Empiric Therapy of Bone and Joint Infections

Septic Arthritis/Bursitis (cont’d)

MSSA/MRSA = methicillin-sensitive/resistant S. aureus. Duration of therapy represents total time IV, PO, or IV + PO.. Most patients on IV therapy able to take PO meds should be switched to PO therapy after clinical improvement..

*Itraconazole solution provides more reliable absorption than capsules..

Acute Septic Arthritis/Bursitis

Clinical Presentation:  Acute joint pain with fever.. Septic joint unable to bear weight.. Septic bursitis presents with pain on joint motion, but patient is able to bear weight..

Diagnostic Considerations:  Diagnosis by demonstrating organisms in synovial fluid by stain/culture.. In septic bursitis (knee most common), there is pain on joint flexion (although the joint can bear weight), and synovial fluid findings are negative for septic arthritis.. Except for N.. gonorrhoeae, polyarthritis is not usually due to bacterial pathogens.. Post-infectious polyarthritis is usually viral in origin, most commonly due to parvovirus B19, rubella, or HBV..

C.. trachomatis, or C.. difficile infections.. Synovial fluid cultures are negative.. Reactive arthritis is usually asymmetrical and is monoarticular/oligoarticular..

Therapeutic Considerations:  See specific pathogen, below.. Treat septic bursitis as septic arthritis..

Staphylococcus aureus (MSSA/MRSA)

Diagnostic Considerations:  Painful hot joint; unable to bear weight.. Diagnosis by synovial fluid pleocytosis and positive culture for joint pathogen.. Examine synovial fluid to rule out gout (doubly birefringent crystals) and pseudogout (calcium pyrophosphate crystals).. May occur in setting of endocarditis with septic emboli to joints; other manifestations of endocarditis are usually evident..

Pitfalls:  Rule out causes of noninfectious arthritis (sarcoidosis, Whipple’s disease, EhlersDanlos, etc. .), which are less severe, but may mimic septic arthritis. . In reactive arthritis following urethritis (C.. trachomatis, Ureaplasma urealyticum, N.. gonorrhoeae) or diarrhea (Shigella, Campylobacter, Yersinia, Salmonella), synovial fluid culture is negative, and synovial fluid WBCs counts are usually < 10,000/mm3 with normal synovial fluid lactic acid and glucose.. Do not overlook infective endocarditis­ in mono/polyarticular MSSA/MRSA septic arthritis without apparent source..

Therapeutic Considerations:  For MRSA septic arthritis, vancomycin penetration into synovial fluid is poor; use linezolid instead.. Immobilization of infected joint during therapy is helpful.. Local installation of antibiotics into synovial fluid has no advantage over IV/PO antibiotics..

Prognosis:  Treat as early as possible to minimize joint damage.. Repeated aspiration/open drainage may be needed to preserve joint function..

Group A, B, C, G Streptococci

Diagnostic Considerations:  Usually monoarticular.. Not usually due to septic emboli from endocarditis.. Prognosis:  Related to extent of joint damage and rapidity of antibiotic treatment..

Enterobacteriaceae

Diagnostic Considerations:  Diagnosis by isolation of gram-negative bacilli from synovial fluid.. Pitfalls:  Septic arthritis involving an unusual joint (e..g.., sternoclavicular, sacral) should suggest IV drug abuse until proven otherwise..

Therapeutic Considerations:  Joint aspiration is essential in suspected septic arthritis of the hip and may be needed for other joints; obtain orthopedic surgery consult.. Local installation of antibiotics into joint fluid is of no proven value..

Prognosis:  Related to extent of joint damage and rapidity of antibiotic treatment..

Pseudomonas aeruginosa

Diagnostic Considerations  P. . aeruginosa septic arthritis/osteomyelitis may occur after water contaminated puncture wound (e..g.., nail puncture of heel through shoes).. Sternoclavicular/sacroiliac joint involvement is common in IV drug abusers (IVDAs)..

Pitfalls:  Suspect IVDA in P.. aeruginosa septic arthritis without a history of trauma..

