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Propionibacterium acnes infection after shoulder arthroplasty: A diagnostic challenge
J Shoulder Elbow Surg (2010) 19, 303-307
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Propionibacterium acnes infection after shoulder arthroplasty: A diagnostic challenge Christopher C. Dodson, MDa,b,*, Edward V. Craig, MDb, Frank A. Cordasco, MDb, David M. Dines, MDb, Joshua S. Dines, MDb, Edward DiCarlo, MDb, Barry D. Brause, MDb, Russell F. Warren, MDb a b
Sports Medicine Service, Rothman Institute, Philadelphia, PA, USA Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, NY, USA Hypothesis: This study reviewed a series of patients diagnosed with Propionibacterium acnes infection after shoulder arthroplasty in order to describe its clinical presentation, the means of diagnosis, and provide options for treatment. Materials and methods: From 2002 to 2006, 11 patients diagnosed with P acnes infection after shoulder arthroplasty were retrospectively reviewed and analyzed for (1) clinical diagnosis; (2) laboratory data, including white blood cell count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP); (3) fever; (4) number of days for laboratory growth of P acnes; (5) organism sensitivities; (6) antibiotic regimen and length of treatment; and (7) surgical management. Infection was diagnosed by 2 positive cultures. Results: Five patients had an initial diagnosis of infection and underwent implant removal, placement of an antibiotic spacer, and staged reimplantation after a course of intravenous antibiotics. In the remaining 6 patients, surgical treatment varied according to the clinical diagnosis. When infection was recognized by intraoperative cultures, antibiotics were initiated. The average initial ESR and CRP values were 33 mm/h and 2 mg/dL, respectively. The average number of days from collection to a positive culture was 9. All cultures were sensitive to penicillin and clindamycin and universally resistant to metronidazole. Discussion: Prosthetic joint infection secondary to P acnes is relatively rare; yet, when present, is an important cause of clinical implant failure. Successful treatment is hampered because clinical findings may be subtle, many of the traditional signs of infection are not present, and cultures may not be positive for as long as 2 weeks. Level of evidence: Level IV, Case series, Treatment study. Ó 2010 Journal of Shoulder and Elbow Surgery Board of Trustees. Keywords: P acnes; Shoulder; arthroplasty; infection; Propionibacterium acnes
Infection after shoulder arthroplasty can be a devastating complication. The reported prevalence of deep periprosthetic infection involving shoulder arthroplasty ranges *Reprint requests: Christopher C. Dodson, MD, Attending Orthopaedic Surgeon, Rothman Institute, 925 Chestnut St., Philadelphia, PA 19107. E-mail address: [email protected] (C.C. Dodson).
from 3.9% to 15.4%.4,23 A delay in the diagnosis of infection in the shoulder can lead to chronic pain, prosthetic instability, and even sepsis; therefore, it is important that a timely diagnosis be made. Postoperative infection subsequent to shoulder arthroplasty is most commonly caused by the bacterial species Staphylococcus aureus and coagulase-negative
1058-2746/2010/$36.00 - see front matter Ó 2010 Journal of Shoulder and Elbow Surgery Board of Trustees. doi:10.1016/j.jse.2009.07.065
304 Staphylococcus. Propionibacterium acnes (P acnes) is a gram-positive, non-spore-forming, anaerobic bacillus found in the cutaneous, upper respiratory, and digestive mucosae.2,6,11 Traditionally considered nonpathogenic,8,12 this anaerobe has been reported to be responsible for severe infections at various body sites, including central nervous system infections,13,17 endocarditis,9,15 and peritonitis.7 Recently and most significantly, P acnes has also been recognized as an orthopedic pathogen.1,3-5,10,14,16,18-24 This is a review of a series of P acnes infections after shoulder arthroplasty. Often presenting in the subacute to late time frame, its diagnosis has proven to be difficult because the usual clinical and laboratory indicators of infection are frequently absent, and the standard time frame during which cultures are held in laboratories is frequently exceeded. The following series details the clinical presentation, diagnostic experience, and treatment suggestions for this difficult clinical problem.
