Local cefuroxime tissue concentrations in the hand after single and repeated administration to 16 patients undergoing trapeziectomy: a randomized controlled trial.

BACKGROUND AND PURPOSE:  The duration of antibiotic coverage in hand tissues during surgery is unknown. We investigated the time the free concentration of cefuroxime was above the minimal inhibitory concentration (fT>MIC) of 4 µg/mL in hand tissues after single and repeated administration. METHODS:  In a prospective, unblinded randomized study 16 patients (13 female, age range 51-80 years) underwent trapeziectomy. Microdialysis catheters were placed in the metacarpal bone (primary effect parameter), synovial sheath, and subcutaneous tissue. Patients were randomized to postoperative administration of either intravenous single administration of cefuroxime (1,500 mg) (Group 1, n = 8) or repeated dosing (2 x 1,500 mg) with a 4 h interval (Group 2, n = 8). Samples were taken over 8 h. RESULTS: The fT>MIC of 4 µg/mL was found to be significantly longer in the metacarpal bone in Group 2 compared with Group 1 with a mean difference of 199 min (95% confidence interval 158-239). The same trend was evident in the remaining compartments. A concentration of 4 µg/mL was reached in all compartments in both groups within a mean time of 6 min (range 0-27 min). In Group 1, the mean concentrations decreased below 4 µg/mL between 3 h 59 min and 5 h 38 min. CONCLUSION:  The fT>MIC was longer after repeated administration compared with single administration in all compartments. A single administration of cefuroxime 1,500 mg provided antimicrobial hand tissue coverage for a minimum of 3 h 59 min. Cefuroxime administration in hand surgeries should be done minimum 27 min prior to incision to achieve sufficient coverage in all individuals. Cefuroxime readministration should be considered in hand surgeries lasting longer than 4 h from time of administration.

Suspensions of antibiotics in self-emulsifying oils as a novel approach to formulate eye drops with substances which undergo hydrolysis in aqueous environment.

The aim of this study was to develop eye-drops with cefuroxime (CEF) sodium or vancomycin (VAN) hydrochloride, antibiotics that are instable in water. Anhydrous self-emulsifying oils (SEO) are proposed as a carrier and antibiotics are suspended. In the contact with tear fluid, the formulation should transform into emulsion, with fast dissolution of an antibiotic. CEF or VAN (5% w/w) was suspended in SEO carriers prepared by dissolving surfactants (Tween 20 or Span 80 5% w/w) in Miglyol, castor oil, or olive oil. Formulations with or without sodium citrate (2% w/w) were compared. Six-months or 1-year stability tests were carried out at 40 °C. The content of CEF and VAN was evaluated using HPLC and the potency of the antibiotic was assessed with agar diffusion method. In contact with water, drug particles suspended in SEO dissolved rapidly and o/w emulsion was formed. After 1-year at 40 °C, the content of degradation products was at most 0.5% in CEF and 4.0% in VAN formulations. The agar diffusion assay has shown that CEF and VAN loaded into SEO retained its potency against the sensitive microorganisms comparable to an aqueous solution. Therefore, SEO can be used as a novel carrier for the active substances which may not require improved solubility or absorption but need to be protected from moisture. This is a formulation that can be produced on industrial scale, with no limitation of stability or drug concentration.

[Injection of cefuroxime into the vitreous cavity leading to toxic retinal damage: a case report].

A 36-year-old male patient presented with a decrease in vision after undergoing scleral suturing for a left eye injury caused by an iron hook, combined with intravitreal injection of cefuroxime. Ocular examination revealed extensive gray-white edematous areas in the macular region, along with focal serous shallow retinal detachment in the posterior pole. Following admission, comprehensive ophthalmic examinations were conducted, leading to the diagnosis of toxic retinal damage in the left eye. Treatment with oral corticosteroids and interventions to improve microcirculation were initiated, resulting in improved visual acuity. At the six-month follow-up, the patient's visual acuity had recovered to 0.5.

Incorporating patient, nursing and environmental factors into antimicrobial stewardship: effects of simplifying treatment from cefuroxime to ceftriaxone.

