Therapeutic Drug Monitoring

Vancomycin

Refer to dosing algorithm below

Levels

Collect predose level before 4th dose of vancomycin. Give the dose. Any adjustments necessary can be made to the 5th dose onwards.

Predose level should be between 10- 15μg/ml. (In severe/complicated infection 15-20 μg/ml).

If continuing vancomycin and renal function is stable, repeat level twice weekly. Daily levels may be required if renal function is unstable.

Note: 1-hour post dose levels are not necessary.

Clearly state dose, time of dose and time of blood sample collection on the request form.

Comments

Must be administered slowly IV at a maximum rate of 10mg/min to avoid reaction such as red man syndrome.

In severe/complicated infections a loading dose of 25 mg/kg can be used to facilitate rapid attainment of target trough serum vancomycin concentration.

Complicated Infections:

1. Bacteraemia
2. Endocarditis
3. Osteomyelitis
4. Meningitis
5. Hospital Acquired Infections caused by Staph aureus

Gentamicin

General Information

• Gentamicin is an aminoglycoside antibiotic and has a narrow therapeutic index.
• Weight-based dosing and therapeutic drug monitoring (TDM) are essential to ensure therapeutic efficacy and to minimise the risk of adverse effects such as nephrotoxicity, vestibular toxicity and ototoxicity.
• Standard Once Daily regimen is recommended for the treatment of sepsis and most other infections.
• These recommendations do not apply to the use of gentamicin in cystic fibrosis, renal replacement therapy, or those on multiple daily dosing schedules.
• Use dose calculations as outlined below; however do not delay 1 ^st doses in patients requiring urgent therapy if renal function information is not available.
• A stat or single dose is often sufficient.
• Review need for ongoing treatment with gentamicin on a daily basis . Treatment courses extending beyond 3-5 days are rarely required and are associated with an increased risk of adverse effects.
• Please discuss patients on extended treatment courses of gentamicin with the clinical microbiology team.

Adverse Effects

• Vestibular and ototoxicity can occur independently of serum gentamicin levels and duration of treatment however the risk increases significantly with higher cumulative doses and courses of longer durations.
• Nephrotoxicity : Consider renal function, volume status, and the use of concomitant nephrotoxic agents such as NSAIDs, ACE inhibitors, and diuretics, when prescribing aminoglycosides.

Cautions and Contraindications

• Caution is advised in patients with auditory and vestibular disorders, and conditions characterised by muscular weakness.
• Aminoglycosides (Gentamicin, Amikacin, Tobramycin) are contraindicated in patients with myasthenia gravis as they may impair neuromuscular transmission in these patients.

Endocarditis:

3mg/kg once daily

Multiple daily dosing may be warranted in certain instances – please consider consulting Microbiology/Infectious Diseases.

Pregnancy:

3-5mg/kg once daily

Please discuss with the microbiology team if needed and see the algorithm

Dose Calculations

Step 1: Weigh patient (kg) to determine Actual Body Weight. Record height.

Step 2: Calculate the Body Mass Index and/or Ideal Body Weight to determine if the patient is obese. (Please see formula for weight calculation)

Step 3 : Obese Dosing Weight/Adjusted Body Weight should be used in CrCl and dose calculations if BMI >30 kg/m ² or Actual Body Weight is 20% more than Ideal Body Weight. (Please see formula for weight calculation)

Step 4: Calculate Creatinine clearance using Cockcroft-Gault equation using either Actual Body Weight or Obese Dosing Weight/Adjusted Body Weight as indicated above. The Cockcroft Gault formula is less reliable in children, acute renal failure, oedematous states, muscle wasting, amputees, and malnourished patients.

(Please see MdCalc Creatinine Clearance Calculator)

Step 5: Calculate the gentamicin dose to be administered based on CrCl AND weight (Actual Body Weight or Obese Dosing Weight/Adjusted Body Weight) as per the table below.

Monitoring and Dose Adjustment

• Order serum trough level to be taken 16-24h post first dose. Monitor renal function.
• Gentamicin trough (pre-dose) level should be ≤1 mcg/ml.
• Ensure laboratory request form is labelled with sample time and date and gentamicin dose time is recorded accurately.
• Check and interpret trough level result, renal function AND review need for continued treatment prior to prescribing subsequent doses. NB. Doses should never be held whilst awaiting trough levels in patients with sepsis or severe infection.
• These recommendations do not apply to TDM and target trough levels for patients on multiple daily dosing schedules. Discuss these patients with pharmacy and/or clinical microbiology.

References

1. Gentamicin: Guidelines for Once Daily Usage in Adult and Paediatric Settings. HSE/RCPI 2016.
2. BNF https://doi.org/10.18578/BNF.632013114 . 20 ^th October 2020

Amikacin

General Information

• Amikacin is an aminoglycoside antibiotic and has a narrow therapeutic index.
• Both weight based dosing and therapeutic drug monitoring (TDM) are essential to ensure therapeutic efficacy and to minimise the risk of adverse effects such as nephrotoxicity, vestibular and ototoxicity.
• Standard Once Daily regimen is recommended for the treatment of sepsis and most other infections.
• These recommendations do not apply to the use of amikacin in endocarditis, cystic fibrosis, pregnancy, renal replacement therapy, or those on multiple daily dosing schedules.
• Use dose calculations as recommended below, however do not delay 1 ^st doses in patients requiring urgent therapy if renal function information is not available.
• A stat or single dose if often sufficient.
• Review need for ongoing treatment with amikacin on a daily basis . Treatment courses extending beyond 3-5 days are rarely required and are associated with an increased risk of adverse effects.
• A maximum total adult dose of 15 g (i.e. entire treatment course) should not be exceeded.
• Please discuss patients on prolonged courses of amikacin with the clinical microbiology team.

Adverse Effects

• Vestibular and ototoxicity can occur independently of serum amikacin levels and duration of treatment however the risk increases significantly with higher cumulative doses and courses of longer durations.
• Nephrotoxicity : Consider renal function, volume status, and the use of concomitant nephrotoxic agents such as NSAIDs, ACE inhibitors, and diuretics, when prescribing aminoglycosides.

Cautions and Contraindications

• Amikacin is a restricted antimicrobial and should only be prescribed for the treatment of infections due to gentamicin resistant Gram negative bacilli or if recommended by a consultant microbiologist
• Consider renal function, hydration status and concomitant nephrotoxic medicines
• Therapeutic Drug Monitoring is necessary to prevent toxicity notably nephrotoxicity & ototoxicity.
• Risk of ototoxicity increases with higher cumulative doses and longer treatment courses.
• Caution advised in patients with auditory and vestibular disorders, and conditions characterised by muscular weakness.
• Aminoglycosides (Gentamicin, Amikacin, Tobramycin) are contraindicated in patients with myasthenia gravis as they may impair neuromuscular transmission in these patients

Dose Calculations

Step 1: Weigh patient (kg) to determine Actual Body Weight and record height.

Step 2: Calculate the Body Mass Index and/or Ideal Body Weight to determine if the patient is obese. (Please see formulae for weight calculation)

Step 3 : Obese Dosing Weight/Adjusted Body Weight should be used in CrCl and dose calculations if BMI >30 kg/m ² or if ABW is 20% more than Ideal Body Weight. (Please see formula for weight calculation)

Step 4: Calculate Creatinine clearance using Cockcroft-Gault equation using either Actual Body Weight or Obese Dosing Weight/Adjusted Body Weight as indicated above. Use of Cockcroft Gault formula is less reliable in children, acute renal failure, oedematous states, muscle wasting, amputees, and malnourished patients.

