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Stanford Hospital & Clinics Antibiotic Dosing Reference Guide 2011
This document is also located on the SHC Intranet (http://portal.stanfordmed.org/depts/pharmacy) P&T Approved April 15, 2011 Formulas for dosing weights: Ideal body weight IBW (male) = 50 kg + (2.3 x height in inches > 60 inches)· IBW (female) = 45 kg + (2.3 x height inches > 60 inches)
Adjusted BW (kg) = IBW + 0.4 (TBW – IBW) Intermittent
CrCl >50 mL/min
CrCl 10–50 mL/min
CrCl <10 mL/min
Hemodialysis (IHD)
Acyclovir (IV)1,4,5, 6,7,8
(Use ideal BW for
Acyclovir (PO)1,5
Ambisome1(Ampho
BLiposomal)
Amikacin1,2,3, 7
(Use ideal or adjusted
BW for obese)
Timing of levels: Draw trough 30 min prior to 4th dose. Draw peak 30 min after infusion ends
See appendix for
Once daily dosing: goal peak 35–60; goal trough <4. Consult Hartford Nomogram
complete guidelines
Conventional dosing: goal peak 25–35 for serious infections, 15–20 for UTI
Ampicillin (IV)1,3,4,6
Ampicillin/sulbactam1,2,4
(SHC Restriction)
Azithromycin (IV/PO)1
Aztreonam1,2, 6
Severe: pseudomonas,
Caspofungin1
Consider 70 mg x 1, then 35mg q24h if severe hepatic dysfunction (Child–Pugh score >7); (Hepatic adjustment)
70 mg q24h if on phenytoin, rifampin, other strong enzyme inducers Cefazolin1,2, 5, 6,7, 8
Cefepime1,4, 5, 6, 7
(SHC Interchange)
Severe: endocarditis/CF
Ceftriaxone1, 5, 9
Meningitis, E. faecalis endocarditis: 2 gm q12h Ciprofloxacin(IV/PO)1,2, 5,
Clindamycin1,2(caution in
Colistin1,5,6
(Use ideal BW in obese)
Daptomycin1, 10, 11, 21(Use
adjusted BW in obese)
(SHC Restriction)
Doxycycline (IV/PO)1
Ertapenem1
Ethambutol (PO)1,7
Fluconazole(IV/PO)1,5,6, 8
Load 800 mg for
Foscarnet1
Please see Lexi-comp or Micromedex for renal dosing table. Note that dosing is by CrCl per kg (ml/min/kg)
CrCl/kg > 1.4: CMV Induction treatment: 60 mg/kg q8h or 90 mg/kg q12h x 14-21 days
Ganciclovir1, 6
5mg/kg for all patients
*Manufacturer’s CrCl cutoffs. Please refer to BMT protocols if applicable
Gentamicin6
(SHC interchange to
Gram positive
tobramycin. Exception:
gram positive synergy)
Timing of levels: Draw trough 30 min prior to 4th dose. Draw peak 30 min after infusion ends (4th dose). (For CrCl <60, check levels sooner than 4th dose)
In HD, check trough before each HD session, and peak 30 minutes after each dose. See appendix for
Goal levels:
For synergy,goal peak 3–5mg/L (3-4 if using IDSA endocarditis guidelines). Goal trough <1 mg/L complete guidelines
* Streptococci, Streptococcus bovis, Strep. viridans endocarditis: optional dosing 3mg/kg q24h for CrCl > 60 Imipenem/Cilastatin1,2, 6
(Nonformulary)
Isoniazid1
Intermittent
CrCl >50 mL/min
CrCl 10–50 mL/min
CrCl <10 mL/min
Hemodialysis (IHD)
Levofloxacin(IV/PO)1,2, 5,
Linezolid(IV/PO)1,4
(SHC Restriction)
Meropenem1,2, 6, 8, 18
(SHC Restriction)
Consider extended
infusion (3 hours) or more
frequent dosing intervals
for pseudomonas or
resistant pathogens
Moxifloxacin1
Metronidazole(IV/PO)1
Nafcillin1
Oseltamivir (PO)1,2, 15,16,17
Give after every other HD
Penicillin G (IV)1, 5, 6
Piperacillin/tazobactam
1,2,4, 5, 6, 8
Extended infusion for CrCl > 20: 3.375 Posaconazole (PO)1,2, 22
No change. Posaconazole levels shown to have great degree of interpatient variability. Many clinicians would recommend (SHC Restriction)
blood levels to assess efficacy. Consider drawing a trough 4 - 7 days after initiating dose Pyrazinamide (PO)1, 5, 12
(Use ideal BW)
Rifampin(IV/PO)1, 13, 14
Tobramycin20
(Use ideal or adjusted
BW for obese)
Goal levels:
Goal peak (4–8mg/L), and trough (<1-2mg/L) for treatment.
