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]

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

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

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

Antimicrobial regimen

Septic arthritis, Brucella melitensis

• Septic arthritis, Brucella melitensis

• Preferred Regimen: 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
• Alternative Regimen: Doxycycline 100 mg PO bid for ≥ 6 weeks AND Gentamicin 5 mg/kg IV qd for 7 days

Septic arthritis, candidal

• Septic arthritis, candidal

• Preferred regimen (1): Fluconazole 400 mg/day (6 mg/kg/day) for at least 6 weeks

• Preferred regimen (2): Amphotericin B 3–5 mg/kg/day for several weeks THEN Fluconazole to completion
• Alternative regimen (1): Anidulafungin 200-mg loading dose THEN 100 mg/day

• Alternative regimen (2): Caspofungin 70-mg loading dose THEN 50 mg/day

• Alternative regimen (3): Micafungin 100 mg/day

• Alternative regimen (4): Amphotericin B deoxycholate 0.5–1 mg/kg/day for several weeks THEN Fluconazole to completion
• Note: Duration of therapy usually is for at least 6 weeks, but few data are available; Surgical debridement is recommended for all cases; For infected prosthetic joints, removal is recommended for most cases.

Septic arthritis, gonococcal

• Septic arthritis, gonococcal

• Preferred regimen: Ceftriaxone 1 g intramuscularly IM/IV q24h
• Alternative regimen (1): Cefotaxime 1 g IV q8h

• Alternative regimen (2): Ceftizoxime 1 g IV q8h

• Alternative regimen (3): Spectinomycin 2 g IV q12h (Penicillin allergies)
• Alternative regimen (4): Ciprofloxacin 500 mg IV q12h OR Ofloxacin 400 mg IV q12h (β-lactam-allergic patient)
• Note: The tetracyclines (except in pregnant women) or penicillins may be used if the infecting organism is proven to be susceptible
• Pediatric regimen:

• >45 kg

• Preferred regimen: Ceftriaxone 50 mg/kg (Maximum, 2 g/dose) IM/IV single dose for 10 to 14 days

• <45 kg

• Preferred regimen: Ceftriaxone 50 mg/kg (Maximum, 1 g/dose) IM/IV single dose for 7 days

Septic arthritis, Gram-negative bacilli

• Septic arthritis, Gram-negative bacilli

• Preferred regimen (1): Ceftazidime 2 g IV q8h

• Preferred regimen (2): Cefepime 2 g IV q8–12h

• Preferred regimen (3): Piperacillin-Tazobactam 4.5 g IV q6h
• Alternative regimen (1): Aztreonam 2 g IV q8h

• Alternative regimen (2): Imipenem 500 mg IV q6h

• Alternative regimen (3): Meropenem 1 g IV q8h

• Alternative regimen (4): Doripenem 500 mg IV q8h

• Alternative regimen (5): Carbapenems

Septic arthritis, Histoplasmosis

• Septic arthritis, histoplasmosis

• 1. Mild disease

• Preferred regimen: Nonsteroidal anti-inflammatory drug

• 2. Severe disease

• Preferred regimen: Prednisone 0.5–1.0 mg/kg/day (Maximum, 80 mg/day) in tapering doses over 1–2 weeks AND Itraconazole 200 mg tid for 3 days, followed by qd or bid for 6–12 weeks

Septic arthritis, Lyme disease

• Septic arthritis, Lyme disease

• 1. Patients without clinical evidence of neurologic disease

• Preferred regimen (1): Doxycycline 100 mg bid for 28 days

• Preferred regimen (2): Amoxicillin 500 mg tid for 28 days

• Preferred regimen (3): Cefuroxime axetil 500 mg bid for 28 days
• Pediatric regimen (1): Amoxicillin 50 mg/kg/day tid (Maximum, 500 mg/dose)

• Pediatric regimen (2): Cefuroxime axetil 30 mg/kg/day bid (Maximum, 500 mg/dose)

• Pediatric regimen (3): (if the patient is ≥8 years of age) Doxycycline 4 mg/kg/day bid (Maximum, 100 mg/dose)

