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Antibiotic Assays

Assays

Patients receiving intravenous vancomycin, teicoplanin or an aminoglycoside (gentamicin, tobramycin and amikacin) need regular monitoring of serum antibiotic levels.

The Biochemistry department carry out the assays of serum antibiotic levels. All advice and enquires are dealt with by the Microbiology department, Antimicrobial Pharmacist or Pharmacy Medicines Information.

Assays for vancomycin and gentamicin are performed in house. Assays for amikacin, tobramycin and teicoplanin are currently sent away for testing at another laboratory. For assays that require sending away, try to ensure that specimens are collected during the normal working week; if specimens need to be done at weekends, prior arrangement is required.

Collection of blood for monitoring of therapeutic levels of antibiotics must be done from a peripheral vein. Specimens are collected into serum gel tubes (brown cap).

For aminoglycoside assays it is essential to indicate on the request form if the patient is on a once-daily dosing regimen, multiple-daily dosing regimen, or renal impairment regimen. The time the sample is taken and the time the last dose was administered must be stated on the sample bottle to avoid confusion and speed processing. This information should also be recorded in the patient’s medical notes.

Patients receiving either aminoglycosides, vancomycin or teicoplanin MUST have their renal function checked at least twice weekly in stable renal function, or daily in patients with impaired or unstable renal function.

Vancomycin Monitoring (Adults)

Vancomycin Monitoring Guidelines Summary (Adults)
Introduction	Suspected or proven MRSA infections and other Gram positive organisms in penicillin allergic patients.
Dose regime Creatinine clearance calculator	CrCl >70mL/min 1g bd CrCl 30-70 mL/min 1g od CrCl <30mL/min 1g stat
Administration	Slow IV infusion in either Sodium chloride 0.9% or Glucose 5% over 2 hours (maximum rate 10mg/min).
What levels should I monitor?	Pre-dose (trough) level immediately prior to administration of dose There is NO need to routinely monitor peak vancomycin levels (for list of exceptions refer to policy on Intranet)
When should I take levels initially?	Twice daily dosing Check pre-dose level before 4th dose Once daily dosing Check pre-dose level before 2nd dose
When should I repeat levels?	If renal function remains stable Repeat pre-dose levels every 3-4 days If dose is adjusted Twice daily dosing – repeat trough level before 4th new dose then every 3-4 days Once daily dosing – repeat trough level before the 2nd new dose then every 3-4 days If renal function changes Contact Microbiology
Target assay levels	Pre-dose (trough) level 10-20mg/L In the case of severe infections such as endocarditis, pre-dose levels can be run at 15-20mg/L, as long a renal function is monitored regularly
Recommendations for dose adjustment	Pre-dose <10mg/L Dose increase or reduction in dosing interval (e.g. once daily to twice daily) required Pre-dose 10-20mg/L No dose adjustment necessary Pre-dose >20mg/L Dose reduction or increased in dosing interval (e.g. twice daily to once daily) required Beware of accumulation of vancomycin even though levels are still within range. This may require a dose reduction or increase in dosing interval.
Do I need to wait for the level to come back before I give the next dose?	No, not unless specifically advised
Further advice	Oncall microbiologist via bleep 774 or switchboard or antimicrobial pharmacist bleep 448.

Extended interval
gentamicin dosing(Adults)

Appendix 1: Extended interval gentamicin dosing guidelines summary (Adults) Click here for full guideline
Introduction	Preferred regimen for the treatment of Gram negative sepsis Do NOT use extended interval dosing for the following groups of patients: (without discussion with pharmacist or microbiologist) Bronchiectasis Burns (>20% body surface area) Cystic fibrosis Ascites Infective endocarditis Renal impairment (Creatinine clearance <30mL/min), unstable or deteriorating renal function (see Renal dosing) Renal dialysis
Dose regimen	Gentamicin dose = 5mg/kg (maximum 500mg) Use adjusted body weight if obese (ie. if 20% over ideal body weight) Round to nearest 20mg e.g.260mg if 50kg, 300mg if 60kg, 360mg if 70kg, 400mg if 80kg
Prescribing first dose	Check no previous dose given in last 24hours. May prescribe on regular antibiotics section and indicate on the drug chart the need to monitor Pre-dose Level before 2nd Dose
Administration	Dilute with 100mL sodium chloride 0.9% or glucose 5% and give by IV infusion over 30-60mins
What levels should I monitor?	Pre-dose level before 2nd dose (1-4 hours before next dose is due)
When should I take levels initially?	Check before 2nd dose due (unless single dose therapy)
Target assay levels	Pre-dose level LESS THAN 1mg/L
Recommendations for dose adjustment	Normal pre-dose level (<1mg/L) -Continue current regimen -Repeat pre-dose levels after 3-4 days if renal function remains stable Pre-dose level 1-2mg/L (and renal function unchanged) -Increase the dosing interval to 36-hourly Pre-dose level greater than 2mg/L -Omit any further doses of gentamicin and discuss with Microbiology -The need for gentamicin therapy MUST be reviewed If the patient cannot safely be maintained on an extended interval dosing regimen, consider the renal dosing regimen.
Do I need to wait for the level result?	IF NORMAL and STABLE RENAL FUNCTION - Monitor pre-dose level before 2nd dose, GIVE 2nd dose and WAIT for the result of the pre-dose level before prescribing and administering 3rd or subsequent doses
When should I repeat levels?	Check pre-dose levels every 3-4 days if renal function remains stable. Monitor pre-dose levels daily if adjustments are being made or if the patient is renally impaired.
How do I prescribe subsequent doses?	Subsequent doses may be prescribed on the regular section of the drug chart, and administration boxes MUST be marked to ensure the correct dosing interval is followed, and indicate when the next level is due.

