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学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

人工関節感染 治療

人工関節感染 再手術 後の感染について整形外科医とディスカッション。

血液培養や関節液などから、細菌検出せず、心不全も合併する難しい症例



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SUMMARY AND RECOMMENDATIONS

Treatment of prosthetic joint infections (PJIs) involves both surgery and antimicrobial therapy. The type of surgery and the antimicrobial regimen depend on the timing of infection, the etiologic organism, and other individual patient circumstances.

The majority of delayed-onset and late-onset infections require resection arthroplasty; two-stage procedures are associated with highest success rates and are the most common procedures performed in the United States. 

A two-stage exchange consists of prosthesis resection, debridement of soft tissue and bone, and placement of a spacer. Subsequently, a prolonged course of antimicrobial therapy is administered, after which a new prosthesis is implanted. Some favor proceeding directly with implantation of a new prosthesis following completion of antimicrobials if there are no clinical signs of infection, while others favor an observation period of two to eight weeks off of antimicrobials prior to implantation of a new prosthesis, with repeat culture to assess sterilization of the joint space.

A one-stage exchange consists of prosthesis resection, debridement of soft tissue and bone, and reimplantation of new hardware during the same surgery. Antimicrobial management for one-stage exchange consists of prolonged initial therapy, followed by antibiotic suppression in some cases. 

Debridement and retention of prosthesis may be appropriate in the setting of early-onset PJI or in acute cases of PJI. Antimicrobial therapy consists of prolonged initial therapy followed by oral antimicrobial suppression in some cases. 

The approach to selection of antimicrobial therapy depends on culture and in vitro susceptibility data.


CHOICE OF ANTIBIOTIC THERAPY

The goal of antimicrobial therapy in patients with prosthetic joint infections (PJIs) is to cure or control the infectious process. There is a paucity of randomized controlled trials that have evaluated the efficacy of antimicrobial therapy in patients with PJIs. The literature on this issue mostly consists of retrospective case series in which widely different regimens and durations of therapy are reported.

Empiric antibiotic therapy

In general, it is preferable to delay antibiotic therapy until specimens for culture are obtained by joint aspiration, joint debridement, and/or prosthesis removal. In rare cases, administration of empiric antibiotic therapy may be justified for patients with PJI who present with sepsis or are otherwise too unstable to wait for culture data to guide therapy. In such cases, empiric antimicrobial therapy should include coverage against staphylococci (including methicillin-resistant strains) and aerobic gram-negative bacilli (ie, vancomycin and cefepime). Subsequently, antibiotic therapy should be adjusted to the results of culture and in vitro susceptibility.

Pathogen-specific antibiotic therapy 

Most patients treated with one- or two-stage surgery, debridement surgery, or resection arthroplasty without delayed reimplantation require a four- to six-week course of pathogen-directed parenteral antibiotic antimicrobial therapy or highly oral bioavailable agent following surgery. In patients treated with debridement and retention, parenteral antimicrobial therapy is typically followed by a long-term course of oral antimicrobial therapy when possible, the duration of which varies and is dependent on several factors.

Staphylococci 

  • Nafcillin or oxacillin (2 g intravenously every four to six hours) is the most effective therapy against methicillin-sensitive S. aureus (MSSA). 
  • Cefazolin (1 to 2 g intravenously every eight hours) may be used as an alternative agent. Retrospective data suggests that ceftriaxone (2 g intravenously every 24 hours) may be as effective as other anti-staphylococcal beta-lactams for treatment of oxacillin-susceptible staphylococcal PJIs. 
  • For outpatient antimicrobial therapy in hospitalized patients started on an anti-staphylococcal semisynthetic penicillin (such as methicillin, nafcillin, or oxacillin), treatment can be continued via infusion pump; alternatively, administration of a cephalosporin with less frequent dosing may allow greater convenience. 
  • In one retrospective study, outpatient treatment of serious MSSA infections with cefazolin was associated with fewer drug emergent effects (12 versus 31 percent) and premature discontinuations (7 versus 34 percent) compared with nafcillin.
  • Patients with an MSSA infection and a history of type I allergy (anaphylaxis) to penicillin can be treated with either clindamycin (900 mg intravenously every eight hours) or vancomycin (15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose).

Methicillin-resistant S. aureus (MRSA) infection should be treated with vancomycin; daptomycin, linezolid, or telavancin can be used as alternative agents.
Treatment regimens for coagulase-negative staphylococci (CoNS) are identical to those for S. aureus. However, most strains of CoNS that cause PJI are methicillin resistant.
  • Combination therapy with rifampin (300 to 450 mg orally twice daily or 600 mg once daily) is used in the setting of staphylococcal PJI treated with debridement and retention of the prosthesis and/or in the setting of one-stage arthroplasty.

Streptococci (beta-hemolytic)

  • The treatment of choice for streptococcal PJI is penicillin (12 to 18 million units/day in four divided doses) or ampicillin (2 g every six hours) . 
  • Ceftriaxone (1 to 2 g intravenously every 24 hours) is an equally acceptable agent and is favored for dosing convenience in the outpatient setting. 
  • Patients allergic to penicillin may be treated with clindamycin (900 mg intravenously every eight hours) or vancomycin (15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose).

