Mayo Clinic Antimicrobial Therapy quick guide - part 3 pptx

Dose as for Cl dialysis days, schedule after HDFirst episode genital herpes Dose as for Cl dialysis days, schedule after HD Recurrent genital herpes Dose as for Cl dialysis days, sch

No specific data; could start with 45-60 mg/kg after each HD

foscarnet maintenance

<10 mL/min (or anuric)

Intermittent HD dosing CRRT dosing information on

3-7 mg/kg/24h in divided doses or daily as pulse dosing; monitor levels

itraconazole cap or oral liquid

200 mg q24h or 200 mg bid; higher doses may be used based on levels

No data; probably unchanged

No data; probably not affected

<10 mL/min (or anuric)

Intermittent HD dosing CRRT dosing information on

Not affected by HD; 500- 750 mg load then 250- 500 mg q48h

<10 mL/min (or anuric)

Intermittent HD dosing CRRT dosing information on

No data; probably unchanged

No data; probably not affected

<10 mL/min (or anuric)

Intermittent HD dosing CRRT dosing information on

<10 mL/min (or anuric)

Intermittent HD dosing CRRT dosing information on

<10 mL/min (or anuric)

Intermittent HD dosing CRRT dosing information on

quinidine gluconate IV (for malaria)

10 mg/kg load then 0.02 mg/kg/min x72 hours; or 24 mg/kg over 4-hour load then 12 mg/kg over 4 hours q8h x7 days (modify based on ECG, BP, and serum levels, as appropriate)

Consider 75-100% of dose (modify based on clinical response, ECG, BP, and serum levels)

5-20% excreted by HD; dose for Cl

No data; probably no change

No data; probably no change

No data; probably no change

No information; dose change probably not needed

No information available; probably no change

saquinavir plus ritonavir1,000 mg saquinavir plus ritonavir 100 mg bid

No information; dose change probably not needed

No information available; probably no change

<10 mL/min (or anuric)

Intermittent HD dosing CRRT dosing information on

30 mg bid; or 75 mg q24h (for XR formulation)

30 mg bid; or 75 mg q24h (for XR formulation)

40 mg bid; or 100 mg q24h (for XR formulation)

40 mg bid; or 100 mg q24h (for XR formulation)

No data; probably unchanged

tobramycin Inh formulationCF: 300 mg bid for 28-day cycle Non-CF: Usually 300 mg bid or 60-80 mg tid

3-7 mg/kg/24h in divided doses or daily as pulse dosing; monitor serum levels

About 60% removed; dose based on serum levels

<10 mL/min (or anuric)

Intermittent HD dosing CRRT dosing information on

1 DS tab on dialysis days after HD

Most other indications (oral)

Dose as for Cl dialysis days, schedule after HD

First episode genital herpes

Dose as for Cl dialysis days, schedule after HD

Recurrent genital herpes

Dose as for Cl dialysis days, schedule after HD

Suppression of genital herpes (non-HIV patients)Less frequent recurrences: 500 mg q24h Frequent recurrences: 1 g q24h

Dose as for Cl dialysis days, schedule after HD Dose as for Cl dialysis days, schedule after HD

Suppression of genital herpes (HIV patients)

<10 mL/min (or anuric)

Intermittent HD dosing CRRT dosing information on

15-20 mg/kg q12h; consider load; monitor serum levels

20-25 mg/kg; monitor levels; 25-40% removed by high-flux HD (not appreciably dialyzed by traditional HD)

vancomycin oral (for Clostridium difficile

a Usual doses are for most common indications Doses may differ for meningitis, atypical or serious infections, or atypical orga

b Loading doses should generally not be modified in patients with renal dysfunction Subsequent (maintenance) doses or dosing in

c Serum creatinine levels may be deceptively low in elderly, malnourished, or debilitated patients because of reduced muscle mas

d For conventional (not high-flux) hemodialysis Dosing does not apply for continuous renal replacement therapy.

e Serum levels are similar with oral and intravenous therapy Use oral route when possible.

40 kg: 200 mg q12h (increase to 300 mg q12h if inadequate response)

<40 kg: 100 mg q12h (increase to 150 mg q12h if inadequate response)

<10 mL/min (or anuric)

Intermittent HD dosing CRRT dosing information on

c Dosing recommendations apply to total CRRT flow rates of 3-4 L/h Other forms of continuous replacement therapy (eg, SLED) or u

d Assuming minimal residual renal function, normal liver function, and total flow rates of 3-4 L/h.

e Support in the medical literature is unavailable or limited; check levels when possible to confirm dose.

