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RavLect15: GLOS

Glycopeptides, Lipoptide, Oxazolidinones, Streptogramins

Glycopeptides Vancomycin Telavancin
Vancomycin MoA Irreversibly binds to bacterial cell wall to inhibit the formation of peptidoglycan Not rapidly bactericidal
Vancomycin PK Concentration INdependent! T>MIC/AUIC/MIC Good concentration into bone. Low in epithelial lining and meninges. Inadequate for meningitis, pneumonia response is slow, sometimes inadequate.
Vancomycin SoA G+ aerobic cocci: Staphylococci, Streptococci, Enterococci G+ anaerobic cocci: Peptostreptococci G+ aerobic bacilli: Corynebacterium, Listeria G+ anaerobic bacilli: Clostridium Rarely used: G- b/c Vanco has very limited activity
Vancomycin ADRs Red Man Syndrome (avoid by slowing infusion) Nephrotox & Ototoxicity (rare) increased w/ AGs & loop diuretics Eosinophilia, neutropenia
Resistance to Vanco Enterococcus faecium & faecalis: VRE Staph aureus: VISA, VRSA. Inducible due to Van genes.
Vancomycin clinical use Used for moderate to severe infections caused by MRSA, MRSE, Enterococcus, gram positive sepsis, bacteremia, endocarditis, osteomyelitis for ptx w/ life threatening beta-lactam allergies/gram positive infection PO vanco metronidazole-resistant C dif
Vancomycin dosing regimen Based on Matzke Nomogram CrCl>90 ml/min : 12 hr dosing interval 75-90 ml/min: 18 hr 55-74 ml/min: 24 hr 35-54 ml/min: 38 hr 25-34 ml/min: 48 hr Monitor troughs (5-15mcg/ml desired) only when needed! (no need for peaks b/c conc INdependent)
When to monitor Vanco troughs? Ptx w/ anticipated therapy > or = 7 days Ptx w/ fluctuating renal function, or on dialysis Ptx on other nephrotoxic agents Ptx on higher than normal doses Obese ptx Pediatric ptx Critical ptx who aren't hemodynamically stable MIC valu
Lipoglycopeptide Telavancin (Vibativ) Like Vanco, but w/ addtl hydrophobic side chain & hydrophilic side chain
Telavancin (Vibativ) MoA Dual mechanism: inhibiting bacterial cell wall synthesis by disrupting peptidoglycan & depolarization of the bacterial cell membrane. Thus, more rapidly bactericidal than Vanco
Telavancin SoA G+ organisms •Staphylococcus including MRSA and MRSE •Streptococcus including DRSP •Enterococcus faecalis and faecium but not all VRE •Corynebacterium Indicated for cSSSI (complicated skin & skin structure infection)
Telavancin PK Linear, concentration-dependent, bactericidal activity against G+
Telavancin ADRs Teratogenic NVD, headache, dizziness Taste disturbance (metal/soapy) Increased creatinine Decreased platelet counts Microalbuminuria QTc prolongation Red man syndrome w/ rapid infusion Increase INR,PT,APTT,ACT of anticoag tests
Lipopeptide Daptomycin (Cubicin)
Daptomycin MoA Depolarizes bacterial membrane Inhibit protein DNA and RNA synthesis Bactericidal activity by disrupting plasma membrane (cell wall leaks, but stays intact)
Daptomycin PK Bactericidal Post antibiotic effect 80% renal excretion Deactivated by pulmonary surfactant (NOT good for pneumonia Tx)
Daptomycin SoA Similar to vancomycin, anti-staph PCN, linezolid, quinipristin-dalfopristin Good clinical activity against MRSA, VRSA, VISA(GISA), VRE No well documented studies against anaerobes, in-vitro activity against Clostridium difficile & perfringens
Daptomycin ADRs Abnormal LFTs Elevation in CPK Muscle pain (myalgia) and weakness usually distal extremities, some peripheral neuropathy reports Injection site reactions
Daptomycin Clinical Use skin and soft tissue infections diabetic foot caused by gram(+) organisms - Synergistic activity with ampicillin against E. faecalis, with gentamicin against E. faecium NOT used for pneumonia’s
Oxazolidinones Linezolid (Zyvox)
Linezolid (Zyvox) MoA Inhibits bacterial cell wall synthesis by binding to bacterial ribosomes (23S) Static mostly, but cidal against Strep
Linezolid PK 100% bioavailability Distributes well into highly perfused tissues Good penetration into epithelial lining
Linezolid SoA Most gram (+) organisms, including MRSA, VRE Bacteriostatic against Staph and Enterococcus Good activity against Listeria monocytogenes Bactericidal against many Streptococci
Linezolid ADRs thrombocytopenia MAOi: avoid tyramine foods & adrenergic, serotonergic agents
Linezolid Clinical Use VRE Nosocomial Pneumonia - MRSA Good survival/cure rates with linezolid against MRSA pneumonia as compared to vancomycin**** Skin and soft tissue infections
Linezolid monitoring Monitor platelet counts (in select ptx) Monitor WBC & differential & anemia markers
Streptogramin Quinupristin & Dalfopristin (Synercid) A synergistic combination
Quinupristin & Dalfopristin (Synercid) MoA binds to 50s ribosome to inhibit protein synthesis cidal drug mainly, but static for VRE
Synercid SoA G+, some G- and anaerobes MSSA, MRSA, Coagulase (-) Staph, Streptococci, Enterococus faecium (most common VRE), Not active against faecalis G-: N. mening, H. flu, M. catarrhalis, Legionella Atypicals M. pneumoniae, Chlamydophila Anaerobes
Synercid ADRs Pain and burning at the injection site (like Nafcilin) so central line required! DDIs w/ 3A4 drugs Hyponatremia Increased LFTs Severe myalgias possible
Created by: cheeoh