Materials and methods The Investigational Review Board (IRB) of the Hospital for Special Surgery, New York, approved this study (IRB #26057). During a 4-year period (2002-2006), 11 patients (8 men, 3 women) were diagnosed with P acnes infection after shoulder arthroplasty. To ensure that a positive culture represented infection rather than specimen contamination, 2 positive intraoperative specimens were required for infection diagnosis. The medical records of these 11 patients were analyzed and retrospectively reviewed for the following data: (1) preoperative diagnosis, (2) laboratory values for white blood cells (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP); (3) fever, (4) average time for culture in days, (5) organism sensitivities, (6) antibiotic treatment, (7) pathology, and (8) surgical management. All patients were under the care of an infectious disease specialist (B. M. B.). Four primary surgeons treated the 11 patients. Infection was documented with positive intraoperative cultures from surgical specimens or by histologic evidence of inflammation with more than 10 polymorphonuclear cells per high power field, or both. Infection was classified as acute if it developed within 3 months from the time of the arthroplasty, subacute if it developed between 3 months and 1 year postoperatively, and late if it developed more than 1 year from the time of arthroplasty. The average interval from the index arthroplasty to the diagnosis of infection was 2.1 years (range, 1-4 years). We were unable to identify any systemic risk factors for infection in any of the 11 patients other than prior surgery. All patients were prepared for the operation with standard Betadine (Purdue Pharma L.P., Stamford, CT) microbicide solution and were draped in the usual sterile fashion. We typically do not wear spacesuits when performing shoulder arthroplasty. The mean age of the patients was 60.1 years, (range 47-78 years). The dominant shoulder was involved in 8 patients. The indications for the initial shoulder arthroplasty were osteoarthritis in 7, cuff tear arthropathy in 3, and traumatic arthritis in 1. The average number of surgical procedures performed before the index arthroplasty was 0.4, (range, 0-2), and the average follow up was 4.0 years (range, 2-6 years). The index shoulder arthroplasty was
C.C. Dodson et al. done at our institution in 7 patients. The index procedure in 4 patients was performed elsewhere, and they were referred to our institution for definitive management. The patients were divided into 2 groups according to a preoperative diagnosis of infection. Group I consisted of 5 patients who were diagnosed with infection before revision surgery by examination, laboratory values, radiographs, or isolation of P acnes from at least 2 different aspiration samples. None of these patients received preoperative antibiotics, and all 5 underwent implant removal and placement of an antibiotic spacer. Group II consisted of 6 patients who presented with a painful prosthesis without suspicion of infection before revision surgery. Three underwent revision shoulder arthroplasty for loosening of the glenoid component, 2 patients with cuff arthropathy and hemiarthroplasties were converted to a reverse prosthesis, and 1 patient with recurring dislocations of a reverse prosthesis had revision of the polyethylene component. Preoperative imaging identified a source of mechanical dysfunction and pain in all 6 of these patients, but it was not suspicious for infection, and thus, none of these patients received antimicrobial therapy before revision surgery. As part of their definitive treatment, all 11 patients had insertions of peripherally inserted central catheters and were treated systemically with intravenous antibiotics for a variable length of time.
Results In group I, the average WBC was 7,280 cells/L (range, 6,000-9,000 cells/L), the average ESR was 44.4 mm/h (range, 13-86 mm/h), and the average CRP was 3.42 mg/dL (range, 0.8-8.8 mg/dL). The normal values at our institution for ESR are 0 to 12 mm/h for men and 0 to 27 mm/h for women, and for CRP, less than 0.7 mg/dL. No patients presented with fever. A mean of 0.8 de´bridements (range, 0-3) after the reimplantation were necessary for the eradication of infection. One patient required a second explantation. Tissue pathology in all patients demonstrated acute and chronic inflammation with necrosis and granulation tissue of variable amounts consistent with infection (Table I). The average time to receive pathologic results was 30 minutes for frozen sections and 2 days (range 1-3 days) for routine histopathology. The average time for growth in culture was 9 days (range 8-10 days). All cultures were positive for P acnes. After surgery, all patients were treated prophylactically with IV cefazolin (1 g/8 h) until P acnes was identified, at which time the antibiotic regimen was switched to IV penicillin G K þ salt (3 million U every 4 hours) or IV clindamycin (900 mg, three times daily). The IV antibiotics were administered for a mean of 6.3 weeks (range, 6-9 weeks). After IV antibiotics, 3 patients received oral antibiotics for a mean of 3.3 weeks (range 2-8 weeks). All organisms were sensitive to both penicillin and clindamycin and resistant to metronidazole. Preoperative aspiration of the joint in 2 patients produced a positive culture in 1. The infection completely resolved after staged implant exchange in 3 patients in group I. Infection resolution was
Acnes after shoulder arthroplasty
305
Table I Patient laboratory values, number of days for the laboratory to grow Propionibacterium acnes, the pathology results, and the type of antibiotic administered) Patient
ESR (mm/h)
CRP (mg/dL)
WBC (109/mL)
Time to culture (days)
Pathologyy
Antibiotics
1 2 3 4 5 6 7 8 9 10 11
13 86 23 40 11 53 16 20 30 45 25
0.8 8.8 1 2 0.6 2.5 3 1.1 3 1.5 1
6.4 9 6 7 9 6 8 7 8 7.5 6
8 9 10 10 8 8 9 8 10 9 9
Positive Positive Positive Positive . Positive . Positive Positive Positive .
Penicillin G Penicillin G Clindamycin Penicillin G Penicillin G Penicillin G Penicillin G Penicillin G Penicillin G Penicillin G Penicillin G
CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; WBC, white blood cell. ) No patients presented with a fever, and all cultures grew Propionibacterium acnes. y Pathology was positive when the tissue sample demonstrated acute and chronic inflammation with necrosis and granulation tissue of variable amounts but of the type and degree that is usually associated with infection with or without implant debris.