Vancomycin Adult Dosing and Monitoring (Several vancomycin-dosing or monitoring protocols exist; this is the one used at Mayo Clinic.) Usual Dose •

serious infections (eg, meningitis) and for health care– associated pneumonia, endocarditis, and critically ill or hemodialysis (HD) patients

weight for most patients (an adjusted weight may be reasonable for very obese patients) See also HD and continuous renal replacement therapy (CRRT) sections below

interval or a larger dose may be considered when initiating therapy Serum levels can be measured to determine necessary dosage modifications, as the drug will likely accumulate over time.

administration The infusion rate can be further extended if poorly tolerated (

Table 12 Vancomycin Infusion Rate a It may be appropriate in some instances (eg, outpatient therapy) to

Monitoring Renal Function •

is chosen using the nomogram above, if renal function is stable, and if the expected duration of therapy is <5 days

levels Trough level–only monitoring can be done in most patients

Peak levels do not correlate well with efficacy so do not need to be checked in most patients Checking peak levels may be reasonable in special patient populations

For patients with severe renal dysfunction, drawing 2 levels after the same dose at least 1 half-life apart allows for calculation of Ke, half-life, and time needed for level to drop to desired value This information is useful when determining the appropriate time to redose without requiring daily random levels A pharmacist can assist with these calculations

Trough Level–Only Monitoring (See also the following sections on peak and trough monitoring, first-dose levels, HD, and CRRT.) •

half-lives) immediately before dose •Half-life can be estimated with the following equation:

Goal trough levels •

at least once per week thereafter More frequent monitoring is needed for serious infections, with concurrent nephrotoxic agents, or with changing renal function

Peak and Trough Monitoring or First-Dose Levels in Special Patient Populations

(peak-independent) antimicrobial activity Thus peak levels do not correlate well with efficacy Toxicity also is typically not seen until peak levels are >80 mcg/mL Since peak levels are unlikely to be in the toxic range if trough levels are appropriate, trough level monitoring can be used in most patients In some patients, initial peak and trough levels may be appropriate to ensure penetration or to allow for pharmacokinetic analysis and individualization of the dosing regimen Then most patients can often be followed with trough-only monitoring Special Patient Populations for Whom Peak and Trough Monitoring May Be Reasonable •

Patients with serious infections (eg, meningitis or hospital- or ventilator-acquired pneumonia) for which higher doses and trough targets are used

Patients whose levels were previously uninterpretable or considerably out of the desired range

Peak and Trough Monitoring in Special Populations •

state (after 4-5 half-lives) If the dosing interval chart (Table 11) is used and renal function is relatively stable, steady state typically occurs on the 3rd to 4th dose A pharmacist can assist with a determination of time to steady state •

Half-life can be estimated with the following equation:

hour after infusion, and up to 2-3 hours after infusion in patients with renal dysfunction, to ensure that complete distribution has taken place

Usual Goal Levels • Trough levels •

peak and trough levels, most patients should be followed with trough-only monitoring every 5-7 days or when renal function changes

reasonable to allow for rapid dose individualization based on pharmacokinetic parameters Levels drawn after the first dose can be used to determine pharmacokinetic parameters, estimated steady-state levels, and dosing needs This approach allows for rapid dose adjustment rather than waiting for steady state

meningitis or other serious infections; in patients with unpredictable renal function, critical illness, or morbid obesity; or in patients on HD or CRRT Levels should be scheduled over about 1.5 half-lives A pharmacist can assist with appropriate scheduling and interpretation of levels Patients Receiving Intermittent Hemodialysis •

load of 25 mg/kg should be used initially (to target a peak level of about 28 mcg/mL, assuming a Vd of about 0.9 L/kg) Doses and intervals can be modified on the basis of serum levels

many treatment centers remove 25-40% of vancomycin (removal by filters at other hospitals may differ) Thus dosing intervals should be more frequent than the previous interval of every 5-7 days that is used with conventional, lower-efficiency HD filters For institutions

high-flux HD every 2-3 days is a 25-mg/kg load followed by 7-10 mg/kg after each dialysis Another empiric option is 25 mg/kg after every 2-3 HD sessions (A couple of small studies support a load of 1 g followed by 500 mg at the end of high-flux HD.) Levels should be done to confirm attainment of appropriate target levels

after the first dose, a predialysis level, and a 6-hour post- HD level to individualize dosing, determine kinetic variables, and determine percentage of drug removed by HD Occasional predialysis random levels can be used to monitor ongoing therapy; redosing can typically occur when the level is (or is anticipated to be) 8-15 mcg/mL, depending on type of infection A pharmacist can provide assistance

Patients Receiving CRRT •

vary by flow rates Empiric dosing of about 15-25 mg/kg q24-48h is reasonable initially, and serum levels can be used to make adjustments

allow for individualization of dosing interval Check initial level 2 hours after dose and check random level about 24 hours after dose Consult with pharmacist for assistance in calculating doses based on pharmacokinetic analysis (eg, half-life, Vd)

For obese patients (>20% of ideal body weight [IBW]), use dosing weight (DW) rather than actual body weight for calculating mg/kg dosing per table below.

