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]

Overview

The treatment for septic arthritis requires an adequate drainage of the joint fluid and appropriate antibiotic therapy. Empiric therapy should be started after the collection joint fluid and blood sample for culture. There are no indications for intra-articular antibiotic therapy.

Medical Therapy

Antibiotics are used to treat the infection and most of them achieve excellent bactericidal concentrations in the synovial fluid. The initial therapy depends on the clinical presentation, whether the patient is at risk for a Gonoccocal infection or not, and Gram stain of joint aspiration. The final therapy depends on the culture and sensitivity results. During the acute phase of the disease is important to keep the the joint still and raised, and the patient need to rest. Using cool compresses may help relieve pain. After the acute phase, exercise and physical therapy is important for the recovery process. Severe cases may need surgery to drain the infected joint fluid.

Duration of Antimicrobial Therapy

• The duration of antimicrobial therapy should be individualized in accordance with patient's clinical response.

Recommended Duration of Antimicrobial Therapy Based on Isolated Pathogen.

Microorganism	Duration of Therapy
▸ Staphylococcus aureus	3-4 weeks
▸ Streptococcus groups A, B, C, G	3-4 weeks
▸ Gram-negative bacilli	4 weeks
▸ Brucella	6 weeks
▸ Borrelia burgdorferi	30 days
▸ Mycobacterium tuberculosis	9 months
▸ Candida albicans	6 weeks

Special cases	Duration of Therapy
▸ Prosthetic joint infection	6 weeks
▸ Post intra-articular injection or post-arthroscopy infection	14 days

Empiric Therapy Adapted from Lancet 375:846, 2010.

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Pediatric     Newborns (< 1 week)   ▸  Newborns (1 -4 week)   ▸  Infants (1 - 3 months)   ▸  Children (3 mo - 14 yr)     Adults   ▸  Acute Monoarticular   ▸  Chronic Monoarticular   ▸  Polyarticular

Newborn (< 1 week) Preferred Regimen High suspicion of MRSA ▸ Vancomycin 18 mg/kg IV divided q12h PLUS ▸ Cefotaxime 50 mg/kg IV q12h Low suspicion of MRSA ▸ Nafcillin 25 mg/kg q8h OR ▸ Oxacillin 25 mg/kg q8h PLUS ▸ Cefotaxime 50 mg/kg IV q12h Alternative Regimen (For low suspicion of MRSA) ▸ Clindamycin 5mg/kg q8h Newborn (1 - 4 weeks) Preferred Regimen High suspicion of MRSA ▸ Vancomycin 22 mg/kg q12h PLUS ▸ Cefotaxime 50 mg/kg IV q8h Low suspicion of MRSA ▸ Nafcillin 37 mg/kg q6h OR ▸ Oxacillin 37 mg/kg q6h PLUS ▸ Cefotaxime 50 mg/kg IV q8h Alternative Regimen (For low suspicion of MRSA) ▸ Clindamycin 5mg/kg q6h Infants (1- 3 months) Preferred Regimen High suspicion of MRSA ▸ Vancomycin 40 mg/kg/day divided q6-8h PLUS ▸ Cefotaxime 50 mg/kg IV q8h Low suspicion of MRSA ▸ Nafcillin 37 mg/kg q6h (max 8-12 g/day) OR ▸ Oxacillin 37 mg/kg q6h (max 8-12 g/day) PLUS ▸ Cefotaxime 50 mg/kg IV q8h Alternative Regimen (For low suspicion of MRSA) ▸ Clindamycin 7.5mg/kg q6h Children (3 mo - 14 yr) Preferred Regimen ▸ Vancomycin 40 mg/kg/day IV q6-8h PLUS ▸ Cefotaxime 50 mg/kg IV q8h Alternative Regimen ▸ Linezolid 10 mg/kg IV q8h OR ▸ Clindamycin 7.5 mg/kg IV q6h PLUS ▸ Aztreonam 30 mg/kg IV q6h Acute Monoarticular Preferred Regimen At risk for Gonococcal infection ▸ Ceftriaxone 1 g IV q24h OR ▸ Cefotaxime 1 g IV q8h OR ▸ Ceftizoxime 1 g IV q8h Not at risk for Gonococcal infection ▸ Vancomycin 15-20 mg/kg IV q8-12h PLUS ▸ Ceftriaxone 1g IV q24h OR ▸ Cefepime 2g IV q8h Alternative Regimen (If not at risk for Gonococcal infection) ▸ Vancomycin 15-20 mg/kg IV q8-12h PLUS ▸ Ciprofloxacin 400 mg IV q12h OR ▸ Levofloxacin 750 mg IV q24h Chronic Monoarticular Empirical therapy is not recommended. Treatment should be addressed for the specific etiology Polyarticular Preferred Regimen ▸ Ceftriaxone 1 gm IV q24h

