Stanford Hospital & Clinics Antimicrobial Dosing Reference Guide 2013

This document is also located on the SHC Intranet (http://portal.stanfordmed.org/depts/pharmacy) and http://bugsanddrugs.stanford.edu ABX Subcommittee Approved: May 08, 2013 Formulas for dosing weights: Ideal body weight IBW (male) = 50kg + (2.3 x height in inches > 60 inches) Ideal body weight IBW (female) = 45kg + (2.3 x height in inches > 60 inches) Adjusted Body Weight ABW (kg) = IBW + 0.4 (TBW IBW) Drug
Acyclovir (IV)1,4,5, 6,7,8 (Use ideal BW for obese)

CrCl >50 mL/min

HSV: 5 mg/kg q8h HSV encephalitis/zoster: 10 mg/kg q8h

CrCl 1050 mL/min

Same dose CrCl 2550: q12h CrCl 1025: q24h CrCl > 25

CrCl <10 mL/min

HSV: 2.5 mg q24h HSV encephalitis/zoster: 5 mg/kg q24h

Intermittent Hemodialysis (IHD)

HSV: 2.5 mg/kg q24h HSV encephalitis/zoster: 5 mg/kg q24h Dose after HD on HD days

CRRT
HSV: 5 7.5 mg/kg q24h HSV encephalitis/zoster: 7.5 10 mg/kg q12h

CrCl 1025 200 mg q8h 800 mg q8h

CrCl <10 200 mg q12h 800 mg q12h No change No change No change See CrCl < 10 mL/min Administer after HD on HD days No Data

Acyclovir (PO)1,5

HSV mucocutaneous VZV, HSV zoster

400 mg q8h 800 mg q4h (or 5x daily) No change CrCl 4060: 5 7.5 mg/kg q12h 15 mg/kg q36h
th

Amphotericin B Liposomal1

3 6 mg/kg/day CrCl >60 5 7.5 mg/kg q8h 15 20 mg/kg q24h

Amikacin1,2,3,7 (Use ideal BW; use adjusted BW in morbidly obese) See appendix for complete guidelines

Conventional dosing High-dose extendedinterval dosing

CrCl 2040 5 7.5 mg/kg q24h CrCl > 30: 15 mg/kg q48h CrCl < 30: Not recommended

CrCl < 20 5 mg/kg load, then by level

5 7.5 mg/kg post HD only consult pharmacist

10 mg/kg load, then 7.5 mg/kg q2448h consult pharmacist

Timing of levels: Draw trough 30 min prior to 4 dose. Draw peak 30 min after infusion ends Once daily dosing: goal peak 3560; goal trough <4. Consult Hartford Nomogram Conventional dosing: goal peak 2535 for serious infections; 1520 for UTI goal trough:<5-8 1 2 g q46h Meningitis/endocarditis: 2 g q4h 3 g q6h 500 mg q24h 1 2 g q8h Severe: 2 g q68h same dose q612h Meningitis/endocarditis: 2 g q6h CrCl <50: 3 g q8h CrCl <30: 3 g q12h No change CrCl 10 30: 1 g q8h Severe: 1 g q68h same dose q12h Meningitis/endocarditis: 2 g q12h CrCl <15 3 g q24h No change 500 mg q8h Severe: 500 mg q68h 1 g q12h Meningitis/endocarditis: 2 g q12h 3 g q1224h Dose after HD on HD days No change 12g LD, then 500mg q12h Severe: 1 2 g LD, then 500 mg q8h No change 1 g q24h Dose after HD on HD days General: 1 g q24h CNS/FN: 2 g q24h Give post HD on HD days 200 mg q12h Give post HD on HD days No Change Dose after HD on HD days 1 2 g q68h Meningitis/endocarditis: 2 g q6h 3 g q68h No change 1 g q8h - or 2 g q12h No change

Ampicillin (IV)1,3,4,6 Ampicillin/sulbactam1,2,4,

6,7

Azithromycin (IV/PO)1 Aztreonam1,2, 6 Severe: pseudomonas, meningitis Caspofungin1 (Hepatic adjustment) Cefazolin1,2, 5, 6,7, 8

