2b FEBRILE NEUTROPENIA Year 4 Internal Medicine Notes

2b FEBRILE NEUTROPENIA Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / IMED 4.2 / Mogere -- Slide 1 FEBRILE NEUTROPENIA Dr Alex Mogere Consultant physician Slide 2 Introdn Primary cause of mortality in 36% of cancer cases Secondary cause of mortality on 68% of cancer cases Most c’m cause of mortality and morbidity in cancer pts Ns are the most abundant type of wbcs in mammals 1st responders of inflammatory cells following bacterial infection Short lifespan of 4-5 days in circulation Slide 3 Febrile neutropenia Is a single oral temp 38.3 C or Temp 38 for 1 hour or more Neutrophil count < 500 cells/uL C’m complication of chemotherapy Slide 4 Abnormalities that predispose to infection: Lymphoid system Pts with ab deficiency are predisposed to overwhelming infection with encapsulated bacteria (including S. pneumoniae, H. influenzae, and N. meningitidis) Pts undergoing intensive chemotx for any form of cancer will have not only defects due to granulocytopenia but also lymphocyte dysfunction, which may be profound. \nThus, these patients—especially those receiving glucocorticoid-containing regimens or drugs that inhibit either T cell activation (calcineurin inhibitors or drugs like fludarabine, which affect lymphocyte function) or cytokine induction—should be given prophylaxis for Pneumocystis pneumonia. Slide 5 Cont. Abnormalities that predispose to infection: Lymphoid system Pts receiving Tx that eliminates B cells ((e.g., with anti-CD20 antibodies or rituximab) are especially vulnerable to intercurrent viral infections The incidence of progressive multifocal leukoencephalopathy(PML) (caused by JC virus) is elevated in these patients. Slide 6 Hematopoietic system Aerobic pathogens (both gram-positive and gram negative) predominate in all series,\nInfections with anaerobic organisms are uncommon Tuberculosis and malaria are common causes of fever in the developing world and may present in this setting as well.\nLike most immunocompromised patients, neutropenic patients are threatened by their own microbial flora, including gram-positive and gram-negative organisms found commonly on the skin and mucous membranes and in the bowel Slide 7 Hematopoietic system the initial regimen should target all pathogens likely to be the initial causes of bacterial infection in neutropenic hosts.\nadministration of antimicrobial agents is routinely continued until neutropenia resolves—i.e., the granulocyte count is sustained above 500 μL for at least 2 days. \nIn some cases, patients remain febrile after resolution of neutropenia.\nCauses may include:(1) fungal infection, (2) bacterial abscesses or undrained foci of infection, and (3) drug fever (including reactions to antimicrobial agents as well as to chemotherapy or cytokines). Slide 8 Hematopoietic system If the patient remains febrile, a search for viral diseases or unusual pathogens is conducted while unnecessary cytokines and other drugs are systematically eliminated from the regimen. Slide 9 Algorithm for the diagnosis and Tx of fever and neutropenia Slide 10 Antibacterial tx in cancer pts In the initial regimen, it is necessary to use antibiotics active against both gram-negative and gram-positive bacteria \nMonotherapy with an aminoglycoside or an antibiotic lacking good activity against gram-positive organisms (e.g., ciprofloxacin or aztreonam) is not adequate in this setting.\nThe agents used should reflect both the epidemiology and the antibiotic resistance pattern of the hospital.\nIf the pattern of resistance justifies its use, a single third-generation cephalosporin constitutes an appropriate initial regimen in many hospitals. Slide 11 Antibacterial tx in cancer pts Most standard regimens are designed for patients who have not previously received prophylactic abx.\nThe devt of fever in a patient who has received abx affects the choice of subsequent tx, which should target resistant organisms and organisms known to cause infections in patients being txd with the abx already administered. Randomized trials have indicated the safety of oral abx regimens in the tx of “low-risk” pts with fever and neutropenia. Outpts who are expected to remain neutropenic for <10 days and who have no concurrent medical problems (such as hypotension, pulmonary compromise, or abdominal pain) can be classified as low risk and treated with a broadspectrum oral regimen. Slide 12 Antibacterial tx in cancer pt Several large-scale studies indicate that prophylaxis with a fluoroquinolone (ciprofloxacin or levofloxacin) decreases morbidity and mortality rates among afebrile patients who are anticipated to have neutropenia of long duration. Slide 13 Antibacterial tx in cancer pt Commonly used antibiotic regimens for the treatment of febrile patients in whom prolonged neutropenia ( 7 days) is anticipated include\n(1) ceftazidime or cefepime,\n(2) piperacillin/tazobactam, or\n(3) imipenem/cilastatin or meropenem.\nAll three regimens have shown equal efficacy in large trials Imipe