14 Vancomycin, Telavancin, Aminoglycosides, Polymyxins Minejima Flashcards
What is Vancomycin?
A large complex, tricyclic antibiotic with a molecular mass of 1,500 Da. Contains a glycosylated hexapeptide chain rich in unusual amino acids (Glycopeptide)
What is Vancomycins MOA?
Inhibits peptidoglycan synthesis and assembly. Acts as a specific peptide receptor by binding with high affinity for the D-alanyl-D-alanine terminus of cell wall precursor units –> inhibits peptidoglycan synthesis –> bactericidal. Rate of inhibition is much slower than with B-lactam agents
What is Vancomycins spectrum of activity?
Narrow-spectrum: Gram (+) bacteria: S. aureus, S. epidermidis, Streptococci, Enterococci, Corynebacterium, Clostridium difficile. NO Gram (-) activity
What are the clinical use indications for Vancomycin?
Infections d/t MRSA, S. epidermidis (prosthetic device infections). Penicillin-resistant Streptococci, Enterococci. C. difficile colitis (PO) failing metronidazole or life-threatening. Patients infected with Gram (+) bacteria with allergy to PCNs and CEPHs. Prophylaxis for surgical procedures involving prosthetic device or endocarditis per AHA
What is Vancomycin NOT recommended for?
Routine surgical prophylaxis. Empiric therapy for febrile neutropenia, unless patient has initial evidence of an infection caused by Gram (+) AND the prevalence of MRSA is high. Treatment of a single blood culture positive for coagulase-negative staphylococci, if other blood cultures taken during the same time frame are negative. Continued empiric use for presumed infections in patients whose CXs are negative for B-lactam resistant Gram (+) organisms. Systemic or local prophylaxis for infection/colonized of indwelling central or peripheral intravascular catheters. Eradication of MRSA colonization. Routine prophylaxis for patients on hemodialysis or ambulatory peritoneal dialysis. Use of vanco solution for topical application or irrigation. Treatment of infections caused by B-lactam sensitive Gram (+) organisms in patients who have renal failure
What is the resistance mechanism of vancomycin-resistant Enterococci and VRSA?
Vancomycin-resistant enterococci in the presence of vancomycin make cell-wall precursors that have low affinity for vancomycin (alter the “lock and key”)
What is Vanco-Resistant S. Aureus (VRSA)?
First clinical case demonstrating transfer of VRE resistance (vanA gene) to S. aureus through exchange of genetic material
What is Vanco-Intermediate S. Aureus (VISA)?
All developed from pre-existing MRSA strains. All had prolonged vanco therapy. Thickened cell wall, vanco unable to cross
What is the role of vancomycin vs. MRSA?
Increasing reports of treatment failure despite attaining therapeutic throughs. Emergence of clinical strains with reduced susceptibility (hVISA, VISA, VRSA)
What are the characteristics of VRSA?
Rare; MIC 32-1028 mcg/ml. Fully resistant likely; vanA operon acquired from VRE. Patients infected with both MRSA and VRE
What are the characteristics of VISA?
MIC 4-16 mcg/ml, “intermediate” R. Overproduce a matrix that captures vanco and keeps it from entering the cell; “thickened” cell wall on electron microscopy. Patients have had long term vancomycin therapy
What are the characteristics of Vanco tolerance?
MBC:MIC > 32; “stunted” not killed
What are the characteristics of hVISA?
MIC in “S” range: 0.5-8 mcg/ml. Prevalence 2-76%; not detected by routine tests. Accounts for treatment failure to vanco vs. “S” strains
What is the lab detection problem with hVISA?
Available tests do not reliably detect resistance. The MIC will show on an E-test, but there will still be some small random colonies in the zone of inhibition
What are the MIC breakpoints for S. aureus?
S: < 2, I: 4-8, R: > 16
What is the IV dosage like for Vancomycin?
“Usual” daily dosage, need to calculate based on renal function to achieve “target” levels. Adults: 20-30 mg/kg/d (10-15mg/kg Q6h to Q12h). Children: 40 mg/kg/d (10mg/kg Q6h or 15mg/kg Q8h)
What is the PO dosage like for Vancomycin?
125-500mg Q6h (for C. difficile colitis ONLY!)
What can happen with rapid IV infusion of Vancomycin?
Red-man syndrome. Dilute to 100-250 mL; doses 0.5-1g infuse over 60 min at least. Relates to histamine release
What is the PK of vancomycin like?
F < 5%; may reach therapeutic serum concentration in presence of inflammatory bowel disease and renal failure. CSF penetration variable, meningitis requires intrathecal administration (5mg). Elimination by GF almost exclusively (dose adjustment needed). T1/2 normal: 6-8 hrs; anuric ~7.5 days
What is the PD of vancomycin like?
Time-dependent killing, moderate persistent effects. Maximal bactericidal activity at 4-5x MIC or AUC/MIC 400. Target trough levels based on sensitivity of organism and severity of infections
What is the goal PD of vancomycin?
Maintain unbound levels 4-5x above MIC throughout dosing interval or AUC/MIC 400
What is the trough target for vanco at MIC 1?
Trough target 10 mg/L accounting for 50% ppb
What is the trough target for vanco at MIC 2?
Trough target 15-20 mg/L. Higher concentrations for deep tissue infections, endocarditis, meningitis, osteomyelitis
What are the ADRs of Vancomycin?
Red-man syndrome. Ototoxicity. Nephrotoxicity. Hypersensitivity reactions: rash, anaphylaxis
What is Red-Man Syndrome?
Flushing of the face, neck and thorax, increased HR, decreased BP. Caused by rapid infusion rate, large dosage. Histamine-release (NOT allergic hypersensitivity)
How do you manage Red-Man Syndrome?
Prolong infusion time, dilute concentration, premedicate with diphenhydramine