Abstract
Background
In patients with haematological or oncological malignancies, we aimed to assess the rate of intestinal colonisation and blood stream infections (BSI) with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) and vancomycin-resistant enterococci (VRE), mortality and risk factors associated with ESBLE/VRE BSI, as well as the impact of faecal screening for ESBLE and VRE in combination with adapted empiric treatment of febrile neutropenia.
Methods
Within 72 h of admission to our department, an ESBLE and VRE screening stool sample was collected. In the case of neutropenic fever, blood cultures were drawn. Data of all admitted patients were prospectively documented. Explorative forward-stepwise logistic regression analyses were used to identify risk factors for progression from intestinal colonisation to BSI.
Results
During the study period, 1,805 stool samples were obtained from 513 patients during 1,012 inpatient stays, and 2,766 blood cultures were obtained from 578 patients during 1,091 inpatient stays. Ninety (17.5 %) of these patients were colonised with ESBLE and 51 (9.9 %) with VRE. Proportions of 40 % (36/90) of ESBLE and 61 % (31/51) of VRE colonisations were healthcare-associated. Six of 90 (6.6 %) ESBLE-colonised patients and 1/51 (2 %) VRE-colonised patients developed BSI with the respective organism. None of these patients died after receiving early appropriate empiric antibiotics based on colonisation status. Colonisation with ESBLE or VRE was associated with increased risk ratios (RR) towards developing ESBLE BSI [RR 4.5, 95 % confidence interval (CI): 2.89–7.04] and VRE BSI (RR 10.2, 95 % CI: 7.87–13.32), respectively. Acute myelogenous leukaemia and prior treatment with platinum analogues or quinolones were identified as independent risk factors for ESBLE BSI in colonised patients.
Conclusions
Intestinal ESBLE/VRE colonisation predicts BSI. Faecal screening in haematology/oncology patients in combination with directed empiric treatment may reduce ESBLE BSI-related mortality.
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References
Bodey GP, Buckley M, Sathe YS, Freireich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966;64:328–40.
Wisplinghoff H, Cornely OA, Moser S, et al. Outcomes of nosocomial bloodstream infections in adult neutropenic patients: a prospective cohort and matched case–control study. Infect Control Hosp Epidemiol. 2003;24:905–11.
Coque TM, Baquero F, Canton R. Increasing prevalence of ESBL-producing Enterobacteriaceae in Europe. Euro Surveill. 2008;13.pii:19044.
Soderblom T, Aspevall O, Erntell M, et al. Alarming spread of vancomycin resistant enterococci in Sweden since 2007. Euro Surveill. 2010;15.pii:19620.
Blijlevens NM, Donnelly JP, De Pauw BE. Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview. Bone Marrow Transpl. 2000;25:1269–78.
Ubeda C, Taur Y, Jenq RR, et al. Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J Clin Invest. 2010;120:4332–41.
Cornely OA, Schirmacher P. Clinical picture: bacterial translocation in neutropenic sepsis. Lancet. 2001;358:1842.
Mauch H. MiQ: mikrobiologisch-infektiologische Qualitätsstandards in der mikrobiologischen-infektiologischen Diagnostik. Stuttgart: G Fischer; 2007.
Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing. Twenty-first informational supplement, M100-S21. Wayne, PA; 2011.
Vehreschild JJ, Rüping MJ, Wisplinghoff H, et al. Clinical effectiveness of posaconazole prophylaxis in patients with acute myelogenous leukaemia (AML): a 6 year experience of the Cologne AML cohort. J Antimicrob Chemother. 2010;65:1466–71.
Reddy P, Malczynski M, Obias A, et al. Screening for extended-spectrum beta-lactamase-producing Enterobacteriaceae among high-risk patients and rates of subsequent bacteremia. Clin Infect Dis. 2007;45:846–52.
Friedmann R, Raveh D, Zartzer E, et al. Prospective evaluation of colonization with extended-spectrum beta-lactamase (ESBL)-producing enterobacteriaceae among patients at hospital admission and of subsequent colonization with ESBL-producing enterobacteriaceae among patients during hospitalization. Infect Control Hosp Epidemiol. 2009;30:534–42.
Arnan M, Gudiol C, Calatayud L, et al. Risk factors for, and clinical relevance of, faecal extended-spectrum beta-lactamase producing Escherichia coli (ESBL-EC) carriage in neutropenic patients with haematological malignancies. Eur J Clin Microbiol Infect Dis. 2011;30:355–60.
Geser N, Stephan R, Hächler H. Occurrence and characteristics of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae in food producing animals, minced meat and raw milk. BMC Vet Res. 2012;8:21.
Rhee MS, Lee SY, Hillers VN, McCurdy SM, Kang DH. Evaluation of consumer-style cooking methods for reduction of Escherichia coli O157:H7 in ground beef. J Food Prot. 2003;66:1030–4.
Stringer SC, George SM, Peck MW. Thermal inactivation of Escherichia coli O157:H7. Symp Ser Soc Appl Microbiol. 2000;29:79S–89S.