defined as no clinical sequelae of infection after surgery, normal appearance on radiographs, and negative final intraoperative cultures taken at the time of reimplantation of the prosthetic components. One patient required an additional irrigation and de´bridement for a persistently draining wound and superficial infection. No subsequent organism was identified, and the implant components were stable at the time of the de´bridement. The remaining patient had a persistent infection after the reimplantation that required 3 irrigation and de´bridement procedures, and then ultimately, an explantation for recurrent infection. At the latest follow-up, the patient had no clinical or radiographic evidence of infection and declined reimplantation. In group II, the average WBC count was 7,500 cells/L (range 6000-9000 cells/L), the average ESR was 25.6 mm/h (range, 11-45, mm/h), and the average CRP was 1.44 mg/dL (range, 0.6-3 mg/dL). No patients presented with fever. The tissue pathology in 3 patients demonstrated acute and chronic inflammation and granulation consistent with infection, whereas the other 3 patients demonstrated nondiagnostic granulation tissue in addition to particulate implant reaction. The average time for the treating surgeon to receive pathologic results was 30 minutes for frozen sections and 2 days (range 1-3 days) for routine histopathology. One frozen section and 5 cultures were sent for each patient. The average time to receive positive culture results was 8.8 days (range 8-10 days), and all cultures were positive for P acnes. Each of these patients, when informed of the ‘‘incidental’’ positive intraoperative cultures, chose medical management instead of surgical de´bridement. They were administered perioperative IV cefazolin (1 g every 8 hours) for 36 hours postoperatively and then clindamycin or penicillin when the intraoperative cultures grew P acnes. After IV antibiotic therapy, 5 patients received oral ampicillin (500 mg, twice daily) for a mean of 9 weeks (range, 8-10 weeks) until the
ESR and CRP had returned to normal values. One patient has remained on oral suppressive therapy for 24 months and does not have any clinical or radiographic signs of infection. Complications secondary to prolonged oral antibiotic therapy were not observed in this series. As in group I, all organisms in group II were sensitive to both penicillin and clindamycin and resistant to metronidazole. According to the timing of the infections relative to the index arthroplasty, there were 0 acute, 1 subacute, and 10 late infections. A summary of the laboratory values for both groups is reported in Table I, and a summary of the index and revision diagnoses as well as procedures is in Table II.
Discussion The shoulder is thought to have has a propensity for infection with P acnes because the organism is the dominant anaerobic bacteria isolated from healthy skin in moist areas such as the axilla.1,17,23 Until recently, the organism was thought to be a contaminant rather than a true pathogen. P acnes is known to be a common causative organism in infections after shoulder instability surgery22 and arthroplasty.23 Several authors have also reported that P acnes was the most common infecting organism of deep infection after rotator cuff repair.1,10,18 Infection after total shoulder arthroplasty is, fortunately, relatively uncommon but is nonetheless a devastating problem, and guidelines relative to the diagnosis and treatment of P acnes would seem valuable. The successful diagnosis and treatment of patients who are infected with P acnes remains a challenge, and the clinician has little information available for guidance in management. This is particularly true because of the difficulty diagnosing this organism, the subtlety of its presentation, its resistance to standard broad-spectrum antibiotics,
306
C.C. Dodson et al.
Table II
Patient summary of the index and revision diagnosis and procedure
Patient
Index diagnosis
Index procedure
Revision diagnosis
Revision procedure
1 2 3 4 5 6 7 8 9 10 11
Osteoarthritis Osteoarthritis Humeral head fracture Osteoarthritis Osteoarthritis CTA Humeral Head Fracture CTA Osteoarthritis Osteoarthritis Osteoarthritis
Noncemented TSR Noncemented TSR Cemented hemiarthroplasty Noncemented TSR Noncemented TSR Cemented Reverse TSR Cemented Hemiarthroplasty Cemented Reverse TSR Noncemented TSR Noncemented TSR Noncemented TSR
Infection Infection CTA Infection Glenoid loosening Infection CTA Instability Infection Glenoid loosening Glenoid loosening
Prosthesis removal; abx spacer Prosthesis removal; abx spacer Conversion to reverse TSA Prosthesis removal; abx spacer Glenoid removal Prosthesis removal; abx spacer Conversion to reverse TSA Spacer conversion Prosthesis Removal; abx Spacer Glenoid removal Glenoid removal
Abx, antibiotics; CTA, cuff tear arthropathy; TSR, total shoulder replacement.
and because this slowly growing organism requires a prolonged culture for at least 8 days to ensure a negative culture. Lutz et al16 reported that the WBC count is often within normal reference ranges in the setting of P acnes infection, and that values for ESR and CRP are more diagnostic. In addition, Mirzayan et al18 and Kwon et al14 found that the ESR and CRP were elevated in most cases of deep infection, with the former stating that the ESR was the most useful laboratory test for diagnostic purposes. Our experience in this series is similar: no patient had a preoperative leukocyte count of more than 10,000 cells/L, 5 patients (46%) had an ESR of 30 mm/h or higher, and 8 patients (72%) had a CRP of 1.0 mg/dL or higher. Adding to the difficulty and frustration surrounding P acnes infection is the observation that many laboratories routinely discard culture samples after 3 to 5 days. Although this is an adequate length of time to identify many typical organisms, this is not so for P acnes. Lutz et al reported 52 cases of