Vancomycin Dosing and Monitoring in Adults Clinical Guideline PDF

Clinical Guideline No.: CG251 Vancomycin Dosing and Monitoring in Adults Clinical Guideline Version No.: 1.1 Approval date: 30/12/2019 Disclaimer This statewide guideline has been prepared to promote and facilitate standardisation and consiste...

Clinical Guideline No.: CG251 Vancomycin Dosing and Monitoring in Adults Clinical Guideline Version No.: 1.1 Approval date: 30/12/2019 Disclaimer This statewide guideline has been prepared to promote and facilitate standardisation and consistency of practice, using a multidisciplinary approach. The guideline is based on a review of published evidence and expert opinion. Health practitioners in the South Australian public health sector are expected to review specific details of each patient and professionally assess the applicability of the relevant guideline to that clinical situation. If for good clinical reasons, a decision is made to depart from the guideline, the responsible clinician must document in the patient’s medical record, the decision made, by whom and detailed reasons for the departure from the guideline. This statewide guideline does not address all the elements of clinical practice and assumes that the individual clinicians are responsible for: Discussing care with consumers in an environment that is culturally appropriate and which enables respectful confidential discussion. This includes the use of interpreter services where necessary; Advising consumers of their choice and ensure informed consent is obtained; Providing care within scope of practice, meeting all legislative requirements and maintaining standards of professional conduct; and Documenting all care in accordance with mandatory and local requirements. Information in this statewide guideline is current at the time of publication. SA Health does not accept responsibility for the quality or accuracy of material on websites linked from this site and does not sponsor, approve or endorse materials on such links. INFORMAL COPY WHEN PRINTED Vancomycin Dosing and Monitoring in Adults Clinical Guideline Page 2 of 14 Public-I4-A2 Contents 1. Introduction....................................................................................................................... 4 2. Background....................................................................................................................... 4 3. Definitions and acronyms................................................................................................ 4 4. Loading dose..................................................................................................................... 5 5. Maintenance dose and dose adjustments...................................................................... 5 6. Frequency of monitoring and dose adjustment............................................................. 6 7. Target therapeutic range.................................................................................................. 6 8. Administration................................................................................................................... 6 9. Special Considerations.................................................................................................... 7 Continuous infusions........................................................................................................... 7 Red man syndrome............................................................................................................. 7 Dosing in obesity................................................................................................................. 8 Low body weight Infectious Diseases / Clinical Microbiology advice; or > Intensive Care Units; or > Haematology / Oncology as per febrile neutropenia guidelines; or > Surgical prophylaxis as per statewide clinical guidelines for patients allergic to penicillin or at high risk of methicillin-resistant Staphylococcus aureus (MRSA) infection; or > Continuous Ambulatory Peritoneal Dialysis (CAPD) peritonitis involving MRSA and/or coagulase- negative staphylococcus (CoNS); or > Empiric treatment of sepsis for 48 hours only (continuing therapy only with ID / Microbiology advice). 2. Background Therapeutic drug monitoring is recommended for all patients treated with vancomycin for longer than 48 hours to avoid under-dosing. Monitoring is also important to minimise the risk of toxicity, especially in patients with renal impairment (including those receiving renal replacement therapy). Recent evidence has shown that the best determinant of vancomycin efficacy is the AUC/MIC. A 24-hour AUC/MIC of 400 or more is the target for clinical success [2, 3]. For practical reasons, a trough (pre-dose) plasma concentration is used as a surrogate measure of efficacy. 