Infection Control for Neutropenic Cancer Patients : the Libraryuse of Prophylactic Antibiotics Lecture Author Jean A
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Infection control for neutropenic cancer patients : the Libraryuse of prophylactic antibiotics Lecture author Jean A. Klastersky Onlineby Institut Jules Bordet,© Université Libre de Bruxelles (ULB) Brussels, Belgium ESCMID Complications and mortality associated with febrile neutropenia Library No Bacteremia Bacteremia Total ComplicationsLectureDeaths Total Complications Deaths author Solid tumors 784 60 (8 %) 25 135 30 (22 %) 17 Onlineby (3 %) (13 % ) © Hematological cancer 859 111 (13 %) 32 364 76 (21 %) 32 (4 %) (9 %) ESCMID J. Klastersky et al., 2007 2 Complications associated with febrile neutropenia Library Hypotension : systolic blood pressure less than 90 mmHg or need for pressor support to maintain blood pressure Respiratory failure : arterial oxygen pressure less than 60mmHg while breathing room air or needLecture for mechanical ventilation Disseminated intravascular coagulation Confusion or altered mental state author Congestive cardiac failure seen on chest X-ray and requiring treatment Onlineby Bleeding severe enough to require© transfusion Arrhythmia or ECG changes requiring treatment Renal failure requiring investigation and/or treatment with IV fluids, dialysis, or any other intervention ESCMID J. Klastersky et al., 2000 3 Cost of febrile neutropenia Library Initial hospitalization Initial hospitalization plus all downstreamLecture neutropenia care author 2.010 $ Onlineby 14.407 $ © ESCMID D. Weyckler et al., 2008 4 Use of oral antibiotics in protected units environment : clinical effectiveness and role in the emergence of antibiotic-resistantLibrary strains « … the incidence of proven infection was significantly reduced … Lecture» « … no advantage of isolationauthor in addition to antibiotics could be detected … » Onlineby « … bacteria isolated© from decontamined patients were considerably more resistant … » ESCMID J. Klastersky et al., 1973 5 Infection-control interventions for cancer patients after chemotherapy : a systematic review and meta-analysis Library « … protective isolation, including air quality control, prophylactic antibioticsLecture and barrier isolation (29 studies) brought about a significant reduction in all-cause mortalityauthor : risk ratio 0.60 … » « … inclusion ofOnline prophylacticby antibiotics in the © intervention was necessary to show the effect on mortality … » ESCMID A. Schlesinger et al., 2009 6 Occurrence of infections among placebo and trimethoprim-sulfamethoxazole (TMP-SXT)-treated patientsLibrary Treatment group Total N of No (%) Patients with Patients LectureAny Infection Bacteremia Placebo 165 author64 (39) • 32 (19) * TMP-SXT Online177 by 46 (26) • 22 (12) * © • p = 0.016 * P = 0.106 (p = 0.005 if patients with acute leukemia were excluded) ESCMID EORTC Antimicrobial Therapy Project Group 1984 7 Prophylaxis with fluoroquinolones (Levofloxacin) in patients with expected neutropenia (adapted from L. Leibovici et al., 2006) Library Patients Relative Absolute Risk in the N of treated Patients Risk Control Group needed to prevent 1 Event Acute leukemia and stem cell transplantation* Lecture Febrile neutropenia 0.76 85 4 Bacterial Infection 0.56 39 5 author Solid Tumors and Lymphomas • Onlineby Febrile Neutropenia 0.71© 15 23 Bacterial Infection 0.82 42 13 ESCMID * G. Bucaneve et al., 2005 • M. Cullen et al., 2005 8 Deaths caused by infection in patients receiving prophylaxis for febrile neutropenia Library Levofloxacin Placebo P value Lecture Bucaneve et al. (2005) 10 / 373 (2.8 %)author18 / 363 (4.9 %) 0.15 Onlineby © Cullen et al. (2005) 4 / 781 (0.5 %) 3 / 784 (0.3 %) NS ESCMID 9 Meta-analysis of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in patients with solid tumors or/and lymphomas (3.493 patients) Library Absolute Occurrence Relative Risk Reduction Lecture Infection-related 1.5 % (← 2.8author %) 45 % (p = 0.018) mortality Onlineby Febrile neutropenia 22.4© % (← 39.5 %) 46 % (p < 0.0001) ESCMID N. Kuderer et al., 2007 10 Meta-analysis of prophylaxis with granulocyte colony- stimulating factors (G-CSF and GM-CSF) on febrile neutropenia and mortality autologous and allogeneic stem cell transplantation (2.669 patients)Library Relative Risk Reduction Documented infections Lecture13 % (p = 0.05) Duration parenteral antibiotics - 1.39 days (p = 0.02) Infection-related mortality author24 % (p = 0.4) Grade 2-4 GVHD Onlineby 0 % (p = 0.8) Treatment-related mortality © 0 % (p = 0.9) ESCMID A. Dekker et al., 2006 11 Prophylactic antibiotics or G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapyLibrary : The Cochrane Collaboration Lecture « … there is no evidence for or against antibiotics compared to G(M)-CSF’s forauthor prevention of infections in cancerOnline patientsby … » © ESCMID C. Herbst et al., 2009 12 Bacterial isolates from cases of bacteremia due to a single organism Library Trial Total n of isolates Gram-negative Gram-positive I: 1973-1976 145 103 (71 %) 42 (29 %) II: 1977-1980 111 Lecture74 (67 %) 37 (33 %) III: 1980-1983 141 83 (59 %) 58 (41 %) IV: 1983-1985 219 author129 (59 %) 90 (41 %) V: 1986-1988 Online213 by 78 (37 %) 135 (63 %) VIII: 1989-1991 151 © 47 (31 %) 104 (69 %) IX: 1991-1993 161 53 (33 %) 108 (67 %) ESCMID EORTC International Antimicrobial Therapy Cooperative Group, 1999 13 Gram-positive organisms isolated during trial VIII Organism LibraryNisolated Streptococcus species 57 Viridans group 44 Group D Lecture 5 Streptococcus pneumoniae 4 Other author 4 Coagulase-negative staphylococci 49 Staphylococcus aureus Onlineby 20 Corynebacterium species © 5 Other gram-positive organisms 3 ESCMID EORTC International Antimicrobial Therapy Cooperative Group, 1999 14 « New » gram-positive pathogens in patients with neutropenia Library Viridans streptococci e.g., Streptococcus mitis, Streptococcus milleri Leuconostoc species Enterococcus species, especially vancomycin-resistant Corynebacterium jeikeium, CorynebacteriumLecture urealyticum Rhodococcus equi author Stomatococcus mucilaginosus Lactobacillus rhamnosusOnlineby Bacillus cereus © Clostridium septicum, Clostridium tertium ESCMID S.H. Zinner, 1999 15 « New » gram-negative pathogens in patients with neutropenia Stenotrophomonas (Xanthomonas, Pseudomonas) maltophiliaLibrary Alteromonas (Pseudomonas) putrifaciens Legionella pneumophila, Legionella micdadei Vibrio parahaemolyticus Capnocytophaga species Lecture Alcaligenes xylosoxidans Chryseobacterium meningosepticum author Burkholderia cepacia Onlineby Fusobacterium nucleatum © Leptotrichia buccalis Methylobacterium species Moraxella-like organisms ESCMID S.H. Zinner, 1999 16 Antibiotic-resistant bugs in the 21st century – a clinical super-challenge Library « … we have come almost full circle and arrived at a point as frighteningLecture as the preantibiotic era : for patients infectedauthor with multidrug- resistant bacteria, there is no magic bullet … » Onlineby © ESCMID C.A. Arias and B.E. Murray, 2009 17 Bacteremia due to viridans streptococci that are highly resistant to penicillin : increase among neutropenic patients with cancer (260 episodes of bacteremia) Library « … rates of bacteremia due to highly penicillin- resistant … increased significantly from zero (1987) to 17 episodes (1992)Lecture per 1.000 admissions (p = 0.003) … » author « … the administrationOnlineby of β-lactam antibiotics during the 2 previous© weeks was the only factor significantly associated… » ESCMID J. Carratala et al., 1995 18 Use of fluoroquinolone prophylaxis and frequency of fluoroquinolone-resistant bacteremia isolates in neutropenic patients with cancer Library Variable 1983-1985 1986-1990 1991-1993 Patients given prophylaxis/all patients (%) Prophylaxis 3/219 (1.4) 228/694 (33) 318/706 (45) Lecture Fluoroquinolone-resistant strains/strains tested (%) Isolate author Escherichia coli 0/26 0/66 11/40 (28) Coagulase-negative Online0/22 by 44/172 (26) 23/38 (61) staphylococci © Pseudomonas aeruginosa 1/25 (4) 1/39 (3) 1/13 (8) Klebsiella pneumoniae 0/3 1/17 (6) 1/13 (8) ESCMID A. Cometta et al., 1994 19 Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center : incidence of fluoroquinolone-resistant E. coli per yearly number of discharges from the medical service Library Incidence (per 10.000 discharges) Year Leukemia Other diseases P value 1988 69.2a Lecture< 1.5b 0.002 1989 80.6 author3.7 0.008 1990 35.6 3.6 0.13 1991 Online153.8 by 3.8 0.00003 1992 327.3a© 3.6b < 0.00001 a P = 0.03 b P = 0.17 ESCMID W.V. Kern et al., 1994 20 Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center Library « … bacteremia … increased from < 0.5 % in 1988-1989 and 0.8 % in 1990-1991 to 4.5 % in 1992-1993 (p < 0.01) … » Lecture « … MIC raised between 8-16 µg/ml… and indicated resistance to TMP/SXT, ampicillin,author doxycycline and chloramphenicol … » Onlineby « … 4 genotypes were identified,© suggesting both independant development and horizontal spread… » ESCMID W.V. Kern et al., 1994 21 Fluoroquinolone resistance of Escherichia coli at a cancer center : epidemiologic evolution and effects of discontinuing prophylactic fluoroquinolone use in neutropenic patients with leukemia Library Pre-intervention Discontinuation of Post-intervention (1995-1997) fluoroquinolones (1999) (1998) Resistance Lecture rate > 50 % 15 % > 50 % author E. coli bacteremia 8 Online% • by 20 % • * 9 % * © • p < 0.01 * p = 0.03 ESCMID W.V. Kern et al., 2005 22 Recent changes in bacterial epidemiology and the emergence of fluoroquinolone- resistant Escherichia coli