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Mycobacterium fortuitum infection following total knee arthroplasty: A case report and literature review
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The Knee 15 (2008) 61 – 63
Short communication
Mycobacterium fortuitum infection following total knee arthroplasty: A case report and literature review Ian Cheung ⁎, Anthony Wilson Toowoomba Hospital, Pechey Street, Toowoomba, Queensland 4350, Australia Received 3 May 2007; received in revised form 22 August 2007; accepted 27 August 2007
Abstract Although Mycobacterium fortuitum is ubiquitous in our environment, infection of total knee arthroplasties with this organism is uncommon. This particular mycobacterium belongs to a group of organisms known as rapidly growing mycobacteria that distinguishes itself from the more typical Mycobacterium tuberculosis by their lower virulence and lack of human-to-human transmission. Another distinguishing feature is their resistance to almost all traditional anti-tuberculous medications and many antibiotics. Because such infections are encountered so infrequently, delays in reaching a microbiological diagnosis are not unusual. This inevitably compromises patient care. At present, there is no universally accepted treatment protocol. Management tends to be individualized, but cure may be possible with a prolonged course of appropriate anti-microbial therapy, removal of the implant, biopsy to confirm eradication of the organism, and finally, reimplantation of a new prosthesis. This paper presents the successful treatment of such an infection. Use of the combination of meropenem and moxifloxacin has not been previously reported in this setting. This case suggests that their in vivo activity is clinically effective against M. fortuitum peri-prosthetic infections when combined with surgical therapy. Crown Copyright © 2007 Published by Elsevier B.V. All rights reserved. Keywords: Total knee arthroplasty; Total knee arthroplasty infection; Mycobacterium fortuitum; Non-tuberculous mycobacteria
1. Introduction Mycobacterium fortuitum is a recognized cause of soft tissue infections, often associated with trauma, injection or surgery [1–4]. In contrast, only a few cases of M. fortuitum peri-prosthetic infections have been reported in the literature [5–10]. Of the three infected knee arthroplasties reported, only one successful reimplantation was noted [9]. In contrast, two-stage reimplantation in the setting of the more common bacterial peri-prosthetic infections fare better, with success rates of 90% in the short term [11] and of 77% at ten years [12]. Other issues arise in the management of this unusual infection. One such issue is the lack of a universally accepted anti-microbial guideline. Combination therapy for a total of 6 months is recommended [2], though previous authors have all reported differing ⁎ Corresponding author. Orthopaedics Department, Toowoomba Hospital, Pechey Street, Toowoomba, Queensland 4350, Australia. Tel.: +61 7 4616 6000. E-mail address: [email protected] (I. Cheung).
regimes. In this case, meropenem and moxifloxacin were used for 8 months pre-implantation followed by a further three months post-implantation. This prolonged duration and a conservative approach may well have contributed to the successful eradication of the mycobacterial infection. It also confirms that the newer quinolone, moxifloxacin, is an effective alternative when used in vivo. 2. Case report A 68-year-old man was transferred to our hospital with a proven prosthetic knee joint infection. He had undergone a total knee replacement in Chennai, India, 3 months ago. He started to develop an erythematous wound, a hot, swollen joint, a limp, and weight loss 9 weeks post-operatively, by which time he had returned to his Australian residence. Also noted was a sinus opening at the distal end of the surgical scar. On initial assessment, his white cell count was 6.1 × 109 cells per litre and C-reactive protein was 56 mg/L. A knee joint aspirate performed
0968-0160/$ - see front matter. Crown Copyright © 2007 Published by Elsevier B.V. All rights reserved. doi:10.1016/j.knee.2007.08.007
62
I. Cheung, A. Wilson / The Knee 15 (2008) 61–63
