GUIDELINES FOR ANTIBIOTIC MANAGEMENT OF

NEUTROPENIC SEPSIS OR FEBRILE NEUTROPENIA IN ADULT

ONCOLOGY PATIENTS AT THE EDINBURGH CANCER CENTRE
IF febrile (>38 o C) or other signs or symptoms of infection and suspected neutropenia (<1x109/litre):
• Admit all patients for initial assessment:
• Assign to high or standard risk according to SEWS score and MASCC score (see definition below) and record scores in notes.
• Identify specific risks such as central venous catheters, previous MRSA colonisation or possible atypical respiratory pathogens.
• Consult notes overleaf for recommended investigations.
• Discuss all patients with specialist registrar (SpR).

MASCC risk-index score (see note 6 overleaf)

Characteristic Score
Burden of illness (including underlying cancer and current illness):
None or mild symptoms (e.g. Performance status 0 and SEWS score < 2) 5
Moderate symptoms (e.g. Performance status 1 or 2 and SEWS score < 4) 3
Severe symptoms (e.g. Performance status 3 or 4 or SEWS score > 4) 0
No hypotension (systolic BP >90 mmHg) 5
No chronic obstructive pulmonary disease 4
No previous fungal infection 4
No dehydration requiring parenteral fluids 3
Outpatient status at onset of fever 3
Age <60 years 2

The maximum theoretical total score is 26. Patients with a MASCC score index 21 are standard risk and <21 are high risk.
NB: Any SEWS score > 6 is automatically high risk, independent of the MASCC score.

STANDARD RISK PATIENTS HIGH RISK PATIENTS

MASCC SCORE > 21 AND SEWS SCORE < 6 MASCC SCORE <21 OR SEWS SCORE > 6

IV tazocin 4.5g qds (see note 3 overleaf) IV tazocin 4.5g qds (see note 3 overleaf)
Note: no gentamicin IV gentamicin (refer to gentamicin guidance table on
AND cover any specific risks identified page 4 for dose and see note 3 overleaf).
e.g. vancomycin for MRSA or central line infection (see AND cover any specific risks identified
note 4 overleaf) e.g. vancomycin for MRSA or central line infection (see
clarithromycin for atypical pneumonias note 4 overleaf)
See note 5 overleaf if allergy to penicillin or other -lactam clarithromycin for atypical pneumonias

Reassess antibiotics after 48 hrs therapy (or earlier if Reassess antibiotics after 72 hrs therapy (or earlier if
concerned). If etiologic agent identified, cover it concerned). If etiologic agent identified, cover it (but also
(but also continue broad spectrum coverage). continue broad spectrum coverage).

Afebrile and well Febrile or Unwell Febrile or Unwell Well

Inform SpR INITIATE HIGH RISK 2nd line therapy: Inform SpR
When afebrile and ALGORITHM IV meropenem 1g tds Continue Tazocin
recovering count Discuss with SpR IV vancomycin (see note 4 overleaf). but stop gentamicin.
>0.5x109/litre for Inform consultant Consider changing IV access devices. When afebrile and
a total of 24 Discuss with consultant and take recovering count
hours, switch to microbiological advice >0.5x109/litre for a
oral coamoxiclav total of 24 hours,
and ciprofloxacin switch to oral
and consider coamoxiclav and
discharge. Reassess after 72hrs on 2nd line therapy ciprofloxacin and
Complete total of (or earlier if concerned). consider discharge.
7 days antibiotics. If aetiologic agent identified, cover it. Complete total of 7
If not and unwell or febrile, then consider days antibiotics.
antifungal and G-CSF therapy.
Version 10: Active from March 2008 Discuss with consultant and take
Prepared by Professor Jodrell, Dr Williamson and 1
microbiological advice
Dr Hayward. Review date January 2009.
Notes to ‘GUIDELINES FOR ANTIBIOTIC MANAGEMENT OF NEUTROPENIC SEPSIS OR
FEBRILE NEUTROPENIA IN ADULT ONCOLOGY PATIENTS AT THE EDINBURGH CANCER
CENTRE’. If in doubt seek senior advice immediately, in order to AVOID DELAYING therapy.