Synovial Fluid Gram Stain-Based Therapy Adapted from Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases

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Gram-Positive   ▸  Gram-Positive Cocci   ▸  Gram-Positive Bacilli Gram-Negative   ▸  Gram-Negative Cocci   ▸  Gram-Negative Rods   ▸  Negative Gram Stain

Gram-Positive Cocci Preferred Regimen ▸ Vancomycin 15-20 mg/kg IV q8—12h (trough 15—20 μg/mL) Alternative Regimen (For patients allergic to vancomycin) ▸ Linezolid 600 mg PO/IV q12h OR ▸ Daptomycin 6 mg/kg IV q24h Gram-Positive Bacilli Preferred Regimen ▸ Penicillin G 2 MU IV q4h Alternative Regimen ▸ Vancomycin 15-20 mg/kg IV q8—12h (trough 15—20 μg/mL) OR ▸ Nafcillin 1.5-2 g IV q4h Gram-Negative Cocci Preferred Regimen ▸ Ceftriaxone 1 g IV q24h Gram-Negative Rods Preferred Regimen ▸ Ceftazidime 2 g IV q8h OR ▸ Cefepime 2g IV q12h OR ▸ Piperacillin-tazobactam 4.5 g q6h OR ▸ Imipenem 500 mg IV q6h OR ▸ Meropenem 1 g IV q8h Alternative Regimen (For patients allergic to cephalosporins) ▸ Aztreonam 2 g q8h OR ▸ Ciprofloxacin 400 mg IV q12h OR ▸ Levofloxacin 750 mg IV q24h Negative Gram Stain Preferred Regimen ▸ Vancomycin 15-20 mg/kg IV q8—12h PLUS ▸ Ceftazidime 2 g IV q8h Alternative Regimen ▸ Ciprofloxacin 750 mg IV q12h OR ▸ Levofloxacin 750 mg IV q24h OR ▸ Tobramycin 300mg q12h OR ▸ Gentamycin 5-7 mg/kg once daily or 5 mg/kg divided in 3 doses/day

Pathogen-Based Therapy — Bacteria Adapted from Bacterial septic arthritis in adults. and CLIN. MICROBIOL. REV. Acute Septic Arthritis

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Bacteria   ▸  Brucella   ▸  E. coli   ▸  Enterococcus spp.   ▸  Haemophilus influenzae   ▸  Neisseria gonorrhoeae   ▸  Proteus mirabilis   ▸  Pseudomonas aeruginosa   ▸  Staphylococcus aureus   ▸  Staphylococcus epidermidis   ▸  Streptococcus groups A, B, C, G   ▸  T. whipplei Mycobacteria   ▸  Mycobacterium tuberculosis Spirochetes   ▸  Borrelia burgdorferi   ▸  Treponema pallidum

