Version July 2025
INTRODUCTION —
Treatment of osteomyelitis may include both surgical management and antimicrobial therapy.
General issues related to treatment of native-bone osteomyelitis are discussed here. This topic excludes hardware-associated infections, details of which are discussed separately. (See "Prosthetic joint infection: Treatment" and "Osteomyelitis associated with open fractures in adults".)
Details related to treatment of specific types of osteomyelitis are found separately:
●(See "Diabetic foot infections, including osteomyelitis: Treatment".)
●(See "Vertebral osteomyelitis: Treatment".)
●(See "Pelvic osteomyelitis and other infections of the bony pelvis in adults", section on 'Treatment'.)
Issues related to clinical manifestations and diagnosis of osteomyelitis are discussed separately. (See "Osteomyelitis in the absence of hardware: Approach to diagnosis in adults".)
Issues related to treatment of osteomyelitis in children are presented separately. (See "Hematogenous osteomyelitis in children: Management".)
ROLE OF SURGERY —
For many patients with osteomyelitis, surgical intervention is a critical component of management.
Surgery for osteomyelitis removes nonviable infected tissue and allows for collection of a bone and tissue samples for culture, as well as biopsy for histopathology. (See 'Removal of infected tissue' below and 'Bone biopsy' below.)
Removal of infected tissue — Surgical removal of infected tissue optimizes the likelihood of cure in two ways. First, tissue that is necrotic or otherwise nonviable is not well perfused, which may prevent systemically administered antibiotic therapy from reaching the site of infection. Second, surgery serves to debulk the infection, reducing the residual organism burden and optimizing the ability of antibiotics to kill remaining pathogens before spread occurs.
Indications for surgery — In certain situations, the need for surgical management of osteomyelitis is clear. Such indications include:
●Extensive or severe soft tissue infection that requires debridement
●Necrotic bone
●Subperiosteal or intraosseous abscess
●Exposed bone when the need for surgical soft tissue coverage is anticipated
●Concomitant joint infection for which arthrotomy is indicated
●Need for mechanical stabilization (eg, impending pathologic fracture)
In addition, vascular intervention or surgery is often necessary in patients who have poor vascular supply to the area of infection due to peripheral artery disease or scar tissue from prior trauma. If poor vascular supply is due to peripheral artery disease, vascular intervention (via angioplasty or bypass) may obviate the need for debridement in some patients. Poor vascular supply hinders antibiotic delivery to the site of infection.
In patients who do not meet the above indications for surgery, the decision to operate is more nuanced and depends on specific circumstances and patient preferences. For example, in patients with diabetic foot osteomyelitis without a clear indication for surgery, a trial of antibiotic therapy is sometimes attempted because such patients are at risk for poor postoperative wound healing due to uncorrectable microvascular disease [1-6]. As another example, patients with certain forms of hematogenous osteomyelitis are often cured with antibiotic therapy alone because the infection is confined to highly vascular anatomic sites. (See "Diabetic foot infections, including osteomyelitis: Treatment", section on 'Indications for surgery'.)
Extent of surgery — Surgery for osteomyelitis involves either debridement (removal of infected and necrotic tissue), resection (removal of a piece of bone), or amputation (removal of part or all of a bone or bones).
To maintain stability and physical function, the least aggressive surgery is generally preferred if the care team has confidence in the likelihood of cure.
For all patients undergoing surgical management of osteomyelitis, soft tissue coverage must be achieved, either via primary closure or through a tissue transfer procedure. Depending on the scope of the debridement, bone grafting or other orthopedic reconstruction may be required. (See "Overview of treatment of chronic wounds", section on 'Wound coverage/closure'.)
Bone biopsy — Bone biopsy is the only definitive way to confirm osteomyelitis. For patients undergoing surgery for osteomyelitis, bone biopsy should be obtained during surgery for culture to guide therapy. Bone biopsy should be sent for histopathology whenever the diagnosis of osteomyelitis is not clear, when alternative diagnoses are being considered, and when the presence or absence of osteomyelitis would change management. (See "Osteomyelitis in the absence of hardware: Approach to diagnosis in adults", section on 'Bone biopsy as gold standard'.)
Many patients undergo surgical debridement after antibiotic therapy has been initiated. In such cases, there is concern that growth of pathogens in bone culture may be inhibited, thereby hindering antibiotic selection. However, the effect of antibiotics on bone culture results is unclear. Because antimicrobial delivery is diminished in necrotic bone and in areas of diminished vascular flow, cultures may still be positive even after antibiotic administration. Therefore, we advise bone biopsy still be performed during surgery, as it may provide additional data on which to base subsequent treatment decisions. (See "Osteomyelitis in the absence of hardware: Approach to diagnosis in adults", section on 'Timing and technique'.)