1. Separate guidelines apply to haematology patients and to paediatric patients.

2. Investigation should include:

a. A meticulous and well documented physical examination including mouth and perineum.
b. Peripheral blood cultures are required, and central blood cultures if a central line is
present. These cultures should be taken urgently before antibiotic therapy is commenced, and
should be repeated daily whilst febrile.
c. Urine culture and CXR are required, but antibiotic therapy should not be delayed for trips
to radiology or if micturition is not immediately possible. High risk or unwell patients must not
leave the ward for longer than one hour and must be escorted.

d. Stool cultures and Clostridium difficile toxin testing are required if diarrhoea present.
e. Daily CRP, FBC, urea, creatinine, electrolytes and liver function tests are recommended
during therapy, and these must be requested urgently on first admission (telephone to alert the
laboratory staff).

3. Because of the importance of prompt antibiotic therapy in neutropenic sepsis, the first dose of
gentamicin if required can be given without knowledge of renal function in patients with no prior
history of renal impairment. If there is a clear history of prior renal impairment then refer to NHS
Lothian University Hospitals Division Antibiotic Prescribing Guidelines in Adults. After the first dose
gentamicin levels should be monitored and doses adjusted as specified in those guidelines. The relevant
extracts from those guidelines dated December 2007 is adapted and appended to this document for ease
of reference.

The first dose of Tazocin 4.5g IV is safe whatever the renal function. Thereafter, if the calculated
creatinine clearance is less than 80 ml/min, dosing frequency should be adjusted according to renal
function as specified in the NHS Lothian University Hospitals Division Antibiotic Prescribing
Guidelines in Adults. Use Ideal Body Weight for this calculation.

4. Use of vancomycin requires assessment of renal function and monitoring of drug levels, as per
NHS Lothian University Hospitals Division Antibiotic Prescribing Guidelines in Adults (copies on all
wards). After 3 days on vancomycin, consider stopping the drug if no relevant culture isolates obtained
(discuss with microbiology). Teicoplanin can be used instead of vancomycin to facilitate early
discharge or outpatient management. An infusion rather than a bolus is required for central line
infections. Discuss Teicoplanin use with microbiology.

5. If there is a clear cut history of severe reaction to any -lactam drugs (e.g anaphylaxis,
angioedema, bronchospasm) then all -lactam drugs carry risk, including the penicillins co-amoxiclav
and tazocin, all the cephalosporins, and also meropenem. Therefore if severe -lactam reaction replace
oral coamoxiclav with oral clarithromycin 500 mg bd and oral metronidazole 400 mg tds throughout
the guideline. For intravenous therapy a combination of a glycopeptide (vancomycin or teicoplanin)
with gentamicin and metronidazole may be appropriate. If the -lactam reaction consists of a rash only
it should be safe to replace tazocin with ceftazidime (2g tds)/gentamicin. Ceftazidime has less good
staphylococcal cover. If in doubt discuss with microbiology.

6. The MASCC score used here is adapted by inclusion of guidance on ‘burden of illness’ by
reference to the patients underlying performance status and to the SEWS score utilised throughout
LUHD for assessment of acutely ill patients. The MASCC score is validated and published (Innes et al
Support Care Cancer. 2007 Sep 25).

7. This is Version 9 adapted from the Infectious Diseases Society of America 2002 guidelines, CID
2002:34(739). Prepared and updated in consultation with Dr Emma Williamson, Microbiology, NRIE,
modified and ratified by the Cancer Therapy Advisory Committee of the Edinburgh Cancer Centre.
Please address comments to larry.hayward@luht.scot.nhs.uk.