70 mg x 1, then 50 mg q24h Consider 70 mg x 1, then 35 mg q24h if severe hepatic dysfunction (ChildPugh score >7); 70 mg q24h if on phenytoin, rifampin, other strong enzyme inducers CrCl 35: CrCl 10 34: Mild/moderate: 1 g q8h Mild/moderate: 1 g q12h 1 g q24h Severe: 2 g q8h Severe: 1 2 g q12h CrCl >60 1 g q8h or 2 g q12h 2 g q8h CrCl 30 60: 1 g q12h or 2 g q24h 2 g q12h CrCl < 30 1 g q24h 1 g q12h or 2 g q24h General: 0.5 g q24h Severe infections/CNS/FN: 1 g q24h CrCl <15: 200 mg q12h

2 g q12h General: 1 g q8h Severe infections: 2 g q12h No Data

Cefepime

1,4, 5, 6, 7

General CNS/FN

Ceftaroline1 (SHC Restriction) Ceftriaxone1, 5, 9

600 mg q12h

CrCl 30-50: 400 mg q12h CrCl 15-30: 300 mg q12h

1 2 g q24h Endocarditis, osteomyelitis: 2 g q24h Meningitis, E. faecalis endocarditis: 2 g q12h CrCl >50 400 mg IV q12h 500 mg PO q12h 400 mg IV q8h 750 mg PO q12h CrCl 30 50 same 400 mg IV q812h 500 mg PO q12h No change Scr 1.3 1.5: 1.25 1.9 mg/kg q12h Scr 1.62.5: 2.5mg/kg q24h CrCl < 30: Same dose q48h No change CrCl <30: 500 mg q24h

No change CrCl < 30 400 mg IV q24h 500 mg PO q24h 400 mg IV q24h 500 mg PO q24h No change Scr 2.6 4: 1.5 mg/kg q24h

No Change

Ciprofloxacin (IV/PO)1,2,
5, 6, 8

General infections Pseudomonas, severe

400 mg IV q24h 500 mg PO q24h Give post HD on HD days

400 mg IV q1224h 500 mg PO q1224h

Clindamycin1,2 Colistin (IV) (SHC Restriction) (Use ideal BW in obese) Daptomycin1, 10, 11, 21 (SHC Restriction) (Use adjusted BW in obese) Doxycycline (IV/PO)1 Ertapenem (IV/IM)1
1,5,6

600 900 mg IV q8h 150 450 mg PO q6h 1.25 2.5 mg/kg q12h Skin/Soft tissue: 4 6 mg/kg q24h Endocarditis/Bacteremia: 6 8 mg/kg q24h 100 mg q12h 1 g q24h Dose by ideal body weight: 40 55 kg: 800 mg q24h 56 75 kg: 1200 mg q24h 76 90 kg: 1600 mg q24h (max dose: 1600 mg/day) 200 mg q12h x 10 days 200 400 mg q24h Severe/CNS infections: up to 800 mg q24h

No change

No change

1.5 mg/kg q24h Same dose q48h Give post HD on HD days alt: 6 mg/kg post-HD only

2.5 mg/kg q1224h

Same dose q48h

4 8 mg/kg q48h

No change 500 mg q24h

No change 500 mg q24h Give post HD on HD days

No change 1 g q24h

Ethambutol (PO)1,7 (Use ideal body weight) Fidaxomicin (PO) (SHC Restriction) Fluconazole (IV/PO)1,5,6, 8 Dose by indication. Load 800 mg for candidemia

Same dose q24-36h

Same dose q48h

Same dose post HD only

Same dose q24-36h

No change 100 200 mg (50% of normal dose) q24h

No change 50 100 mg (25% of normal dose) q24h

No change Dose by indication: 200 800 mg post HD only

No change 400 800 mg q24h

Drug

CrCl >50 mL/min

ClCr(mL/min/kg) > 1.4 > 1.0 1.4 > 0.8 1.0

CrCl 1050 mL/min

CMV induction 60 mg/kg q8h 45 mg/kg q8h 90 mg/kg q12h 70 mg/kg q12h 50 mg/kg q12h

CrCl <10 mL/min

CMV maintenance 90 mg/kg q24h 70 mg/kg q24h 50 mg/kg q24h 80 mg/kg q48h 60 mg/kg q48h 50 mg/kg q48h Not recommended No data

Intermittent Hemodialysis (IHD)

HSV 40 mg/kg q12h 30 mg/kg q12h 20 mg/kg q12h 35 mg/kg q24h 25 mg/kg q24h 20 mg/kg q24h Not recommended No data 120 mg/kg q24h 90 mg/kg q24h 65 mg/kg q24h 105 mg/kg q48h 80 mg/kg q48h 65 mg/kg q48h Not recommended No data

