Dosing of antimicrobials in obesity

Background

• Obesity can affect several parameters important for drug dosing: oral drug absorption (delayed gastric emptying decreasing C_max); IM drugs being given into subcutaneous far; increased volume of distribution (V_d), more for lipophilic than hydrophilic drugs; protein binding, with increased plasma concentrations of 1-acid glycoprotein and free fatty acids; increased free fatty acids, which can increase or decrease protein binding of certain drugs; drug clearance by liver.

Calculating Body Weight

Weight-based dosing can use total body weight (TBW) in some instances, but often requires adjustments.

Statistic	Equation	Notes
Body mass index (BMI) (kg/m2)	[math]\displaystyle{ \frac{weight}{height^{2}} }[/math]	kg and m
Body surface area (BSA) (m2)	[math]\displaystyle{ BSA = \sqrt{\frac{height \times weight}{3600}} }[/math]	kg and cm
Ideal body weight (IBW) (kg)	male: [math]\displaystyle{ 50 + 2.3 \times \text{(inches over 5 ft)} }[/math]	in inches
	female: [math]\displaystyle{ 45.5 + 2.3 \times \text{(inches over 5 ft)} }[/math]
Adjusted body weight (ABW) (kg)	[math]\displaystyle{ IBW + C \times (TBW - IBW) }[/math]	C = 0.3 to 0.4 or more; drug-specific
Lean body weight (LBW) (kg)	male: [math]\displaystyle{ \frac{9270 \times TBW}{6680} + 216 \times BMI }[/math]
	female: [math]\displaystyle{ \frac{9270 \times TBW}{8780} + 244 \times BMI }[/math]

Calculating CrCl

• Salazer-Cocoran equation is more reliable in obesity but requires both height and weight.

Antibiotics

β-lactams

• Evidence is poor that we need higher doses of beta lactams in obesity, though it should be considered for deep-seated or severe infections, including osteomyelitis

Penicillins

Drug	Usual Dose	Obesity	Notes
Amoxicillin	250-500 mg q8h	1 g PO q8h
Ampicillin	1-2 g q4-6h	2 g IV q4h
Nafcillin		2 g IV q4h
Piperacillin-tazobactam	4.5 g IV q8h (q6h for Pseudomonas)	Prolonged infusion

Cephalosporins

Drug	Usual Dose	Obesity	Notes
Cephalexin	500-1000 g PO qid	1000 g PO qid
Cefazolin	1-2 g IV q8h	2 g IV q6h once ≥120 kg
Cefipime	2 g IV q8h	2 g IV q8h prolonged infusion
Ceftazidime	1-2 g IV q8h	2 g IV q8h prolonged infusion
Ceftriaxone	1-2 g IV q24h	2 g IV q12h
Ceftazidime-avibactam		Usual dose
Ceftolozane-tazobactam		Usual dose
Ceftaroline		Consider q8h

Carbapenems

Drug	Usual Dose	Obesity	Notes
Doripenem		Consider extended infusion
Ertapenem	1 g IV q24h	Usual dose
Imipenem		Usual dose
Meropenem	500 mg q6h (1 g IV q8h for febrile neutropenia)	Consider prolonged infusion

Quinolones

Drug	Usual Dose	Obesity	Notes
Ciprofloxacin	500-750 mg PO q12h or 400 mg IV q6-8h	400 mg IV q8h or 750 mg PO q12h
Levofloxacin	500-750 mg PO q24h	Consider up to 1000 mg PO q24h
Moxifloxacin	400 mg q24h	Usual dose

Macrolides

Drug	Usual Dose	Obesity	Notes

Tetracyclines

Drug	Usual Dose	Obesity	Notes

Aminoglycosides

Drug	Usual Dose	Obesity	Notes
Amikacin	15 mg/kg	Use ABW0.4	Use Hartford nomogram with a (halved) random level
Gentamicin	7 mg/kg	Use ABW0.4	Use Hartford nomogram with a random level
Tobramycin	7 mg/kg	Use ABW0.4	Use Hartford nomogram with a random level

Others

Drug	Usual Dose	Obesity	Notes
Aztreonam		2 g IV q6-8h
Colistin	5 mg CBA/kg IBW x1 loading (max 300 mg) followed by 5 mg/kg/day divided q8h	Use IBW	Max 360 mg daily (nephrotoxicity)
Polymyxin B		Use ABW0/4	Max 200 mg or 2 MU daily (toxicity)
Clindamycin	300-450 mg PO q6-8h 600-900 mg IV q8h	600 mg IV q6h 900 mg IV q8h 450-600 mg PO q6h 600-900 mg PO q8h	Max 2700 mg daily, or 4800 mg daily IV if life-threatening
Dalbavancin		Usual dose
Daptomycin	4-6 mg/kg q24h	Use ABW0.4
Linezolid	600 mg PO/IV q12h	Usual dose
Oritavancin		Usual dose
TMP-SMX	Up to 320 mg(TMP) PO q12h 8-10 mg(TMP)/kgABW in divided doses	Consider ABW0.4 when doing high dose
Telavancin		Usual dose
Tigecycline		Usual dose
Vancomycin	20-25 mg/kg load (max 2.5 g) 10-15 mg/kg q12h (maintenance)	Use TBW; or 25-30 mg/kg load and 15 mg/kg q12h with ABW0.4

Antifungals

Echinocandins

Drug	Usual Dose	Obesity	Notes
Anidulafungin		200 mg load followed by 100 mg IV q24h
Caspofungin		70 mg IV q24h
Micafungin		Candida albicans (<115 kg): 150 mg IV q24h Candida albicans (115-185 kg): 200 mg IV q24h Candida glabrata (<115 kg): 200 mg IV q24h

Azoles

Drug	Usual Dose	Obesity	Notes
Fluconazole		6-12 mg/kg IV q24h (max 1600 mg)	using TBW
Isavuconazole		200 mg q8h for 6 doses followed by 200 mg q24h
Itraconazole		200 mg q12h
Posaconazole		300 mg q12h for 2 doses followed by 300 mg q24h
Voriconazole		Oral: 400 mg q12h for 2 doses followed by 200 mg q12h IV: 6 mg/kg q12h for 2 doses followed by 4 mg/kg q12h	using ABW0.

Others

Drug	Usual Dose	Obesity	Notes
Liposomal amphotericin B		3-5 mg/kg IV	using TBW
Flucytosine		25-40 mg/kg q6h	using IBW

Antivirals

Drug	Usual Dose	Obesity	Notes
Acyclovir		10-15 mg/kg IV q8h	ABW0.4
Cidofovir		5 mg/kg q1wk for 2 doses followed by 3-5 mg/kg q2wk	ABW0.4
Foscarnet			ABW0.4
Ganciclovir		Treatment: 5 mg/kg q12h Prophylaxis: 5 mg/kg q24h	ABW0.4
Valganciclovir		Treatment: 900 mg q12h Prophylaxis: 900 mg q24h
Oseltamivir		75 mg q12h

Further Reading

• Comprehensive Guidance for Antibiotic Dosing in Obese Adults. Pharmacotherapy. 2017;37(11):1415-1431. doi: 10.1002/phar.2023
• Updated antimicrobial dosing recommendations for obese patients. Antimicrob Agents Chemother. 2024;68(5):e0171923. doi: 10.1128/aac.01719-23