Therapeutic Drug Monitoring

of Vancomycin

Presented by:
Saqib Saeed Chaudhary (D18M133)
Hammad Hassan Bhatti (D18M150)
THERAPEUTIC DRUG
MONITORING
DEFINITION
 Therapeutic drug monitoring may best be defined as a strategy whereby the
dosing regimen for a patient is guided by repeated measurement of plasma (or
serum) drug concentrations (Spector et al., 1988).
TDM refers to the measurement of blood or plasma drug concentration
measurements with the purpose of optimizing a patient’s drug therapy and
clinical outcome while minimizing the risk of drug-induced toxicity.
CRITERIA FOR TDM (Drug related)
1. Drug with a narrow therapeutic index.

2. Drugs should exhibit non-linear kinetics.

3. Tdm is based on the principle that there is a relationship between the

plasma level of the drug and the clinical effect.
INDICATIONS for TDM
 Suspected Dose-related Toxicity
 Suspected Noncompliance
 Acute Overdose
 Drug adjustment
 Chronic Abuse
 Reduced Kidney Or Liver Function
 Potential Interaction With Other Drugs
 Evaluation Of Absorption
 And Optimization Of Treatment.
CLINICAL SIGNIFICANCE
OF TDM
 To optimize and/or individualize dosage regimens.
 To maintain efficient and safe drug therapy.
 Monitoring maintains plasma drug concentration within
the target range with minimum risk of adverse
responses.
 Increase the probability of a successful outcome.
 Identifies therapeutic failure.
VANCOMYCIN
Vancomycin was first discovered in 1950 , used clinically
in 1955, and was approved by FDA in 1958.
MRSA was first seen in 1961.
It is extracted from the soil bacteria streptococcus orientalis
It is a glycopeptide antibiotic.
MECHANISM OF ACTION
 Vancomycin inhibits cell wall synthesis by binding firmly to the
D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide.
 This inhibits the transglycosylase preventing further elongation of
peptidoglycan and cross-linking.
 The peptidoglycan is weakened and the cell becomes susceptible
to lysis.
 The cell membrane is also damaged which contributes to the
antibacterial effect.
Specifically, vancomycin
prevents the incorporation of
N-acetylmuramic acid
(NAM)- and N-
acetylglucosamine (NAG)-
peptide subunits from being
incorporated into the
peptidoglycan matrix; which
forms the major structural
component of Gram-positive
cell walls.
This action is bactericidal for
gram-positive bacteria in the
concentration of 0.5-10mcg/ml.
SPECTRUM OF ACTIVITY
 Gram-positive cocci:
 Streptococci
 Staphylococci (S. aureus, coagulation-negative Staph)
 Enterococci (most E. faecalis, variable E. faecium)
 Bacteriostatic against Enterococci (add an aminoglycoside to obtain bactericidal activity)
 Gram-positive bacilli
 Listeria monocytogenes
 Bacillus spp
 Corynebacterium
 Gram-positive anaerobes:
 Peptosterptococcus spp
 Actinomyces spp
 Clostridium spp (including C. difficile)
INDICATIONS
Treatment of serious infections caused by susceptible organisms resistant to
penicillin MRSA and MRSE
For infections caused by gram-positive microorganisms in patients with serious
allergies to beta-lactam antibodies.
To treat clostridium difficile-associated diarrhea.
Antibacterial prophylaxis for endocarditis.
Empirical Therapy for infections associated with central lines, hemodialysis
shunts, vascular grafts, prosthetic heart valves
Consider last resort medication for septicemia(gram-positive bacteria).
The gold standard for Hospital-acquired Infections such as; ventilator-associated
pneumonia, catheter-associated urinary tract infections, central line-associated
bloodstream infections, and surgical site infections.
 VANCOMYCIN
ADMINISTRATION
 Should not be given I/M(injection site necrosis)
 The primary route of administration is I/V infusion in
0.9% NaCl or 5 %glucose
 Is given slowly(usually over 60 min) to reduce the risk
of tissue necrosis and infusion reactions like Red man
syndrome
 Rate of infusion; no faster than 10mg/min
PHARMACOKINETICS
ABSORPTION;
 Vancomycin is poorly absorbed orally in GIT

