Sandbox septic arthritis

# 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 -lactamaseproducing 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
- Neonate
- Infant < 2 years
- Infant > 2 years
- Young adults (sexually active)
- Elderly adults
- Post-aspiration or injection
- Trauma
- Prosthesis
- Injecting drug use
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Sickle cell anemia
- Hemophilia
- Immunosuppression
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 (1520 mg/kg/dose IV every 812 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 610 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 1013 mg/kg/dose PO/IV every 68 hours in children), and trimethoprim-sulfamethoxazole (3.54.0 mg/kg/dose PO/IV every 812 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.
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

# Antimicrobial Regimen  Empiric Therapy

## Newborn (< 1 week)

### High Risk for MRSA
- Preferred Regimen
Vancomycin 18 mg/kg/day IV q12h AND
Cefotaxime 50 mg/kg IV q12h
- Vancomycin 18 mg/kg/day IV q12h AND
- Cefotaxime 50 mg/kg IV q12h

### Low Risk for MRSA
- Preferred Regimen
Cefotaxime 50 mg/kg IV q12h AND
Nafcillin 25 mg/kg IV q8h OR Oxacillin 25 mg/kg IV q8h
- Cefotaxime 50 mg/kg IV q12h AND
- Nafcillin 25 mg/kg IV q8h OR Oxacillin 25 mg/kg IV q8h
- Alternative Regimen
Clindamycin 5 mg/kg IV q8h
- Clindamycin 5 mg/kg IV q8h

## Newborn (14 weeks)

### High Risk for MRSA
- Preferred Regimen
Vancomycin 22 mg/kg/day IV q12h AND
Cefotaxime 50 mg/kg IV q8h
- Vancomycin 22 mg/kg/day IV q12h AND
- Cefotaxime 50 mg/kg IV q8h

### Low Risk for MRSA
- Preferred Regimen
Cefotaxime 50 mg/kg IV q8h AND
Nafcillin 37 mg/kg IV q6h OR Oxacillin 37 mg/kg IV q6h
- Cefotaxime 50 mg/kg IV q8h AND
- Nafcillin 37 mg/kg IV q6h OR Oxacillin 37 mg/kg IV q6h
- Alternative Regimen
Clindamycin 5 mg/kg IV q6h
- Clindamycin 5 mg/kg IV q6h

## Infants (13 months)

### High Risk for MRSA
- Preferred Regimen
Vancomycin 40 mg/kg/day IV q68h AND
Cefotaxime 50 mg/kg IV q8h
- Vancomycin 40 mg/kg/day IV q68h AND
- Cefotaxime 50 mg/kg IV q8h

### Low Risk for MRSA
- Preferred Regimen
Cefotaxime 50 mg/kg IV q8h AND
Nafcillin 37 mg/kg IV q6h OR Oxacillin 37 mg/kg IV q6h
- Cefotaxime 50 mg/kg IV q8h AND
- Nafcillin 37 mg/kg IV q6h OR Oxacillin 37 mg/kg IV q6h
- Alternative Regimen
Clindamycin 7.5 mg/kg IV q6h
- Clindamycin 7.5 mg/kg IV q6h

## Children (3 months14 years)
- Preferred Regimen
Vancomycin 40 mg/kg/day IV q68h AND
Cefotaxime 50 mg/kg IV q8h
- Vancomycin 40 mg/kg/day IV q68h AND
- Cefotaxime 50 mg/kg IV q8h

## Adults (Monoarticular)

### At risk for sexually-transmitted disease
- Preferred Regimen
Ceftriaxone 1 g IV q24h OR Cefotaxime 1 g IV q8h OR Ceftizoxime 1 g IV q8h
- Ceftriaxone 1 g IV q24h OR Cefotaxime 1 g IV q8h OR Ceftizoxime 1 g IV q8h
- Alternative Regimen
Vancomycin 1 g IV q12h
- Vancomycin 1 g IV q12h

### Not at risk for sexually-transmitted disease
- Preferred Regimen
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
- Ceftriaxone 1 g IV q24h OR Cefotaxime 1 g IV q8h OR Ceftizoxime 1 g IV q8h
- Alternative Regimen
Vancomycin 1 g IV q12h AND
Ciprofloxacin 400 mg IV q12h OR Levofloxacin 750 mg IV q 24 h
- Vancomycin 1 g IV q12h AND
- Ciprofloxacin 400 mg IV q12h OR Levofloxacin 750 mg IV q 24 h

