GUIDELINES FOR TREATMENT OF BONE AND JOINT INFECTIONS IN ADULTS

Pelvic Osteomyelitis Hematogenous Vertebral Osteomyelitis Septic Arthritis Associated with Chronic Osteomyelitis Decubitus Ulcers

Osteomyelitis following Diabetic Foot Ulcers with Prosthetic Joint Infections Trauma and/or Orthopedic References Osteomyelitis Procedures

Antimicrobial Subcommittee Approval: 06/2016 Originated: 06/2016 P&T Approval: 07/2016 Last Revised: 03/2021 Revision History: 02/2021: Added fungi, mycobacteria, and Actinomyces comment 03/2021: Updated vancomycin dosing & hyperlinks 09/2021: Updated vancomycin infusion reaction terminology The recommendations in this guide are meant to serve as treatment guidelines for use at Michigan Medicine facilities. If you are an individual experiencing a medical emergency, call 911 immediately. These guidelines should not replace a provider’s professional medical advice based on clinical judgment, or be used in lieu of an Infectious Diseases consultation when necessary. As a result of ongoing research, practice guidelines may from time to time change. The authors of these guidelines have made all attempts to ensure the accuracy based on current information, however, due to ongoing research, users of these guidelines are strongly encouraged to confirm the information contained within them through an independent source.

If obtained from a source other than https://www.med.umich.edu/asp, please visit the webpage for the most up-to-date document.

Table of Contents

Hematogenous Osteomyelitis Clinical Setting Empiric Therapy Duration Comments Usually associated with: Consider holding antibiotics until deep tissue cultures can be obtained in • Patients under age 17 hemodynamically stable patients years or over 50 years (recommendations Preferred: Approximately 45% of S. aureus at UMHS are MRSA, intended for adults only) Vancomycin* IV (see nomogram) so initial treatment to cover MRSA is warranted. De- • IV drug use escalate to a beta-lactam if methicillin-susceptible S. • Other risk for bacteremia If known MSSA colonization or infection: aureus (MSSA) is identified. e.g., central line, dialysis, Cefazolin* 2 g IV q8h

sickle cell disease, Infectious Diseases Consultation recommended. urethral catheterization, Alternative for vancomycin allergy (not vancomycin infusion reaction**):

UTI Daptomycin* 6 mg/kg IV daily Daptomycin requires prior approval.

Bacterial Etiology: If Sickle Cell disease: Baseline CK followed by weekly CK should be • S. aureus Vancomycin* IV (see nomogram) 4-6 weeks measured in patients placed on daptomycin due to • 30% Gram negative bacilli + Ceftriaxone 2 g IV daily increased risk of rhabdomyolysis. (consider if fresh water

exposure, recent broad If IVDU or other Gram negative risk (see bacterial etiology): Increased dose of daptomycin may be indicated spectrum antibiotics in Vancomycin* IV (see nomogram) with documented MRSA bacteremia. the prior 90 days, recent + Piperacillin-tazobactam 4.5 g IV q6h

>2 days hospitalized in Infections due to fungi, mycobacteria, or prior 90 days, or Alternative for patient with mild penicillin allergy: Actinomyces require longer durations of therapy – hemodynamic instability) Vancomycin* IV (see nomogram) consult appropriate national guidelines for • + Cefepime 2 g IV q8h Salmonella in sickle cell guidance. disease • Serratia and Alternative for patients with life-threatening penicillin allergy: Pseudomonas spp. in Vancomycin* IV (see nomogram) IVDU + Aztreonam 2 g IV q8h * Adjust dose based on renal function; vancomycin dose may require adjustment for select organisms or patients Target vancomycin AUC 400-600 mcg*hr/mL

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Vertebral Osteomyelitis Clinical Setting Empiric Therapy Duration Comments Consider holding antibiotics until deep Evaluation for epidural infection is critical. See full Vertebral Osteomyelitis FGP Guideline tissue cultures can be obtained in hemodynamically stable patients Infectious Diseases consultation strongly recommended. Usually hematogenous source Preferred: Step down therapy to oral antibiotic usually indicated after 6 weeks of therapy. Vancomycin* IV (see nomogram) Persons at risk: + Ceftriaxone 2 g IV q12h Approximately 45% of S. aureus at UMHS are MRSA, so initial treatment to cover MRSA is • Age >60 years warranted. De-escalate to a beta-lactam if methicillin-susceptible S. aureus (MSSA) is identified. If known MSSA colonization or infection: • IVDU Oxacillin 2 g IV q4h Cefazolin may replace oxacillin, if no epidural extension of infection is present. • Urinary tract

infections Alternative for suspected or documented Linezolid requires prior approval.