3. Definitions and acronyms ABW Actual body weight AUC/MIC Ratio of area under the curve (plasma concentration vs time) to minimum inhibitory concentration (Units: mg.hr/Litre) 2 BMI Body Mass Index = (Bodyweight in kilograms) / (height in meters) BSI Blood stream infection/s CAPD Continuous ambulatory peritoneal dialysis CNS Central nervous system CrCl Creatinine Clearance GFR Glomerular filtration rate ID/micro Infectious diseases / Clinical microbiology INFORMAL COPY WHEN PRINTED Vancomycin Dosing and Monitoring in Adults Clinical Guideline Page 4 of 14 Public-I4-A2 Low weight Body weight < 50kg MER Medical Emergency Response MET Medical Emergency Team MIC Minimum inhibitory concentration MRSA Methicillin-resistant Staphylococcus aureus NSQHS National Safety and Quality Health Service Standards 2 Obese BMI > 30kg/m PO Orally SAAGAR South Australian SA expert Advisory Group on Antimicrobial Resistance SBP Systolic blood pressure TDM Therapeutic drug monitoring Trough level Serum vancomycin level taken towards the end of the dosing interval, approximately one hour prior to next dose 4. Loading dose Based on the currently available evidence, clinical data support a loading dose of 25mg / kg (actual body weight). A loading dose will facilitate more rapid attainment of therapeutic target range. Higher loading doses may be required for critically ill patients (e.g. meningitis, sepsis, burns) – consult ID/micro. See table 1 in the Appendix for loading dose determination. 5. Maintenance dose and dose adjustments Start maintenance dosing 12 hours after loading dose if CrCl more than/equal to 40mL/min, OR 24 hours after loading dose if CrCl = 20-39 mL/min. If CrCl is less than 20mL/min check trough level 24 hours after loading dose; wait for trough to fall below 20mg/L prior to re-dosing. To estimate CrCl, use the Cockcroft-Gault equation (see table 5, Appendix). Do not use eGFR for dosing. Table 2 in the Appendix presents suggested maintenance dosing for patients within the weight range between 40 & 120 kg, according to CrCl. Outside of this range, dosing based on actual body weight at 15 - 20 mg/kg per dose may be indicated (see under Special Considerations (Section 9) for information on dosing in obesity or low body weight). The doses in Table 2 (Appendix) are for initial dosing, up to 48 hours; Subsequent dosage adjustments for intermittent infusions should be according to recommendations in Table 3 (Appendix), and based on trough plasma concentrations. INFORMAL COPY WHEN PRINTED Vancomycin Dosing and Monitoring in Adults Clinical Guideline Page 5 of 14 Public-I4-A2 6. Frequency of monitoring and dose adjustment Therapeutic Drug Monitoring (TDM) is recommended for all patients treated with intravenous vancomycin for more than 48 hours to reduce the risk of under-dosing and minimise the risk of toxicity. The time of the first TDM (trough) will depend on the patient’s renal function and/or if renal function is potentially unstable. Trough monitoring For patients with normal renal function, the first TDM (trough) should occur just prior (within one hour) to the fourth dose (including the loading dose) or on day 3, whichever occurs earlier. In patients with CrCl between 20-39 mL/min check trough level before (within one hour) of the third dose (including the loading dose). In changing renal function, earlier or more frequent TDM may be required. For patients with CrCl less than 20mL/min or on peritoneal dialysis check trough level 24 hours after loading dose. Repeat TDM trough (pre-dose) level every 3 days until levels are stable within the therapeutic range, and at least once weekly thereafter [5, 6]. Unless stated in the Appendix Table 3 (i.e. CrCl less than 20mL/min), doses should NOT be routinely withheld pending trough level result. Renal function monitoring Creatinine levels should be checked daily for the first 2 to 3 days of therapy, even if creatinine levels are in the normal range. Measure serum creatinine twice weekly. For patients with unstable renal function TDM should occur more frequently (possibly daily) to ensure toxicity is avoided. 7. Target therapeutic range Target concentrations vary depending upon the disease, the MIC of the pathogen, and the mode of administration : Intermittent infusion: Aim for trough levels of 15 - 20mg/L; Continuous infusion: Aim for blood levels of 20 - 25mg/L at steady state (36 – 48 hours after a dose change). See under ‘Special considerations’ for further guidance on continuous infusions. Due to its relatively large molecular weight, the penetration of vancomycin into the cerebrospinal fluid from the IV route is variable and dependent upon the degree of meningeal inflammation. Depending upon the MIC of the pathogen, clinicians may aim for targets of 20 - 25mg/L to ensure sufficient CNS concentrations – for further information seek advice from Infectious Diseases / Clinical Microbiology/ Clinical Pharmacist. 8. Administration Doses of 1g should be administered over at least 60 minutes. For higher doses the duration of infusion should be extended by 30 minutes for each additional 500mg. This is recommended to reduce the risk of ‘red man syndrome’. The usual dilution is 5mg/mL. For fluid-restricted patients, concentrations of up to 10mg/mL may be used. Minimum recommended infusion durations are shown in Table 4 (Appendix), adapted from Wilson & Estes (eds), 2011. INFORMAL COPY WHEN PRINTED Vancomycin Dosing and Monitoring in Adults Clinical Guideline Page 6 of 14 Public-I4-A2 9. Special Considerations Continuous infusions Continuous infusion of vancomycin may be preferable in patients where the target range is difficult to achieve via intermittent infusion, and may be necessary to maintain adequate blood levels in patients with augmented