Brucella Preferred Regimen ▸ Doxycycline 100 mg PO q12h x 6 weeks PLUS ▸ Streptomycin 1 g IM/IV q24h x 2-3 weeks OR ▸ Rifampin 600-900 mg q24h x 6 weeks Alternative Regimen ▸ Doxycycline 100 mg PO q12h x 6 weeks PLUS ▸ Gentamicin 5 mg/kg IM/IV x 7-10 days Adapted PLoS Med. Dec 2007; 4(12): e317. Staphylococcus aureus, Methicillin sensitive Preferred Regimen ▸ Nafcillin 1.5-2 g IV q4h OR ▸ Oxacillin 1.5-2 g IV q4h OR ▸ Cefazolin 1 g IV q8h OR ▸ Flucloxacillin 2 g IV q6h Alternative Regimen ▸ Dicloxacillin 500 mg PO q6h OR ▸ Cephalexin 500 mg PO q6h OR ▸ Clindamycin 300 mg PO q8h OR ▸ TMP-SMX 160/800 mg PO q12h Staphylococcus aureus, Methicillin resistant Preferred Regimen ▸ Vancomycin 15-20 mg/kg IV q8-12h Alternative Regimen ▸ Daptomycin 6 mg IV q24h OR ▸ Linezolid 600 mg IV/PO q12h Adapted from IDSA Guidelines for MRSA Staphylococcus epidermidis Preferred Regimen ▸ Nafcillin 1.5-2 g IV q4h OR ▸ Oxacillin 1.5-2 g IV q4h OR ▸ Cefazolin 1 g IV q8h Alternative Regimen Methicillin-resistant ▸ Vancomycin 15-20 mg/kg IV q8h|} Streptococcus groups A, B, C, G Preferred Regimen ▸ Penicillin G 20 MU IV q24h or divided in 6 doses/day OR ▸ Ceftriaxone 2 g IV or IM q24h OR ▸ Cefotaxime 2g IV q8h Alternative Regimen ▸ Vancomycin 15mg/kg IV q12h E. coli Preferred Regimen ▸Ampicillin sulbactam 3g IV q6h Alternative Regimen ▸ Cefazolin 1g IV q8 h OR ▸ Levofloxacin 750 mg IV q24h OR ▸ Gentamicin 3-5 mg/kg/day divided q8h OR ▸ Trimethoprim/sulfamethoxazole 160/800 mg PO q12h Pseudomonas aeruginosa Preferred Regimen ▸ Cefepime 2 g q12h OR ▸ Piperacillin 3 g q6h OR ▸ Imipenem 500mg q6h Alternative Regimen ▸ Ticarcillin-clavulanate OR ▸ Tobramycin 3-5 mg/kg/day divided q8h OR ▸ Amikacin OR ▸ Ciprofloxacin 400 mg IV q8h Neisseria gonorrhoeae Preferred Regimen ▸ Ceftriaxone 1 g IV q24h for 1-2 days after clinical improvement FOLLOWED BY ▸ Cefixime 400 mg po q12h for 1 week OR ▸ Ciprofloxacin 500 mg po q12h for 1 week OR ▸ Ofloxacin 400 mg PO q12h for 1 week Alternative Regimen ▸ Ciprofloxacin 400 mg IV q12h for 1-2 days after clinical improvement OR ▸ Ofloxacin 400 mg iv q12h for 1-2 days after clinical improvement OR ▸ Spectinomycin 2 g IM q12h for 1-2 days after clinical improvement FOLLOWED BY ▸ Ciprofloxacin 500 mg po q12h for 1 week OR ▸ Ofloxacin 400 mg po q12h for 1 week 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 Alternative Regimen ▸ Levofloxacin 750 mg IV/PO q24h OR ▸ Moxifloxacin 400 mg IV/PO q24h OR ▸ Clarithromycin 500 mg PO q12h Mycobacterium tuberculosis Intensive Phase ▸ Isoniazid 5mg/kg PO q24h for 2 months OR ▸ Isoniazid 10 mg/kg PO 3 times per week × 2 months PLUS ▸ Rifampicin 10 mg/kg PO q24h for 2 months OR ▸ Rifampicin 10 mg/kg PO 3 times per week × 2 months PLUS ▸ Pyrazinamide 25mg/kg PO q24h for 2 months OR ▸ Pyrazinamide 35 mg/kg PO 3 times per week × 2 months PLUS ▸ Ethambutol 15mg/kg PO q24h for 2 months Continuation Phase ▸ Isoniazid 5mg/kg PO for 4-7 months OR ▸ Isoniazid 10 mg/kg PO 3 times per week × 4-7 months PLUS ▸ Rifampicin 10 mg/kg PO q24h for 4-7 months OR ▸ Rifampicin 10 mg/kg PO 3 times per week for 4-7 months Adapted from Treatment of Tuberculosis: Guidelines. 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 Alternative Regimen ▸ 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 Adapted from IDSA Guidelines: The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Treponema pallidum Preferred Regimen ▸ Penicillin G 2.4 MU IM single dose Alternative Regimen ▸ Doxycycline 100 mg PO q12h x 14 days OR ▸ Tetracycline 500 mg PO q6h x 14 days OR ▸ Ceftriaxone 1 g IM/IV q24h x 10 -14 days Adapted from MMWR Recomm Rep. 2006;55(RR-11):1-94 T. whipplei Preferred Regimen ▸ Penicillin G 2 MU IV q4h for 2 weeks PLUS ▸ Streptomycin 1 g IM/IV q24h for 2 weeks FOLLOWED BY ▸ Trimethoprim/Sulfamethoxazole 160mg/800mg PO q24h for 1 year Alternative Regimen ▸ Ceftriaxone 2 g IV q24h FOLLOWED BY ▸ Trimethoprim/Sulfamethoxazole 160mg/800mg PO q24h for 1 year Adapted from N Engl J Med 2007; 356:55-66 Enterococcus spp. Preferred Regimen ▸ Ampicillin 2g IV q6h OR ▸ Vancomycin 1g q12h Alternative Regimen ▸ Ampicillin sulbactam 3g IV q6h OR ▸ Linezolid 600 mg IV/PO q12h Proteus mirabilis Preferred Regimen ▸ Ampicillin 2g IV q6h OR ▸ Levofloxacin 500 mg q24h Alternative Regimen ▸ Cefazolin 1g IV q8 h OR ▸ TMP-SMX 160/800 mg PO q12h

