, 4-5 mg/mL of unreacted TDA, and 40-60 mg/mL of the by-product, 1(H)-tetrazolylacetic acid (TzAA). Testing of optimized CEZ synthesis using IECASA in a batch reactor has proved sufficiently high operational stability of the biocatalyst, with its residual activity after the 25th cycle accounting for about 83 ± 2% of its starting value. The half-inactivation period of IECASA was estimated as 85 cycles of CEZ synthesis.

Cefazolin-loaded polycaprolactone fibers produced via different electrospinning methods: Characterization, drug release and antibacterial effect.

Antibiotic containing polycaprolactone (PCL) fibers were produced by using three electrospinning methods: blend, emulsion and co-axial electrospinning (labeled as S1, S2 and S3, respectively). The profiles of drug release from three different systems were studied and antimicrobial properties of produced materials were evaluated. Morphology of the produced fibers was characterized and revealed that cefazolin-loaded PCL fibers had smaller diameter compared to neat PCL fibers, while the chemical interaction between the antibiotic and PCL showed that cefazolin neither had reacted with PCL phase, nor had degraded during the electrospinning process. The crystallinity and thermal characterization of fabricated fibers showed that the addition of cefazolin decreased the crystallinity of PCL. The results of the drug release behavior of the blend and co-axial electrospun fibers was on a higher level (~68% and ~43%, respectively) compared to the emulsion electrospun fibers (~5%), after a period of 30 days. The obtained data had the best fitting with the first order model and the Higuchi model, while the Korsmeyer-Peppas model showed a Pseudo-Fickian diffusion of the drug. Antibacterial evaluations showed that cefazolin-loaded PCL fibers had better effects on Staphylococcus aureus compared to Escherichia coli during the treatment period and that the effect of the emulsion fibers was notably weaker than the other two studied systems. The aim of the study was to test different systems for control drug release of different dynamics, which will be applied for prevent bacterial accumulation when indwelling urinary catheters, applied for different periods of time.

Simultaneous quantification of fentanyl, sufentanil, cefazolin, doxapram and keto-doxapram in plasma using liquid chromatography-tandem mass spectrometry.

A simple and specific UPLC-MS/MS method was developed and validated for simultaneous quantification of fentanyl, sufentanil, cefazolin, doxapram and its active metabolite keto-doxapram. The internal standard was fentanyl-d5 for all analytes. Chromatographic separation was achieved with a reversed-phase Acquity UPLC HSS T3 column with a run-time of only 5.0 min per injected sample. Gradient elution was performed with a mobile phase consisting of ammonium acetate or formic acid in Milli-Q ultrapure water or in methanol with a total flow rate of 0.4 mL min-1 . A plasma volume of only 50 µL was required to achieve adequate accuracy and precision. Calibration curves of all five analytes were linear. All analytes were stable for at least 48 h in the autosampler. The method was validated according to US Food and Drug Administration guidelines. This method allows quantification of fentanyl, sufentanil, cefazolin, doxapram and keto-doxapram, which is useful for research as well as therapeutic drug monitoring, if applicable. The strength of this method is the combination of a small sample volume, a short run-time, a deuterated internal standard, an easy sample preparation method and the ability to simultaneously quantify all analytes in one run.

Fast and sensitive HPLC/UV method for cefazolin quantification in plasma and subcutaneous tissue microdialysate of humans and rodents applied to pharmacokinetic studies in obese individuals.

Antimicrobial prophylactic dosing of morbidly obese patients may differ from normal weighted individuals owing to alterations in drug tissue distribution. Drug subcutaneous tissue distribution can be investigated by microdialysis patients and animals. The need for cefazolin prophylactic dose adjustment in obese patients remains under discussion. The paper describes the validation of an HPLC-UV method for cefazolin quantification in plasma and microdialysate samples from clinical and pre-clinical studies. A C18 column with an isocratic mobile phase was used for drug separation, with detection at 272 nm. Total and unbound cefazolin lower limit of quantitation was 5 µg/mL in human plasma, 2 µg/mL in rat plasma, and 0.5 and 0.025 µg/mL in human and rat microdialysate samples, respectively. The maximum intra- and inter-day imprecisions were 10.7 and 8.1%, respectively. The inaccuracy was <9.7%. The limit of quantitation imprecision and inaccuracy were < 15%. Cefazolin stability in the experimental conditions was confirmed. Cefazolin plasma concentrations and subcutaneous tissue penetration were determined by microdialysis in morbidly obese patients (2 g i.v. bolus) and diet-induced obese rats (30 mg/kg i.v. bolus) using the method. This method has the main advantages of easy plasma clean-up and practicability and has proven to be useful in cefazolin clinical and pre-clinical pharmacokinetic investigations.

Stability of Cefazolin in Polyisoprene Elastomeric Infusion Devices.

PURPOSE: The aim was to investigate the stability of cefazolin in elastomeric infusion devices. METHODS: Elastomeric devices (Infusor LV) that contain cefazolin (3 g/240 mL and 6 g/240 mL) were prepared and stored at 4°C for 72 hours and then at 35°C for 12 hours, followed by 25°C for 12 hours. An aliquot was withdrawn at predefined time points and analyzed for the concentration of cefazolin. Samples were also assessed for changes in pH, solution color, and particle content. FINDINGS: Cefazolin retained acceptable chemical and physical stability over the studied storage period and conditions. IMPLICATIONS: These findings will allow the administration of cefazolin by the Infusor LV elastomeric device in the outpatient and remote settings.