*certain qualifications for once–daily dosing
See appendix for
Timing of levels:
Draw trough 30 min prior to 4th dose. Draw peak 30 minutes after infusion ends (4th dose). (For CrCL <20, may check levels sooner than 4th dose) complete guidelines
For once-daily dosing, draw a single random level 8 to 12 hours after dose given adjustments are made based on a published Hartford nomogram.
For HD, draw trough pre-HD, and peak 30 min after end of each infusion
Trimethoprim (TMP)/
Sulfamethoxazole1, 5,
6(Dose by ideal or
2.5 – 5 mg/kg/day TMP divided q8 – 12h adjusted BW in obese)
PCP/Stenotrophomonas: 7.5 – 10 mg/kg/day TMP divided Valganciclovir(PO)1
Please refer to
transplant protocols if
applicable
Vancomycin6, 19, 21
(Use actual body
Goal levels: Goal trough 10–15 mcg/ml (cellulitis, skin/soft tissue infections)
Consider loading dose
Goal trough 15–20 mcg/ml (pneumonia, bacteremia, endocarditis, osteomyelitis)
of 20–25mg/kg (max
Timing of levels: Draw trough< 30 minutes before 4th dose of new regimen. When SCr acutely
2gm) for severe
rises, hold dose, restart when level <15 - 20 See appendix for complete guidelines
Caution with IV: accumulation of IV vehicle cyclodextran occurs. Consider PO unless benefits justify risks of IV use. Voriconazole (IV/PO)1,22
Levels shown to have great degree of interpatient variability. Many clinicians would recommend blood levels to assess (SHC Restriction)
efficacy. Consider drawing a trough 4 - 7 days after new dose Abbreviations: SCr = serum creatinine LD = loading dose; MU= million units; PNA = pneumonia; HD = hemodialysis; CAP = community acquired pneumonia; CRRT = continuous renal
replacement therapy; TMP = trimethoprim; PCP: pneumocystis jiroveci pneumonia TB = tuberculosis; UF = ultrafiltration
CRRT dosing: doses listed are for CVVHDFand CVVHD modalities, which are the most common modes at SHC. Note that these are generally higher than doses used in CVVH.
All SHC formulary Restrictions/Interchange program descriptions can be accessed using Lexi-Comp and the intranet under pharmacy policies (intranet > Departments > Pharmacy)
References:
1.
