Bloodstream infections in patients with hematological malignancies: which is more fatal - cancer or resistant pathogens?

Habip Gedik, Funda Simşek, Arzu Kantürk, Taner Yildirmak, Deniz Arica, Demet Aydin, Naciye Demirel, Osman Yokuş, Habip Gedik, Funda Simşek, Arzu Kantürk, Taner Yildirmak, Deniz Arica, Demet Aydin, Naciye Demirel, Osman Yokuş

Abstract

Background: The primary objective of this study was to report the incidence of bloodstream infections (BSIs) and clinically or microbiologically proven bacterial or fungal BSIs during neutropenic episodes in patients with hematological malignancies.

Methods: In this retrospective observational study, all patients in the hematology department older than 14 years who developed febrile neutropenia during chemotherapy for hematological cancers were evaluated. Patients were included if they had experienced at least one neutropenic episode between November 2010 and November 2012 due to chemotherapy in the hematology ward.

Results: During 282 febrile episodes in 126 patients, 66 (23%) episodes of bacteremia and 24 (8%) episodes of fungemia were recorded in 48 (38%) and 18 (14%) patients, respectively. Gram-negative bacteria caused 74% (n=49) of all bacteremic episodes. Carbapenem-resistant Gram-negative bacteria (n=6) caused 12% and 9% of Gram-negative bacteremia episodes and all bacteremia episodes, respectively. Carbapenem-resistant Gram-negative bacteria included Acinetobacter baumannii (n=4), Pseudomonas aeruginosa (n=1), and Serratia marcescens (n=1). Culture-proven invasive fungal infection occurred in 24 episodes in 18 cases during the study period, with 15 episodes in ten cases occurring in the first study year and nine episodes in eight cases in the second study year. In 13 of 18 cases (72%) with bloodstream yeast infections, previous azole exposure was recorded. Candida parapsilosis, C. glabrata, and C. albicans isolates were resistant to voriconazole and fluconazole.

Conclusion: BSIs that occur during febrile neutropenic episodes in hematology patients due to Gram-negative bacteria should be treated initially with non-carbapenem-based antipseudomonal therapy taking into consideration antimicrobial stewardship. Non-azole antifungal drugs, including caspofungin and liposomal amphotericin B, should be preferred as empirical antifungal therapy in the events of possible or probable invasive fungal infections with an absence of pulmonary findings due to increase azole resistance.

Keywords: antifungal treatment; azole resistance; bacteremia; bloodstream infection; carbapenem resistance; febrile neutropenia; fungemia; hematological malignancies.