Pseudomonal infection (see bacterial Minimum 6 Bacterial Etiology: etiology): weeks Baseline CBCP and weekly CBCP are recommended with linezolid therapy due to risk of • S. aureus Vancomycin* IV (see nomogram) cytopenia, especially thrombocytopenia; alternative therapy should be considered in patients • Occ. Coagulase + Cefepime* 2 g IV q8h with thrombocytopenia. negative

staphylococcus Alternative for severe penicillin allergy: Linezolid should be used with caution in patients on medications with serotonergic activity, • Enteric Gram Vancomycin* IV (see nomogram) e.g., SSRI and MAOI. See SSRI & Linezolid Education. negatives + Aztreonam* 2 g IV q6h • Pseudomonas Daptomycin may replace linezolid if no epidural extension of infection is present. in IVDU or Alternative for vancomycin allergy or water exposure intolerance (not vancomycin infusion Empiric dosing takes into account epidural abscess with possible CNS extension. reaction**): Linezolid 600 mg PO/IV q12h Infections due to fungi, mycobacteria, or Actinomyces require longer durations of therapy – + other antibiotic as indicated above consult appropriate national guidelines for guidance. * Adjust dose based on renal function; vancomycin dose may require adjustment for select organisms or patients Target vancomycin AUC 400-600 mcg*hr/mL

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Septic Arthritis Clinical Setting Empiric Therapy Duration Comments Approximately 45% of S. aureus at UMHS are MRSA, so initial treatment to cover MRSA is warranted. De- Usually associated with: Consider holding antibiotics until deep tissue cultures escalate to a beta-lactam if methicillin-susceptible S. • Age >80 years can be obtained in hemodynamically stable patients aureus (MSSA) is identified. • Diabetes mellitus

• Rheumatoid arthritis Preferred: Consult Orthopedic surgery for joint drainage. • Prosthetic joint Vancomycin* IV (see nomogram) 2-4 weeks • Recent joint surgery ID consultation recommended.

• Skin infection If known MSSA colonization or infection: For S. aureus: • IV drug abuse Cefazolin* 2 g IV q8h Linezolid and daptomycin require prior approval. minimum 4 weeks • Alcoholism

• Prior intra-articular steroid injection Alternative for vancomycin allergy (not vancomycin Baseline CBCP and weekly CBCP are recommended

infusion reaction**): with linezolid therapy due to risk of cytopenia, For N. gonorrhea: Bacterial Etiology: Linezolid 600 mg PO/IV q12h especially thrombocytopenia; alternative therapy After 24-48h of • S. aureus OR should be considered in patients with ceftriaxone with • Streptococcal species, including S. Daptomycin* 6 mg/kg IV daily thrombocytopenia. substantial clinical pneumoniae improvement, • Gram negative bacilli associated with If risk for gonorrhea: Linezolid should be used with caution in patients on transition to oral trauma, intravenous drug users, older Vancomycin* IV (see nomogram) medications with serotonergic activity, e.g., SSRI and stepdown therapy adults, and in association with + Ceftriaxone 1 g IV daily MAOI. See SSRI & Linezolid Education. to complete total underlying immunosuppression. + Azithromycin 1 g PO in a single dose of at least 7 days • N. gonorrhea in oligoarthritis, Baseline CK followed by weekly CK should be measured (particularly young, sexually active), If risk for Gram negative bacilli (see bacterial in patients placed on Daptomycin due to increased risk associated tenosynovitis, vesicular etiology): of rhabdomyolysis. pustules, late complement deficiency, Vancomycin* IV (see nomogram) negative synovial fluid culture and Gram + Piperacillin-tazobactam* 4.5 g IV q6h Infections due to fungi, mycobacteria, or Actinomyces stain require longer durations of therapy – consult appropriate national guidelines for guidance. * Adjust dose based on renal function; vancomycin dose may require adjustment for select organisms or patients Target vancomycin AUC 400-600 mcg*hr/mL

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Pelvic Osteomyelitis Associated with Chronic Decubitus Ulcers Clinical Setting Empiric Therapy Duration Comments Consider holding antibiotics until deep tissue cultures can be obtained in hemodynamically stable patients Infectious Disease consultation recommended.