SYSTEMIC ANTIBIOTIC THERAPY —
In selecting an antibiotic regimen for osteomyelitis, several factors should be considered including the severity of infection, known or suspected pathogens, and host factors including allergies, comorbidities, and drug interactions. Often, treatment of osteomyelitis includes an initial empiric regimen followed by a pathogen-specific regimen based on culture results.
Intravenous versus oral therapy — The most appropriate route of therapy primarily depends on severity of infection since available data suggest equivalent outcomes with intravenous and oral regimens when used for definitive therapy. In most recent randomized trials, oral regimens were preceded by an initial intravenous regimen. (See 'Evidence comparing oral to intravenous therapy' below.)
Indications for intravenous therapy — Broad-spectrum intravenous therapy is appropriate initial therapy in patients with severe infections. Once the patient stabilizes and surgical debridement is complete, the decision to transition to oral therapy or continue intravenous therapy for the full duration of treatment is based on clinical features, known or suspected pathogens, and patient preference.
Prolonged intravenous therapy is often necessary in certain situations:
●Extensive remaining infected tissue without ability to undergo debridement, risking limb loss.
●Suspected or proven infection with a pathogen for which no oral antibiotic options with high bioavailability exist. (See 'Oral regimens used in studies' below.)
●Inability to absorb oral medications due to suspected or documented gastrointestinal dysfunction.
●Inability to identify a suitable oral regimen due to allergy, prior antimicrobial intolerances, drug toxicities, and/or drug interactions.
●Significant lower extremity ischemia (including microvascular disease) or edema that may hinder antibiotic delivery to the site of infection. This criterion may be especially important if the only oral options have poor bioavailability.
●Known infection at another site that requires intravenous therapy (eg, Staphylococcus aureus bacteremia, endocarditis).
Finally, there remains limited research on the reliability of oral therapy for osteomyelitis treatment in obese patients, given that physiologic changes may lead to reduced concentration of some oral antibiotics [7,8]. Until more data demonstrating the equivalence of oral and intravenous therapy becomes available, clinicians should carefully consider the optimal approach for patients with obesity.
Candidates for oral therapy — We consider oral therapy for all patients who do not meet criteria for intravenous therapy. (See 'Indications for intravenous therapy' above.)
In most studies in which oral therapy is supported for bone and joint infection, initial intravenous therapy was utilized before transition to oral therapy. There are few studies reporting outcomes in patients in whom a fully oral regimen was employed without initial intravenous therapy [3,9,10]. A fully oral regimen may be considered in the patient with chronic stable osteomyelitis, no need for empiric treatment while awaiting cultures, and a highly bioavailable regimen based on deep cultures. Further data is needed before fully oral therapy is employed in other settings.
Patients initially treated with intravenous therapy can often be transitioned to oral therapy once indications for intravenous therapy are no longer present. We consider transition to oral therapy when the patient is clinically improved, when further surgery is not anticipated, when cultures are available to guide definitive management, and when the patient is able to take medications orally. The optimal timing of transition has not been formally studied and should be based on clinical judgment.
Outpatient oral therapy may be especially beneficial for patients who are unable to manage home intravenous therapy due to home circumstances or cost [11].
Many patients with osteomyelitis meet qualifications for oral therapy. A 2020 observational study in England found that 80 percent of patients receiving intravenous outpatient therapy for osteomyelitis qualified for oral therapy [12]. In the United States, oral therapy for osteomyelitis may be significantly underutilized; in a study of 145 patients with bone and joint infections at eight hospitals from 2018-2020, 109 (75 percent) were eligible for oral therapy but only 18 (12 percent) received it [13].
Evidence comparing oral to intravenous therapy — Because treatment of osteomyelitis involves prolonged courses of antibiotics, oral administration is preferable for many patients. Oral antibiotics offer convenience, shorter hospital stays, lower costs, and eliminate risk of catheter-related complications.
In the United States, osteomyelitis has traditionally been treated with intravenous antibiotics. An exception is diabetic foot osteomyelitis for which oral therapy has been an acceptable practice in select patients.
Published studies — Based on clinical studies, we believe oral antibiotic therapy is a viable option for selected patients with osteomyelitis.
●Randomized trials comparing intravenous to oral therapy – Randomized controlled trials have evaluated different approaches to treatment, including regimens that used oral therapy for the entire course, intravenous therapy for the entire course, or initial intravenous therapy followed by oral step-down therapy. Regardless of the approach, all randomized trials have found that regimens including oral therapy were as effective as regimens including intravenous therapy.
The largest randomized trial (the “OVIVA” trial) included more than 1000 adults with bone or joint infection randomized to intravenous or oral antibiotic therapy for at least six weeks (median duration of therapy 78 and 71 days, respectively) [14]. The rates of treatment failure within one year were comparable (14 versus 13 percent). Surgical debridement occurred in 92 percent of cases, and a variety of bone and joint infections were included, including osteomyelitis with or without an associated implant.
