Gewählte Publikation:
Wunsch, S.
Linezolid-Resistant Enterococci: Risk Factors and Clinical Impact
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2015. pp.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
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Krause Robert
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Valentin Thomas
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- Abstract:
- Objectives:
Linezolid is standardly used as part of a second-line treatment for patients with febrile neutropenia at our hospital. Despite the low prevalence of linezolid resistance in enterococci monitored by international surveillance programs, we registered an increase in linezolid resistance at our hospital. The aim of the present study was to identify the mechanism of resistance and risk factors for the acquisition of linezolid-resistant E. faecium as well as to evaluate the clinical impact of colonisation or infection.
Methods:
The study was conducted at the Department of Internal Medicine, Division of Hematology, and Section of Infectious Diseases and Tropical Medicine, Medical University of Graz. All patients colonised or infected with E. faecium at the hematology ward between January 1st, 2008 and March 31st, 2014 were included.
We compared patients with linezolid-resistant E. faecium (LRE; N=57) to patients with linezolid-susceptible E. faecium (LSE; N=80) from the same ward during the same period by retrospectively reviewing charts and electronic medical records. The identification of resistance mechanisms was performed at the Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England using PCR methods. To determine the institutional linezolid, vancomycin and daptomycin consumption we reviewed our hospital pharmacy data.
Results:
All tested LRE isolates were positive for heterozygous G2576T mutations in the 23S rRNA; testing for plasmid-mediated resistance via the cfr-gene was negative. No statistically relevant differences between LSE and LRE patients concerning age, underlying diseases, receipt of hematopoietic stem cell transplantation, comorbidities, duration of neutropenia, previous hospitalisations, length of stay, in-hospital mortality and one-year mortality could be found.
Statistically significant variables for the acquisition of LRE infections comprise previous linezolid exposure (Chi square p<0,0001) and previous treatment with cefepime (p=0,031) and piperacillin/tazobactam (p=0,031). The administration of trimethoprim/sulfamethoxazole was associated with significantly lower LRE rates (p=0,001).
Risk factors for the acquisition of invasive LRE infections include age (T-test p=0,018), duration of neutropenia (T-test p=0,001), duration of linezolid therapy (T-test p=0,016) and the number of LRE isolations (Mann-Whitney U-test p=0,007).
Conclusion:
We confirmed previous linezolid exposure as significant risk factor for the acquisition of LRE, irrespective of the duration of treatment and the number of linezolid exposures. Additional risk factors include previous treatment with cefepime and piperacillin/tazobactam. In terms of LOS and cumulative survival, no significant difference between LSE and LRE patients could be found.