Vancomycin

Question 1

What drug class is vancomycin?

Answer 1

Glycopeptide

Question 2

What is the MOA of vancomycin?

Answer 2

Bactericidal; inhibit bacterial cell wall synthesis by preventing formation of peptidoglycan polymers.

Question 3

What is the indication for treatment with vancomycin?

Answer 3

Due to the incidence of clinical isolates resistant to vancomycin, eg vancomycin-resistant enterococci (VRE), Australia has adopted guidelines recommended by the Centers for Disease Control Hospital Infection Control Practices Advisory Committee (USA) for its use. Similar considerations apply to teicoplanin.

Severe infections caused by susceptible organisms in cases of penicillin resistance or intolerance, eg MRSA, MRSE, meningitis, endocarditis (with other agents)

Clostridium difficile-associated disease (oral)

Endocarditis prophylaxis in penicillin allergy (selected indications)

Surgical prophylaxis (selected indications)

Question 4

What are the precautions for use of vancomycin?

Answer 4

Allergy to teicoplanin—allergic cross-reactivity between teicoplanin and vancomycin has occurred.

Inflammatory GI conditions—may allow significant oral vancomycin absorption, increasing likelihood of adverse effects, especially in renal impairment.

Renal (Increase dose interval or reduce dose, or both, in renal impairment).

Elderly (Increased risk of toxicity).

Thrombocytopenia during vancomycin or teicoplanin treatment—may recur as it may have been immune-mediated.

Hearing impairment—may increase risk of ototoxicity from glycopeptides

Treatment with ototoxic drugs, eg aminoglycosides—may increase risk of ototoxicity, particularly with vancomycin.(especially vancomycin).

Question 5

What is the renal precaution surrounding vancomycin use?

Answer 5

Ototoxicity and nephrotoxicity may be more likely in renal impairment, particularly with vancomycin; reduce dose.

Treatment with nephrotoxic drugs, eg aminoglycosides, may increase risk of nephrotoxicity; monitor renal function and drug concentration.

Increase dose interval or reduce dose, or both, in renal impairment.

Question 6

How would you change the administration of vancomycin in someone who was renal impaired?

Answer 6

Increase dose interval or reduce dose, or both, in renal impairment.

Question 7

What is surgery risk associated with vancomycin use?

Answer 7

General anaesthetics increase risk of vancomycin infusion-related adverse effects, including hypotension; complete vancomycin infusion before induction of anaesthesia.

Question 8

Is vancomycin safe in pregnancy and breastfeeding patients?

Answer 8

Pregnany -Considered safe to use.

Breastfeeding - Safe to use; may cause loose bowel actions in the baby

Question 9

What are the common oral adverse effects of vancomycin?

Answer 9

Oral vancomycin may cause indigestion, nausea, vomiting, diarrhoea and chills.

Oral: vancomycin usually only causes GI adverse effects unless significant serum concentrations occur, eg in renal impairment.

Question 10

What are some rare adverse effects of vancomycin?

Answer 10

superinfection, thrombocytopenia (may be immune-mediated), neutropenia (when due to vancomycin more likely after at least 1 week and total dose >25 g), 
leucopenia, 
agranulocytosis, 
ototoxicity, 
multi-organ hypersensitivity syndrome

Question 11

What are the infrequent adverse effects of vancomycin?

Answer 11

Nephrotoxicity

Question 12

Explain the nephrotoxicity association with vancomycin?

Answer 12

Nephrotoxicity is more common when glycopeptides are used with aminoglycosides and in renal impairment. It appears to be related to vancomycin serum concentration. Teicoplanin is less nephrotoxic than vancomycin

Question 13

Explain the ototoxicity association with vancomycin?

Answer 13

Dizziness, vertigo and tinnitus can occur.

Ototoxicity is very rare with teicoplanin. Vancomycin alone rarely causes ototoxicity; risk is higher with prolonged use, in renal impairment and when given with other ototoxic drugs, eg aminoglycosides; deafness may be permanent.