• 2. Patients with arthritis and objective evidence of neurologic disease

• Preferred regimen: Ceftriaxone administered parenterally for 2–4 weeks
• Alternative regimen: Cefotaxime OR Penicillin G administered parenterally
• Pediatric regimen: Ceftriaxone OR Cefotaxime OR Penicillin G administered intravenously

• Note (1): For patients who have persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy, we recommend re-treatment with another 4-week course of oral antibiotics or with a 2–4-week course of Ceftriaxone IV
• Note (2): If patients have no resolution of arthritis despite intravenous therapy and if PCR results for a sample of synovial fluid (and synovial tissue if available) are negative, symptomatic treatment is recommended, which consist of nonsteroidal anti-inflammatory agents, intra-articular injections of corticosteroids, or disease-modifying antirheumatic drugs (DMARDs), such as Hydroxychloroquine.

Septic arthritis, Mycobacterium tuberculosis

• Septic arthritis, Mycobacterium tuberculosis

• 1. Septic arthritis caused by susceptible Mycobacterium tuberculosis

• 1.1 Adults

• 1.1.1 Intensive phase

• Preferred regimen: Isoniazid 5 mg/kg (max, 300 mg) for 2 months AND Rifampin 10 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months

• 1.1.2 Continuation phase

• Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 7 months AND Rifampin 10 mg/kg (max: 600 mg) for 7 months

• 1.2 Pediatric

• 1.2.1 Intensive phase

• Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 2 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months

• 1.2.2 Continuation phase

• Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 7 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 7 months

• 2. Specific considerations

• 2.1 Pregnancy and breastfeeding

• With the exception of streptomycin, the first line anti-TB drugs are safe for use in pregnancy: Streptomycin is ototoxic to the fetus and should not be used during pregnancy.
• After active TB in the baby is ruled out, the baby should be given 6 months of isoniazid preventive therapy, followed by BCG vaccination.
• Pyridoxine supplementation is recommended for all pregnant or breastfeeding women taking isoniazid.

• 2.2 Liver disorders

• Two hepatotoxic drugs (rather than the three in the standard regimen):

• 9 months of Isoniazid AND Rifampicin AND Ethambutol (until or unless Isoniazid susceptibility is documented).
• 2 months of Isoniazid AND Rifampicin AND Streptomycin AND Ethambutol, followed by 6 months of Isoniazid AND Rifampicin.
• 6–9 months of Rifampicin AND Pyrazinamide AND Ethambutol

• One hepatotoxic drug:

• 2 months of Isoniazid AND Ethambutol AND Streptomycin, followed by 10 months of Isoniazid AND Ethambutol

• No hepatotoxic drugs:

• 18–24 months of Streptomycin AND Ethambutol AND a Fluoroquinolone

• 2.3 Renal failure and severe renal insufficiency

• The recommended initial TB treatment regimen for patients with renal failure or severe renal insufficiency is 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by 4 months of isoniazid and rifampicin.
• There is significant renal excretion of ethambutol and metabolites of pyrazinamide, and doses should therefore be adjusted.
• Three times per week administration of these two drugs at the following doses is recommended: pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg)
• While receiving isoniazid, patients with severe renal insufficiency or failure should also be given pyridoxine in order to prevent peripheral neuropathy.
• Because of an increased risk of nephrotoxicity and ototoxicity, Streptomycin should be avoided in patients with renal failure. If Streptomycin must be used, the dosage is 15 mg/kg, two or three times per week, to a maximum of 1 gram per dose, and serum levels of the drug should be monitored.

• 2.4 Previously treated patients in settings with rapid DST

• TB patients whose treatment has failed or other patient groups with high likelihood of multidrug-resistant TB (MDR) should be started on an empirical MDR regimen.
• TB patients returning after defaulting or relapsing from their first treatment course may receive the retreatment regimen containing first-line drugs 2HRZES/1HRZE/5HRE if country-specific data show low or medium levels of MDR in these patients or if such data are not available.