AIM: Our antimicrobial guidelines (AGs) were changed in 2021 to recommend once-daily ceftriaxone in place of three-times-daily cefuroxime as preferred cephalosporin. This analysis sought to assess the effects of this on incidence of Clostridioides difficile infection (CDI), third-generation cephalosporin-resistant Enterobacterales (3GCR-E) and resource utilisation. METHOD: Before and after analysis of 30-day CDI and 3GCR-E incidence following receipt of cefuroxime/ceftriaxone pre- and post-AG change. Total nursing time and waste production relating to cefuroxime/ceftriaxone delivery were calculated pre- and post-change. RESULTS: CDI incidence was 0.6% pre- and 1.0% post-change (adjusted odds ratio [aOR] 1.44, p=0.07) and 3GCR-E incidence 3.5% and 3.1% (aOR 0.90, p=0.33). Mean per-quarter estimated nursing administration time decreased from 2,065 to 1,163 hours (902 nurse-hour reduction) and antibiotic-related waste generation from 1,131kg to 748kg (383kg reduction). Overall days of therapy per-quarter of cefuroxime/ceftriaxone were unchanged between periods. CONCLUSION: This simplification of our AG from a three-times-daily to a once-daily antibiotic resulted in considerable savings for our hospital (roughly 1.7 full-time equivalent nurses and over a tonne of waste yearly), with no significant increases in CDI or 3GCR-E. The impact of dosing schedules on non-antibiotic-spectrum factors, such as nursing time and resource usage, is worthy of consideration when designing AGs.

Optimal time window for initiating cefuroxime surgical antimicrobial prophylaxis in spinal fusion surgery: a nested case-control study.

BACKGROUND CONTEXT: Surgical site infections (SSI) are one of the common complications following spinal fusion surgery. Unfortunately, several studies had shown conflicting results regarding optimal timing of surgical antimicrobial prophylaxis (SAP) administration. Due to limitations in population homogeneity and sample size, these studies have not provided significant statistical correlations or clear practical recommendations. PURPOSE: The purpose of the study was to investigate the impact of timing of cefuroxime SAP on the risk of SSI in patients undergoing spinal fusion surgery, and to determine the optimal timing of administration. DESIGN: Retrospective nested case-control study. PATIENT SAMPLE: We retrospectively analyzed consecutive patients who underwent spinal fusion surgery at our institution between October 2011 and October 2021. OUTCOME MEASURE: In the current study, the primary outcome measure was SSI. METHODS: This was a retrospective nested case-control study. All consecutive patients who underwent spinal fusion surgery at our institution between October 2011 and October 2021 formed a retrospective cohort. For each SSI case, 2 controls free of SSI at the time of the index date of their corresponding case were selected, matched by age, sex, and calendar year. Electronic record and radiographic data were reviewed retrospectively in electronic database. SAP related data included timing of administration, preoperative dose, intraoperative second dose, and postoperative use. To examine the effects of mismatched variables, we further adjusted for possible confounding factors using conditional logistic regression models. Subsequently, subgroup analyses were conducted to assess the robustness of the statistical associations. RESULTS: According to the preplanned statistical scheme and matching factors, we matched 236 controls for these SSI cases, and the subsequent statistical analysis was performed on these 354 patients. After adjusting for confounding factors, the results indicated that the risk of SSI was 70% higher in the group receiving SAP 31 to 60 minutes before incision compared to the group receiving SAP 0 to 30 minutes before incision (OR=1.732, 95%CI 1.031-2.910, p=.038). Additionally, the risk of SSI was 150% higher in the group receiving SAP 61 to 120 minutes before incision compared to the group receiving SAP 0 to 30 minutes before incision (OR=2.532, 95%CI 1.250-5.128, p=.010). In subgroup analysis, this statistical trend persisted for both deformity surgeries and different SSI classifications. CONCLUSION: Administering cefuroxime SAP within 30 minutes before skin incision significantly reduces the risk of SSI, whether they are deep or superficial, in spinal fusion surgery. This pattern remains consistent among spinal deformity patients.

Weight-based cefuroxime dosing provides comparable orthopedic target tissue concentrations between weight groups - a microdialysis porcine study.

