General recommendations and organism-specific therapeutic regimens for osteomyelitis (as shown in the radiograph below) are provided. However, treatment of bone infections can quickly become complicated, and significant morbidity and loss of function can result from failure to treat infections appropriately. It is recommended that consultation with an infectious diseases and orthopedic specialist be obtained to assist in management.
Antibiotic therapy for hematogenous osteomyelitis should be pathogen-directed, based on the results of cultures from bone biopsy and/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); unless MRSA is grown, surgical bone biopsy is recommended to define the correct pathogen.
Orthopedic surgical debridement and drainage is a mainstay of therapy and is necessary to remove sequestrum and prevent chronic osteomyelitis and disease recurrence.
For MRSA, a minimum of 8 weeks of antibiotic therapy is recommended. Parenteral therapy or administration of antibiotics with high oral bioavailability is preferred; however, oral therapy at the end of the course can be used, depending on the severity of the disease.
For MRSA, new data suggest that organisms with a vancomycin minimum inhibitory concentration (MIC) of 2 µg/mL or greater have a greater rate of treatment failure with vancomycin therapy. In this situation, an alternative agent such as daptomycin should be used.
For non-MRSA disease, 4-6 weeks of intravenous (IV) therapy or therapy with drugs with high oral bioavailability is preferred. However, a longer course may be indicated in any type of more complicated disease.
Chronic osteomyelitis with multiple recurrences of disease in the same location with the same organism, usually S aureus, may require extensive debridement followed by a prolonged (up to 8 weeks) IV antibiotic course for cure; however, failing this, lifelong suppression may be needed.
Treatment of osteomyelitis in conjunction with an infected orthopedic device is complicated and often necessitates surgical resection of the device or a very prolonged course of medication if the device is retained (and sometimes lifelong antibiotic suppression if further surgical manipulation can result in significant morbidity and loss of function). Appropriate consultation with an infectious diseases specialist and an orthopedic surgeon, both with experience in dealing with infected prostheses, is highly recommended.
Guidelines from the Infectious Diseases Society of America (IDSA) have provided guidance for management of osteomyelitis with prosthetic joints but not for other kinds of orthopedic hardware infections (though extrapolations can be made from the IDSA guidance).[1]
The IDSA guidelines advocate the removal of all hardware if at all possible, with reimplantation of the prosthetic joint after a 6-week course of targeted antimicrobial therapy.[1] During this period, the patient will require an internal cement spacer, an external fixator, or traction to maintain future limb function and joint integrity. For some individuals, this would result in unacceptable morbidity and loss of limb function. In such cases, the orthopedic surgeon may perform a one-stage explantation of the joint and immediate reimplantation of a joint or may perform a simple surgical washout and debridement of infected tissue without any exchange of hardware.
In cases where hardware is retained involving the knee, a 6-month course of targeted antimicrobial therapy is recommended, whereas in cases involving all other joints, a 3-month course is recommended. Between 2 and 6 weeks of the course should be with IV or IV-equivalent antimicrobial therapy. More recent data, however, suggest that oral therapy is equivalent to IV therapy (see Intravenous vs Oral Antimicrobial Agents, below) but have yet to be incorporated into guidelines.[1]
In cases involving rifampin-sensitive S aureus, the IDSA guidelines advocate adding rifampin at 450 mg PO q12hr if the patient can tolerate the medication and does not have significant liver disease.[1]
Vertebral osteomyelitis infections involving infected neurosurgical or orthopedic hardware often require a 2- to 8-week course of IV therapy followed by 1-2 years of long-term oral suppression in order to allow the vertebral bones to heal enough so that they will be stable enough for another washout or hardware resection if disease recurs.
Owing to the high rates of development of resistance to treatment, rifampin should never be used alone to treat S aureus.
Similarly, owing to the risk of development of resistance when there is a high burden of disease, trimethoprim-sulfamethoxazole should not be used as initial therapy alone for S aureus, even when the isolate is sensitive to trimethoprim-sulfamethoxazole; it should only be used after any necessary debridement of disease occurs and at least a 1- to 2-week course of treatment with another antibiotic has been carried out.
