Sandbox septic arthritis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Acute non-gonococcal septic arthritis is a medical emergency requiring prompt drainage followed by empiric antimicrobial therapy according to patient's history, clinical presentation, and synovial fluid analysis. Vancomycin is recommended as 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. Antibiotic regimen may be deescalated as culture results and susceptibility tests permit. 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.
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:
- Gram stain results of synovial fluid analysis
- Local prevalence of organisms and resistance patterns
- Predisposing factors including intravenous drug use, hospitalization, or colonization of infectious pathogens, and risk for methicillin-resistant Staphylococcus aureus (MRSA)
If the patient fails to respond to initial treatment, consider:
- Misidentification of causative pathogen
- Infection with atypical pathogen
- Concurrent osteomyelitis
- Occult nidus of infection
Specific Considerations
Tailoring antibiotic coverage to clinical scenario
- Neonate
- Infant < 2 years
- Infant > 2 years
- Young adults (sexually active)
- Elderly adults
- Post-aspiration or injection
- Trauma
- Prosthesis
- Staphylococcus epidermidis (early infection)
- Gram-positive cocci, anaerobes (late infection)
- Injecting drug use
- Atypical gram-negative bacilli including Pseudomonas
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Sickle cell anemia
- Hemophilia
- Immunosuppression
Methicillin-resistant Staphylococcus aureus (MRSA)
Risk factors for septic arthritis caused by methicillin-resistant Staphylococcus aureus (MRSA) include:
- 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/dose 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.
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.
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.
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.
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
- Vancomycin 18 mg/kg/day IV q12h AND
- Cefotaxime 50 mg/kg IV q12h
Low Risk for MRSA
- Cefotaxime 50 mg/kg IV q12h AND
- Nafcillin 25 mg/kg IV q8h OR Oxacillin 25 mg/kg IV q8h
- Clindamycin 5 mg/kg IV q8h
Newborn (1–4 weeks)
High Risk for MRSA
- Vancomycin 22 mg/kg/day IV q12h AND
- Cefotaxime 50 mg/kg IV q8h
Low Risk for MRSA
- Cefotaxime 50 mg/kg IV q8h AND
- Nafcillin 37 mg/kg IV q6h OR Oxacillin 37 mg/kg IV q6h
- Clindamycin 5 mg/kg IV q6h
Infants (1–3 months)
High Risk for MRSA
- Vancomycin 40 mg/kg/day IV q6–8h AND
- Cefotaxime 50 mg/kg IV q8h
Low Risk for MRSA
- Cefotaxime 50 mg/kg IV q8h AND
- Nafcillin 37 mg/kg IV q6h OR Oxacillin 37 mg/kg IV q6h
- Clindamycin 7.5 mg/kg IV q6h
Children (3 months–14 years)
- Vancomycin 40 mg/kg/day IV q6–8h AND
- Cefotaxime 50 mg/kg IV q8h
Adults (Monoarticular)
At risk for sexually-transmitted disease
- Ceftriaxone 1 g IV q24h OR Cefotaxime 1 g IV q8h OR Ceftizoxime 1 g IV q8h
- Vancomycin 1 g IV q12h
Not at risk for sexually-transmitted disease
- Vancomycin 1 g IV q12h AND
- Ceftriaxone 1 g IV q24h OR Cefotaxime 1 g IV q8h OR Ceftizoxime 1 g IV q8h
- Vancomycin 1 g IV q12h AND
- Ciprofloxacin 400 mg IV q12h OR Levofloxacin 750 mg IV q 24 h
Adults (Polyarticular)
- Ceftriaxone 1 g IV q24h
Antimicrobial Regimen – Synovial Fluid Gram Stain-Based Therapy
Negative Gram stain
- Vancomycin 15–20 mg/kg q8–12h AND
- Ceftazidime 2 g IV q8h OR Cefepime 2 g IV q8–12h
- Daptomycin 6-8 mg/kg IV q24h OR Linezolid 600 mg IV/PO q12h AND
- Piperacillin-Tazobactam 4.5 g IV q6h OR Aztreonam 2 g IV q8h OR Imipenem 500 mg IV q6h OR Meropenem 1 g IV q8h OR Doripenem 500 mg IV q8h OR Carbapenems
Gram-positive cocci
- Vancomycin 15–20 mg/kg q8–12h