Antibiotic prophylaxis is a key element in prevention of surgical site infections. For the majority of orthopedic procedures, antibiotic administration follows fixed dosing regimens irrespective of weight. However, this may result in insufficient antibiotic target tissue concentrations and higher risk of surgical site infections in obese individuals. The aim of this study was to investigate the effect of weight-based cefuroxime dosing on plasma and target tissue concentrations. Eighteen female pigs were allocated into three groups differentiated by weight: 53-57 kg, 73-77 kg, and 93-97 kg. Microdialysis catheters were placed for continuous sampling in bone, muscle, and subcutaneous tissue during an 8h sampling interval. Blood samples were collected as reference. Cefuroxime was administered intravenously as a bolus according to weight (20 mg/kg). The primary endpoint was the time above the cefuroxime minimal inhibitory concentration for Staphylococcus aureus (T > MIC (4 µg/mL)). Comparable target tissue T > MICs (4 µg/mL) were found between weight groups. Mean T > MIC ranged between 116-137 min for plasma, 118-154 min for bone, 109-146 min for the skeletal muscle, and 117-165 min for subcutaneous tissue across the groups. Weight-based cefuroxime (20 mg/kg) dosing approach provides comparable perioperative plasma and target tissue T > MIC (4 µg/mL) in animals between 50-100 kg body weight, and thus a comparable prophylaxis of surgical site infections.

Association Between Antimicrobial Prophylaxis With Double-Dose Cefuroxime and Surgical Site Infections in Patients Weighing 80 kg or More.

Importance: Many guidelines recommend a weight-adopted dose increase of cefuroxime for surgical antimicrobial prophylaxis (SAP). However, the evidence that this approach is associated with lower rates of surgical site infection (SSI) is limited. Objective: To assess whether double-dose cefuroxime SAP was associated with a decreased SSI rate in patients weighing at least 80 kg. Design, Setting, and Participants: This cohort study included adult patients (>18 years) weighing at least 80 kg who underwent 9 major surgical procedures with a cefuroxime SAP administration from the Swissnoso SSI surveillance system between January 2015 and December 2019 at 142 Swiss hospitals. The follow-up was 30 days for all surgical procedures and 1 year for implant-related operations. Exposures: Cefuroxime SAP dose (1.5 vs 3.0 g). Main Outcomes and Measures: Overall SSI. A mixed-effects logistic regression adjusted for institutional, epidemiological, and perioperative variables was applied. Results were stratified by weight categories as well as by wound contamination classes. Results: Of 41 076 eligible patients, 37 640 were included, with 22 625 (60.1%) men and a median (IQR) age of 61.9 (49.9-71.1) years. The outcome SSI was met by 1203 patients (3.2%). Double-dose cefuroxime was administered to 13 246 patients (35.2%) and was not significantly associated with a lower SSI rate (adjusted odds ratio [aOR], 0.89; 95% CI, 0.78-1.02; P = .10). After stratification by weight category, double-dose SAP vs single-dose SAP was associated with lower SSI rates among 16 605 patients weighing at least 80 to less than 90 kg (aOR, 0.76; 95% CI, 0.61-0.97; P = .02) but not in the other weight categories (≥90 to <100 kg, 10 342 patients: aOR, 1.12; 95% CI, 0.87-1.47; P = .37; ≥100 to <120 kg, 8099 patients: aOR, 0.99; 95% CI, 0.76-1.30; P = .96; ≥120 kg, 2594 patients: aOR, 0.65; 95% CI, 0.42-1.04; P = .06). After stratification by contamination class, double-dose SAP was associated with lower SSI rates among 1946 patients with contaminated wounds (aOR, 0.49; 95% CI, 0.30-0.84; P = .008) but not those with clean wounds (25 680 patients; aOR, 0.92; 95% CI, 0.76-1.12; P = .44) or clean-contaminated wounds (10 014 patients; aOR, 0.90; 95% CI, 0.73-1.12; P = .37) compared with a single dose. Conclusions and Relevance: In this study, double-dose SAP with cefuroxime for patients weighing at least 80 kg was not consistently associated with a lower SSI rate.

PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Kidney in Pregnant Subjects and Fetus.