 The bioavailability following intravenous administration is 100%; that of orally

administered vancomycin is less than 10%.
 C max 3mcg/ml, T max is 1 hour
DISTRIBUTION
 With IV. infusion, distribution typically occurs over a period of about 30 minutes
 10 -55 percent protein binding
 Children; Vd is 0.26 to 1.05 L/kg
 Adult; Vd is 0.5 to 0.9 L/kg
 Vancomycin has a wide distribution and distributes well into the pleural pericardial synovial
fluid.
PHARMACOKINETICS
ELIMINATION;
 Intravenous about 75 % is excreted in urine by GFR
(in 24 hours) as an unchanged
 The mean half-life is 6 hours Oral; faeces
 In patients with normal renal function the clearance
shows a mean value of 1 ml/min/kg.
 VANCOMYCIN DOSE
 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
 For serious infections; consider a loading dose of 25mg/kg i.v. followed
by 15-20mg/kg 8-12h (45-60 mg/kg/day divided 12h or 8h)
 BASIS OF RESISTANCE
Alteration in the D-Ala-D-Ala unite of peptidoglycan
to D-Ala-D-Lactate which cannot be bonded to
vancomycin.
 This results in the loss of a critical hydrogen bond that
facilitates the high-affinity binding of vancomycin to
its target and loss of activity.
Why monitor vancomycin?

 It has a low therapeutic index

 Can cause
 Nephrotoxicity

 Ototoxicity

 A dose greater than 4 g/day is likely to cause toxicity

 The toxicity of vancomycin is related to total drug exposure as compared
to peak
When To Monitor
Vancomycin?
 Vancomycin therapy longer than 5 days
 Patients receiving aggressive dosing (to achieve trough levels 15-20
mg/L)
 Impaired renal function
 Impaired hepatic function
 Pregnancy
 Severe burns
 Obesity
 Concomitant therapy with nephrotoxic drugs
Clinical Signs
Of Toxicity
 Red Man Syndrome
 Angioedema
 Leucopenia
 Thrombocytopenia
 Ototoxicity
 Nephrotoxicity
Monitoring Guide For
Vancomycin:
 No peak is necessary
 Trough needs to be above the MIC of the targeted organism
 The MIC of vancomycin is approximately 1.5mg/L for many susceptible
organisms
How To Monitor?
 Target trough level: 10-15mg/L (15-20mg/L in severe infections)
 Trough rather than peak levels are monitored in the case of vancomycin
 Trough levels should be taken within 1 hour before the 3rd dose
 3rd dose is administered
 Trough levels are again taken before 4th dose
Dose Adjustment According To
Trough Levels?
 Dosing interval is adjusted based on the steady-state
concentration of the drug’s trough
 Low trough: give more frequently
 High trough: give less frequently
Continuous infusion v/s intermittent infusion?
 The theoretical advantages of continuous administration of
vancomycin include consistently maintaining drug
concentration above the MIC without large fluctuations.
Any Questions?
 BIBLIOGRAPHY:
• Assadoon, Maha S, et al. “Evaluation of Vancomycin Accumulation in Patients with Obesity.” Open
Forum Infectious Diseases, vol. 9, no. 10, 21 Sept. 2022, 10.1093/ofid/ofac491. Accessed 16 Jan.
2023.
• Launay-Vacher, Vincent, et al. “Clinical Review: Use of Vancomycin in Haemodialysis Patients.”
Critical Care, vol. 6, no. 4, 2002, p. 313, 10.1186/cc1516. Accessed 25 Nov. 2019.
• Brunetti, Luigi, et al. “The Risk of Vancomycin Toxicity in Patients with Liver Impairment.” Annals of
Clinical Microbiology and Antimicrobials, vol. 19, no. 1, 31 Mar. 2020, 10.1186/s12941-020-00354-2.
• Martin, Jennifer H, et al. “Therapeutic Monitoring of Vancomycin in Adult Patients: A Consensus
Review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of
America, and the Society of Infectious Diseases Pharmacists.” The Clinical Biochemist. Reviews, vol.
31, no. 1, 2010, pp. 21–4, www.ncbi.nlm.nih.gov/pmc/articles/PMC2826264/#:~:text=Optimal
%20Trough%20Concentration%20for%20Complicated. Accessed 16 Jan. 2023.
• Mulla, Rohinton, and Nisha Patel. VANCOMYCIN DOSING and MONITORING Patient Factors Starting
Dose. 2011.