Other published randomized trials are older and smaller in scope than the OVIVA trial [15-22]. Like OVIVA, each found that oral antibiotic therapy was as effective as intravenous.
●Observational studies comparing intravenous to oral therapy – Multiple observational studies have evaluated intravenous compared with oral therapy for osteomyelitis [9,11,23-34]. Acknowledging the potential for bias, all have found comparable outcomes.
●Studies reporting outcomes with oral therapy – Many observational studies have reported outcomes with a broad range of oral therapies for bone and joint infections [35]. In general, outcomes in these studies have been comparable to those of intravenous regimens in other studies.
Oral regimens used in studies — Numerous oral antibiotics have been used in studies of osteomyelitis, many of which included patients with prosthetic joint infection. No oral regimen has been found to be superior to others.
●Importance of bioavailability – Favored oral options have high bioavailability (ie, the oral formulation achieves high blood concentrations). High blood concentrations increase the likelihood that the antibiotic will penetrate bone at a level high enough to kill microorganisms.
Oral antibiotics that have high bioavailability include fluoroquinolones, clindamycin, tetracyclines (eg, doxycycline), trimethoprim-sulfamethoxazole, linezolid, and metronidazole. Pharmacokinetic data suggest that amoxicillin, cephalexin, and cefadroxil have adequate bioavailability [36]. Amoxicillin-clavulanate is the only beta-lactam agent with substantial published clinical data, particularly in patients with diabetic foot osteomyelitis [3,24,37,38].
Rifamycins (eg, rifampin) also have high bioavailability but are only used as part of combination therapy, as discussed below and separately. (See 'Role of adjunctive rifampin' below and "Prosthetic joint infection: Treatment", section on 'Use of adjunctive rifampin'.)
●Regimens used in the OVIVA trial – In the largest randomized trial comparing oral to intravenous regimens (the OVIVA trial), the following oral antibiotics were administered among those randomized to oral therapy (n=523) (not including rifampin) [14]:
•A fluoroquinolone (191 patients); ciprofloxacin was the most common fluoroquinolone. Of patients who received a quinolone, 84 percent also received rifampin at some point during the trial.
•Combination therapy (87 patients); most non-rifampin combination regimens were either ciprofloxacin/clindamycin or ciprofloxacin/doxycycline.
•A penicillin (83 patients); the specific penicillin was not reported.
•Clindamycin (62 patients).
•Doxycycline (57 patients).
•Other (60 patients).
Oral antibiotics utilized in other studies include levofloxacin and other fluoroquinolones, trimethoprim-sulfamethoxazole, amoxicillin, amoxicillin-clavulanate, cephalexin, cefadroxil, cefuroxime, minocycline, and linezolid [9,15-22,29,31-33]. Rifampin was utilized in some of these studies as part of combination therapy.
Regimens for initial therapy — Initial therapy is typically given intravenously while awaiting culture results.
Empiric antibiotic selection is based in part on the likely pathogens associated with a patient’s specific syndrome:
●(See "Diabetic foot infections, including osteomyelitis: Treatment", section on 'Intravenous therapy' and "Diabetic foot infections, including osteomyelitis: Treatment", section on 'Oral therapy'.)
●(See "Vertebral osteomyelitis: Treatment", section on 'Empiric therapy'.)
●(See "Pelvic osteomyelitis and other infections of the bony pelvis in adults", section on 'Treatment'.)
●(See "Osteomyelitis associated with open fractures in adults", section on 'Antibiotic selection'.)
Once culture results from bone or an appropriately collected deep tissue culture are available, regimens should be tailored to target isolated pathogens. (See 'Pathogen-specific regimens' below.)
Pathogen-specific regimens — If an appropriately collected bone or deep tissue culture was submitted, antibiotic therapy should be tailored once culture and susceptibility results return.
Intravenous and oral regimens are listed in the tables (table 1). Studies comparing specific regimens are scarce, so suggested regimens are often based on clinical experience, indirect comparisons in osteomyelitis studies, and adverse effects.
Staphylococci — Staphylococci, including both S. aureus and coagulase-negative staphylococci, are the most common cause of bone and joint infections. (See "Osteomyelitis in the absence of hardware: Approach to diagnosis in adults", section on 'Microbiology'.)
Traditionally, definitive therapy for osteomyelitis due to S. aureus has consisted of intravenous antibiotic therapy for the full course of therapy. However, oral therapy has been shown to be effective in select patients [9,11,14,17,21,29,31-33]. (See 'Candidates for oral therapy' above.)
Intravenous regimens — Our preferred intravenous regimens for staphylococcal osteomyelitis are described below (table 1):
●Methicillin-susceptible S. aureus (MSSA) – For patients with MSSA osteomyelitis who require intravenous therapy, we suggest one of the following regimens (table 1):
•Cefazolin (2 g intravenously every eight hours).
