vancomycin protocol

Page 1

Guideline : Vancomycin

MRSA PRACTICE GUIDELINE

Clinical pharmacy department Cairo University Hospitals Prepared by :

Page 2


TABLE OF CONTENTS Background......................................................................................................... 3 Indications.......................................................................................................... 4 Prevalence ...................................................................................................... 5 Neonatel Dose ..................................................................................................... 6 Infants and Children dose .................................................................................... 7 Dosing according to indication ....................................................................... 10 Administration .................................................................................................... 10 Vancomycin Toxicity............................................................................................ 11 Monitoring Parameters................................................................................... 12 Renal function based dosing................................................................................. 14 Appendix 1……………………………………………………………………………………………………… 16 Appendix 2……………………………………………………………………………………………………… 17 Appendix 3……………………………………………………………………………………………… …… 18

Page 3


Background Vancomycin is a glycopeptide antibiotic that has activity against gram positive organisms including methicillin resistant staphylococcus aureus (MRSA), and some enterococcus species. It has been shown that higher doses of vancomycin may be required in some pediatric patients. Patients who are at high risk of developing infections with MRSA include patients with current or prior skin and soft tissue infections, musculoskeletal infections, patients treated with frequent courses of antibiotics, and frequent hospitalizations.

Introduction Methicillin resistance in S. aureus is defined as an oxacillin minimum inhibitory concentration (MIC) ≥4 mcg/mL. Isolates resistant to oxacillin or methicillin also are resistant to all beta-lactam agents Methicillin resistance is mediated by the mecA gene, which encodes for an abnormal low-affinity binding protein, PBP-2a, that permits the organism to grow and divide in the presence of methicillin and other beta-lactam antibiotics

http://uptodate.papi.h12o.es/contents/oxacillin-pediatric-drug-information?source=see_link

Page 4


Indications

Treatment of patients with the following infections or conditions: Infections due to documented or suspected methicillin-resistant S. Aureus or beta-

lactam resistant coagulase negative Staphylococcus. Serious or life-threatening infections (eg, endocarditis, meningitis, osteomyelitis) due to

documented or suspected staphylococcal or streptococcal infections in patients who are allergic to penicillins and/or cephalosporins.

Empiric therapy of infections associated with central lines, hemodialysis shunts, vascular

grafts, prosthetic heart valves . Prophylaxis of peritonitis in patients with peritoneal dialysis (PD) catheters undergoing

invasive gastrointestinal procedure, and for the treatment of peritonitis in patients with peritoneal catheters.

Treatment of C. Difficile-associated diarrhea and Enterocolitis caused by Staphylococcus

aureus (including methicillin-resistant strains)(oral ).

Page 5


Prevalence

Collective antibiogram of respiratory specimens from July – December

ER ICU 4 ICU 6

Augmentin 0% 0% 0%

unasyn 0% 0% 0%

cefoxitin 14% 0% 0%

vancomycin 100% 100% 100%

clindamycin 71% 0% 0%

Eryhromycin 71% 50% 0%

ciprofloxacin 14% 50% 0%

Doxocyclin 28% 50% 0%

Trimrthoprim /sulphomethoxazole

28% 0% 60%

gentamicine 28% 50% 0%

amikacine 28% 50% 0%

Teicoplanin 43% Not found Not found

Collective antibiogram of wound and pus specimens (ER) antibiotic Sensitivity

augmentin 0%

unasyn 0%

cefoxitin 0%

vancomycin 100%

clindamycin 33%

erythromycin 33%

ciprofloxacine 0%

doxocyclin 0%

Trimethoprim/ sulphomethoxazole 66%

Page 6


Neonatel Dose IV infusion by syringe pump over 60 minutes Meningitis : 15 mg/ kg per dose Bacteremia : 10 mg /kg per dose

Dosing interval chart

PMN (weeks)

PostNatal Interval (hours)

≤ 29 0 to 14 ˃ 14

18 12

0 to 14 ˃14

12 8

37 to 44 0 to 7 ˃7

12 8

≥45 ALL 6

Page 7


Infant and children dose :

General dosing, susceptible infection (Empirical)

Age Infection severity Dose Interval Maximum Dose

Infants ≤2 months Mild to moderate infection

40 to 45 mg/kg/day

6 to 8 hours 2,000 mg/day

Severe infection 45 to 60 mg/kg/day


Infants >2 months Mild to moderate infection

40 to 45 mg/kg/day


Severe infection 45 to 60 mg/kg/day


Infants 3 months to Children <2

years

70 mg/kg/day 6 to 8 hours

Children 2 to <12 years

60 mg/kg/day *Higher doses

may be needed if SCr < 0.45 mg/dL

70 mg/kg/day

6 to 8 hours

6 to 8 hours

Page 8


Dosage according to indication (proven infection)

Indication Dose/ Frequency (IV) Duration

Bacteremia(MRSA) 15 mg/kg/dose every 6 hours 2 to 6 weeks

(Depending on

severity)