Renal gentamicin dosing (Adults)

Appendix 2: Renal gentamicin dosing guidelines summary (Adults) Click here for full guideline
Introduction	This regimen should be used where the prescriber wishes to use an extended interval gentamicin dosing regimen for the treatment of Gram negative sepsis in patients WITH severe renal impairment (CrCl <30ml/min, but if <10ml/min - discuss with microbiologist or pharmacy) or elderly patients e.g. >70years
Dose regimen	Gentamicin dose = 3mg/kg (maximum 300mg) Use adjusted body weight if obese (ie. if 20% over ideal body weight) Round to nearest 20mg e.g.160mg if 50kg, 180mg if 60kg, 220mg if 70kg, 240mg if 80kg
Prescribing first dose	Check no previous dose given in last 24hours Prescribe the first dose on the “once only” section of the drug chart
Administration	Dilute with 100mL sodium chloride 0.9% or glucose 5% and give by IV infusion over 30-60minutes
What levels should I monitor?	Pre-dose level before 2nd dose (1-4 hours before next dose is due)
When should I take levels initially?	Check before 2nd dose due (unless single dose therapy)
Target assay levels	Pre-dose level LESS THAN 1mg/L
Recommendations for dose adjustment	If level less than 1mg/L Prescribe 2nd dose on “once only” section of drug chart or regular section of the chart (but highlighting the need to wait for pre dose level before administration . Repeat level 24 hours after dose administered (pre-dose before the next dose due) If level 1mg/L OR greater than 1mg/L Do NOT prescribe any further doses Repeat level 24 hours later If level < 1mg/L, prescribe 2nd dose on “once only” section of drug chart or regular section of the chart (but highlighting the need to wait for pre dose level before administration . If level still remains >1mg/L, keep repeating gentamicin level at periodic intervals until gentamicin level has fallen to <1mg/L No further doses should be prescribed or administered until level is <1mg/L
Do I need to wait for the level result?	WAIT for the result of the pre-dose level before prescribing and administering any subsequent doses
When should I repeat levels?	DAILY levels are required for patients on the renal gentamicin dosing regimen or those with unstable renal function.
How do I prescribe subsequent doses?	Subsequent doses may be prescribed on the “once only” section of the drug chart or regular section of the chart (but highlighting the need to wait for pre dose level before administration . Doses should only be administered once the pre-dose level is less than 1mg/L.
Continuation of treatment	If the patient requires gentamicin beyond 48 hours, this MUST be discussed with a Consultant Microbiologist. The risk of nephrotoxicity and ototoxicity increases with prolonged courses.

Traditional multiple daily
gentamicin dosing (Adults)

Appendix 3: Traditional multiple daily dosing guidelines summary (Adults) Click here for full guideline
Introduction	Treatment of patients with endocarditis.
Dose regimen Creatinine Clearance calculator	1mg/kg (max 80mg) 12 hourly - modified according to renal function and level (round to nearest 20mg). Use adjusted body weight if obese (ie. if 20% over ideal body weight)
Prescribing first dose	Prescribe gentamicin at chosen dose and dose interval The dosing regimens recommended above are starting dose regimens only. Blood levels must be monitored to ensure target peaks and troughs are achieved.
Administration	IV bolus over 3-5 minutes. Dilution is not normally necessary.
What levels should I monitor?	Check Pre and Post dose levels around the 3rd or 4th dose. If renally impaired, check around the 2nd dose.
When should I take levels initially?	Check pre-dose (trough) level around the 3rd or 4th dose before administering the dose. Administer dose. There is no need to wait for pre-dose level to be reported before administering dose, unless instructed to do so by your ward pharmacist or Consultant Microbiologist. Check one hour post-dose (peak) level around the 3rd or 4th dose. Level to be taken one hour after completion of the bolus/infusion. If renally impaired, check around the 2nd dose. Label your sample tubes and request form clearly with pre and post dose level as appropriate.
Target assay levels	Pre-dose (trough) level -less than 1mg/L for endocarditis One hour post dose (peak) level: 3-5mg/L for streptococcal or enterococcal infections e.g. endocarditis
Recommendations for dose adjustment Please contact your ward Pharmacist or Consultant Microbiologist for advice on changes to the dose and/or dosing interval.	Pre-dose levels: Normal pre-dose (<1mg/L) - Regimen can be continued - Further pre-dose levels MUST be monitored twice weekly so long as renal function is stable Pre-dose level is between 1-3mg/L (and renal function unchanged) - Increase the dosing interval e.g. from 12-hourly to 24-hourly Pre-dose greater than 3mg/L - Further gentamicin doses MUST be withheld - Discuss with microbiology before recommencing therapy One-hour post-dose levels: Post-dose level is below the target range (<3mg/L) - Gentamicin is sub-therapeutic - The dose should be increased Post-dose level is above the target range (>5mg/L); pre-dose level is normal (<1mg/L) - Reduce the dose Both the post-dose (>5mg/L) and pre-dose (>1mg/L) levels are above the target range - The next dose(s) MUST be omitted - Discuss with Microbiology before recommencing therapy