The purpose of this study was to develop a physiologically based pharmacokinetic (PBPK) model predicting the pharmacokinetics (PK) of different compounds in pregnant subjects. This model considers the differences in tissue sizes, blood flow rates, enzyme expression levels, glomerular filtration rates, plasma protein binding, and other factors affected during pregnancy in both the maternal and fetal models. The PBPKPlus™ module in GastroPlus® was used to model the PK of cefuroxime and cefazolin. For both compounds, the model was first validated against PK data in healthy non-pregnant volunteers and then applied to predict pregnant groups PK. The model accurately described the PK in both non-pregnant and pregnant groups and explained well differences in the plasma concentration due to pregnancy. The fetal plasma and amniotic fluid concentrations were also predicted reasonably well at different stages of pregnancy. This work describes the use of a PBPK approach for drug development and demonstrates the ability to predict differences in PK in pregnant subjects and fetal exposure for compounds excreted renally. The prediction for pregnant groups is also improved when the model is calibrated with postpartum or non-pregnant female group if such data are available.

Comparison of the local effects of different intracameral cefuroxime solutions on rabbit cornea.

PURPOSE: We aimed to compare the local effects of intracameral cefuroxime diluted in normal saline (SF groups) against those of cefuroxime in balanced salt solution (BSS group) on the cornea of rabbits. MATERIALS AND METHODS: Fourteen New Zealand albino rabbits were randomised into two groups. The right eyes of the rabbits in the SF group I were injected intracamerally with 1 mg cefuroxime diluted with 0.1 mL normal saline (n = 7), whereas the right eyes of the BSS group II were injected with 1 mg intracameral cefuroxime diluted with 0.1 mL with balance salt solution, and the left eyes of all rabbits received no treatment group III (control group). Corneal thickness was measured with pachymetry before and 1 week after the injection. Corneal samples were evaluated with light, specular and electron microscopy. RESULTS: Mean endothelial cell count was lower in the SF than in the BSS and control groups. Although an increase in corneal thickness was found in both treatment groups, this was not the case for the control group. The corneal endothelium preserved its hexagonal structure in all groups. Although both treatment groups showed a loss of endothelial microvilli, this was more prevalent in the SF group. However, microvilli were preserved in the control group. Dissolution of tight junctions in corneal endothelium was observed in the SF group only. Mitochondrial swelling, coarsening of endoplasmic reticulum, cytoplasmic vacuolisation, and increased endothelial cell sizes were the same in both treatment groups but was not observed in the control group. Thicker and more oedematous corneal stroma were observed in the SF group compared with the BSS and control groups. CONCLUSION: Dilution of intracameral cefuroxime in BSS yielded superior results compared with dilution in normal saline owing to toxicity to the endothelial cells and decline in the endothelial cell number, resulting in intracellular and intercellular morphological changes. BSS or any other solution with proven safety should be used in clinical studies.

Timing of Antimicrobial Prophylaxis and Tourniquet Inflation: A Randomized Controlled Microdialysis Study.

BACKGROUND: Tourniquets are widely used during extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimum inhibitory concentration (t > MIC) in porcine subcutaneous adipose tissue and calcaneal cancellous bone during 3 clinically relevant tourniquet application scenarios. METHODS: Twenty-four female Danish Landrace pigs were included. Microdialysis catheters were placed bilaterally for sampling of cefuroxime concentrations in calcaneal cancellous bone and subcutaneous adipose tissue, and a tourniquet was applied to a randomly picked leg of each pig. Subsequently, the pigs were randomized into 3 groups to receive 1.5 g of cefuroxime by intravenous injection 15 minutes prior to tourniquet inflation (Group A), 45 minutes prior to tourniquet inflation (Group B), and at the time of tourniquet release (Group C). The tourniquet duration was 90 minutes in all groups. Dialysates and venous blood samples were collected for 8 hours after cefuroxime administration. Cefuroxime and various ischemic marker concentrations were quantified. RESULTS: Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 µg/mL) in calcaneal cancellous bone and subcutaneous adipose tissue throughout the 90-minute tourniquet duration in Groups A and B. Cefuroxime administration at the time of tourniquet release (Group C) resulted in concentrations of >4 µg/mL for approximately of 3.5 hours in the tissues on the tourniquet side. Furthermore, tourniquet application induced ischemia (increased lactate:pyruvate ratio) and cell damage (increased glycerol) in subcutaneous adipose tissue and calcaneal cancellous bone. Tissue ischemia was sustained for 2.5 hours after tourniquet release in calcaneal cancellous bone. CONCLUSIONS: Administration of cefuroxime (1.5 g) in the 15 to 45-minute window prior to tourniquet inflation resulted in sufficient concentrations in calcaneal cancellous bone and subcutaneous adipose tissue throughout the 90-minute tourniquet application. Furthermore, tourniquet-induced tissue ischemia fully resolved 2.5 hours after tourniquet release. CLINICAL RELEVANCE: Cefuroxime administration 15 to 45 minutes prior to tourniquet inflation seems to be a safe window. If the goal is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at the time of tourniquet release.

