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RavLect15: GLOS
Glycopeptides, Lipoptide, Oxazolidinones, Streptogramins
| Question | Answer |
|---|---|
| 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
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