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 |