Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.

Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

These guidelines are intended for use by infectious disease specialists, orthopedists, and other healthcare professionals who care for patients with prosthetic joint infection (PJI). They include evidence-based and opinion-based recommendations for the diagnosis and management of patients with PJI treated with debridement and retention of the prosthesis, resection arthroplasty with or without subsequent staged reimplantation, 1-stage reimplantation, and amputation.

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Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guidelines by the Infectious Diseases Society of America

Based on the proposed criteria, definite PJI exists when:

(1)

There is a sinus tract communicating with the prosthesis; or




(2)

A pathogen is isolated by culture from at least two separate tissue or fluid samples obtained from the affected prosthetic joint; or




(3)

Four of the following six criteria exist:

(a)

Elevated serum erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) concentration,




(b)

Elevated synovial leukocyte count,




(c)

Elevated synovial neutrophil percentage (PMN%),




(d)

Presence of purulence in the affected joint,




(e)

Isolation of a microorganism in one culture of periprosthetic tissue or fluid, or




(f)

Greater than five neutrophils per high-power field in five high-power fields observed from histologic analysis of periprosthetic tissue at ×400 magnification.













PJI may be present if fewer than four of these criteria are met.

New definition for periprosthetic joint infection: from the Workgroup of the Musculoskeletal Infection Society.

Prosthetic joint infection (PJI) is a tremendous burden for individual patients as well as the global health care industry. While a small minority of joint arthroplasties will become infected, appropriate recognition and management are critical to preserve or restore adequate function and prevent excess morbidity. In this review, we describe the reported risk factors for and clinical manifestations of PJI. We discuss the pathogenesis of PJI and the numerous microorganisms that can cause this devastating infection. The recently proposed consensus definitions of PJI and approaches to accurate diagnosis are reviewed in detail. An overview of the treatment and prevention of this challenging condition is provided.

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Prosthetic Joint Infection

The definition of the heterogeneous group of coagulase-negative staphylococci (CoNS) is still based on diagnostic procedures that fulfill the clinical need to differentiate between Staphylococcus aureus and those staphylococci classified historically as being less or nonpathogenic. Due to patient- and procedure-related changes, CoNS now represent one of the major nosocomial pathogens, with S. epidermidis and S. haemolyticus being the most significant species. They account substantially for foreign body-related infections and infections in preterm newborns. While S. saprophyticus has been associated with acute urethritis, S. lugdunensis has a unique status, in some aspects resembling S. aureus in causing infectious endocarditis. In addition to CoNS found as food-associated saprophytes, many other CoNS species colonize the skin and mucous membranes of humans and animals and are less frequently involved in clinically manifested infections. This blurred gradation in terms of pathogenicity is reflected by species- and strain-specific virulence factors and the development of different host-defending strategies. Clearly, CoNS possess fewer virulence properties than S. aureus, with a respectively different disease spectrum. In this regard, host susceptibility is much more important. Therapeutically, CoNS are challenging due to the large proportion of methicillin-resistant strains and increasing numbers of isolates with less susceptibility to glycopeptides.

Coagulase-Negative Staphylococci

Background Culturing of samples of periprosthetic tissue is the standard method used for the microbiologic diagnosis of prosthetic-joint infection, but this method is neither sensitive nor specific. In prosthetic-joint infection, microorganisms are typically present in a biofilm on the surface of the prosthesis. We hypothesized that culturing of samples obtained from the prosthesis would improve the microbiologic diagnosis of prosthetic-joint infection. Methods We performed a prospective trial comparing culture of samples obtained by sonication of explanted hip and knee prostheses to dislodge adherent bacteria from the prosthesis with conventional culture of periprosthetic tissue for the microbiologic diagnosis of prosthetic-joint infection among patients undergoing hip or knee revision or resection arthroplasty. Results We studied 331 patients with total knee prostheses (207 patients) or hip prostheses (124 patients); 252 patients had aseptic failure, and 79 had prosthetic-joint infection. With the use o...

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Sonication of Removed Hip and Knee Prostheses for Diagnosis of Infection

We recently described a sonication technique for the diagnosis of prosthetic knee and hip infections. We compared periprosthetic tissue culture to implant sonication followed by sonicate fluid culture for the diagnosis of prosthetic shoulder infection. One hundred thirty-six patients undergoing arthroplasty revision or resection were studied; 33 had definite prosthetic shoulder infections and 2 had probable prosthetic shoulder infections. Sonicate fluid culture was more sensitive than periprosthetic tissue culture for the detection of definite prosthetic shoulder infection (66.7 and 54.5%, respectively; P = 0.046). The specificities were similar (98.0% and 95.1%, respectively; P = 0.26). Propionibacterium acnes was the commonest species detected among culture-positive definite prosthetic shoulder infection cases by periprosthetic tissue culture (38.9%) and sonicate fluid culture (40.9%). All subjects from whom P. acnes was isolated from sonicate fluid were male. We conclude that sonicate fluid culture is useful for the diagnosis of prosthetic shoulder infection.

Microbiologic Diagnosis of Prosthetic Shoulder Infection by Use of Implant Sonication

Background: Infection due to methicillin-resistant Staphylococcus aureus (MRSA) is increasingly common in nosocomial and community settings. Daptomycin is a cyclic lipopeptide anti-infective with activity against MRSA, approved for treatment of complicated skin and skin structure infections. Daptomycin may be useful in systemic or local treatment of chronic osteomyelitis. Methods: We measured mechanical strength of daptomycin- and vancomycin-loaded polymethylmethacrylate (PMMA), assayed in vivo release of daptomycin and vancomycin from daptomycin- and vancomycinloaded PMMA, respectively, and compared the efficacy of two systemic doses of daptomycin with that of vancomycin, each with or without the respective anti-infective loaded into PMMA, using a rat model of MRSA chronic osteomyelitis. Results: Neither tensile nor compressive strength of PMMA was impacted by impregnation with these antimicrobials at a concentration of 7.5% by weight. The peak concentrations of daptomycin and vancomycin in rat tibial bone surrounding a 7.5% daptomycin- and vancomycin-loaded 3 mm PMMA bead were 178 and 49 mg/L, respectively. In the treatment of experimental osteomyelitis, rats assigned to no treatment, daptomycin 50 mg/kg subcutaneously twice daily, daptomycin 60 mg/kg subcutaneously twice daily, and vancomycin 50 mg/kg intraperitoneally twice daily had 6.4, 4.1, 4.0 and 4.5 median log10 cfu/g of bone at the end of 21 days of therapy. All systemic anti-infectives studied were more active than was no treatment. Daptomycin- or vancomycin-loaded PMMA did not, however, exhibit microbiological efficacy alone or adjunctively, as assessed 21 days after implantation. Conclusions: Daptomycin is released from PMMA in vivo at a rate similar to that of vancomycin. Systemic daptomycin is as active as vancomycin in a rat model of chronic MRSA experimental osteomyelitis.

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Daptomycin treatment of Staphylococcus aureus experimental chronic osteomyelitis

We tested the activity of anidulafungin against 30 Candida albicans isolates. The planktonic MICs for 50 and 90% of the isolates tested (MIC(50) and MIC(90)) were 16 microg/ml).

In Vitro Activity of Anidulafungin against Candida albicans Biofilms

Planktonic and sessile susceptibilities to micafungin were determined for 30 clinical isolates of Candida albicans obtained from blood or other sterile sites. Planktonic and sessile MIC(90)s for micafungin were 0.125 and 1.0 microg/ml, respectively.

Melissa J. Jacobson

Papers

Sonication of Removed Hip and Knee Prostheses for Diagnosis of Infection

Microbiologic Diagnosis of Prosthetic Shoulder Infection by Use of Implant Sonication

Daptomycin treatment of Staphylococcus aureus experimental chronic osteomyelitis

In Vitro Activity of Anidulafungin against Candida albicans Biofilms

In Vitro Activity of Micafungin against Planktonic and Sessile Candida albicans Isolates