•Nafcillin or oxacillin (2 g intravenously every four hours).
•Ceftriaxone (2g intravenously every 24 hours).
•For patients with serious beta-lactam allergy: vancomycin (see table for dosing (table 2)) or daptomycin (6 to 10 mg/kg intravenously once daily).
Nafcillin and oxacillin are associated with more adverse effects than cephalosporins; in the absence of an alternative indication such as endocarditis, we reserve their use for those who cannot tolerate cephalosporins [39,40]. (See "Clinical approach to Staphylococcus aureus bacteremia in adults", section on 'Clinical approach'.)
Use of ceftriaxone for definitive treatment of staphylococcal osteomyelitis is increasingly supported [41,42]. Some contributors on this topic use ceftriaxone for once-daily dosing in patients who require outpatient intravenous therapy, have no concomitant bacteremia, and have undergone through debridement; if ceftriaxone is used, a higher dosing strategy (2 g once daily) is recommended and susceptibility should be confirmed using oxacillin MIC testing (rather than cefoxitin) [41,43,44]. Other contributors on this topic avoid ceftriaxone in favor of cefazolin because of concerns for antimicrobial stewardship. Historically, ceftriaxone was avoided due to concerns about decreased efficacy for S. aureus infections, but more recent retrospective studies suggest no difference in treatment outcome when used for definitive treatment of staphylococcal osteomyelitis [41,42].
●Methicillin-resistant S. aureus (MRSA) – Our preferred regimen for intravenous therapy for MRSA osteomyelitis is vancomycin if drug levels and necessary laboratory tests can be monitored (table 1) (see table for dosing (table 2)). Vancomycin is the antibiotic for which there is the greatest cumulative clinical experience, although there are no controlled trials [45,46].
Acceptable alternative agents to vancomycin for treatment of osteomyelitis due to MRSA include daptomycin (6 to 10 mg/kg intravenously once daily), or teicoplanin where available (table 1) [47-52]. An observational study including over 400 patients with osteomyelitis due to gram-positive organisms noted a success rate of 82 percent with daptomycin for treatment of staphylococcal osteomyelitis [50].
●Coagulase-negative staphylococci – Most coagulase-negative staphylococci are methicillin-resistant and should be treated with a regimen used for MRSA. If the organism tests susceptible to methicillin, one of the regimens for MSSA can be used (table 1).
Staphylococcus lugdunensis is unique because it is frequently susceptible to all beta-lactams, even penicillin. For susceptible isolates, intravenous penicillin is an option. Penicillin-resistant organisms usually remain susceptible to methicillin and cephalosporins, such that they can be treated like methicillin-sensitive S. aureus (MSSA). For prolonged intravenous therapy, ceftriaxone is effective and convenient due to once-daily dosing. For patients with serious beta-lactam allergy, intravenous vancomycin is appropriate. (See "Staphylococcus lugdunensis", section on 'Treatment'.)
Intravenous antibiotics that warrant further study for treatment of staphylococcal osteomyelitis include ceftaroline, dalbavancin, oritavancin, and ceftobiprole [53-62]. Dalbavancin and oritavancin have the unique advantage of weekly intravenous dosing; dalbavancin, in particular, has been used successfully for treatment of osteomyelitis in multiple studies [54-57,60,61,63]. These antibiotics should be reserved for use in patients in whom other therapies are not an option and the organism is susceptible. We avoid telavancin due to increased risk of adverse events observed with its use for treatment of other conditions [64-66].
Oral regimens — Oral therapy has been shown to be effective for staphylococcal osteomyelitis in select patients [9,11,14,17,21,29,31-33]. (See 'Candidates for oral therapy' above.)
In the largest randomized trial of bone and joint infections, 378 cases of S. aureus and 272 cases of coagulase-negative staphylococci were included and there was no difference in outcome between oral and intravenous regimens [14].
Data comparing oral regimens to each other for osteomyelitis are scarce. For individual patients, we base our selections on the susceptibility of the patient’s organism, drug toxicities, and drug interactions. We try to select agents that have been used most frequently in studies of staphylococcal osteomyelitis.
Our suggested oral regimens for staphylococcal osteomyelitis are as follows (see table for oral regimens):
●Preferred regimen – Combination therapy with levofloxacin (750 mg orally once daily) plus rifampin 300 to 450 mg orally twice daily is our preferred regimen for oral treatment of staphylococcal osteomyelitis. For rifampin dosing, some experts use 600 mg orally once daily.
In the largest published studies of oral therapy for osteomyelitis, combination therapy with a fluoroquinolone and rifampin is the most common regimen [14,67,68]. In early studies, ciprofloxacin was the most used fluoroquinolone, but levofloxacin is now more commonly used by many experts based on improved activity in preclinical models against staphylococcus species, dosing convenience, and bioavailability [69,70]. (See 'Role of adjunctive rifampin' below.)
