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SECTION I: SYMPOSIUM I: Papers Presented at the 2005 Meeting of the Musculoskeletal Infection Society

Unusual Aerobic and Anaerobic Bacteria Associated with Prosthetic Joint Infections

Marculescu, Camelia E, MD, MSCR*; Berbari, Elie F, MD; Cockerill, Franklin R III, MD; Osmon, Douglas R, MD, MPH

Section Editor(s): Garvin, Kevin MD, Guest Editor

Author Information
Clinical Orthopaedics and Related Research®: October 2006 - Volume 451 - Issue - p 55-63
doi: 10.1097/01.blo.0000229317.43631.81
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The association of certain microorganisms with prosthetic joint infection (PJI) has been recognized for many years. The majority of PJIs (65%) are caused by S. aureus, coagulase-negative staphylococci, beta-hemolytic streptococci, viridans group streptococci, and enterococci.79 Aerobic Gram-negative bacilli, including members of the family of Enterobacteriaceae (E. coli, Proteus mirabilis, and others) and Pseudomonas aeruginosa cause infection less frequently. The recognition of PJI due to such micro-organisms is important, since it may have both prognostic and therapeutic consequences for the patient with these infections.

The presence of such unusual bacteria causing various infections is mentioned in book chapters,12,17,22,33,42,46,79 case reports,26,34,39,43 and review articles.32,41 Most of these book chapters and review articles focus on descriptions of the microbiologic characteristics, nomenclature, and classification of these bacteria and are in general without specific application to PJIs. One review79 briefly mentions these unusual microorganisms as potential pathogens causing PJIs, without exploring in depth the diagnostic or therapeutic modalities used to treat pathogen-induced PJI.

We summarize current medical literature regarding the diagnosis and management of PJI due to unusual aerobic and anaerobic bacteria so clinicians can readily access the information.


We conducted a Medline search for all case reports or series of less commonly encountered aerobic and anaerobic microorganism species between 1966 and 2005. The primary author (CEM) also performed secondary manual reference searches of articles identified through the Medline search. Organisms included in the search were less common species of coagulase-negative staphylococci, nutritional-variant streptococci, aerobic non-spore and spore forming Gram-positive bacteria, and unusual Gram-negative and anaerobic bacteria published in the English and non-English literature between 1966 and 2005. We included reports this review if the diagnosis of PJI was made based on suggested criteria.59,79

Aerobic Gram-positive Bacteria

Coagulase-negative staphylococci (CoNS), followed by Staphylococcus aureus, are the most common pathogens causing PJI. Most investigators, however, have not described the various CoNS species causing PJI, and thus differences in the incidence, clinical presentation, and outcome of PJI due to different CoNS species is unknown. CoNS are easily isolated using conventional microbiology testing media and incubation conditions.

Staphylococcus caprae (S. caprae) was originally isolated from goat's milk.26 Staphylococcus caprae infections in humans have been acquired nosocomially following the administration of antimicrobials. These staphylococcal strains harbor resistance to several antimicrobials, including intrinsic resistance to β-lactams encoded by the mec A gene. Furthermore, slime production may contribute to the virulence of S. caprae and might prevent antimicrobials from accessing the microorganism. Four cases of S. caprae total hip arthroplasty (THA) and total knee arthroplasty (TKA) PJI have been reported to date.6 None of the patients had contact with goats. The infected prosthesis was removed in two reported cases 7 to 19 months after implantation.6 One patient with an infected THA underwent removal of the prosthesis 3 months after treatment with fusidic acid and pefloxacin. Reim-plantation arthroplasty was performed two months after discontinuation of antimicrobials. The reimplanted THA became infected with S. caprae. The presence of retained cement may have limited the thoroughness of the débridement and allowed the pathogen to persist. The reimplanted THA was subsequently resected.6 In another report, a TKA became infected with S. caprae 1 month after the end of antimicrobial treatment for a primary infection caused by S. epidermidis.6

Razonable et al69 reported a case of a THA infection with S. simulans in a 70-year-old farmer who was active in birthing and milking his cows and drank unpasteurized milk. The patient had concomitant S. simulans vertebral osteomyelitis. In this case, S. simulans THA PJI presented as an acute and presumably hematogenous infection. The patient was treated with resection arthroplasty, 6 weeks of parenteral ceftriaxone, and 4 weeks of oral cephalexin. His THA was reimplanted 12 weeks later. The outcome at 3 months after the staged reimplantation was favorable, with no evidence of recurrence of the THA infection or vertebral osteomyelitis.69

