Infectious Diseases II
| (e) | The 2011 IDSA guidelines for the treatment of MRSA state that the treatment of isolates |
|---|
with a vancomycin MIC of 2 mcg/mL or less should be determined by the patient’s
response to vancomycin, independent of the MIC.
| d. | MRSA pneumonia |
|---|
Community-acquired MRSA pneumonia can be treated with either vancomycin or linezolid.
Clindamycin can be considered if the strain is susceptible.
ii.
Community-acquired MRSA infections may be associated with the presence of Panton-
Valentine leukocidin, which is a two-component staphylococcal membrane toxin that targets
leukocytes. This toxin has been linked with severe infections, necrotizing pneumonia, and
abscess formation. Theoretically, clindamycin and linezolid, being ribosomal subunit and
protein synthesis inhibitors, may attenuate the amount of toxin production.
iii.
A randomized controlled study comparing linezolid to vancomycin included patients with
hospital-acquired pneumonia and ventilator-associated pneumonia who had a baseline
respiratory culture positive for MRSA.
| (a) | Vancomycin was dosed by weight and adjusted locally according to trough levels. |
|---|---|
| (b) | This was a noninferiority study with nested superiority criteria where the primary end |
point was clinical response at the end of the study.
| (c) | Clinical response was defined as resolution of signs of pneumonia with no further need |
|---|
for other antibiotics.
| (d) | Study met both the noninferiority and the superiority criteria with respect to clinical |
|---|
response and microbiological clearance.
| (e) | Study may have been confounded by less than 50% of patients reaching vancomycin |
|---|
target concentrations by day 3 and the vancomycin patients having a slightly higher rate
of baseline bacteremia.
| (f) | No difference in mortality was seen. |
|---|---|
| (g) | Many clinicians interpret the results from this study as suggesting that either vancomycin |
or linezolid can be considered for the treatment of MRSA pneumonia.
Updates to vancomycin dosing and monitoring
Consensus guidelines for therapeutic monitoring of vancomycin were published in 2020.
ii.
AUC24 of 400–600 mg/hour/L is recommended target to improve clinical efficacy and patient
safety. For most isolates, an MIC of 1 mg/L can be assumed.
iii.
Trough targets are no longer recommended for patients with serious MRSA infections.
iv.
Bayesian dosing is the recommended method for dosing adjustments. Bayesian dosing does
not require steady-state vancomycin concentrations for early determination of AUC target
attainment.
Novel agents for the treatment of MRSA
Tedizolid is FDA-approved for the treatment of bacterial skin and skin structure infection.
| (a) | Antimicrobial class: Oxazolidinone |
|---|---|
| (b) | Spectrum of activity: Gram-positive pathogens including MRSA, vancomycin-resistant |
enterococci, vancomycin-resistant staphylococci, drug-resistant S. pneumoniae, and
linezolid-resistant gram-positive pathogens
| (c) | PK and dosing |
|---|---|
| (1) | Bioavailability 91% – Can be administered as a parenteral solution or oral tablets |
| (2) | Half-life: 12 hours |
| (3) | Dosing: 200 mg once daily |
| (d) | Studies: |
| (1) | Tedizolid once daily for 6 days was compared with linezolid twice daily for 10 days |
for the treatment of acute bacterial skin and skin structure infection and was found
to be noninferior.