Septic arthritis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jumana Nagarwala, M.D., Senior Staff Physician, Department of Emergency Medicine, Henry Ford Hospital; Cafer Zorkun, M.D., Ph.D. [2]; Alejandro Lemor, M.D. [3] Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [4]

Overview

Acute non-gonococcal septic arthritis is a medical emergency which causes severe joint destruction and may increase both morbidity and mortality. So prompt diagnosis and treatment with antibiotic therapy and prompt drainage which reduces long-term complications. Vancomycin is recommended as either empirical therapy for patients with Gram-positive cocci on a synovial fluid Gram stain or as a component of regimen for those with a negative Gram stain if methicillin-resistant Staphylococcus aureus (MRSA) is prevalent. If Gram-negative bacilli are observed, an anti-pseudomonal Cephalosporin (e.g., Ceftazidime, Cefepime) should be administered. Carbapenems should be considered in conditions such as colonization or infection by extended-spectrum β-lactamase–producing pathogens. The optimal duration of therapy for septic arthritis remains uncertain. A minimum 3- to 4-week course is suggested for septic arthritis caused by S. aureus or Gram-negative bacteria. The use of Corticosteroids or intraarticular antibiotics is not advisable.[1][2]

Medical Therapy

Empiric treatment should be commenced as soon as possible after culture samples have been obtained. The choice of empiric antibiotics should be determined on the basis of:[3][4][5]

If the patient fails to respond to initial treatment, consider:[6]

  • Misidentification of causative pathogen
  • Infection with atypical pathogen
  • Concurrent osteomyelitis
  • Occult nidus of infection

Specific Considerations

Tailoring antibiotic coverage to clinical scenario
Type of risk factor Micro orgnanism
Neonate Staphylococcus aureus
Infant < 2 years Haemophilus influenzae, Staphylococcus aureus
Infant > 2 years Staphylococcus aureus
Young adults

(sexually active)

Neisseria gonorrhoeae
Elderly adults Staphylococcus aureus, streptococci, Gram-negative bacilli
Post-aspiration or

injection

Staphylococcus aureus
Trauma Gram-negative bacilli, anaerobes, Staphylococcus aureus
Prosthesis Staphylococcus epidermidis (early infection)

Gram-positive cocci, anaerobes (late infection)

Injecting drug use Atypical gram-negative bacilli including Pseudomonas
Rheumatoid arthritis Staphylococcus aureus
Systemic lupus

erythematosus

Salmonella
Sickle cell anemia Salmonella
Hemophilia Staphylococcus aureus, streptococci, Gram-negative bacilli
Immunosuppression Staphylococcus aureus, Mycobacterium, fungi[7]
Methicillin-resistant Staphylococcus aureus (MRSA)

Risk factors for septic arthritis caused by methicillin-resistant Staphylococcus aureus (MRSA) include:[8][9]

  • Known MRSA colonization or infection
  • Recent hospitalization
  • Nursing-home resident
  • Presence of leg ulcers
  • Indwelling catheters

Drainage or debridement of the joint space should always be performed in septic arthritis caused by MRSA. A 3- or 4-week course of therapy with Vancomycin (15–20 mg/kg/dose IV every 8–12 hours in adults or 15 mg/kg/dose IV every 6 hours in children), Daptomycin (6 mg/kg/day IV every 24 hours in adults or 6–10 mg/kg/dose IV every 24 hours in children), Linezolid (600 mg PO/IV twice daily in adults or 10 mg/kg/dose PO/IV every 8 hours in children), Clindamycin (600 mg PO/IV every 8 hours in adults or 10–13 mg/kg/dose PO/IV every 6–8 hours in children), and Trimethoprim-Sulfamethoxazole (3.5–4.0 mg/kg PO/IV every 8–12 hours in adults) have been used with success. A prolonged treatment of 4 to 6 weeks may be required if the condition is complicated by osteomyelitis.[10][11]