●Alternative regimens – Trimethoprim-sulfamethoxazole, clindamycin, linezolid, and tetracyclines (eg, doxycycline) have each been used in studies that included staphylococcal osteomyelitis.
Some experts routinely add rifampin to these agents. We do not typically use rifampin in combination with partner drugs other than fluoroquinolones, unless there has been prior treatment failure or there is implant-associated osteomyelitis. In Europe, combination therapy including rifampin is commonly used. (See 'Role of adjunctive rifampin' below.)
Before prescribing rifampin, several considerations are important:
●Rifampin must be combined with another active antibacterial agent because rapid emergence of resistance in the setting of rifampin monotherapy is common [71-73]. (See "Rifamycins (rifampin, rifabutin, rifapentine)", section on 'Resistance'.)
●In patients undergoing surgical debridement, we typically initiate rifampin several days after surgery, because resistance may be less likely to emerge once the burden of organisms has been reduced.
●A thorough review of the patient’s medication list is necessary because of potential drug interactions. Rifampin can cause clinically significant reductions in concentrations of certain drugs because it is a potent inducer of several drug-metabolizing enzymes, including P450 CYP3A. (See "Rifamycins (rifampin, rifabutin, rifapentine)", section on 'Drug interactions'.)
●Like any other antibiotic, rifampin has potential to cause adverse effects that should be reviewed with the patient. (See "Rifamycins (rifampin, rifabutin, rifapentine)", section on 'Adverse effects'.)
If rifampin is not available, fusidic acid may be used as a substitute if available [74-76].
Role of adjunctive rifampin — For treatment of staphylococcal osteomyelitis, rifampin is often included in combination antibiotic regimens.
We often include rifampin in two clinical scenarios:
●Hardware infections due to Staphylococcus spp [73,77-79]. (See "Prosthetic joint infection: Treatment", section on 'Use of adjunctive rifampin'.)
●Staphylococcal native-bone osteomyelitis being treated with oral antibiotics, especially fluoroquinolones. (See 'Oral regimens' above.)
The value of adding rifampin to a regimen for nonimplant associated osteomyelitis is uncertain. Studies comparing regimens with and without rifampin in patients without hardware-associated infections are scarce. However, it was frequently used in many of the studies demonstrating the effectiveness of oral antimicrobial therapy for staphylococcal osteomyelitis when combined with fluoroquinolones. (See 'Oral regimens' above.)
Including rifampin in antibiotic regimens for osteomyelitis provides potential benefits:
●Rifampin is more effective than other antibiotics within experimental biofilm models [80,81]. Biofilm is associated with necrotic bone even in the absence of implants [82], highlighting the potential benefit of rifampin.
●Rifampin achieves high concentrations within bone following oral administration [83].
●Rifampin may be more effective at eliminating intracellular bacteria [84], an important component of the pathogenesis of staphylococcal osteomyelitis [82].
●Rifampin may prevent the emergence of resistance to fluoroquinolones when the two agents are used together for staphylococcal infections. Neither fluoroquinolones nor rifampin should be used as monotherapy for staphylococcal infections because resistance emerges rapidly when either agent is used alone.
Like any antibiotics, rifampin is not without potential drawbacks, as described above. (See 'Oral regimens' above.)
Gram-negative organisms — Several antibiotics are available for treatment of osteomyelitis due to gram-negative organisms, if culture results confirm susceptibility.
Our preferred antibiotic is an oral fluoroquinolone (eg, ciprofloxacin) if the patient qualifies for oral therapy (see 'Candidates for oral therapy' above). Intravenous therapy offers no advantages in patients with normal gastrointestinal absorption because fluoroquinolones have high bioavailability and bone penetration with oral administration [85,86].
For patients in whom oral fluoroquinolone therapy is not an option, alternative oral options include trimethoprim-sulfamethoxazole (TMP-SMX), amoxicillin-clavulanate, or amoxicillin based on susceptibility results.
Preferred intravenous options include beta-lactams (eg, ceftriaxone, cefepime) (table 1). Carbapenems (eg, ertapenem, meropenem) are an alternative, but we try to avoid them in favor of narrower-spectrum agents unless susceptibilities require use of a carbapenem (eg, extended-spectrum beta-lactamase-producing organisms).
Some gram-negative organisms, such as Pseudomonas aeruginosa, have fewer treatment options [18,87]. In an observational study including 66 patients with P. aeruginosa osteomyelitis who underwent surgical debridement, most patients were treated with two weeks of intravenous therapy followed by oral fluoroquinolone therapy (median duration of treatment 45 days); clearance of infection was demonstrated in 94 percent of cases. Most patients received monotherapy and no emergence of resistance was observed [87].
