Vancomycin

general topic

1. Vancomycin Lakshmi Narayana M.

2. Now you follow… Introduction Mechanism of action Pharmacokinetics Indications Recommended dosing schedule contraindications Possible side effects Acquired resistance

3. Introduction Vancomycin is an antibiotic used to treat a no. of bacterial infections Vancomycin was first discovered in 1950 and was approved by the Federal Drug and Agency (FDA) in 1958 It is extracted from soil bacteria S. orientalis It is a glycopeptide antibiotic used to treat infections caused by gram-positive bacteria Named vancomycin because it was going to vanquish penicillinase producing S. aureus

4. Mechanism of action Vancomycin acts by inhibiting proper cell wall synthesis in Gram-positive bacteria Inhibit Cell wall synthesis by binding with ala-D-ala   Inhibit trans glycosylase. Alter cell membrane permeability Cell become susceptible to lysis

5. Pharmacokinetics ABSORPTION: Vancomycin is poorly absorbed orally in GIT When given parenterally drug distributes widely into tissues Cmax 63mcg/ml. Tmax is 1h DISTRIBUTION: 55% protein bound. Vd is 0.3 to 0.43 L/kg  Distributes well into pleural ,pericardial synovial fluid. ELIMINATION Intravenous: about 75% is excreted in urine by GFR (in 24 hours) as a unchanged. Mean half life is 4-6hours  Oral: faeces

6. Indications Treatment of serious infections caused by susceptible organisms resistant to penicillin's MRSA (methicillin-resistant  S. aureus) and MRSE (multidrug-resistant Staphylococcus epidermidis ) For treatment of infections caused by Gram-positive microorganisms in patients with serious allergies to beta-lactam antimicrobials Antibacterial prophylaxis for endocarditis following certain procedures in penicillin-hypersensitive individuals at high risk Vancomycin is considered a last resort medication for the treatment of septicemia and lower respiratory tract, skin, and bone infections caused by Gram-positive bacteria Vancomycin has been the gold standard for treating hospital acquired infections such as: ventilator associated pneumonia, Bacteremia ( septicemia ), Catheter associated urinary tract infection, Central line associated blood stream infections, Surgical site infections (SSI)

7. Recommended dosing schedule ≥ 1 month – 6 years: 40mg/kg/day divided every 6 hours > 6 years – 18 years: 40mg/kg/day divided every 8 hours > 18 years: 15mg/kg/dose every 12 hours Uncomplicated Infections: 10-15 mg/kg q12h1 Serious Infections: Consider loading dose of 25mg/kg iv , followed by 15-20 mg/kg 8-12h (45-60mg/kg/day divided 12h or 8h)

8. Contraindications Hypersensitive to drug. Caution if renal impairment Caution if concurrent nephrotoxic agent use Caution if hearing impairment Caution if concurrent ototoxic agent use Caution in elderly pts Pregnancy Category C for parenteral route May use while breastfeeding; Patients with Renal disease, inflammatory bowel disorders may have an increased chance of adverse effects

9. Possible side effects Fever Chills Flushing Phlebitis Ototoxicity** Nephrotoxicity** Rapid iv infusion may cause diffuse flushing (red man syndrome)** Anaphylaxis/anaphylactoid reaction (Allergy)

10. Acquired resistance The alteration to the terminal amino acid residues of the NAM/NAG-peptide subunits, under normal conditions, D-ala-D-ala, to which vancomycin binds. This loss of just one point of interaction results in a 1000-fold decrease in affinity Three main resistance variants have been characterised to date among resistant  Enterococcus faecium  and  E. faecalis  populations: VanA - enterococcal resistance to vancomycin and teicoplanin; inducible on exposure to these agents VanB - lower-level enterococcal resistance; inducible by vancomycin, but strains may remain susceptible to teicoplanin VanC - least clinically important; enterococci resistant only to vancomycin; constitutive resistance

11. Bullet points Helpful in MRSA (methicillin-resistant  S. aureus) and MRSE (multidrug-resistant Staphylococcus epidermidis ) A last resort medication for the treatment of septicemia and lower respiratory tract, skin, and bone infections caused by Gram-positive bacteria Gold standard for hospital acquired diseases.