Antimicrobial Stewardship (AMS)

• Nephrotoxicity: more likely if trough levels persistently 15–20 mg/L 
• Cytopenias especially neutropenia and thrombocytopenia
• Ototoxicity with prolonged use
• Histamine-release causes a vancomycin flushing reaction characterized by an immediate, generalized erythema during rapid infusion which disappears when the infusion stops. It is not a true allergy. Refer to the IV manual for recommended minimum infusion time. 

Last reviewed June 2021

• Oral vancomycin administration is suitable only for C. difficile infection as it is not absorbed from the GI tract. Do not use oral vancomycin as stepdown therapy for IV vancomycin.
• Vancomycin is a less effective choice than a beta-lactam antimicrobial for methicillin-susceptible staphylococcal (MSSA) infections. 
• S. aureus with an MIC of greater than or equal to 2 mg/L has a high failure rate; consider an ID consult.

Last reviewed June 2021

• Loading dose of 25–30 mg/kg IV x 1 (round to the nearest 250mg. Use actual body weight, maximum dose 3000 mg) if
  • Serious MRSA infections or serious MSSA infections with absolute contraindication to beta-lactams where rapid attainment of target trough level is desired, e.g., pneumonia, epidural abscess, septic shock, meningitis.
  • Patients with significant renal dysfunction in order to decrease the time required to attain target trough level.
  • Peritoneal dialysis
• For other indications, start with maintenance dose as the loading dose as below

*If targeting a higher trough, near 15 mg/L, and patient’s creatinine clearance is greater than or equal to 90mL/min and less than 60 years old, may use 15mg/kg q8h for critically ill patients

**For most patients based on serum monitoring

THERAPEUTIC DRUG MONITORING (TDM)

Trough Target

• The IDSA has recommended against using target trough concentrations of 15-20 mg/L 
• Serum trough levels in the 15-20mg/L range have increased risk of renal toxicity with minimal evidence of increased efficacy.

Trough Monitoring

• Pre-vancomycin (trough) level within 30 min prior to 4th dose (or 3rd dose for q24h dosing) if patient is expected to be on vancomycin for longer than 48 hours
  • For patients receiving q 48-hour dosing, draw a trough level prior to the second dose to ensure level is not above target range.
  • Monitor levels more frequently in patients with variable kidney function, altered volume of distribution (e.g.: burns, cystic fibrosis, sepsis, critical care, pregnancy), requiring larger doses, and/or addition of nephrotoxic drug or agent (e.g.: IV contrast)
  • Do not hold further scheduled vancomycin doses while trough level is pending, unless there has been an acute deterioration in the patient's creatinine clearance
• If level outside desired range, contact clinical pharmacist for assistance with dosing and interpretation of levels as required
  • Usually adjust dose in increments of 250mg and/or the frequency to q12h, q24h, or q48h as appropriate
  • If pre 3^rd or 4^th level is low but near target, can maintain the dose and repeat level, since vancomycin level will likely increase with subsequent doses
• Repeat pre-vancomycin level at least weekly to ensure it is within desired range once target trough is achieved and serum creatinine is stable

Other Monitoring

• Serum creatinine - baseline and at least weekly while on therapy, provided creatinine is stable
• Complete blood count with differential (for cytopenias) - baseline and weekly while on therapy
• May monitor laboratory values more frequently if warranted by clinical scenario (site of infection organism, residual renal function)

Special considerations:

• Peritoneal Dialysis (PD) peritonitis
  • Use intraperitoneal (IP) administration and consult nephrology

Last reviewed June 2021

Last reviewed June 2021

• Treatment of serious infections caused by susceptible Gram-negative microorganisms such as Pseudomonas
• Synergy for some Gram-positive infections (i.e. infective endocarditis)

Last reviewed Jan 2023

• Cranial nerve VIII toxicity
  • Usually NOT reversible 
  • Cochlear: hearing loss, tinnitus
  • Vestibular: nausea, vertigo, balance
  • Must inform patients and monitor for toxicity
    • Daily assessment of hearing, balance, dizziness
    • Audiogram Monitoring: Baseline and serial audiograms should be ordered for patients whose therapy is anticipated to exceed 14 days or in those at high risk for toxicity.
      • How to order an audiogram: Referral information can be downloaded at http://www.nshsc.nshealth.ca/
         
• Nephrotoxicity
  • May be reversible, single dose safe in sepsis
• Neuromuscular blockade
  • Rare, flaccid paralysis, respiratory muscle weakness, contraindicated in myasthenia gravis

Risk factors for toxicity: more than 3 days of therapy, renal insufficiency, elevated trough levels, elderly, volume depletion, concomitant nephrotoxic or ototoxic drugs (i.e. amphotericin B, cisplatin), pre-existing hearing/vestibular disorder, prior aminoglycoside exposure (within 3 months).