Therapeutic Considerations:  If ciprofloxacin is used, treat with 750 mg (not 500 mg) dose for P.. aeruginosa septic arthritis/osteomyelitis..

Prognosis:  Related to extent of joint damage and rapidity of antibiotic treatment..

Neisseria gonorrhoeae

Diagnostic Considerations:  Gonococcal arthritis may present as a monoarticular arthritis, or multiple joints may be affected as part of gonococcal arthritis-dermatitis syndrome (disseminated gonococcal infection).. Bacteremia with positive blood cultures occurs early during rash stage while synovial fluid cultures are negative.. Joint involvement follows with typical findings of septic arthritis and synovial fluid cultures positive for N.. gonorrhoeae; blood cultures are negative at this stage.. Acute tenosynovitis is often a clue to gonococcal septic arthritis..

Pitfalls:  Spectinomycin is ineffective against pharyngeal gonorrhea..

Therapeutic Considerations:  Gonococcal arthritis-dermatitis syndrome is caused by very susceptible strains of N.. gonorrhoeae.. Cephalosporins also eliminate incubating syphilis..

Prognosis:  Excellent with arthritis-dermatitis syndrome; worse with only monoarticular arthritis..

Salmonella sp.

Diagnostic Considerations:  Occurs in sickle cell disease and hemoglobinopathies. . Diagnosis by blood/joint cultures..

Pitfalls:  S.. aureus, not Salmonella, is the most common cause of septic arthritis in sickle cell disease.. Prognosis:  Related to severity of infection and underlying health of host..

Septic Arthritis Secondary to Animal Bite Wound

Clinical Presentation:  Penetrating bite wound into joint space..

Diagnostic Considerations:  Diagnosis by smear/culture of synovial fluid/blood cultures.. Pitfalls:  May develop metastatic infection from bacteremia..

Therapeutic Considerations:  Treat for at least 2 weeks of combined IV/PO therapy.. Prognosis:  Related to severity of infection and underlying health of host..

Chronic Septic Arthritis

Clinical Presentation:  Subacute/chronic joint pain with decreased range of motion and little or no fever.. Able to bear weight on joint..

Diagnostic Considerations:  Diagnosis by smear/culture of synovial fluid/synovial biopsy..

Coccidioides immitis

Diagnostic Considerations:  Must grow organisms from synovium/synovial fluid for diagnosis.. Pitfalls:  Synovial fluid the same as in TB (lymphocytic pleocytosis, low glucose, increased protein).. Therapeutic Considerations:  Oral therapy is preferred; same cure rates as amphotericin regimens.. HIV patients need life-long suppressive therapy..

Prognosis:  Related to severity of infection and underlying health of host..

Sporothrix schenckii

Diagnostic Considerations:  Usually a monoarticular infection secondary to direct inoculation/trauma. Pitfalls:  Polyarticular arthritis suggests disseminated infection..

Therapeutic Considerations:  SSKI is useful for lymphocutaneous sporotrichosis, not bone/joint involvement..

Prognosis:  Excellent for localized disease (e..g.., lymphocutaneous sporotrichosis).. In disseminated disease, prognosis is related to host factors..

Mycobacterium tuberculosis (TB)

Diagnostic Considerations:  Clue is subacute/chronic tenosynovitis over involved joint.. Unlike other forms of septic arthritis, which are usually due to hematogenous spread, TB arthritis may complicate adjacent TB osteomyelitis. . Synovial fluid findings include lymphocytic pleocytosis, low glucose, and increased protein..

Pitfalls:  Send synovial biopsy for AFB smear/culture in unexplained chronic monoarticular arthritis.. Therapeutic Considerations:  TB arthritis is usually treated for 6–9 months..

Prognosis:  Related to severity of infection and underlying health of host..

Lyme Disease*/Lyme Arthritis

Duration of therapy represents total time IV, PO, or IV + PO.. Most patients on IV therapy able to take PO meds should be switched to PO therapy after clinical improvement..