CRRT

40 mg/kg q8h 30 mg/kg q8h 35 mg/kg q12h 25 mg/kg q12h 40 mg/kg q24h 35 mg/kg q24h Not recommended No data

50 mg/kg q12h

Foscarnet1, 5

> 0.6 0.8 > 0.5 0.6 0.4 0.5 < 0.4 IHD CRRT CMV

40 mg/kg q12h 80 mg/kg q24h 60 mg/kg q24h 60 mg/kg q24h 50 mg/kg q24h 50 mg/kg q24h Not recommended Not recommended 60 90 mg/kg loading dose (post-HD), then 45 60 mg/kg/dose post-HD only

No data Dose as for CrCL 10 50 mL/min CrCl >70* 5 mg/kg q12h 5 mg/kg q24h CrCl >50 2.5 mg/kg q12h 2.5 mg/kg q24h CrCl >25 2.5 mg/kg q24h 1.25 mg/kg q24h CrCl >10 1.25 mg/kg q24h 0.625 mg/kg q24h CrCl <10 1.25 mg/kg 3x/wk 0.625 mg/kg 3x/wk

Ganciclovir1, 6 Consider loading dose of 5mg/kg for all patients

Induction (I) Maintenance (M)

LD 5mg/kg, then I: 1.25 mg/kg post HD only M: 0.625 mg/kg post HD only

LD 5mg/kg, then I: 2.5 mg/kg q1224h M: 1.25 2.5 mg/kg q24h

*Manufacturers CrCl cutoffs. Please refer to BMT protocols if applicable

CrCl >60 1.7 mg/kg q8h or 4 7 mg/kg q24h (high-dose extended-interval*)

CrCl 4059 1.7 mg/kg q12h or 4 7 mg/kg q36h (high-dose extended-interval*)

Gram negative Gentamicin6 (SHC interchange to tobramycin. Exception: gram positive synergy) See appendix for complete guidelines

CrCl 2039 1.7 mg/kg q24h or CrCl > 30: 4 7 mg/kg q48h CrCl < 30: Not recommended (high-dose extended-interval*) 1 mg/kg q24h

CrCl <20

HD

CRRT

2 mg/kg loading dose, then per level

2 mg/kg loading dose, then 1.5 mg/kg post HD

1.52.5 mg/kg q2448h

1 mg/kg q48-72h; 1mg/kg q24h, consider redosing then per level when level <1 mg/L Goal levels: (Gram-negative infections): Goal peak for traditional dosing (48mg/L), trough (<1-2mg/L) for treatment. (Gram-positive synergy): Goal peak 35mg/L (3-4 if using IDSA endocarditis guidelines). Goal trough <1 mg/L Timing of levels: Draw trough 30 min prior to 4th dose. Draw peak 30 minutes after infusion ends (4 th dose). (For CrCL <20, may check levels sooner than 4th dose) 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 ** Streptococci, Streptococcus bovis, Strep. viridans endocarditis: optional dosing 3mg/kg q24h for CrCl > 60 Gram positive synergy 1 mg/kg q8h** 1 mg/kg q12h 1 mg/kg load, then by level 500 mg q6h 300 mg q24h CrCl 50 500 mg q8h No change CrCl 2049: 250 500 mg q48h 750 mg q48h No change CrCl >50 CrCl 2650: 1 g q12h or 0.5 g q6h 2 g q12h CrCl 1025 0.5 g q812h 1 g q12h or 0.5 g q8h 250 500 mg q12h No change CrCl < 20 500 mg x1, then 250 mg q48h 750 mg x1, then 500 mg q48h No change CrCl <10 0.5 g q1224h 0.5 g q1224h 250 500 mg q12h Dose after HD on HD days No change Dose after HD on HD days See CrCl < 20 ml/min Dose after HD on HD days No change. Dose after HD on HD days 500 mg q24h Give post HD on HD days Severe/CF/CNS: 1 g q24h Give post HD on HD days 500 mg q8h No change No change Treatment/prophylaxis: 30 mg after every other session Severe/ICU: 60 mg after every other session 4mu x1, then 1 2 mu q6h General: 2.25 g q12h Pseudomonas/PNA/ severe infections: 2.25 g q8h Pseudomonas/CAP: 750 mg LD, then 250 750 mg q24h No change 1 g q12h - or 500 mg q6h Severe/CF/CNS: 2g q12h 500 mg q68h No change No change Prophylaxis: 75 mg q24h Treatment: 75 mg BID Severe/ICU: 150 mg BID 4mu x1, then 2 3 mu q6h 3.375 g q6h or Extended infusion 3.375 g q8h (infused over 4 h) 500 mg q8h Severe: 500 mg q6h No change 500 mg q48h