Staphylococcus lugdunensis (S. lugdunensis) is another CoNS whose pathogenic potential is similar to S. aureus. To date, 3 cases of TKA PJI related to S. lugdunensis have been reported, two in immunocompromised76 and one in an immuno-competent patient.92 All reported episodes had late onset and acute presentation. All S. lugdunensis isolates involved in PJI were β-lactamase negative and susceptible to oxacillin. Two patients were treated with débridement and retention of the pros-thesis and parenteral antimicrobial therapy of 6 weeks of cefazolin and 10 days of flucloxacillin and fusidic acid, respectively.76,92 Though the infection recurred in the patient treated with a short course of parenteral antimicrobials, the outcome of both patients at 8 months and one year, respectively, was favorable using chronic oral antimicrobial suppression. Another patient was treated with resection arthroplasty, 6 weeks of ceftriaxone, and reimplantation 2 weeks after discontinuation of antimicrobials.76 There was no evidence of recurrence of the infection after 10 months. There are insufficient data to determine whether the outcome of S. lugdunensis PJI treated with débridement and retention of the prosthesis will be similar to the outcome of S. aureus PJI.15,76,92

Aerobic Catalase-negative Gram-positive Cocci

Streptococcus bovis (S. bovis). Two cases of S. bovis THA and TKA infections have been reported in the literature.29,95 The infections occurred 6 and 22 months after implantation. Emerton et al29 reported one case of S. bovis THA PJI occurring 1 month after a nonspecific flu-like illness in the absence of endocarditis. The patient presented with sudden onset of hip pain.29 The microorganism is usually susceptible to penicillin. Joint aspiration followed by antimicrobial therapy for the S. bovis TKA infection in a patient in the series reported by Wilde and Ruth was unsuccessful.95 No details are given regarding the number of joint aspirations or the duration of antimicrobial therapy for this patient. Subsequently, both patients underwent two-stage exchange and the outcome was favorable after 6 and 74 months, respectively. A colonoscopy in the patient with THA infection29 revealed a large polypoid lesion in the proximal colon and a histology compatible with premalignant changes. The polyp was resected. The association between S. bovis bacteremia and endocarditis and the presence of an underlying colonic tumor has been extensively reported.57 The author suggested colonic investigation should also be considered for patients diagnosed with S. bovis PJI, since isolation of this microorganism from prosthetic joints raises the possibility of a prior bacteremia.

Gemella morbillorum (formerly Streptococcus morbillorum) and Gemella haemolysans PJI have been reported in two cases.27,91 Both cases occurred in patients with rheumatoid arthritis and involved an elbow and a knee prosthesis, respectively. Gemella haemolysans has been reported in one case as a late chronic infection.91 Gemella morbillorum was isolated from joint fluid at the time of revision of a total elbow arthroplasty in a patient with a sinus tract.91 Testing of the susceptibility of the G. haemolysans case showed resistance to gentamicin, trim-ethoprim, and cotrimoxazole.27 The microorganism is typically susceptible to penicillin, erythromycin, tetracycline, and vancomycin. Both reported patients were treated with two-stage exchange. The patient with G. haemolysans was treated with re-section arthroplasty and 6 weeks of parenteral penicillin G and reimplanted with favorable outcome after 2 months.27 No details about medical therapy or outcome were provided for the second case.27 Other streptococcal species uncommonly reported as a cause of PJI include Abiotrophia (one case),72 and Streptococcus pneumoniae.66,71,74,79,82 In general, all aerobic streptococci, with the exception of nutritionally variant streptococci like Abiotrophia spp., can be cultivated using standard media and incubation conditions. Nutrionally variant streptococci require supplemented media for adequate growth.