## Adults (Polyarticular)
- Preferred Regimen
Ceftriaxone 1 g IV q24h
- Ceftriaxone 1 g IV q24h

# Antimicrobial Regimen  Synovial Fluid Gram Stain-Based Therapy

## Negative Gram stain
- Preferred Regimen
Vancomycin 1520 mg/kg q812h AND
Ceftazidime 2 g IV q8h OR Cefepime 2 g IV q812h
- Vancomycin 1520 mg/kg q812h AND
- Ceftazidime 2 g IV q8h OR Cefepime 2 g IV q812h
- Alternative Regimen
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
- 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
- Preferred Regimen
Vancomycin 1520 mg/kg q812h
- Vancomycin 1520 mg/kg q812h
- Alternative Regimen
Daptomycin 6-8 mg/kg IV q24h OR Linezolid 600 mg IV/PO q12h
- Daptomycin 6-8 mg/kg IV q24h OR Linezolid 600 mg IV/PO q12h

## Gram-negative cocci
- Preferred Regimen
Ceftriaxone 1 g IV q24h OR Cefotaxime 1 g IV q8h
- Ceftriaxone 1 g IV q24h OR Cefotaxime 1 g IV q8h

## Gram-negative bacilli
- Preferred Regimen
Ceftazidime 2 g IV q8h OR Cefepime 2 g IV q812h OR Piperacillin-Tazobactam 4.5 g IV q6h
- Ceftazidime 2 g IV q8h OR Cefepime 2 g IV q812h OR Piperacillin-Tazobactam 4.5 g IV q6h
- Alternative Regimen
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
- 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
- Preferred Regimen
Clindamycin 900 mg IV/IM q8h OR Metronidazole 500 mg IV q8
- Clindamycin 900 mg IV/IM q8h OR Metronidazole 500 mg IV q8
- Alternative Regimen
Ampicillin-Sulbactam 3 g IV q6h OR Ticarcillin-Clavulanate 3.1 g IV q46h
- Ampicillin-Sulbactam 3 g IV q6h OR Ticarcillin-Clavulanate 3.1 g IV q46h

### Brucella melitensis
- Preferred Regimen
Doxycycline 100 mg PO bid for  6 weeks AND
Streptomycin 15 mg/kg IM qd for 23 weeks OR Rifampin 600900 mg qd for  6 weeks
- Doxycycline 100 mg PO bid for  6 weeks AND
- Streptomycin 15 mg/kg IM qd for 23 weeks OR Rifampin 600900 mg qd for  6 weeks
- Alternative Regimen
Doxycycline 100 mg PO bid for  6 weeks AND
Gentamicin 5 mg/kg IV qd for 7 days
- Doxycycline 100 mg PO bid for  6 weeks AND
- Gentamicin 5 mg/kg IV qd for 7 days

### Enterococcus
- Preferred Regimen
Ampicillin 2 g IV q6h OR Vancomycin 1 g IV q12h
- Ampicillin 2 g IV q6h OR Vancomycin 1 g IV q12h
- Alternative Regimen
Ampicillin-Sulbactam 3 g IV q6h OR Linezolid 600 mg PO/IV q12h
- Ampicillin-Sulbactam 3 g IV q6h OR Linezolid 600 mg PO/IV q12h

### Escherichia coli
- Preferred Regimen
Ampicillin-Sulbactam 3 g IV q6h
- Ampicillin-Sulbactam 3 g IV q6h
- Alternative Regimen
Cefazolin 0.251 g IV/IM q68h OR Levofloxacin 500750 mg IV/PO q24h OR Gentamicin 35 mg/kg/day IV q68h OR TMP-SMX 810 mg/kg/day IV/PO q612h (TMP component)
- Cefazolin 0.251 g IV/IM q68h OR Levofloxacin 500750 mg IV/PO q24h OR Gentamicin 35 mg/kg/day IV q68h OR TMP-SMX 810 mg/kg/day IV/PO q612h (TMP component)