• 2.5 TB treatment in people living with HIV

• TB patients with known positive HIV status and all TB patients living in HIV prevalent settings should receive daily TB treatment at least during the intensive phase.
• For the continuation phase, the optimal dosing frequency is also daily for these patients.
• If a daily continuation phase is not possible for these patients, three times weekly dosing during the continuation phase is an acceptable alternative.
• It is recommended that TB patients who are living with HIV should receive at least the same duration of TB treatment as HIV-negative TB patients.

Septic arthritis, post-intraarticular injection

• Septic arthritis, post-intraarticular injection

• NO empiric therapy.

Septic arthritis, prosthetic joint infection

• Septic arthritis, prosthetic joint infection (device-related osteoarticular infections)

• 1. Empiric antimicrobial therapy

• It is preferable to delay antibiotic therapy until specimens for culture are obtained by joint aspiration, joint debridement, and/or prosthesis removal.

• 2. Pathogen-directed antimicrobial therapy

• 2.1 Staphylococcus aureus, methicillin-susceptible (MSSA)

• Preferred regimen (1): Nafcillin 2 g IV q4–6h

• Preferred regimen (2): Oxacillin 2 g IV q4–6h
• Alternative regimen (1): Cefazolin 1–2 g IV q8h

• Alternative regimen (2): Ceftriaxone 2 g IV q24h
• Alternative regimen (3): (if allergic to penicillins) Clindamycin 900 mg IV q8h

• Alternative regimen (4): (if allergic to penicillins) Vancomycin 15–20 mg/kg IV q8–12h (Maximum, 2 g/dose)

• 2.2 Staphylococcus, methicillin-resistant (MRSA)

• 2.2.1 Early-onset or acute hematogenous prosthetic joint infections involving a stable implant with short duration (< 3 weeks) of symptoms and debridement (but device retention)

• Preferred regimen: Vancomycin AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
• Alternative regimen: (Daptomycin 6 mg/kg IV q24h OR Linezolid 600 IV q8h) AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
• Note: The above regimen should be followed by Rifampin plus a fluoroquinolone, TMP/SMX, a tetracycline or Clindamycin for 3 or 6 months for hips and knees, respectively.

• 2.2.2 Early-onset spinal implant infections or implants in an actively infected site

• Initial parenteral therapy plus Rifampin followed by prolonged oral therapy is recommended.
• Long-term oral suppressive antibiotics (eg, TMP-SMX, a tetracycline, a fluoroquinolone [which should be given in conjunction with Rifampin due to the potential emergence of fluoroquinolone resistance)

• 2.3 Streptococci, beta-hemolytic

• Preferred regimen (1): Penicillin 12–18 MU/day IV q6h

• Preferred regimen (2): Ampicillin 2 g IV q6h

• Preferred regimen (3): Ceftriaxone 1–2 g IV q24h
• Alternative regimen (1): (if allergic to penicillins) Clindamycin 900 mg IV q8h
• Alternative regimen (2): (if allergic to penicillins) Vancomycin 15–20 mg/kg IV q8–12h (Maximum, 2 g/dose)

• 2.4 Enterococci

• 2.4.1 Monotherapy

• Preferred regimen (1): Ampicillin 6-12 g/day q4-6h
• Preferred regimen (2): Penicillin G 18-30 MU/day continuously or q4h
• Preferred regimen (3): Vancomycin 15-20 mg/kg/dose q8-12h (Maximum, 2 g/dose)

• 2.4.2 Combination therapy (one of the monotherapy agents, and one of the following agents)

• Preferred regimen (1): Gentamicin 1 mg/kg IV q8h
• Preferred regimen (2): Streptomycin 7.5 mg/kg IV q12h
• Preferred regimen (3): Ampicillin 2 g/day IV q6h AND Ceftriaxone 2 g IV q12h

