Empiric Therapy Regimens
Most cases of osteomyelitis in adults require a combination of medical and surgical therapy for successful eradication of infection.
If possible, antimicrobials should be withheld until percutaneous or surgical deep cultures have been obtained. Once cultures are obtained, a parenteral antimicrobial regimen is initiated to cover suspected pathogens. However, if the patient is acutely ill (with sepsis or concomitant soft tissue infection), antibiotic therapy should not be delayed.
In hematogenous long bone osteomyelitis, infection is usually monobacterial; whereas in contiguous infection, it is usually polymicrobial.
The most commonly encountered organisms in osteomyelitis are Staphylococcus aureus, coagulase-negative streptococci, aerobic gram-negative bacteria, and anaerobes including Finegoldia (formerly Peptostreptococcus) species. Beta-lactams and vancomycin are commonly used as initial empiric therapy.
Antibiotic therapy for hematogenous osteomyelitis should be pathogen-directed, based on the results of bone biopsy or blood cultures.
For osteomyelitis from contiguous spread of infection, wound culture is poorly correlated with bone biopsy culture for all organisms except methicillin-resistant Staphylococcus aureus (MRSA).
Duration of therapy for acute osteomyelitis is 4-8 weeks.
The optimal duration of therapy for chronic osteomyelitis is uncertain, but duration is usually a minimum of 6 weeks. 
Osteomyelitis from contiguous spread of infection
Recommended agents are as follows:
Piperacillin-tazobactam 3.375 g IV q6h or
Ampicillin-sulbactam 3 g IV q6h or
Ticarcillin-clavulanate 3.1 g IV q6h
Patients with penicillin allergy and osteomyelitis from contiguous spread of infection:
If MRSA is suspected:
Add vancomycin 15 mg/kg IV q12h
If a contraindication exists to the use of vancomycin, an alternative anti-MRSA agent such as linezolid, daptomycin, or ceftaroline  may be used
Oral therapy following IV treatment for patients with osteomyelitis from contiguous spread of infection: