Adult outpatient parenteral antimicrobial therapy (OPAT) good practice prescribing guide

Daptomycin

Daptomycin is a cyclic lipopeptide with activity against Gram-positive bacterial only. It is licensed for complicated skin and soft tissue infections and right-sided infective endocarditis as a result of Staphylococcus aureus including Staphylococcus aureus bacteraemia.

This guide shares practical experience of the use of daptomycin in an OPAT setting. We took an evidence based approach to create the guidance. We also used expert consensus and practical experience from across NHS Scotland.

This drug summary does not provide specific treatment guidance. Individual patient treatment should take into account the core principles of antimicrobial stewardship. This includes selection of the appropriate antimicrobial for the shortest duration with oral therapy being preferred, whenever possible.

For information on Route and method of administration, Contraindications, Cautions and adverse effects and Drug interactions please refer to the following approved resources:

These resources also have more information on licensed indication, use in pregnancy and use in breast feeding. When using unlicensed medicines, and/or off-label doses or indications, follow local health board governance processes.  

It is strongly recommended that OPAT services in Scotland adhere to the Key performance indicators for the management of patients in an outpatient parenteral antimicrobial therapy (OPAT) setting.

Daptomycin

1. Indication and dose

Licensed indication(s) in the OPAT setting Dose
Complicated skin and soft tissue infection (cSSTI) without Staphylococcus aureus bacteraemia Licensed dose is 4mg/kg but in practice some centres use off-label 6mg/kg (see cSSTI pathway below)
cSSTI with Staphylococcus aureus bacteraemia 6mg/kg 24 hourly

Right-sided endocarditis

 Licensed dose is 6mg/kg but in practice higher doses are frequently used (see off-label indications below)

 

Off-label indications in the OPAT setting Dose

Bone and joint infection
OR
Bacteraemia (excluding Enterococcal organisms)

8-10mg/kg* 24 hourly

Right or left sided native/prosthetic valve or device related infective endocarditis
OR
Bacteraemia involving Enterococcal organisms

10-12mg/kg* 24 hourly

*Use Total Body Weight (TBW) or if body mass index (BMI) is 30kg/m2 or higher use adjusted body weight (AdjBW)  (See also obesity section below)

Complicated skin and soft tissue infections (cSSTI)
Daptomycin is used as an alternative to ceftriaxone in the SAPG OPAT pathway for the management of adults with complicated skin and soft tissue infections (SSTI) for patients with anaphylaxis or other life-threatening penicillin or beta-lactam allergy or C.difficile concern (including episode in previous 3 months). 
This pathway supports reduced hospital admissions and promotes early discharge for patients with complicated skin and soft tissue infections.

Suggested dosing guidance in (cSSTI)
Recommended dose of daptomycin IV is 4-6mg/kg and review daily.
The following dosing advice for cSSTIs in the table below is an example of pragmatic dosing in practice based on a 6mg/kg (actual body weight) dosing regimen. It is for guidance only and may be locally adapted or modified.

Doses have been rounded up to the nearest 350mg or 500mg vials.

Table: Daptomycin SSTI 6mg/kg dosing regimen adapted from Greater Glasgow and Clyde OPAT

Body weight 6mg/kg dosing*
less than 59kg 350mg
59-83kg 500mg
84-117kg 700mg
118-142kg 850mg
more than 142kg discuss with pharmacy

*Dose rounded to nearest vial

Rounding of doses

  • Where possible use whole vials (350mg and 500mg vial strengths are available).
  • If the total calculated dose is 10% or less over the available whole vial round the dose down (eg calculated dose 530mg, prescribe 500mg).
  • Dose rounding may result in a higher mg/kg dose than recommended above. Doses over 12mg/kg are not recommended.  Discuss with pharmacy if the dose is unclear.

2. Dose adjustments

2a. Renal impairment

As renal function may fluctuate it is important to monitor renal function at least weekly and adjust dosing interval if required during the treatment course.

Information on optimal dosing and efficacy in CrCl less than 30ml/min is limited.  The following dose suggestions are unlicensed.

Note: Calculate the mg/kg dose using Total Body Weight (TBW) or if body mass index (BMI) is 30kg/m2 or higher use adjusted body weight (AdjBW)  (See also obesity section below)

Renal function
(Creatinine clearance (CrCl))		 Dose adjustment

Less than 30ml/min
OR
if patient is receiving irregular or daily haemodialysis

Reduce frequency to 48 hourly and more frequent monitoring is required (see below for monitoring requirements)
Regular three times weekly haemodialysis (eg Mon/Wed/Fri) Give on haemodialysis days only (after haemodialysis)


2b. Other dosage adjustments

Patient characteristic Dosage advice
Hepatic impairment No dose adjustment necessary
Obesity

If BMI is 30kg/m2 or more use the patient’s adjusted body weight (AdjBW) to calculate the daptomycin mg/kg dose:

BMI is calculated using the following equation:
BMI = Weight (kg)/ (Height (m))2

If the patient’s BMI is over 30 use AdjBW equation to calculate weight for daptomycin dosing.

AdjBW equation: 
AdjBW = (0.4 x (TBW – Ideal body weight (IBW))) + IBW

IBW is calculated using the following equation:
IBW = ((Ht (cm) – 152.4 cm)/ 2.54) * 2.3 + 50kg (male) or 45.5kg (female)


3. Monitoring requirements

Frequency Recommended monitoring
Baseline Urea and Electrolytes (U&Es) , LFTs, CRP and FBC, creatine phosphokinase (CPK)
Weekly monitoring
(Note this may be more frequent if clinically necessary)

U&Es, LFTs, CRP, FBC, CPK (2-3 times weekly if poor renal function or receiving renal replacement therapy)

Monitoring advice for patients that should be discussed at weekly appointment;
Patients should be advised to report any muscle pain
Monitor for and review urgently if breathlessness or new cough as this may indicate eosinophilic pneumonitis (Note not usually associated with peripheral blood eosinophilia)
Therapeutic drug monitoring

Routine daptomycin therapeutic drug monitoring (TDM) is not recommended because there is no clear evidence that links daptomycin concentration monitoring with clinical outcome.  However, daptomycin trough concentrations may be useful in patients requiring renal replacement therapy to predict toxicity. Discuss with Pharmacy if TDM required.

CPK should be measured at least weekly as a useful and easily measured surrogate marker of potential toxicity. More frequent monitoring may be required in renal impairment or those at risk of developing myopathy eg patients on statins. Please consider the following pragmatic approach.  

Daptomycin should be discontinued if:

  • Symptomatic rise in CPK observed (especially if CPK is more than 5 times upper normal limit)
  • Asymptomatic rise in CPK observed (CPK is more than 10 times upper limit normal)
Follow up

Ensure follow-up arranged with referring specialty and/ or an infection specialist


For the use of other antibiotics in an OPAT setting please refer to the SAPG website

 

Scottish Antimicrobial Prescribing Group (SAPG) | January 2024 for review January 2027

Content updated: April 2024