The outcome of PJI due to penicillin-susceptible streptococci treated with debridement and prolonged antibiotic therapy is generally good. In one retrospective series, the cumulative risk of relapse in patients who underwent debridement early after onset of symptoms was 11 percent.

Enterococci

Enterococcal PJIs are rare. Selection of antibiotic therapy should be tailored to susceptibility results. In a retrospective review of 47 patients, there was no difference in outcome between patients receiving combination and those receiving monotherapy. 

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Gram-negative bacilli

Gram-negative bacilli cause 15 percent of all first-time episodes of PJIs. Patients with gram-negative infections tended to be older, to develop infections earlier after surgery, and may have worse outcomes with prolonged antibiotic therapy and debridement than patients with PJI due to gram-positive organisms.

  • Gram-negative bacilli that are susceptible to fluoroquinolones can usually be treated orally with an agent, such as ciprofloxacin (500 to 750 mg twice daily). PJIs due to P. aeruginosa are difficult to cure even with debridement and prosthesis removal. One of the following regimens may be used:
  • Cefepime 2 g intravenously every 12 hours (preferred)
  • Meropenem 1 g intravenously every 8 hours (preferred)
  • Ciprofloxacin 750 mg orally every 12 hours (alternative)
  • Ceftazidime 2 g intravenously every 8 hours (alternative)

Anaerobes

Prosthetic hip or knee infections due to anaerobes are relatively uncommon; shoulder infections due to Propionibacterium acnes are the most common presentation of anaerobic PJI. 
  • Options for treatment of infection due to P. acnes include penicillin (24 million units intravenously every 24 hours given in six equally divided doses or as continuous infusion) or ceftriaxone (1 to 2 g intravenously once daily). 
  • Vancomycin and clindamycin are also active against most Propionibacterium acnes isolates. Metronidazole (500 mg orally three times a day) may be used for other types of anaerobic infections that are susceptible to this agent.

Mycobacterium tuberculosis 

PJIs due to Mycobacterium tuberculosis can sometimes be cured without joint removal if the infection is recognized early. 

  • The optimal duration of therapy for treatment of musculoskeletal tuberculosis is uncertain. For patients receiving treatment with first-line agents in the absence of extensive or advanced disease, we suggest 6 months of therapy (rather than 9 or 12 months) (Grade 2B). 
  • A longer duration of therapy (9 to 12 months) is warranted for patients on regimens that do not include rifampin and/or for patients with extensive or advanced disease.

Fungi 

  • Antifungal treatment recommendations for septic arthritis include oral fluconazole (400 mg [6 mg/kg]) daily for at least six weeks or an intravenous (IV) echinocandin (caspofungin 50 to 70 mg IV daily, micafungin 100 mg IV daily, anidulafungin 100 mg IV daily) daily for at least 2 weeks, followed by oral fluconazole (400 mg [6 mg/kg]) daily for at least 4 weeks. 
  • In addition to antifungal drugs, the cure of prosthetic joint infections almost always requires removal of all prosthetic material.
  • Treatment recommendations for osteomyelitis include oral fluconazole (400 mg [6 mg/kg]) daily for 6 to 12 months or an IV echinocandin (caspofungin 50 to 70 mg IV daily, micafungin 100 mg IV daily, anidulafungin 100 mg IV daily) daily for at least 2 weeks followed by oral fluconazole (400 mg [6 mg/kg]) for 6 to 12 months. 

Culture negative

A small proportion of patients with PJIs have negative cultures. In a review of 897 episodes of PJIs, 7 percent of patients had culture-negative PJI; about one-half of these patients had received prior antibiotics.

Patients with culture-negative PJIs should receive antimicrobial agents with activity against gram-positive and gram-negative pathogens. Suggested regimens include vancomycin with ciprofloxacin or cefazolin with ciprofloxacin at doses outlined above.

Patients with culture-negative PJI have similar outcomes as patients with positive cultures following standard treatment regimens. In one retrospective study including 60 patients with PJI and negative cultures, five-year survival free of treatment failure was 94 percent in patients treated with two-stage exchange arthroplasties and 71 percent in patients who underwent debridement with retention of their prosthesis.

おすすめ 

N Engl J Med. 2004;351(16):1645.
Prosthetic-joint infections.

Clin Infect Dis. 2013;56(1):e1.
Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America.

Antimicrob Agents Chemother. 2013 Jan;57(1):350-5. Epub 2012 Oct 31.
Outcome of debridement and retention in prosthetic joint infections by methicillin-resistant staphylococci, with special reference to rifampin and fusidic acid combination therapy.

Clin Infect Dis. 2013 Jan;56(2):182-94. Epub 2012 Dec 12.
A large multicenter study of methicillin-susceptible and methicillin-resistant Staphylococcus aureus prosthetic joint infections managed with implant retention.

Clin Infect Dis. 2014;59(3):369.
Comparative evaluation of the tolerability of cefazolin and nafcillin for treatment of methicillin-susceptible Staphylococcus aureus infections in the outpatient setting.