Question 14

What is an infusion reaction that can occur with vancomycin?

Answer 14

Red man syndrome

Usually due to infusion being given too quickly. It is not an allergic reaction although symptoms are partly due to histamine release; they include fever, chills, erythema, facial and upper torso rash, which may be followed by hypotension, angioedema and itch. May be treated with antihistamines (eg promethazine); successful administration is usually possible by increasing the infusion time to >60 minutes.

These reactions occur far less often with teicoplanin than vancomycin

Question 15

What is the adult dose for IV vancomycin?

Answer 15

IV, 1–1.5 g every 12 hours (consider using a loading dose of 25–30 mg/kg, followed by 15–20 mg/kg every 8–12 hours, eg if the patient is critically ill or obese).
Use concentration monitoring to guide continued dosing if necessary.

Question 16

What type of calculation should be used regarding weight for vancomycin dose calculation?

Answer 16

Use actual body weight for dose calculations, including obese patients (more frequent dosing may be necessary; monitor vancomycin concentration). Larger doses and/or more frequent dosing may also be needed in other patients if high trough concentrations are necessary

Question 17

Is dosing adjustment necessary for vancomycin treatment?

Answer 17

Renal impairment:
Seek specialist advice, especially when patients are obese or when CrCl <30 mL/minute.

Use trough concentration monitoring to guide dosage interval.

CrCl 30–60 mL/minute, IV 500 mg – 1 g every 24 hours.

CrCl 10–30 mL/minute, IV 1 g every 1–5 days.

CrCl <10 mL/minute, IV 1 g every 4–10 days.

Question 18

What is the vancomycin treatment dose for clostridium difficle-associateddisease?

Answer 18

Adult, oral 125 mg every 6 hours for 10–14 days (higher doses are not thought to improve outcomes and may lead to toxicity, so are not generally used).

Question 19

When would you use concentration monitoring for vancomycin treatment?

Answer 19

Measure to enable dose individualisation:

• when given with an aminoglycoside or other nephrotoxic drugs
• where pharmacokinetics are altered, eg burns patients, morbidly obese (may require higher doses due to large volume of distribution and increased drug clearance)
• during high-dose and/or prolonged treatment
• when treating infections due to MRSA with heterogeneous (hVISA) susceptibility
• in patients on haemodialysis receiving infrequent doses of vancomycin (half-life varies according to ultrafiltration rate and dialyser pore size)
• in patients with unstable or impaired renal function
• after a dose change.

Question 20

What is the therapeutic range for vancomycin treatment?

Answer 20

For twice daily dosing, trough level should be 10–20 mg/L (take first sample just before the fourth dose). A trough >10 mg/L minimises resistance developing but may increase the risk of nephrotoxicity, especially if other nephrotoxic agents are being used, eg aminoglycosides.

Some authorities recommend a trough level of 15–20 mg/L (based on susceptibility, pharmacokinetic and pharmacodynamic data, and clinical experience) to treat serious infections. However, the higher doses required may result in increased adverse effects, eg nephrotoxicity.

Peak levels for vancomycin have not been proven to correlate with efficacy or toxicity.

Question 21

How is vancomycin administered parentally?

Answer 21

Give over at least 60 minutes (rate not >10 mg/minute for doses >500 mg) via central venous catheter if possible; avoid extravasation; never give IM.
Do not mix with other drugs in parenteral solutions.

Question 22

Why is vancomycin given orally for clostridium difficle-associated disease?

Answer 22

•vancomycin is poorly absorbed from the GIT; oral vancomycin is used only for recurrent, refractory or serious cases of Clostridium difficile-associated disease

Question 23

What monitoring is required for vancomycin?

Answer 23

• monitor renal function and complete blood count at least once a week; more frequently during prolonged and/or high-dose treatment and in people with impaired renal function including the elderly
• consider monitoring hearing during long courses