Preferred: Surgical debridement of overlying ulcer with deep tissue or Vancomycin* IV (see nomogram) bone biopsy is an important component of management. + Piperacillin-tazobactam* 4.5 g IV q6h

Acute osteomyelitis Tailor therapy based on culture data. Alternative for patients with penicillin allergy: associated with contiguous Mild allergy (rash) spread from pressure ulcer Treatment should be modified to cover previously isolated Vancomycin* IV (see nomogram) 6-8 weeks of pathogens with recurrent or relapse of the same site. + Cefepime* 2 g IV q8h therapy Bacterial Etiology: + Metronidazole 500 mg PO/IV q8h depending Mixed infections due to Daptomycin requires prior approval. on response Staphylococcus sp., Anaphylaxis: Streptococcus sp. and Baseline CK followed by weekly CK should be followed in Vancomycin* IV (see nomogram) enteric organisms patients placed on daptomycin due to increased risk of + Aztreonam* 2 g IV q8h rhabdomyolysis. + Metronidazole 500 mg PO/IV q8h

Infections due to fungi, mycobacteria, or Actinomyces Alternatives for vancomycin intolerance (not vancomycin infusion require longer durations of therapy – consult appropriate reaction**) or allergy: national guidelines for guidance. Daptomycin* 6 mg/kg IV daily + other antibiotic as indicated above. * Adjust dose based on renal function; vancomycin dose may require adjustment for select organisms or patients Target vancomycin AUC 400-600 mcg*hr/mL

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Diabetic Foot Ulcers with Osteomyelitis Clinical Setting Empiric Therapy Duration Comments

Consider holding antibiotics until deep tissue cultures can be obtained in hemodynamically Acute osteomyelitis with recent ulcer stable patients Infectious Disease consultation recommended. • Staphylococcus spp (esp S. Preferred: aureus) Vancomycin* IV (see nomogram) Surgical debridement of overlying ulcer with deep tissue or bone • Streptococcus spp biopsy is an important component of management. • Corynebacterium and other skin Alternatives for Vancomycin intolerance (not flora vancomycin infusion reaction**) or allergy: Tailor therapy based on culture data. Daptomycin* 6 mg/kg IV daily OR Treatment should be modified to cover previously isolated Linezolid 600 mg PO/IV q12h pathogens with recurrent or relapse of the same site.

Preferred if risk for Gram negative: Linezolid and daptomycin require prior approval. Vancomycin* IV (see nomogram) Risk for Gram negative bacillus + Piperacillin-tazobactam* 4.5 g IV q6h infection: 6-8 weeks of Baseline CBCP and weekly CBCP are recommended with linezolid

• Chronic ulcer with osteomyelitis therapy depending therapy due to risk of cytopenia, especially thrombocytopenia; Alternative for patients with penicillin allergy • Osteomyelitis with fresh water on response alternative therapy should be considered in patients with Mild allergy (rash) exposure thrombocytopenia. Vancomycin* IV (see nomogram) • recent broad spectrum + Cefepime* 2 g IV q8h antibiotics in the prior 90 days Linezolid should be used with caution in patients on medications + Metronidazole 500 mg PO/IV q8h • recent >2 days hospitalized in with serotonergic activity, e.g., SSRI and MAOI. See SSRI & Linezolid

prior 90 days hemodynamic Education. Anaphylaxis instability Vancomycin* IV (see nomogram) Baseline CK followed by weekly CK should be followed in patients + Aztreonam* 2 g IV q8h Bacterial etiology placed on daptomycin due to increased risk of rhabdomyolysis. + Metronidazole 500 mg PO/IV q8h • Staphylococcus spp (esp S.

aureus) Infections due to fungi, mycobacteria, or Actinomyces require longer Alternatives for Vancomycin intolerance (not • Streptococcus spp durations of therapy – consult appropriate national guidelines for vancomycin infusion reaction**) or allergy • guidance. Enterobacteraciae Daptomycin* 6mg/kg IV daily • Obligate anaerobes OR • Rarely Pseudomonas Linezolid 600mg PO/IV q12h + other antibiotic as indicated above. * Adjust dose based on renal function; vancomycin dose may require adjustment for select organisms or patients Target vancomycin AUC 400-600 mcg*hr/mL

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Prosthetic Joint infections Clinical Setting Empiric Therapy Duration Comments