Aerobic Nonspore-forming Gram-positive Bacilli

Corynebacterium jeikeium (C. jeikeium)

Four cases of PJI caused by C. jeikeium have been reported in the literature. Three involved a THA and one involved a TKA.86,99 In all cases C. jeikeium PJI presented as late chronic, indolent infection. This microorganism is susceptible to vancomycin and resistant to penicillins. It has variable susceptibility to erythromycin, tetracycline, rifampin, and quinolones.32 Three patients with C. jeikeium THA PJI were successfully treated with resection arthroplasty, 6 weeks of vancomycin, and reim-plantation. One patient was successfully treated with partial removal of the prosthesis and administration of 6 weeks of vancomycin and chronic oral suppression with minocycline.86 All patients were free of infection after 6 months to 1 year. Resection arthroplasty, repeated débridement and prolonged therapy (5 weeks of vancomycin and 8 weeks of oral tetracycline) were used to cure the infection of the patient with C. jeikeium TKA infection. The followup for this patient was 7 months.99

Listeria monocytogenes (L. monocytogenes)

To date, 15 cases of PJI due to Listeria have been reported in the literature.1,2,5,13,19,21,24,28,45,54,83,93 The source is usually unknown, but a number of reports have implicated the consumption of unpasteurized milk,5,13 vegetables, or processed meat. Listeria monocytogenes PJIs tend to occur in elderly or immunocompromised patients. PJIs caused by Listeria typically present as late infections. In the reported cases, it was thought infection was probably the result of transient bacteremia. Listeria is susceptible in vitro to ampicillin, trimethoprim-sulfamethoxazole, aminoglycosides, and vancomycin. Cephalosporins are not effective against Listeria and false positive in vitro sensitivity reports can result from the use of disk diffusion tests.5 Prosthesis removal eventually led to elimination of the infection in five of the reported 15 patients. Attempts can be made to salvage the pros-thesis in patients whose medical conditions preclude surgical intervention. Failure of nonoperative management resulting in one-stage exchange was recently reported after 8 months of followup.24 There was no evidence of infection after 1 year of followup in this patient.83 The recommended medical therapy is parenteral ampicillin with or without gentamicin. Gentamicin should not be used as monotherapy.5 Little information about the optimal duration of treatment is available. Six weeks of intravenous antimicrobials appeared to be adequate in reported cases. Profoundly immunocompromised patients may require lifelong oral antimicrobial suppression.1 The duration of follow-up in reported patients varied between 6 months and 2 years. Both C. jeikeium and L. monocytogenes grow adequately from clinical specimens obtained from usual sterile sites by using standard media and incubation parameters. Culture enrichment techniques may be required to isolate Listeria monocytogenes from specimens obtained from nonsterile sites.

Actinomyces israelii (A. israelii) and naeslundii (A. naeslundii)

Unusual cases of PJI have been caused by Actinomyces israelii (A. israelii) and naeslundii (A. naeslundii),4,10,23,63,98,100 Nocardia nova (N. nova) and asteroides (N. asteroides),8,73 Tsukamurella paurometabolum (T. paurometabolum),47 Oerskovia xanthineolytica (O. xanthineolytica),38 Dietzia maris (D. maris),64 and Rothia dentocariosa (R. dentocariosa).88 Many reported cases occurred in immunocompromised patients with systemic lupus erythematosus (SLE), intravenous drug use, ethanol abuse, or steroid use. Some cases occurred in immunocompetent patients.47,64,73,98 Actinomyces israelii and A. naeslundii typically present as late THA infections in immunocompetent patients after dental work, after intrauterine device insertion, or in intravenous drug users.100 These infections are thought to occur as a result of hematogenous spread. To date, five cases have been reported in the literature. Actinomyces infections usually respond to high doses of penicillin, ceftriaxone, tetracycline, or erythromycin. Quinolones have limited activity against A. israelii.36 The optimal duration of treatment is unknown. Patients have been effectively treated with parenteral penicillin G for 2 to 6 weeks, followed by oral amoxicillin, ampicillin, or penicillin VK for 6 to 12 months.100 The prosthesis was removed in three patients.63,81,100 Two-stage exchange was performed in another patient, with good outcome after 6 months.81 Parenteral antimicrobials without surgical therapy were administered in the fifth case with complete recovery.98 The long-term outcome is not known for this patient. In general, isolation of Actinomyces spp. from clinical specimens requires culture in an anaerobic environment.