Similar risk of complete revision for infection with single-dose versus multiple-dose antibiotic prophylaxis in primary arthroplasty of the hip and knee: results of an observational cohort study in the Dutch Arthroplasty Register in 242,179 patients.

Background and purpose - The optimal type and duration of antibiotic prophylaxis for primary arthroplasty of the hip and knee are subject to debate. We compared the risk of complete revision (obtained by a 1- or 2-stage procedure) for periprosthetic joint infection (PJI) after primary total hip or knee arthroplasty between patients receiving a single dose of prophylactic antibiotics and patients receiving multiple doses of antibiotics for prevention of PJI. Patients and methods - A cohort of 130,712 primary total hip and 111,467 knee arthroplasties performed between 2011 and 2015 in the Netherlands was analyzed. We linked data from the Dutch arthroplasty register to a survey collected across all Dutch institutions on hospital-level antibiotic prophylaxis policy. We used restricted cubic spline Poisson models adjusted for hospital clustering to compare the risk of revision for infection according to type and duration of antibiotic prophylaxis received. Results - For total hip arthroplasties, the rates of revision for infection were 31/10,000 person-years (95% CI 28-35), 39 (25-59), and 23 (15-34) in the groups that received multiple doses of cefazolin, multiple doses of cefuroxime, and a single dose of cefazolin, respectively. The rates for knee arthroplasties were 27/10,000 person-years (95% CI 24-31), 40 (24-62), and 24 (16-36). Similar risk of complete revision for infection among antibiotic prophylaxis regimens was found when adjusting for confounders. Interpretation - In a large observational cohort we found no apparent association between the type or duration of antibiotic prophylaxis and the risk of complete revision for infection. This does question whether there is any advantage to the use of prolonged antibiotic prophylaxis beyond a single dose.

Quimioterapia intraperitoneal en aerosol presurizado (PIPAC) / Pressurized intraperitoneal aerosol chemotherapy (PIPAC)

RESUMEN La técnica PIPAC se presenta como una variante de tratamiento para los pacientes con carcinomato sis peritoneal que no son candidatos a una resección. Se describen de manera detallada los pasos y el procedimiento quirúrgico para la administración de quimioterapia intraperitoneal presurizada con dispositivo PIPAC.

ABSTRACT Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a therapeutic option for patients with unresectable peritoneal carcinomatosis. The steps and the surgical technique of the PIPAC technique are thoroughly described.

Preoperative antibiotic prophylaxis regimen in brain tumour surgery in Sweden: a quasi-experimental study.

BACKGROUND: There has been varied clinical practice concerning antibiotic prophylaxis in patients undergoing craniotomy. In Sweden, both Cloxacillin and Cefuroxime have frequently been used. We aimed to study the clinical effectiveness of these two regimens. METHODS: A quasi-experimental design was used. The sample consisted of 580 adult (> 18 years) patients operated 2012-2015, of which 375 received Cloxacillin (pre-intervention group) and 205 received Cefuroxime (intervention group). Primary endpoint was the incidence of surgical site infection (SSI) 12 months after surgery, while secondary endpoints were the need for reoperation due to SSI, the amount antibiotics used and the number of visits in the outpatient clinic related to SSI. A control group from another institution was reviewed to rule out clinical trial effects. RESULTS: When analysed by intention to treat, the pre-intervention group had a significant higher incidence of SSI, 13.3% (50/375) vs 5.4% (11/205) in the intervention group (p < 0.01). A treatment per protocol analysis confirmed the result. The number of reoperations due to SSI were significantly reduced in the intervention group, 3.4% (7/205) vs 8.3% (31/375) (p = 0.02), as was the total antibiotic use (p = 0.03) and the number of visits in the outpatient clinic (p < 0.01). In the control group, the reoperation rate as result of SSI was lower (p = 0.02) prior to the opposite change from Cefuroxime to Cloxacillin, 1.8% (27/1529) vs 3.1% (43/1378). CONCLUSION: In Sweden, Cefuroxime as prophylaxis in brain tumour surgery by craniotomy seems to be superior to Cloxacillin.

Are oral cefuroxime axetil, cefixime and cefditoren pivoxil adequate to treat uncomplicated acute pyelonephritis after switching from intravenous therapy? A pharmacokinetic/pharmacodynamic perspective.

OBJECTIVES: The goal of this study is to assess, by means of pharmacokinetic/pharmacodynamic (PK/PD) analysis using the Monte Carlo simulation, the adequacy of oral cephalosporins cefuroxime axetil, cefixime and cefditoren at different dosing regimens as switch therapy after intravenous cephalosporin treatment in uncomplicated acute pyelonephritis. METHODS: The methodology included: (i) dosing regimen selection and acquisition of pharmacokinetic data; (ii) microbiological data acquisition; and (iii) Monte Carlo simulation to estimate the PTA (probability of PK/PD target attainment) and CFR (cumulative fraction of response), as indicators of treatment success. RESULTS: At the current susceptibility breakpoints defined by EUCAST and CLSI for either cefuroxime axetil or cefixime, the probability of bactericidal target attainment is zero for the dosage regimens simulated. Considering the bactericidal target %fT>MIC>70%, the likelihood of the cefuroxime 500-mg q8h regimen or the cefixime 200-mg q12h regimen producing this exposure or achieving this target is only above 90% for organisms yielding MICs≤0.5mg/l and MICs≤0.25mg/l, respectively. Cefditoren pivoxil 400mg q12h provided probabilities of bactericidal target attainment of 80% or higher for MICs≤0.03mg/l, and ≤0.25mg/l if considering total instead of free drug concentrations. CONCLUSIONS: The results of the PK/PD target attainment analysis reveal that the likelihood of treatment success based upon the current breakpoints proposed by either EUCAST or CLSI is low. Of the three cephalosporins, cefixime 400mg q12h prove to be the best option in oral APN treatment, although this regimen is currently off label.

Cefuroxime pharmacokinetics and pharmacodynamics for intravenous dosage regimens with 750 mg or 1500 mg doses in healthy young volunteers.

Introduction. Cefuroxime is an important antibiotic to treat several serious infections. Rapid elimination through the kidneys and the variation in MICs of various susceptible pathogens such as Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae give rise to dosing issues, especially in otherwise healthy patients.Aim. To investigate the probability of target attainment (PTA) for obtaining the optimal dosage regimens for cefuroxime in healthy young people.Methodology. Two weeks apart 750 and 1500 mg cefuroxime were administered as an intravenous bolus to 20 healthy volunteers (mean age: 27 years). Population modelling and simulation studies were done based on the obtained data for cefuroxime plasma concentration.Results. With a target value of time above MIC (T >MIC) greater than 50 % the simulations revealed that a PTA of >99 % is obtained for S. pneumoniae with a dosage regimen of 750 mg q12h. For E. coli and K. pneumoniae the PTA was <90 % even with the highest, simulated dosage of 1500 mg q6h. For S. aureus a dosage of 1500 mg q8h gave a PTA above 97 %.Conclusions. S. pneumoniae is most likely treatable with a two-daily dose of 750 mg cefuroxime. Not treatable are K. pneumoniae and E. coli. For S. aureus 1500 mg q8h constitutes an optimal dosing schedule.

Salmonella enterica serovar Paratyphi A isolated from a hard-to-heal diabetic ulcer: a case report.

Chronically infected diabetic wounds have a polymicrobial aetiology. However, Salmonella Paratyphi A is a very rare cause of wound infection. A 76-year-old female patient with type II diabetes presented with a wound on the left leg of two months' duration. The wound was painful, erythematous and a thick, foul-smelling discharge was present. There was a history of delayed wound healing. Salmonella Paratyphi A and Pseudomonas aeruginosa were isolated from the wound tissue. The patient was treated with cefuroxime and cloxacillin empirically and following the antibiotic susceptibility testing (ABST) report, ciprofloxacin was given for 10 days. The wound was treated with multiple debridements and topical antiseptic. On follow-up, the patient remained afebrile with subsiding discharge from the ulcer. This is the first reported case of Salmonella Paratyphi A from an infected diabetic ulcer in Sri Lanka and it serves to further define the spectrum of illnesses caused by this uncommon pathogen.

Influence of some ß-lactam drugs on selected antioxidant enzyme and lipid peroxidation levels in different rat tissues.