Lexi–Drug, Lexi–Comp® [Internet database]. Hudson, OH: Lexi–Comp, Inc. Available at http://www.crlonline.com. Accessed March, 2011 The Sanford Guide to Antimicrobial Therapy, 39th ed. Sperryville, VA: Antimicrobial Therapy. 2009 Drug Prescribing in Renal Failure, 5th ed. Philadelphia, PA: Dosing Guidelines for Adults and Children, 2007 McEvoy G (Ed). American Hospital Formulary Service Drug Information. Bethesda, MD: American Society of Health–System Pharmacists; 2008 Micromedex® Healthcare Series [Internet database]. Greenwood Village, CO: Thomson Reuters (Healthcare), Inc. Available at http://www.thomsonhc.com/hcs/librarian. Accessed March, 2011 Heinz et al., Antimicrobial Dosing Concepts and Recommendations forCritically Ill Adult Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis, Pharmacotherapy 2009 Aranoff GR et al., Drug Prescribing in Renal Failure, 5th edition, American College of Physicians, Philadephia, 2007 Trotman RL et al, Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy, CID 2005 Guglielmo BJ et al., Ceftriaxone Therapy for Staphylococcal Osteomyelitis, CID 2000 Pai MP et al, Influence of Morbid Obesity on the Single–Dose Pharmacokinetics of Daptomycin,AAC 2007 Dvorchik BH and Damphousse,D,The Pharmacokinetics of Daptomycin in Moderately Obese, Morbidly Obese, and Matched Nonobese Subjects, Journal of Clinical Pharmacology, 2005 ATS Guidelines for Treatment of Tuberculosis, Am J RespirCrit Care Med Vol 167. pp 603–662, 2003 Baddour et al , Infective Endocarditis: Diagnosis and Management, Circulation. 2005 Zimmerli W et al., Role of Rifampin for Treatment of Orthopedic Implant–Related Staphylococcal Infections, JAMA 1998 15. http://www.cdc.gov/H1N1flu/recommendations.htm Robson R, et al. The pharmacokinetics and tolerability of oseltamivir suspension in patients on hemodialysis and continuous ambulatory peritoneal dialysis Nephrol Dial Transplant 2006;21:2556–62. Taylor RJ et al. Oseltamivir is adequately absorbed following nasogastric administration to adult patients with severe H5N1 influenza. PLoS ONE 2008;3:e3410. Kuti et al., Use of Monte Carlo Simulation to Design an Optimized Pharmacodynamic Dosing Strategy for Meropenem, J ClinPharmacol2003 43: 1116 Rybak M, Lomaestro B, Rotschafer JC 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. Am J Health–Syst Pharm. 2009; 66:82–98 Nicolau DP et al, Experience with a Once–Daily Aminoglycoside Program Administered to 2,184 Adult Patients, AAC 1995; 39(3): 650–65 Liu et al, Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin–Resistant Staphylococcus Aureus Infections in Adults and Children, Clinical Infectious Diseases 2011;1–38 Andes D, Pascual A, and Marchetti O. Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother 2009; 53:24-34 Stanford Hospital & Clinics Vancomycin Dosing Guidelines

Vancomycin is a tricyclic Glycopeptide antibiotic that exhibits bactericidal activity by preventing the synthesis and assembly of a
growing bacterial cell wall, altering the permeability of the bacterial cytoplasmic membrane, and selectively inhibiting bacterial
RNA synthesis. Vancomycin is considered to be a concentration-independent or time-dependent killer of bacteria.

