Impact of vancomycin resistance on mortality in neutropenic patients with enterococcal bloodstream infection: a retrospective study

BMC Infectious Diseases

Jin-Hong Yoo²  Jung-Hyun Choi²  Yeon-Joon Park⁵  Sun Hee Park²  Jae-Ki Choi²  Si-Hyun Kim¹  Jae-Cheol Kwon⁴  Su-Mi Choi²  Dong-Gun Lee³  Sung-Yeon Cho² 

[1] Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea;Division of Infectious Diseases, Department of Internal Medicine, Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;The Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;Department of Internal Medicine, Daniel Hospital, GyeongGi-Do, Republic of Korea;Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

关键词: Vancomycin resistance;    Risk factors;    Neutropenia;    Mortality;    Enterococcus;    Bacteremia;   

Others  :  1145669
DOI  :  10.1186/1471-2334-13-504

 received in 2013-03-31, accepted in 2013-10-22,  发布年份 2013

【 摘 要 】

Background

Vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) is generally associated with the delayed administration of adequate antibiotics. The identification of risk factors and outcomes of VRE BSI is necessary for establishing strategies for managing neutropenic fever in patients with hematological malignancies.

Methods

We retrospectively analysed consecutive cases of enterococcal BSI in patients with neutropenia after chemotherapy or stem cell transplantation between July 2009 and December 2011 at a single center.

Results

During the 30-month period, among 1,587 neutropenic patients, the incidence rate of enterococcal BSI was 1.76 cases per 1,000 person-days. Of the 91 enterococcal BSIs, there were 24 cases of VRE. VRE BSI was associated with E. faecium infection (P < .001), prolonged hospitalization (P = .025) and delayed administration (≥48 hours after the febrile episode) of adequate antibiotics (P = .002). The attributable mortality was 17% and 9% for VRE and vancomycin-susceptible Enterococcus (VSE), respectively (P = .447). The 30-day crude mortality was 27% and 23% for VRE and VSE, respectively (OR 1.38, 95% CI 0.53–3.59; P = .059). Only SAPS-II was an independent predictive factor for death (adjusted OR 1.12, 95% CI 1.08–1.17; P < .001).

Conclusions

In conclusion, vancomycin resistance showed some trend towards increasing 30-day mortality, but is not statistically significant despite the delayed use of adequate antibiotics (≥48 hours). Only underlying severity of medical condition predicts poor outcome in a relatively homogeneous group of neutropenic patients.

