Challenges in management of infections on a burn injury unit.

Bhavik Patel (2011). Challenges in management of infections on a burn injury unit. MPhil Thesis, School of Medicine, The University of Queensland.

       
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Author Bhavik Patel
Thesis Title Challenges in management of infections on a burn injury unit.
School, Centre or Institute School of Medicine
Institution The University of Queensland
Publication date 2011-12
Thesis type MPhil Thesis
Supervisor Prof. David Paterson
Prof.Jeffrey Lipman
Dr Jenny Paratz
Dr Jason Roberts
Total pages 97
Total black and white pages 97
Language eng
Subjects 110309 Infectious Diseases
110310 Intensive Care
111502 Clinical Pharmacology and Therapeutics
Abstract/Summary Burn injury patients are a special subset of patients with an increased likelihood of developing infections as well as reduced capacity to fight them. This Thesis focuses on two aspects of infections in burn injury patients, the issues surrounding blood stream infections (BSI) which were defined according to The American Burn Association Consensus Conference on sepsis and infections in this subset of patients and a possible method to optimise drug dosing in burns patients using therapeutic drug monitoring (TDM). BSI is a known negative predictor in the outcome of burn injury patients. This is the first description from a tertiary referral burn centre in Australia of the organisms responsible, the antibiotics prescribed and the various other factors that are associated with clinical outcome in burn injury patients that develop BSI. Data were collected from various databases on admitted patients with burn injuries from January 1998 to December 2008. Selected information from databases was analysed using SPSS version 17 (SPSS Inc. Chicago). Descriptive, univariate and multivariate analysis was undertaken to determine factors predictive of clinical outcome. The factors analysed by univariate analysis were selected on clinical plausibility. Univariate analysis used a crosstabs procedure initially to estimate maximum likelihood. Factors that were associated with a P value <0.15 were entered into a binary logistic regression to detect which covariates were independent predictors of mortality in BSI and outcome according to specific organisms. Ninety-nine out of 2364 (4%) patients developed 240 documented BSI. The median time from burn injury to BSI was 7 (interquartile range 3-16) days. There were 13 deaths during the hospital stay for this cohort; Pseudomonas aeruginosa BSI was associated with six deaths. Factors associated with P.aeruginosa mortality by univariate analysis included inhalational injury, percentage total body surface area burn (%TBSA), days of antibiotic prescribed and Acute Physiological and Chronic Health Evaluation (APACHE) II scores. Univariate analysis of the 2364 patients admitted to our center over the 11-year period found BSI to be predictive of mortality (p < 0.001). Multivariate analysis identified inhalational injury to be the only factor associated with BSI-related mortality. The second part of this Thesis was a prospective study where TDM was performed on all patients admitted to a tertiary referral burns unit that were prescribed a beta−lactam antibiotic. Steady state blood samples and Creatinine levels were collected immediately prior to a scheduled dose. Therapeutic concentrations were based on pharmacokinetic (PK) / pharmacodynamic (PD) data from previous studies. For the purpose of this study, treatment outcome was considered positive if there was completion of treatment course without change or addition of antibiotic therapy or commencement of additional antibiotics within 48 hours of discontinuation of antibiotic therapy. The PK/PD targets assessed were: (a) unbound trough antibiotic concentrations exceeding the minimum inhibitory concentration (MIC; f T >MIC) and (b) unbound concentrations greater than or equal to 4 x MIC of the known or suspected pathogen (f T>4xMIC). Duration of therapy was independently determined by the treating clinician independent of dose adjustment. A total of 50 patients were included for TDM over a 12 month period. The mean (+ standard deviation) age was 49 + 16 years. The mean % TBSA burn was 17+13%. The mean serum creatinine concentration was 86 + 20 umol/L. Sixty percent of patients did not achieve f T >MIC and only 18% achieved the higher target of f T>4xMIC. Although all patients achieved a positive clinical outcome, the duration of antibiotic treatment was shorter in patients that achieved f T >MIC compared with those that did not (4.2 + 1.1 v/s 5.3 + 2.3 days; P= 0.03). This study demonstrates that empiric beta-lactam dosing does not consistently achieve therapeutic targets and there is significant antibiotic trough concentration variability in burn injury patients. The clinical ramifications of this clinically remain unclear, although patients with therapeutic beta-lactam concentrations did have a shorter duration of antibiotic therapy. This data does suggest that a TDM programme is a useful intervention to optimise beta-lactam dosing in stable ward based burn injury patients.
Keyword Burns
Bloodstream infections
Mortality
Beta-lactam antibiotics
Therapeutic drug monitoring

 
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