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.

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

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

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 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

Microorgnaism		First choice antibiotic	Second choice antibiotic
Staphylococcus aureus	Methicillin-sensitive	Nafcillin 2 g every QID or Clindamycin 900 mg TID	Cefazolin Vancomycin
	Methicillin resistant	Vancomycin 1 g BD or Linezolid 600 mg BD	Sulfamethoxazole-trimethoprim or Minocycline ± rifampin
Coagulase-negative Staphylococcus spp	Methicillin-sensitive	Nafcillin 2 g QID or Clindamycin 900 mg TID	Cefazolin, vancomycin
	Methicillin resistant	*Vancomycin 1 g BD or Linezolid 600 mg BD	* Sulfamethoxazole-trimethoprim or * Minocycline ± rifampin or * Clindamycin

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 epidermidis (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