### Haemophilus influenzae
- Preferred Regimen
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
- 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
- Alternative Regimen
Levofloxacin 750 mg IV/PO q24h OR Moxifloxacin 400 mg IV/PO q24h OR Clarithromycin 500 mg PO q12h
- Levofloxacin 750 mg IV/PO q24h OR Moxifloxacin 400 mg IV/PO q24h OR Clarithromycin 500 mg PO q12h

### Morganella morganii
- Preferred Regimen
Cefotaxime 2 g IV q6h OR Imipenem 500 mg IV q6h OR Levofloxacin 500 mg IV/PO q24h
- Cefotaxime 2 g IV q6h OR Imipenem 500 mg IV q6h OR Levofloxacin 500 mg IV/PO q24h
- Alternative Regimen
Gentamicin 35 mg/kg/day IV q68h OR Ticarcillin-Clavulanate 3.1 g IV q46h
- Gentamicin 35 mg/kg/day IV q68h OR Ticarcillin-Clavulanate 3.1 g IV q46h

### Neisseria gonorrhoeae
- Preferred Regimen
Ceftriaxone 2 g IV q24h OR Cefotaxime 1 g IV q8h
- Ceftriaxone 2 g IV q24h OR Cefotaxime 1 g IV q8h
- Alternative Regimen
Levofloxacin 500 mg IV/PO q24h OR Ampicillin 2 g IV q6h
- Levofloxacin 500 mg IV/PO q24h OR Ampicillin 2 g IV q6h

### Proteus mirabilis
- Preferred Regimen
Ampicillin  2 g IV q6h OR Levofloxacin 500 mg IV/PO q24h
- Ampicillin  2 g IV q6h OR Levofloxacin 500 mg IV/PO q24h
- Alternative Regimen
Cefazolin 0.251 g IV/IM q68h OR Gentamicin 35 mg/kg/day IV q68h OR TMP-SMX 810 mg/kg/day IV/PO q612h (TMP component)
- Cefazolin 0.251 g IV/IM q68h OR Gentamicin 35 mg/kg/day IV q68h OR TMP-SMX 810 mg/kg/day IV/PO q612h (TMP component)

### Proteus vulgaris or Proteus rettgeri
- Preferred Regimen
Cefotaxime 2 g IV q6h OR Imipenem 500 mg IV q6h OR Levofloxacin 500 mg IV/PO q24h
- Cefotaxime 2 g IV q6h OR Imipenem 500 mg IV q6h OR Levofloxacin 500 mg IV/PO q24h
- Alternative Regimen
Gentamicin 35 mg/kg/day IV q68h OR Ticarcillin-Clavulanate 3.1 g IV q46h
- Gentamicin 35 mg/kg/day IV q68h OR Ticarcillin-Clavulanate 3.1 g IV q46h

### Pseudomonas aeruginosa
- Preferred Regimen
Cefepime 2 g IV q12h  OR Piperacillin 34 g IV q46h OR Imipenem 500 mg IV q6h
- Cefepime 2 g IV q12h  OR Piperacillin 34 g IV q46h OR Imipenem 500 mg IV q6h
- Alternative Regimen
Ticarcillin-Clavulanate 3.1 g IV q46h OR Tobramycin 3-5 mg/kg/day IV q68h OR Amikacin 15 mg/kg/day IV/IM q812h OR Ciprofloxacin 400 mg IV q812h
- Ticarcillin-Clavulanate 3.1 g IV q46h OR Tobramycin 3-5 mg/kg/day IV q68h OR Amikacin 15 mg/kg/day IV/IM q812h OR Ciprofloxacin 400 mg IV q812h

### Serratia marcescens
- Preferred Regimen
Cefotaxime 2 g IV q6h
- Cefotaxime 2 g IV q6h
- Alternative Regimen
Levofloxacin 500 mg IV/PO q24h OR Gentamicin 35 mg/kg/day IV q68h OR Imipenem 500 mg IV q6h
- Levofloxacin 500 mg IV/PO q24h OR Gentamicin 35 mg/kg/day IV q68h OR Imipenem 500 mg IV q6h