References

    1. Crawford J, Dale DC, Lyman GH. Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management. Cancer. 2004;100:228–237.
    1. Carratala J, Gudiol F. Changing epidemiology of bacterial infection in neutropenic patients with cancer. Antibiot Chemother. 2000;50:1–9.
    1. Nørgaard M, Larsson H, Pedersen G, et al. Haematological malignancies – a predictor of a poor outcome in patients with bacteraemia. J Infect. 2006;53:190–198.
    1. Pagano L, Tacconelli E, Tumbarello M, et al. Bacteremia in patients with haematological malignancies. Analysis of risk factors, etiological agents and prognostic indicators. Haematologica. 1997;82:415–419.
    1. Nørgaard M. Risk of infections in adult patients with haematological malignancies. The Open Infectious Diseases Journal. 2012;6(Suppl 1 M4):46–51.
    1. Sipsas NV, Lewis RE, Tarrand J, et al. Candidemia in patients with haematologic malignancies in the era of new antifungal agents (2001–2007): stable incidence but changing epidemiology of a still frequently lethal infection. Cancer. 2009;115:4745–4752.
    1. Marr KA, White TC, van Burik JA, Bowden RA. Development of fluconazole resistance in Candida albicans causing disseminated infection in a patient undergoing marrow transplantation. Clin Infect Dis. 1997;25:908–910.
    1. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52:56–93.
    1. Maertens J, Theunissen K, Verbeken E, et al. Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients. Br J Haematol. 2004;126:852–860.
    1. Caillot D, Couaillier JF, Bernard A, et al. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computerised tomography scans in patients with neutropenia. J Clin Oncol. 2001;19:253–259.
    1. Ascioglu S, Rex HB, De Pauw B, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002;34:7–14.
    1. Braun E, Hussein K, Geffen Y, Rabino G, Bar-Lavie Y, Paul M.Predominance of Gram-negative bacilli among patients with catheter-related bloodstream infections Clin Microbiol Infect January 24, 2014[Epub ahead of print]
    1. Bousquet A, Malfuson JV, Sanmartin N, et al. An 8-year survey strains identified in blood cultures in a clinical haematology unit. Clin Microbiol Infect. 2014;20:7–12.
    1. Chen CY, Tsay W, Tang JL, et al. Epidemiology of bloodstream infections in patients with haematological malignancies with and without neutropenia. Epidemiol Infect. 2010;138:1044–1051.
    1. Gedik H, Yıldırmak MT, Şimşek F, et al. The outcome of non-carbapenem-based empirical antibacterial therapy and VRE colonisation in patients with hematological malignancies. Afr Health Sci. 2013;13:362–368.
    1. Blay JY, Chauvin F, Le Cesne A, et al. Early lymphopenia after cytotoxic chemotherapy as a risk factor for febrile neutropenia. J Clin Oncol. 1996;14:636–643.
    1. Mendes RE, Farrell DJ, Sader HS, Jones RN. Comprehensive assessment of tigecycline activity tested against a worldwide collection of Acinetobacter spp. (2005–2009) Diagn Microbiol Infect Dis. 2010;68:307–311.
    1. Rosa RG, Goldani ZL, dos Santos RP. Risk factors for multidrug-resistant bacteremia in hospitalized cancer patients with febrile neutropenia: a cohort study. Am J Infect Control. 2014;42:74–76.
    1. Huang ST, Chiang MC, Kuo SC, et al. Risk factors and clinical outcomes of patients with carbapenem-resistant Acinetobacter baumannii bacteremia. J Microbiol Immunol Infect. 2012;45:356–362.
    1. Tumbarello M, Repetto E, Trecarichi EM, et al. Multidrug-resistant Pseudomonas aeruginosa bloodstream infections: risk factors and mortality. Epidemiol Infect. 2011;139:1740–1749.
    1. Yang YS, Lee YT, Tsai WC, et al. Comparison between bacteremia caused by carbapenem resistant Acinetobacter baumannii and Acine-tobacter nosocomialis. BMC Infect Dis. 2013;13:311.
    1. Satlin MJ, Jenkins SG, Walsh TJ. The global challenge of carbapenem-resistant enterobacteriaceae in transplant recipients and patients with hematologic malignancies. Clin Infect Dis. 2014;58:1274–1283.
    1. Kochar S, Sheard T, Sharma R, et al. Success of an infection control program to reduce the spread of carbapenem-resistant Klebsiella pneumoniae. Infect Control Hosp Epidemiol. 2009;30:447–452.
    1. Siegel JD, Rhinehart E, Jackson M, Chiarello L, Healthcare Infection Control Practices Advisory Committee Management of multidrug-resistant organisms in healthcare settings, 2006. Am J Infect Control. 2007;35(10 Suppl 2):165–193.
    1. Centers for Disease Control and Prevention 2012 CRE Toolkit: Guidance for control of carbapenem-resistant Enterobacteriaceae. [Accessed April 5, 2014]. Available from: .
    1. Lim SK, Lee SO, Choi SH, et al. The outcomes of using colistin for treating multidrug resistant acinetobacter species bloodstream infections. J Korean Med Sci. 2011;26:325–331.
    1. Santimaleeworagun W, Wongpoowarak P, Chayakul P. Clinical outcomes of patients infected with carbapenem-resistant Acinetobacter baumannii treated with single or combination antibiotic therapy. J Med Assoc Thai. 2011;94:863–869.
    1. Simsek F, Gedik H, Yildirmak MT, et al. Colistin against colistin-only-susceptible Acinetobacter baumannii-related infections: monotherapy or combination therapy? Indian J Med Microbiol. 2012;30:448–452.
    1. Mikulska M, Del Bono V, Prinapori R, et al. Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2010;12:505–512.
    1. 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 Transplant. 2007;13:615–621.
    1. Olivier CN, Blake RK, Steed LL, Salgado CD. Risk of vancomycin-resistant Enterococcus (VRE) bloodstream infection among patients colonized with VRE. Infect Control Hosp Epidemiol. 2008;29:404–409.
    1. Vincent JL, Anaissie E, Bruining H, et al. Epidemiology, diagnosis and treatment of systemic Candida infection in surgical patients under intensive care. Intensive Care Med. 1998;24:206–216.
    1. Wey SB, Mori M, Pfaller MA, Woolson RF, Wenzel RP. Risk factors for hospital-acquired candidemia. A matched case control study. Arch Intern Med. 1989;149:2349–2353.
    1. Clark TA, Slavinski SA, Morgan J, et al. Epidemiologic and molecular characterization of an outbreak of Candida parapsilosis bloodstream infections in a community hospital. J Clin Microbiol. 2004;42:4468–4472.
    1. Bassetti M, Ansaldi F, Nicolini L, et al. Incidence of candidaemia and relationship with fluconazole use in an intensive care unit. J Antimicrob Chemother. 2009;64:625–629.
    1. Messer SA, Jones RN, Fritsche TR. International surveillance of Candida spp. and Aspergillus spp.: report from the SENTRY Antimicrobial Surveillance Program (2003) J Clin Microbiol. 2006;44:1782–1787.
    1. Yildirmak MT, Gedik H, Şimşek F, Iris NE, Gücüyener A. Is timely and appropriate antifungal drug enough for survival of adult cases with candidaemia? Five-year experience. West Indian Med J. 2013;62:724–730.
    1. Yenigün BK, Kuloğlu F, Doğan ÇA, Akata F. Evaluation of epidemiological characteristics and risk factors of candidemia in adult patients in a tertiary-care hospital. Mikrobiyol Bul. 2011;45:489–503. Turkish.
    1. Arendrup MC, Fuursted K, Gahrn-Hansen B, et al. Seminational surveillance of fungemia in Denmark: notably high rates of isolates with reduced azole susceptibility. J Clin Microbiol. 2005;43:4434–4440.
    1. Nucci M, Anaissie E, Betts RF, et al. Early removal of central venous catheter in patients with candidemia does not improve outcome: analysis of 842 patients from 2 randomized clinical trials. Clin Infect Dis. 2010;51:295–303.
    1. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49:1–45.
    1. Imhof A, Balajee SA, Fredricks DN, Englund JA, Marr KA. Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole. Clin Infect Dis. 2004;39:743–746.
    1. Morrell M, Fraser VJ, Kollef MH. Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother. 2005;49:3640–3645.
    1. Miceli MH, Diaz JA, Lee SA. Emerging opportunistic yeast infections. Lancet Infect Dis. 2011;11:142–151.
    1. Colombo AL, Padovan AC, Chaves GM. Current knowledge of Trichosporon spp. and trichosporonosis. Clin Microbiol Rev. 2011;24:682–700.
    1. Martino P, Venditti M, Micozzi A, et al. Blastoschizomyces capitatus: an emerging cause of invasive fungal disease in leukemia patients. Clin Infect Dis. 1990;12:570–582.
    1. Saghrounia F, Abdeljelila JB, Youssef YB, et al. Geotrichum capitatum septicemia in patients with acute myeloid leukemia. Report of three cases. Med Mycol Case Rep. 2012;1:88–90.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren