A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine Johannesburg, 2017 / Background: Infections post cardiac surgery can have potentially devastating consequences. Adequate antimicrobial prophylaxis is therefore crucial to limit the occurrence of such complications. Cefazolin is a commonly prescribed prophylactic agent for major cardiac surgery requiring cardiopulmonary bypass (CPB). The effects of CPB on the pharmacokinetic profile of cefazolin are largely unknown. To date there is no published work determining the optimal bolus dosing of cefazolin required to achieve acceptable concentrations intra-operatively during and post CPB. Aim: The aim of this study was to describe the total serum cefazolin levels during elective valve replacement surgery on CPB at CMJAH. Method: A prospective, contextual, descriptive design was used in this study. Cefazolin plasma concentrations were analysed at specific pre-determined time intervals in adults patients scheduled for elective valve replacement surgery. Convenience sampling was used. Results: Sixteen patients were enrolled in the study with equal number of males and females, ranging from 18 years to 59 years of age and with a mean BMI of 28.2 kg/m² (range of 18.1 to 40.2 kg/m²). The mean trough for the unbound concentration of cefazolin was 5.02 μg/ml (range of 2.79 to 10.35 μg/ml). For 5 out of the 16 patients (31.25%) the targeted therapeutic goal of time above MIC (4 μg/ml) of 100% (T > MIC 100%) was not achieved. Seven corresponding pre and post CPB serum samples (A1-A7) were statistically analysed using the paired t-test. The results indicated no statistically significant differences between samples A1-A5 (p = 0.11, 0.34, 0.46, 0.32 and 0.98 respectively). There was a statistically significant difference between the samples A6 and A7 (p = 0.024 and 0.025), however, the clinical significance of these small differences is questionable. Conclusion: Surgical site infections not only result in significant morbidity and mortality but also lead to an increased financial burden to the country’s economy. This study has shown that potentially 31.25% of the patients undergoing cardiac surgery may have an increased risk of acquiring infections due to sub-optimal levels of prophylactic antibiotic during the surgery. In addition, the findings point towards no sequestration of cefazolin in the CPB circuits. / MT2017

Master of Science in Biomedical Sciences / Department of Clinical Sciences / Walter C. Renberg / OBJECTIVE: The purpose of the study reported here was to evaluate pharmacokinetics of cefazolin in dogs receiving a single IV injection of cefazolin (22 mg/kg) and dogs receiving simultaneous IV and IM injections of cefazolin (total dose, 44 mg/kg). METHODS: Twelve purpose-bred Beagles (6/group) were assigned to receive a single injection of cefazolin (22 mg/kg, IV) or simultaneous injections (22 mg/kg, IV, and 22 mg/kg, IM). Interstitial fluid was collected over a 5-hour period using ultrafiltration probes for pharmacokinetic analysis. RESULTS: Mean cefazolin concentration in the interstitial fluid at 1, 1.5, 2, 3, 4, and 5 hours after injection was 39.6, 29.1, 21.1, 10.3, 6.4, and 2.7 μg/mL, respectively, for the IV group and 38.3, 53.3, 46.4, 31.7, 19.1, and 8.9 μg/mL, respectively, for the IV + IM group. The mean area under the concentration-time curve extrapolated to infinity, maximum concentration, half life and time to the maximum concentration was 74.99 and 154.16 h•μg/mL, 37.3 and 51.5 μg/mL, 0.96 and 1.11 hours, 1.28 and 1.65 hours, respectively, for the IV and IV + IM groups. CONCLUSIONS AND CLINICAL RELEVANCE: Cefazolin concentrations in interstitial fluid of dogs were maintained at > 4 μg/mL for 4 hours after a single IV injection and for 5 hours after simultaneous IV and IM injections. Based on these results, simultaneous administration of cefazolin IV + IM 30 to 60 minutes before surgery should provide interstitial fluid concentrations effective against the most common commensal organisms (Staphylococcus spp and Streptococcus spp) on the skin of dogs for surgical procedures lasting ≤ 4 hours.