Melzer M, Petersen I. Mortality following bacteraemic infection caused by extended spectrum beta-lactamase (ESBL) producing E. coli compared to non-ESBL producing E. coli. J Infect. 2007;55:254–9.
Auerbach U. Epidemiologische Untersuchung zum Auftreten Glykopeptid-resistenter Enterokokken in einer Normalpopulation und bei definierten Patientengruppen. Inaugural-Dissertation zur Erlangung der Doktorwürde der Hohen Medizinischen Fakultät zu Köln. Köln: Universität zu Köln, 2002;118.
Matar MJ, Tarrand J, Raad I, Rolston KV. Colonization and infection with vancomycin-resistant Enterococcus among patients with cancer. Am J Infect Control. 2006;34:534–6.
Weinstock DM, Conlon M, Iovino C, et al. Colonization, bloodstream infection, and mortality caused by vancomycin-resistant enterococcus early after allogeneic hematopoietic stem cell transplant. Biol Blood Marrow Transpl. 2007;13:615–21.
Kamboj M, Chung D, Seo SK, et al. The changing epidemiology of vancomycin-resistant Enterococcus (VRE) bacteremia in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Biol Blood Marrow Transpl. 2010;16:1576–81.
Schuster F, Graubner UB, Schmid I, Weiss M, Belohradsky BH. Vancomycin-resistant-enterococci—colonization of 24 patients on a pediatric oncology unit. Klin Padiatr. 1998;210:261–3.
Moulin F, Dumontier S, Saulnier P, et al. Surveillance of intestinal colonization and of infection by vancomycin-resistant enterococci in hospitalized cancer patients. Clin Microbiol Infect. 1996;2:192–201.
Bossaer JB, Hall PD, Garrett-Mayer E. Incidence of vancomycin-resistant enterococci (VRE) infection in high-risk febrile neutropenic patients colonized with VRE. Support Care Cancer. 2010;19:231–7.
Zaas AK, Song X, Tucker P, Perl TM. Risk factors for development of vancomycin-resistant enterococcal bloodstream infection in patients with cancer who are colonized with vancomycin-resistant enterococci. Clin Infect Dis. 2002;35:1139–46.
Padiglione AA, Wolfe R, Grabsch EA, et al. Risk factors for new detection of vancomycin-resistant enterococci in acute-care hospitals that employ strict infection control procedures. Antimicrob Agents Chemother. 2003;47:2492–8.
Kosack A, Riedel E, Kiehn TE, Small TN, Wexler LH, Dunkel IJ. Vancomycin-resistant enterococcus in pediatric oncology patients: an analysis of potential consequences of colonization and infection. Pediatr Blood Cancer. 2009;52:300–2.
Avery R, Kalaycio M, Pohlman B, et al. Early vancomycin-resistant enterococcus (VRE) bacteremia after allogeneic bone marrow transplantation is associated with a rapidly deteriorating clinical course. Bone Marrow Transpl. 2005;35:497–9.
Acknowledgements
We would like to thank the entire staff of the Institute for Medical Microbiology, Immunology and Hygiene (IMMIH), as well as our documentation assistants Bibi Bos, Daniela Ziegler, Juliane Pickenhain, Luisa Weise, Marie Baltes and Meike Freund for their support. We would like to extend a special thanks to Susanna Proske for her extensive support during the file search.
Funding
The study was funded by the University Hospital Cologne.
Conflict of interest
O.A.C is supported by the German Federal Ministry of Research and Education (BMBF grant 01KN1106), has received research grants from Actelion, Astellas, Basilea, Bayer, Biocryst, Celgene, F2G, Genzyme, Gilead, Merck/Schering, Miltenyi, Optimer, Pfizer, Quintiles and Viropharma, is a consultant to Astellas, Basilea, F2G, Gilead, Merck/Schering, Optimer and Pfizer, and received lecture honoraria from Astellas, Gilead, Merck/Schering and Pfizer.
M.J.G.T.V. has been a speaker for Astellas Pharma, Gilead Sciences, Merck/MSD and Pfizer.
J.J.V. has received research grants from or has been a speaker for Astellas, Merck, Pfizer and Schering-Plough.
G.F. is supported by the German Federal Ministry of Research and Education (BMBF grant 01KI0771) and has received lecture fees from Gilead, Glaxo Smith Kline, Janssen, Merck Sharp & Dohme, Novartis and Pfizer.
H.S. is supported by research grants from Basilea, Novartis and Pfizer, has received speaking fees from Bayer, Gilead, Novartis, Oxoid and Pfizer, and is a consultant to Astellas, Astra-Zeneca and Novartis.
H.W. has been a speaker for bioMérieux, Siemens, Bruker and GenProbe.
M.H. and B.J.L. have no conflicts of interest.
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Liss, B.J., Vehreschild, J.J., Cornely, O.A. et al. Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies. Infection 40, 613–619 (2012). https://doi.org/10.1007/s15010-012-0269-y
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DOI: https://doi.org/10.1007/s15010-012-0269-y