at the referring hospital demonstrated frank purulent material. Cephalexin and dicloxacillin were commenced as empiric therapy until cultures demonstrated non-tuberculous Mycobacterium on day 4–5. He was then transferred to our facilities. At our hospital, he underwent an initial surgical debridement. The draining sinus communicated with an abscess cavity that extended to the tibial component of the knee replacement. Extensive synovitis was noted, as were areas of osteolysis affecting the anterior tibia and lateral femoral condyle. Further specimens were sent for culture. The patient was then commenced on intravenous antibiotics (amikacin 1250 mg once daily and cefoxitin 2 g every 4 h). After 5 days, cefoxitin was changed to meropenem 1 g every 8 h because of lack of hospital supply. Cultures from the operative specimen confirmed M. fortuitum as the causative organism. He was taken back to theatre for removal of prosthesis and insertion of a cement spacer made with CMW2 (Depuy) and amikacin 2 g. Over the course of 2 weeks, the combination of meropenem 1 g every 8 h and moxifloxacin 400 mg every 8 h was settled upon. The latter was chosen because of its supposedly greater activity over older quinolones such as ciprofloxacin. Furthermore, given the low success rate reported in the literature, a conservative approach of 6 months' therapy was chosen pre-implantation (though this extended to eight months because of non-clinical delays in arranging operating time) and 3 months' therapy postimplantation. When clinical improvements were noted and C-reactive protein remained normal (b 5) on multiple samples, an open biopsy of the knee was performed. This suggested no further infection, and thus, implantation of a new prosthesis was performed. The combination of meropenem and moxifloxacin was continued for 3 more months as planned. On last review, the patient had no pain, no evidence of infection, and had a range of motion of 5–85°. 3. Discussion Despite the high volume of arthroplasty performed, very few cases of peri-prosthetic M. fortuitum infections have occurred. To our knowledge this is the fourth case reported in the literature of an infected total knee arthroplasty. A similar number of M. fortuitum total hip arthroplasty infections have been described: one in the English literature [5] and four in the French [6,7]. M. fortuitum belongs to a group of organisms known as rapidly growing mycobacteria (RGM), equivalent to Runyon group IV in the classification scheme of non-tuberculous mycobacteria (NTM). Over 150 NTM species have been described, one-third of which demonstrating clinical significance. As a general rule, NTM are distinguished from Mycobacterium tuberculosis by their lower virulence and lack of human-to-human transmission, though as this case demonstrates, serious infections can still occur [13]. RGM are widely distributed in the environment: in natural water, tap water, and soil. Contaminated water, water-based solutions and ice are important sources for nosocomial infections [1]. Povidone–iodine (10%), saline and various injectable medications, EMG needles, haemodialysis units, continuous ambula-
tory peritoneal dialysis systems, and cooling solutions for cardioplegia have all been implicated in RGM infections [2,14]. Though epidemics and outbreaks are reported, the majority of cases occur sporadically. M. fortuitum, along with Mycobacterium chelonae and Mycobacterium abscessus, account for the majority of human diseases caused by RGM [2]. They are important causes of cutaneous, pulmonary and nosocomial infections. According to various authors, the M. fortuitum group accounts for 19–45% of non-tuberculous mycobacterial infections. In a study by Martin-Casabona et al. [15], data from 14 countries were collected between the years 1991–1996. Of the clinical specimens that demonstrated the presence of an NTM, M. fortuitum accounted for 2.1% (Belgium) to 53.9% (Iran) of the samples. The figure for India is unknown. Certainly, M. tuberculosis is more prevalent in India, and the proportion of mycobacterial infections attributable to NTM is considered low [16]. M. fortuitum infections often occur in the setting of trauma or local surgical procedures, such as post-injection abscesses and post-operative wound infections [1,3]. Outbreaks following cardiac surgery and mammaplasty have been well described. Infections with M. fortuitum rarely result in disseminated disease, though this can occur in immunocompromised hosts. They are also an infrequent cause of peri-prosthetic joint infections. Managing such infections can be challenging. Kalita et al. observed that atypical mycobacterial wound infections