Pathogen-Based Therapy — Fungi

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Fungi   ▸  Aspergillus   ▸  Blastomyces   ▸  Candida spp.   ▸  Coccidioides   ▸  Histoplasma   ▸  Sporothrix

Aspergillus Preferred Regimen Loading Dose ▸ Voriconazole 6 mg/kg IV q12h for 24 h Maintenance Dose ▸ Voriconazole 4 mg/kg IV or 200 mg PO q12h for 9 months Alternative Regimen ▸ Liposomal Amphotericin B 3-5 mg/kg/day IV OR ▸ Amphotericin B lipid complex 5 mg/kg/day IV OR ▸ Caspofungin 70 mg IV loading dose, then 50 mg q24h OR ▸ Micafungin 100-150 mg IV q24h OR ▸ Itraconazole 600 mg/day for 3 days, then 400 mg/day Adapted from Clin Infect Dis. 2008; 46:327–60 Blastomyces Moderate Severe to Severe Disease ▸ Liposomal Amphotericin B 3-5 mg/kg/day IV × for 1-2 weeks OR ▸ Amphotericin B deoxycholate 0.7-1 mg/kg/day IV × 1-2 weeks FOLLOWED BY ▸ Itraconazole 200 mg PO q12h x 12 months Mild to Moderate Disease ▸ Itraconazole 200 mg PO q12-24h x 12 months Adapted from Clin Infect Dis. 2008;46(12):1801-12. Candida spp. Preferred Regimen ▸ Fluconazole 400mg PO q24h OR ▸ Liposomal Amphotericin B 3-5 mg/kg/day IV × for 2-3 weeks FOLLOWED BY ▸ Fluconazole 400mg PO q24h to complete a total duration of therapy of 6 weeks. Alternative Regimen ▸ Anidulafungin 200-mg loading dose, then 100 mg/day × 2 weeks OR ▸ Caspofungin 70 mg IV loading dose, then 50 mg q24h × 2 weeks OR ▸ Micafungin 100 mg IV q24h × 2 weeks OR ▸ Amphotericin B deoxycholate 0.5-1 mg/kg/day IV × 2 weeks FOLLOWED BY ▸ Fluconazole 400mg PO q24h to complete a total duration of therapy of 6 weeks. Adapted from Clin Infect Dis. 2009;48(5):503-35. Coccidioides Preferred Regimen ▸ Itraconazole 400-800 mg/day OR ▸ Fluconazole 400-2000 mg/day OR ▸ Ketoconazole 400 mg/day Alternative Regimen ▸ Amphotericin B 0.5–1.5 mg/kg/day Adapted from Clin Infect Dis. 2005;41(9):1217-23. Histoplasma capsulatum Preferred Regimen Moderate Severe to Severe Disease ▸ Liposomal Amphotericin B 3 mg/kg/day IV × 1-2 weeks OR ▸ Amphotericin B deoxycholate 0.7-1 mg/kg/day IV × 1-2 weeks OR ▸ Amphotericin B lipid complex 5 mg/kg/day IV × 1-2 weeks FOLLOWED BY ▸ Itraconazole 200 mg PO q12h x 12 months Mild to Moderate Disease ▸ Itraconazole 200 mg PO q12h x 12 months Adapted from Clin Infect Dis. 2007;45(7):807-25. Sporothrix Preferred Regimen ▸ Itraconazole 400 mg/day for at least 12 months

