laboratory diagnosis of prosthetic joint infection, part ii

8
Clinical Microbiology Newsletter 33:9,2011 © 2011 Elsevier 0196-4399/00 (see frontmatter) 63 Periprosthetic tissue cultures Gram stain of periprosthetic tissue is rarely clinically helpful due to low sensitivity (0 to 30%) (38 to 42). Iden- tification and susceptibility testing of the microorganism(s) involved in pros- thetic joint infection (PJI) are critical to appropriate selection of antimicrobial therapy. However, bacterial detection with conventional periprosthetic tissue cultures has a sensitivity between 37% and 61% (11,43,44). The poor sensitiv- ity of periprosthetic tissue culture may relate to the relative concentration of organisms on the implant surface per se and not specifically in the surrounding tissue. Some organisms causing PJI may be slow growing due to either their phenotypic state (i.e., biofilm) or inherent characteristics (e.g., Propioni- bacterium acnes)(44,45). Administra- tion of antimicrobials within 3 months of arthroplasty revision is associated with negative cultures (46,47). To increase the sensitivity of culture, some authors advocate the culture of at least five separate tissue samples (48). Also, extended incubation of peripros- thetic cultures improves the sensitivity of cultures. Schäfer et al. (49) obtained five tissue cultures from 284 patients undergoing hip or knee arthroplasty revision and incubated them for 14 days. The median time to positivity was 4 days. At day 7 of incubation, 73.6% of positive cultures had been detected) and at day 13, all positive cultures were detected. A good proportion of late cultures was due to Propionibac- terium species and peptostreptococci, indicating that the benefit of prolonged incubation applies mainly to anaerobic cultures. One concern about prolonging incubation time is potential enhanced recovery of contaminants; however, that was not the case in this study. Late growers with ≥2 positive cultures were associated with histopathologic acute inflammation (P < 0.001), which sug- gests that they were not contaminants. The median time to detection of con- taminants was 7 days. The specificity of periprosthetic tis- sue cultures is also an issue. False-posi- tive results can be due to contamination during surgery, transport to the labora- tory, or processing of specimens (50). Several studies (51-53) have shown that positive intraoperative cultures are often encountered in patients undergo- ing primary joint implantation with no other evidence of infection. Such cul- tures not only represent contamination with skin flora, but also do not predict subsequent development of PJI. Dietz et al. (51) found that 58% of patients undergoing clean orthopedic surgery had positive intraoperative cultures. None of the patients with positive cul- tures developed subsequent infection. The most common organisms isolated were coagulase-negative Staphylococcus species, followed by Propionibacterium Laboratory Diagnosis of Prosthetic Joint Infection, Part II * Eric Gomez, M.D. 1 and Robin Patel, M.D., 1,2 1 Division of Infectious Diseases, Department of Medicine, 2 Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota Abstract Prosthetic joint infection (PJI), although a rare complication of primary or revision arthroplasty, is reported more frequently as the number patients undergoing arthroplasty increases. Accurate diagnosis of PJI is essential for adequate management and outcome. Although multiple tests have been applied, in some cases, differentiation of PJI from aseptic loosening of the prosthesis remains a challenge. Here, we review the current diagnostic laboratory modalities used for the diagnosis PJI. In Part I of this two- part article, components of the preoperative evaluation of the patient and the histology of the intraoperative evaluation were dis- cussed. Part II of the article discusses the remaining components of the intraoperative evaluation, including periprosthetic tissue and sonicate fluid cultures. In addition, recent investigational approaches for the diagnosis of PJI, antimicrobial susceptibility testing, and management of PJIs are reviewed. Vol. 33, No. 9 www.cmnewsletter.com May 1, 2011 *Editor’s Note: Part I of this article appeared in the April 15, 2011 issue of Clinical Microbiology Newsletter (CMN Vol. 33, No. 8). Corresponding Author: Robin Patel, M.D., Mayo Clinic, 200 First St. SW, Rochester, MN 55905. Tel: 507-538-0579 Fax: 507- 284-4272. E-mail: [email protected] Clinical Microbiology Newsletter $99

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Clinical Microbiology Newsletter 33:9,2011 © 2011 Elsevier 0196-4399/00 (see frontmatter) 63