A. Determine creatinine clearance and dose
a) Determine the dose with total body weight (TBW) b) Calculate creatinine clearance with the Cockcroft-Gault equation using an ideal body weight (IBW) or an adjusted body weight (ABW) if the patient is obese (TBW >20% over IBW) CrCL (mL/min) = (140 – age) x IBW ( x 0.85 for females ) IBW (male) = 50 kg + (2.3 x height in inches > 60 inches) IBW (female) = 45 kg + (2.3 x height inches > 60 inches) ABW (kg) = IBW + 0.4 (TBW – IBW)
B. Initial Empiric Dosing

Loading Dose: Consider a loading dose of 20-25mg/kg (max 2gm) for severe infections and ICU patients
Creatinine Clearance
Interval
(mL/min)
Total body weight (TBW)
Hemodialysis
Post-dialysis when levels <15mg/L or <20 mg/L in severe infections (i.e. meningitis, pneumonia)
C. Administration
Vancomycin Dose
Infusion Rate
Red man syndrome may occur if the infusion is too rapid. It is not an allergic reaction, but may be characterized by hypotension and/or a maculopapular rash appearing on the face, neck, trunk, and/or upper extremities. If this should occur, slow the infusion rate to over 11/2 to 2 hours and increase the dilution volume. Reactions are often treated with antihistamines D. Therapeutic Drug Monitoring
1. Clinical situations to obtain serum trough concentrations
Patients with rapidly changing renal function Concomitant administration of nephrotoxic medication (i.e. aminoglycosides, amphotericin B) Patients on intermittent or continuous dialysis Patients requiring higher than usual doses of vancomycin (>20 mg/kg/dose) Altered volume of distribution (i.e. Morbidly obese patients) Patients receiving prolonged course of therapy Trough levels should be obtained within 30 minutes before the 4th dose of a new regimen For q24h and q48h regimens, consider drawing levels prior to 3rd or 2nd dose respectively Recommend trough levels >10 mcg/mL to avoid microbial resistance When SCr acutely rises, hold dose and draw level. Restart therapy when level <15 - 20 CRRT: obtain level within 30 minutes prior to 3rd or 4th dose Intermittent hemodialysis (IHD): obtain levels daily before dialysis or consider waiting >4 hours after dialysis to avoid rebound effect Dosing assumes that HD is high flux and removes ~20% of vancomycin per 3 hour session 10–15 mcg/ml (cellulitis, skin/soft tissue infections) 15–20 mcg/ml (pneumonia, bacteremia, endocarditis, osteomyelitis) Stanford Hospital & Clinics Aminoglycoside Dosing Guidelines

Aminoglycosides are concentration dependent antibiotics, meaning that as aminoglycoside concentration increases, the rate and
extent of bacterial killing increases. Optimum bactericidal activity for the aminoglycosides is achieved when the exposure
concentration is approximately 8 to 10 times the MIC.
Determining dose and creatinine clearance
a) Use of ideal body weight (IBW) for determining the mg/kg/dose appears to be more accurate than dosing on the basis of total
body weight (TBW). In morbid obesity, dosage requirement may best be estimated using an adjusted body weight (ABW) of: IBW + 0.4 (TBW - IBW) Obese patients: Obese is defined as a Total body weight (TBW) > 20% over Ideal body weight (IBW) IBW (male) = 50 kg + (2.3 x height in inches > 60 inches) IBW (female) = 45 kg + (2.3 x height inches > 60 inches) b) Calculate creatinine clearance with the Cockcroft-Gault equation using an ideal body weight (IBW) or an adjusted body weight CrCL (mL/min) = (140 – age) x IBW ( x 0.85 for females )
Extended-Interval Therapy (Once daily dosing)

Hartford Nomogram
The method of once-daily dosing intends to optimize the peak/MIC ratio in the majority of clinical situations by administering a
dose of 7mg/kg of either gentamicin or tobramycin. Similar to that of conventional regimens, once-daily protocols also require
modification for patients with renal dysfunction in order to minimize drug accumulation. Due to high peak concentrations obtained
and the drug-free period at the end of the dosing interval, it is usually not necessary to draw standard peak and trough samples,
rather a single random blood sample is obtained between 6 to 14 hours after the start of the aminoglycoside infusion. This
concentration is used to determine the dosing interval based on a nomogram for once-daily dosing.
Non-Hartford Nomogram
The second method of extended-interval therapy utilizes a 5mg/kg gentamicin or tobramycin dose in patients without renal
dysfunction. If dosage adjustment is required to compensate for impaired renal function, the dose and/or dosing interval may be
modified to optimize therapy and minimize drug accumulation.
Exclusion Criteria for Extended Interval Therapy:
Renal insufficiency (CrCL <30 mL/min or rapidly declining renal function)
Traditional Dosing
Tradition dosing includes reduced doses and frequent administration of aminoglycosides using pharmacokinetic parameters to
determine dose and frequency to achieve target peak and trough values.