- Daptomycin 6-8 mg/kg IV q24h OR Linezolid 600 mg IV/PO q12h
Gram-negative cocci
- Ceftriaxone 1 g IV q24h OR Cefotaxime 1 g IV q8h
Gram-negative bacilli
- Ceftazidime 2 g IV q8h OR Cefepime 2 g IV q8–12h OR Piperacillin-Tazobactam 4.5 g IV q6h
- Aztreonam 2 g IV q8h OR Imipenem 500 mg IV q6h OR Meropenem 1 g IV q8h OR Doripenem 500 mg IV q8h OR Carbapenems
Antimicrobial Regimen – Pathogen-Based Therapy
Bacteroides fragilis
- Clindamycin 900 mg IV/IM q8h OR Metronidazole 500 mg IV q8
- Ampicillin-Sulbactam 3 g IV q6h OR Ticarcillin-Clavulanate 3.1 g IV q4–6h
Brucella melitensis
- Doxycycline 100 mg PO bid for ≥ 6 weeks AND
- Streptomycin 15 mg/kg IM qd for 2–3 weeks OR Rifampin 600–900 mg qd for ≥ 6 weeks
- Doxycycline 100 mg PO bid for ≥ 6 weeks AND
- Gentamicin 5 mg/kg IV qd for 7 days
Enterococcus
- Ampicillin 2 g IV q6h OR Vancomycin 1 g IV q12h
- Ampicillin-Sulbactam 3 g IV q6h OR Linezolid 600 mg PO/IV q12h
Escherichia coli
- Ampicillin-Sulbactam 3 g IV q6h
- Cefazolin 0.25–1 g IV/IM q6–8h OR Levofloxacin 500–750 mg IV/PO q24h OR Gentamicin 3–5 mg/kg/day IV q6–8h OR TMP-SMX 8–10 mg/kg/day IV/PO q6–12h (TMP component)
Haemophilus influenzae
- Amoxicillin-Clavulanate 875/125 mg PO q12h OR Cefprozil 500 mg PO q12h OR Cefuroxime 500 mg PO q12h OR Cefdinir 600 mg PO q24h
- Levofloxacin 750 mg IV/PO q24h OR Moxifloxacin 400 mg IV/PO q24h OR Clarithromycin 500 mg PO q12h
Morganella morganii
- Cefotaxime 2 g IV q6h OR Imipenem 500 mg IV q6h OR Levofloxacin 500 mg IV/PO q24h
- Gentamicin 3–5 mg/kg/day IV q6–8h OR Ticarcillin-Clavulanate 3.1 g IV q4–6h
Neisseria gonorrhoeae
- Ceftriaxone 2 g IV q24h OR Cefotaxime 1 g IV q8h
- Levofloxacin 500 mg IV/PO q24h OR Ampicillin 2 g IV q6h
Proteus mirabilis
- Ampicillin 2 g IV q6h OR Levofloxacin 500 mg IV/PO q24h
- 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
- Cefotaxime 2 g IV q6h OR Imipenem 500 mg IV q6h OR Levofloxacin 500 mg IV/PO q24h
- Gentamicin 3–5 mg/kg/day IV q6–8h OR Ticarcillin-Clavulanate 3.1 g IV q4–6h
Pseudomonas aeruginosa
- Cefepime 2 g IV q12h OR Piperacillin 3–4 g IV q4–6h OR Imipenem 500 mg IV q6h
- Ticarcillin-Clavulanate 3.1 g IV q4–6h OR Tobramycin 3-5 mg/kg/day IV q6–8h OR Amikacin 15 mg/kg/day IV/IM q8–12h OR Ciprofloxacin 400 mg IV q8–12h
Serratia marcescens
- Cefotaxime 2 g IV q6h
- Levofloxacin 500 mg IV/PO q24h OR Gentamicin 3–5 mg/kg/day IV q6–8h OR Imipenem 500 mg IV q6h
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)
- Nafcillin 2 g IV q6h OR Clindamycin 900 mg IV q8h
- Cefazolin 0.25–1 g IV/IM q6–8h OR Vancomycin 500 mg IV q6h or 1 g IV q12h
Staphylococcus epidermidis (methicillin-resistant)
- Vancomycin 500 mg IV q6h or 1 g IV q12h OR Linezolid 600 mg IV q12h
- 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 aureus (methicillin-susceptible)
- Nafcillin 2 g IV q6h OR Clindamycin 900 mg IV/IM q8h
- Cefazolin 0.25–1 g IV/IM q6–8h OR Vancomycin 500 mg IV q6h or 1 g IV q12h
Streptococcus agalactiae
- Penicillin G 2 MU IV/IM q4h OR Ampicillin 2 g IV q6h
- Clindamycin 600–1200 mg/day IV/IM q6–12h OR Cefazolin 0.25–1 g IV/IM q6–8h
Streptococcus pyogenes
- Penicillin G 2 MU IV/IM q4h OR Ampicillin 2 g IV q6h
- Clindamycin 600–1200 mg/day IV/IM q6–12h OR Cefazolin 0.25–1 g IV/IM q6–8h
Tropheryma whipplei
- Penicillin G 2 MU IV q4h for 2 weeks AND
- Streptomycin 1 g IM/IV q24h for 2 weeks, then TMP-SMX 160mg/800mg PO q24h for 1 year
- Ceftriaxone 2 g IV q24h, then TMP-SMX 160mg/800mg PO q24h for 1 year
Borrelia burgdorferi
- Amoxicillin 500 mg q8h for 28 days OR Doxycycline 100 mg q12h for 28 days OR Cefuroxime 500 mg q12h for 28 days
- Azithromycin 500 mg PO q24h for 7–10 days OR Clarithromycin 500 mg PO q12h for 14–21 days OR Erythromycin 500 mg PO q6h for 14–21 days