Nocardia nova and N. asteroides

The opportunistic behavior of Nocardia facilitates the development of infection in immunocompromised patients (cancer, hematological malignancies, particularly lymphoid, chronic respiratory diseases, corticosteroid treatment, transplant recipients). Nocardia spp. will grow best in aerobic conditions on a variety of media including media used for isolation of bacteria, Myco-bacteria spp., and fungi. Two cases of Nocardia THA infection have been reported, one in an immunocompetent patient and the other in a patient with SLE.8,73 Nocardia nova presented as a late, indolent infection in this patient with SLE, 2 years after being diagnosed with pulmonary nocardiosis. The infection in the immunocompetent patient occurred in the early postoperative period, and it was thought to be a result of perioperative contamination of the prosthesis.73 Susceptibilities should be interpreted in accordance with the Clinical Laboratory Standards Institute (CLSI, formally National Committee on Clinical Laboratory Standards, NCCLS) guidelines.58 The drugs of choice for the treatment of N. asteroides infections are sulfonamides. In the reported cases of PJI, N. nova was susceptible to imipenem, erythromycin, and amikacin. Imipenem-amikacin combination appears to be more effective than trimethoprimsulfamethoxazole in infections caused by Nocardia, in particular N. nova, which is resistant to sulfonamides. Though N. nova may demonstrate susceptibility to ampicillin or amoxicillin in vitro, it consistently carries a beta-lactamase, which may hydro-lyze these antibiotics.7 Linezolid is active in vitro against all Nocardia species.16,56,89 Removal of the prosthesis was performed in both reported patients. Intravenous minocycline and oral ofloxacin for 6 weeks were administered for N. asteroides THA infection, followed by reimplantation. Oral drug therapy was continued after reimplantation for 6 months, with a favorable outcome after 1 year. In another patient, administration of imipenem and erythromycin for 35 days after resection arthroplasty, followed by erythromycin alone for 2 months, had a favorable outcome after 6 months.8

Dietzia maris

Dietzia maris (formerly Rhodococcus maris) is an environmental actinomycete. To date, one case of D. maris, diagnosed at the time of revision of a THA, has been reported.64 The microorganism was susceptible, by disk-diffusion method, to amoxicillin, imipenem, gentamicin, trimethoprim-sulfamethoxazole, rifampin, clindamycin, vancomycin and pristinamycin. This patient was treated with teicoplanin for 4 months. No surgical procedure was performed and no followup data were reported.

Tsukamurella paurometabolum

Tsukamurella paurometabolum is a Gram-positive, weakly or variable acid fast, nonmotile, obligate aerobic bacillus that exists primarily as a saprophyte in the soil. Tsukamurella should be recognized as a potential pathogen in patients with immunosuppression, indwelling foreign bodies, and postoperative wounds. In one case, Tsukamurella was found after repeated débridements and removal of a TKA for a mixed (peptostreptococcus and CoNS) infection.47 The microorganism is susceptible to sulfamethoxazole, clarithromycin, imipenem, amikacin, ciprofloxacin, rifampin, vancomycin and third generation cephalosporins. The patient was treated with resection arthroplasty and 2 months of clarithromycin and ciprofloxacin. Reimplantation was performed 4 months after resection arthroplasty and had a successful outcome. The duration of followup was not mentioned.

O. xanthineolytica

Oerskovia species are Gram-positive, Nocardia-like bacilli that inhabit the soil. To date, one case of TKA late infection with O. xanthineolytica has been reported.38 The infection had a chronic, indolent course and was identified at the time of revision arthroplasty for presumed aseptic loosening. Penicillin or ampicillin, rifampin, and vancomycin are the drugs of choice to treat infections caused by this microorganism.30 The patient was treated with resection arthroplasty, and 5 weeks of trimethoprimsulfamethoxazole. Reimplantation was performed 3 months after resection arthroplasty. The outcome was excellent after 6 months.

Aerobic Spore-forming Gram-positive Bacilli

Nonanthrax-Bacillus species often occur in immunocompromised patients or intravenous drug users. Bacillus alvei has previously been associated with European foulbrood of honeybee larvae.22 It was described as a cause of late acute THA infection in a patient with sickle-cell disease who presented with B. alvei bacteremia. The patient was treated with prosthesis removal and administration of 6 weeks of vancomycin (to which the organism was susceptible) and ceftriaxone. The patient remained well after 18 months.70 Bacillus spp. grow readily on conventional media in an aerobic environment.