Pathogen-Based Therapy — Virus

The treatment for viral arthritis is symptomatic, with the use of analgesics and NSAID. No antimicrobial therapy is recommended for treating arthritis caused by a virus.
Vaccination and safe sex are the most important measures to avoid viral infections in the joint.

Pathogen-Based Therapy in Patients with Prosthetic Joint Adapted from Diagnosis and Management of Prosthetic Joint Infection CID 2013:56

▸ Click on the following categories to expand treatment regimens.

Bacteria   ▸  Staphylococci, oxacillin-susceptible   ▸  Staphylococci, oxacillin-resistant   ▸  Enterococcus spp, penicillin-susceptible   ▸  Enterococcus spp, penicillin-resistant   ▸  Pseudomonas aeruginosa   ▸  Enterobacter spp   ▸  Enterobacteriaceae   ▸  β-hemolytic streptococci   ▸  Propionibacterium acnes

Staphylococci, oxacillin-susceptible Preferred Regimen ▸ Nafcillin 1.5-2 g IV q4-6h OR ▸ Cefazolin 1–2 g IV q8 h OR ▸ Ceftriaxone 1–2 g IV q24h Alternative Regimen ▸ Vancomycin IV 15 mg/kg q12h OR ▸ Daptomycin 6 mg/kg IV q24h OR ▸ Linezolid 600 mg PO/IV q12h Staphylococci, oxacillin-resistant Preferred Regimen ▸ Vancomycin 15 mg/kg IV q12h Alternative Regimen ▸ Daptomycin 6 mg/kg IV q24h OR ▸ Linezolid 600 mg PO/IV q12h Enterococcus spp, penicillin-susceptible Preferred Regimen ▸ Penicillin G 20-40 MU IV q24h continuously or divided in 6 doses Alternative Regimen ▸ Vancomycin IV 15 mg/kg q12h OR ▸ Daptomycin 6 mg/kg IV q24h OR ▸ Linezolid 600 mg PO/IV q12h Enterococcus spp, penicillin-resistant Preferred Regimen ▸ Vancomycin IV 15 mg/kg q12h Alternative Regimen ▸ Daptomycin 6 mg/kg IV q24h OR ▸ Linezolid 600 mg PO/IV q12h Pseudomonas aeruginosa Preferred Regimen ▸ Cefepime 2 g IV q12 h OR ▸ Meropenem 1 g IV q8 h Alternative Regimen ▸ Ciprofloxacin 750 mg PO q12h or 400 mg IV q12h OR ▸ Ceftazidime 2 g IV q8h Enterobacter spp Preferred Regimen ▸ Cefepime 2 g IV q12h OR ▸ Ertapenem 1 g IV q24 h Alternative Regimen ▸ Ciprofloxacin 750 mg PO q12h or 400 mg IV q12h Enterobacteriaceae Preferred Regimen ▸ IV β-lactam based on in vitro susceptibilities OR ▸ Ciprofloxacin 750 mg PO q12h β-hemolytic streptococci Preferred Regimen ▸ Penicillin G 20-40 MU IV q24h continuously or divided in 6 doses OR ▸ Ceftriaxone 2 g IV q24h Alternative Regimen ▸ Vancomycin 15mg/kg IV q12h Propionibacterium acnes Preferred Regimen ▸ Penicillin G 20-40 MU IV q24h continuously or divided in 6 doses OR ▸ Ceftriaxone 2 g IV q24h Alternative Regimen ▸ Clindamycin 600–900 mg IV q8h OR ▸ Clindamycin300–450 mg PO q6h OR ▸ Vancomycin 15mg/kg IV q12h

References

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