【 授权许可】

   
2013 Cho et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]DiazGranados CA, Zimmer SM, Klein M, Jernigan JA: Comparison of mortality associated with vancomycin-resistant and vancomycin-susceptible enterococcal bloodstream infections: a meta-analysis. Clin Infect Dis 2005, 41:327-333.
• [2]Bonten MJ, Willems R, Weinstein RA: Vancomycin-resistant enterococci: Why are they here, and where do they come from? Lancet Infect Dis 2001, 1:314-325.
• [3]Moellering RC Jr: Emergence of Enterococcus as a significant pathogen. Clin Infect Dis 1992, 14:1173-1176.
• [4]Kwon JC, Kim SH, Choi JK, Cho SY, Park YJ, Park SH, Choi SM, Lee DG, Choi JH, Yoo JH: Epidemiology and clinical features of bloodstream infections in hematological wards: one year experience at the catholic blood and marrow transplantation center. Infect Chemother 2013, 45:51-61.
• [5]McKinnell JA, Patel M, Shirley RM, Kunz DF, Moser SA, Baddley JW: Observational study of the epidemiology and outcomes of vancomycin-resistant Enterococcus bacteraemia treated with newer antimicrobial agents. Epidemiol Infect 2011, 139:1342-1350.
• [6]Han SH, Chin BS, Lee HS, Jeong SJ, Choi HK, Kim CO, Yong D, Choi JY, Song YG, Lee K, Kim JM: Vancomycin-resistant enterococci bacteremia: risk factors for mortality and influence of antimicrobial therapy on clinical outcome. J Infect 2009, 58:182-190.
• [7]Shay DK, Maloney SA, Montecalvo M, Banerjee S, Wormser GP, Arduino MJ, Bland LA, Jarvis WR: Epidemiology and mortality risk of vancomycin-resistant enterococcal bloodstream infections. J Infect Dis 1995, 172:993-1000.
• [8]Vergis EN, Hayden MK, Chow JW, Snydman DR, Zervos MJ, Linden PK, Wagener MM, Schmitt B, Muder RR: Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia. A prospective multicenter study. Ann Intern Med 2001, 135:484-492.
• [9]Edmond MB, Ober JF, Dawson JD, Weinbaum DL, Wenzel RP: Vancomycin-resistant enterococcal bacteremia: natural history and attributable mortality. Clin Infect Dis 1996, 23:1234-1239.
• [10]Bhavnani SM, Drake JA, Forrest A, Deinhart JA, Jones RN, Biedenbach DJ, Ballow CH: A nationwide, multicenter, case–control study comparing risk factors, treatment, and outcome for vancomycin-resistant and -susceptible enterococcal bacteremia. Diagn Microbiol Infect Dis 2000, 36:145-158.
• [11]Lodise TP, McKinnon PS, Tam VH, Rybak MJ: Clinical outcomes for patients with bacteremia caused by vancomycin-resistant enterococcus in a level 1 trauma center. Clin Infect Dis 2002, 34:922-929.
• [12]DiazGranados CA, Jernigan JA: Impact of vancomycin resistance on mortality among patients with neutropenia and enterococcal bloodstream infection. J Infect Dis 2005, 191:588-595.
• [13]Linden PK, Pasculle AW, Manez R, Kramer DJ, Fung JJ, Pinna AD, Kusne S: Differences in outcomes for patients with bacteremia due to vancomycin-resistant Enterococcus faecium or vancomycin-susceptible E. faecium. Clin Infect Dis 1996, 22:663-670.
• [14]Kamboj M, Chung D, Seo SK, Pamer EG, Sepkowitz KA, Jakubowski AA, Papanicolaou G: The changing epidemiology of vancomycin-resistant Enterococcus (VRE) bacteremia in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Biol Blood Marrow Transplant 2010, 16:1576-1581.
• [15]Lautenbach E, Bilker WB, Brennan PJ: Enterococcal bacteremia: risk factors for vancomycin resistance and predictors of mortality. Infect Control Hosp Epidemiol 1999, 20:318-323.
• [16]Lucas GM, Lechtzin N, Puryear DW, Yau LL, Flexner CW, Moore RD: Vancomycin-resistant and vancomycin-susceptible enterococcal bacteremia: comparison of clinical features and outcomes. Clin Infect Dis 1998, 26:1127-1133.
• [17]Garbutt JM, Ventrapragada M, Littenberg B, Mundy LM: Association between resistance to vancomycin and death in cases of Enterococcus faecium bacteremia. Clin Infect Dis 2000, 30:466-472.
• [18]Yoo JH, Lee DG, Choi SM, Choi JH, Shin WS, Kim M, Yong D, Lee K, Min WS, Kim CC: Vancomycin-resistant enterococcal bacteremia in a hematology unit: molecular epidemiology and analysis of clinical course. J Korean Med Sci 2005, 20:169-176.