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 Using repeated doses of gentamicin in adults:
The Hartford Nomogram and renal impairment protocol
Adapted for ease of reference from
NHS Lothian – University Hospitals Division Antibiotic Prescribing Guidelines in Adults – 12/2007

Indications for gentamicin

Gentamicin is the most toxic antibiotic in common use. This repeat-dosing protocol therefore
recommends its use only for severe infections known or suspected of being caused by Gram-negative
bacteria resistant to first-line drugs. These include:
• Empirical therapy in neutropenic sepsis
• Therapy for severe sepsis due to pathogens known or suspected of being resistant to other
suitable agents (e.g. co-amoxiclav, ceftriaxone, ciprofloxacin).

Gentamicin has substantial renal and oto-toxicity. To avoid toxicity, therapeutic monitoring of serum
levels is required. This document describes:
• How to calculate a dose using Ideal Body Weight (IBW)
• How to monitor blood levels for patients with normal renal function (CrCl >60ml/min) using
the Hartford nomogram
• How to monitor blood levels for patients with impaired renal function (CrCl 20-60ml/min).

The following are at increased risk of toxicity, and gentamicin should be used with caution:
• Volume-depleted patients,
• Patients with deteriorating renal function from any cause
• Patients on other nephrotoxic drugs such as NSAIDs, ACE inhibitors or diuretics
• Patients with actual weight substantially less than IBW.

Therapy for endocarditis is excluded from this protocol: consult pharmacist or microbiologist for
appropriate gentamicin dosing regimen. Therapy for pregnant patients is excluded from this protocol:
consult obstetrician or microbiologist for an alternative regimen. Seek pharmacy advice if patient has
ascites.

Because of the importance of prompt antibiotic therapy in severe sepsis, the first dose of gentamicin
can be given without knowledge of renal function in patients with no history of renal impairment, see
Section 1 below. If there is a clear history of prior renal impairment refer to Section 2 and 3 below. If
in doubt seek senior advice immediately, in order to avoid delaying therapy.

To calculate gentamicin dose

1) Before dosing gentamicin you will need a calculator and the following:
• Patient’s age
• Patient’s height
• Patient’s ideal body weight, calculated from Table A (below)
• Recent creatinine (micromol/l)

2) Determine Creatinine Clearance (CrCl) using the Cockcoft and Gault equation:

CrCl (ml/min) = (140 - age[years]) x IBW[kg] x 1.23 [male] or 1.04 [female]

serum creatinine [micromol/l]

• CrCl must be calculated using the above equation: note dependence on gender
• Estimated GFR [eGFR] from the patient’s biochemistry result is not appropriate.
• If serum creatinine is less than 60micromol/l, use 60micromol/l

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 Section 1 Patients not known to have renal impairment (CrCl >60ml/min)

The dose is 7 mg/kg of the patients’ ideal body weight (derived from their height), in 100ml of
glucose 5% or sodium chloride 0.9% administered by intravenous infusion over 1 hour. Individualised
doses are shown in Table A below.
• Record patients’ height
• Refer to table A below to obtain appropriate dose.
• If height falls out-with table calculate IBW (formula below table) and then multiply by
7mg/kg to obtain dose (round to nearest 20mg).
• Record the time infusion was started.
• Monitor serum levels 6-14hours after the start of the first dose.

Table A: Gentamicin dose if Creatinine Clearance (CrCl) is > 60ml/min

Female
Height 5’ 5’1” 5’2” 5’3” 5’4” 5’5” 5’6” 5’7” 5’8” 5’9” 5’10” 5’11” 6’ 6’1” 6’2” 6’3” 6’4”
Feet
Height 152 155 157 160 163 165 168 170 173 175 178 180 183 185 188 190 193
cm
IBW 45.5 47.8 50.1 52.4 54.7 57 59.3 61.6 63.9 66.2 68.5 70.8 73.1 75.4 77.7 80 82.3
kg
Gent 320 340 360 360 380 400 420 440 440 460 480 500 520 520 540 560 580
7mg/kg