Other gram-negative organisms with limited treatment options include AmpC-producing organisms (eg, Enterobacter cloacae complex, Klebsiella aerogenes, Citrobacter freundii), Acinetobacter spp, Stenotrophomonas spp, and carbapenem-resistant Enterobacterales. Treatment for these pathogens is complex and the reader should refer to dedicated organism-specific topics. (See "Acinetobacter infection: Treatment and prevention", section on 'Suggested antibiotic regimens' and "Stenotrophomonas maltophilia", section on 'Suggested antibiotic regimens' and "Carbapenem-resistant E. coli, K. pneumoniae, and other Enterobacterales (CRE)", section on 'Antibiotic selection'.)
Streptococci and enterococci — Osteomyelitis due to penicillin-susceptible streptococci may be treated with intravenous penicillin G, cefazolin, or ceftriaxone (table 1).
Our preferred oral option is amoxicillin (875 to 1000 mg three times daily). If amoxicillin is not an option, selection of alternative agents (eg, clindamycin, levofloxacin, linezolid) is based on susceptibility results.
For patients with osteomyelitis due to enterococci and no hardware who underwent thorough debridement, we favor monotherapy. Preferred intravenous options include ampicillin, penicillin G, or vancomycin (table 1). Our preferred oral option is amoxicillin; an alternative oral option is linezolid.
For infections due to penicillin-susceptible enterococci in the setting of extensive remaining necrotic material, some experts would advise initial combination therapy with intravenous ampicillin and ceftriaxone for several weeks before transitioning to monotherapy [88]. If antibiotic-impregnated material containing gentamicin is implanted at the time of debridement, monotherapy for the entire course may be sufficient.
Anaerobic bacteria — Anaerobic bacteria may be part of a polymicrobial infection or be the only bacteria isolated from culture.
The specific regimen depends on the susceptibility profile of the isolated anaerobe as well as any other bacteria. Classes of antibiotics that cover particular anaerobes are available in intravenous and oral forms, including nonstaphylococcal penicillins, beta-lactam/beta-lactamase inhibitor combinations, metronidazole, and clindamycin. Carbapenems also have anaerobic activity but are not available in oral formulation and we generally avoid them in favor of narrower-spectrum agents (table 1).
Duration of therapy — The appropriate duration of therapy for osteomyelitis is uncertain even though it has been studied in numerous observational studies and a few randomized trials.
It is important to note that the discussion and recommendations in this section apply to patients with native-bone osteomyelitis (ie, no hardware is present) caused by typical pyogenic bacteria. Atypical organisms that cause osteomyelitis often require much longer durations, and the duration is specific to the organism (eg, tuberculosis, fungi, Brucella spp, Coxiella burnetii). (See "Brucellosis: Treatment and prevention", section on 'Spondylitis' and "Bone and joint tuberculosis", section on 'Treatment'.)
Residual infected bone — We typically treat patients with native-bone osteomyelitis for six weeks from the date of the last debridement, assuming the patient did not undergo amputation.
If we are uncertain whether residual infected bone remains after surgical intervention, we use a combination of the following factors to determine duration of therapy: intraoperative findings as described by the surgeon, preoperative radiographic findings compared to level of surgery, and “bone margin” histopathology and culture obtained intraoperatively. The clinical significance of a positive or negative bone margin following surgery is uncertain [89-93] and we review these results in the context of other findings such as whether the surgeon believes there is residual infection.
Data suggest that treatment beyond six weeks is usually unnecessary in patients who undergo debridement, as long as necrotic bone and soft tissue was adequately removed during surgery [10,67,94-99]. Despite this, therapy is often prolonged in clinical practice and in the literature, with 77 percent of patients in the OVIVA trial treated longer than six weeks [14].
For patients in whom debridement is not an option, we reassess the need for ongoing antibiotic treatment at six weeks of therapy. In those who have not responded clinically, longer courses of antibiotics and/or reassessment for surgical debridement may be appropriate. We stop antibiotics when there is no longer active clinical evidence of infection on examination, and we encourage the patient to observe for evidence of relapse of infection. (See 'Refractory or relapsed infection' below.)
Emerging data suggest that durations shorter than six weeks may be sufficient in some situations [3,37,100,101], but we continue to follow a conservative approach until more data become available.
For more detailed recommendations regarding duration of therapy for native-bone osteomyelitis, see syndrome-specific topics:
●(See "Diabetic foot infections, including osteomyelitis: Treatment", section on 'Duration of therapy'.)
●(See "Vertebral osteomyelitis: Treatment".)
●(See "Pelvic osteomyelitis and other infections of the bony pelvis in adults", section on 'Treatment'.)
●(See "Osteomyelitis associated with open fractures in adults", section on 'Duration'.)
No residual infected bone (amputation) — These are patients who underwent complete resection of infected bone, usually in the form of an amputation. (See 'Extent of surgery' above.)
In the absence of residual soft tissue infection, we agree with other experts that antibiotics may not be necessary at all, and no more than five days of antibiotics should be administered.