may not occur as an immediate post-operative complication [4]. Apparent healing occurs early before the scar breaks down, a sinus develops, and an infection declares itself. In the series of four M. fortuitum infections, symptoms developed an average of 5.4 weeks post-total knee arthroplasty (range 18 days to 9 weeks). Evident in all four cases were local symptoms and signs of infection: the patients presented with painful, red, hot, swollen knees. Purulent discharge drained from the wound in two cases. Three of the four patients demonstrated systemic symptoms of fever, chills or weight loss. Understandably, antibiotics for pyogenic infections were commenced as initial empiric therapy. In the present case, the patient was given cephalexin and dicloxacillin until NTM was seen in the knee joint aspirate cultures. Difficulties can arise in establishing a microbiological diagnosis. Five to 7 days may be required for colonies of RGM to become visible on culture, by which time, routine specimens may have been discarded already [8]. At times, a negative culture may be attributed to prior antibiotic therapy, and the differential diagnosis of a mycobacterial infection may not have been considered [9]. As M. fortuitum is resistant to almost all traditional anti-tuberculous medications and many antibiotics, delays in diagnosis result in prolonged morbidity, delay in treatment with appropriate chemotherapy and/or unnecessary use of ineffective anti-microbials. This potential difficulty is highlighted in a paper by Uslan et al. [3]. In their series of RGM skin and soft tissue infections, the median time between symptom onset and microbiological diagnosis was 86 days. Admittedly, the seriousness of periprosthetic infections will justify a more aggressive diagnostic process, the paper emphasizes the need for a high index of
I. Cheung, A. Wilson / The Knee 15 (2008) 61–63
suspicion in cases where a septic joint is clinically evident but routine cultures remain negative. In three peri-prosthetic infections reviewed in this paper, microbiological diagnosis was established within 18 days of symptom onset. In the fourth case, diagnosis took 14 months because mycobacteria were not considered [9]. Difficulties also arise in the treatment of these infections. Because of the small numbers of M. fortuitum peri-prosthetic infections, there are no standardized treatment protocols. Combined medical and surgical therapy will optimize outcome, but treatment remains individualized. At least 6 months of anti-microbial therapy is recommended for peri-prosthetic infections. In vitro studies suggest M. fortuitum is susceptible to agents such as amikacin, cefoxitin, imipenem and sulfonamides [1,14]. Thus, a combination of amikacin and cefoxitin (or imipenem) can be used for a minimum of 4 to 8 weeks for susceptible isolates, and adjusted according to the organism's specific sensitivities. After a minimum of 12 weeks of cefoxitin or imipenem, oral therapy can be commenced to make up a total of 6 months of antibiotics [2]. Alternatively, a quinolone, such as ciprofloxacin or ofloxacin, can be used as part of combination therapy. In contrast, quinolone monotherapy is associated with acquired resistance among RGM and thus should be avoided. Likewise, even though 80% of M. fortuitum isolates is susceptible to clarithromycin, its use is also cautioned against because of the ubiquitous occurrence of a macrolide resistance gene, erm(39) [17]. Newer alternatives such as moxifloxacin (an 8-methoxyfluoroquinolone) may demonstrate greater activity against M. fortuitum than older quinolones, such as ciprofloxacin. As mentioned, since most cases are sporadic, there are no controlled trials comparing different therapeutic regimes. The anti-microbial therapy used in the four cases differed from each other. In the case reported here, combination therapy with meropenem and moxifloxacin for 8 months proved effective. Although anti-microbial therapy can suppress the symptoms and signs of infection, cure requires prosthesis removal. This was performed in all four cases of infected total knee arthroplasties, including ours. Once cure is obtained, reimplantation of new prostheses can be attempted. This was done in three of the four cases (arthrodesis was performed in the remaining case). In Saccente's [9] and in our experience, the patient improved following revision surgery and demonstrated a satisfactory outcome in the early follow up period. Unfortunately, in the third case, a chronic infection persisted, and because of unsatisfactory knee function, the patient opted for removal of prosthesis and arthrodesis of the knee joint. In this instance, intra-operative cultures were positive for M. fortuitum two weeks after implantation [10]. In light of this long incubation period, it may be prudent to perform an open biopsy as a separate procedure and only embark on a second stage revision after a negative culture is confirmed. 4. Conclusion M. fortuitum infection following arthroplasties is an uncommon occurrence. Difficulties can arise in establishing
