Septic Arthritis of Native Joints Empiric Therapy

Updated: Dec 12, 2022
  • Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD  more...
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Empiric Therapy Regimens

Empiric antibiotic therapy of septic arthritis of native joints(SA) has been guided primarily by the findings of the Gram staining of synovial fluid. The sensitivity of the Gram stain ranges from 30-50%. [1]  Examination of the joint fluid typically shows marked leukocytosis often greater than 50,000/ML; low glucose levels; and lack of crystals. The Gram stain is positive in less than 50% of cases. When the Gram stain is negative and there are no crystals apparent, it may be reasonable to withhold antibiotics and treat for a crystalline arthritis, unless there is a significant potential source of bacteremia such as a urinary tract infection or the patient exhibits significant systemic deterioration. In this situation, measurement of pro calcitonin and CRP may be helpful. The Gram stain is positive in less than 50% of cases. Most commonly encountered pathogens of SA may take up to 1 to 2 days to grow out and be identified on solid media. Results of antibiotic sensitivity testing require at least 72 more hours. Newer methods, such as the Maldi-Tof technique, when combined with the Phoenix M50 system, have considerably shortened the turnaround time of organism identification (from 48 to 28 hrs) and antibiotic sensitivity results (from 72 to 50.3 hrs). [2]

The COVID-19 pandemic has triggered secondary pandemics such as a significant increase in opioid abuse and its various infectious complications, in part due to the effects of social isolation. Patients have avoided seeking treatment of a variety of diseases out of fear of contracting the viruse from a variety of healthcare settings. There has been a significant increase in the use of antibiotics in both community and inpatient settings. This overuse may rise from the unfamiliarity with the proper use of antibiotics in the febrile individual with COVID. In addition, there has been a marked increase in MRSA infections and resistant P aeruginosa. [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]

The usefulness of vancomycin is being challenged for several reasons: 1) the ability to acheive therapeutic levels (peak level 25-40mcg/ml and trough levels 5-12mcg/ml) may be extremely difficult to achieve in the seriously ill patient with fluctuating renal function; and 2) the prevalence of resistance of Gram-positive cocci to it has increased. The author would advocate use of linezolid or daptomycin instead. For further discussion please refer to Medscape reference article Septic Arthritis.

Gram stain negative or unavailable 

Diagnosis of the septic joint is particularly challenging in patients with underlying inflammatory disease, such as rheumatoid arthritis or SLE, and a negative Gram stain. [11] In these cases, measurement of serum procalcitonin (PCT) should be considered. [12] This test appears to be more useful in ruling in than in excluding the diagnosis of septic arthritis because the specificity of PCT is quite low. There is growing interest in the usefulness of C-reactive protein (CRP) in documenting a therapeutic response to empirically prescribed antimicrobial through serial measurements. [13]

Medications given when Gram stain results are negative or unavailable include the following [14, 15] :


Gram-positive cocci in clusters

The following medications are given for Gram-positive cocci in clusters:

  • Linezolid 600 mg IV q12hr or
  •  Daptomycin 6mg /kg - 12mg /kg 

Gram-positive cocci in chains

The following medications are given for Gram-positive cocci in chains:

Gram-negative cocci

The following medications are given for Gram-negative cocci:

  • Ceftriaxone 1 g IV q24h or

  • Ciprofloxacin 400 mg IV or 500 mg PO q12h (only if susceptibility testing will be available)

Gram-negative rods

The following medications are given for Gram-negative rods:

  • Ceftriaxone 2 g IV q24h or

  • Cefepime 2 g IV q8h or

  • Piperacillin-tazobactam 3.375-4.5 g IV q6-8h or

  • Aztreonam 1-2 g IV q8h or

  • Ciprofloxacin 400 mg IV or 750 mg PO q12h or

  • Levofloxacin 750 mg IV or PO q24h

  • Daptomycin 6mg/kg -12mg /kg every 24 hr. The dose should be determined by the severity of illness and the patient's clinical responsiveness. Recent exposure to vancomycin may induce partial resistance daptomycin. Such would support the 12mg/kg dosage regimen