9 The flood of study feasibilities and the value of a centralised approach (original) (raw)
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The Indian Journal of Pediatrics, 2020
Though a decline has been seen in child mortality and morbidity over the last decades, sepsis in neonates and infants remains a major cause of death. Optimal use of antibiotics in sepsis management is a key factor which can further reduce the number of poor clinical outcomes. Selecting the right antibiotic to which the offending bacteria is susceptible and administrating the antibiotic within the first hour can save many lives. However, the pharmacokinetic profile of an antibiotic is affected by developmental changes such as capacity of drug metabolizing enzymes and maturation of organ function. This can affect antibiotic exposure and response in neonates and infants. While suspecting sepsis, the primary focus of empiric treatment during the initial phase is to assure efficacy and it must be broad based to cover all suspected pathogens. Once the bacterial etiology is confirmed as a cause of sepsis and the in vitro antibiotic susceptibility is established, targeted treatment can be started which ensures optimal balance between efficacy and safety.
BMC Anesthesiology, 2011
Background: Critical illness, mediated by trauma or sepsis, can lead to physiological changes that alter the pharmacokinetics of antibiotics and may result in sub-therapeutic concentrations at the sites of infection. The first aim of this project is to identify the clinical characteristics of critically ill patients with significant trauma that have been recently admitted to ICU that may predict the dosing requirements for the antibiotic, cefazolin. The second aim of this is to identify the clinical characteristics of critically ill patients with sepsis that may predict the dosing requirements for the combination antibiotic, piperacillin-tazobactam. Methods/Design: This is an observational pharmacokinetic study of patients with trauma (cefazolin) or with sepsis (piperacillin-tazobactam). Participants will have samples from blood and urine, collected at different intervals. Patients will also have a microdialysis catheter inserted into subcutaneous tissue to measure interstitial fluid penetration of the antibiotic. Participants will be administered sinistrin, indocyanine green and sodium bromide as well as have cardiac output monitoring performed and tetrapolar bioimpedance to determine physiological changes resulting from pathology. Analysis of samples will be performed using validated liquid chromatography tandem mass-spectrometry. Pharmacokinetic analysis will be performed using non-linear mixed effects modeling to determine individual and population pharmacokinetic parameters of antibiotics. Discussion: The study will describe cefazolin and piperacillin-tazobactam concentrations in plasma and the interstitial fluid of tissues in trauma and sepsis patients respectively. The results of this study will guide clinicians to effectively dose these antibiotics in order to maximize the concentration of antibiotics in the interstitial fluid of tissues.
The International Arabic Journal of Antimicrobial Agents
Critically septic patients carry high mortality; however, it may be ameliorated to some extent by the appropriate prescription of antimicrobials and appropriate dosing strategy. Drug metabolism in critically septic patients differ from other less critical patients, and antimicrobial treatment need to be adjusted to prevent under dosing. The augmented clearance, acute kidney injury, microvascular ischemia, all affect antimicrobials' levels. Methods of antimicrobial administration were explored, continuous infusion versus intermittent bolus, with the aim of maximizing drug exposure, hitherto, apart from PK/PD advantage, it was not translated clearly into patients' clinical outcome. Biofilms have a unique management as they need elevated antimicrobial dosages to assure adequate drug exposure, and agents that work directly on biofilms to assure its disruption. Application of PK/PD knowledge in the management of critically septic patients maximize the clinical outcome and assures proper drug exposure, avoiding under dosing and drug toxicity, and decreasing the chance of antimicrobials mutant's selection, and therapy failures.
International Journal of Basic & Clinical Pharmacology, 2018
Background: Sepsis with septic shock has remained a dreadful disease inspite of early intervention mostly due to lack of sensitivity to first line antibiotics. This observational study was conducted to evaluate the utilization of antimicrobials and sensitivity-resistance pattern in paediatric patients suffering from sepsis due to various causes.Methods: A prospective, non-interventional, pharmaco-vigilant study. 38 patients suffering from sepsis admitted in paediatric ward and PICU from September 2012 to February 2014 were evaluated. The research protocol was approved by Institutional Ethical Committee, KIMS. Data were collected from case sheets of patients from the ward as well as Medical Record and Data section. Average of Data on a continuous scale was expressed as a mean along with standard deviation, Categorical data was expressed as percentage. Comparative statistical analysis was done by using student's t-test in respect of data measured on a continuous scale. All differe...
Critical Care, 2015
Introduction Early administration of antibiotics for sepsis, and of fluid boluses and vasoactive agents for septic shock, is recommended. Evidence for this in children is limited. Methods The Alberta Sepsis Network prospectively enrolled eligible children admitted to the Pediatric Intensive Care Unit (PICU) with sepsis from 04/2012-10/2014. Demographics, severity of illness, and outcomes variables were prospectively entered into the ASN database after deferred consent. Timing of interventions were determined by retrospective chart review using a study manual and case-report-form. We aimed to determine the association of intervention timing and outcome in children with sepsis. Univariate (t-test and Fisher’s Exact) and multiple linear regression statistics evaluated predictors of outcomes of PICU length of stay (LOS) and ventilation days. Results Seventy-nine children, age median 60 (IQR 22–133) months, 40 (51 %) female, 39 (49 %) with severe underlying co-morbidity, 44 (56 %) with s...
Antibiotic-related acute effects within the intestinal microcirculation in experimental sepsis
Critical Care, 2008
all 10 cities including the rural areas of the province of Kerman. All data were finally analyzed by SPSS software (version 11.5). Results On the basis of recorded statistical analysis, the mortality cases of human rabies in the province of Kerman during one decade was 10 persons (eight males and two females). One-half of them (50%) were bitten by dogs and the others (50%) by foxes. Among the reported deaths, 40% were from Kahnooj county (Jiroft region). The reported data indicated that 21,546 persons were bitten by animals during 10 years in the province of Kerman. The mean of age of the people who were bitten by dogs was 24.80 years (SD = ±14.6), while the mean age of the people who were bitten by foxes was 57.25 years (SD = ±1.50). There was a significant difference between the mean age of these two groups of the people (P < 0.05). The most frequent rate of injured people was reported in the age group 10-19 years old and the frequency rate of males (76.00%) was more than females (24.00%). Therefore, there was a statistically significant difference between males and females in this study (P < 0.01). About 60% of all persons that were bitten by animals were from rural areas and 40% of them were from urban areas (P < 0.05). Among the people who were bitten and injured by animals during one decade in the province of Kerman, 85.70% of them were not treated by the rabies prophylaxis treatment regimen. Among all of them who were bitten by animals, 50% were injured through hands and feet, 40%
Critically septic patients carry high mortality; however, it may be ameliorated to some extent by the appropriate prescription of antimicro-bials and appropriate dosing strategy. Drug metabolism in critically septic patients differ from other less critical patients, and antimicrobial treatment need to be adjusted to prevent under dosing. The augmented clearance, acute kidney injury, microvascular ischemia, all affect antimicrobials' levels. Methods of antimicrobial administration were explored, continuous infusion versus intermittent bolus, with the aim of maximizing drug exposure, hitherto, apart from PK/PD advantage, it was not translated clearly into patients' clinical outcome. Biofilms have a unique management as they need elevated antimicrobial dosages to assure adequate drug exposure, and agents that work directly on bio-films to assure its disruption. Application of PK/PD knowledge in the management of critically septic patients maximize the clinical outcome and assures proper drug exposure, avoiding under dosing and drug toxicity, and decreasing the chance of antimicrobials mutant's selection , and therapy failures.