arthroplastic and osteosynthetic infections due to P acnes, and the average time for culture was 13.3 days (range, 4-21 days). In this series, the average time for a positive culture was 9 days (range, 8-10 days). Because of this, we now request that all fluid cultures be held for at least 10 days before being discarded. Many authors have recommended preoperative aspiration to diagnose and confirm infection.5,14,16,23 Although certainly a reasonable guideline for management, we have found this most helpful only if there is a distinct collection that is visible either on magnetic resonance imaging (MRI) or ultrasound imaging. An effective organism-specific antibiotic regimen is crucial to completely eradicate any infection. Unlike most anaerobes, P acnes appears not to be sensitive to metronidazole. In this series, all cultures were resistant to metronidazole and sensitive to penicillin and clindamycin, and this information now guides our choice of antibiotic. This current study identified 2 distinct groups that were infected with P acnes based on preoperative suspicion for infection. Group I consisted of patients who were diagnosed with infection clinically on the basis of wound erythema or drainage, positive cultures, or evidence of a fluid collection
by MRI or ultrasound imaging. Group II consisted of patients who were diagnosed with prosthetic or soft tissue dysfunction, and in whom preoperative and intraoperative infection was not suspected, with the positive cultures being ‘‘ incidental’’ to treatment for the painful implant undergoing revision surgery. The patients in this group had been discharged to home by the time at least 2 intraoperative cultures became positive. This subset of patients was the most challenging regarding appropriate decision making, because in many instances they were doing well clinically, and both patients and clinicians were taken by surprise by the laboratory report of positive intraoperative cultures. Optimal treatment of any chronically infected prosthesis includes the removal of infected and necrotic tissue and all the components of the prosthesis, systemic antibiotics, and staged revision where clinically appropriate. Reimplantation may not always be possible because of the poor general condition of the patient, because of acceptable function despite removal of the prosthesis, or because of patient reluctance to have further surgery. Because of this, some have recommended retention of the prosthesis with longterm oral suppressive antibiotic therapy as an alternative to further surgery. Rao et al20 reported 36 patients who were treated with prosthetic retention and long-term suppressive oral antibiotic therapy for an average of 52.6 months. Their study confirmed a favorable outcome in 82.6% of patients after a mean follow-up of 5 years. The goal of any suppressive therapy is to achieve a functioning prosthesis without pain and drainage, while recognizing that infection is not completely eradicated. We generally maintain suppressive therapy until the laboratory values are normalized and consider longer-term suppression in those patients where normalization takes much longer; however, we have no data to support this. The ideal antibiotic regimen, optimal duration of oral suppressive therapy, and ideal patient population in which this treatment plan is best used is still unclear and needs additional data with prospective studies. The present study has the identifiable limitations of a retrospective, observational cohort. In addition, the sample
Acnes after shoulder arthroplasty size is small, thus limiting statistical power. Finally, although one infecting organism was involved, variability existed in antibiotic selection and duration.
Conclusion In conclusion, although this is a small series, it demonstrates that P acnes can be a true pathogen in the setting of shoulder arthroplasty and underscores that variables such as ESR, WBC, CRP, local wound condition, preoperative joint aspiration, and even intraoperative cultures if discarded prematurely can cloud the diagnosis of a clinically significant joint infection. The clinical effect of this study is to make clinicians aware of the significance of this organism and its role in affecting patients who have undergone some type of shoulder arthroplasty. More specifically, we hope this study can provide clinicians with an understanding of not only how to diagnose but also how to effectively treat this organism. From our experience with these patients, we have several recommendations that we have now incorporated into our standard practice: First, before the skin incision, the axilla is isolated with a commercially available adhesive antimicrobial drape (Ioban; #M, St. Paul, MN) to decrease the potential colonization by local P acnes. Second, all cultures from potential surgical site infections are incubated for a minimum of 10 days specifically to assess for Propionibacterium. Third, all patients undergoing revision shoulder arthroplasty are made aware that intraoperative culture results may alter planned treatment. Finally, consideration is now given for preoperative infectious disease consultation in all patients with painful implants so that supervision of and reaction to intraoperative cultures occurs in timely fashion.
Disclaimer No funding was necessary for this study. The authors, their immediate families, and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article.
References 1. Athwal GS, Sperling JW, Rispoli DM, Cofield RH. Deep infection after rotator cuff repair. J Shoulder Elbow Surg 2007;16:306-11.