Male
Height 5’ 5’1” 5’2” 5’3” 5’4” 5’5” 5’6” 5’7” 5’8” 5’9” 5’10” 5’11” 6’ 6’1” 6’2” 6’3” 6’4”
Feet
Height 152 155 157 160 163 165 168 170 173 175 178 180 183 185 188 190 193
cm
IBW 50 52.3 54.6 56.9 59.2 61.5 63.8 66.1 68.4 70.7 73 75.3 77.6 79.9 82.2 84.5 86.8
kg
Gent 360 360 380 400 420 440 440 460 480 500 520 520 540 560 580 600 600
7mg/kg

IBW calculation for patients whose height falls out-with above table

Male 50kg + 2.3kg for every 1 inch over 5 feet or – 2.3kg for every 1 inch under 5 feet
Female 45.5kg + 2.3kg for every 1 inch over 5 feet or – 2.3kg for every 1 inch under 5 feet

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Adapted for ease of reference from
NHS Lothian – University Hospitals Division Antibiotic Prescribing Guidelines in Adults – 12/2007

Section 1 continued: monitoring in patients not known to have renal impairment

(CrCl >60ml/min) by means of Hartford Nomogram

It is essential that the exact times of start of infusion and taking of blood sample are documented in the
patient’s notes. Gentamicin is stable so does not have to be assayed immediately: samples taken after
8pm will be assayed the following day
• Determine timing of next dose using the Hartford Nomogram from the level obtained (see
below).
• Repeat serum levels 6-14hours after every third dose and determine timing of subsequent
doses using same Hartford Nomogram

If the level falls in the areas designated Q24h, Q36h or Q48h, then the dosing interval should be every
24, 36 or 48 hours respectively. If the point is on the line between two dosing intervals, choose the
longer interval. If the level is off the top of the nomogram (eg >13mg/L at 6h, or >5mg/L at 14h), then
stop gentamicin, repeat levels every 24h and do not re-dose until serum level is <2mg/L. If the level is
off the bottom of the nomogram (i.e. <2mg/L), re-dose at 24hours.

Hartford Hospital once-daily aminoglycoside nomogram

14
13
12
Concentration (mg/L)

11
10
9 Q48h
8
7
6 Q36h
5
4
3
Q24h
2
6 7 8 9 10 11 12 13 14

Time between start of infusion and sample draw (hours)

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Adapted for ease of reference from NHS Lothian – University Hospitals Division Antibiotic
Prescribing Guidelines in Adults – 12/2007

Section 2 Patients with renal impairment (CrCl 20-60ml/min)

Dose according to Table B below.

Ideal Body Weight

CrCl(ml/min) 40-49 kg 50-59 kg 60-69 kg 70-79 kg >79 kg
20-29 100mg 100mg 100mg 160mg 180mg
once daily once daily once daily every 48 hours every 48 hours
30-39 120mg 120mg 140mg 140mg 160mg
once daily once daily once daily once daily once daily
40-49 120mg 140mg 140mg 160mg 180mg
once daily once daily once daily once daily once daily
50-59 100mg 140mg 160mg 180mg 180mg
twice daily once daily once daily once daily once daily

Designed to achieve : Peak concentrations of 7-10mg/L Trough concentrations of < 2mg/L

The initial levels should be checked at the third dose. Check trough level immediately pre–dose and
peak level one hour post dose. If the levels are within the therapeutic range, the gentamicin levels and
U&E should be checked every 3-4 days. If trough is >2mg/L, withhold drug until trough is <2mg/L and
increase dosing interval. If peak is >10mg/L, reduce dose. If peak is <7mg/L, increase dose. If the dose
or dosing interval requires to be adjusted, levels should be checked at the third dose after the dose
change. Consult pharmacist for advice.

Section 3 Patients with renal impairment (CrCl< 20ml/min)

If CrCl is <20ml/min, discuss with your consultant whether gentamicin is suitable.

Adapted for ease of reference from

NHS Lothian – University Hospitals Division Antibiotic Prescribing Guidelines in Adults – 12/20