Imipenem/Cilastatin1,2, 6 (Non-formulary) Isoniazid1

Levofloxacin (IV/PO)1,2, 5,
6, 8

General Pseudomonas /CAP:

250 500 mg q24h 750 mg q24h

Linezolid (IV/PO)1,4 (SHC Restriction)

600 mg q12h

Meropenem1,2, 6, 8, 18 (SHC Restriction)

General Severe/CF/CNS

1 g q8h 2 g q8h

Metronidazole (IV/PO) Moxifloxacin (IV/PO) Nafcillin

1 1

500 mg q6 8h 400 mg IV/PO q24h 2 g q4h Mild infections: 1gm q4h CrCl 30 CrCl < 30 Prophylaxis 75 mg q24h 75 mg q48h

No change Severe hepatic impairment: can consider 500 mg q12h No change No change Treatment 75 mg q12h 75 mg q24h 2 3mu q4h CrCl >40 CrCl 2040 3.375 g q6h 2.25 g q6h 4.5 g q6h 3.375 g q6h Extended infusion for CrCl > 20: 3.375 4.5 g q8h over 4h No change No change Treatment (severe/ICU) 150 mg q12h 150 mg q24h 1 2mu q6h CrCl <20: 2.25 g q8h 2.25 g q6h 3.375 g q12h over 4h

Oseltamivir (PO)1,2, 15,16,17

Penicillin G (IV)1, 5, 6

2 4 mu q4h

Piperacillin/tazobactam
1,2,4, 5, 6, 8, 22

General Pseudomonas/ nosocomial PNA/ severe: Treatment: 200 mg q6h or 400 mg q12h

Posaconazole (PO)1,2, 22 (SHC Restriction) Pyrazinamide (PO)1, 5, 12 (Use ideal BW) Round to nearest tablet size Rifampin (IV/PO)1, 13, 14

No change. Posaconazole levels shown to have great degree of interpatient variability. Many clinicians would recommend blood levels to assess efficacy. Consider drawing a trough 4 - 7 days after initiating dose

Dose by ideal body weight: 40 55 kg: 1000 mg 56 75 kg: 1500 mg 76 90 kg: 2000 mg (max 2000 mg/day) TB: 600 mg q24h Endocarditis: 300 mg q8h

CrCl < 30: Same dose 3 times per week

Same dose administer after HD only

No data

No change

No change

No change

No change

Drug

CrCl >50 mL/min

CrCl >60 1.7 mg/kg q8h or 4 7 mg/kg q24h (high-dose extendedinterval*)

CrCl 1050 mL/min

CrCl 4060 1.7 mg/kg q12h or 4 7 mg/kg q36h (high-dose extendedinterval*)

CrCl <10 mL/min

CrCl 2040

Intermittent Hemodialysis (IHD)

CrCl <20 HD

CRRT
CRRT

Tobramycin20 (Use ideal or adjusted BW for obese) See appendix for complete guidelines

1.7 mg/kg q24h or CrCl > 30: 4 7 mg/kg q48h CrCl < 30: Not recommended (high-dose extended-interval*)