Thermokinetic profile of NDM-1 and its inhibition by small carboxylic acids.

The New Delhi metallo-ß-lactamase (NDM-1) is an important clinical target for antimicrobial research, but there are insufficient clinically useful inhibitors and the details of NDM-1 enzyme catalysis remain unclear. The aim of this work is to provide a thermodynamic profile of NDM-1 catalysed hydrolysis of ß-lactams using an isothermal titration calorimetry (ITC) approach and to apply this new method to the identification of new low-molecular-weight dicarboxylic acid inhibitors. The results reveal that hydrolysis of penicillin G and imipenem by NDM-1 share the same thermodynamic features with a significant intrinsic enthalpy change and the release of one proton into solution, while NDM-1 hydrolysis of cefazolin exhibits a different mechanism with a smaller enthalpy change and the release of two protons. The inhibitory constants of four carboxylic acids are found to be in the micromolar range. The compounds pyridine-2,6-dicarboxylic acid and thiazolidine-2,4-dicarboxylic acid show the best inhibitory potency and are confirmed to inhibit NDM-1 using a clinical strain of Escherichia coli The pyridine compound is further shown to restore the susceptibility of this E. coli strain to imipenem, at an inhibitor concentration of 400 µM, while the thiazoline compound also shows a synergistic effect with imipenem. These results provide valuable information to enrich current understanding on the catalytic mechanism of NDM-1 and to aid the future optimisation of ß-lactamase inhibitors based on these scaffolds to tackle the problem of antibiotic resistance.

3D printed Polycaprolactone scaffolds with dual macro-microporosity for applications in local delivery of antibiotics.

Advanced scaffolds used in tissue regenerating applications should be designed to address clinically relevant complications such as surgical site infection associated with surgical procedures. Recognizing that patient-specific scaffolds with local drug delivery capabilities are a promising approach, we combined 3D printing with traditional salt-leaching techniques to prepare a new type of scaffold with purposely designed macro- and micro-porosity. The dual macro/micro porous scaffolds of medical-grade polycaprolactone (mPCL) were characterized for their porosity, surface area, mechanical properties and degradation. The use of these scaffolds for local prophylactic release of Cefazolin to inhibit S. aureus growth was investigated as an example of drug delivery with this versatile platform. The introduction of microporosity and increased surface area allowed for loading of the scaffold using a simple drop-loading method of this heat-labile antibiotic and resulted in significant improvement in its release for up to 3 days. The Cefazolin released from scaffolds retained its bioactivity similar to that of fresh Cefazolin. There were no cytotoxic effects in vitro against 3 T3 fibroblasts at Cefazolin concentration of up to 100 µg/ml and no apparent effects on blood clot formation on the scaffolds in vitro. This study therefore presents a novel type of scaffolds with dual macro- and micro-porosity manufactured by a versatile method of 3D printing combined with salt-leaching. These scaffolds could be useful in tissue regeneration applications where it is desirable to prevent complications using local delivery of drugs.

The interactions of cephalosporins on polyol pathway enzymes from sheep kidney.

CONTEXT: Cephalosporins are derived from the fungus Acremonium. Due to their strong bactericidal ability, these drugs have to a wide usage in medicine. OBJECTIVE: An investigation of the effects on sheep renal aldose reductase (AR) and sorbitol dehydrogenase (SDH) of cefoperazone, cefazolin, cefuroxime, ceftazidime and ceftriaxone as cephalosporin drugs was carried out in the present study. METHODS: AR and SDH were purified from sheep kidney by ion exchange, gel filtration and affinity methods with approximately 219- and 484-fold, respectively. Some kinetic properties of the enzymes were determined such as optimal pH, optimal ionic strength, optimal temperature, stable pH, Km and Vmax. IC50 values of the drugs were found for each enzyme. RESULTS: While the AR was inhibited by all drugs, SDH enzyme was inhibited by only CXM (IC50 8.10 mM). Interestingly, CZO activated SDH enzyme. This result was evaluated as important for the flow of the polyol reactions. Ki values and inhibition types were determined for AR. However, these values could not have determined for SDH, due to insufficient inhibition. CONCLUSIONS: From these results, it was concluded that cephalosporins may have an important effect on flow of the polyol metabolism.

Antibiotic-eluting orthopedic device to prevent early implant associated infections: Efficacy, biocompatibility and biodistribution studies in an ovine model.

Infection of orthopedic devices is a major complication in the postsurgical period generating important health issues and economic consequences. Prevention strategies could be based on local release of antibiotics from the orthopedic device itself to avoid adhesion and growth of bacteria. The purpose of this work is to demonstrate the efficiency to prevent these infections by a cefazolin-eluting, perforated stainless steel implant in an in vivo ovine model. The device was placed in the tibia of sheep, one group receiving cefazolin-loaded implants whereas the control group received empty implants. All implants were experimentally infected by direct inoculation of Staphylococcus aureus ATCC 6538. In vitro cytotoxicological studies were also performed to check the effect of antibiotic on cell viability, integrity, and cycle. Results showed that sheep receiving cefazolin-loaded devices were able to avoid implant-associated infections, with normal tissue healing process. The antibiotic release followed a local concentric pattern as demonstrated by high-performance liquid chromatography detection in tissues. The in vitro results indicate the lack of relevant cytotoxic effects for the maximum antibiotic concentration released by the device. These results demonstrate the efficiency and safety of cefazolin-eluting implants in an ovine model to prevent early postsurgical infections of orthopedic devices. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1976-1986, 2018.