307 2. Brook I. Anaerobic gram-positive non-sporulating bacilli. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett’s principles and practice of infectious disease. 4th edition. New York: Churchill Livingstone; 1995. p. 2206-8. 3. Brook I, Frazier E. Infections caused by Propionibacterium species. Rev Infect Dis 1991;13:819-22. 4. Cofield RH, Edgerton BC. Total shoulder arthroplasty: complications and revision surgery. Instr Course Lect 1990;39:449-62. 5. Cuckler JM, Star AM, Alavi A, Noto RB. Diagnosis and management of the infected total joint arthroplasty. Orthop Clin North Am 1991;22: 523-30. 6. Desplaces N. Les bacteries anaerobes en pathologie osseuse. Med Mal Infect 2000;30(suppl 2):97-101. 7. Dunkle LM, Brotherton TJ, Feigin RD. Anaerobic infections in children: a prospective study. Pediatrics 1976;57:311-20. 8. Finegold SM. Anaerobic bacteria in human disease. New York: Academic; 1977. p. 577-602. 9. Gunthard H, Hany A, Turina M, Wust J. Propionibacterium acnes as a cause of aggressive aortic valve endocarditis and importance of tissue grinding-a case report and review. J Clin Microbiol 1994;32: 3043-5. 10. Herrera MF, Bauer G, Reynolds F, Wilk RM, Bigliani LU, Levine WN. Infection after mini-open rotator cuff repair. J Shoulder Elbow Surg 2002;11:605-8. 11. Hillier SL, Moncla BJ. Peptostreptoccus, Propionibacterium, Eubacterium and other nonsporeforming anaerobic gram-positive bacteria. In: Murray R, Baron EJ, Pfaller MA, Tenover FC, Yolken RH, editors. Manual of clinical microbiology. 6th edition. Washington, DC: ASM; 1999. p. 587-602. 12. Jakab E, Zbinden R, Gubler J, Ruef C, von Graevenitz A, Krause M. Severe Infections caused by Propionibacterium acnes: an underestimated pathogen in late postoperative infections. Yale J Biol Med 1996;69:477-82. 13. Kaufman DM, Miller MH, Steigbigel NH. Subdural empyemaanalysis of 17 recent cases and review of the literature. Medicine 1975;54:485-98. 14. Kwon YW, Kalainov DM, Rose HA, Bisson LJ, Weiland AJ. Management of early deep infection after rotator cuff repair surgery. J Shoulder Elbow Surg 2005;14:1-5. 15. Lewis JF, Abrahamson JH. Enodcarditis due to Propionibacterium acnes. Am J Clin Pathol 1980;74:690-2. 16. Lutz MF, Berthelot P, Fresard A, et al. Arthroplastic and osteosynthetic infections due to Propionibacterium acnes: a retrospective study of 52 cases, 1995-2002. Eur J Clin Microbiol Infect Dis 2005;24: 739-44. 17. Mathisen GE, Meyer RD, George WL, Citron DM, Finegold SM. Brain abscess and cerebritis. Rev Infect Dis 1984;6(suppl 1):101-6. 18. Mirzayan R, Itamura JM, Vangsness CT Jr, Holtom PD, Sherman R, Patzakis MJ. Management of chronic deep infection following rotator cuff repair surgery. Orthop Clin North Am 1997;28:205-13. 19. Nakata MM, Lewis RP. Anaerobic bacteria in bone and joint infections. Rev Infect Dis 1984;6(suppl 1):165-70. 20. Rao N, Crossett LS, Sinha RK, LeFrock JL. Long-term suppression of infection in total joint arthroplasty. Clin Orthop Relat Res 2003;414: 55-60. 21. Richards BS. Delayed infections following posterior spinal instrumentation for treatment of idiopathic scoliosis. J Bone Jont Surg Am 1996;77:524-9. 22. Sperling JW, Cofield RH, Torchia ME, Hanssen AD. Infection after shoulder instability surgery. Clin Orthop Relat Res 2003:61-4. 23. Sperling JW, Kozak TK, Hanssen AD, Cofield RH. Infection after shoulder arthroplasty. Clin Orthop Rel Res 2001;382:206-16. 24. Yocum RC, McArthur J, Petty BG, Diehl AM, Moench TR. Septic arthritis caused by Propionibacterium acnes. JAMA 1982;248:1740-1.
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Propionibacterium acnes infection after shoulder arthroplasty: A diagnostic challenge Christopher C. Dodson, MDa,b,*, Edward V. Craig, MDb, Frank A. Cordasco, MDb, David M. Dines, MDb, Joshua S. Dines, MDb, Edward DiCarlo, MDb, Barry D. Brause, MDb, Russell F. Warren, MDb a b
Sports Medicine Service, Rothman Institute, Philadelphia, PA, USA Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, NY, USA Hypothesis: This study reviewed a series of patients diagnosed with Propionibacterium acnes infection after shoulder arthroplasty in order to describe its clinical presentation, the means of diagnosis, and provide options for treatment. Materials and methods: From 2002 to 2006, 11 patients diagnosed with P acnes infection after shoulder arthroplasty were retrospectively reviewed and analyzed for (1) clinical diagnosis; (2) laboratory data, including white blood cell count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP); (3) fever; (4) number of days for laboratory growth of P acnes; (5) organism sensitivities; (6) antibiotic regimen and length of treatment; and (7) surgical management. Infection was diagnosed by 2 positive cultures. Results: Five patients had an initial diagnosis of infection and underwent implant removal, placement of an antibiotic spacer, and staged reimplantation after a course of intravenous antibiotics. In the remaining 6 patients, surgical treatment varied according to the clinical diagnosis. When infection was recognized by intraoperative cultures, antibiotics were initiated. The average initial ESR and CRP values were 33 mm/h and 2 mg/dL, respectively. The average number of days from collection to a positive culture was 9. All cultures were sensitive to penicillin and clindamycin and universally resistant to metronidazole. Discussion: Prosthetic joint infection secondary to P acnes is relatively rare; yet, when present, is an important cause of clinical implant failure. Successful treatment is hampered because clinical findings may be subtle, many of the traditional signs of infection are not present, and cultures may not be positive for as long as 2 weeks. Level of evidence: Level IV, Case series, Treatment study. Ó 2010 Journal of Shoulder and Elbow Surgery Board of Trustees. Keywords: P acnes; Shoulder; arthroplasty; infection; Propionibacterium acnes
Infection after shoulder arthroplasty can be a devastating complication. The reported prevalence of deep periprosthetic infection involving shoulder arthroplasty ranges *Reprint requests: Christopher C. Dodson, MD, Attending Orthopaedic Surgeon, Rothman Institute, 925 Chestnut St., Philadelphia, PA 19107. E-mail address: [email protected] (C.C. Dodson).
