STREPTOGAMINS

QUINOPRISTIN-DALFOPRISTIN Dalfopristin streptogramin A Quinupristin streptogramin B Quinopristin-Dalfopristin = 30:70 ratio Bactericidal (most organisms, except Enterococcus faecium)

Antibacterial activity
G (+) cocci (inc. resistant strains of Streptococci) Staphyloccoci (Methicillin-resistant & suscebtible strains) PCN-resistant strains of S. pneumoniae E. faecium (not E. faecalis)

Pharmacokinetics
Administered IV

Rapid metabolism: Quinopristin (0.85 hrs) Dlafopristin (0.7 hrs) Not metabolized by CYP450 enzymes BUT significantly inhibits CYP3A4(metabolizes
warfarin, diazepam, astemizole, terfenadine, cisapride, cyclosporine, non-nucleoside reverse transcriptase inhibitors)

Pharmacokinetics
Elimination: Fecal route : 75 % Urine : < 20 % Dose adjustments NOT necessary in: Renal failure, peritoneal- or hemodialysis Dose adjusted in Hepatic insufficiency

Adverse effects:
Infusion-related events: pain at injection site
phlebitis arthralgia-myalgia syndrome

OXAZOLIDINONES

LINEZOLID
MOA: Prevents formation of ribosome complex that initiates protein synthesis : Binds to 23S ribosomal RNA of the 50S subunit Resistance : mutation of linezolid binding site on 23S ribosomal RNA

Antibacterial activity
BACTERIOSTATIC: G (+) pathogens : Staphyloccoci, anaerobic cocci G (+) rods: Corynebacteria, Listeria monocytogenes

BACTERICIDAL: Streptococci

Pharmacokinetics
Oral = 100% bioavailability

Metabolism: Oxidation = 2 inactive metabolites Does not induce/inhibit CYP450 enzymes

Dose: 600 mg 2x/day

Pear serum conc. = 18 ug/ml

Indications
Nosocomial pneumonias

Community-acquired pneumonia
Vancomycin-resistant E. faecium infxns.

Skin infections
Multiple drug-resistant G(+) bacteria

Toxicity
Thrombocytopenia - > 2 weeks admn. Neutropenia (in predisposed pxs. or pxs with bone marrow suppression)