Septic arthritis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [3]

Overview

Acute nongonococcal 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

Intra-articular antibiotics are not useful as it may increase infection rate and also causes chemical synovitis and cartilage toxicity.

Methicillin-resistant Staphylococcus aureus (MRSA)

Patient at high risk of 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.

Antimicrobial Regimen – Empiric Therapy

Newborn (< 1 week)	Newborn (1–4 weeks)	Infants (1–3 months)	Children (3 months–14 years)	Adults
High Risk for MRSA Preferred Regimen 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	High Risk for MRSA Preferred Regimen Vancomycin 22 mg/kg/day IV q12h AND Cefotaxime 50 mg/kg IV q8h Alternative Regimen Clindamycin 5 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 Alternative Regimen Clindamycin 5 mg/kg IV q6h	High Risk for MRSA Preferred Regimen Vancomycin 40 mg/kg/day IV q6–8h 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 Alternative Regimen Clindamycin 7.5 mg/kg IV q6h	Preferred Regimen Vancomycin 40 mg/kg/day IV q6–8h AND Cefotaxime 50 mg/kg IV q8h	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 Alternative Regimen 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 Alternative Regimen Vancomycin 1 g IV q12h AND Ciprofloxacin 400 mg IV q12h OR Levofloxacin 750 mg IV q 24 h Polyarticular Preferred Regimen Ceftriaxone 1 g IV q24h

Antimicrobial Regimen – Synovial Fluid Gram Stain-Based Therapy

Gram stain result	First choice antibiotic	Second choice antibiotic
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

Antimicrobial Regimen – Pathogen Based Therapy

Microorgnaism		First choice antibiotic	Second choice antibiotic
Staphylococcus aureus	Methicillin-sensitive	Nafcillin 2 g IV QID or Clindamycin 900 mg IV TID	Cefazolin 0.25–1 g IV/IM q6–8h, Vancomycin 500 mg IV q6h or 1 g IV q12h
	Methicillin-resistant	Vancomycin 15–20 mg/kg IV q8–12h in adults or 15 mg/kg IV q6h in children or Linezolid 600 mg PO/IV q12h in adults or 10 mg/kg PO/IV q8h in children	Sulfamethoxazole-trimethoprim 3.5–4.0 mg/kg PO/IV q8–12h in adults or Minocycline ± rifampin
Coagulase-negative Staphylococcus spp	Methicillin-sensitive	Nafcillin 2 g IV QID or Clindamycin 900 mg IV/IM TID	Cefazolin 0.25–1 g IV/IM q6–8h vancomycin 500 mg IV q6h or 1 g IV BD
	Methicillin-resistant	Vancomycin 1 g BD or Linezolid 600 mg BD	Sulfamethoxazole-trimethoprim or Minocycline ± rifampin or Clindamycin
Group A streptococcus, Strep. pyogenes		Penicillin G 2 million IV/IM every 4 h or Ampicillin 2 g IV QID	Clindamycin 600–1200 mg/day IV/IM q6–12h Cefazolin 0.25–1 g IV/IM q6–8h
Group B streptococcus, Strep. agalactiae		Penicillin G 2 million IV/IM every 4 h or Ampicillin 2 g IV every 6 h	Clindamycin 600–1200 mg/day IV/IM q6–12h Cefazolin 0.25–1 g IV/IM q6–8h
Enterococcus spp.		Ampicillin 2 g IV QID or Vancomycin 1 g IV BD	Ampicillin-sulbactam 3 g IV QID Linezolid 600 mg PO/IV BD
Escherichia coli		Ampicillin-sulbactam 3 g IV QID	Cefazolin 0.25–1 g IV/IM q6–8h, levofloxacin 500–750 mg IV/PO OD Gentamicin 3–5 mg/kg/day IV q6–8h Sulfamethoxazole-trimethoprim 8–10 mg/kg/day IV/PO q6–12h
Proteus mirabilis		Ampicillin 2 g IV QID or Levofloxacin 500 mg IV/PO OD	Cefazolin 0.25–1 g IV/IM q6–8h Sulfamethoxazole-trimethoprim 8–10 mg/kg/day IV/PO q6–12h Gentamicin 3–5 mg/kg/day IV q6–8h
Proteus vulgaris, Proteus rettgeri, Morganella morganii		Cefotaxime 2 g IV QID Imipenem 500 mg IV QID, or Levofloxacin 500 mg IV/PO OD	Gentamicin 3–5 mg/kg/day IV q6–8h, or Ticarcillin-clavulanate 3.1 g IV q4–6h
Serratia marcescens		Cefotaxime 2 g IV QID	Levofloxacin 500 mg IV/PO OD Gentamicin 3–5 mg/kg/day IV q6–8h Imipenem 500 mg IV QID
Pseudomonas aeruginosa		Cefepime 2 gm IV BD or Piperacillin 3 gm IV QID or Imipenem 500 IV QID	Ticarcillin-clavulanate 3.1 g IV q4–6h Tobramycin 3-5 mg/kg/day IV q6–8h Amikacin 15 mg/kg/day IV/IM q8–12h Ciprofloxacin 400 mg IV q8–12h
Neisseria gonorrhea		Ceftriaxone 2 g IV OD or Cefotaxime 1 g TID	Levofloxacin 500 mg IV/PO OD Ampicillin 2 g IV QID
Bacteroides fragilis group		Clindamycin 900 mg IV/IM TID or Metronidazole 500 mg TID	Ampicillin-sulbactam 3 g IV QID or Ticarcillin-clavulanic acid 3.1 g IV QID
Brucella melitensis		Doxycycline 100 mg PO BD and Streptomycin 15 mg/kg IM QID or Rifampin 600–900 mg QID	Doxycycline 100 mg PO BD and Gentamicin 5 mg/kg IV QID
Haemophilus influenzae		Amoxicillin-Clavulanate 875/125 mg PO BD or Cefprozil 500 mg PO BD or Cefuroxime 500 mg PO BD or Cefdinir 600 mg PO OD	Levofloxacin 750 mg IV/PO OD or Moxifloxacin 400 mg IV/PO OD or Clarithromycin 500 mg PO BD
Morganella morganii		Cefotaxime 2 g IV QID or Imipenem 500 mg IV QID or Levofloxacin 500 mg IV/PO OD	Gentamicin 3–5 mg/kg/day IV q6–8h or Ticarcillin-Clavulanate 3.1 g IV q4–6h
Tropheryma whipplei		Penicillin G 2 million units IV q4h for 2 weeks and Streptomycin 1 g IM/IV OD for 2 weeks, then TMP-SMX 160mg/800mg PO OD for 1 year	Ceftriaxone 2 g IV OD, then TMP-SMX 160mg/800mg PO OD for 1 year
Borrelia burgdorferi		Amoxicillin 500 mg TID for 28 days or Doxycycline 100 mg BD for 28 days or Cefuroxime 500 mg BD for 28 days	Azithromycin 500 mg PO OD for 7–10 days or Clarithromycin 500 mg PO BD for 14–21 days or Erythromycin 500 mg PO QID for 14–21 days

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

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.