from 3.9% to 15.4%.4,23 A delay in the diagnosis of infection in the shoulder can lead to chronic pain, prosthetic instability, and even sepsis; therefore, it is important that a timely diagnosis be made. Postoperative infection subsequent to shoulder arthroplasty is most commonly caused by the bacterial species Staphylococcus aureus and coagulase-negative
1058-2746/2010/$36.00 - see front matter Ó 2010 Journal of Shoulder and Elbow Surgery Board of Trustees. doi:10.1016/j.jse.2009.07.065
304 Staphylococcus. Propionibacterium acnes (P acnes) is a gram-positive, non-spore-forming, anaerobic bacillus found in the cutaneous, upper respiratory, and digestive mucosae.2,6,11 Traditionally considered nonpathogenic,8,12 this anaerobe has been reported to be responsible for severe infections at various body sites, including central nervous system infections,13,17 endocarditis,9,15 and peritonitis.7 Recently and most significantly, P acnes has also been recognized as an orthopedic pathogen.1,3-5,10,14,16,18-24 This is a review of a series of P acnes infections after shoulder arthroplasty. Often presenting in the subacute to late time frame, its diagnosis has proven to be difficult because the usual clinical and laboratory indicators of infection are frequently absent, and the standard time frame during which cultures are held in laboratories is frequently exceeded. The following series details the clinical presentation, diagnostic experience, and treatment suggestions for this difficult clinical problem.
Materials and methods The Investigational Review Board (IRB) of the Hospital for Special Surgery, New York, approved this study (IRB #26057). During a 4-year period (2002-2006), 11 patients (8 men, 3 women) were diagnosed with P acnes infection after shoulder arthroplasty. To ensure that a positive culture represented infection rather than specimen contamination, 2 positive intraoperative specimens were required for infection diagnosis. The medical records of these 11 patients were analyzed and retrospectively reviewed for the following data: (1) preoperative diagnosis, (2) laboratory values for white blood cells (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP); (3) fever, (4) average time for culture in days, (5) organism sensitivities, (6) antibiotic treatment, (7) pathology, and (8) surgical management. All patients were under the care of an infectious disease specialist (B. M. B.). Four primary surgeons treated the 11 patients. Infection was documented with positive intraoperative cultures from surgical specimens or by histologic evidence of inflammation with more than 10 polymorphonuclear cells per high power field, or both. Infection was classified as acute if it developed within 3 months from the time of the arthroplasty, subacute if it developed between 3 months and 1 year postoperatively, and late if it developed more than 1 year from the time of arthroplasty. The average interval from the index arthroplasty to the diagnosis of infection was 2.1 years (range, 1-4 years). We were unable to identify any systemic risk factors for infection in any of the 11 patients other than prior surgery. All patients were prepared for the operation with standard Betadine (Purdue Pharma L.P., Stamford, CT) microbicide solution and were draped in the usual sterile fashion. We typically do not wear spacesuits when performing shoulder arthroplasty. The mean age of the patients was 60.1 years, (range 47-78 years). The dominant shoulder was involved in 8 patients. The indications for the initial shoulder arthroplasty were osteoarthritis in 7, cuff tear arthropathy in 3, and traumatic arthritis in 1. The average number of surgical procedures performed before the index arthroplasty was 0.4, (range, 0-2), and the average follow up was 4.0 years (range, 2-6 years). The index shoulder arthroplasty was
C.C. Dodson et al. done at our institution in 7 patients. The index procedure in 4 patients was performed elsewhere, and they were referred to our institution for definitive management. The patients were divided into 2 groups according to a preoperative diagnosis of infection. Group I consisted of 5 patients who were diagnosed with infection before revision surgery by examination, laboratory values, radiographs, or isolation of P acnes from at least 2 different aspiration samples. None of these patients received preoperative antibiotics, and all 5 underwent implant removal and placement of an antibiotic spacer. Group II consisted of 6 patients who presented with a painful prosthesis without suspicion of infection before revision surgery. Three underwent revision shoulder arthroplasty for loosening of the glenoid component, 2 patients with cuff arthropathy and hemiarthroplasties were converted to a reverse prosthesis, and 1 patient with recurring dislocations of a reverse prosthesis had revision of the polyethylene component. Preoperative imaging identified a source of mechanical dysfunction and pain in all 6 of these patients, but it was not suspicious for infection, and thus, none of these patients received antimicrobial therapy before revision surgery. As part of their definitive treatment, all 11 patients had insertions of peripherally inserted central catheters and were treated systemically with intravenous antibiotics for a variable length of time.
Results In group I, the average WBC was 7,280 cells/L (range, 6,000-9,000 cells/L), the average ESR was 44.4 mm/h (range, 13-86 mm/h), and the average CRP was 3.42 mg/dL (range, 0.8-8.8 mg/dL). The normal values at our institution for ESR are 0 to 12 mm/h for men and 0 to 27 mm/h for women, and for CRP, less than 0.7 mg/dL. No patients presented with fever. A mean of 0.8 de´bridements (range, 0-3) after the reimplantation were necessary for the eradication of infection. One patient required a second explantation. Tissue pathology in all patients demonstrated acute and chronic inflammation with necrosis and granulation tissue of variable amounts consistent with infection (Table I). The average time to receive pathologic results was 30 minutes for frozen sections and 2 days (range 1-3 days) for routine histopathology. The average time for growth in culture was 9 days (range 8-10 days). All cultures were positive for P acnes. After surgery, all patients were treated prophylactically with IV cefazolin (1 g/8 h) until P acnes was identified, at which time the antibiotic regimen was switched to IV penicillin G K þ salt (3 million U every 4 hours) or IV clindamycin (900 mg, three times daily). The IV antibiotics were administered for a mean of 6.3 weeks (range, 6-9 weeks). After IV antibiotics, 3 patients received oral antibiotics for a mean of 3.3 weeks (range 2-8 weeks). All organisms were sensitive to both penicillin and clindamycin and resistant to metronidazole. Preoperative aspiration of the joint in 2 patients produced a positive culture in 1. The infection completely resolved after staged implant exchange in 3 patients in group I. Infection resolution was
Acnes after shoulder arthroplasty
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Table I Patient laboratory values, number of days for the laboratory to grow Propionibacterium acnes, the pathology results, and the type of antibiotic administered) Patient
ESR (mm/h)
CRP (mg/dL)
WBC (109/mL)
Time to culture (days)
Pathologyy
Antibiotics
1 2 3 4 5 6 7 8 9 10 11
13 86 23 40 11 53 16 20 30 45 25
0.8 8.8 1 2 0.6 2.5 3 1.1 3 1.5 1
6.4 9 6 7 9 6 8 7 8 7.5 6
8 9 10 10 8 8 9 8 10 9 9
Positive Positive Positive Positive . Positive . Positive Positive Positive .
