Introduction
In his 1920 commentary in the British Journal of Surgery , Lord Berkeley Moynihan commented, “Every operation in surgery is an experiment in bacteriology.” What the renowned surgeon was implying was the fact that all surgical wounds are in fact contaminated by bacteria. These bacteria may be harmless flora with minimal threat of infection or they may be dangerous virulent pathogens that can jeopardize the success of a procedure. Moynihan’s statement continues to hold merit even in the modern world of medicine, because in many instances we remain uncertain as to why surgical infections occur. Nonetheless, substantial developments in microbiology as well as improvements in safety and control in the operating room have led surgical procedures to become much less of the “experiment” they once were.
From a microbiologic viewpoint, true infection after surgery occurs when the dose of a given bacteria with its innate virulence factors is able to overcome the host defenses in place to prevent the infection. These host defenses are highly variable from person to person, and in part this explains why some patients are able to use immune factors to withstand clinical infection whereas others end up with failed surgical outcomes. Additionally, we are just beginning to recognize that not all infections may be considered the same. In combination with patient factors and immune status, varying bacteriologic properties across and even within a microorganism species affect the potential for infection after any type of surgical procedure.
Infection of joint replacement prostheses is a highly studied yet persistent and devastating complication of total joint arthroplasty (TJA). This chapter discusses properties of biofilm formation on prosthetic implants, common microorganisms responsible for periprosthetic joint infection (PJI), emergence of antibiotic resistance, and the effect that microbiology ultimately has on treatment options.
Biofilm
Deep infection of the joint is an extraordinarily difficult complication after TJA. Years of research on the pathogenesis of PJI have led to the idea of the bacterial “biofilm” to explain why these infections are so persistent and difficult to treat after orthopedic procedures. Although biofilm formation is undoubtedly not unique to infection of orthopedic implants, by now it is a well-accepted concept used to elucidate the resilience of bacterial virulence mechanisms in PJI.
In basic science research models, bacterial adherence to implant material serves as the basis of biofilm formation. In general, bacteria may use both host proteins and their own virulence factors to promote adhesion of quickly aggregating pathogens, which, when encased in a matrix of polysaccharides and proteins, form the thick, slimy layer known as a biofilm.
It is out of the scope of this chapter to delve deeply into the specific cell proteins and polysaccharides that assist with bacterial virulence and pathogenicity. Even so, it should be noted that in recent decades the boom in genomic and then proteomic scientific research endeavors has led to discovery of many genes and proteins responsible for the invasive, fibrinolytic, and adhesive properties of infectious bacteria. Scanning electron microscopy has allowed detection of both the adherence phase, during which rapidly layering bacteria attach to polymer material, and the subsequent accumulation phase, during which bacteria proliferate and form multilayered clusters embedded in extracellular material. By creating this environment within the joint and around the implant, bacteria are ostensibly able to switch their metabolism from free-floating planktonic to sessile surface growth via quorum-sensing signals.
The important clinical role of the biofilm is in its promotion of insidious bacterial growth as well as the more dangerous resistance to cellular, humoral, and antibacterial insults. It has been shown repeatedly now that biofilm bacteria are 1000 times more resistant to antibiotic administration than their planktonic counterparts, as shown by their much higher minimal inhibitory concentrations in vitro. In particular, Staphylococcus strains are able to form some of the most resistant biofilms. Not only are biofilm bacteria more difficult to treat, but their adhesive property makes them much more difficult to detect, frequently yielding negative Gram stain and culture results despite clinical signs of infection. Further, these slimy layers may even persist as a nidus for sporadic infection from which recurrent exacerbations of infection can arise in the future ( Fig. 32.1 ).
Although several studies have replicated biofilm formation in vitro, only a few studies have definitively demonstrated the existence of bacterial biofilm directly on freshly removed implant surfaces. Some scientists now say that biofilms can form not only on polymer surfaces of foreign materials but also on surrounding bone cement and innate host tissue as a potential reservoir for future infection. Regardless of the area of biofilm formation deep within the joint, the stark reality currently is that prosthetic infection will not clear without removal of the implants, thorough irrigation and débridement of surrounding tissues, and administration of antibiotics. The future of PJI will surely center on preventing bacterial biofilm formation, and exciting research on topics such as quorum-sensing inhibition is already under way.
Organism Profile
Infection after TJA may be caused by a wide variety of pathogens, including bacterial and, less commonly, fungal microorganisms. The distribution of the organisms responsible for septic joints may vary slightly from nation to nation and even across hospitals within the United States. Nevertheless, based on several studies in the past couple of decades, the general trends regarding infecting organisms remain comparable between institutions and over the years ( Fig. 32.2 ).