* See p.. 21 for Lyme neuroborreliosis and p.. 78 for Lyme myocarditis..

†Doxycycline therapy × 10 days as effective as 2 weeks..

‡For adult patients intolerant of Amoxicillin, Doxycycline, and Cefuroxime axetil, Azithromycin (500 mg orally per day for 7–10 days), Clarithromycin (500 mg orally twice per day for 14–21 days, if the patient is not pregnant), or Erythromycin (500 mg orally 4 times per day for 14–21 days) may be given.. The recommended dosages of these agents for children are as follows: Azithromycin, 10 mg/kg per day (maximum of 500 mg per day); Clarithromycin, 7..5 mg/kg twice per day (maximum of 500 mg per dose); and Erythromycin, 12..5 mg/kg 4 times per day (maximum of 500 mg per dose)..

Lyme Disease

Clinical Presentation:  Presents acutely with local or disseminated disease following bite of tick infected with Borrelia.. Erythema migrans (annular lesion with central clearing) occurs in ~ 75% within 2 weeks of tick bite and may be associated with fever, headache, arthralgias/myalgias, meningismus.. Other possible acute manifestations include aseptic meningitis, Bell’s palsy, peripheral neuropathy, mild hepatitis, or heart block.. Chronic disease may present with arthritis, peripheral neuropathy, or acrodermatitis chronica atrophicans (usually > 10 years after infection)..

Diagnostic Considerations:  Diagnosis by clinical presentation plus elevated IgM Lyme titers.. If the IgM ELISA Lyme titer is borderline or suspected to be a false-positive, obtain an IgM Western blot to confirm the diagnosis.. False negative early IgM titers are common.. IgM cross-reactivity common with EBV, CMV.. After ruling out EBV/CMV, retest for Lyme disease IgM and IgG by ELISA/immunoblot 4 weeks later (false + IgM titers revert to negative).. IgM titers may take 4–6 weeks to increase after tick bite..

Pitfalls:  Rash is not always seen, and tick bite often goes unnoticed (tick often spontaneously falls off after 1–2 days of feeding).. Do not overlook Lyme disease in patients with ­sudden unexplained heart block in areas where Ixodes ticks are endemic..

Therapeutic Considerations:  B.. burgdorferi is highly susceptible to all beta-lactams.. For Bell’s palsy or neuroborreliosis, minocycline (100 mg PO q12h ×2 weeks) may be preferred to doxycycline.. Highest failure rates with macrolide therapy.. Symptoms may persist for 1 year or more after adequate therapy.. No rationale to re-treat persistent symptoms..

Prognosis:  Excellent in normal hosts..

Lyme Arthritis

Clinical Presentation:  Acute Lyme arthritis presents with joint pain, decreased range of motion, ability to bear weight on joint, and little or no fever.. Chronic Lyme arthritis resembles rheumatoid arthritis.. Diagnostic Considerations:  Usually affects children and large weight-bearing joints (e..g.., knee).. Acute Lyme arthritis is diagnosed by clinical presentation plus elevated IgM Lyme titer.. Chronic Lyme arthritis is suggested by rheumatoid arthritis-like presentation with negative ANA and rheumatoid factor, and positive IgG Lyme titer and synovial fluid PCR..

Pitfalls:  Acute Lyme arthritis joint is red but not hot, in contrast to septic arthritis.. In chronic Lyme arthritis, a negative IgG Lyme titer essentially rules out chronic Lyme arthritis, but an elevated IgG Lyme titer indicates only past exposure to B.. burgdorferi and is not diagnostic of Lyme arthritis.. Joint fluid in chronic Lyme disease is usually negative by culture, but positive by PCR; synovial fluid PCR, however, does not differentiate active from prior infection..

Therapeutic Considerations:  IgG Lyme titers remain elevated for life, and do not decrease with treatment.. Joint symptoms often persist for months/years after effective antibiotic therapy due to autoimmune joint inflammation; treat with anti-inflammatory drugs, not repeat antibiotic courses.. Oral therapy as effective as IV therapy..

