Drug Monitoring von Ciprofloxacin bei Patienten mit allogener Stammzelltransplantation
by Helin Tas née Tas
Date of Examination:2024-10-22
Date of issue:2024-10-28
Advisor:Dr. Hani Kaba
Referee:Prof. Dr. Simone Scheithauer
Referee:Prof. Dr. Andreas Fischer
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Abstract
English
Patients undergoing allogeneic stem cell transplantation are highly immunosuppressed and have an increased likelihood of acquiring an infection. Especially nosocomial infections with Pseudomonas aeruginosa are a particular problem. Accordingly, this group of patients in Germany receives prophylactic antibiotic therapy consisting of ciprofloxacin 500 mg twice daily in accordance with guidelines. However, this recommendation is based on data from male and healthy volunteers. Various studies have already shown that there are altered pharmacokinetics and pharmacodynamics in critically ill patients in the intensive care unit. In our study, we investigate how high the drug level of ciprofloxacin, expressed as AUC/MIC, are in patients with allogeneic stem cell transplantation and whether the defined targets (125 mg*h/l and 72 mg*h/l) are achieved. The study was conducted over the period 2018-2019 at the Universitätsmedizin Göttingen, and data from a total of 63 patients undergoing an allogeneic stem cell transplantation was analyzed. The blood samples were measured using high-pressure/performance-liquid-chromatography. The defined target indices were not achieved by the majority of patients, particularly with a MIC of 0,5 for the pathogen Pseudomonas aeruginosa. The average AUC/MIC was 53,5 mg*h/l. The target index 125 mg*h/l was achieved in 3,16% of cases, the target index of 72mg*h/l in 22,5%. Furthermore, there was no significant correlation between the AUC and failure of antibiotic, which was defined as a change in antibiotics in this study. Patients with a change in antibiotics had a median AUC value of 25,18 mg*h/l and patients without a change in antibiotics of 22,09 mg*h/l (p = 0,71). Patients with series of measurements that reached the target level of 72mg*h/l had a 54% lower risk of change in antibiotics immediately afterwards compared to patients with series of measurements that did not reach the target level (p = 0,03, [0,23;0,94]). It was also noticeable that both, intraindividual and interindividual variance (178 mg*h/l) were strikingly high. The highest variance was 2376,74 mg*h/l while the lowest was 5,07 mg*h/l. A total of nine patients (14,3%) were transferred to the intensive care unit (ICU). All of these patients had a change in antibiotics. Patients who had a change in antibiotics had a 1,2-fold increased risk of ICU admission compared to patients who did not have a change in antibiotics (p = 0,003, [1,07;1,35]). There was also a significant difference in survival time (p = 0,006) between patients with and without a stay in the intensive care unit. Patients in the intensive care unit had an average survival time of 46 days, while patients without ICU admission had an average survival time of 57 days. In this study a significant difference in AUC and gender was shown. Men (with bloodstream infection) are 0,23 times more likely to haven an AUC below the median value (24,04 mg*h/l) compared to women (with bloodstream infection). It was shown that AUC has a negative correlation with alkaline phosphatase, bilirubin, γ-GT, GFR and dosing of tacrolimus.
Keywords: Drug monitoring; ciprofloxacin; antibiotic prophylaxis; allogeneic stem cell transplantation