Chapter 13
Antimicrobial Management of Patients with Fever and Neutropenia Following Hematopoietic Stem Cell Transplantation
13.1 Stepwise approach to empiric antimicrobial therapy in febrile neutropeniaa
| Step | Therapy | Notes |
| Step 1: Initial therapy | Anti-pseudomonal beta-lactam (e.g. piperacillin-tazobactam) + aminoglycoside | Alternatives: monotherapy - piperacillin-tazobactam, cefepime or a carbapenem. Other agents may be used as part of the initial regimen (e.g., fluoroquinolones or vancomycin) depending on the presence of complications (e.g., hypotension) or if there are specific concerns about antimicrobial resistance. |
| Step 2: Afebrile within first 3 days | No etiology identified: Low riskc – change to an oral agent (e.g. amoxicillin-clavulanate + ciprofloxacin) High risk – continue same antibiotics Etiology identified: adjust to most appropriate treatment |
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| Step 3: Persistent fever during first 3–5 days | If no clinical change: continue antibiotics; consider stopping vancomycin if cultures are negative | |
| If progressive disease: change antibiotics and add antifungal therapy (see Section 13.2) | Regimens vary and depend on local flora. Broader and/or a different class of antibiotics may be used | |
| Step 4: Persistent fever after 5–7 days | Consider adding antifungal therapy ∓ antibiotic changes | Fungal work-up initiated at days 4-5 (e.g. CT chest/abdomen, serum galactomannan). Some experts will start antifungal therapy earlier, e.g. at day 3 For antifungal agents, see Section 13.2 |
| Step 5: Reassess duration of antimicrobial therapy | Duration of antimicrobials is dependent on neutrophil recovery and whether etiology was identified | Antibiotics should be continued for at least the duration of neutropenia. Longer durations may be required as clinically indicated. |
ANC, Absolute neutrophil count; CT, computed tomography.
aFever is defined as single oral temperature of ≥ 38.3 °C or a temperature of ≥ 38.0 °C for at least 1 hour. Neutropenia is defined as a count < 0.5 × 109/L add cells/L. The units should be × 109 cells/L or an ANC that is expected to decrease to < 0.5 × 109/L during the next 48 hours.
bVancomycin use is indicated if there is severe mucositis, obvious catheter-related infection, hypotension, prior colonization with MRSA or penicillin/cephalosporin-resistant pneumococci, recent or current fluoroquinolone prophylaxis.
cIndicators of high-risk for severe infection include: anticipated prolonged (>7 days duration) and profound neutropenia (ANC < 0.1 × 109 cells/L) and/or co-morbid conditions, including hypotension, pneumonia, new-onset abdominal pain, or neurologic changes.
13.2 Agents for empiric antifungal therapy in febrile neutropenia
| Acceptable agents | Comments |
| Lipid amphotericn B products Amphotericin B lipid complex Liposomal amphotericin B |
Conventional amphotericin B is usually not preferred post-HSCT due to nephrotoxicity and less evidence of efficacy |
| Echinocandins Caspofungin Micafungin |
The echinocandins are favored in patients with renal impairment or are intolerant of amphotericin products |
| Azoles Voriconazole Posaconazole |
Fluconazole is often used as prophylaxis HSCT patients. This limits its used for empiric therapy in persistently febrile neutropenics More pediatric data are required for posaconazole |
HSCT, hematopoietic stem cell transplant.
Freifeld AG, 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. CID 2011;52(4):e56–e93.