Antibiotic therapy for treatment of osteomyelitis or prosthetic joint infection in adults
| Infectious agent | Antibiotic regimen | Dosing |
| Empiric therapy | Vancomycin PLUS a third- or fourth-generation cephalosporin (such as ceftriaxone, ceftazidime, or cefepime) | As summarized below |
| ______________________________________________________________________________________________________________________________________ | ||
| Pathogen-specific therapy | ||
| Staphylococci, methicillin susceptible* | Nafcillin | 2 g IV every 4 hours |
| Oxacillin | 2 g IV every 4 hours | |
| Cefazolin | 2 g IV every 8 hours | |
| Flucloxacillin | 2 g IV every 6 hours | |
| Ceftriaxone¶ | 2 g IV every 24 hours | |
| ______________________________________________________________________________________________________________________________________ | ||
| Staphylococci, methicillin resistant* | Regimen of choice: | |
| VancomycinΔ | 20 mg/kg loading dose, then 15 mg/kg/dose IV every 12 hours, not to exceed 2 g per dose initially | |
| Alternative regimens:◊ | ||
| Daptomycin§ | 6 to 10 mg/kg IV once daily | |
| Teicoplanin (where available)¥‡ | 12 mg/kg IV every 12 hours for 3 to 5 doses, followed by 12 mg/kg once daily | |
| ________________________________________________________________________________________________________________________________________ | ||
| Staphylococci, adjunctive agents* | Rifampin | 300 to 450 mg orally twice daily |
| Fusidic acid (where available)¥ | 500 mg orally 3 times daily | |
| _________________________________________________________________________________________________________________________________________ | ||
| Gram-negative organisms | Ciprofloxacin†,**,¶¶ | 750 mg orally twice daily or 400 mg IV every 12 hours; if treating Pseudomonas, increase IV dose to 400 mg IV every 8 hours |
| Levofloxacin**,¶¶ | 750 mg orally or IV once daily | |
| CeftriaxoneΔΔ | 2 g IV every 24 hours | |
| Ceftazidime** | 2 g IV every 8 hours | |
| Cefepime** | 2 g IV every 8 to 12 hours | |
| ErtapenemΔΔ | 1 g IV every 24 hours | |
| Meropenem** | 1 g IV every 8 hours | |
| ____________________________________________________________________________________________________________________________________________ | ||
| Enterococci◊◊ | Monotherapy regimens: | |
| Ampicillin | 12 g IV every 24 hours, either continuously or in 6 equally divided doses | |
| Aqueous crystalline penicillin G | 20 to 24 million units IV every 24 hours, either continuously or in 6 equally divided doses | |
| VancomycinΔ | 20 mg/kg loading dose, then 15 mg/kg IV every 12 hours, not to exceed 2 g per dose | |
| Daptomycin§ | 6 to 10 mg/kg IV once daily | |
| Teicoplanin (where available)¥‡ | 12 mg/kg IV every 12 hours for 3 to 5 doses, followed by 12 mg/kg once daily | |
| Combination therapy regimen: | ||
| Ampicillin | 12 g IV every 24 hours, given either continuously or in 6 equally divided doses | |
| PLUS | ||
| Ceftriaxone | 2 g IV every 12 to 24 hours | |
| _______________________________________________________________________________________________________________________________________ | ||
| Streptococci, penicillin sensitive | One of the following: | |
| Aqueous crystalline penicillin G | 20 to 24 million units IV every 24 hours, either continuously or in 6 equally divided doses | |
| Ampicillin | 12 g IV every 24 hours, either continuously or in 6 equally divided doses | |
| Ceftriaxone | 2 g IV every 24 hours | |
| VancomycinΔ | 20 mg/kg loading dose, then 15 mg/kg/dose IV every 12 hours, not to exceed 2 g per dose, initially | |
| __________________________________________________________________________________________________________________________________________ | ||
| Cutibacterium (formerly Propionibacterium) acnes§§ | One of the following: | |
| Aqueous crystalline penicillin G | 20 million units IV every 24 hours, either continuously or in 6 divided doses | |
| Ceftriaxone | 2 g IV every 24 hours | |
In stable patients, antibiotics may be held pending establishment of microbiologic diagnosis or obtaining cultures from bone debridement or biopsy. The total duration of antibiotic therapy depends on individual patient circumstances (refer to the UpToDate content on treatment of osteomyelitis and prosthetic joint infection for further discussion). The doses in this table are intended for adults with normal renal function. The doses of many of these agents must be adjusted in the setting of renal insufficiency; refer to the Lexicomp drug-specific monographs for renal dose adjustments.
