Empiric antibiotic treatment of fever in the neutropenic patient July 2011 *

Introduction and Definitions: Pyrexia (temperature >38.0 C on two occasions separated by one hour or temperature >38.5 C on one occasion) in the neutropenic (<1.0 x 109/L) patient. While non-infective causes are possible, infection must be considered in all neutropenic patients with a fever. Assessment and Investigations: Before commencing antibiotic therapy, the patient should be thoroughly examined, including examination of the chest, mucosa, abdomen, all intravenous lines, peri-rectal areas and other possible sites of infection, such as wounds or surgical sites. Screening investigations before commencement of antibiotics should include: peripheral and central line blood cultures (if patients have a line, please state on the blood culture request form which type of line is present), CXR, MSU, swab from central line sites/wounds and if symptomatic, stool sample (for C&S and C. diff toxin) and sputum for C&S. If the patient has coryzal symptoms, consider nasopharyngeal aspirates for immunofluoresence and viral culture. A careful review of recent microbiology results as well as recent antibiotic use should be undertaken as this will guide choice of initial empiric antibiotic treatment. * Early consultation with a microbiologist is recommended to discuss previous positive microbiology and appropriate antibiotic choice. Empiric Antibiotic Treatment: Below is a suggested step wise introduction of antibiotics in the neutropenic patient who requires antibiotic treatment. Antibiotic treatment may be subsequently altered on the basis of positive microbiology results Piperacillin-tazobactam1, 2 4.5g QDS IV + gentamicin 3 5mg/kg OD IV (Aim for pre-dose levels of <1mg/L for gentamicin)

Fever settles and blood cultures negative continue antibiotics for 5 7 days

Ongoing pyrexia after 48 hours, add vancomycin 1g bd (if central line in situ and evidence of line infection or patient has severe mucositis. The addition of vancomycin may be indicated before 48 hours. Aim for pre-dose levels of 10 15mg/L

Ongoing pyrexia after a further 48 hours, add caspofungin 70mg stat, then 50mg OD IV . Consider HRCT thorax and removal of any lines in situ

1. May be used as monotherapy if no evidence of septic shock (systolic BP<100), patient is haemodynamically stable and duration of neutropenia is less than 10 days. 2. Penicillin allergy: substitute with ceftazidime 2g TDS IV Penicillin anaphylaxis: contact microbiology for advice 3. Regular serum assays (pre-dose samples) and dose adjustment in renal impairment required. If fever persists despite antibacterial and antifungal therapy contact microbiologist for advise. Consideration should be given to other infective causes such as: CMV infection. CMV can present as pneumonitis, gastrointestinal or CNS symptoms. These patients should have an EDTA blood sample collected together with BAL and biopsy (as appropriate clinically) sent for CMV PCR. Treatment: ganciclovir 5mg/kg BD (dose adjustment in renal impairment). Vesicular or ulcerative lesions. Consider HSV and VZ. Add aciclovir 5mg/kg TDS IV for herpes simplex, 10mg/kg TDS IV for VZ infection. For early lesions if not widespread or haemorrhagic consider oral aciclovir 400mg five times a day for HSV, 800mg five times a day for VZ. Respiratory viruses. These include RSV, Influenza, and Adenovirus etc. BAL should be sent for immunofluoresence and viral culture. Sinus tenderness or nasal ulcerative lesions . Suspect fungal infection e.g. aspergillus or zygomycetes such as mucor. Pneumocystis jirovecii (carinii) pneumonia. These patients should have BAL sent for staining to histopathology (cytology) and if indicated treatment with cotrimoxazole , 120mg/kg/daily in 2 4 divided doses (dose adjustment in renal impairment) Discontinuing antibiotics: In those patients where cultures are negative and non-infective causes of pyrexia are considered more likely, antibiotics may be discontinued after 5 days, or sometimes earlier if the fever has resolved for >48 hours or the patient is clinically well and especially if the neutrophil count has risen to >0.5x109/L. In those patients in whom an infective cause is likely but has not been identified, continue antibiotics so that patient receives at least 10 days treatment in total or until neutrophil count >0.5x109/L. If no organisms are isolated or identified by other means as the cause of the fever, and the patient is apyrexial, when the neutrophil count has recovered oral antibiotics are not usually necessary.

Antimicrobial Stewardship Committee

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Prof H Humphreys

Dr F Fitzpatrick

Dr K Burns

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