If soft tissue infection is present, the duration should be dependent on resolution of the soft tissue infection, which typically requires five to seven days of therapy.
ADJUNCTIVE THERAPIES
●Local antibiotic delivery – Local antimicrobials mixed with absorbable carriers (eg, calcium sulfate beads) or nonabsorbable carriers (eg, polymethyl methacrylate, PMMA, beads or cement) placed in and around the site of infection have been evaluated for bone and joint infections [102].
At times, PMMA is utilized to fill a bone defect created by surgical debridement of osteomyelitis; in these cases, we advise the use of targeted antimicrobial agents within the cement for local antibiotic delivery.
In the absence of a mechanical indication or the use of cement fixation of implanted hardware, we do not endorse routine use of local antibiotic delivery; it may be considered in refractory cases. Further research is necessary before a definitive recommendation can be made.
Most studies have focused on using local antibiotic delivery to prevent infection of trauma-related fractures, but some studies have evaluated their use for treating chronic osteomyelitis or hematogenous osteomyelitis in children [103-111].
The materials and antibiotics used in the studies are heterogenous, and the results across studies are inconsistent.
Increased wound drainage is a commonly reported complication with calcium sulfate beads [106,109]. Systemic antibiotic exposure does not appear to be a significant side effect since there is minimal translocation of the antibiotics into the bloodstream [106].
●Hyperbaric oxygen – Hyperbaric oxygen (HBO) has been suggested as an adjunctive therapy in patients with refractory osteomyelitis [112]. We do not favor routine use of HBO for treatment of osteomyelitis, given lack of sufficient data.
Issues related to HBO are discussed further separately. (See "Hyperbaric oxygen therapy".)
MONITORING AND FOLLOW-UP —
Patients with osteomyelitis should undergo regular outpatient follow-up. We often examine patients one to two weeks after starting therapy and again at the end of therapy. Additional evaluation for antimicrobial toxicities and side effects may also be needed during therapy.
●History and physical examination – Patients should be questioned regarding systemic symptoms of infection as well as pain (type and severity). Symptoms of side effects from antibiotic therapy should be assessed, such as diarrhea (for Clostridioides difficile) and rash.
The site of infection should be examined for improvement. If a wound is present, it should be examined for healing and soft tissue envelope.
●Role of inflammatory markers (eg, ESR, CRP) – We typically obtain erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) tests at the time of diagnosis and at the end of therapy to establish a new baseline. We do not routinely monitor weekly serum inflammatory markers during antibiotic therapy.
Several studies have found that the trajectory of ESR and CRP during therapy correlate with response to therapy [113-117], but other studies have found no correlation [118,119]. Even among the studies that found correlation, there is no definitive evidence that ESR and CRP results provide actionable information beyond the information provided by history and physical examination.
Not infrequently, ESR and CRP remain elevated at the end of therapy, but we do not change our management plan based solely on the results. We carefully assess for evidence of continued infection and follow the patient more closely after completion of therapy to assess for relapse. ESR resolves more slowly than CRP due to its physiology and may remain elevated for weeks to months [115,118]. We do not monitor ESR and CRP following antimicrobial completion in the absence of clinical cause.
●Laboratory monitoring – Patients on outpatient intravenous antibiotics warrant regular laboratory evaluation for adverse effects. (See "Outpatient parenteral antimicrobial therapy", section on 'Monitoring'.)
Certain oral antibiotics may also warrant monitoring, depending on side effects. For example, trimethoprim-sulfamethoxazole (TMP-SMX) can cause hyperkalemia in high-risk patients or patients on certain medications (eg, angiotensin-converting enzyme [ACE]-inhibitors or spironolactone) and linezolid can cause cytopenias when given for longer than two weeks. Clinicians should consider whether laboratory monitoring is appropriate based on the selected antibiotics and patient comorbidities.
●Imaging – We do not routinely follow radiographic imaging; frequently, residual inflammatory changes may be mistaken for persistent infection. The decision to pursue radiographic imaging should be guided by clinical suspicion for treatment failure.
REFRACTORY OR RELAPSED INFECTION —
If we suspect treatment failure based on history and examination, we obtain imaging and inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein) to guide further management.
For patients confirmed to have refractory or relapsed infection, further debridement is often necessary and should be based on examination and imaging. Clinicians should also review microbiology results, assess the patient’s compliance with antibiotic and wound therapy, and assess for peripheral vascular disease or edema, which can decrease delivery of the antibiotic to the site of infection. Development of antibiotic resistance and/or new organism inoculation is also possible; if these are suspected, repeat bone biopsy can be helpful.
Patients with extensive residual necrotic bone may require chronic suppressive therapy, but this approach should only be considered for patients who can’t undergo debridement (table 3). For chronic recurrent osteomyelitis, time-limited antimicrobial treatment of symptomatic flares may also be considered, depending on the frequency of exacerbations. Determining when suppressive antibiotics can be discontinued is challenging. Clinical gestalt, inflammatory markers, and imaging may be of value. Rifampin should not be part of suppressive therapy.