Bone and

joint

infection

Osteomyelitis

(MRSA)

15 mg/kg/dose every 6 hours 4 to 6 weeks

Septic arthritis

(MRSA)


C. difficile-associated diarrhea

Severe or recurrent infection 40 mg/kg/day in 4 divided doses

≥10 day

CNS

infection

Brain abscess, subdural empyema, spinal epidural abscess


Meningitis 5 mg/kg/dose every 6 hours 2 weeks

VP-shunt infection,

ventriculitis

(use preservative-free preparation)

10 or 20 mg/day

Endocarditis

(AHA guidelines)

40 mg/kg/day divided every 6 to 12

hours

at least 6 weeks

Prophylaxis

(GI or genitourinary procedures)

20 mg/kg over 1 hour

complete infusion 30 min prior procedure

Enterocolitis

40 mg/kg/day divided every 6 to 8 hours

7 to 10 days

Intra-abdominal infection

complicated (MRSA)

40 mg/kg/day divided every 6 to 8

hours

Page 9


Peritonitis

(peritoneal

dialysis)

Prophylaxis Touch contamination of PD line

Intraperitoneal: 25 mg per liter

(known MRSA Colonization)

High-risk gastrointestinal procedures

10 mg/kg administered 60 to 90

minutes before procedure

Treatment Intermittent: Intraperitoneal

Initial dose: 30 mg/kg in the

long dwell

subsequent doses: 15

mg/kg/dose every 3 to 5

days during the long dwell

Continuous: Intraperitoneal

Loading dose: 1,000 mg per

liter of dialysate

maintenance dose: 25 mg

per liter

Pneumonia (CAP): Infants ≥3

months, Children

60 mg/kg/day divided every 6 hours 7 to 21 days

(HAP) : MRSA 60 mg/kg/day divided every 6 hours 7 to 21 days

Skin and skin structure infections,

complicated

60 mg/kg/day divided every 6 hours 7 to 14 days

*If Complete ileus , rectal enema dosage form may be preferable.

Page 10


Administration :

Route of administration Method of preparation

Oral Using a vial of vancomycin powder for injection (reconstituted to 50 mg/mL) using water for injection

Nasogastric tube 1. Stop the enteral feed. 2. Flush the enteral feeding tube with the recommended volume of water. 3. Reconstitute injection as directed (the reconstituted solution can be stored in the fridge for 24 hours for enteral use). 4. Draw the medication solution into an appropriate size and type of syringe. 5. Flush the medication dose down the feeding tube. 6. Finally, flush with the recommended volume of water. 7. Re-start the feed.

Parentral 1. Reconstitute vials with SWFI to a final concentration of 50 mg/mL.

2. Further dilute the reconstituted solution to

A final concentration ≤5 mg/mL In fluid restricted patients ,conc 10

mg/mL

Page 11


Vancomycin toxicity Nephrotoxicity:

Risk Factors

preexisting renal impairment

concomitant nephrotoxic medication

dehydration

If multiple sequential (≥2) serum creatinine concentrations demonstrate an increase of 0.5

mg/dL or ≥50% increase from baseline (whichever is greater) in the absence of an alternative

explanation, the patient should be identified as having vancomycin-induced nephrotoxicity .

Discontinue treatment if signs of nephrotoxicity occur; renal damage is usually reversible.

Ototoxicity:

Although rarely associated with monotherapy, is proportional to the amount of drug given and the

duration of treatment.

Tinnitus or vertigo may be indications of vestibular injury and impending bilateral irreversible damage.

Discontinue treatment if signs of ototoxicity occur.

Hypersensitivity reactions:

The most common hypersensitivity reaction is an infusion-related anaphylaxis-like

reaction, known as ‘red man syndrome’.It is common and is related to the

speed of infusion.

• Suggested management of ‘red man syndrome’:

Stop the infusion.

Assess for signs of anaphylaxis (i.e. urticaria, stridor, wheeze).

-If these are present, manage as an anaphylactic reaction

including IM adrenaline. In these cases, vancomycin avoided in the future.

- If no signs of anaphylaxis are present, administer an antihistamine.

Once symptoms have subsided, the infusion can be re-started at one-half

the original rate.

Future infusions of vancomycin should be administered over four hours.

Consider pre-medicating with an antihistamine before infusions.

Page 12


Vancomycin monitoring parameters

Recommendations for Vancomycin Therapeutic Drug Monitoring (TDM)

Recommended TDM Parameters Recommendation

Optimal monitoring parameter Trough serum vancomycin concentrations are the most accurate and practical method for monitoring efficacy.

Timing of monitoring Troughs should be obtained just prior to the next dose at steady-state conditions (just before the fourth dose).

Optimal trough concentration -Minimum serum vancomycin trough concentrations should always be maintained above 10 mg/L to avoid development of resistance. -For a pathogen with an MIC of 1 mg/L, the minimum trough concentration would have to be at least 15 mg/L to generate the target AUC:MIC of 400.