### Staphylococcus aureus (methicillin-resistant)
- Preferred Regimen
Vancomycin 1520 mg/kg IV q812h in adults or 15 mg/kg IV q6h in children
- Vancomycin 1520 mg/kg IV q812h in adults or 15 mg/kg IV q6h in children
- Alternative Regimen
Daptomycin 6 mg/kg IV q24h in adults or 610 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 1013 mg/kg/dose PO/IV q68h in children OR TMP-SMX 3.54.0 mg/kg PO/IV q812h in adults
- Daptomycin 6 mg/kg IV q24h in adults or 610 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 1013 mg/kg/dose PO/IV q68h in children OR TMP-SMX 3.54.0 mg/kg PO/IV q812h in adults

### Staphylococcus aureus (methicillin-susceptible)
- Preferred Regimen
Nafcillin 2 g IV q6h OR Clindamycin 900 mg IV q8h
- Nafcillin 2 g IV q6h OR Clindamycin 900 mg IV q8h
- Alternative Regimen
Cefazolin 0.251 g IV/IM q68h OR Vancomycin 500 mg IV q6h or 1 g IV q12h
- Cefazolin 0.251 g IV/IM q68h OR Vancomycin 500 mg IV q6h or 1 g IV q12h

### Staphylococcus epidermidis (methicillin-resistant)
- Preferred Regimen
Vancomycin 500 mg IV q6h or 1 g IV q12h OR Linezolid 600 mg IV q12h
- Vancomycin 500 mg IV q6h or 1 g IV q12h OR Linezolid 600 mg IV q12h
- Alternative Regimen
TMP-SMX 3.54.0 mg/kg PO/IV q812h (TMP component) OR Minocycline 200 mg PO x 1 dose, then 100 mg PO q12h AND
Rifampin 300600 mg PO/IV q12h
- TMP-SMX 3.54.0 mg/kg PO/IV q812h (TMP component) OR Minocycline 200 mg PO x 1 dose, then 100 mg PO q12h AND
- Rifampin 300600 mg PO/IV q12h

### Staphylococcus aureus (methicillin-susceptible)
- Preferred Regimen
Nafcillin 2 g IV q6h OR Clindamycin 900 mg IV/IM q8h
- Nafcillin 2 g IV q6h OR Clindamycin 900 mg IV/IM q8h
- Alternative Regimen
Cefazolin 0.251 g IV/IM q68h OR Vancomycin 500 mg IV q6h or 1 g IV q12h
- Cefazolin 0.251 g IV/IM q68h OR Vancomycin 500 mg IV q6h or 1 g IV q12h

### Streptococcus agalactiae
- Preferred Regimen
Penicillin G 2 MU IV/IM q4h OR Ampicillin 2 g IV q6h
- Penicillin G 2 MU IV/IM q4h OR Ampicillin 2 g IV q6h
- Alternative Regimen
Clindamycin 6001200 mg/day IV/IM q612h OR Cefazolin 0.251 g IV/IM q68h
- Clindamycin 6001200 mg/day IV/IM q612h OR Cefazolin 0.251 g IV/IM q68h

### Streptococcus pyogenes
- Preferred Regimen
Penicillin G 2 MU IV/IM q4h OR Ampicillin 2 g IV q6h
- Penicillin G 2 MU IV/IM q4h OR Ampicillin 2 g IV q6h
- Alternative Regimen
Clindamycin 6001200 mg/day IV/IM q612h OR Cefazolin 0.251 g IV/IM q68h
- Clindamycin 6001200 mg/day IV/IM q612h OR Cefazolin 0.251 g IV/IM q68h

### Tropheryma whipplei
- Preferred Regimen
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
- 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
- Alternative Regimen
Ceftriaxone 2 g IV q24h, 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
- Preferred Regimen
Amoxicillin 500 mg q8h for 28 days OR Doxycycline 100 mg q12h for 28 days OR Cefuroxime 500 mg q12h for 28 days
- Amoxicillin 500 mg q8h for 28 days OR Doxycycline 100 mg q12h for 28 days OR Cefuroxime 500 mg q12h for 28 days
- Alternative Regimen
Azithromycin 500 mg PO q24h for 710 days OR Clarithromycin 500 mg PO q12h for 1421 days OR Erythromycin 500 mg PO q6h for 1421 days
- Azithromycin 500 mg PO q24h for 710 days OR Clarithromycin 500 mg PO q12h for 1421 days OR Erythromycin 500 mg PO q6h for 1421 days