Septic Arthritis Medication

Updated: Dec 09, 2022
  • Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD  more...
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Medication Summary

The empiric choice of antibiotic therapy is based on results of the Gram stain, the clinical picture, and the medical background of the patient. When the Gram stain fails to reveal any microorganisms (40-50% of cases), the individual's age and sexual activity become the major determinants to differentiate gonococcal from nongonococcal arthritis. When there is no evidence supporting any extra-articular infection, antibiotics must cover S aureus, streptococcal species, and gonococci (in patients who are sexually active). Synovial fluid examination may be helpful in approximately 50% of cases. Because of the significant adverse consequences of inadequate therapy, the author empirically covers for the presence of MSSA, MRSA, CoNS, N gonnorhea, and gram-negative aerobes. A typical combination would be ceftriaxone and vancomycin. In the presence of implanted material, rifampin should be added because of its unique ability to penetrate the biofilms of infected prosthetic devices. [53, 54, 55]  

Evidence exists that earlier initiation of an appropriate antibiotic regimen produces better functional results. Generally, treatment is administered intravenously for 3 to 4 weeks. The major exception to this is gonococcal infection, for which total therapy is approximately 2 weeks with an eventual switch to oral therapy.

No indication exists for direct installation of antibiotics into the joint cavity. Such a practice may increase the inflammatory surge that can add to permanent joint damage.

The following section presents antibiotics frequently used by the author. [56]

Documenting the efficacy of the antibiotic regimen by serial improvement and eventual normalization of inflammatory markers is key in managing PJI.

Please see the following articles on empiric and organism-specific therapy of native and prosthetic septic arthritis for more detailed discussion of antibiotic choices as well as dosing strategies:

Septic Arthritis of Native Joints Empiric TherapySeptic Arthritis of Native Joints Organism-Specific TherapySeptic Arthritis of Prosthetic Joints Empiric Therapy; and Septic Arthritis of Prosthetic Joints Organism-Specific Therapy.




Ciprofloxacin (Cipro)

Ciprofloxacin is an alternative antibiotic to ceftriaxone to treat N gonorrhoeae and gram-negative enteric rods.

Linezolid (Zyvox)

Linezolid is an alternative antibiotic that is used in patients allergic to vancomycin and for the treatment of vancomycin-resistant enterococci.


Oxacillin and nafcillin are bactericidal semisynthetic penicillins that inhibit cell wall synthesis. Useful against methicillin-sensitive S aureus (MSSA). Nafcillin has the advantage in not requiring adjustment in renal failure and does not lead to leukopenia and thrombocytopenia with prolonged usage.

Dalbavancin (Dalvance)

The prolonged half-life (360 hours) allows weekly dosing of dalbavancin. In addition, its effectiveness against gram-positive cocci, including biofilm producers, makes it a very desirable agent for the outpatient treatment of native and prosthetic joint infections.


Cephalosporins, 3rd Generation

Cefixime (Suprax)

Cefixime is a third-generation oral cephalosporin with broad activity against gram-negative bacteria. By binding to one or more of the penicillin-binding proteins, this agent arrests bacterial cell wall synthesis and inhibits bacterial growth.

Oral cefixime is used as a follow-up to intravenous (IV) ceftriaxone to treat N gonorrhoeae.


Cephalosporin with long half-life effective against essentially all the gram-negative and enteric organisms involved in SA.




Linezolid is effective against many positive pathogens including MSSA, MRSA, VSE, VRE. Serum levels are essentially equal whether given either by oral or intravenous administration. Dosing does not need to be adjusted according to renal function. Side effects include potential severe hepatotoxicity. After 2 weeks of administration, the risk for severe leukopenia and thrombocytopenia and various types of neuropathy markedly increase.



Vancomycin (Vancocin)

Vancomycin is an anti-infective agent used against MSSA, MRSA, methicillin-resistant CoNS, and ampicillin-resistant enterococci, and in patients allergic to penicillin. It is key to ensure that therapeutic serum levels have been achieved (trough level 5-12mcg/ml). In the face of fluctuating renal function, this may be an impossible task. Switching to linezolid is advisable.



Daptomycin (Cubicin)

Prior vancomycin administration may induce resistance to this medication.

Concurrent use of nafcillin or ampicillin may potentiate its bactericidal effect. 

Dosing may range from 4mg/kg -12mg/kg per 24 hrs.





Rifampin is used in combination with other drugs. It inhibits RNA synthesis in bacteria by binding to the beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription. It has the unique ability to penetrate the protective biofilms of S aureus and CoNS that form on prosthetic material. It is essential in treating Staphylococcal infections. Many pathogens rapidly develop resistance to it; 2 appropriate antibiotics should be administered several days before starting rifampin and to protect the rifampin. They should be continued throughout the course of rifampin.


Fourth generation cephalosporin

Class Summary

Cefepime is effective against enterococcal streptococci, MSSA, CoNS, and most aerobic gram negatives including Pseudomonas. It is not effective against ESBL producers.



Class Summary

Minocycline doxycycline