Periprosthetic tissue culturesGram stain of periprosthetic tissue

is rarely clinically helpful due to lowsensitivity (0 to 30%) (38 to 42). Iden-tification and susceptibility testing ofthe microorganism(s) involved in pros-thetic joint infection (PJI) are critical toappropriate selection of antimicrobialtherapy. However, bacterial detectionwith conventional periprosthetic tissuecultures has a sensitivity between 37%and 61% (11,43,44). The poor sensitiv-ity of periprosthetic tissue culture mayrelate to the relative concentration oforganisms on the implant surface per seand not specifically in the surroundingtissue. Some organisms causing PJImay be slow growing due to eithertheir phenotypic state (i.e., biofilm) orinherent characteristics (e.g., Propioni-bacterium acnes) (44,45). Administra-

tion of antimicrobials within 3 monthsof arthroplasty revision is associatedwith negative cultures (46,47).

To increase the sensitivity of culture,some authors advocate the culture of atleast five separate tissue samples (48).Also, extended incubation of peripros-thetic cultures improves the sensitivityof cultures. Schäfer et al. (49) obtainedfive tissue cultures from 284 patientsundergoing hip or knee arthroplastyrevision and incubated them for 14days. The median time to positivity was4 days. At day 7 of incubation, 73.6%of positive cultures had been detected)and at day 13, all positive cultureswere detected. A good proportion oflate cultures was due to Propionibac-terium species and peptostreptococci,indicating that the benefit of prolongedincubation applies mainly to anaerobiccultures. One concern about prolongingincubation time is potential enhancedrecovery of contaminants; however,that was not the case in this study. Lategrowers with ≥2 positive cultures wereassociated with histopathologic acuteinflammation (P < 0.001), which sug-gests that they were not contaminants.The median time to detection of con-

taminants was 7 days.The specificity of periprosthetic tis-

sue cultures is also an issue. False-posi-tive results can be due to contaminationduring surgery, transport to the labora-tory, or processing of specimens (50).Several studies (51-53) have shownthat positive intraoperative cultures areoften encountered in patients undergo-ing primary joint implantation with noother evidence of infection. Such cul-tures not only represent contaminationwith skin flora, but also do not predictsubsequent development of PJI. Dietzet al. (51) found that 58% of patientsundergoing clean orthopedic surgeryhad positive intraoperative cultures.None of the patients with positive cul-tures developed subsequent infection.The most common organisms isolatedwere coagulase-negative Staphylococcusspecies, followed by Propionibacterium

Laboratory Diagnosis of Prosthetic Joint Infection, Part II*

Eric Gomez, M.D.1 and Robin Patel, M.D.,1,2 1Division of Infectious Diseases, Department of Medicine, 2Division of ClinicalMicrobiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MinnesotaAbstract

Prosthetic joint infection (PJI), although a rare complication of primary or revision arthroplasty, is reported more frequentlyas the number patients undergoing arthroplasty increases. Accurate diagnosis of PJI is essential for adequate management andoutcome. Although multiple tests have been applied, in some cases, differentiation of PJI from aseptic loosening of the prosthesisremains a challenge. Here, we review the current diagnostic laboratory modalities used for the diagnosis PJI. In Part I of this two-part article, components of the preoperative evaluation of the patient and the histology of the intraoperative evaluation were dis-cussed. Part II of the article discusses the remaining components of the intraoperative evaluation, including periprosthetic tissueand sonicate fluid cultures. In addition, recent investigational approaches for the diagnosis of PJI, antimicrobial susceptibilitytesting, and management of PJIs are reviewed.

Vol. 33, No. 9 www.cmnewsletter.com May 1, 2011

*Editor’s Note: Part I of this articleappeared in the April 15, 2011 issue ofClinical Microbiology Newsletter(CMN Vol. 33, No. 8).

Corresponding Author: Robin Patel, M.D.,Mayo Clinic, 200 First St. SW, Rochester,MN 55905. Tel: 507-538-0579 Fax: 507-284-4272. E-mail: [email protected]

