Fever and Neutropenia FN

Definition

• Fever: single oral temp :38.3 C (101F) or .38 C (100.4 F) for ,1 h

• Neutropenia: ANC 500 cells p.1 or 1000 cells pilwith predicted nadir 500 cells jil

Pathophysiology and microbiology

• Predisposing factors: catheters, skin breakdown, mucositis throughout Gl tract, obstruction

(lymphatics, biliary tract. Gl. urinary tract), immune defect associated with malignancy

• Majority of episodes thought to result from seeding of bloodstream by Gl flora

• GNRs (especially P. aeruginosa) were historically most common

• Gram infections have recently become more common (60-70% of identified organisms)

• Fungal superinfection often results from prolonged neutropenia & antibiotic use

• Infection with atypical organisms and bacterial meningitis is rare Prevention

• Levofloxacin (500 mg qd) I febrile episodes & bacterial infections in chemo-related high-

risk neutropenic patients: no difference in mortality (NEJM 2005:353:977.988)

Diagnostic evaluation

• Exam: skin, oropharynx, lung, perirectal area, surgical & catheter sites: avoid DRE

• Labs: CBC with differential, electrolytes. BUN Cr. LFTs. U A

• Micro: blood (peripheral & through each indwelling catheter port), urine. & sputum cx;

for localizing s s -* ✓ stool, peritoneal. CSF or skin biopsy cultures

• Imaging: CXR: for localizing s s — CNS. sinus, chest, or abdomen pelvis imaging

• Caveats: neutropenia — impaired inflammatory response • exam and radiographic findings may be subtle: absence of neutrophils by Gram stain does not r o infection

Risk stratification (factors that predict lower risk)

• History: age 60. no symptoms, no major comorbidities, cancer in remission, solid tumor.

no h o fungal infection or recent antifungal Rx

• Exam: temp 39 C. no tachypnea, no hypotension, no A MS. no dehydration

• Studies: ANC 100 cells jjlI. anticipated duration of neutropenia 10 d. normal CXR Initial antibiotic therapy

• Empiric regimens should include a drug with antipseudomonal activity

• PO abx can be used in low-risk Pts: Cipro + amoxicillin-davulanate (nejm 1999:341:305.312)

• IV antibiotics: no clearly superior regimen: monotherapy or 2-drug regimens can be used

Monotherapy: ceftazidime, cefepime. imipenem-cilastatin. or meropenem 2-drug therapy: aminoglycoside + antipseudomonal (3-lactam PCN-allergic: levofloxacin aztreonam or aminoglycoside

• Vancomycin added in select cases (hypotension, indwelling catheter, severe mucositis.

MRSA colonization, h o quinolone prophylaxis), discontinue when cultures ) * 48 h

Modification to initial antibiotic regimen

• Low-risk Pts who become afebrile w in 3-5 d can be switched to PO antibiotics

• Empiric antibiotics are changed for fever -3-5 d with progressive disease

• Antifungal therapy is added for neutropenic fever -5 d liposomal amphotericin B. caspofungin, micafungin. anidufafungin. voriconazole, posaconazole all options (nejm 2002:346 225 & 2007:356:348)

Duration of therapy

• Known source: complete standard course (eg. 14 d for bacteremia)

• Unknown source: continue antibiotics until afebrile and ANC 500 cells jil

• Less clear when to d/c abx when Pt is afebrile but prolonged neutropenia

Role of hematopoietic growth factors (jco 2000:183558)

• Granulocyte (G-CSF) and granulocyte-macrophage (GM-CSF) colony-stimulating factors can be used as 1° prophylaxis when expected FN incidence 40% or as 2° prophylaxis after FN has occurred in a previous cycle (to maintain dose-intensity for curable tumors)

• Colony-stimulating factors can be considered as adjuvant therapy in high-risk FN Pts

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