Prosthetic joint infection

Management of prosthetic joint infection typically requires both surgical intervention and extended courses of antimicrobial therapy. Options of surgical approach include debridement with retention of prosthesis, two-stage procedure (removal of prosthesis and cement with debridement of infected tissue and placement of a joint spacer, followed by prolonged antibiotics and replacement of prosthesis), one-stage procedure (removal of prosthesis, debridement, and replacement of prosthesis in a single procedure), permanent resection arthroplasty, and amputation. The surgical decision should be made by orthopedic surgeon with specialty consultation, such as infectious disease or plastic surgery as necessary.[12]

Antibiotic selection and duration are determined according to the causative organisms and the surgical intervention performed. Antimicrobial agent should achieve adequate tissue concentrations and be effective against slow-growing organisms and biofilms in conformity with local antibiogram. Liaison with microbiology services is recommended. Empiric antibiotics may be required while culture results are pending and for the duration of treatment for culture-negative infection. MRSA coverage with glycopeptide (e.g., Vancomycin, Daptomycin) or Gram-negative coverage with Ceftriaxone should be considered when necessary. Empiric or pathogen-directed antibiotic therapy is generally instituted following the procedure.[13]

The duration of antibiotic treatment varies depending on the surgical procedure undertaken. A six-week course of parenteral therapy is preferred if an infected prosthesis is retained, while two to four weeks of intravenous antibiotics may be sufficient if revision arthroplasty is performed. Oral antibiotics are commonly prescribed for three to six months in the setting of retained prosthesis compared with six weeks for revision arthroplasty.[14]

Duration of Antimicrobial Therapy

Clinical Setting Duration
Staphylococcus aureus infection 3–4 weeks
Streptococcus groups A, B, C, G infection 3–4 weeks
Gram-negative bacilli infection 4 weeks
Brucella infection 6 weeks
Borrelia burgdorferi infection 30 days
Mycobacterium tuberculosis infection 9 months
Candida albicans infection 6 weeks
Prosthetic joint infection 6 weeks
Post-intraarticular injection or post-arthroscopy 14 days

Antimicrobial Regimen – Empiric Therapy

Newborn (< 1 week)

High Risk for MRSA

  • Low Risk for MRSA

  • Newborn (1–4 weeks)

    High Risk for MRSA

  • Low Risk for MRSA

  • Infants (1–3 months)

    High Risk for MRSA

  • Low Risk for MRSA

  • Children (3 months–14 years)

  • Adults (Monoarticular)

    At risk for sexually-transmitted disease

  • Not at risk for sexually-transmitted disease

  • Adults (Polyarticular)

  • Antimicrobial Regimen – Synovial Fluid Gram Stain-Based Therapy

    Negative Gram stain

  • Gram-positive cocci

  • Gram-negative cocci

  • Gram-negative bacilli

  • Antimicrobial Regimen – Pathogen-Based Therapy

    Bacteroides fragilis

  • Brucella melitensis

  • Enterococcus

  • Escherichia coli

  • Haemophilus influenzae

  • Morganella morganii

  • Neisseria gonorrhoeae

  • Proteus mirabilis

    • Cefazolin 0.25–1 g IV/IM q6–8h OR Gentamicin 3–5 mg/kg/day IV q6–8h OR TMP-SMX 8–10 mg/kg/day IV/PO q6–12h (TMP component)
  • Proteus vulgaris or Proteus rettgeri

  • Pseudomonas aeruginosa

  • Serratia marcescens

  • Staphylococcus aureus (methicillin-resistant)

    • Vancomycin 15–20 mg/kg IV q8–12h in adults or 15 mg/kg IV q6h in children
    • Daptomycin 6 mg/kg IV q24h in adults or 6–10 mg/kg IV q24h in children OR Linezolid 600 mg PO/IV q12h in adults or 10 mg/kg PO/IV q8h in children OR Clindamycin 600 mg PO/IV q8h in adults or 10–13 mg/kg/dose PO/IV q6–8h in children OR TMP-SMX 3.5–4.0 mg/kg PO/IV q8–12h in adults
  • Staphylococcus aureus (methicillin-susceptible)

  • Staphylococcus epidermidis (methicillin-resistant)

    • TMP-SMX 3.5–4.0 mg/kg PO/IV q8–12h (TMP component) OR Minocycline 200 mg PO x 1 dose, then 100 mg PO q12h AND
    • Rifampin 300–600 mg PO/IV q12h
  • Staphylococcus epidermidis (methicillin-susceptible)