ClinicalMicrobiologyNewsletter

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species.The problems with specificity trans-

late into difficulties in determining theclinical significance of growth of com-mon skin flora in intraoperative cultures.Recognized pathogens, such as Staphy-lococcus aureus, beta-hemolytic strep-tococci, Streptococcus pneumoniae, andmembers of the Enterobacteriaceae,are less likely than coagulase-negativestaphylococci and Propionibacteriumspecies to be considered contaminantsand should raise the suspicion of infec-tion, prompting some authors to con-sider any growth in culture significant(21,51,54). On the other hand, the sig-nificance of less virulent skin floraorganisms in cultures should be care-fully assessed to avoid misclassifyingcontaminants as pathogens. In a studyof coagulase-negative staphylococcirecovered from patients with suspectedorthopedic infections (62% arthroplastyrevisions), only 36% of isolates wereconsidered clinically significant (55).Among the clinically significant iso-lates, Staphylococcus epidermidis wasthe most commonly species isolated(81%), followed by Staphylococcus lug-dunensis (7%), Staphylococcus capitis(7%) and Staphylococcus caprae (5%).Special distinction should be made forS. lugdunensis, as it can cause a moreaggressive infection, behaving likeS. aureus (56).

P. acnes, an anaerobic gram-positivebacillus that forms part of the humanskin flora, was for many years consid-ered a culture contaminant. However,recently, P. acnes has been considereda pathogen in PJI, especially PJI involv-ing shoulder implants. In a study ofprosthetic shoulder infections from theMayo Clinic (10), P. acnes was the sec-ond most common organism isolated(after Staphylococcus spp.), causingtwo-fifths of the microbiologicallyconfirmed cases of PJI. However, as

with coagulase-negative staphylococci,culture results with P. acnes should beinterpreted with caution, especiallysingle positive cultures. Dramis et al.(57) reported 56 patients with totaljoint replacements (only one shoulderimplant) who had positive synovialfluid aspirate and/or tissue cultures forP. acnes. The majority did not receiveantimicrobial treatment, and subsequentinfection developed in just one patient.Only eight patients had ≥2 positive cul-tures (two of whom were treated withantimicrobial agents), and none devel-oped subsequent infection. In a reportof 75 revision shoulder arthroplastieswithout overt clinical findings of infec-tion and with positive intraoperativecultures (mostly single positive cul-tures), Topolski et al. (58) reported thatP. acnes was the most commonly iso-lated organism (60%). The majority ofpatients did not receive antimicrobialtreatment, and only 10 required asecond revision arthroplasty.

In an effort to increase the specificityof tissue cultures, Kamme and Lindberg(54) proposed that by using a standard-ized method of multiple sample collect-ion, pathogens can be differentiatedfrom contaminants. Thirty-one patientsundergoing primary arthroplasty (con-trol) and 63 undergoing arthroplastyrevisions were studied. Five tissue spec-imens were taken from the joint withseparate sterile instruments for eachspecimen. Patients in the control groupand those with aseptic loosening had≤2 positive tissue cultures. In contrast,patients with PJI had five positive tissuecultures. However, the definition ofinfected cases was not clear. Atkinset al. (48), using a mathematical model,determined that five tissue samples areneeded to obtain good sensitivity andspecificity. The authors propose that,using a cutoff of ≥2 positive tissue cul-tures out of 5 samples, the microbiolog-

ical diagnosis of infection can be made.In this study, acute inflammation on his-topathology was used to define infection,and all samples were taken with a freshscalpel blade to decrease the chanceof contamination. Other authors havereported that by increasing the numberof specimens taken, the specificity, butnot the sensitivity, improves (59).

Swab cultures (of capsular mem-brane, bone or synovial fluid) have lim-itations compared to tissue and synovialfluid cultures. Levine et al. reportedthat the inoculation of intraoperatively-collected synovial fluid inoculated intoblood culture bottles achieved highersensitivity (92%) than tissue (46%) orswab (64%) cultures (60). Swab cultureswere more prone to contamination, as50% of cultures showed polymicrobialgrowth compared to one-third of posi-tive blood culture bottles. A Spanishstudy (61) also showed that intraopera-tively collected synovial fluid culturedusing blood culture bottles was superiorto tissue and swab cultures, withoutfalse-positive results. Swab cultures hada high rate of false-positive results dueto contamination with coagulase-nega-tive Staphylococcus spp. and Propioni-bacterium spp. Anaerobes are morecommonly isolated using blood culturebottles than with swabs and tissue cul-tures, showing that loss of viability ofbacteria during transport may accountfor some false-negative culture results(60).

