Guarascio 6 Vancomycin and Gram Positive Covering Agents

General characteristics of vancomycin

Time and concentration dependent bactericidal activity

• Focus on AUC > MIC

Requires therapeutic drug monitoring

No gram negative coverage

Renal elimination → dose adjustment for renal dysfunction

General characteristics of vancomycin derivatives

Concentration dependent bactericidal activity

• Focus on peak

Does not require therapeutic drug monitoring

No gram negative coverage

Renal elimination → dose adjustment for renal dysfunction

Adverse reactions associated with glycopeptides

Nephrotoxicity

Phlebitis

Red Man Syndrome

Ototoxicity (rare)

Drug Interaction with glycopeptides

Warfarin (Oritavancin) and INR lab testing

Two main monitoring parameters for vancomycin

Drug levels

Kidney function tests

Glycopeptides are DOC for _____

MRSA

Penicillin-resistant S. pneumoniae

Oral vancomycin is used for _____ colitis

C. difficile

Characteristics of Vancomycin Resistant Enterococci (VRE)

Usually E. faecium

Binding issue, not like beta-lactamase

• Modified drug target: D-Ala-D-Ala in cell wall converted to D-Ala-D-Lactate or D-Ala-D-Ser

Van A gene conformation most common

Red Man Syndrome

Adverse effect NOT a drug allergy

Erythematous, flushing (histamine-mediated reaction)

Appears within 5-10 minutes of infusion and usually goes away within 30-60 minutes after stopping infusion

• Main differences from a true drug allergy

No hives or blotchiness

Treatment/Prevention of Red Man Syndrome

Slow infusion to no greater than 1 g/hour

Pre-medicate with antihistamine

Characteristics of telavancin

Once daily administration without therapeutic drug monitoring

Treatment of SSTIs, MRSA, and HAP/VAP

Concentration dependent bactericidal activity

Slightly higher incidence of nephrotoxicity than vancomycin

Black box warning for pregnancy

Avoid with agents that prolong QTc

Characteristics of dalbavancin

Treatment of SSTIs, osteomyelitis

Extended half-life

Often single dose or two doses separated by a week

Reduces IV infusions and lines in outpatient setting

Excreted primarily by kidney → watch renal impaiment

IV infusion should be no faster than 30 minutes (red-man like reaction)

Characteristics of oritavancin

Treatment of SSTIs, osteomyelitis

Extended half-life

Reduces IV infusions and lines in outpatient setting

Hepatic metabolism and clearance → may be useful for patients with renal dysfunction

Can cause coagulation test interference (falsely prolonged aPTT for up to 120 hours and prolonged PT and INR for up to 12 hours)

• False reading NOT true coagulation problems

Less infusion site reactions than vancomycin

Characteristics of daptomycin

Covers staph, strep, enterococcus (including VRE)

Concentration dependent

• Peaks drive efficacy

Good choice if you can’t use vancomycin

NOT used for pneumonia because it is inactivated by lung surfactant

Can cause CPK elevations and myopathies

• Monitor, especially when used with statins (not a contraindication)

Renal clearance and dosage adjustment for renal function

Daptomycin is DOC for _____

MRSA

VRE

Daptomycin-Induced Eosinophilic Pneumonia

Eosinophils deposit in the lung → difficulty breathing

Rare

If this occurs, discontinue daptomycin and use a different agent

Common streptogramins and oxazolidinones

Quinupristin/dalfopristin (IV)

Linezolid (IV, PO)

Tedizolid (IV, PO)

Mechanism of streptogramins and oxazoladinones

Inhibit protein synthesis at the 50S ribosomal subunit

• Bacteriostatic

Spectrum of streptogramins and oxazoladinones

Gram positives ONLY

Streptogramins and oxazoladinones are DOC for _____

MRSA

VRE

Notable concerns with quinapristin/dalfopristin (Synercid)

Severe thrombophlebitis

Hepatotoxicity

CYP3A4 inhibition

Characteristics of linezolid

Complete oral bioavailability

Significant thrombocytopenia

• Decreased platelets → bleeding risk

• Usually not until 10-14 days of therapy

Monoamine oxidase inhibition and risk for serotonin syndrome

Hepatic clearance

Characteristics of tedizolid

Complete oral bioavailability

Potentially:

• Reduced activity in neutropenic host

• Less thrombocytopenia

• Shorter course for SSTIs

MAOI effects not well described

Hepatic clearance