Optimal trough concentration complicated infections (bacteremia, endocarditis, osteomyelitis, meningitis, and hospital-acquired pneumonia caused by Staphylococcus aureus)

Vancomycin serum trough concentrations of 15–20 mg/L are recommended to improve penetration, increase the probability of obtaining optimal target serum concentrations, and improve clinical outcomes.

Page 13


TDM for Vancomycin-Induced Nephrotoxicity

Variable Recommendation

Definition A minimum of two or three consecutive documented increases in serum creatinine concentrations (defined as an increase of 0.5 mg/dL or a ≥50% increase from baseline, whichever is greater) after several days of vancomycin therapy.

Criteria for monitoring Trough monitoring is recommended for patients receiving aggressive dosing (i.e., to achieve sustained trough levels of 15–20 mg/L) and all patients at high risk of nephrotoxicity (e.g., patients receiving concurrent nephrotoxins). Monitoring is also recommended for patients with unstable (i.e., deteriorating or significantly improving) renal function and those receiving prolonged courses of therapy (more than three to five days).

Frequency of monitoring Frequent monitoring (more than one trough before the fourth dose) for short course or lower intensity dosing (to attain target trough concentrations below 15 mg/L) is not recommended. All patients on prolonged courses of vancomycin (exceeding three to five days) should have at least one steady-state trough concentration obtained no earlier than at steady state (just before the fourth dose) . There are limited data supporting the safety of sustained trough concentrations of 15–20 mg/L. Clinical judgment should guide the frequency of trough monitoring when the target trough is in this range. Once-weekly monitoring is recommended or hemodynamically stable patients. More frequent or daily trough monitoring is advisable in patients who are hemodynamically unstable.

TDM for Vancomycin-Induced Ototoxicity

Criteria for monitoring Monitoring for ototoxicity is not recommended for patients receiving vancomycin monotherapy. Monitoring should be considered for patients receiving additional ototoxic agents, such as aminoglycosides.

Page 14


Vancomycin levels should be monitored in patients with any renal impairment:

Neonatal dose

Initial dosage recommendations:

Renal function-based dosing:

Scr Gestational age ≤28 weeks

Scr Gestational age >28 weeks

Dose adjustment Dose adjustment

<0.5 mg/dL 15 mg/kg/dose every 12 hours

<0.7 mg/dL 15 mg/kg/dose every 12 hours

0.5 to 0.7 mg/dL

20 mg/kg/dose every 24 hours

0.7 to 0.9 mg/dL


0.8 to 1 mg/dL


1 to 1.2 mg/dL


1.1 to 1.4 mg/dL


1.3 to 1.6 mg/dL


>1.4 mg/dL 15 mg/kg/dose every 48 hours

1.6 mg/dL 15 mg/kg/dose every 48 hours

Page 15


Infants and Children Doses : Renally adjusted dose recommendations are based on doses of 10 mg/kg/dose

every 6 hours or 15 mg/kg/dose every 8 hours

GFR Dose adjustment

GFR 30 to 50 mL/minute/1.73 m2 10 mg/kg/dose every 12 hours

GFR 30 to 50 mL/minute/1.73 m2 10 mg/kg/dose every 18 to 24 hours

GFR <10 mL/minute/1.73 m2 10 mg/kg/dose; redose based on serum concentrations

Intermittent hemodialysis 10 mg/kg/dose; redose based on serum concentrations

Peritoneal dialysis (PD) 10 mg/kg/dose; redose based on serum concentrations

Continuous renal replacement therapy (CRRT)

10 mg/kg/dose every 12 to 24 hours;

monitor serum concentrations

Page 16


Appendix 1: Governance Information

Document Title Vancomycin prescription and therapeutic drug monitoring guideline

Date Issued/Approved:

Date Valid From:

Date Valid to:

Department responsible (author/owner):

Brief summary of contents: Guidance on the safe and effective prescribing and monitoring of intravenous vancomycin

Executive Director responsible for Policy:

Names Of Committees /Consultation:

Antimicrobial Stewardship Management Committee

Clinical pharmacist approval

Staff approval

Page 17


Appendix 2: Version Control Table

Date Summary of Changes Changes Made by (Name and Job Title)

Page 18


Appendix 3. Initial Equality Impact Assessment Form Name of the policy to be assessed (Provide brief description): Clinical Guideline for Vancomycin Prescribing and Therapeutic Drug Monitoring

Directorate and service area: Pharmacy Is this a new or existing Policy? NEW

Name of individual completing assessment:

1. Policy Aim/ Who is the policy function aimed at? To provide guidance to staff on the appropriate prescription and therapeutic drug monitoring of vancomycin therapy

2. Policy Objectives To provide guidance to RCHT staff on the prescription and therapeutic drug monitoring for vancomycin therapy

3. Policy – intended Outcomes Safe and effective prescribing of vancomycin

4. How will you measure the outcome? Six monthly vancomycin audits

5. Who is intended to benefit from the policy? All prescribers and nurses administering vancomycin

Documents

vancomycin protocol