Prognosis:  Good in normal hosts.. Chronic/refractory arthritis may develop in genetically predisposed patients with DRW 2/4 HLA types..

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Infected Joint Prosthesis

MRSA/MSSA = methicillin-resistant/sensitive S. aureus; MSSE/MRSE = methicillin-sensitive/resistant S. epidermidis­.

Duration of therapy represents total time IV or IV + PO.. Most patients on IV therapy able to take PO meds should be switched to PO therapy after clinical improvement..

* Treat for 1 week after joint prosthesis is replaced..

†Only if MSSE strain susceptible..

Clinical Presentation:  Pain in area of prosthesis with joint loosening/instability ± low-grade fevers.. Diagnostic Considerations:  Infected prosthesis is suggested by prosthetic loosening/lucent areas adjacent to prosthesis on plain films ± positive blood cultures.. Diagnosis confirmed by bone scan.. Use joint aspiration to identify organism..

Pitfalls:  An elevated ESR with prosthetic loosening suggests prosthetic joint infection.. Mechanical loosening without infection is comon many years after joint replacement, but ESR is normal..

Therapeutic Considerations:  Infected prosthetic joints usually must be removed for cure.. Replacement prosthesis may be inserted anytime after infected prosthesis is removed. . To prevent infection of new joint prosthesis, extensive debridement of old infected material is important.. If replacement of

infected joint prosthesis is not possible, chronic suppressive therapy may be used with oral antibiotics e..g.., minocycline 100 mg (PO) q12h.. TMP–SMX 5 mg/kg (PO) q6h may be successful in long-term suppression/cure in total hip replacement (treat × 6 months) or total knee replacement (treat × 9 months) due to susceptible strains of MSSA/MSSE; adding rifampin 300 mg (PO) q12h may be helpful..

Prognosis:  Related to adequate debridement of infected material when prosthetic joint is removed..

Osteomyelitis

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Osteomyelitis (cont’d)

Osteomyelitis (cont’d)

MSSA/MRSA = methicillin-sensitive/resistant S.. aureus.. Duration of therapy represents total time IV, PO, or IV + PO.. Most patients on IV therapy able to take PO meds should be switched to PO therapy soon after clinical improvement..

* Treat for 1 week after adequate debridement or amputation..

†Moxifloxacin 400 mg or Levofloxacin 500 mg..

Acute Osteomyelitis

Clinical Presentation:  Tenderness over infected bone.. Fever and positive blood cultures common.. Diagnostic Considerations:  Diagnosis by elevated ESR with positive bone scan.. Bone biopsy is not needed for diagnosis.. Bone scan is positive for acute osteomyelitis in first 24 hours..

Pitfalls:  Earliest sign on plain films is soft tissue swelling; bony changes evident after 2 weeks.. Therapeutic Considerations:  Treat 4–6 weeks with antibiotics.. Debridement is not necessary for cure.. Prognosis:  Related to adequacy/promptness of treatment..

Chronic Osteomyelitis

Diabetes Mellitus

Clinical Presentation:  Afebrile or low-grade fever with normal WBC counts and deep penetrating ulcers ± draining sinus tracts..

Diagnostic Considerations:  Diagnosis by elevated ESR and bone changes on plain films.. Bone scan is not needed for diagnosis.. Bone biopsy is preferred method of demonstrating organisms, since blood cultures are usually negative and cultures from ulcers/sinus tracts are unreliable..

Pitfalls:  P.. aeruginosa is a common colonizer and frequently cultured from deep ulcers/sinus tracts, but is not a pathogen in chronic osteomyelitis in diabetics..

Therapeutic Considerations:  Surgical debridement is needed for cure; antibiotics alone are ineffective.. Revascularization procedures usually do not help, since diabetes is a microvascular disease.. Do not culture penetrating foot ulcers/draining sinus tracts; culture results reflect superficial flora.. Bone biopsy during debridement is the best way to identify pathogen; if biopsy not possible, treat empirically..

Prognosis:  Related to adequacy of blood supply/surgical debridement..