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:
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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
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