Glycopeptides

Agents: vancomycin, telavancin

To date, there are three glycopeptides in clinical use: vancomycin, teicoplanin, and telavancin. Teicoplanin is not used in the United States, and telavancin was only recently approved. At least two more glycopeptides are in late stages of clinical development: oritavancin and dalbavancin.

Vancomycin is invaluable, because it has activity against all things Gram-positive that have not learned to become resistant to it. Many enterococci  (especially  E. faecium) have figured this out—we call them vancomycin-resistant enterococci (VRE).  A few staphylococci have learned vancomycin-resistance from the enterococci, but these staphylococci are currently very rare. In general they are susceptible.

Telavancin is a somewhat different agent. It is a lipoglycopeptide that was modified from vancomycin’s structure. It has some unique properties that may be advantageous compared with vancomycin, such as improved activity against MRSA that is less susceptible to vancomycin, but its place in therapy is still being determined

Spectrum

Good: MSSA, MRSA, streptococci, Clostridium difficile

Moderate: enterococci

Poor : anything Gram-negative

Adverse Effects

Ototoxicity and nephrotoxicity are adverse effects classically assigned to vancomycin. Although the historical evidence linking these with vancomycin is poor, recent studies have shown that it may be nephrotoxic in high doses. The early formulation of vancomycin was brown, and clinicians trying to amuse themselves dubbed it “Mississippi mud.”  The current formulation is clear and lacks those potentially toxic excipients. A histamine-mediated re-action called red man syndrome can occur; the patient may feel warm, flushed, and can be hypotensive. This reaction can be prevented by slowing the infusion rate and is not a true allergy.  Antihistamines can also ameliorate the reaction.  Telavancin has renal toxicity issues as well.  Taste disturbances and foamy urine are more common. Telavancin should not be given to pregnant women because of problems seen in animal studies.  Because telavancin is a modification of vancomycin,  red man syndrome may also occur with telavancin.

Dosing Issues

Vancomycin is often pharmacokinetically monitored, but the evidence that these concentrations mean anything is lacking, particularly for peak concentrations. Trough concentrations can be used to ensure that the drug is not being eliminated too quickly or slowly, and different indications have different preferred trough ranges. Recent data indicate that higher troughs may be associated with nephrotoxicity.

Important Facts

• Oral vancomycin is absorbed poorly. Its only use is for the treatment of  Clostridium difficile–associated disease. Also, IV vancomycin does not reach intracolonic concentrations high enough to kill  C. difficile, so oral is the only way to go.

• Do not overreact if your vancomycin trough is too high. Was it drawn correctly? If so, increase your dosing interval.

• Although vancomycin is active against staphylococci, it does not kill MSSA as quickly as beta-lactams do. Does your patient have MSSA? Use nafcillin or cefazolin instead.

• Recently, a phenomenon described as “MIC creep” has been seen with staphylococci and

vancomycin. MICs have been rising to vancomycin in many institutions, and while they have not yet reached the level of resistance,  they are increasing within the range labeled as susceptible, that is, ≤ 2 mcg/ml. However, patients receiving vancomycin for serious infections caused by staphylococci with an MIC  =  2 mcg/ml to vancomycin have been shown to have worse outcomes than those with lower MICs. This issue warrants careful attention.

• Telavancin is more rapidly bactericidal than vancomycin. This activity may be an advantage in the treatment of some infections, but clinical evidence that shows a benefit is lacking at this point.

What They’re Good For

Vancomycin is a drug of choice for MRSA infections and for empiric use when MRSA is a concern, such as for nosocomial pneumonia. It is also useful in other Gram-positive infections when the patient has a severe beta-lactam allergy. Telavancin is indicated only for skin and skin structure infections at this time. It has activity against organisms with decreased vancomycin susceptibility, but its role is still being defined.

Don’t Forget!

Are you sure that vancomycin trough concentration was drawn correctly?

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.