Penicillin G Penicillin G Clindamycin Penicillin G Penicillin G Penicillin G Penicillin G Penicillin G Penicillin G Penicillin G Penicillin G
CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; WBC, white blood cell. ) No patients presented with a fever, and all cultures grew Propionibacterium acnes. y Pathology was positive when the tissue sample demonstrated acute and chronic inflammation with necrosis and granulation tissue of variable amounts but of the type and degree that is usually associated with infection with or without implant debris.
defined as no clinical sequelae of infection after surgery, normal appearance on radiographs, and negative final intraoperative cultures taken at the time of reimplantation of the prosthetic components. One patient required an additional irrigation and de´bridement for a persistently draining wound and superficial infection. No subsequent organism was identified, and the implant components were stable at the time of the de´bridement. The remaining patient had a persistent infection after the reimplantation that required 3 irrigation and de´bridement procedures, and then ultimately, an explantation for recurrent infection. At the latest follow-up, the patient had no clinical or radiographic evidence of infection and declined reimplantation. In group II, the average WBC count was 7,500 cells/L (range 6000-9000 cells/L), the average ESR was 25.6 mm/h (range, 11-45, mm/h), and the average CRP was 1.44 mg/dL (range, 0.6-3 mg/dL). No patients presented with fever. The tissue pathology in 3 patients demonstrated acute and chronic inflammation and granulation consistent with infection, whereas the other 3 patients demonstrated nondiagnostic granulation tissue in addition to particulate implant reaction. The average time for the treating surgeon to receive pathologic results was 30 minutes for frozen sections and 2 days (range 1-3 days) for routine histopathology. One frozen section and 5 cultures were sent for each patient. The average time to receive positive culture results was 8.8 days (range 8-10 days), and all cultures were positive for P acnes. Each of these patients, when informed of the ‘‘incidental’’ positive intraoperative cultures, chose medical management instead of surgical de´bridement. They were administered perioperative IV cefazolin (1 g every 8 hours) for 36 hours postoperatively and then clindamycin or penicillin when the intraoperative cultures grew P acnes. After IV antibiotic therapy, 5 patients received oral ampicillin (500 mg, twice daily) for a mean of 9 weeks (range, 8-10 weeks) until the
ESR and CRP had returned to normal values. One patient has remained on oral suppressive therapy for 24 months and does not have any clinical or radiographic signs of infection. Complications secondary to prolonged oral antibiotic therapy were not observed in this series. As in group I, all organisms in group II were sensitive to both penicillin and clindamycin and resistant to metronidazole. According to the timing of the infections relative to the index arthroplasty, there were 0 acute, 1 subacute, and 10 late infections. A summary of the laboratory values for both groups is reported in Table I, and a summary of the index and revision diagnoses as well as procedures is in Table II.
Discussion The shoulder is thought to have has a propensity for infection with P acnes because the organism is the dominant anaerobic bacteria isolated from healthy skin in moist areas such as the axilla.1,17,23 Until recently, the organism was thought to be a contaminant rather than a true pathogen. P acnes is known to be a common causative organism in infections after shoulder instability surgery22 and arthroplasty.23 Several authors have also reported that P acnes was the most common infecting organism of deep infection after rotator cuff repair.1,10,18 Infection after total shoulder arthroplasty is, fortunately, relatively uncommon but is nonetheless a devastating problem, and guidelines relative to the diagnosis and treatment of P acnes would seem valuable. The successful diagnosis and treatment of patients who are infected with P acnes remains a challenge, and the clinician has little information available for guidance in management. This is particularly true because of the difficulty diagnosing this organism, the subtlety of its presentation, its resistance to standard broad-spectrum antibiotics,
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Table II
Patient summary of the index and revision diagnosis and procedure
Patient
Index diagnosis
Index procedure
Revision diagnosis
Revision procedure
1 2 3 4 5 6 7 8 9 10 11
Osteoarthritis Osteoarthritis Humeral head fracture Osteoarthritis Osteoarthritis CTA Humeral Head Fracture CTA Osteoarthritis Osteoarthritis Osteoarthritis
Noncemented TSR Noncemented TSR Cemented hemiarthroplasty Noncemented TSR Noncemented TSR Cemented Reverse TSR Cemented Hemiarthroplasty Cemented Reverse TSR Noncemented TSR Noncemented TSR Noncemented TSR
Infection Infection CTA Infection Glenoid loosening Infection CTA Instability Infection Glenoid loosening Glenoid loosening
Prosthesis removal; abx spacer Prosthesis removal; abx spacer Conversion to reverse TSA Prosthesis removal; abx spacer Glenoid removal Prosthesis removal; abx spacer Conversion to reverse TSA Spacer conversion Prosthesis Removal; abx Spacer Glenoid removal Glenoid removal
Abx, antibiotics; CTA, cuff tear arthropathy; TSR, total shoulder replacement.