The two groups of pathogens that are most frequently responsible for PJI are coagulase-negative Staphylococcus species (mainly S. epidermidis ) and Staphylococcus aureus , accounting for between 30% and 40% and between 20% and 30% of all PJI cases, respectively. Other commonly isolated bacteria include Streptococcus and Enterococcus species (5% to 15%), gram-negative organisms such as Escherichia coli and Pseudomonas aeruginosa (8% to 17%), and anaerobes, including Propionibacterium acnes (5% to 14%). Table 32.1 depicts three published series from varying time periods showing the relative stability of microorganism distribution from infected joint isolates.
| Microorganism | Study, No. of Isolates, and Prevalence of Microorganisms | ||
|---|---|---|---|
| Fitzgerald, 1995 % ( N = 108) | Frommelt et al, 2000 % ( N = 1077) | Laffer et al, 2006 % ( N = 40) | |
| Coagulase-negative Staphylococcus | 29.4 | 41.0 | 21.4 |
| Staphylococcus aureus (including MRSA) | 18.7 | 26.2 | 33.3 |
| Streptococcus and Enterococcus spp. | 19.6 | 8.4 | 19.0 |
| Gram-negative spp. | 17.6 | 7.4 | 14.3 |
| Anaerobe spp. | 9.8 | 13.7 | 7.2 |
| Other (fungal, mycobacterial, culture-negative) | 4.9 | 3.3 | 4.8 |
∗ Three studies done over three different decades depict the relative microorganism profile of infected total joint arthroplasties. Although there was a relative increase in virulent S. aureus species, the overall profile of organisms remained somewhat stable.
Traditionally, orthopedic surgeons have considered PJI caused by gram-negative organisms to be more difficult to successfully eradicate and manage. Few studies have directly compared the outcomes of treatment for PJI caused by gram-negative versus gram-positive species, and the existing literature is conflicting. Two groups retrospectively reviewed success rates of débridement and two-stage exchange arthroplasty for PJI with regard to the infecting organisms. For treatment with débridement, Zmistowski and colleagues found a success rate of 70% for gram-negative PJI, whereas Hsieh and co-workers found a 27% success rate; both groups reported a success rate of about 40% for débridement after gram-positive PJI. There was no difference in success rates between gram-negative and gram-positive PJI treated with two-stage exchange in these two studies. A subsequent study by Uçkay and Bernard showed no difference in eradication rates when comparing infecting organisms. It has been hypothesized that within the subset of gram-negative infections, those specifically due to Pseudomonas species are particularly resilient.
Importantly, polymicrobial infections, in which more than one infecting organism is isolated, are responsible for a large portion of PJI cases and can make the choice of empirical antibiotic therapy more complex. Further, some studies have concluded that polymicrobial infections are becoming more common, with some reporting that they account for 19% to 37% of PJIs. The majority of these infections include Staphylococcus species as one of the invading microorganisms. Risk factors for polymicrobial infection include age 65 years or older, presence of soft tissue defect or wound dehiscence, and presence of drainage. Furthermore, the 2-year probability of success in treating polymicrobial PJI by either two-stage exchange, débridement and retention, or resection arthroplasty was 63.8%, compared with 72.8% for monomicrobial PJIs.
A final consideration when discussing the organism profile of PJI is the culture-negative case, in which no organism can be isolated from culture. One group looking at a large cohort of PJI cases reported that the prevalence of this culture-negative cohort may be as high as 7%. One of the biggest risk factors for obtaining negative cultures among patients with PJI is the prior use of antibiotic therapy. Although it is debated strongly whether the use of antibiotics should be withheld before culture, there are reports that favorable treatment outcomes for culture-negative PJI are comparable to those associated with PJI due to known bacterial pathogens. Although relatively little comprehensive literature exists pertaining to the microbiologic spectrum of PJI, having data regarding the specific pathogen responsible for a patient’s infection is a very important aspect of guiding therapy and management.
Emergence of Antibiotic Resistance
Given that the organism profile of PJI after TJA has remained relatively uniform, the biggest and most concerning microbiologic change with regard to infection has been the emergence of virulent strains with antibiotic resistance. Although there is resistance across several bacterial families, the main new culprit complicating TJA is methicillin-resistant S. aureus (MRSA), which has developed resistance against virtually all beta-lactam antibiotics.
The increasing prevalence of MRSA in hospitals and the community has caused serious problems for the health care community. In 2001, the incidences in the United States of MRSA causing skin infections and soft tissue infections were 44.4% and 75.2%, respectively. As a leading cause of nosocomial infections in surgical patients, MRSA has created a new challenge for orthopedic surgeons dealing with PJI. MRSA infection after TJA has led to higher costs, increased length of stay by as much as 7 to 14 days, additional number of procedures, and development of more complications.
Much basic science and microbiologic research has gone into determining virulence factors of methicillin-sensitive S. aureus (MSSA) and MRSA species that allow evasion of host defenses and prevent infection eradication. As discussed previously, S. aureus strains are particularly adept at forming impenetrable biofilms on implanted prostheses. In addition, they possess the ability to hide within host cells such as osteoblasts and to form subpopulations that persist intracellularly. Transmission electron microscopy has shown that S. aureus can actively reside inside epithelial and other types of cells, causing apoptosis of infected cells when the bacteria begin to replicate. These subpopulations may also account for antibiotic resistance, chronic unremitting infection, and persisting dormant infection that can relapse at a future date ( Fig. 32.3 ).