Last reviewed Jan 2023

1. Preferred: Extended interval dosing (once daily dosing)
2. Traditional dosing
3. Cystic fibrosis dosing
4. Dosing for synergy in Gram-positive infections

*Note: cystic fibrosis patients often require higher dosing regimens; consult with CF team

Last reviewed Jan 2023

• Preferred dosing strategy: similar efficacy and less toxicity than traditional dosing
• Exclusion criteria:
  • Renal failure  (CrCl less than 20mL/min)    
  • Burns (greater than 20% BSA)    
  • Synergistic therapy
  • Surgical prophylaxis
  • Ascites

Step 1. Calculate dosing rate

Step 2. Calculate maintenance dose

Use dosing weight:

• Tobramycin/gentamicin: 5-7 mg/kg (round to nearest 20mg)
  • 5mg/kg for less severe infections or urinary infections
• Amikacin: 15 mg/kg (round to nearest 50mg)

Step 3. Choose dosing interval based on creatinine clearance

Step 4. Therapeutic drug monitoring

• TROUGH level 6 hours prior to 2^nd dose
• Repeat at least once weekly*

*If initial trough level on target and renal function stable (i.e., not expecting drug accumulation or toxicity), may draw future troughs 30 minutes prior to dose for practicality

Other Monitoring:

Serum creatinine 2 or more times per week; daily clinical assessment of acute changes to hearing or balance/dizzines; audiogram as necessary.

Last reviewed Jan 2023

• Use if patient meets exclusion criteria for extended interval dosing

Step 1. Calculate dosing weight

Step 2. Calculate and give loading dose

Use dosing weight:    

• Tobramycin/gentamicin: 2 mg/kg (round to nearest 20mg)
• Amikacin: 7.5 mg/kg (round to nearest 5 mg)

Step 3. Calculate maintenance dose and choose dosing interval based on creatinine clearance (CrCl)

*Give one dose, check level in 24h, re-dose when level less than 2 mg/L

Step 4. Therapeutic drug monitoring

• TROUGH level 30 minutes prior to 4^th dose
• PEAK level 30-60 minutes after the end of the 4^th dose infusion
• Repeat once weekly or more

*Target peak may need to be in excess of 10 mg/L (greater than 25mg/L for amikacin) for patients with severe Gram-negative infections

Other Monitoring:

• Serum creatinine 2 times or more per week; daily clinical assessment of acute changes to hearing or balance/dizziness; audiogram as necessary

Last reviewed Jan 2023

• Should discuss with CF team as soon as possible
• Tobramycin is preferred agent – round to nearest 20mg
• Infusion should be over 1 hour
• If  CrCl less than 60 mL/min: avoid or consult the CF team

^ or use previous known dose if no change in weight or kidney function
*After the end of the infusion

Obese Dosing

• If body weight is 30% above ideal body weight (IBW), calculate Dosing Weight 
• IBW (male) = 50 kg + 2.3 kg x (each inch above 5 feet)
• IBW (female) = 45.5 kg + 2.3 kg x (each inch above 5 feet)
• Dosing Weight: IBW + 0.4 x (actual body weight - IBW)

Other Monitoring 

• Creatinine at least 3 times a week, daily if over 40 years or kidney injury
• Daily assessment of acute changes to hearing or balance. Inform patient of risks of ototoxicity and to report any symptoms

Consult CF team or pharmacy for dose adjustments

• If trough level pre 3^rd dose is greater than 1mg/mL, change dosing interval to q36 hours
• If both levels are low, increase dose by 40-100 mg.
• If both levels are high, decrease dose by 40-100 mg.
• If levels are discordant, consult CF physician and/or clinical pharmacist.
• If dose is changed, repeat levels after new third dose.
• If levels are within the therapeutic range, recheck levels twice a week.

Last updated January 2023

Ensure gentamicin synergy susceptible by high-level aminoglycoside resistance testing (HLAR)

• Used for:
  • Enterococcus spp. 
  • Staphylococcal prosthetic valve endocarditis
    • NOT indicated for Staphylococcal native valve endocarditis
  • Some Streptococcal spp. depending on penicillin MIC
• Recommend consulting Infectious Diseases 

Step 1. Calculate dosing rate

Step 2. Calculate maintenance dose

Use dosing weight:

• Gentamicin: 1 mg/kg (round to nearest 20mg)

Step 3. Choose dosing interval based on creatinine clearance

Step 4. Therapeutic drug monitoring

• TROUGH level 30 minutes prior to 4^th dose
• PEAK level 30-60 minutes after the end of the 4^th dose infusion
• Repeat once weekly or more

Other Monitoring:

• Serum creatinine 2 or more times per week; daily clinical assessment of acute changes to hearing or balance/dizziness; audiogram as necessary

Last reviewed Jan 2023

Last reviewed Jan 2023