Aerobic Gram-negative bacteria

Achromobacter xylosoxidans (A. xylosoxidans)

Achromobacter xylosoxidans (A. xylosoxidans) is an aerobic, Gram-negative nonfermentative bacillus. Saline contaminated with A. xylosoxidans used in processing specimens was found to be the cause of two THA pseudoinfections.37 It has been suggested when A. xylosoxidans is cultured from a hospitalized patient, an environmental source of infection should be considered. However, this organism has been reported as a cause of acute TKA infection in a 53-year-old woman with rheumatoid arthritis who had been treated with methotrexate (MTX) and prednisone.85 Achromobacter xylosoxidans is usually susceptible to carbenicillin, imipenem, and trimethoprim-sulfamethoxazole and resistant to aminoglycosides. It has variable susceptibilities to chloramphenicol, ureidopenicillins, and third-generation cephalosporins. Treatment involved implant removal, administration of imipenem and trimethoprim-sulfamethoxazole for 6 weeks, and reimplantation 4 months after discontinuation of antimicrobials. The outcome was favorable. The duration of the followup was not mentioned.85

Pseudomonas oryzihabitans (P. oryzihabitans) (formerly Flavimonas oryzihabitans) and Pseudomonas luteola (P. luteola) (formerly Chryseomonas uteola)

Rahav et al68 described three cases of late chronic THA PJI caused by P. oryzihabitans within a 4-year period. Two of the reported cased occurred in patients with diabetes mellitus. Pseudomonas oryzihabitans is susceptible to penicillin, third-generation cephalosporins, mezlocillin, imipenem, aminoglyco-sides, cotrimoxazole, and ciprofloxacin, and is resistant to first and second-generation cephalosporin, tetracycline and ampicillin. All three reported patients were treated with ciprofloxacin.68 The prosthesis was removed in one case, secondary to an infection with S. aureus.68 Long-term outcome was not mentioned, especially for patients treated nonoperatively.


Salmonella infection is mainly seen in young or debilitated patients, in patients with sickle cell disease, collagen vascular disease, or HIV. To date, only 14 cases have been reported in the literature. Three involved a TKA. Among the 14 reported cases, one patient had sickle cell trait and five patients had other immunocompromising conditions (rheumatoid arthritis, renal transplantation, familial Mediterranean fever, ankylosing spondylitis).67,77,94 Salmonella typhimurium (S. typhimurium) was the isolate most frequently seen. The presentation is acute and usually secondary to bacteremia and/or gastroenteritis. Infections may occur in the early or late postoperative period. Antimicrobial choices for Salmonella PJI include ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, third-generation cephalosporins, and fluoroquinolones. In 1996, the prevalence of S. typhimurium isolates with resistance to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline was 34%.35 In 2001, 60% of S. choleraesuis isolates were resistant to ciprofloxacin.20 Given the increasing rate of resistance among Salmonella strains, therapy should be guided by the in vitro susceptibility studies. For susceptible isolates, fluoroquinolones may be the preferred agent. Overall, six of 14 reported patients underwent removal of the prosthesis. Day et al25 reported a case of a TKA infection with Salmonella enteritidis who was treated with débridement and retention, exchange of tibial polyethylene component, and 6 weeks of ceftriaxone. In this case, the outcome was excellent after 6 years. In a second case, a patient with Salmonella dublin (S. dublin) THA infection was treated with débridement and component retention. Trimethoprimsulfamethoxazole was administered for 2 years. The patient did not show any clinical signs of recurrence.18 One case of S. dublin THA PJI relapsed after one-stage exchange arthroplasty. Ciprofloxacin was administered for 1 year, and had an excellent outcome after 3.5 years.94 Two-stage exchange for Salmonella THA infection was associated with an excellent outcome in two patients.31,84 In three cases no surgical intervention was performed and patients were maintained on chronic oral suppression.50,67,77 The infection relapsed in one patient. All of the Gram-negative bacilli discussed above grow readily using standard media and aerobic incubation conditions.

Aerobic Gram-negative Cocci and Coccobacilli

Neisseria meningitides (N. meningitides)

A case of primary meningococcal TKA PJI was described by Vikram et al in an 80-year-old woman with no obvious risk factors for PJI or meningococcal disease.90 The onset of symptoms was acute, and the patient had associated meningococcal bacteremia, without evidence of meningitis. The patient was treated with débridement and retention of components, 6 weeks of parenteral ceftriaxone, and chronic antimicrobial suppression with oral penicillin. The patient had resolution of the symptoms with no evidence of infection after 5 months.90 N. meningitidis, unlike its more fastidious counterpart, N. gonnorhoeae, will grow on standard media cultured under aerobic conditions.

Haemophilus influenzae (H. influenzae)

There are sporadic reported cases of Haemophilus influenzae (H. influenzae) PJI of THA14 and TKA11 in the literature. Due to its fastidious nature, H. influenzae requires chocolatized blood agar incubated under aerobic conditions, for isolation. Risk factors for Haemophilus influenzae septic arthritis include multiple myeloma, SLE, common variable hypogammaglobulinemia, and alcohol abuse. Two reported patients with H. influenzae PJI had rheumatoid arthritis and SLE.2,11 Blood cultures are usually positive. The infections were acute. Haemophilus influenzae is usually susceptible to cefuroxime, ceftriaxone, quinolones, and trimethoprim-sulfamethoxazole. Between 5-30% of the β-lactamase producing Haemophilus spp are resistant to ampicillin, and in certain areas the resistance may exceed 60%.46 Septic loosening occurred after 3 months in one case44 and the patient underwent two-stage exchange. Chronic suppression was attempted in another patient with H. influenzae TKA PJI. The patient improved after an 8 week course of intravenous ceftriaxone, and oral antimicrobials (trimethoprim-sulfamethoxazole and subsequent oral ciprofloxacin) for 2 years.51

Moraxella catarrhalis (M. catarrhalis)

A case of TKA PJI due to Moraxella catarrhalis (M. catarrhalis) was reported in a patient with rheumatoid arthritis and interstitial lung disease treated with anakinra. The patient had a successful outcome with discontinuation of anakinra, closed joint drainage, and a 40-day course of ciprofloxacin and clindamycin. Long term followup for this patient was not reported.48 M. catarrhalis is easily cultured using standard media and incubation conditions.

Anaerobic Bacteria

Anaerobic bacteria should not be disregarded as contaminants, especially when isolated in pure culture from clinical specimens involving cases of PJI. In general, all cultures plated for bacteria for specimens obtained from patients with PJI should be cultured under both aerobic and anaerobic conditions.

Clostridium difficile (C. difficile)

In a retrospective study performed at a tertiary care hospital, out of 14 cases of extracolonic C. difficile identified, only one involved a THA in a patient with sickle cell disease and a history of C. difficile diarrhea.97 Previous antimicrobial use was reported in all cases of C. difficile THA PJI. Sickle cell disease with functional asplenia3 and femoral osteosarcoma65 were the underlying diseases in two of the three reported cases. Two cases presented as late chronic infections and occurred after C. difficile-associated diarrhea (CDAD) at variable intervals. A sinus tract developed in one case65 and abscess occurred in two patients.3,55 McCarthy and Stingemore55 reported a case of C. difficile THA infection that occurred 12 months after resolution of CDAD. In one patient, the C. difficile TKA infection was discovered when an external arthrotomy was performed after a traumatic fracture of the patella.65 Pron et al65 reported a case of a TKA infection that underwent amputation in a patient with femoral osteosarcoma. All reported cases have been treated with metronidazole. Vancomycin is also active against Clostridium difficile. Resection arthroplasty and limb amputation after failure of open arthrotomy and antimicrobial therapy were performed in two patients, respectively. One patient died as a result of complications of the primary disease.

Veillonella dispar (V. dispar), Veillonella parvula (V. parvula), Prevotella melaninogenica (P. melaninogenica) and Clostridium perfringens (C. perfringens)

Cases of PJI caused by Veillonella dispar (V. dispar), Veillonella parvula (V. parvula), Prevotella melaninogenica (P. melaninogenica) and Clostridium perfringens (C. perfringens) have been reported or included in PJI series.53,62,75,79,80,101 Surgical modalities used to treat C. perfringens PJI included débridement and prosthesis retention,52 resection arthroplasty and intravenous antimicrobial therapy,62 two-stage exchange,80,96 and intravenous antimicrobial therapy alone.75 Complications included a persistent sinus tract infection in one of the patients treated with antimicrobial therapy alone and reinfection with a different micro-organism after reimplantation.96 One patient died 20 months after resection arthroplasty from noninfectious causes.62