Males: 50 kg + 2.3 kg/inch >60 inches Females: 45.5 kg + 2.3 kg/inch >60 inches*

a Loading dose can be given regardless of renal function to achieve therapeutic levels quickly Loading doses for gentamicin-tobr typically 2-3 mg/kg for gram-negative infections.

b The appropriate dose and resulting serum concentrations depend on the seriousness and the site of infection. c Fluid status may also affect the required dosing regimen to achieve goal serum levels Patients with considerably higher than status have higher volumes of distribution (Vd) and may require higher doses to achieve desired serum concentrations Subsequen may need adjustment with diuresis.

mg/kg (see Table 14 for frequency)

Table 14 Empiric Dosing Interval Selection: Based on Estimated Creatinine Clearance Serum Level and Toxicity Monitoring for Conventional Aminoglycoside Therapy Renal Function and Ototoxicity Monitoring •

hospitalized patients and more often in patients with changing renal function or critical illness or who are receiving another nephrotoxic medication

Monitor signs and symptoms consistent with ototoxicity (eg, tinnitus, feeling of ear-fullness, hearing loss) Instruct patients to alert their physician if these symptoms occur Consider audiology or vestibular

Pulse Dosing Aminoglycoside Therapy Guidelines Rationale for Pulse Dosing of Aminoglycosides •

Aminoglycosides display concentration- or peak- dependent killing Goal peak levels are about 10 times the minimum inhibitory concentration (MIC) of the organism

Pulse dosing may reduce costs associated with drug administration and monitoring

Patients (or Conditions) That May NOT Be Good Candidates for Pulse Dosing (Limited Data) •

traditional (multiple daily dose) dosing is more effective than pulse dosing for treatment of enterococcal endocarditis However, data support pulse dosing of aminoglycosides in combination with a

with pulse dosing, but pediatric patients may need more frequent dosing because of altered pharmacokinetics With pulse dosing, it may be advisable to administer aminoglycosides with another active agent and to monitor serum levels to determine whether the dose or interval needs to be modified (q12h dosing may be required)

increased volume of distribution and more rapid clearance than other patients Higher daily doses or q12h dosing may be necessary

the optimal dosing method and the possibility of increased nephrotoxicity due to prolonged drug exposure in patients with renal dysfunction, we suggest using traditional dosing in patients with an estimated Cl

serious liver disease or ascites, and in patients with burns covering >20% of their body surface area The volume of distribution can be altered in these subpopulations as well as in critically ill patients.

Patient Selection for Pulse Dosing of Aminoglycosides •

Most studies have been performed in patients with low failure rates (eg, those with urinary tract infections, abdominal infections, or pelvic infections) These patient groups may be good candidates for pulse dosing

coverage This will ensure adequate serum concentrations of an appropriate antibiotic in the event that the postantibiotic or sub-MIC effects of the aminoglycoside are exceeded

Dosing Pulse (Extended-Interval) Aminoglycoside Therapy

c For amikacin use in mycobacterial infections, peak levels of 35-45 for a 15 mg/kg dose and 65-80 for a 25 mg/kg dose are recom

d At Mayo Clinic, we do not recommend pulse dosing in patients with a Cl

give pulse doses of aminoglycoside over 60 minutes Renal Function and Ototoxicity Monitoring •

hospitalized patients or more often in patients with changing renal function or who are receiving another nephrotoxic medication

Monitor for signs and symptoms consistent with ototoxicity (eg, tinnitus, feeling of ear-fullness, hearing loss) Instruct patients to alert their physician when these symptoms occur Consider audiology or vestibular testing at baseline and periodically for longer-term use

Aminoglycoside Levels •

Stable patients not expected to have abnormal pharmacokinetics:

<4 doses, consider no levels unless patient is severely ill or receiving concomitant nephrotoxins

patients (see “individualized dosing” below for critically ill or volume-overloaded patients), draw a level 6-14 hours after the start of the first infusion and apply the nomogram (see below)

Other clinicians have suggested just a periodic trough level to ensure that the drug is not accumulating (goal would be an undetectable trough) in stable patients

volume-overloaded patients, it may be desirable to individualize dosing at least once It may be prudent to measure levels at 2 hours and then at 8-12 hours after the end of the first dose These levels can be used to calculate individual patient pharmacokinetic parameters (eg, extrapolated peak, trough, half-life) and to optimize the dose Anticipated extrapolated peaks for gentamicin and tobramycin are typically 20-24 mcg/mL, and peaks for amikacin are about 40-70 mcg/mL Extrapolated troughs should be undetectable A pharmacist can assist with pharmacokinetic and dosing calculations

Interpretation of 6- to 14-Hour Level (After Start of Infusion) According to Hartford Nomogram or Urban and Craig Nomogram

q24h or q36h, the dosing interval should be every 24 hours and every 36 hours, respectively At Mayo Clinic, we suggest discontinuing pulse dosing and changing to conventional dosing if the level is above the q36h dosing interval area

the use of the Hartford nomogram Consider multiplying the serum concentration scale for gentamicin and tobramycin by a factor of 3 or use individualized dosing