IV: intravenously; PJI: prosthetic joint infection.
* For patients with Staphylococcus aureus PJI and residual hardware following surgery, we favor use of adjunctive rifampin. To mitigate the emergence of resistance, rifampin should not be started until the patient has received several days of anti-staphylococcal therapy. We favor administration of rifampin 450 orally twice daily; the dose may be reduced to 300 mg orally twice daily in the setting of nausea. There should be careful screening drug-drug interactions prior to initiation of rifampin.
¶ Use of ceftriaxone for treatment of staphylococcal osteomyelitis is not universally accepted. In our practice, we use it as an alternative regimen for isolates with oxacillin minimum inhibitory concentration <0.5 mcg/mL in the absence of concomitant bacteremia; once-daily dosing is a convenient outpatient regimen.
Δ In adults, vancomycin is dosed based on actual body weight. Target troughs for vancomycin should be chosen with the guidance of a local infectious disease physician based on the pathogen, in vitro susceptibility, and the use of rifampin or local vancomycin therapy, with a target trough concentration of at least 10 mcg/mL. It is unknown if a higher vancomycin trough level of 15 to 20 mcg/mL is routinely needed. Refer to the UpToDate topic review on vancomycin parenteral dosing and serum concentration monitoring in adults.
◊ Ceftaroline has been used successfully for treatment of osteomyelitis but has been associated with increased risk of neutropenia. Pending further study, use of ceftaroline should be reserved for patients unable to receive other therapies. Ceftaroline susceptibility must be confirmed; the prevalence of resistance is high in some regions. Daptomycin may be used for vancomycin-resistant enterococci; confirm susceptibility.
§ Standard daptomycin dosing (as approved by the US Food and Drug Administration) for treatment of bacteremia or osteomyelitis is 6 mg/kg IV once daily. Because daptomycin exhibits concentration-dependent killing, some experts recommend doses of up to 8 to 10 mg/kg IV once daily, which appear safe; further study is needed.
¥ Not available in the United States. Fusidic acid should not be used alone; it must be combined with a second active agent to reduce the likelihood of selection for drug resistance. When rifampin is combined with fusidic acid, fusidic levels may be reduced.
‡ The teicoplanin dose should be adjusted to attain a trough concentration of >20 mcg/mL.
† Oral ciprofloxacin at dose shown in table achieves therapeutic levels for treatment of Pseudomonas aeruginosa.
** Ciprofloxacin, levofloxacin, ceftazidime, cefepime, and meropenem have activity against P. aeruginosa; confirm susceptibility.
¶¶ The possibility of prolonged QTc interval, tendinopathy, neuropathy, or development of an aneurysm should be reviewed and monitored when using fluoroquinolones. For more information, please refer to the UpToDate topic on fluoroquinolones.
ΔΔ Ceftriaxone and ertapenem have no activity against P. aeruginosa, but are appropriate for other gram-negative organisms, if susceptible.
◊◊ For treatment of infection due to penicillin-susceptible enterococci, it is unclear whether combination therapy is superior to monotherapy, particularly if thorough debridement is performed. In the setting of retained hardware, we favor combination therapy for PJI due to Enterococcus faecalis with ampicillin and ceftriaxone. We do not use this approach for treatment of PJI due to non-faecalis species of penicillin-susceptible enterococci because synergy with these agents in vitro is variable and clinical data are not available in patients with PJI due to non-faecalis species [11]. If antibiotic-impregnated material containing gentamicin is implanted at the time of debridement, then monotherapy is likely sufficient and we favor treatment with either intravenous ampicillin or penicillin (vancomycin or daptomycin are acceptable alternative agents for patients with proven beta-lactam hypersensitivity). For treatment of infection due to penicillin-resistant enterococci, the preferred agent is vancomycin; daptomycin or teicoplanin (where available) are acceptable alternative agents.
