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Names & IDs Slide No. Omar Ashraf - 180501 2 Seifallah Salaheldin - 184211 3 Sara Hesham - 180947 - Rawan Ayman - 181763 - Shaimaa Gamal - 180543 4 & 5 Tasneem Magdy - 180467 6 & 7 Noran Islam - 182019 8 Yehia Taher – 180889 9 & 10 Peter Hany - 184641 11

Task Sheet

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Vancomycin

Vancomycin is one of the antibiotics which is can be taken orally (taken by mouth). Vancomycin fights bacteria that present in the intestine. And treat a certain intestinal condition (colitis) caused by bacteria. It also is used to treat an infection of the intestines caused by Clostridium difficult, which can cause watery or bloody diarrhea. This medicine is also used to treat staph infections that can cause inflammation of the colon and small intestines.

Uses

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Pharmacological Actions

Vancomycin has bactericidal action which inhibit cell-wall biosynthesis which blocks N-acetyl-muramic acid (NAM) - and N-acetyl-glucosamine (NAG)-peptide subunits integration from being integrated into the peptidoglycan matrix that forms the main structural component of Gram-positive cell walls. It forms H- bonds with the terminal D-alanyl-D-alanine moieties of the NAM and NAG-peptides which is blocking NAM/NAG-peptide subunits integration into the peptidoglycan matrix. In addition, vancomycin changes bacterial-cell-membrane permeability and RNA synthesis. - Vancomycin hasn't cross-resistance with other antibiotics. - In vitro, vancomycin is not active against gram-negative mycobacteria, fungi, or bacilli

GlcNAc-MurNAc Disaccharide

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Monitoring Parameters

Highly recommended for optimizing vancomycin therapeutic effect

We should monitor each of: Serum-vancomycin trough plasma conc. Clinical response to the drug. CBC weekly for long term therapy Serum Creatinine level (SCr)

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Monitoring Parameters Cont.

Nephrotoxicity & Ototoxicity To monitor toxicity, trough monitoring is suggested on: Aggressive dosing recipients. High risk patients who are taking nephrotoxins / ototoxins concurrently. Patients suffering unstable renal function . Patients on prolonged therapy (> 5 days)

Vancomycin is cleared through the kidneys , thus require dose adjustment based on GFR changes.

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Therapeutic & Toxic Range

When vancomycin was first used in the 1980s, the target trough level was 5-10 mg/L over time, bacteria have grown more resistance to vancomycin To avoid development of resistance, vancomycin trough levels should remain above 10.0 mcg/mL 15-20 mg/kg every 8-12 hours in patients with normal renal function. In seriously ill patients ( eg , sepsis, meningitis, infective endocarditis) with suspected MRSA infection, a loading dose of 25-30 mg/kg may be considered.

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Therapeutic & Toxic Range Cont.

If the trough and/or peak concentrations are above the maximum levels, then the person is at an increased risk of vancomycin nephrotoxicity, trough plasma levels >20 μg / mL. The reference range for vancomycin trough levels is 5-15 mcg/ mL. The reference range for vancomycin peak levels is 20-40 mcg/ mL. Therapeutic: 20.0-45.0 mcg/ml.

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Mild-to-severe: Initial dose should be no less than 15 mg/kg

Dose Adjustment in Patients with Renal Failure

The half life of the vancomycin in Patients with normal renal function 4to 6 hours. While patients with impaired renal functions half life of vancomycin is 7.5days . as elimination differs from each person differently . Patients maintain dose of 10mg/ml for all infections,in severe or complicated infections concentrations range from 15 to 20mg/ml

In case of patients who are not obese: doctors adjust loading dose from 20-35mg/kg If patient is obese: loading dose is adjusted from 20-25mg/kg

Nine studies of patients with impaired liver function Had a much longer t1/2 beta (37 h) and a decrease in the rate of total clearance to 48 ml/min. These factors resulted in an increase in the value of area under the concentration-time curve These results have demonstrated the importance of the effects of liver function on vancomycin disposition. The vancomycin dose and schedule should be adjusted for patients with liver impairment

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A trough sample should be taken after 48 hours have passed from the start of the treatment that is approximately taken in the third day, within 30 minutes before the morning dose Trough should be taken at new steady state with the dose changing once achieving target trough it will be taken every (7-10 days) Maintain trough serum vancomycin concentrations of at least 10 mg/L for all infections to avoid the potential for resistance Maintain trough serum vancomycin concentrations of 15-20mg/L for complicated infections It is not appropriate to monitor routine levels more than twice a week in thermodynamically stable cases but in cases of instability, it needs to be more frequent as in the case of disturbance in the renal functions and patients on antimicrobials (Thomson et al., 2009).

100 10 10 • 11 12 Time (hour)

Plasma Concentration Monitoring Guidelines

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With unstable renal functions (Nephrotoxicity) With age over than 65 years old (adult patients) Who have taken aggressive doses of vancomycin

Who receive vancomycin with medicines that can cause damage to the kidneys on the prolonged use Antimicrobials such as aminoglycosides Specific types of chemotherapies

Who have taken vancomycin in combination with ototoxic agents as aminoglycosides leading to ototoxicity(Thomson et al., 2009)

Nephrotoxicity

OtotoxieÄLw Sig a Treat rnerat

Monitoring should be recommended continuously and intensively for patients

peak serum concentrations of vancomycin don’t support any information to monitor nephrotoxicity (peak:25-40 mg/ml)

NB

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Side effects

Bitter taste Reddish rash on face and upper body Low blood pressure accompanied by flushing Nausea Vomiting Fatigue Urinary tract infection Headache Kidney damage mood changes Steven-Johnson syndrome Wheezing hearing loss Shortness of breath Itching