TABLE 4.

Therapeutic options for treatment of S. aureus and S. epidermidis osteomyelitis^a

Agent (class)	Dose	Methicillin susceptibility status	Interactions	Side effects	Comments
Recommended i.v. agents for treatment of S. aureus and S. epidermidis osteomyelitis
Flucloxacillin (penicillin)	2 g q6h	MSSA/MSSE	No significant interactions	Rash, nausea, vomiting, diarrhea, cholestatic hepatitis	First-line treatment for MSSA/MSSE infection
Nafcillin (penicillin)	2 g q4h	MSSA/MSSE	Tetracyclines, warfarin	Phlebitis, rash, neutropenia, interstitial nephritis	First-line treatment for MSSA/MSSE infection
Oxacillin (penicillin)	2 g q4h	MSSA/MSSE	Tetracyclines	Phlebitis, rash, hepatitis	First-line treatment for MSSA/MSSE infection
Cefazolin (cephalosporin)	2 g q8h	MSSA/MSSE	Probenecid (increase in cephalosporin serum concn), warfarin	Phlebitis, rash, fever, eosinophilia	Convenient for OPAT
Ceftriaxone (cephalosporin)	2 g q24h	MSSA/MSSE	Calcium-containing solutions, probenecid (as described above), warfarin, lansoprazole	Pseudocholelithiasis, phlebitis, rash, fever	Convenient for OPAT
Vancomycin (glycopeptide)	15 mg/kg of body wt q12h	MRSA/MRSE	Nondepolarizing muscle relaxants, nephrotoxic agents	Nephrotoxicity, ototoxicity, thrombocytopenia, red man syndrome	Target trough of 15–20 mg/liter, consider combination therapy, may be less effective against strains with MICs of 1–2 μg/ml
Teicoplanin (glycopeptide)	12 mg/kg q24h	MRSA/MRSE	Nephrotoxic agents, ototoxic agents	Thrombophlebitis, rash, neutropenia, eosinophilia, ototoxicity	Target trough of >20 μg/ml
Daptomycin (cyclic lipopeptide)	6 mg/kg q24h	MRSA/MRSE	Statins	CK elevation, eosinophilic pneumonia	Monitor CK, convenient for OPAT
Oral treatment options for either MSSA/MSSE or MRSA/MRSE osteomyelitis (if isolates are susceptible)
Levofloxacin (fluoroquinolone)	750 mg q24h	MSSA/MSSE, MRSA/MRSE	QTc-prolonging agents, warfarin	Diarrhea, phototoxicity, QTc prolongation, tendon rupture, seizures	Use combination therapy
Trimethoprim-sulfamethoxazole (antifolate)	DS 2 tabs q12h	MSSA/MSSE, MRSA/MRSE	ACE inhibitors, azathioprine, cyclosporine, folinic acid, para-aminobenzoic acid, phenytoin, sulfonylureas, oral contraceptives, warfarin	Nausea, vomiting, rash, hyperkalemia, bone marrow suppression	Consider combination therapy
Doxycycline (tetracycline)	100 mg q12h	MSSA/MSSE, MRSA/MRSE	Acitretin, barbiturates, bismuth salts, carbamazepine, digoxin, oral contraceptives, penicillins, warfarin	GI intolerance, photosensitivity, dental deposition
Minocycline (tetracycline)	100 mg q12h	MSSA/MSSE, MRSA/MRSE	Acitretin, barbiturates, bismuth salts, carbamazepine, digoxin, oral contraceptives, penicillins, warfarin	Vertigo, ataxia, hypersensitivity pneumonitis, rash, GI intolerance, photosensitivity, dental deposition	Consider combination therapy
Linezolid (oxazolidinone)	600 mg q12h	MSSA/MSSE, MRSA/MRSE	SSRIs, MAOIs, tricyclic antidepressants, adrenergic agents, rifampin	Thrombocytopenia, anemia, optic neuropathy, peripheral neuropathy	Reserve for use when alternatives not available, monitor FBC
Clindamycin (lincosamide)	600 mg q6h (i.v.), 450 mg q6h (p.o.)	MSSA/MSSE, MRSA/MRSE	Erythromycin, kaolin-pectin, loperamide, nondepolarizing muscle relaxants	Diarrhea, nausea, vomiting, anorexia, rash	Check for inducible clindamycin resistance if erythromycin resistant
Rifampin (rifamycin)	300–450 mg q12h or 600 mg q24h	MSSA/MSSE, MRSA/MRSE	Numerous—check interactions when prescribing	Orange discoloration of urine, tears, and sweat, hepatitis, GI intolerance, flu-like syndrome	Use in combination therapy only, as S. aureus resistance develops quickly in response to monotherapy; particularly effective in treatment of biofilms and infected prosthetic material
Fusidic acid (fusidane)	500 mg q6h	MSSA/MSSE, MRSA/MRSE	Statins, ritonavir	Phlebitis, nausea, vomiting, diarrhea, elevated bilirubin	Use in combination therapy only, as S. aureus resistance develops quickly in response to monotherapy
Newer i.v. agents with unproven but potential future role in treatment of MRSA osteomyelitis
Ceftaroline (cephalosporin)	600 mg q8h	MRSA/MRSE	No significant interactions	Nausea, vomiting, diarrhea, crystalluria, elevated transaminases	Limited data, new agent with activity against MRSA/MRSE
Tigecycline (glycylcycline)	100-mg load, then 50 mg q12h	MRSA/MRSE	Oral contraceptives	Nausea, vomiting, hepatic failure, pancreatitis	Limited data, new agent with activity against MRSA/MRSE, spectrum may be excessively broad
Telavancin (lipoglycopeptide)	10 mg/kg q24h	MRSA/MRSE	QTc-prolonging agents, nephrotoxic agents	Nephrotoxicity, QTc prolongation, taste disturbances, nausea, vomiting	Limited data, new agent with activity against MRSA/MRSE
Dalbavancin	1,000–1,500-mg first dose, then 500 mg once a week	MRSA/MRSE	Unknown	Diarrhea, headache, nausea, abdominal pain, blood disorders, Clostridium difficile colitis, constipation, cough, fungal infection, oral candidiasis, phlebitis, pruritus, rash, urticaria, vomiting, vulvovaginal mycotic infection, red man syndrome	Limited data, new agent with activity against MRSA/MRSE

^aData are from references 133, 134, 137, and 211 to 213. Abbreviations: ACE, angiotensin-converting enzyme; CK, creatine kinase; FBC, full blood count; GI, gastrointestinal; i.v., intravenous; MAOI, monoamine oxidase inhibitor; MRSA, methicillin-resistant Staphylococcus aureus; MRSE, methicillin-resistant Staphylococcus epidermidis; MSSA, methicillin-susceptible Staphylococcus aureus; MSSE, methicillin-susceptible Staphylococcus epidermidis; OPAT, outpatient parenteral antimicrobial therapy; p.o., per os; SSRI, selective serotonin reuptake inhibitor; q6h, every 6 h.