  • Streptococcus agalactiae

  • Streptococcus pyogenes

  • Tropheryma whipplei

  • Borrelia burgdorferi

  • References

    1. Mathews, Catherine J.; Weston, Vivienne C.; Jones, Adrian; Field, Max; Coakley, Gerald (2010-03-06). "Bacterial septic arthritis in adults". Lancet. 375 (9717): 846–855. doi:10.1016/S0140-6736(09)61595-6. ISSN 1474-547X. PMID 20206778.
    2. Sharff, Katie A.; Richards, Eric P.; Townes, John M. (2013-06). "Clinical management of septic arthritis". Current Rheumatology Reports. 15 (6): 332. doi:10.1007/s11926-013-0332-4. ISSN 1534-6307. PMID 23591823. Check date values in: |date= (help)
    3. Shirtliff, Mark E.; Mader, Jon T. (2002-10). "Acute septic arthritis". Clinical Microbiology Reviews. 15 (4): 527–544. ISSN 0893-8512. PMC 126863. PMID 12364368. Check date values in: |date= (help)
    4. Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
    5. Mathews, Catherine J.; Weston, Vivienne C.; Jones, Adrian; Field, Max; Coakley, Gerald (2010-03-06). "Bacterial septic arthritis in adults". Lancet. 375 (9717): 846–855. doi:10.1016/S0140-6736(09)61595-6. ISSN 1474-547X. PMID 20206778.
    6. Shirtliff, Mark E.; Mader, Jon T. (2002-10). "Acute septic arthritis". Clinical Microbiology Reviews. 15 (4): 527–544. ISSN 0893-8512. PMC 126863. PMID 12364368. Check date values in: |date= (help)
    7. Firestein, Gary (2013). Kelley's textbook of rheumatology. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1437717389.
    8. Liu, Catherine; Bayer, Arnold; Cosgrove, Sara E.; Daum, Robert S.; Fridkin, Scott K.; Gorwitz, Rachel J.; Kaplan, Sheldon L.; Karchmer, Adolf W.; Levine, Donald P.; Murray, Barbara E.; J Rybak, Michael; Talan, David A.; Chambers, Henry F.; Infectious Diseases Society of America (2011-02-01). "Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 52 (3): –18-55. doi:10.1093/cid/ciq146. ISSN 1537-6591. PMID 21208910.
    9. Sharff, Katie A.; Richards, Eric P.; Townes, John M. (2013-06). "Clinical management of septic arthritis". Current Rheumatology Reports. 15 (6): 332. doi:10.1007/s11926-013-0332-4. ISSN 1534-6307. PMID 23591823. Check date values in: |date= (help)
    10. Liu, Catherine; Bayer, Arnold; Cosgrove, Sara E.; Daum, Robert S.; Fridkin, Scott K.; Gorwitz, Rachel J.; Kaplan, Sheldon L.; Karchmer, Adolf W.; Levine, Donald P.; Murray, Barbara E.; J Rybak, Michael; Talan, David A.; Chambers, Henry F.; Infectious Diseases Society of America (2011-02-01). "Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 52 (3): –18-55. doi:10.1093/cid/ciq146. ISSN 1537-6591. PMID 21208910.
    11. Mathews, Catherine J.; Weston, Vivienne C.; Jones, Adrian; Field, Max; Coakley, Gerald (2010-03-06). "Bacterial septic arthritis in adults". Lancet. 375 (9717): 846–855. doi:10.1016/S0140-6736(09)61595-6. ISSN 1474-547X. PMID 20206778.
    12. Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
    13. Matthews, Philippa C.; Berendt, Anthony R.; McNally, Martin A.; Byren, Ivor (2009). "Diagnosis and management of prosthetic joint infection". BMJ (Clinical research ed.). 338: –1773. ISSN 1756-1833. PMID 19482869.
    14. Matthews, Philippa C.; Berendt, Anthony R.; McNally, Martin A.; Byren, Ivor (2009). "Diagnosis and management of prosthetic joint infection". BMJ (Clinical research ed.). 338: –1773. ISSN 1756-1833. PMID 19482869.