Infection severity	Antibiotic therapy*	Pathogen coverage	Treatment considerations
Mild foot infection	Cephalexin (Keflex), 500 mg orally every 6 hours	GPC with or without GNR	First-line alternative for GBS or MSSA
	Amoxicillin/clavulanate (Augmentin), 875/125 mg orally every 12 hours	GPC, GNR, anaerobes	First-line alternative, especially if concern for polymicrobial infection
	Trimethoprim/sulfamethoxazole, 320/1,600 mg orally every 12 hours	MSSA, MRSA, with or without GNR	Use in combination with other antibiotics to cover GBS; may cause a rash, acute kidney injury, and increased hyperkalemia risk
	Doxycycline, 100 mg orally every 12 hours	MSSA, MRSA, with or without GNR, anaerobes	Use in combination with other antibiotics to cover GBS; causes photosensitivity and GI intolerance; must be separated from di- and trivalent cations
	Clindamycin, 300 to 450 mg orally every 8 hours	GPC, with or without MRSA, anaerobes	Weaker coverage overall and can develop resistance; may be used in combination with other antibiotics to improve gram-negative coverage; causes GI intolerance and increased Clostridioides difficile infection risk
Moderate foot infection	Nafcillin, 1 to 2 g IV every 4 hours	GPC	First-line option given IV for GBS or MSSA
	Cefazolin, 1 to 2 g IV every 8 hours	GPC, with or without GNR	First-line option given IV for GBS or MSSA
	Vancomycin loading dose, 20 to 30 mg per kg IV, then based on local institutional policy	GPC including MRSA	Drug of choice given IV for MRSA; requires therapeutic drug monitoring for effectiveness and nephrotoxicity concern
	Ampicillin/sulbactam (Unasyn), 3 g IV every 6 hours	GPC, GNR, anaerobes	Good option for more severe infections, but does not cover Pseudomonas
	Ertapenem (Invanz), 1 g IV every 24 hours	GPC, GNR, anaerobes	Alternative option if needing treatment IV once per day
	Ceftriaxone, 1 to 2 g IV every 24 hours	GPC, GNR	Good option for more severe infections, but does not cover Pseudomonas; often combined with metronidazole (Flagyl) to improve anaerobic coverage
	Metronidazole, 500 mg IV vs. 500 mg orally every 8 hours	Anaerobes	Often used in combination with other antibiotics to improve anaerobic coverage; avoid alcohol
	Levofloxacin (Levaquin), 750 mg IV or 750 mg orally every 24 hours	GPC, GNR including Pseudomonas aeruginosa, ESBL-producing organism	Less preferred with multiple precautions (e.g., QTc prolongation, tendon rupture, hypoglycemia or hyperglycemia, aortic aneurism or dissection, peripheral or optic neuropathy, seizure); must be separated from di- and trivalent cations
	Delafloxacin (Baxdela), 300 mg IV every 12 hours or 450 mg orally every 12 hours	GPC, MRSA, GNR including P. aeruginosa, anaerobes	See levofloxacin precautions, which are class warnings
Severe foot infection	Vancomycin loading dose, 20 to 30 mg per kg IV, then based on local institutional policy	GPC including MRSA	Drug of choice given IV for MRSA; requires therapeutic drug monitoring for effectiveness and nephrotoxicity concern
	Daptomycin (Cubicin), 4 to 6 mg per kg IV every 24 hours (may increase to 8 to 10 mg per kg for a bone or joint infection)	GPC including MRSA	Alternative option to vancomycin given IV for MRSA; requires baseline and weekly creatine kinase monitoring for rhabdomyolysis
	Linezolid (Zyvox), 600 mg IV every 12 hours (also available as a 600-mg tablet if patient is stable enough for oral therapy)	GPC including MRSA	Alternative option to vancomycin given IV for MRSA; requires complete blood count monitoring if treatment > 2 weeks with pancytopenia risk; watch drug-drug interactions that could cause serotonin syndrome
	Piperacillin/tazobactam (Zosyn), 4.5 g IV every 6 hours	GPC, GNR including P. aeruginosa, anaerobes	Often a drug of choice with broad empiric coverage; could cause acute kidney injury risk especially in combination with other nephrotoxins
	Cefepime, 2 g IV every 8 hours	GPC, GNR including P. aeruginosa	Good alternative to piperacillin/tazobactam if concern for acute kidney injury; often combined with metronidazole to improve anaerobic coverage
	Meropenem (Merrem IV), 1 g IV every 8 hours	GPC, ESBL-producing organism, GNR including P. aeruginosa, anaerobes	Treatment of choice with ESBL-producing organism or if other broad-spectrum gram-negative coverage is ineffective