§§ For patients with Cutibacterium spp infection and beta-lactam hypersensitivity, reasonable alternative agents include vancomycin, a tetracycline (doxycycline or minocycline), or moxifloxacin.
* For patients with Staphylococcus aureus PJI and residual hardware following surgery, we favor use of adjunctive rifampin. To mitigate the emergence of resistance, rifampin should not be started until the patient has received several days of anti-staphylococcal therapy. We favor administration of rifampin 450 orally twice daily; the dose may be reduced to 300 mg orally twice daily in the setting of nausea. There should be careful screening drug-drug interactions prior to initiation of rifampin.
¶ Use of ceftriaxone for treatment of staphylococcal osteomyelitis is not universally accepted. In our practice, we use it as an alternative regimen for isolates with oxacillin minimum inhibitory concentration <0.5 mcg/mL in the absence of concomitant bacteremia; once-daily dosing is a convenient outpatient regimen.
Δ In adults, vancomycin is dosed based on actual body weight. Target troughs for vancomycin should be chosen with the guidance of a local infectious disease physician based on the pathogen, in vitro susceptibility, and the use of rifampin or local vancomycin therapy, with a target trough concentration of at least 10 mcg/mL. It is unknown if a higher vancomycin trough level of 15 to 20 mcg/mL is routinely needed. Refer to the UpToDate topic review on vancomycin parenteral dosing and serum concentration monitoring in adults.
◊ Ceftaroline has been used successfully for treatment of osteomyelitis but has been associated with increased risk of neutropenia. Pending further study, use of ceftaroline should be reserved for patients unable to receive other therapies. Ceftaroline susceptibility must be confirmed; the prevalence of resistance is high in some regions. Daptomycin may be used for vancomycin-resistant enterococci; confirm susceptibility.
§ Standard daptomycin dosing (as approved by the US Food and Drug Administration) for treatment of bacteremia or osteomyelitis is 6 mg/kg IV once daily. Because daptomycin exhibits concentration-dependent killing, some experts recommend doses of up to 8 to 10 mg/kg IV once daily, which appear safe; further study is needed.
¥ Not available in the United States. Fusidic acid should not be used alone; it must be combined with a second active agent to reduce the likelihood of selection for drug resistance. When rifampin is combined with fusidic acid, fusidic levels may be reduced.
‡ The teicoplanin dose should be adjusted to attain a trough concentration of >20 mcg/mL.
† Oral ciprofloxacin at dose shown in table achieves therapeutic levels for treatment of Pseudomonas aeruginosa.
** Ciprofloxacin, levofloxacin, ceftazidime, cefepime, and meropenem have activity against P. aeruginosa; confirm susceptibility.
¶¶ The possibility of prolonged QTc interval, tendinopathy, neuropathy, or development of an aneurysm should be reviewed and monitored when using fluoroquinolones. For more information, please refer to the UpToDate topic on fluoroquinolones.
ΔΔ Ceftriaxone and ertapenem have no activity against P. aeruginosa, but are appropriate for other gram-negative organisms, if susceptible.
◊◊ For treatment of infection due to penicillin-susceptible enterococci, it is unclear whether combination therapy is superior to monotherapy, particularly if thorough debridement is performed. In the setting of retained hardware, we favor combination therapy for PJI due to Enterococcus faecalis with ampicillin and ceftriaxone. We do not use this approach for treatment of PJI due to non-faecalis species of penicillin-susceptible enterococci because synergy with these agents in vitro is variable and clinical data are not available in patients with PJI due to non-faecalis species [11]. If antibiotic-impregnated material containing gentamicin is implanted at the time of debridement, then monotherapy is likely sufficient and we favor treatment with either intravenous ampicillin or penicillin (vancomycin or daptomycin are acceptable alternative agents for patients with proven beta-lactam hypersensitivity). For treatment of infection due to penicillin-resistant enterococci, the preferred agent is vancomycin; daptomycin or teicoplanin (where available) are acceptable alternative agents.
§§ For patients with Cutibacterium spp infection and beta-lactam hypersensitivity, reasonable alternative agents include vancomycin, a tetracycline (doxycycline or minocycline), or moxifloxacin.