Empiric Therapy Regimens
Removal and replacement of an infected prosthetic joint is required, with the possible exception of those cases of prosthetic joint infection (PJI) that are recognized within 30 days of implantation, are without evidence of significant peri-prosthetic involvement, and have a high likelihood to respond to simple debridement combined with antibiotic therapy (70-90%). This response progresssively lessens past this point. Please see Septic Arthritis.
Empiric therapeutic regimens for septic arthritis of prosthetic joints, or peri-prosthetic joint infection (PJI), have been based primarily on physical findings, history, and in particular, the results of the Gram stain of synovial fluid.The most common pathogens are MSSA, MRSA, CoNS, coliforms, and N gonorrhea. [1, 2, 3, 4, 5, 6, 7, 8] Inadequate initial treatment often results in unsatisfactory outcomes because of continued bone and tissue damage brought about by unchecked infection.
Candida auris has rapidly become a significant nosocomial infection due to its high transmissibility between patients and care givers, resistance to most antifunngal medications, and its potentiation by concurrent COVID-19 infection. [9]
It is challenging to differentiate aseptic loosening of prosthetic joints from low-grade chronic periprosthetic joint infections. In such cases, debridement and measurement of circulating biomarkers, including various blood tests for bacterial DNA, hold promise in making these determinations. The specificity of procalcitonin measurements is low in these situations (27.8%). The combination of a C-reactive protein (CRP) level [10] greater than 0.3 mg/dL and IL-6 level greater than 5.12 pg/mL is superior, with a sensitivity of 75% and specificity of 98.2% in high-risk patients. [11, 12]
General recommendations
Cultures of blood, synovial fluid, and, if possible, periprosthetic tissue, should be obtained before initiating antibiotic therapy for PJI. [13]
Response to antibiotic therapy should be monitored by measuring the response of inflammatory markers such as CRP, procalcitonin, and erythrocyte sedimentation rate (ESR). [14] It is important to remember that the in vitro culture and sensitivity results obtained at the beginning of infection do not reflect the actual activity of the anticrobial agent. It is increasingly recognized that ongoing inflammation can significantly blunt activity of the medication. If the patient is not responding, repeat cultures of blood, drainage, and tissue should be performed.
Duration of total antibiotic therapy is at least 6 wks extended to 12 weeks. At least 10 days of such should be given parenterally. Essentially, such therapy should be continue until cultures and inflammatory markers have normalized.
Ongoing suppressive antibiotic therapy is indicated when not all the infected prosthetic material and surrounding bone and soft tissue can be removed.
Rifampin 600 mg PO q24h should be added for staphylococcal infections whenever infected prosthetic material is retained. To prevent the development of resistance to it, rifampin should be started 2 days after initiation of the other antibiotic agents. [1, 2, 3, 4] The primary purpose of these other agents is to prevent the development of resistance by the infecting microbe.
For coverage of MSSA, MRSA, CoNS, and E faecalis, vancomycin commonly is begun at 15 mg/kg IV q12h in those with normal renal function. Vancomycin has lost a good deal of effectiveness against these pathogens. In seriously ill patients with renal sufficiency, it is challenging to reach an adequate therapeutic level (5-12 µg/ML). In addition, MRSA, MSSA, CoNS, and E faecalis have developed varying degrees of resistance. [8, 15, 16]
The author recommends the use of linezolid for empiric coverage of all streptococci, MSSA, MRSA, and most isolates of CoNS. When given longer than 2 weeks, significant hematologic side effects may occur, including thrombocytopenia, pancytopenia, leukopenia, and anemia, as well as peripheral neuropathies.
Ceftriaxone provides coverage against gram-negative enterics, as well as N gonorrhea and a large variety of streptococci. The author's usual empiric coverage for patients with PJI would be a combination of ceftriaxone and linezolid.
Daptomycin is effective against aerobic gram-positive organisms such as MSSA, MRSA, CoNS, VSE,and VRE. Previous treatment with vancomyin can markedly reduce its effectiveness. Addition of nafcillin or ampicillin lowers the daptomycin MIC versus S Aureus and enterococci, respectively.
Minocycline provides good coverage against MRSA, VRE, and enteric organisms.
Aztreonam is useful in covering gram-negative aerobes in those with severe beta-lactam allergies. [17, 18]
Ecinocandins, such as capsofungin, exhibit the lowest rate of resistance to Candida auris. Such may develop during prolonged treatment.