Aminoglycosides generally have poor bone penetration and should only be used if all other antibiotic options are unavailable; however, they can theoretically be used synergistically to improve the bactericidal activity of beta-lactam antibiotics, vancomycin, and daptomycin in streptococcal and enterococcal infections, though clinical data are lacking.
As with any prolonged course of antibiotic treatment, monitoring for adverse effects is appropriate, and drug level monitoring of vancomycin and, in particular, aminoglycosides is necessary to avoid toxicity and maintain efficacy.
Long-term toxicities should be taken into account before any prolonged antibiotic course. Of particular concern are the following:
Methicillin-sensitive S aureus[2, 3, 4, 5, 6, 1]
Preferred intravenous therapy:
Alternative intravenous options for patients with penicillin allergy:
Preferred oral therapy
Alternative oral options for patients with penicillin allergy:
MRSA and coagulase-negative staphylococci[2, 6, 7, 8]
Preferred intravenous options guided by results of sensitivity testing:
Alternative intravenous options guided by results of sensitivity testing and intolerance of agents above:
Oral therapy guided by results of sensitivity testing:
Penicillin-sensitive streptococci[2, 6, 8]
Preferred intravenous options:
Alternative intravenous options for patients with penicillin allergy:
Preferred oral therapy:
Alternative oral options for patients with penicillin allergy:
Intermediately sensitive streptococci (penicillin MIC ≥0.5)[2, 6, 8]
Preferred intravenous options:
Oral therapy:
Enterococci[2, 6, 8]
Preferred intravenous options guided by susceptibility testing:
Oral therapy guided by susceptibility testing:
Gram-negative bacilli (other than Pseudomonas)[2, 6, 8]
Preferred intravenous options guided by susceptibility testing:
Oral therapy guided by susceptibility testing:
Pseudomonas aeruginosa[2, 6, 8]
Preferred intravenous options guided by susceptibility testing:
Oral therapy guided by susceptibility testing:
Anaerobes[2, 6, 8]
Newer agents for gram-positive organisms[9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20]
The following agents could theoretically be used to treat osteomyelitis caused by MRSA and other gram-positive organisms, though at present, there are no good data on their use. There are more anecdotal reports of ceftaroline and telavancin being used with reportedly good results, but reporting bias could be taking place.
The most promising agent is ceftaroline; it is a cephalosporin derivative, and successful use of cephalosporins in osteomyelitis is well documented. In view of their very long half-lives, dalbavancin and oritavancin could be useful in treating osteomyelitis for a long course, but there currently are no good data to support their use, and therefore these drugs should be used only as a last resort. There are no known data regarding the use of tedizolid, omadacycline, or delfaloxacin for osteomyelitis, though the oral dosing and good bioavailability make these attractive options. Tedizolid has the same concerns as linezolid in terms of its side-effect profile.
Newer agents for highly resistant gram-negative organisms
Theoretically, the following antibiotics could be used to treat osteomyelitis when caused by a highly resistant gram-negative organism that is resistant to all other antibiotics; however, they should be used only as a last resort, given that there are absolutely no data regarding their efficacy in the treatment of osteomyelitis or the likelihood of adverse effects with long-term administration.[21, 22, 23, 24, 25, 26, 27, 28, 29, 30]
Intravenous vs oral antimicrobial agents
In January 2019, the OVIVA (Oral Versus IntraVenous Antibiotics for bone and joint infection) study was published. In this multicenter one-to-one randomized open-label noninferiority trial comparing IV with oral therapy in 1054 patients, oral antibiotic therapy was found to be noninferior to IV antibiotic therapy when used during the first 6 weeks for complex orthopedic infections. As of December 2020, the use of oral antibiotic therapy had not been included in the IDSA guidelines. However, we have changed our designations of options for treatment to remove the preference for IV therapies.[31]