Sonicate fluid culturesThe growth of bacteria in biofilms

may elude detection by periprosthetictissue cultures. Sampling biofilm bac-teria is a strategy used to diagnose PJI.Surgical scraping of the prosthesissurface has shown higher sensitivitythan periprosthetic tissue culture, indi-cating a higher bacterial load on thebiomaterial surface (44). However,scraping seems to be insufficient to

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Clinical Microbiology Newsletter 33:9,2011 © 2011 Elsevier 0196-4399/00 (see frontmatter) 65

remove the biofilm and risks introduc-tion of contaminants (62). An efficientmethod to disrupt the biofilm is the useof sonication (63). With sonication,ultrasound waves are propagated in aliquid medium to create microscopic airbubbles that explode, due to high sur-face tension, generating high energythat can disrupt the biofilm (63). In astudy (64) using an in vitro model ofimplant infection, treatment of an inertsurface with sonication yielded higherbacterial recovery (39.9 colony-formingunits [CFU] per plate) than when nosonication was used (1.6 CFU per plate)(64). Sonication has been used in thediagnosis of infection of multiple typesof medical devices, including orthopedicdevices (65-67), vascular grafts (68),breast implants (69), vascular catheters(70), cardiac devices (71), and ureteralstents (72).

Tunney and colleagues (73) usedsonication to dislodge bacteria from theprosthesis, obtaining more positive cul-tures with sonicate fluid than with theconventional periprosthetic tissue cul-tures. The sonication technique pro-posed by Tunney et al. was modifiedby Trampuz et al. and evaluated in thediagnosis of PJI. In a study of 331patients (252 patients with aseptic fail-ure and 79 with PJI), sonicate fluidcultures had a sensitivity of 78.5%and tissue cultures had a sensitivity of60.8% (P < 0.001), with specificities of98.8 and 99.2%, respectively (43). Theimproved sensitivity of sonicate-fluidcultures was predominant in the groupof patients who had received priorantimicrobial therapy. It is importantto note that a cutoff to define clinicallysignificant results should be appliedto sonication culture results; failure toapply such a cutoff will substantiallylower specificity. Figure 2 describesthe sonication procedure initially usedin the study by Trampuz et al. with amodification that was introduced subse-quently (11). Sonicate fluid cultureshave a shorter time to positivity thanperiprosthetic tissue cultures. In aretrospective review of patients whounderwent revision arthroplasty andsonication of the implant, sonicate tis-sue cultures were positive on averageafter 1 day (for coagulase-negativestaphylococci, enterococci, and strepto-cocci) compared to tissue cultureswhich were positive after 2 days (74).

Investigational approachesfor the diagnosis of PJI

Several new non-culture methodshave been reported for the diagnosisand the microbial identification of PJI.Some of these new methods look prom-ising but are not yet in routine use forthe assessment of septic arthroplastyfailure (Table 2).

Synovial fluid biomarkersDeirmengian et al. (75) evaluated

gene expression of neutrophils in syn-ovial fluid obtained from native joint

S. aureus septic arthritis and neutrophilsfrom crystal-induced arthritis (gout).Using microarrays, neutrophils frominfected synovial fluid showed a spe-cific gene expression signature (126genes) different from that of patientswith gout. Some genes, such as cyto-kine genes, had been previously notedto be up-regulated when neutrophilswere exposed to bacteria. Based onthese results, the authors (76) reporteda subsequent study evaluating a selectnumber of biomarkers from synovialfluid for the diagnosis of PJI in 53

Figure 2. Procedure for orthopedic implant sonication used at Mayo Clinic. Ringer’s solution(400 ml) is added to the container, which is vortexed for 30 seconds. Then, the container issubjected to sonication in a Bransonic 5510 ultrasound bath (Branson, Danbury, CT) for5 minutes (40 kHz frequency). The container is vortexed for another 30 seconds. A 100-foldconcentration step has been added since the original procedure described by Trampuz et al.(43) Sonicate fluid is placed in a 50 ml tube and centrifuged at 3,150 x g for 5 minutes. Thesupernatant is aspirated, and 0.1 ml of specimen is inoculated to a sheep blood agar platewhich is incubated aerobically for 4 days and a CDC anaerobic plate, which is incubatedfor 14 days.

Table 2. New approaches for the diagnosis of PJIDiagnosis of PJI Microbiological diagnosis of PJI

IL-6 Serology

Procalcitonin Molecular methods

TNF-αa Immunofluorescence microscopy

Synovial fluid biomarkers (IL-6, IL-1β)aTNF-α, tumor necrosis factor alpha.

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patients (14 PJI and 37 aseptic failures).Of 23 biomarkers tested, interleukin 6(IL-6) and IL-1β were found to be 100%sensitive and specific for the diagnosisof PJI. Compared to C-reactive pro-tein, erythrocyte sedimentation rate,and synovial fluid leukocytes, IL-6 andIL-1β had higher accuracy (100% ver-sus 80%). As there is a “distinctive”expression of certain biomarkers withbacterial exposure that is different fromthat with other inflammatory noninfec-tious processes, patients with systemicinflammatory disease were included inthis study (two patients with PJI andthree patients with aseptic failure).Although this is a promising approachfor the diagnosis of PJI, including inpatients with inflammatory disease,further clinical studies are needed.

Serologic detection of microorganismsKamme and Lindberg (54) evaluated

the immunologic response of patientswith PJI against the organism isolatedfrom tissue culture. Patient’s serumantibody titers against P. acnes andpeptostreptococci were compared toantibody titers in normal human sera.Although there was a trend towardhigher antibody titers in patients withpeptostreptococcal PJI, the authorsdetermined that this test had limiteddiagnostic value.

Detecting antibodies against orga-nisms associated with PJI, although afairly easy test to perform, lacks speci-ficity due to the low basal antibodytiters against organisms, such as coagu-lase-negative staphylococci, which arepart of the normal human flora. How-ever, Rafiq et al. (77) identified andreported the use of a short-chain-lengthform of cellular lipoteichoic acid ofcoagulase-negative staphylococci forthe detection of gram-positive bacterialPJI with good results. Fifteen patientswith proven gram-positive PJI and 32control patients were tested for antibod-ies against lipoteichoic acid. Patientswith a history of infection not relatedto the prosthesis 6 months prior to thestudy were excluded. IgG levels wereelevated in 14 of the infected patientsand in only 1 patient of the controlgroup, corresponding to a sensitivityof 93% and specificity of 97%.

Immunofluorescence microscopyDirect visualization of bacteria from

sonication fluid with pathogen-targeted

antibodies (immunofluorescence micro-scopy [IFM]) has been used as a non-culture method for the microbiologicaldiagnosis of PJI. Tunney et al. (78)developed monoclonal antibodies toP. acnes and polyclonal antibodiesagainst Staphylococcus species andused them on sonicate fluid. Largeaggregates of bacteria were visualizedwith a fluorescence microscope in allpatients with positive cultures and in47 out of 89 prostheses with negativecultures. However, as no clear defini-tion of PJI was provided, it is difficultto assess the performance of IFM in thisstudy. According to the authors, conta-minating bacteria were differentiatedfrom pathogens, as contaminantsappeared as single bacteria or smallaggregates, whereas pathogensappeared as large aggregates.

Piper et al. (11) evaluated the useof IFM for the diagnosis of prosthetic-shoulder infection, using monoclonalantibodies against P. acnes and staphy-lococci. The sensitivity of IFM to detectP. acnes and staphylococci was 67% and58%, respectively. IFM did not improvemicrobiological detection compared tosonicate fluid cultures, as all IFM-posi-tive specimens had positive cultures.

Molecular methodsSome authors (79) have stated that

biofilm infections cannot be reliablydiagnosed using cultural methods, asprior antimicrobial use, low metabolicactivity of sessile bacteria within bio-films, fastidious growth characteristicsof the organisms present, loss of via-bility during transport, small-colonyvariants, and/or the presence of gener-ally viable but nonculturable organismscould result in negative cultures. Mole-cular methods may theoretically over-come these issues. However, the limitedavailable studies using PCR for thediagnosis of PJI have shown mixedresults. In a study of 34 patients withPJI, Vandercam et al. (80) evaluated theuse of broad-range PCR using 16S ribo-somal RNA (rRNA) genes on intraoper-ative samples (tissue, synovial fluid,and/or swabs) at the time of revisionarthroplasty. PCR improved bacterialdetection from 64.7% to 91.2% com-pared to cultures. Moojen el al. (81)used 16S rRNA PCR and reverse lineblot hybridization on intraoperative tis-sue of 76 patients undergoing orthope-

dic surgeries (57 arthroplasty revisions).PCR had a sensitivity and specificityof 81 and 96%, respectively comparedto cultures. Tunney et al. (78) detectedbacterial DNA in prosthesis sonicatesby broad-range PCR amplification of aregion of the bacterial 16S rRNA genewith universal primers in all culture-positive samples and in a further 64%of the culture-negative samples.