Made available in DSpace on 2015-07-22T20:50:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-11-25 / As BMPs, proteínas indutoras de crescimento ósseo, desde o início de sua utilização têm sido avaliadas em diferentes modelos experimentais objetivando determinar sua eficácia. Sabemos que algumas substâncias podem interferir positiva ou negativamente quando utilizadas de forma sistêmica ou local,associadas à BMP.Objetivo:Este estudo tempo objetivo avaliar as possíveis interferências da utilização de antibioticoterapia profilática pré e pós-operatória,utilizando-se como princípio ativo a cefazolina,aplicada a um modelo experimental em coelhos.Métodos:Foram utilizados dois grupos de coelhos fêmea, neozelandeses,submetidos à artrodese intertransversa da coluna lombar,segmento L5-L6,por via posterior.No primeiro grupo foi utilizado o enxerto autólogo associado ao biocomposto BMP bovino, 1,0mg e hidroxiapatita,9,0mg).No segundo grupo foi realizado o mesmo procedimento e utilizado o mesmo biocomposto porém os animais foram submetidos a antibioticoterapia profilática com cefazolina iniciada duas horas antes e mantida por 24 horas após o término do procedimento.Os animais foram acompanhados por 15 semanas,isolados em cativeiro e avaliados diariamente por veterinário sob o ponto de vista clínico e neurológico,sendo posteriormente sacrificados e retiradas as peças cirúrgicas para serem submetidas à análise radiográfica e histológica.Resultados:Para o grupo 1,a quantidade e localização do material implantado variaram entre os indivíduos, porém,na maioria dos casos(6 amostras),a quantidade de partículas de osso homólogo era insignificante e estava dispersa ao longo do tecido mole que recobre o dorso da vértebra,circundado por tecido reacional com área de necrose.Nos demais casos as partículas com reabsorção preenchiam o reduzido espaço entre os processos transversos.Para o grupo 2,a quantidade do material e sua localização também variaram entre os indivíduos.Na maioria dos casos inúmeras partículas de osso mole preenchiam o espaço entre os processos laterais cuja neoformação óssea levou ao aprisionamento de algumas dessas partículas.Todos os casos exibiram formação em maior ou menor intensidade de tecido cartilaginoso na superfície dos processos transversos.A análise radiográfica mostrou em sua frequência relativa maior frequência de fusão completa para o grupo 2 quando comparado ao grupo 1. Conclusão:Do ponto de vista histológico para o modelo e período experimental analisado,inferimos que,embora nenhum dos tratamentos propostos tenha promovido o completo fusionamento das vértebras por tecido ósseo,a utilização de osso homólogo + BMP bovina, associada à aplicação de cefazolina,promoveu maior formação cartilaginosa e óssea com menor índice de rejeição do material enxertado na área doadora, quando comparada ao grupo sem associação de cefazolina.Do ponto de vista radiográfico,a análise relativa também demonstrou-se superior para o grupo onde foi utilizado cefazolina... / TEDE / BV UNIFESP: Teses e dissertações

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Our objective was to compare cefazolin concentrations in biopsied tissue samples collected from surgically created wounds treated with negative pressure wound therapy to those collected from surgically created wounds treated with nonadherent dressings. The study design was a prospective, controlled, experimental study. The animal population included 12 female spayed beagles. We hypothesized there would be a difference between the cefazolin concentrations of wounds treated with negative pressure wound therapy when compared to the cefazolin concentrations of wounds treated with nonadherent dressings. Surgical methods were as follows: Full thickness cutaneous wounds were created on each antebrachium (n=24). Following surgery, cefazolin (22 mg/kg) was administered intravenously to each of the dogs and continued every 8 hours during the study. The right wound was randomly assigned to group I or group II while the wound on the contralateral antebrachium was assigned to the other group. Group I wounds were treated with negative pressure wound therapy (NPWT) and group II wounds were treated with nonadherent dressings for 3 days. Dressings were changed and tissue biopsies obtained from wound beds at 24-hour intervals for both groups. Cefazolin wound tissue and plasma concentrations were measured by liquid chromatography mass spectrometry (LC-MS/MS). Blood samples for measuring plasma cefazolin concentrations were collected prior to biopsy sampling. At the time of surgery and at each bandage change, wound beds were swabbed and submitted for aerobic and anaerobic culture. Our results revealed that after initiating cefazolin treatment, wound tissue antibiotic concentrations between treatment groups were not significantly different at any sampling time. Similarly, after initiating cefazolin treatment, plasma cefazolin concentrations were not significantly different at any sampling time for individual dogs. We concluded that using a canine experimental model, NPWT treatment of surgically created wounds does not statistically impact cefazolin tissue concentrations when compared to conventional nonadherent bandage therapy / Master of Science

京都大学 / 新制・課程博士 / 博士(医学) / 甲第25156号 / 医博第5042号 / 新制||医||1070(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川上 浩司, 教授 森田 智視, 教授 寺田 智祐 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM