PREVENTION AND TREATMENT OF CANCER-RELATED INFECTIONS

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Screening for breast cancer began in the UK in 1988 and the prevalent screening round was completed in 1995. Currently, all women aged 50-64 are invited for mammograms every three years; the age range is to be expanded to women aged 70 by 2004. 17 In 1999-2000, the NHS Breast Screening Programme detected 9,797 cancers by screening about 1,550,000 women. 2 The potential use of magnetic resonance imaging (MRI) for screening high risk women aged 35-50 is being evaluated. Women with symptoms that could be due to breast cancer are referred by their GP to designated breast clinics in local hospitals. In a single year, the average GP, with a patient...

Nội dung Text: PREVENTION AND TREATMENT OF CANCER-RELATED INFECTIONS

 

  1. NCCN Clinical Practice Guidelines in Oncology™ Prevention and Treatment of Cancer- Related Infections V.2.2009 Continue www.nccn.org
  2. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 n NCCN Prevention and Treatment of Cancer-Related Infections Panel Members tio * Brahm H. Segal, MD/Co-Chair F John P. Greer, MD ‡ Guido Marcucci, MD Þ † Vanderbilt-Ingram Cancer Center Arthur G. James Cancer Hospital & Roswell Park Cancer Institute Richard J. Solove Research Institute at Michael G. Ison, MD, MS F * Lindsey Robert Baden, MD/Co-Chair F The Ohio State University bu Robert H. Lurie Comprehensive Dana-Farber/Brigham and Women's Kieren A. Marr, MD F Cancer Center at Northwestern Cancer Center | Massachusetts General The Sidney Kimmel Comprehensive University Hospital Cancer Center Cancer Center at Johns Hopkins James I. Ito, MD F Corey Casper, MD, MPH F Jose G. Montoya, MD City of Hope Fred Hutchinson Cancer Research tri Stanford Comprehensive Cancer Center Center/Seattle Cancer Care Alliance Judith E. Karp, MD ‡ Þ Ashley Morris-Engemann, PharmD å The Sidney Kimmel Comprehensive Erik Dubberke, MD F Duke Comprehensive Cancer Center Cancer Center at Johns Hopkins is Siteman Cancer Center at Barnes- Jewish Hospital and Washington Peter G. Pappas, MD F Daniel R. Kaul, MD F University School of Medicine University of Alabama at Birmingham University of Michigan Comprehensive rD Comprehensive Cancer Center Cancer Center Alison G. Freifeld, MD F Þ UNMC Eppley Cancer Center at The Ken Rolston, MD Earl King, MD X Nebraska Medical Center The University of Texas M.D. Anderson Fox Chase Cancer Center Cancer Center Michael Gelfand, MD F Emily Mackler, PharmD å Susan K. Seo, MD F Þ St. Jude Children's Research fo University of Michigan Comprehensive Hospital/University of Tennessee Memorial Sloan-Kettering Cancer Center Cancer Center Cancer Institute John N. Greene, MD F Þ H. Lee Moffitt Cancer Center & Research F Infectious diseases ot Institute ‡ Hematology/Hematology oncology Þ Internal medicine X Pulmonary medicine Continue N † Medical oncology å Pharmacology * Writing committee member Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  3. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 Table of Contents n Principles of Daily Follow-Up (FEV-8) Panel Members tio For help using these Follow-Up Therapy for Responding Summary of Guideline Updates documents, please click here Patients (FEV-9) Antimicrobial Prophylaxis (INF-1) Follow-Up Therapy for Nonresponding Patients (FEV-12) Antibacterial Prophylaxis (INF-2) bu Discussion Outpatient Therapy for Low Risk Patients Antifungal Prophylaxis (INF-3) (FEV-13) References Antiviral Prophylaxis (INF-4) Antibacterial Agents Table (FEV-A) Antipneumocystis Prophylaxis (INF-5) Antifungal Agents Table (FEV-B) Clinical Trials: The NCCN tri believes that the best management Prevention of Cytomegalovirus Disease (INF-6) Antiviral Agents Table (FEV-C) for any cancer patient is in a clinical Fever and Neutropenia (FEV-1) Appropriate Use of Vancomycin (FEV-D) trial. Participation in clinical trials is is especially encouraged. Initial Therapy (FEV-2) Risk Assessment Resources (FEV-E) To find clinical trials online at NCCN Initial Risk Assessment for Febrile Neutropenic Adjunctive Therapies (FEV-F) member institutions, click here: Patients (FEV-3) rD nccn.org/clinical_trials/physician.html Site Specific Evaluation and Therapy: Guidelines Index NCCN Categories of Evidence and · Mouth, Esophagus, and Sinus/Nasal (FEV-4) Consensus: All recommendations Print the Prevention and Treatment of · Abdominal Pain, Perirectal Pain, Diarrhea, are Category 2A unless otherwise Cancer-Related Infections Guideline specified. Vascular Access Devices (FEV-5) fo · Lung Infiltrates (FEV-6) See NCCN Categories of Evidence and Consensus · Cellulitis, Wound, Vesicular Lesions, Disseminated Papules or Other Lesions, Urinary Tract Symptoms, Central Nervous System Symptoms (FEV-7) ot These guidelines are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to N determine any patient's care or treatment. The National Comprehensive Cancer Network makes no representations or warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These guidelines are copyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. © 2009. Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  4. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 Summary of the Guidelines Updates n Summary of the changes in the 2.2009 version of the Prevention and Treatment of Cancer-Related Infections Guidelines from the 1.2009 version include: · The addition of the updated Discussion section. tio Summary of the changes in the 1.2009 version of the Prevention and Treatment of Cancer-Related Infections Guidelines from the 1.2008 version include: FEV-4 INF-1 · Added clofarabine and nelarabine to the intermediate overall risk Following Mouth/mucosal initial clinical presentation, added bu “Consider leukemic infiltrate” to the evaluation. of infection in cancer patients category. · Added “Purine analogs, intermediate risk when used as single FEV-5 agents, when combined with intensive chemotherapy regimens Following diarrhea added: “IV metronidazole should be used in the risk converts to high.” patient who cannot take oral agents.” · Footnote a is new to the page: “Categories of risk are based on tri several factors, including underlying malignancy, whether disease FEV-6 is in remission, duration of neutropenia, prior exposure to · Footnote t is new to the page: “Rapid immunofluorescent viral chemotherapy, and intensity of immunosuppressive therapy.” antigen tests may be negative for H1N1 (swine flu).” · Footnote b is new to the page: “Multiple immune deficits can co- is · Footnote u is new to the page: “Antiviral susceptibility of influenza exist in the same patient.” strains is variable and cannot be predicted based on prior influenza outbreaks. In cases of seasonal influenza and pandemic strains (eg INF-3 rD H1N1), it is necessary to be familiar with susceptibility patterns and · Itraconazole recommendation as prophylaxis changed from a guidelines on appropriate antiviral treatment.” category 1 to a category 2B level of evidence and consensus. FEV-10 INF-4 · Added Influenza: Oseltamivir is approved by FDA for 5 d based on · Bortezomib was added as a therapy with high risk for varicella data from ambulatory otherwise healthy individuals with intact zoster reactivation for which antiviral prophylaxis should be fo immune systems; longer courses (ie, at least 10 d) and until considered. resolution of symptoms should be considered in the highly immunocompromised. FEV-2 · Footnote e was revised and now states: “Meta-analysis reported FEV-A (page 2 of 4) increased mortality associated with cefepime in randomized trials ot · Added doripenim to the Antibacterial Agents Tables. of neutropenic fever. However the FDA has concluded that cefepime remains appropriate therapy for its approved indications FEV-C (page 3 of 4) based on the results of the FDA’s recent meta-analysis.” · Added tenofovir DF to the Antiviral Agents Tables. N (See Discussion) Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. UPDATES Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  5. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 n OVERALL FEVER & NEUTROPENIA RISK ANTIMICROBIAL PROPHYLAXIS c,d,e,f DISEASE / THERAPY EXAMPLES b INFECTION RISK IN CATEGORY (See FEV-3) CANCER PATIENTS a tio · Standard chemotherapy · Bacterial - None regimens for most solid tumors · Fungal - None Low Low · Anticipated neutropenia less · Viral - None unless prior HSV episode than 7 d bu Usually HIGH, but some · Autologous HSCT experts suggest modifications · Bacterial - Consider fluoroquinolone · Lymphoma depending on patient status. · Multiple myeloma prophylaxis Purine analogs, intermediate · Fungal - Consider fluconazole during · CLL risk when used as single tri · Purine analog therapy (ie, Intermediate neutropenia and for anticipated mucositis agents; when combined with · Viral - During neutropenia and at least 30 d fludarabine, clofarabine, intensive chemotherapy after HSCT nelarabine, 2-CdA) regimens, the risk converts to · Anticipated neutropenia 7 to 10 d high. is · Allogeneic HSCT · Acute leukemia Usually HIGH, but significant · Bacterial - Consider fluoroquinolone > Induction rD variability exists related to > Consolidation prophylaxis duration of neutropenia, · Alemtuzumab therapy · Fungal - See INF-3 High immunosuppressive agents, · GVHD treated with high dose · Viral - during neutropenia and at least 30 d and status of underlying steroids after HSCT malignancy · Anticipated neutropenia greater fo than 10 d KEY: 2-CdA = chlorodeoxyadenosine (cladribine), CLL = chronic lymphocytic leukemia, CMV = cytomegalovirus, GVHD = graft versus host disease, HSCT = hematopoietic stem cell transplant, HSV = herpes simplex virus, VZV = varicella zoster virus. a Categories of risk are based on several factors, including underlying malignancy, whether disease is in remission, duration of neutropenia, prior exposure to chemotherapy, and intensity of immunosuppressive therapy. ot b Multiple immune deficits can co-exist in the same patient. c Pneumocystis prophylaxis (See INF-5). d See Antibacterial Agents (FEV-A) for dosing, spectrum, and specific comments/cautions. e See Antifungal Agents (FEV-B) for dosing, spectrum, and specific comments/cautions. N f See Antiviral Agents (FEV-C) for dosing, spectrum, and specific comments/cautions. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. INF-1 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  6. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 ANTIBACTERIAL PROPHYLAXIS d DURATION DISEASE/THERAPY EXAMPLES OVERALL INFECTION RISK n IN CANCER PATIENTS a tio · Standard chemotherapy regimens for None g most solid tumors Low · Anticipated neutropenia less than 7 d bu · Autologous HSCT · Lymphoma Consider fluoroquinolone · CLL prophylaxis g Intermediate · Multiple myeloma tri or · Purine analog therapy None · Anticipated neutropenia 7 to 10 d is · Allogeneic HSCT (neutropenic) · Acute leukemia (neutropenic) Consider fluoroquinolone prophylaxis · MDS (neutropenic) rD · Anticipated neutropenia greater than 10 d GVHD Penicillin and TMP/SMX High For a minimum of 2 mo after fo Alemtuzumab TMP/SMX alemtuzumab and until CD4 ³ 200 cells/mcL ot a Categories of risk are based on several factors, including underlying malignancy, whether disease is in remission, duration of neutropenia, prior exposure to chemotherapy, and intensity of immunosuppressive therapy. d See Antibacterial Agents (FEV-A) for dosing, spectrum, and specific comments/cautions. g Although data support levofloxacin prophylaxis for low- and intermediate-risk patients, the panel discourages this practice in low-risk patients (because of concerns N about antimicrobial resistance); however, it can be considered in intermediate-risk patients. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. INF-2 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  7. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 ANTIFUNGAL PROPHYLAXIS e DURATION OVERALL INFECTION DISEASE/THERAPY EXAMPLES RISK IN CANCER n · Fluconazole k PATIENTS a ALL h or · Amphotericin B products l (category 2B) tio · Posaconazole (category 1)k or MDS (neutropenic) · Voriconazole (category 2B)k Until resolution of or neutropenia AML h (neutropenic) · Amphotericin B products l (category 2B) bu · Fluconazole (category 1)k With mucositis j or · Micafungin (category1) Autologous HSCT tri Intermediate Consider no prophylaxis (category 2B) Without mucositis to Consider one of the following: High · Fluconazole (category 1)k Continue during is · Micafungin (category 1) Allogeneic HSCT neutropenia and for · Itraconazole (category 2B)k (neutropenic) at least 75 d after · Voriconazole (category 2B)k transplant · Posaconazole (category 2B)k rD · Amphotericin B products l (category 2B) Consider one of the following: · Posaconazole (category 1)k Until resolution of · Voriconazole (category 2B)k Significant GVHD i significant GVHD · Echinocandin (category 2B) fo · Amphotericin B products l (category 2B) a Categories of risk are based on several factors, including underlying malignancy, whether disease is in remission, duration of neutropenia, prior exposure to chemotherapy, and intensity of immunosuppressive therapy. e See Antifungal Agents (FEV-B) for dosing, spectrum, and specific comments/cautions. h Recommendations on antifungal prophylaxis in patients with acute leukemia apply to those receiving induction or re-induction chemotherapy. ot i Consider antifungal prophylaxis in all patients with GVHD receiving immunosuppressive therapy. See Antifungal Prophylaxis section of the Discussion. j Severe mucositis is a risk factor for candidemia in patients with hematologic malignancies and stem cell transplant recipients not receiving antifungal prophylaxis. k Itraconazole, voriconazole, and posaconazole are more potent inhibitors of hepatic cytochrome P450 3A4 isoenzymes than fluconazole and may significantly decrease the clearance of vinca alkaloids. N l A lipid formulation is generally preferred based on less toxicity. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. INF-3 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  8. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 n OVERALL DISEASE / THERAPY DURATION OF ANTIVIRAL PROPHYLAXIS f HERPES ANTIVIRAL INFECTION RISK IN EXAMPLES VIRUSES PROPHYLAXIS CANCER PATIENTS a tio · Standard chemotherapy None unless prior Low HSV During neutropenia HSV episode regimens for solid tumors · Autologous HSCT bu · Lymphoma Acyclovir · Multiple Myeloma During neutropenia and at least 30 d after HSV Famciclovir Intermediate · CLL HSCT VZV Valacyclovir · Purine analog therapy tri (ie, fludarabine) · Acute leukemia Acyclovir > Induction HSV Famciclovir During neutropenia is > Consolidation Valacyclovir Acyclovir Bortezomib Famciclovir High VZV rD Valacyclovir HSV prophylaxis n Acyclovir · Minimum of 2 mo after alemtuzumab and Famciclovir m HSV · Alemtuzumab until CD4 ³ 200 cells/mcL or VZV therapy · During neutropenia and at least 30 d after Valacyclovir as · Allogeneic HSCT fo HSV prophylaxis n HSCT CMV (See INF-6) for CMV Pre-emptive therapy for CMV (See INF-6) KEY: 2-CdA = chlorodeoxyadenosine (cladribine), CLL = chronic lymphocytic leukemia, CMV = cytomegalovirus, GVHD = graft versus host disease, HSCT = hematopoietic stem cell transplant, HSV = herpes simplex virus, VZV = varicella zoster virus. ot a Categories of risk are based on several factors, including underlying malignancy, whether disease is in remission, duration of neutropenia, prior exposure to chemotherapy, and intensity of immunosuppressive therapy. f See Antiviral Agents (FEV-C) for dosing, spectrum, and specific comments/cautions. m Among allogeneic HSCT, there is more experience with acyclovir and valacyclovir than famciclovir. N n Agents used as HSV prophylaxis are also active against VZV (See FEV-C). Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. INF-4 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  9. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 DURATION OF ANTIPNEUMOCYSTIS INFECTION RISK IN DISEASE / THERAPY EXAMPLES n PROPHYLAXIS d CANCER PATIENTS a PROPHYLAXIS tio For at least 180 d Allogeneic stem cell recipients (category 1) Throughout anti-leukemic Acute lymphocytic leukemia (category 1) bu therapy For a minimum of 2 mo after Alemtuzumab alemtuzumab and until CD4 TMP/SMX (preferred) ³ 200 cells/mcL High risk for tri or Pneumocystis jirovecii Dapsone, aerosolized (Pneumocystis carinii) Consider (category 2B): pentamidine, or atovaquone q if · Recipients of fludarabine and other T-cell Until CD4 count is greater is TMP/SMX intolerant q than 200 cells/mcL depleting agents · Patients with neoplastic disease receiving prolonged corticosteroids o rD or receiving temozolomide + radiation therapy p · Autologous peripheral blood stem 3-6 mo after transplant cell transplant recipients fo a Categories of risk are based on several factors, including underlying malignancy, whether disease is in remission, duration of neutropenia, prior exposure to chemotherapy, and intensity of immunosuppressive therapy. d See Antibacterial Agents (FEV-A) for dosing, spectrum, and specific comments/cautions. o Risk of PCP is related to the daily dose and duration of corticosteroid therapy. Prophylaxis against PCP can be considered in patients receiving the prednisone ot equivalent of 20 mg or more daily for 4 or more weeks. p PCP prophylaxis should be used when temozolomide is administered concomitantly with radiation therapy and should be continued until recovery from lymphocytopenia. q Consider trimethoprim/sulfamethoxazole desensitization or dapsone, aerosolized pentamidine, or atovaquone when Pneumocystis jirovecii pneumonia prophylaxis is N required, and patients are trimethoprim/sulfamethoxazole intolerant. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. INF-5 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  10. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 PREVENTION OF CYTOMEGALOVIRUS DISEASE n PRE-EMPTIVE THERAPY f,s SURVEILLANCE PERIOD r INFECTION RISK IN DISEASE / THERAPY EXAMPLES tio CANCER PATIENTS a bu · 1 to 6 months after transplant Allogeneic stem cell · GVHD transplant recipients · CD4 < 100 cells/mcL tri Ganciclovir (IV) or High risk for Foscarnet (IV) is Cytomegalovirus or disease Valganciclovir (PO) rD For a minimum of 2 mo after alemtuzumab and until CD4 Alemtuzumab ³ 100 cells/mcL fo ot a Categories of risk are based on several factors, including underlying malignancy, whether disease is in remission, duration of neutropenia, prior exposure to chemotherapy, and intensity of immunosuppressive therapy. f See Antiviral Agents (FEV-C) for dosing, spectrum, and specific comments/cautions. r CMV surveillance consists of at least weekly monitoring of CMV by PCR or antigen testing. N s Duration of prophylaxis antiviral therapy generally is for at least 2 weeks and until CMV is no longer detected. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. INF-6 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  11. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 CLINICAL PRESENTATION INITIAL EVALUATION OF FEVER AND NEUTROPENIA MICROBIOLOGIC n EVALUATION tio · Blood culture x 2 sets (one set Site specific H&P including: consists of 2 bottles). Options · Intravascular access device · Skin bu include: · Lungs and sinus > One peripheral + one catheter a · Alimentary canal (mouth, pharynx, esophagus, or bowel, rectum) > Both peripheral · Perivaginal/perirectal or Fever: > Both catheter · Single temperature Supplementary historical information: tri · Urine (if symptoms, urinary ³ 38.3°C orally or · Major comorbid illness catheter, abnormal urinalysis) · Time since last chemotherapy administration ³ 38.0°C over 1 h · Site-specific culture: · History of prior documented infections Neutropenia: > Diarrhea (Clostridium difficile See Initial · Recent antibiotic therapy/prophylaxis is · < 500 neutrophils/mcL assay, enteric pathogen screen) Therapy · Medications (FEV-2) or · HIV status > Skin (aspirate/biopsy of skin · Exposures: < 1,000 neutrophils/mcL lesions) > Others at home with similar symptoms rD > Vascular access cutaneous site and a predicted decline > Pets to £ 500/mcL over the with inflammation (consider > Travel next 48 h routine/fungal/mycobacteria) > Tuberculosis exposure · Viral cultures: > Recent blood product administration > Vesicular/ulcerated lesions on Laboratory/radiology assessment: skin or mucosa fo > Throat or nasopharynx for · CBC including differential, platelets, BUN, respiratory virus symptoms, electrolytes, creatinine, and LFTs · Consider chest x-ray, urinalysis, pulse oximetry especially during outbreaks · Chest x-ray for all patients with respiratory symptoms ot N a Preferred for distinguishing catheter-related infections from secondary sources. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. FEV-1 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  12. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 INITIAL THERAPY FOR FEVER AND NEUTROPENIA b,c n · Intravenous antibiotic monotherapy (choose one): > Imipenem/cilastatin (category 1) Initial antibiotic therapy should be > Meropenem (category 1) tio based on: > Piperacillin/tazobactam d (category 1) · Infection risk assessment > Cefepime (category 1)e Site-Specific Evaluation and Therapy: (See FEV-3) > Ceftazidime f (category 2B) Mouth, Esophagus and Sinus/Nasal · Potential infecting organisms · Intravenous antibiotic combination therapy: (FEV-4) include vancomycin-resistant > Aminoglycoside g + antipseudomonal penicillin bu enterococcus (VRE) and (category 1) ± beta-lactamase inhibitor Abdominal Pain, Perirectal Pain, extended spectrum beta- (category 1) Diarrhea, Vascular Access Devices > Aminoglycoside + extended-spectrum lactamase (ESBL) (FEV-5) · Colonization with or prior cephalosporin (cefepime, ceftazidime) > Ciprofloxacin + antipseudomonal penicillin infection with methicillin- tri Lung Infiltrates (FEV-6) resistant Staphylococcus aureus (category 1) (MRSA) > Use of vancomycin, linezolid, daptomycin or Cellulitis, Wound, Vesicular Lesions, · Site of infection Disseminated Papules or other quinupristin/dalfopristin is not routinely · Local antibiotic susceptibility recommended h,i is lesions, Urinary Tract Symptoms, Central Nervous System Symptoms · Oral antibiotic combination therapy for low risk patterns (FEV-7) · Organ dysfunction/drug allergy patients: > Ciprofloxacin + amoxicillin/clavulanate · Broad spectrum of activity rD OR · Previous antibiotic therapy (category 1) (for penicillin-allergic patients, may · Antipseudomonal coverage use ciprofloxacin + clindamycin) Follow-up (FEV-8) > Oral antibiotic regimen recommended should · Bactericidal not be used if quinolone prophylaxis was used bConsider local antibiotic susceptibility patterns when choosing empirical therapy. At hospitals where infections by antibiotic resistant bacteria (eg, MRSA or drug- fo resistant gram-negative rods) are commonly observed, policies on initial empirical therapy of neutropenic fever may need to be tailored accordingly. c See Antibacterial Agents (FEV-A) for dosing, spectrum, and specific comments/cautions. d May interfere with galactomannan measurement. e Meta-analysis reported increased mortality associated with cefepime in randomized trials of neutropenic fever. However the FDA has concluded that cefepime remains appropriate therapy for its approved indications based on the results of the FDA’s recent meta-analysis. (see Discussion). f Weak Gram-positive coverage and increased breakthrough infections limit utility. ot g Some authorities recommend avoidance of aminoglycosides because of potential nephrotoxicity, which may be diminished by once-daily administration. Once-a-day aminoglycoside therapy should be avoided for treatment of meningitis or endocarditis. h Although there are published studies regarding the use of some of these agents in neutropenic patients, the NCCN panel strongly recommends that these agents should not be routinely used as initial empirical therapy for neutropenic fever because of concerns about resistance and breakthrough infections. N i See Appropriate Use of Vancomycin and Other Agents for Gram-positive Resistant Infections (FEV-D). Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. FEV-2 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  13. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 INITIAL RISK ASSESSMENT FOR FEBRILE NEUTROPENIC PATIENTS j SITE OF CARE TREATMENT OPTIONS n tio High-risk (any factor listed below): · Inpatient status at time of development of fever · Significant medical comorbidity or clinically unstable · Anticipated prolonged severe neutropenia: £ 100 cells/mcL and ³ 7 d bu · Hepatic insufficiency (5 times ULN for aminotransferases) · Renal insufficiency (a creatinine clearance of less than 30 mL/min) IV therapy Hospital · Uncontrolled/progressive cancer k · Pneumonia or other complex infections at clinical presentation · Alemtuzumab tri · Mucositis grade 3-4 OR IV therapy · MASCC Risk Index score of less than 21 j or Initial evaluation is Sequential IV/oral therapy Hospital Low-risk (none of the above factors and most of the following): rD Oral therapy OR · Outpatient status at time of development of fever (category 1) · No associated acute comorbid illness, independently Consider ambulatory indicating inpatient treatment or close observation clinic · Anticipated short duration of severe neutropenia (£ 100 cells/mcL for < 7 d) OR See Outpatient · Good performance status (ECOG 0-1) fo Therapy for · No hepatic insufficiency Home for selected Low-Risk · No renal insufficiency low-risk patients with Patients adequate outpatient (FEV-13) OR infrastructure · A score of 21 or greater on the MASCC Risk Index j established ot j Risk categorization refers to risk of serious complications, including mortality, in patients with neutropenic fever. See Risk Assessment Resources (FEV-E). k Uncontrolled/progressivecancer is defined as any leukemic patient not in complete remission, or non-leukemic patients with evidence of disease progression after N more than 2 courses of chemotherapy. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. FEV-3 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  14. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 ADDITIONS TO INITIAL EMPIRIC REGIMEN c,l,m INITIAL CLINICAL FINDING EVALUATION n PRESENTATION All febrile neutropenic patients should receive broad-spectrum antibiotics (FEV-2) · Culture and gram stains (DAY 0) > Viral - Herpes simplex virus tio · Ensure adequate anaerobic activity Necrotizing (HSV) · Consider anti-HSV therapy ulceration > Fungal · Consider systemic antifungal therapy > Consider leukemic infiltrate · Biopsy for lesions · Antifungal therapy Mouth/ bu suspicious for mold > Fluconazole first-line therapy mucosal Thrush > Voriconazole, posaconazole, or membrane echinocandin if refractory to fluconazole Viral cultures or PCR or other diagnostics and Vesicular lesions direct fluorescent antibody Anti-HSV therapy (category 1) tri test for HSV and Varicella- zoster virus (VZV) See Follow-up · Culture suspicious oral · Initial therapy guided by clinical findings is (FEV-8) (eg, thrush or perioral HSV) lesions · Antifungal therapy > HSV > Fungal > Fluconazole, first-line therapy · Retrosternal burning rD > Voriconazole, posaconazole, or · Consider endoscopy, if no · Dysphagia/ Esophagus echinocandin if refractory to fluconazole odynophagia response to therapy · Acyclovir · Consider CMV esophagitis · If at high risk for invasive CMV, consider in patients at high risk for ganciclovir or foscarnet CMV disease fo · High resolution sinus · Add vancomycin if periorbital cellulitis noted · Sinus tenderness CT/orbit MRI · Add lipid amphotericin B preparation to · Periorbital cellulitis Sinus/ · ENT/ophthalmological cover possible aspergillosis and · Nasal ulceration nasal urgent evaluation mucormycosis in high risk patients with · Unilateral eye tearing suspicious CT/MRI findings n · Culture and stains/biopsy ot · Infectious disease consult c See Antibacterial Agents (FEV-A) for dosing, spectrum, and specific comments/cautions. l See Antifungal Agents (FEV-B) for dosing, spectrum, and specific comments/cautions. m See Antiviral Agents (FEV-C) for dosing, spectrum, and specific comments/cautions. n Posaconazole can be considered for salvage therapy or for intolerance to amphotericin B formulations. Posaconazole is not approved by the FDA as either primary or N salvage therapy for invasive fungal infections. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. FEV-4 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  15. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 ADDITIONS TO INITIAL EMPIRIC REGIMEN c,l,m INITIAL CLINICAL FINDING EVALUATION p n PRESENTATION All febrile neutropenic patients should receive broad-spectrum antibiotics (FEV-2) (DAY 0) · Metronidazole if C. difficile tio · Abdominal CT (preferred) or ultrasound Abdominal suspected · Alkaline phosphatase, transaminases, pain o · Ensure adequate anaerobic bilirubin, amylase, lipase therapy · Ensure adequate anaerobic bu therapy · Consider enterococcal q · Perirectal inspection Perirectal · Consider abdominal/pelvic CT pain coverage · Consider local care (sitz baths, stool softeners) tri · Clostridium difficile assay If C. difficile suspected, · Consider testing for rotavirus and consider adding oral See norovirus in winter months and during metronidazole pending assay Follow-up Diarrhea outbreaks is results: IV metronidazole (FEV-8) · Consider stool bacterial cultures and/or should be used in patient who parasite exam if travel/lifestyle history or cannot take oral agents community outbreak indicate exposure rD Vancomycini initially or add it if · Swab exit site drainage (if present) Entry or exit site site not responding after 48 h of for culture inflammation · Blood culture from each port of VAD empiric therapy Vascular access devices (VAD) · Remove catheter and culture Tunnel infection/ Blood culture from fo surgical wound port pocket infection, each port of VAD · Add vancomycini septic phlebitis c See Antibacterial Agents (FEV-A) for dosing, spectrum, and specific comments/cautions. i See Appropriate Use of Vancomycin and Other Agents for Gram-positive Resistant Infections (FEV-D). ot l See Antifungal Agents (FEV-B) for dosing, spectrum, and specific comments/cautions. m See Antiviral Agents (FEV-C) for dosing, spectrum, and specific comments/cautions. o Surgical and other subspecialty (eg, gastroenterology, interventional radiology) consultations should be considered for these situations as clinically indicated. p Lab studies include CMV antigens/PCR and abdominal/pelvic CT. N q Enterococcal colonization must be differentiated from infection. Vancomycin use must be minimized because of the risk of vancomycin resistance. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. FEV-5 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  16. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 ADDITIONS TO INITIAL EMPIRIC REGIMEN c,l,m EVALUATION r,s RISK CATEGORY n All febrile neutropenic patients should receive broad-spectrum antibiotics (FEV-2) tio · Azithromycin or fluoroquinolone added · Blood and sputum cultures · Nasal wash for respiratory viruses, to cover atypical bacteria rapid tests t · Consider adding: > Antiviral therapy during influenza · Legionella urine Ag test Low-risk bu outbreaks u · Consider BAL, particularly if no > Vancomycin or linezolid if MRSA response to initial therapy or if suspected diffuse infiltrates present tri Lung See infiltrates Follow-up · Azithromycin or fluoroquinolone added (FEV-8) · Blood and sputum cultures to cover atypical bacteria is · Nasal wash for respiratory viruses, · Consider adding: > Mold-active antifungal agent rapid tests t > Antiviral therapy during influenza · Legionella urine Ag test outbreaks u rD · Serum galactomannan or β-glucan Intermediate- > TMP-SMX if Pneumocystis jirovecii is to test in patients at risk for mold possible etiology High-risk infections > Vancomycin or linezolid if MRSA · Consider BAL, particularly if no suspected response to initial therapy or if · Adjunctive therapies may be considered diffuse infiltrates present · CT chest to better define infiltrates in certain patient populations v fo c See Antibacterial Agents (FEV-A) for dosing, spectrum, and specific comments/cautions. l See Antifungal Agents (FEV-B) for dosing, spectrum, and specific comments/cautions. m See Antiviral Agents (FEV-C) for dosing, spectrum, and specific comments/cautions. r Other diagnoses to consider include pulmonary edema, hemorrhage, and drug toxicities. ot s Assess for healthcare acquired pneumonia and/or resistant pathogens. t Rapid immunofluorescent viral antigen tests may be negative for H1N1 (swine flu). u Antiviral susceptibility of influenza strains is variable and cannot be predicted based on prior influenza outbreaks. In cases of seasonal influenza and pandemic strains (eg H1N1), it is necessary to be familiar with susceptibility patterns and guidelines on appropriate antiviral treatment. N v See Adjuvant Therapies (FEV-F). Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. FEV-6 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  17. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 ADDITIONS TO INITIAL EMPIRIC REGIMEN c,l,m INITIAL CLINICAL EVALUATION n PRESENTATION All febrile neutropenic patients should receive broad-spectrum antibiotics (FEV-2) (DAY 0) tio Consider aspirate or biopsy Consider vancomycin i Cellulitis for culture Consider vancomycin i Wound Culture bu Aspiration or scraping for Vesicular Consider acyclovir, VZV or HSV direct lesions famciclovir, or valacyclovir fluorescent antibody (DFA)/herpes virus cultures tri · Consider vancomycin i Disseminated Aspiration or biopsy for · Consider mold-active antifungal papules or bacterial, fungal, mycobacterial See other lesions cultures and histopathology therapy in high-risk patients is Follow-up (FEV-8) · Urine culture Urinary tract No additional therapy until rD · Urinalysis symptoms specific pathogen identified · Empiric therapy for presumed meningitis should include an anti-pseudomonal beta- lactam agent that readily enters CSF (eg, cefepime, ceftazidime, meropenem) plus · Infectious disease (ID) consult vancomycin i, plus ampicillin (to cover fo · CT and/or MRI Central nervous listeriosis). If meropenem is used, addition of · Lumbar puncture (if possible) system symptoms ampicillin is unnecessary because meropenem · Neurology consult is active against Listeria. · For encephalitis, add high-dose acyclovir 10 mg/kg/dose 3x/d) with hydration and monitor ot renal function c See Antibacterial Agents(FEV-A) for dosing, spectrum, and specific comments/cautions. i See Appropriate Use of Vancomycin and Other Agents for Gram-positive Resistant Infections (FEV-D). l See Antifungal Agents (FEV-B) for dosing, spectrum, and specific comments/cautions. N m See Antiviral Agents (FEV-C) for dosing, spectrum, and specific comments/cautions. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. FEV-7 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  18. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 PRINCIPLES OF DAILY FOLLOW-UP n tio bu RESPONDING · Decreasing fever trend See Follow-up · Daily site-specific H&P · Signs and symptoms of infection Therapy (FEV-9) · Daily review of laboratory tests and tri are stable or improving · Patient is hemodynamically stable cultures: document clearance of bacteremia, fungemia with repeat Evaluate overall blood cultures · Evaluate for response to therapy and is response to empiric therapy in 3-5 d v drug toxicity: > Fever trends (72-120 h) > Signs and symptoms of infection rD · Evaluation of drug toxicity including NONRESPONDING end-organ toxicity (LFTs and renal · Persistently or intermittently febrile function tests at least 2x/wk) · Signs and symptoms of infection are not See Follow-up improving Therapy (FEV-12) · Patient may be hemodynamically unstable fo · Persistent positive blood cultures ot N v See Adjunctive Therapies (FEV-F). Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. FEV-8 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  19. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 FOLLOW-UP THERAPY FOR n RESPONDING PATIENTS tio bu Documented infection · Bacteremia > Simple (no tissue site) > Complex (tissue infection with bacteremia) See Suggested Duration of Therapy tri · Pneumonia for Documented Infection (FEV-10) · Skin/soft tissue · Sinus · No change in initial empiric regimen · Fungal is · If patients started on “appropriate” · Viral initial vancomycin,i continue course of therapy rD · Initial antibiotic regimen should be continued at least until neutrophil count is ³ 500 cells/mcL and increasing See Suggested Duration of Therapy Fever of unknown origin fo for Fever of Unknown Origin (FEV-11) ot N i See Appropriate Use of Vancomycin and Other Agents for Gram-positive Resistant Infections (FEV-D). Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. FEV-9 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
  20. Guidelines Index NCCN Prevention and Treatment of ® Practice Guidelines Prevention/Treatment Infection TOC Cancer-Related Infections Discussion, References in Oncology – v.2.2009 SUGGESTED DURATION OF THERAPY FOR DOCUMENTED INFECTION c,l,m GENERAL GUIDELINES FOLLOW-UP THERAPY FOR n These are general guidelines and may need to be revised for individual patients. RESPONDING PATIENTS tio · Skin/soft tissue: 7-14 d · Bloodstream infection (uncomplicated) > Gram-negative: 10-14 d > Gram-positive: 7-14 d bu > S. aureus: at least 2 weeks after first negative blood culture and normal transesophageal echocardiogram (TEE) w > Yeast: ³ 2 wks after first negative blood culture > Consider catheter removal for bloodstream infections with Candida, · Initial antibiotic regimen should S. aureus, Pseudomonas aeruginosa, Corynebacterium jeikeium, tri generally be continued until Acinetobacter, Bacillus organisms, atypical mycobacteria, yeasts, neutrophil count is ³ 500 cells/mcL molds, vancomycin-resistant enterococci, and Stenotrophomonas and increasing maltophilia (category 2B) · Duration of antimicrobial therapy · Sinusitis: 10-21 d Documented is may be individualized based upon: · Catheter removal for septic phlebitis, tunnel infection, or port pocket infection > Neutrophil recovery infection > Rapidity of defervescence · Bacterial pneumonia: 10-21 d > Specific site of infection rD · Fungal (mold and yeast): > Infecting pathogen > Candida: minimum of 2 wks after first negative blood culture > Patient's underlying illness > Mold (eg, Aspergillus): minimum of 12 wks · Viral: > HSV/VZV: 7-10 d (category 1); acyclovir, valacyclovir, or famciclovir (uncomplicated, localized disease to the skin) fo > Influenza: Oseltamivir is approved by FDA for 5 d based on data from ambulatory otherwise healthy individuals with intact immune systems; longer courses (eg, at least 10 d) and until resolution of symptoms should be considered in the highly immunocompromised c See Antibacterial Agents (FEV-A) for dosing, spectrum, and specific comments/cautions. ot l See Antifungal Agents (FEV-B) for dosing, spectrum, and specific comments/cautions. m See Antiviral Agents (FEV-C) for dosing, spectrum, and specific comments/cautions. w A TEE should be considered in all cases of S. aureus bacteremia. In patients with conditions that may increase the likelihood of complications (eg, neutropenia, thrombocytopenia, mucositis), a transthoracic echocardiogram (TTE) may be performed initially and, if negative, a TEE should be performed when safe. A TEE N is more sensitive and preferred when compared with TTE. Note: All recommendations are category 2A unless otherwise indicated. Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. FEV-10 Version 2.2009, 08/28/09 © 2009 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
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