TABLE 4

Therapeutic options for treatment of S. aureus and S. epidermidis osteomyelitisa

Agent (class)DoseMethicillin susceptibility statusInteractionsSide effectsComments
Recommended i.v. agents for treatment of S. aureus and S. epidermidis osteomyelitis
    Flucloxacillin (penicillin)2 g q6hMSSA/MSSENo significant interactionsRash, nausea, vomiting, diarrhea, cholestatic hepatitisFirst-line treatment for MSSA/MSSE infection
    Nafcillin (penicillin)2 g q4hMSSA/MSSETetracyclines, warfarinPhlebitis, rash, neutropenia, interstitial nephritisFirst-line treatment for MSSA/MSSE infection
    Oxacillin (penicillin)2 g q4hMSSA/MSSETetracyclinesPhlebitis, rash, hepatitisFirst-line treatment for MSSA/MSSE infection
    Cefazolin (cephalosporin)2 g q8hMSSA/MSSEProbenecid (increase in cephalosporin serum concn), warfarinPhlebitis, rash, fever, eosinophiliaConvenient for OPAT
    Ceftriaxone (cephalosporin)2 g q24hMSSA/MSSECalcium-containing solutions, probenecid (as described above), warfarin, lansoprazolePseudocholelithiasis, phlebitis, rash, feverConvenient for OPAT
    Vancomycin (glycopeptide)15 mg/kg of body wt q12hMRSA/MRSENondepolarizing muscle relaxants, nephrotoxic agentsNephrotoxicity, ototoxicity, thrombocytopenia, red man syndromeTarget 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 q24hMRSA/MRSENephrotoxic agents, ototoxic agentsThrombophlebitis, rash, neutropenia, eosinophilia, ototoxicityTarget trough of >20 μg/ml
    Daptomycin (cyclic lipopeptide)6 mg/kg q24hMRSA/MRSEStatinsCK elevation, eosinophilic pneumoniaMonitor CK, convenient for OPAT
Oral treatment options for either MSSA/MSSE or MRSA/MRSE osteomyelitis (if isolates are susceptible)
    Levofloxacin (fluoroquinolone)750 mg q24hMSSA/MSSE, MRSA/MRSEQTc-prolonging agents, warfarinDiarrhea, phototoxicity, QTc prolongation, tendon rupture, seizuresUse combination therapy
    Trimethoprim-sulfamethoxazole (antifolate)DS 2 tabs q12hMSSA/MSSE, MRSA/MRSEACE inhibitors, azathioprine, cyclosporine, folinic acid, para-aminobenzoic acid, phenytoin, sulfonylureas, oral contraceptives, warfarinNausea, vomiting, rash, hyperkalemia, bone marrow suppressionConsider combination therapy
    Doxycycline (tetracycline)100 mg q12hMSSA/MSSE, MRSA/MRSEAcitretin, barbiturates, bismuth salts, carbamazepine, digoxin, oral contraceptives, penicillins, warfarinGI intolerance, photosensitivity, dental deposition
    Minocycline (tetracycline)100 mg q12hMSSA/MSSE, MRSA/MRSEAcitretin, barbiturates, bismuth salts, carbamazepine, digoxin, oral contraceptives, penicillins, warfarinVertigo, ataxia, hypersensitivity pneumonitis, rash, GI intolerance, photosensitivity, dental depositionConsider combination therapy
    Linezolid (oxazolidinone)600 mg q12hMSSA/MSSE, MRSA/MRSESSRIs, MAOIs, tricyclic antidepressants, adrenergic agents, rifampinThrombocytopenia, anemia, optic neuropathy, peripheral neuropathyReserve for use when alternatives not available, monitor FBC
    Clindamycin (lincosamide)600 mg q6h (i.v.), 450 mg q6h (p.o.)MSSA/MSSE, MRSA/MRSEErythromycin, kaolin-pectin, loperamide, nondepolarizing muscle relaxantsDiarrhea, nausea, vomiting, anorexia, rashCheck for inducible clindamycin resistance if erythromycin resistant
    Rifampin (rifamycin)300–450 mg q12h or 600 mg q24hMSSA/MSSE, MRSA/MRSENumerous—check interactions when prescribingOrange discoloration of urine, tears, and sweat, hepatitis, GI intolerance, flu-like syndromeUse 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 q6hMSSA/MSSE, MRSA/MRSEStatins, ritonavirPhlebitis, nausea, vomiting, diarrhea, elevated bilirubinUse 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 q8hMRSA/MRSENo significant interactionsNausea, vomiting, diarrhea, crystalluria, elevated transaminasesLimited data, new agent with activity against MRSA/MRSE
    Tigecycline (glycylcycline)100-mg load, then 50 mg q12hMRSA/MRSEOral contraceptivesNausea, vomiting, hepatic failure, pancreatitisLimited data, new agent with activity against MRSA/MRSE, spectrum may be excessively broad
    Telavancin (lipoglycopeptide)10 mg/kg q24hMRSA/MRSEQTc-prolonging agents, nephrotoxic agentsNephrotoxicity, QTc prolongation, taste disturbances, nausea, vomitingLimited data, new agent with activity against MRSA/MRSE
    Dalbavancin1,000–1,500-mg first dose, then 500 mg once a weekMRSA/MRSEUnknownDiarrhea, 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 syndromeLimited data, new agent with activity against MRSA/MRSE
  • a Data 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.