( Please see MdCalc Creatinine Clearance Calculator)

Step 5: Calculate the amikacin dose to be administered based on CrCl and weight (use Obese Dosing Weight/Adjusted Body Weight if obese) as per the table below.

Monitoring and Levels

• Order serum trough level to be taken 16-24h after the first dose has been given.
• Amikacin trough (pre-dose) level for once-daily dosing should be ≤5 mcg/ml.
• Ensure laboratory request form and serum sample is labelled with sample time and date . Ensure the timing of the last dose is accurately recorded.
• Monitor renal function.
• Check and interpret trough level result, renal function AND review need for continued treatment prior to prescribing subsequent doses. NB. Doses should never be held whilst awaiting trough levels in patients with sepsis or severe infection.
• These recommendations do not apply to TDM and target trough levels for patients on a multiple daily dosing schedules. Discuss these patients with pharmacy and/or clinical microbiology.

References

1. Renal Drug Database. www.renaldrugdatabse.com . 9th September 2019.
2. BNF. https://doi.org/10.18578/BNF.716968910 . 12 ^th August 2020.

Tobramycin

General Information

Tobramycin is an aminoglycoside antibiotic with a narrow therapeutic index.  Effective use is complex and should be discussed with Microbiology or Infectious Diseases.

Weight-based dosing and therapeutic drug monitoring (TDM) are essential to ensure therapeutic efficacy and to minimise the risk of adverse effects such as nephrotoxicity, vestibular and ototoxicity.  Note: risk is increased in renal impairment, in prolonged therapy, in patients receiving higher doses or for those on concomitant nephrotoxic medications.

Tobramycin is a restricted antimicrobial which should only be prescribed when it is in line with the recommendations of local antimicrobial guidelines or following discussion with Clinical Microbiology/Infectious Diseases.

Once daily dosing of Tobramycin is recommended for most patients. Discuss patients with renal impairment (creatinine clearance <30ml/minute) with Pharmacy/Clinical Microbiology/Infectious Diseases.

Use dose calculations as outlined below however do not delay 1 ^st doses in patients requiring urgent therapy if renal function information is not available. Do NOT hold dose while waiting for level to be reported in a patient <65 years with good renal function (creatinine clearance >80ml/minute) and good urine output, unless specifically advised to do so.

However, in a patient >65 years, or with abnormal renal function (creatinine clearance <80ml/minute), it is preferable to await the result of the first tobramycin level (i.e. before the second dose) before giving the next dose. If the level is <1mg/L and renal function is stable it is not necessary to routinely hold subsequent doses pending levels.

Review need for ongoing treatment with tobramycin on a daily basis - courses should not usually exceed 3 days, except in cystic fibrosis. Please discuss patients on extended treatment courses of tobramycin with Clinical Microbiology/Infectious Diseases.

**** Note: These recommendations do not apply to the use of tobramycin in cystic fibrosis patients - these patients must be discussed with a specialist. ****

Adverse Effects

Vestibular and ototoxicity can occur independently of serum tobramycin levels and duration of treatment, however the risk increases significantly with higher cumulative doses and courses of longer durations.

Nephrotoxicity : Consider renal function, volume status, and the use of concomitant nephrotoxic agents such as NSAIDs, ACE inhibitors, and diuretics, when prescribing aminoglycosides.

Cautions and Contraindications

Caution is advised in patients with auditory and vestibular disorders, and conditions characterised by muscular weakness.

Aminoglycosides (Gentamicin, Amikacin, Tobramycin) are contraindicated in patients with myasthenia gravis as they may impair neuromuscular transmission in these patients.

Dose Calculations

Step 1: Weigh patient (kg) to determine Actual Body Weight. Record height.