Higher risk associated: Consider holding antibiotics until deep tissue cultures can be 4-6 weeks Infectious Diseases consultation strongly • Prior arthroplasty obtained in hemodynamically stable patients recommended. • RA Oral antimicrobial • Periorperative infections Early (<3 mo) and Late (>24 mo) Onset suppression indicated Approximately 45% of S. aureus at UMHS are • Prior joint infections Preferred: in some cases of MRSA, so initial treatment to cover MRSA is • Prolonged surgery Vancomycin* IV (see nomogram) retained hardware warranted. De-escalate to a beta-lactam if • High BMI + Piperacillin-tazobactam 4.5 g IV q6h methicillin-susceptible S. aureus (MSSA) is • Postoperative bleeding identified. • DM Alternative for Suspected or Documented Gram negative • Advanced age Infection: Linezolid and daptomycin require prior approval. Vancomycin* IV (see nomogram) Bacterial Etiology: + Cefepime* 2 g IV q8h Baseline CBCP and weekly CBCP are Early onset: <3 months after surgery recommended with linezolid therapy due to risk Alternative for Severe Penicillin Allergy: of cytopenia, especially thrombocytopenia; • S. aureus Vancomycin* IV (see nomogram) alternative therapy should be considered in • Aerobic Gram negative bacilli + Aztreonam* 2 g IV q8h patients with thrombocytopenia. • Anaerobes

• Mixed infections Alternative for Vancomycin Allergy or Intolerance (not Linezolid should be used with caution in patients Delayed onset: 3-24 months after vancomycin infusion reaction**): on medications with serotonergic activity, e.g., surgery Daptomycin* 6 mg/kg IV daily SSRI and MAOI. See SSRI & Linezolid Education. • Coagulase negative + other antibiotic as indicated above staphylococcus Baseline CK followed by weekly CK should be • Enterocococcus Delayed (3-24 mo) Onset followed in patients placed on daptomycin due to • Propionibacterium Preferred: increased risk of rhabdomyolysis. Late onset: >24 months after surgery Vancomycin* IV (see nomogram) • S. aureus Infections due to fungi, mycobacteria, or • Beta-hemolytic streptococci Alternatives for Vancomycin intolerance (not vancomycin Actinomyces require longer durations of therapy – • Aerobic Gram negative bacilli infusion reaction**) or allergy: consult appropriate national guidelines for Daptomycin* 6 mg/kg IV daily guidance. OR Linezolid 600 mg PO/IV q12h

*Adjust dose based on renal function; vancomycin dose may require adjustment for select organisms or patients Target vancomycin AUC 400-600 mcg*hr/mL

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Osteomyelitis following Trauma and/or Orthopedic Procedures Clinical Setting Empiric Therapy Duration Comments

Associated with contaminated Consider holding antibiotics until deep tissue cultures 6 weeks Infectious Diseases consult strongly recommended. open fractures or surgical can be obtained in hemodynamically stable patients treatment of closed fractures Oral Approximately 45% of S. aureus at UMHS are MRSA, so initial treatment to Preferred: suppression cover MRSA is warranted. De-escalate to a beta-lactam if methicillin- Bacterial Etiology: Vancomycin* IV (see nomogram) indicated in susceptible S. aureus (MSSA) is identified. Most common + Piperacillin-tazobactam* 4.5 g IV q6h some cases of • S. aureus retained Linezolid and daptomycin require prior approval. • Coagulase negative Alternative for Vancomycin Allergy or Intolerance hardware staphylococcus (not vancomycin infusion reaction**): Linezolid should be used with caution in patients on medications with • Enteric Gram negative Daptomycin* 6 mg/kg IV daily serotonergic activity, e.g., SSRI and MAOI. See SSRI & Linezolid Education. bacilli OR Less common Linezolid 600 mg IV q12h Baseline CBCP and weekly CBCP are recommended with linezolid therapy • Enterococcus sp. + other antibiotic as indicated above. due to risk of cytopenia, especially thrombocytopenia; alternative therapy • Acinetobacter should be considered in patients with thrombocytopenia. • Pseudomonas sp. Alternative for Penicillin Allergy (non-anaphylaxis): • Anaerobes Vancomycin* IV (see nomogram) Baseline CK followed by weekly CK should be followed in patients placed on + Cefepime* 2 g IV q8h daptomycin due to increased risk of rhabdomyolysis.

Alternative for Severe Penicillin Allergy: Infections due to fungi, mycobacteria, or Actinomyces require longer Vancomycin* (see nomogram) durations of therapy – consult appropriate national guidelines for guidance. + Aztreonam * 2 g IV q8h * Adjust dose based on renal function; vancomycin dose may require adjustment for select organisms or patients Target vancomycin AUC 400-600 mcg*hr/mL ** For vancomycin infusion reactions, vancomycin infusion should be slowed to >2 hr

References: 1. Lipsky BA, Berendt RA, Cornia PB, etal. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012;54(12):132-173. 2. Berbari EF, Kanj SS, Kowalski TJ, etal. 2015 Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis 2015;61(6):e26-46. 3. Osmon Dr, Berbari EF, Berendt, etal. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2013;56(1);e1-25. 4. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic joint infections. N Engl J Med 2004;351:1645.

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