2 mg/kg loading dose, then per level

2 mg/kg loading dose, then 1.5 mg/kg post HD

1.5 2.5 mg/kg q2448h

Goal levels: Goal peak for traditional dosing (48mg/L), and trough (<1-2mg/L) for treatment. *certain qualifications for oncedaily dosing Timing of levels: Draw trough 30 min prior to 4th dose. Draw peak 30 minutes after infusion ends (4 th dose). (For CrCL <20, may check levels sooner than 4th dose) 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. 5 10 mg/kg/day TMP divided q68h PCP/Stenotrophomonas: 15 20 mg/kg/day TMP divided q6-8h 2.5 5 mg/kg TMP q24h* CrCl < 30: 2.5 5 mg/kg/day TMP divided q8 12h PCP/Stenotrophomonas: 7.5 10 mg/kg/day TMP divided q812h CrCl >30: Treatment HSV/VZV: CrCl >50: 1 g q8h CrCl 30-50: 1g q12h Genital herpes: 1 g q12h Herpes labialis: CrCl >50: 2 g q12h x 2 doses CrCl 30-50: 1g q12h x 2 doses HSV/VZV: 500 mg q8-12h Genital herpes: 1000 mg q24h Herpes labialis: 1g q12h x 2 doses CrCl > 60 Induction (14-21 days) Maintenance/ prophylaxis 900 mg q12h 900 mg q24h CrCl 10-30: HSV/VZV: 1 g q24h <10 HSV/VZV: 500 mg q24h PCP/ Stenotrophomonas: 7.5 10 mg/kg TMP q24h* *Give after HD on HD days 5 10 mg/kg/day TMP divided q12h PCP/ Stenotrophomonas: 10 15mg/kg/day TMP divided q12h

Trimethoprim (TMP)/ Sulfamethoxazole (IV/PO)1, 5, 6 (Dose by ideal or adjusted BW in obese)

SS = 80 mg TMP = 10 ml po soln DS =160 mg TMP = 20ml po soln

Valacyclovir (PO)1 Please refer to transplant protocols if applicable

Genital herpes: 1 g q24h Herpes labialis: 500 mg q12h x 2 doses

Genital herpes: 500 mg q24h Herpes labialis: 500 mg x 1 dose 500 mg q24h Give post HD on HD days No Data

Suppressive

CrCl <30: HSV/VZV: 500 mg q2448h

Valganciclovir (PO)1 Please refer to transplant protocols if applicable Vancomycin (IV)6, 19, 21 (Use actual body weight) Consider loading dose of 2530 mg/kg (max 2 g) for severe infections and ICU Vancomycin PO1 (SHC Restriction: capsules restricted) Oral solution formulary Voriconazole (IV/PO)1,22,23 (SHC Restriction) (Dose by adjusted BW in obese)

CrCl 40 59 450 mg q12h 450 mg q24h

CrCl 25 39: 450 mg q24h 450 mg q48h

CrCl 10 24 450 mg q48h 450 mg twice/week

CrCl < 10, IHD, CRRT Not recommended, use ganciclovir

CrCl >50 CrCl 3049 CrCl 1529 CrCl <15 15 20 mg/kg 15 20 mg/kg 10 15 mg/kg 10 15 mg/kg q812h q24h q24h q2448h Goal trough 1015 mcg/ml (cellulitis, skin/soft tissue infections) Goal trough 1520 mcg/ml (pneumonia, bacteremia, endocarditis, osteomyelitis) Timing of levels: Draw trough< 30 minutes before 4th dose of new regimen. When SCr acutely rises, hold dose, restart when level <15 - 20 See appendix for complete guidelines Poor systemic absorption- used for the treatment of Clostridium difficile-associated diarrhea General: 125 250 mg QID Severe/complicated: 500 mg QID 6 mg/kg IV q12h x 2, then 4 mg/kg IV q12h 400 mg PO q12h x 2, then 200 mg PO q12h

20 25 mg/kg LD, then redose with 10 15mg/kg post dialysis when level <15 20

15 25mg/kg LD, then 10 15mg/kg q24h Draw level prior to 3rddose. Adjust to levels

No change

No change

IVPO conversion 1:1 (round to nearest tablet size- available in 200 mg and 50 mg tablets) Caution with IV: accumulation of IV vehicle cyclodextran occurs. Consider PO unless benefits justify risks of IV use. Levels shown to have great degree of interpatient variability. Many clinicians would recommend blood levels to assess 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 CVVHDF and CVVHD modalities, which are the most common modes at SHC. Note that these are generally higher than doses used in CVVH. References:
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. LexiDrug, LexiComp [Internet database]. Hudson, OH: LexiComp, 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, 5 th 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 SingleDose 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 603662, 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 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; 66:8298 Nicolau DP et al, Experience with a OnceDaily 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 MethicillinResistant Staphylococcus Aureus Infections in Adults and Children, Clinical Infectious Diseases 2011;138 Patel N et al, Identification of optimal renal dosage adjustments for traditional and extended-infusion piperacillin-tazobactam dosing regimens in hospitalized patients. Antimicrob Agents Chemother 2012; 54(1):460-5. Koselke E et al. Evaluation of the effect of obesity on voriconazole serum concentration. J Antimicrob Chemotherapy. Dec 2012;67(12):2957-62.