Antioxidant enzymes play an important role in body defense and free radical removal. Cephalosporins are ß-lactam antibiotics. In this work, the effects of cefazolin, cefuroxime and cefoperazone which are cephalosporins on some selected antioxidant enzyme and levels of malondialdehyde (MDA) as lipid peroxidation product were investigated in kidney, liver, and brain tissues of albino female rats. Ninety-six albino rats were randomly divided into 16 groups of equal number (n = 6). 50 mg/kg cefazolin, 25 mg/kg cefuroxime, and 100 mg/kg cefoperazone were injected intraperitoneally to the groups (5th-8th and 9th-12th, and 13th-16th groups), respectively. The changes in glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GSH-Px) levels were studied in each time point group and a time-dependent manner (at the 1st, 3rd, 5th and 7th hour). In addition, MDA levels were examined in all the tissues. The drugs evaluated in this study had different effects on the same enzyme in different tissues depending on time. MDA levels especially in cefazolin and cefoperazone experiments were lower in all the tissues; however, MDA levels were higher in brain and kidney tissues in the cefuroxime groups in a time-dependent manner (p < 0.05). These results revealed the complex effects of the tested drugs on different tissues at different time points. Therefore, the dose and use of these drugs should be adjusted correctly.

Uptake and pharmacokinetics of cefuroxime in rabbits after intravitreal, intracameral, and topical dosing: relevance to human ocular injection of cefuroxime.

Cefuroxime is one of the widely used antibiotics. The objective of this study was to determine pharmacokinetics and disposition in various ocular tissues following topical (TOP), intracameral (IC) and intravitreal (IVT) administration of cefuroxime to rabbits.Following TOP, IC and IVT dosing plasma and various ocular tissues (aqueous humor (AH), vitreous humor (VH), conjunctiva, trabecular mesh (TM), lens and retina-choroid (RC)) were collected and analyzed to understand the disposition of cefuroxime. Postintravenous administration plasma samples were collected to determine the systemic pharmacokinetics.Post-TOP dosing cefuroxime concentrations were observed only in conjunctiva up to 48 h. IC administration showed cefuroxime concentrations in AH up to 8 h; in conjunctiva, TM and plasma, the concentration lasted up to 4 h and in RC and VH till 1 h. IVT administration of cefuroxime showed concentrations in all ocular tissues (up to 8 h) and lasted up to 48 h except in conjunctiva and RC.There was evidence that the mechanism(s) of cefuroxime entry into the eye by via IVT, IC and TOP routes is clearly different. The present ocular tissue data may aid clinicians for considering appropriate choice in the treatment of post-operative ocular complications due to bacterial infections including endophthalmitis.

Physiologically based pharmacokinetic evaluation of cefuroxime in perioperative antibiotic prophylaxis.

AIMS: Adequate plasma concentrations of antibiotics during surgery are essential for the prevention of surgical site infections. We examined the pharmacokinetics of 1.5 g cefuroxime administered during induction of anaesthesia with follow-up doses every 2.5 hours until the end of surgery. We built a physiologically based pharmacokinetic model with the aim to ensure adequate antibiotic plasma concentrations in a heterogeneous population. METHODS: A physiologically based pharmacokinetic model (PK-Sim® /MoBi® ) was developed to investigate unbound plasma concentrations of cefuroxime. Blood samples from 25 thoracic surgical patients were analysed with high-performance liquid chromatography. To evaluate optimized dosing regimens, physiologically based pharmacokinetic model simulations were conducted. RESULTS: Dosing simulations revealed that a standard dosing regimen of 1.5 g every 2.5 hours reached the pharmacokinetic/pharmacodynamic target for Staphylococcus aureus. However, for Escherichia coli, >50% of the study participants did not reach predefined targets. Effectiveness of cefuroxime against E. coli can be improved by administering a 1.5 g bolus immediately followed by a continuous infusion of 3 g cefuroxime over 3 hours. CONCLUSION: The use of cefuroxime for perioperative antibiotic prophylaxis to prevent staphylococcal surgical site infections appears to be effective with standard dosing of 1.5 g preoperatively and follow-up doses every 2.5 hours. In contrast, if E. coli is relevant in surgeries, this dosing regimen appears insufficient. With our derived dose recommendations, we provide a solution for this issue.