and because this slowly growing organism requires a prolonged culture for at least 8 days to ensure a negative culture. Lutz et al16 reported that the WBC count is often within normal reference ranges in the setting of P acnes infection, and that values for ESR and CRP are more diagnostic. In addition, Mirzayan et al18 and Kwon et al14 found that the ESR and CRP were elevated in most cases of deep infection, with the former stating that the ESR was the most useful laboratory test for diagnostic purposes. Our experience in this series is similar: no patient had a preoperative leukocyte count of more than 10,000 cells/L, 5 patients (46%) had an ESR of 30 mm/h or higher, and 8 patients (72%) had a CRP of 1.0 mg/dL or higher. Adding to the difficulty and frustration surrounding P acnes infection is the observation that many laboratories routinely discard culture samples after 3 to 5 days. Although this is an adequate length of time to identify many typical organisms, this is not so for P acnes. Lutz et al reported 52 cases of arthroplastic and osteosynthetic infections due to P acnes, and the average time for culture was 13.3 days (range, 4-21 days). In this series, the average time for a positive culture was 9 days (range, 8-10 days). Because of this, we now request that all fluid cultures be held for at least 10 days before being discarded. Many authors have recommended preoperative aspiration to diagnose and confirm infection.5,14,16,23 Although certainly a reasonable guideline for management, we have found this most helpful only if there is a distinct collection that is visible either on magnetic resonance imaging (MRI) or ultrasound imaging. An effective organism-specific antibiotic regimen is crucial to completely eradicate any infection. Unlike most anaerobes, P acnes appears not to be sensitive to metronidazole. In this series, all cultures were resistant to metronidazole and sensitive to penicillin and clindamycin, and this information now guides our choice of antibiotic. This current study identified 2 distinct groups that were infected with P acnes based on preoperative suspicion for infection. Group I consisted of patients who were diagnosed with infection clinically on the basis of wound erythema or drainage, positive cultures, or evidence of a fluid collection
by MRI or ultrasound imaging. Group II consisted of patients who were diagnosed with prosthetic or soft tissue dysfunction, and in whom preoperative and intraoperative infection was not suspected, with the positive cultures being ‘‘ incidental’’ to treatment for the painful implant undergoing revision surgery. The patients in this group had been discharged to home by the time at least 2 intraoperative cultures became positive. This subset of patients was the most challenging regarding appropriate decision making, because in many instances they were doing well clinically, and both patients and clinicians were taken by surprise by the laboratory report of positive intraoperative cultures. Optimal treatment of any chronically infected prosthesis includes the removal of infected and necrotic tissue and all the components of the prosthesis, systemic antibiotics, and staged revision where clinically appropriate. Reimplantation may not always be possible because of the poor general condition of the patient, because of acceptable function despite removal of the prosthesis, or because of patient reluctance to have further surgery. Because of this, some have recommended retention of the prosthesis with longterm oral suppressive antibiotic therapy as an alternative to further surgery. Rao et al20 reported 36 patients who were treated with prosthetic retention and long-term suppressive oral antibiotic therapy for an average of 52.6 months. Their study confirmed a favorable outcome in 82.6% of patients after a mean follow-up of 5 years. The goal of any suppressive therapy is to achieve a functioning prosthesis without pain and drainage, while recognizing that infection is not completely eradicated. We generally maintain suppressive therapy until the laboratory values are normalized and consider longer-term suppression in those patients where normalization takes much longer; however, we have no data to support this. The ideal antibiotic regimen, optimal duration of oral suppressive therapy, and ideal patient population in which this treatment plan is best used is still unclear and needs additional data with prospective studies. The present study has the identifiable limitations of a retrospective, observational cohort. In addition, the sample
Acnes after shoulder arthroplasty size is small, thus limiting statistical power. Finally, although one infecting organism was involved, variability existed in antibiotic selection and duration.
Conclusion In conclusion, although this is a small series, it demonstrates that P acnes can be a true pathogen in the setting of shoulder arthroplasty and underscores that variables such as ESR, WBC, CRP, local wound condition, preoperative joint aspiration, and even intraoperative cultures if discarded prematurely can cloud the diagnosis of a clinically significant joint infection. The clinical effect of this study is to make clinicians aware of the significance of this organism and its role in affecting patients who have undergone some type of shoulder arthroplasty. More specifically, we hope this study can provide clinicians with an understanding of not only how to diagnose but also how to effectively treat this organism. From our experience with these patients, we have several recommendations that we have now incorporated into our standard practice: First, before the skin incision, the axilla is isolated with a commercially available adhesive antimicrobial drape (Ioban; #M, St. Paul, MN) to decrease the potential colonization by local P acnes. Second, all cultures from potential surgical site infections are incubated for a minimum of 10 days specifically to assess for Propionibacterium. Third, all patients undergoing revision shoulder arthroplasty are made aware that intraoperative culture results may alter planned treatment. Finally, consideration is now given for preoperative infectious disease consultation in all patients with painful implants so that supervision of and reaction to intraoperative cultures occurs in timely fashion.
Disclaimer No funding was necessary for this study. The authors, their immediate families, and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article.
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