Guidelines for the Treatment of Patients with Neutropenia and Fever

Guidelines for the Treatment of Patients with Neutropenia and FeverRelated documents: UK HealthCare Guidelines for Antifungal Use in Adult Hematopoietic Stem CellTransplant and Leukemia Patient.DefinitionsFever• Single oral temperature ≥ 38.3°C (101.0°F) or• Temperature of ≥ 38.0°C (100.4°F) for ≥ 1 hour or twice in 24 hoursNeutropenia• Absolute neutrophil count (ANC) < 0.5 x 10 9 /L, or• ANC of < 1 x 10 9 /L with a predicted decline to < 0.5 x 10 9 /LA score of ≥ 21 on the following criteria predicts low risk(NOTE: hematologic malignancy and stem cell transplant patients are automatically HIGH risk):CharacteristicPatient RiskExtent of illness (choose one score)No symptomsMild symptomsModerate symptomsScoreNo hypotension 5No chronic obstructive pulmonary disease 4Solid tumor or no fungal infection 3No dehydration 3Outpatient at onset of fever 3Age < 60 years 2553Initial EvaluationCultures prior to initial antimicrobial therapy• Blood cultures from all ports of indwelling catheters and at least 1 peripheral culture; if noindwelling catheters, then 2 peripheral cultures drawn 30 minutes apart• Urinalysis and urine culture• Sputum culture if productive cough present

• If watery diarrhea present, stool culture for routine pathogens (x1), ova and parasites (x1) and C.difficileLaboratory/Radiology evaluation• Electrolytes• Serum creatinine and blood urea nitrogen• Liver enzymes• CBC with differential• Chest X‐Ray if symptoms dictateSubsequent EvaluationCultures prior to changes in antimicrobial therapy• No more than 2 sets of blood cultures per 24 hour period• If initial urine/sputum/stool cultures negative and no new symptoms present, do not repeatculturesLaboratory reassessment• Reassess labs at least every 3 days, more frequent if risk for nephrotoxicity (ex: amphotericin,aminoglycosides)Initial Antimicrobial TherapyIf indwelling catheter is present and appears infected, remove catheter and beginadministration of antibiotics.For inpatients, all new antimicrobial agents should be ordered, prepared, and administeredSTAT.Oral Therapy (a consideration for low­risk patients)• Levofloxacin 750mg daily +amoxicillin/clavulanate 875mg twice a dayIntravenous Therapy• Cefepime 2g every 8 hours OR Piperacillin/tazobactam 4.5g every 6 hours• Consider adding tobramycin to the above regimen (contact pharmacist for dosing)• Consider adding vancomycin when at least one of the following conditions is present (contactpharmacist for dosing)o Clinically suspected serious catheter‐related infections (e.g., bacteremia, cellulitis)o Colonization with penicillin‐ and cephalosporin‐resistant S. pneumoniae or methicillinresistantStaphylococcus species (ex: MRSA, MRSE)o Positive results of blood culture for gram‐positive bacteria before final identification andsusceptibility testing

oooHypotension or other evidence of cardiovascular instabilitySubstantial mucositisProphylaxis with quinolones for afebrile neutropenic patients before onset of fever• For patients with serious beta‐lactam allergieso Aztreonam 2g every 8 hours + vancomycin (contact pharmacist for dosing)• For patients known to be colonized with multidrug‐resistant bacteria,o Tailor therapy accordinglySubsequent Antimicrobial TherapyReassess after 3­5 days of treatmentIf Afebrile• Clinically stable, cultures positive:o Caution should be used in prescribing antibiotics for a single blood culture positive for S.epidermidis without clinical signs of infection (consider contamination)o If cultures reveal a source of infection, alter antibiotics based on cultures and treat for astandard length of time• Clinically stable, cultures negative:ooContinue antibiotics until ANC > 500 or 5‐7 days after last fever (maximum 3 weeks)Consider switching to oral therapy• Levofloxacin 750 mg daily plus amoxicillin‐clavulanate 875 mg twice a dayIf Febrile• Consider other factors or sources of infectiono Nonbacterial infectiono Resistant or slow‐responding bacterial infectiono Secondary infectiono Inadequate serum and tissue levels of the antibiotic(s)o Adverse medication effecto Infection at avascular site (abscesses, or catheters)• Clinically stable, cultures negativeo Continue antibiotics until ANC > 500 (maximum 3 weeks)o Consider switching to oral therapy• Levofloxacin 750 mg daily plus amoxicillin‐clavulanate 875 mg twice a dayo If included in primary treatment, consider discontinuation of vancomycin• Clinically unstable, cultures negative• Consult Infectious Diseases• Consider change or addition of antibiotic• Consider addition of an antifungalooVoriconazole 6mg/kg every 12 hours x2 doses, then 4mg/kg every 12 hours ORLiposomal Amphotericin B 3mg/kg daily. This is the primary option for patientswho have received posaconazole prophylaxis prior to becoming febrile.

Major Reference:Hughes, et al. 2002 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer.Clin Inf Dis 2002;34:730‐51.