Gram positive-synergy Dosing
Synergy dosing is a low dose of aminoglycoside in conjunction with an antimicrobial agent that exhibits activity against the cell
wall of gram-positive bacteria (i.e. beta-lactams, glycopeptides) for the treatment of gram-positive infections
Gentamicin & Tobramycin Initial Empiric Dosing
CrCL (mL/min)
Once daily dosing*
Traditional
Synergy**
Hemodialysis
*See Hartford nomogram for monitoring of once-daily dosing regimens **Alternative for synergy: 3mg/kg Q24H for Streptococci and Streptococcus bovis endocarditis
Amikacin Initial Empiric Dosing
CrCL (mL/min) Once daily dosing*
Traditional
Hemodialysis
* See Hartford nomogram for monitoring of once-daily dosing regimens- divide level by half then plot on graph
Monitoring
High Dose Extended Interval (Hartford Nomogram- for once-daily dosing)
A. Initial
level testing: Single level drawn 8-12 hours after the first dose  Gentamicin/tobramycin: Plot level on graph  Amikacin: Divide level in half, then plot on graph trough level testing- for traditional and synergy dosing regimens  Trough monitoring (30-60 minutes prior to next dose) should be considered in patients demonstrating acute changes in renal function or suspicion of extended interval failure  Maintenance trough levels should be monitored at least once weekly Traditional Regimens
▪ Cp< 1mg/L (mild UTI and synergy) ▪ Cp< 2-3mg/L (moderate-severe UTI) ▪ Cp< 3-5mg/L (severe GNR infection) Gram-Positive Synergy

*Peaks are drawn 30 minutes after the end of the infusion; Cp = concentration in plasma
Target Levels based on Dosing Regimen

Gentamicin and Tobramycin
Amikacin
Interval
Peak
*7mg/kg once daily dosing does not require routine monitoring of target peaks and troughs unless the patient is having flluctuations in renal function or has failed extended interval dosing. Please follow the Hartford nomoggram and check an 8-12 hour post-dose level, this can be done after the first dose **This dose is generally used for cystic fibrosis patients *** Extended interval dosing can be Q24H, Q36H, or Q48H
References:
1.
Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. Jun 14 2005;111(23):e394-434. Bates RD, Nahata MC, Jones JW, et al. Pharmacokinetics and safety of tobramycin after once-daily administration in patients with cystic fibrosis. Chest. Nov 5 1997;112(5):1208-1213. BH. H. Vancomycin Dosing & Monitoring Guidelines. UC Davis Medical Center. 2010. Freeman CD, Nicolau DP, Belliveau PP, Nightingale CH. Once-daily dosing of aminoglycosides: review and recommendations for clinical practice. J Antimicrob Chemother. Jun 1997;39(6):677-686. Nicolau DP, Freeman CD, Belliveau PP, Nightingale CH, Ross JW, Quintiliani R. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother. Mar 1995;39(3):650-655. Nightingale CH, Ambrose PG, Drusano GL, Murakawa T. Antimicrobial Pharmacodynamics in Theory and Clinical Practice. Vol Second Edition: Informa Healthcare; 2007. Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Pharmacotherapy. Nov 2009;29(11):1275-1279. Smyth A, Tan KH, Hyman-Taylor P, et al. Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis--the TOPIC study: a randomised controlled trial. Lancet. Feb 12-18 2005;365(9459):573-578. Vic P, Ategbo S, Turck D, et al. Efficacy, tolerance, and pharmacokinetics of once daily tobramycin for pseudomonas exacerbations in cystic fibrosis. Arch Dis Child. Jun 1998;78(6):536-539. Vic P, Ategbo S, Turck D, et al. Tolerance, pharmacokinetics and efficacy of once daily amikacin for treatment of Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis patients. Eur J Pediatr. Nov 1996;155(11):948-953. Whitehead A, Conway SP, Etherington C, Caldwell NA, Setchfield N, Bogle S. Once-daily tobramycin in the treatment of adult patients with cystic fibrosis. Eur Respir J. Feb 2002;19(2):303-309.

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