• [19]Todeschini G, Tecchio C, Borghero C, D’Emilio A, Pegoraro E, de Lalla F, Benedetti P, Spolaore P, Pellizzer G: Association between Enterococcus bacteraemia and death in neutropenic patients with haematological malignancies. J Infect 2006, 53:266-273.
• [20]Lee DG, Kim SH, Kim SY, Kim C, Park WB, Song YG, Choi JH: Evidence-based guidelines for empirical therapy of neutropenic fever in Korea. Korean J Intern Med 2011, 26:220-252.
• [21]Weissinger F, Auner HW, Bertz H, Buchheidt D, Cornely OA, Egerer G, Heinz W, Karthaus M, Kiehl M, Krüger W, Penack O, Reuter S, Ruhnke M, Sandherr M, Salwender HJ, Ullmann AJ, Waldschmidt DT, Wolf HH: Antimicrobial therapy of febrile complications after high-dose chemotherapy and autologous hematopoietic stem cell transplantation—guidelines of the infectious diseases working party (AGIHO) of the German society of hematology and oncology (DGHO). Ann Hematol 2012, 91:1161-1174.
• [22]Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JA, Boeckh MJ: Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Biol Blood Marrow Transplant 2009, 15:1143-1238.
• [23]Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR, Infectious Diseases Society of America: Clinical practice guidelines for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of America. Clin Infect Dis 2011, 52:e56-e93.
• [24]Lee DG, Yim DS, Choi SM, Park SH, Yoo JH, Choi JH, Min WS, Shin WS, Kim CC: Efficacies of teicoplanin in patients with febrile neutropenia. Infect Chemother 2004, 36:83-91.
• [25]Ortega M, Rovira M, Almela M, Marco F, de la Bellacasa JP, Martínez JA, Carreras E, Mensa J: Bacterial and fungal bloodstream isolates from 796 hematopoietic stem cell transplant recipients between 1991 and 2000. Ann Hematol 2005, 84:40-46.
• [26]Kim SH, Kwon JC, Choi SM, Lee DG, Park SH, Choi JH, Yoo JH, Cho BS, Eom KS, Kim YJ, Kim HJ, Lee S, Min CK, Cho SG, Kim DW, Lee JW, Min WS: Escherichia coli and Klebsiella pneumoniae bacteremia in patients with neutropenic fever: factors associated with extended-spectrum β-lactamase production and its impact on outcome. Ann Hematol 2013, 92:533-541.
• [27]Vydra J, Shanley RM, George I, Ustun C, Smith AR, Weisdorf DJ, Young JH: Enterococcal bacteremia is associated with increased risk of mortality in recipients of allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2012, 55:764-770.
• [28]Peel T, Cheng AC, Spelman T, Huysmans M, Spelman D: Differing risk factors for vancomycin-resistance and vancomycin-sensitive enterococcal bacteraemia. Clin Microbiol Infect 2012, 18:388-394.
• [29]Garsin DA, Sifri CD, Mylonakis E, Qin X, Singh KV, Murray BE, Calderwood SB, Ausubel FM: A simple model host for identifying Gram-positive virulence factors. Proc Natl Acad Sci USA 2001, 98:10892-10897.
• [30]Nannini EC: Vancomycin-resistant enterococcal bloodstream infection-related mortality: focus on the lack of appropriate therapy. Clin Infect Dis 2006, 42:1203-1204.
• [31]Rakita RM, Vanek NN, Jacques-Palaz K, Mee M, Mariscalco MM, Dunny GM, Snuggs M, Van Winkle WB, Simon SI: Enterococcus faecalis bearing aggregation substance is resistant to killing by human neutrophils despite phagocytosis and neutrophil activation. Infect Immun 1999, 67:6067-6075.
• [32]Arduino RC, Jaques-Palaz K, Murray BE, Rakita RM: Resistance of Enterococcus faecium to neutrophil-mediated phagocytosis. Infect Immun 1994, 62:5587-5594.
• [33]Worth LJ, Thursky KA, Seymour JF, Slavin MA: Vancomycin-resistant Enterococcus faecium infection in patients with hematologic malignancy: patients with acute myeloid leukemia are at high-risk. Eur J Haematol 2007, 79:226-233.
• [34]Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM: CDC definitions for nosocomial infections, 1988. Am J Infect Control 1988, 16:128-140.
• [35]Weinstock DM, Conlon M, Iovino D, Aubrey T, Gudiol C, Riedel E, Young JW, Kiehn TE, Zuccotti G: Colonization, bloodstream infection, and mortality caused by vancomycin-resistant enterococcus early after allogeneic hematopoietic stem cell transplant. Biol Blood Marrow Transplant 2007, 13:615-621.