Molecular methods may show anadvantage over cultures in patients withprior antimicrobial use. Using broad-range PCR, bacterial DNA has beendetected in synovial fluid up to 22 daysafter starting antimicrobial therapy inpatients with septic arthritis and PJI,even though cultures were negative(82,83). Achermann et al. (84) evalu-ated a real-time multiplex PCR test(SeptiFast; Roche Diagnostics, Basel,Switzerland) performed on sonicate fluidfor the diagnosis of PJI. This system iscommercially available in Europe foridentification of a limited number ofbacterial and fungal pathogens typicallyisolated from blood. Pathogens wereidentified by tissue culture, sonicatefluid culture, and sonicate fluid PCRin 65%, 64%, and 78% of PJI cases,respectively. Among the patients withPJI who received antibiotics prior toresection arthroplasty, PCR of sonicatefluid detected the offending pathogen in100% of cases compared to 42% withculture methods. On the other hand, DeMan et al. (85) reported that the use ofPCR on intraoperative specimens (syn-ovial fluid and/or periprosthetic tissue)had low sensitivity in patients withrecent antimicrobial agent use. Althoughthere was a small number of patients(n = 26), the authors concluded thatPCR was highly specific (94% versus71%) but that it had low sensitivity(50% versus 58%) compared to culture.

False-positive PCR is always a con-cern as DNA from non-viable bacteriacan contaminate patient specimens andeven reagents, and amplicon contami-nation may occur. Clarke et al. (86)reported that 29% of patients undergo-ing primary total hip arthroplasty with-out infection had positive PCR (16SrRNA) results from intraoperative sam-ples (tissue and synovial fluid), whichwas most likely due to contaminationat the time of specimen collection.Panousis et al. (87) also showed lowspecificity (74%) of broad-range PCR

Clinical Microbiology Newsletter 33:9,2011 © 2011 Elsevier 0196-4399/00 (see frontmatter) 67

from intraoperative synovial fluid sam-ples in 92 patients undergoing arthro-plasty revision. RNA may be a bettertarget than DNA for PCR detection, asit is only present in viable bacteria andhas a very short half-life, making it a lesslikely cause of contamination. Berginet al. (89) used reverse transcription-quantitative PCR targeting 16S rRNAon preoperative joint aspirates for thediagnosis of PJI. The authors showedsensitivity of 71% and specificity of100%.

Molecular techniques have the dis-advantage of not being able to provideantimicrobial susceptibility results,which is important in the managementof PJI. One strategy to overcome thislimitation is molecular detection ofresistance determinants, such as withdetection of the methicillin-resistancegene, mecA, using PCR (89,90).

Antimicrobial susceptibility testingCurrent methods of antimicrobial

susceptibility testing use suspendedplanktonic cells, which might not berepresentative of the bacterial popula-tion within biofilms. Bacteria in bio-films can survive antimicrobial agentconcentrations 1,000-fold higher thantheir corresponding planktonic forms(91). Researchers have developed mul-tiple in vitro models of biofilms thathave been adapted for antimicrobialsusceptibility testing (92). One of themost common methods used is the peglid biofilm assay, of which the CalgaryBiofilm Device (CBD) is a prototype.The CBD consists of multiple polysty-rene pegs lying on an incubation tray(93). Biofilm forms along the peg, whichis later exposed to various antimicrobialconcentrations. The pegs are subjectedto sonication, followed by quantitativeculture of the sonicate fluid to determinethe minimum biofilm eradication concen-tration, which is the minimum concen-tration of antimicrobial agent needed toeradicate the biofilm. Although the clin-ical utility of biofilm antimicrobial sus-ceptibility testing has not been assessed,Sandoe et al. (94) tested 58 enterococcalisolates from patients with intravascular-catheter-related bloodstream infectionto determine the minimal biofilm inhi-bitory concentration (MBIC) usingthe CBD. In a small subset of patients,salvage of the catheter was attemptedwith antimicrobial treatment. In thesepatients, no correlation between the

MBIC and outcome was found. Furtherstudies are needed to determine theclinical utility of such testing.

