Febrile neutropenia medical therapy
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Febrile Neutropenia Microchapters |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: F and N; fever and neutropenia; FN; hot and low; hot leuk; neutropenic fever; neutropenic fever syndrome; neutropenic sepsis
Overview
Generally, patients with febrile neutropenia are treated with empirical antibiotics until the neutrophil count has recovered (Absolute neutrophil counts greater than 500/mm3) and the fever has abated; if the neutrophil count does not improve, treatment may need to continue for two weeks or occasionally more. In cases of recurrent or persistent fever, an antifungal agent should be added.
Medical Therapy
IDSA Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: Recommendations for Antibiotic Therapy
| Class A |
| "1. High-risk patients require hospitalization for IV empirical antibiotic therapy; monotherapy with an anti- pseudomonal b-lactam agent, such as cefepime, a carbapenem (meropenem or imipenem-cilastatin), or piperacillin-tazobactam, is recommended. (Quality of Evidence: I)" |
| "2. Vancomycin (or other agents active against aerobic gram- positive cocci) is not recommended as a standard part of the initial antibiotic regimen for fever and neutropenia (A-I). These agents should be considered for specific clinical indications, including suspected catheter-related infection, skin or soft-tissue infection, pneumonia, or hemodynamic instability. (Quality of Evidence: I)" |
| "3. Most penicillin-allergic patients tolerate cephalosporins, but those with a history of an immediate-type hypersensitivity reaction (eg, hives and bronchospasm) should be treated with a combination that avoids b-lactams and carbapenems, such as ciprofloxacin plus clindamycin or aztreonam plus vancomycin. (Quality of Evidence: II)" |
| "4. Low-risk patients should receive initial oral or IV empirical antibiotic doses in a clinic or hospital setting; they may be transitioned to outpatient oral or IV treatment if they meet specific clinical criteria. Ciprofloxacin plus amoxicillin-clavulanate in combination is recommended for oral empirical treatment. (Quality of Evidence: I)" |
| "5. Patients receiving fluoroquinolone prophylaxis should not receive oral empirical therapy with a fluoroquinolone. (Quality of Evidence: III)" |
| "6. Hospital re-admission or continued stay in the hospital is required for persistent fever or signs and symptoms of worsening infection. (Quality of Evidence: III)" |
| "7. Modifications to the initial antibiotic regimen should be guided by clinical and microbiologic data. (Quality of Evidence: II)" |
| "8. Unexplained persistent fever in a patient whose condition is otherwise stable rarely requires an empirical change to the initial antibiotic regimen. If an infection is identified, antibiotics should be adjusted accordingly. (Quality of Evidence: I)" |
| "9. Documented clinical and/or microbiological infections should be treated with antibiotics appropriate for the site and for the susceptibilities of any isolated organisms. (Quality of Evidence: I)" |
| "10. If vancomycin or other coverage for gram-positive organisms was started initially, it may be stopped after 2 days if there is no evidence for a gram-positive infection. (Quality of Evidence: II)" |
| "11. Patients who remain hemodynamically unstable after initial doses with standard agents for neutropenic fever should have their antimicrobial regimen broadened to include coverage for resistant gram-negative, gram-positive, and anaerobic bacteria and fungi. (Quality of Evidence: III)" |
| "12. Low-risk patients who have initiated IV or oral antibiotics in the hospital may have their treatment approach simplified if they are clinically stable. An IV-to-oral switch in antibiotic regimen may be made if patients are clinically stable and gastrointestinal absorption is felt to be adequate. (Quality of Evidence: I)" |
| "13. If fever persists or recurs within 48 h in outpatients, hospital re-admission is recommended, with management as for high-risk patients. (Quality of Evidence: III)" |
| "14. Empirical antifungal coverage should be considered in high-risk patients who have persistent fever after 4–7 days of a broad-spectrum antibacterial regimen and no identified fever source. (Quality of Evidence: II)" |
| Class C |
| "1. KPCs: Consider early use of polymyxin-colistin or tigecycline. (Quality of Evidence: III)" |
| "2. Alternatively, if an appropriate treatment course has been completed and all signs and symptoms of a documented infection have resolved, patients who remain neutropenic may resume oral fluoroquinolone prophylaxis until marrow recovery. (Quality of Evidence: III)" |
| Class B |
| "1. Other antimicrobials (aminoglycosides, fluoroquinolones, and/or vancomycin) may be added to the initial regimen for management of complications (eg, hypotension and pneumonia) or if antimicrobial resistance is suspected or proven. (Quality of Evidence: III)" |
| "2. Modifications to initial empirical therapy may be considered for patients at risk for infection with the following antibiotic-resistant organisms, particularly if the patient’s condition is unstable or if the patient has positive blood culture results suspicious for resistant bacteria. (Quality of Evidence: III)" i. MRSA: Consider early addition of vancomycin, linezolid, or daptomycin ii. VRE: Consider early addition of linezolid or daptomycin iii. ESBLs: Consider early use of a carbapenem |
| "3. Afebrile neutropenic patients who have new signs or symptoms suggestive of infection should be evaluated and treated as high-risk patients. (Quality of Evidence: III)" |
| "4. Other oral regimens, including levofloxacin or ciprofloxacin monotherapy or ciprofloxacin plus clindamycin, are less well studied but are commonly used. (Quality of Evidence: III)" |
| "5. Selected hospitalized patients who meet criteria for being at low risk may be transitioned to the outpatient setting to receive either IV or oral antibiotics, as long as adequate daily follow-up is ensured. (Quality of Evidence: III)" |
| "6. In patients with clinically or microbiologically documented infections, the duration of therapy is dictated by the particular organism and site; appropriate antibiotics should continue for at least the duration of neutropenia (until ANC is ≥500 cells/mm3) or longer if clinically necessary. (Quality of Evidence: III)" |
| "7. In patients with unexplained fever, it is recommended that the initial regimen be continued until there are clear signs of marrow recovery; the traditional endpoint is an increasing ANC that exceeds 500 cells/mm3. (Quality of Evidence: II)" |