OUTCOMES —
Success rates for treatment of osteomyelitis reported in the literature range from 60 to 90 percent [99,101,120,121] and differ based on the type of infection. The success rate can be highly variable given the heterogeneity in completeness of debridement, the possibility of concomitant vascular insufficiency at the site of infection, and other factors.
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Osteomyelitis and prosthetic joint infection in adults" and "Society guideline links: Outpatient parenteral antimicrobial therapy".)
SUMMARY AND RECOMMENDATIONS
●Overview – This topic discussed the general approach to treatment of osteomyelitis in the absence of hardware. Detailed discussion of specific types of osteomyelitis (eg, diabetic foot infection, vertebral osteomyelitis) can be found separately. (See 'Introduction' above.)
●Indications for surgery – For many patients with osteomyelitis, surgical intervention is a critical component of management. (See 'Role of surgery' above.)
Indications include the following:
•Extensive or severe soft tissue infection that requires debridement
•Necrotic bone
•Subperiosteal or intraosseous abscess
•Exposed bone when the need for surgical soft tissue coverage is anticipated
•Concomitant joint infection for which arthrotomy is indicated
•Need for mechanical stabilization (eg, impending pathologic fracture)
In addition, vascular intervention or surgery is often necessary in patients who have poor vascular supply. (See 'Indications for surgery' above.)
●Intravenous versus oral antibiotic therapy – The most appropriate route of therapy primarily depends on severity of infection since available data suggest equivalent outcomes with intravenous and oral regimens. In most studies, an initial intravenous regimen was administered prior to transitioning to an oral regimen. (See 'Intravenous versus oral therapy' above.)
●Indications for intravenous therapy – We suggest prolonged intravenous therapy in certain situations (Grade 2C):
•Extensive remaining infected tissue without ability to undergo debridement, risking limb loss.
•Suspected or proven infection with a pathogen for which no oral antibiotic options with high bioavailability exist.
•Inability to absorb oral medications due to suspected or documented gastrointestinal dysfunction.
•Inability to identify a suitable oral regimen due to allergy, prior antimicrobial intolerances, drug toxicities, and/or drug interactions.
•Significant lower extremity ischemia (including microvascular disease) or edema that may hinder antibiotic delivery to the site of infection. This criterion may be especially important if the only oral options have poor bioavailability.
•Known infection at another site that requires intravenous therapy (eg, Staphylococcus aureus bacteremia, endocarditis).
The reliability of oral therapy for osteomyelitis treatment in obese patients is uncertain. (See 'Indications for intravenous therapy' above.)
●Candidates for oral therapy – Once patients no longer meet the above criteria for intravenous therapy, we often transition to oral therapy. (See 'Candidates for oral therapy' above.)
●Antibiotic selection – Studies comparing specific regimens are scarce, so suggested regimens are often based on clinical experience, indirect data from osteomyelitis studies, and adverse effects. (See 'Systemic antibiotic therapy' above.)
•Empiric antibiotic selection – Initial therapy for osteomyelitis depends on the patient’s specific syndrome (see 'Regimens for initial therapy' above):
-(See "Diabetic foot infections, including osteomyelitis: Treatment", section on 'Intravenous therapy' and "Diabetic foot infections, including osteomyelitis: Treatment", section on 'Oral therapy'.)
-(See "Vertebral osteomyelitis: Treatment", section on 'Empiric therapy'.)
-(See "Osteomyelitis associated with open fractures in adults", section on 'Antibiotic selection'.)
•Pathogen-directed therapy – Once culture and susceptibility results are available, antibiotic regimens should be tailored to target the specific pathogens (table 1). (See 'Pathogen-specific regimens' above.)
●Duration of therapy – For patients with no hardware and no atypical pathogens (eg, tuberculosis, fungi, Brucella spp), duration of therapy depends on the presence of residual infected bone. (See 'Duration of therapy' above.)
•Residual infected bone – Most patients with native-bone osteomyelitis are treated for six weeks from the date of the last debridement. For patients in whom debridement is not an option, we reassess the need for ongoing antibiotic treatment at six weeks of therapy. (See 'Residual infected bone' above.)
Thorough guidance regarding duration is available in UpToDate topics about specific types and locations of osteomyelitis.
•No residual infected bone (ie, amputation) – In the absence of residual soft tissue infection, we suggest administering no more than five days of antibiotics following amputation (Grade 2C). (See 'No residual infected bone (amputation)' above.)
ACKNOWLEDGMENT —
The UpToDate editorial staff acknowledges Tahaniyat Lalani, MD, MBBS, MHS, and Douglas Osmon, MD, MPH, who contributed to an earlier version of this topic review.