Management of PJIsThe goal of therapy in patients with

PJI is to eradicate or control the infec-tion while maintaining a functionaljoint. This can be achieved through amultidisciplinary approach involvingan orthopedic surgeon, an infectiousdiseases specialist, and a clinical micro-biologist. Current surgical treatmentstrategies include débridement andretention, resection arthroplasty withimmediate or delayed reimplatation(one-stage versus two-stage revision),arthrodesis, and amputation. Resectionarthroplasty with or without delayedreimplantation is performed in patientspresenting with subacute or chronic PJI.In one-stage revision, the prosthesis andcement are removed and a new prosthe-sis is placed during the same procedure(95-101). This procedure is performedin healthy patients with good soft tissueand bone structures with PJI caused byantimicrobial-susceptible organisms(thus, the microbiology of infectionshould be known prior to the proce-dure). If a patient is not a candidate fora one-stage revision, resection arthro-plasty with delayed reimplantation canbe performed. In two-stage revision, allthe hardware is removed and reimplan-tation of the joint is performed in a sub-sequent surgery weeks to months later(102-105). In debridement and retentionof the prosthesis, the devitalized boneand soft tissue are removed and the poly-ethylene cover is exchanged, leavingthe prosthesis in place. Debridementand retention are indicated in patientswith acute hematogenous and/or acutepostoperative infection (usually within4 weeks from the index surgery) andwith well-fixed components in theabsence of a sinus tract. Arthroplastyresection without subsequent reimplan-tation of the joint (Girdlestone proce-dure) and arthrodesis (obliteration ofthe joint), are seldom used to controlthe infection. While these proceduresoften lead to infection eradication, theyare associated with limited joint func-tion (106-108). In selected cases wheresurgery cannot be performed (e.g., highsurgical risk), conservative treatmentwith antimicrobial therapy alone is usedin order to contain the infection to thejoint (109-110). On rare occasions and

when all other treatment options havefailed, amputation of the limb involvedcan be used as a last resort to controlthe infection (111).

Antimicrobial treatment should bebased on in vitro antimicrobial suscep-tibility testing. Antimicrobials can bedelivered systemically or locally intothe joint. Local antimicrobial deliverysystems through antimicrobial-impreg-nated cement or spacers are used inan attempt to improve the chances oferadicating the infection (112). Theantimicrobial drug(s) can be mixedwith cement (polymethylmethacrylate),which when applied to the joint space,will gradually release the antimicrobialdrug(s) over time in the joint space andbone cement interface (113). Systemicantimicrobial drugs can be providedthrough the parenteral or oral (whenagents with high bioavailability areused [e.g., fluoroquinolones]) route. Incases of rifampin-susceptible staphylo-coccal infections treated with débride-ment and retention, rifampin-basedregimens (e.g., a quinolone and rifam-pin) have been shown to be more effica-cious than non-rifampin-based regimens(e.g., quinolone alone) (114-116). Rif-ampin should always be combined withanother antibiotic to prevent the emer-gence of rifampin resistance duringtreatment. Although the optimal dura-tion of antimicrobial therapy has notbeen defined with randomized studies,for hip and knee PJI treated with debride-ment and retention, rifampin-based reg-imens are commonly administered for3 and 6 months, respectively. For PJItreated with one- or two-stage arthro-plasty revisions, 4 to 6 weeks of anti-microbial treatment is usually provided.

SummaryThere has been much progress made

in recent years in the diagnosis of PJI,but there remain limitations to currentdiagnostic methods. Inflammatorymarkers and synovial and periprosthetictissue cultures have limited sensitivityand specificity. Histopathology hasgood specificity and positive predictivevalue but somewhat limited sensitivity.The sensitivity of cultures has improvedwith the use of implant sonication; how-ever, cases of culture-negative PJI stilloccur. PCR may improve the microbialdetection in PJI, but further developmentis needed for clinical use to ensure that,

68 0196-4399/00 (see frontmatter) © 2011 Elsevier Clinical Microbiology Newsletter 33:9,2011

with potentially improved sensitivity,specificity is not compromised. Cur-rently, there is no single test that canaccurately identify PJI. With the currentarmamentarium of tests, the best diag-nostic approach requires a combinationof multiple laboratory tests along withclinical assessment. New diagnosticmethods and/or improvement of currentmethodologies for the diagnosis of PJIis still needed.

AknowledgementsWe thank Natalia Franch-Gomez for

her assistance with the illustrations andElie F. Berbari, M.D., for reviewing thesection on management of PJI.

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