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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Regional Variations in the Further Management of Neutropenic Patients already Receiving Empirical Antimicrobial
J P Donnelly1, B E De Pauw1, E E Lane-Allman2
1a Department of Hematology, University Medical Center St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Abstract:
To investigate whether or not the considerable regional differences in prescribing further modifications to initial empirical regimen were due to differences in the patient populations or were the result of other factors we re-analysed the data from a large multicentre study of monotherapy for the empirical treatment of febrile, neutropenic patients. We matched 151 episodes treated in 14 centres in Europe with the same number treated in 17 centres in North America for age > 46 years, gender, acute leukaemia, antibacterial prophylaxis, intravascular catheter use, receipt of ceftazidime or piperacillin plus tobramycin which were the regimens in the original study, the presence of bacteraemia at the onset of fever and the occurrence of a focus of infection within the first 3 days of empirical therapy. The initial regimen was in fact unchanged and successful after 72h for 74% of episodes treated in European centres and 45% of those treated in North American centres (p <.0001) and 38% and 21% of episodes respectively were managed successfully without any modification of therapy (p =.0044). Amphotericin and acyclovir were given in 35% and 11% of episodes treated in European centres compared with 53% and 25% of episodes treated in North American centres (p =.0053 and.0029). Moreover, empirical therapy was changed after a mean 4.8 days (95% Cl± 0.8) in North American centres but after 7.1 days (95%CI±1.0) in European centres (p =.0004) and there were 2.3±0.3 changes to therapy compared with 1.5±0.3 changes respectively (p =.0002). However there was no significant difference in survival (97% in and 96%), in the number of episodes complicated by a subsequent infection (10% and 11%), in the incidence of other adverse event (11% and 10%) nor in the proportion of episodes in which fever persisted longer than 5 days (53% and 48%) in North American centres and European centres respectively. The duration of fever (8.4±1.4 days and 7.1 ±1.2 days), antimicrobial therapy (19.8±1.9 days and 16.3±1.5 days) and neutropenia <0.5×10(9)/L (19.9±2.9 days and 16.8±2.1 days) were also similar for North American centres and European centres respectively. These results suggest a genuine regional difference in medical practice does, in fact, exist.
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