Step 2: Calculate the Body Mass Index and/or Ideal Body Weight (IBW) to determine if the patient is obese. ( Please see formula for weight calculation )

Step 3 : Obese Dosing Weight/Adjusted Body Weight should be used in CrCl and dose calculations if BMI >30 kg/m ² or Actual Body Weight is 20% more than Ideal Body Weight (IBW). ( Please see formula for weight calculation )

Step 4: Calculate Creatinine clearance using Cockcroft-Gault equation using either Actual Body Weight or Obese Dosing Weight/Adjusted Body Weight as indicated above . The Cockcroft Gault formula is less reliable in children, acute renal failure, oedematous states, muscle wasting, amputees, and malnourished patients.

( Please see MdCalc Creatinine Clearance Calculator )

Step 5: Calculate the Tobramycin dose to be administered based on CrCl AND weight (Actual Body Weight or Obese Dosing Weight/Adjusted Body Weight) as per the table below.

Monitoring and Dose Adjustment

• Order serum trough level to be taken 16-24h post first dose. Monitor renal function.
• Tobramycin trough (pre-dose) level should be ≤1 mcg/mL.
• Ensure laboratory request form is labelled with sample time and date and tobramycin dose time is recorded accurately.
• Check and interpret trough level result, renal function AND review need for continued treatment prior to prescribing subsequent doses. NB. Doses should never be held whilst awaiting trough levels in patients with sepsis or severe infection.

References

1. British National Formulary, ( accessed online via Medicines Complete May 2024 )
2. Renal Drug Database, ( accessed online May 2024 )
3. Tobramycin SPC (Pfizer), ( accessed online at www.hpra.ie May 2024 )
4. Sanford Guide, ( accessed online May 2024 )
5. Cork University Hospital Antimicrobial Guide, ( accessed May 2024 )

Teicoplanin

General Information

• Teicoplanin is a glycopeptide antibiotic similar to vancomycin that has activity against aerobic and anaerobic Gram-positive bacteria only . This includes S. aureus (both MSSA & MRSA), most but not all coagulase-negative staphylococci (S. haemolyticus are often resistant), streptococci and vancomycin susceptible enterococci. Most strains of VRE are also teicoplanin resistant.
• Teicoplanin has a significantly longer duration of action and is associated with a lower incidence of nephrotoxicity in comparison to vancomycin but it may take a longer time to reach therapeutic levels. There is no formulation that is absorbed when given orally and therefore is suitable for IV use only.
• Check renal function and calculate creatinine clearance using the Cockcroft & Gault equation before prescribing.

Cautions and Contraindications

• Teicoplanin hypersensitivity
• Patients with a history of allergy to vancomycin due to the risk of cross-sensitivity
• Patients receiving concomitant nephrotoxic or ototoxic drugs such as aminoglycosides, cyclosporine and furosemide.

Adverse Effects

• Hypersensitivity reactions including fever, rash, anaphylaxis.
• Thrombocytopenia; anaemia; neutropenia.
• Nephrotoxicity; ototoxicity.

Dosing and Monitoring

Dosing is based on weight, clinical indication and renal function (CrCl calculated using Cockcroft & Gault). (Please see MdCalc Creatinine Clearance Calculator)

Higher doses are used for deep-seated infections and may also be indicated in severe infections or critical illness.

Actual body weight is always used for dose calculations (including where BMI ≤18 and ≥30kg/m ² ).

Dose adjustments in renal impairment do not need to be made until after the 4 ^th day.

1. Loading dose regimen is recommended in all patients

1. Maintenance Dosing Regimen

References

1. Renal Drug Database. Teicoplanin, Reviewed 09/09/2019. Accessed 19 ^th July 2023.
2. Bristol Centre for Antimicrobial Research and Evaluation . Accessed 29 ^th July 2023
3. British National Formulary Accessed 25 October 2021.
4. Sanford Guide. Teicoplanin. Accessed 19 ^th July 2023.
5. SPC Targocid Powder and Solvent for Solution for Injection 400mg, Accessed 19 ^th July 2023.
6. John Hopkins Abx Guide. Teicoplanin. Updated 18th October 2022. Accessed 10th May 2024