The majority of literature on PJI focuses on the diagnosis and treatment of PJIs caused by common microorganisms such as S. aureus and S. epidermidis. These microorganisms are typically easily isolated in the microbiology laboratory using conventional media. This article reviews for the first time the available medical literature regarding the diagnosis and management of less commonly encountered PJI pathogens, such as certain species of coagulase-negative staphylococci, nutritional-variant streptococci, aerobic nonspore and spore forming Gram-positive, some aerobic Gram-negative bacilli and cocci or unusual anaerobic microorganisms. The recognition of such micro-organisms causing PJIs is very important, since it may have prognostic and therapeutic implications.

Traditional methods of diagnosis of PJI rely on the isolation of a pathogenic microorganism from the joint space or the periprosthetic site by tissue stain or culture. The sensitivity of these cultures ranges from 65-94%, depending on the definition of infection.102 Several authors have advocated at least three intraoperative tissue specimens for culture.9,60,78,102 The utility of inoculation of synovial fluid into blood culture media for isolation of bacteria has been also demonstrated.40,49

Traditional microbiologic methods of identification by culture of some of the unusual bacteria may be time consuming, and have neither ideal sensitivity nor specificity. In these situations, the clinician is confronted with the challenge of timely and accurate identification of the pathogen causing PJIs, since timely microbiology results are critical to effective treatment and to reduction of the overall cost of patient care. Hence, the emergence of newer techniques such as prosthesis vortexing/sonication, followed by culture, immunofluorescence, fluorescence in situ hybridization or polymerase chain reaction may lead to easier identification, improve recovery of such unusual microorganisms and increase sensitivity of the cultures.61 Molecular diagnostic methods detect bacterial nucleic acid in samples from infected patients even when conventional cultures are negative (because of unusual microbial growth requirements or failure to grow after antimicrobial exposure due to unfavorable environmental conditions).87 Polymerase chain reaction (PCR) assays are able to detect one copy of bacterial DNA under optimal conditions and can have a rapid turnaround time. When the infecting pathogen is not known, and the goal is to identify the presence of any bacterial pathogen causing PJI, broad-range PCR amplification can be used. However, one of the most difficult challenges associated with this method has been prevention of exogenous nucleic acid contamination leading to false-positive reactions. Another limitation of this method is amplification techniques fail to provide antimicrobial susceptibility of the pathogen, which is crucial for appropriate therapy.87

We believe a history of exposure or host susceptibility to a particular pathogen elicited at the time of the patient interview remains key to considering the possibility of infection due to these unusual pathogens. If unusual bacteria are considered causative agents for PJI, consultation with laboratory personnel is advised to assure that proper culture techniques and/or newer, more sensitive techniques of identification, as discussed above, are undertaken.

The clinician has traditionally had a hard time easily accessing references on the presentation and treatment of PJI due to these organisms, since they are published as single case reports or small case series in multiple journals published over the last two to three decades. Due to small numbers of reported cases caused by these unusual micro-organisms, it is difficult to formulate guidelines for their specific management. Case reports and small case series do not assess the optimal treatment of these unusual infections; rather they provide information about the micro-biologic diagnosis, treatment and outcome in a single patient or series of patients.

When the clinician is confronted with the challenges related to the optimal surgical and medical management of PJIs due to an unusual bacteria in a particular patient, several questions arise: (1) what is the best surgical treatment strategy leading to a successful outcome; (2) if the “best strategy” is impractical, are there other therapeutic modalities available and what is their outcome; (3) what is the optimal medical therapy and its duration, considering the important issues of emergence of antimicrobial resistance and antimicrobial adverse effects; (4) what are the newer antimicrobial agents that may become therapeutic alternatives to treat these unusual bacteria and have they been used to treat PJI? While this review article can neither formulate guidelines for treatment, nor provide definitive answers to the above questions, it may serve as a guide for making an appropriate management decision.

When a patient presents with a PJI due to an unknown pathogen in which an unusual microorganism has been isolated, or should be considered based on the history or physical exam, the clinician can then decide the best diagnostic tests and treatment strategy based on the available literature, microbiology laboratory support, in vitro susceptibility testing of the microorganism, and the availability of the most effective and least toxic antimicrobials. We believe the information we provide will help the clinician with this task.


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