renal function or obese patients. It is currently unclear whether administering vancomycin via continuous infusion is associated with less nephrotoxicity than intermittent infusions, as the key correlating factor appears to be the steady-state vancomycin concentration [7, 14]. Switching from intermittent dosing to continuous infusion: For patients initiated on intermittent dosing and then switching to continuous infusion, the starting dose over 24 hours is the same as the total dose for 24 hours administered via intermittent infusion. The continuous infusion should be started immediately after the last intermittent dose. For patients being discharged and continuing treatment at home, and with levels in the upper end of the target range (e.g. 20mg/L), local experts from SAAGAR recommend a dose reduction of approximately 20% when converting from intermittent to 24-hour continuous infusion. Initiating vancomycin with continuous infusion: For critically ill patients initiated on continuous infusion (and not initially treated with intermittent infusion), an initial loading dose is recommended (Table 1, Appendix). If the patient is not critically ill, the initial dose is the same as an intermittent maintenance dose (Table 2, Appendix). Continuous infusion is to be commenced immediately after the completion of the loading dose – a level is not required at this point. The subsequent 24-hour continuous infusion is the sum of the intermittent doses that would have been given over a 24 hour period, according to the patient’s CrCl. For patients with normal renal function, steady-state concentration is reached after 36-48 hours. During continuous infusions blood concentrations may be measured at any time of the day once steady-state is achieved [15, 16]. In unstable patients, true steady state may never be achieved. Levels may be done earlier (e.g. 16 hours after infusion initiated) in critically ill patients to enable early identification of sub-therapeutic levels. Dosage adjustments are made in a simple linear manner. Levels should be monitored every 2-3 days, or more frequently if renal function is unstable, for example, in the ICU setting. Red man syndrome Red man syndrome is a common non-immunological reaction that can occur during or shortly after an infusion of vancomycin and is related to the rate of infusion. For this reason, it is recommended that vancomycin is infused no faster than 1g/hour. The reaction is mediated by histamine release, which can result in pruritus, flushing, erythematous rash (face, neck and upper thorax predominantly), fever, chills and in severe cases angioedema and hypotension. These symptoms are due to non-specific mast cell degranulation. True IgE-mediated allergy can occur but is rare. If a patient experiences an infusion related reaction to vancomycin: > Cease infusion > Administer antihistamine (cetirizine10mg PO) > If newly hypotensive (SBP less than 90mmHg) initiate a call requesting emergency medical assistance (i.e. MET or MER call). Consider giving adrenaline (epinephrine) if unable to do so. INFORMAL COPY WHEN PRINTED Vancomycin Dosing and Monitoring in Adults Clinical Guideline Page 7 of 14 Public-I4-A2  > Consult clinical pharmacist or infectious diseases team for advice on recommencement of vancomycin at a slower rate of infusion. Local experts from SA recommend doubling the time to infuse the solution, or changing to a continuous infusion. Dosing in obesity Obese patients are at higher risk of insufficient vancomycin concentrations leading to poorer clinical outcomes. The volume of distribution is larger in the obese population, protein binding may be altered and clearance of vancomycin may also be greater. Morbidly obese patients are excluded from most clinical trials therefore the evidence to guide dosing regimens in these patients is not strong. Based on current clinical practice, the initial loading dose in obese patients should be as for non-obese patients, using actual body weight (at 25mg/kg) , (maximum 3 grams loading dose if CrCl is more than or equal to60mL/min or 2.5g if CrCl is less than 60mL/min). More frequent dosing (8-hourly) or a continuous infusion may be preferred in obese patients. Higher doses of more than 4g per day, such as those often required in obese patients, are associated with a higher risk of nephrotoxicity [19, 20]. Recommended maintenance dosing in obese adults is variable due to the differing pharmacokinetics secondary to the extent of obesity and any pre-existing renal impairment, and should be guided by TDM. Low body weight 30kg/m ), 2 5'8 173 64 69 5'9 175 66 71 consider using adjusted body weight (AdjBW) to 5'10 178 69 73 calculate CrCl: 5'11 180 71 76 AdjBW = IBW + [0.4 x (ABW-IBW)] 6'0 183 73 78 6'1 185 76 80 IBW (female) = 45.5kg + 0.9kg per cm over 152cm IBW (male) = 50kg + 0.9kg per am over 152cm INFORMAL COPY WHEN PRINTED Vancomycin Dosing and Monitoring in Adults Clinical Guideline Page 13 of 14 Public-I4-A2 For more information National Antimicrobial Utilisation Surveillance Program Communicable Disease Control Branch 11 Hindmarsh Square Adelaide SA 5000 Telephone: 1300 232 272 Email: [email protected] www.sahealth.sa.gov.au/antimicrobials Public-I4–A2 © Department for Health and Wellbeing, Government of South Australia. All rights reserved