• 2.5 Gram-negative bacilli

• Patients susceptible to fluoroquinolones

• Preferred regimen: Ciprofloxacin 500-750 mg bid

• 2.5.1 P. aeruginosa

• Preferred regimen (1): Cefepime 2 g IV q12h

• Preferred regimen (2): Meropenem 1 g IV q8h
• Alternative regimen (1): Ciprofloxacin 750 mg PO bid
• Alternative regimen (2): Ceftazidime 2 g IV q8h

• 2.6 Anaerobes

• 2.6.1Propionibacterium acnes

• Preferred regimen (1): Penicillin 24 MU/day IV q4h or continuously

• Preferred regimen (2): Ceftriaxone 1-2 g/day IV
• Alternative regimen: Vancomycin OR Clindamycin

• 2.6.2 Not Propionibacterium acnes
• Preferred regimen: Metronidazole 500 mg PO tid

• 2.7 Mycobacterium tuberculosis

• Preferred regimen: see (Septic arthritis, Mycobacterium tuberculosis)

• 2.8 Fungi

• Preferred regimen: see (Septic arthritis, candidal)

• 2.9 Culture negative

• Preferred regimen: Vancomycin AND Ciprofloxacin OR Cefazolin AND Ciprofloxacin

Septic arthritis, staphylococcal

• 1.Staphylococcus aureus (methicillin-resistant)

• Preferred regime: Vancomycin 15–20 mg/kg IV q8–12h
• Alternative regimen (1): Daptomycin 6 mg/kg IV q24h
• Alternative regimen (2): Linezolid 600 mg PO/IV q12h
• Alternative regimen (3): Clindamycin 600 mg PO/IV q8h
• Alternative regimen (4): TMP-SMX 3.5–4.0 mg/kg PO/IV q8–12h
• Pediatric regimen（1): Vancomycin 15 mg/kg IV q6h
• Pediatric regimen（1): Daptomycin 6–10 mg/kg IV q24h
• Pediatric regimen（1): Linezolid 10 mg/kg PO/IV q8h
• Pediatric regimen（1): Clindamycin 10–13 mg/kg/dose PO/IV q6–8h

2. Staphylococcus aureus (methicillin-susceptible)

• Preferred regimen (1): Nafcillin 2 g IV q6h

• Preferred regimen (2): Clindamycin 900 mg IV q8h
• Alternative regimen (1): Cefazolin 0.25–1 g IV/IM q6–8h
• Alternative regimen (2): Vancomycin 500 mg IV q6h or 1 g IV q12h

3. Staphylococcus epidermidis (methicillin-resistant)

• Preferred regimen (1): Vancomycin 500 mg IV q6h or 1 g IV q12h
• Preferred regimen (2): Linezolid 600 mg IV q12h
• Alternative regimen: (TMP-SMX 3.5–4.0 mg/kg PO/IV q8–12h (TMP component) OR Minocycline 200 mg PO single dose THEN 100 mg PO q12h) AND Rifampin 300–600 mg PO/IV q12h

4. Staphylococcus epidermidis (methicillin-susceptible)

• Preferred regimen (1): Nafcillin 2 g IV q6h
• Preferred regimen (2): Clindamycin 900 mg IV q8h
• Alternative regimen (1): Cefazolin 0.25–1 g IV/IM q6–8h
• Alternative regimen (2): Vancomycin 500 mg IV q6h or 1 g IV q12h

Septic arthritis, streptococcal

1. Streptococcus agalactiae

• Preferred regimen (1): Penicillin G 2 MU IV/IM q4h
• Preferred regimen (2): Ampicillin 2 g IV q6h
• Alternative regimen (1): Clindamycin 600–1200 mg/day IV/IM q6–12h
• Alternative regimen (2): Cefazolin 0.25–1 g IV/IM q6–8h

2. Streptococcus pyogenes

• Preferred regimen (1): Penicillin G 2 MU IV/IM q4h
• Preferred regimen (2): Ampicillin 2 g IV q6h
• Alternative regimen (1): Clindamycin 600–1200 mg/day IV/IM q6–12h
• Alternative regimen (2): Cefazolin 0.25–1 g IV/IM q6–8h