63
the causative organism in a timely manner. A high index of suspicion is needed if clinical response to the usual antimicrobial agents is not satisfactory. Effective treatment requires a long duration of antibiotic therapy, removal of prosthesis, open biopsy to confirm absence of the causative pathogen, and if suitable, reimplantation of a new prosthesis. This paper suggests that the in vivo activity of meropenem and moxifloxacin is clinically effective against M. fortuitum peri-prosthetic infections when combined with surgical therapy. References [1] Brown-Elliott BA, Wallace RJ. Clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria. Clin Microbiol Rev 2002;15:716–46. [2] McFarland EJ, Kuritzkes DR. Clinical features and treatment of infection due to Mycobacterium fortuitum/chelonae complex. Curr Clin Top Infect Dis 1993;13:188–202. [3] Uslan DZ, Kowalski TJ, Wengenack NL, Virk A, Wilson JW. Skin and soft tissue infections due to rapidly growing mycobacteria: comparison of clinical features, treatment, and susceptibility. Arch Dermatol 2006;142: 1287–92. [4] Kalita JB, Rahman H, Baruah KC. Delayed post-operative wound infections due to non-tuberculous Mycobacterium. Indian J Med Res 2005;122: 535–9. [5] Booth JE, Jacobson JA, Kurrus TA, Edwards TW. Infection of prosthetic arthroplasty by Mycobacterium fortuitum. Two case reports. J Bone Joint Surg Am 1979;61:300–2. [6] Delrieu F, Slaoui O, Evrard J, Amor B, Postel M, Kerboull M. Mycobacterial infection of the hip following total prosthesis. Study of 6 cases. Rev Rhum Mal Osteoartic 1986;53:113–8. [7] Badelon O, David H, Meyer L, Radault A, Zucman J. Mycobacterium fortuitum infection after total hip prosthesis. A report of 3 cases. Rev Chir Orthop Reparatrice Appar Mot 1979;65:39–43. [8] Horadam VW, Smilack JD, Smith EC. Mycobacterium fortuitum infection after total hip replacement. South Med J 1982;75:244–6. [9] Saccente M. Mycobacterium fortuitum group periprosthetic joint infection. Scand J Infect Dis 2006;38:737–9. [10] Herold RC, Lotke PA, MacGregor RR. Prosthetic joint infections secondary to rapidly growing Mycobacterium fortuitum. Clin Orthop Relat Res 1987;216:183–6. [11] Windsor RE, Bono JV. Infected total knee replacements. J Am Acad Orthop Surg 1994;2:44–53. [12] Haleem AA, Berry DJ, Hanssen AD. Mid-term to long-term followup of two-stage reimplantation for infected total knee arthroplasty. Clin Orthop Relat Res 2004;428:35–9. [13] Tortoli E. The new mycobacteria: an update. FEMS Immunol Med Microbiol 2006;48:159–78. [14] Brown TH. The rapidly growing mycobacteria-Mycobacterium fortuitum and Mycobacterium chelonei. Infect Control 1985;6:283–8. [15] Martin-Casabona N, Bahrmand AR, Bennedsen J, Thomsen VO, Curcio M, Fauville-Dufaux M, et al. Non-tuberculous mycobacteria: patterns of isolation. A multi-country retrospective survey. Int J Tuberc Lung Dis 2004;8:1186–93. [16] Katoch VM. Infections due to non-tuberculous mycobacteria (NTM). Indian J Med Res 2004;120:290–304. [17] Nash KA, Zhang Y, Brown-Elliott BA, Wallace RJ. Molecular basis of intrinsic macrolide resistance in clinical isolates of Mycobacterium fortuitum. J Antimicrob Chemother 2005;55:170–7.
The Knee 15 (2008) 61 – 63
Short communication
Mycobacterium fortuitum infection following total knee arthroplasty: A case report and literature review Ian Cheung ⁎, Anthony Wilson Toowoomba Hospital, Pechey Street, Toowoomba, Queensland 4350, Australia Received 3 May 2007; received in revised form 22 August 2007; accepted 27 August 2007
Abstract Although Mycobacterium fortuitum is ubiquitous in our environment, infection of total knee arthroplasties with this organism is uncommon. This particular mycobacterium belongs to a group of organisms known as rapidly growing mycobacteria that distinguishes itself from the more typical Mycobacterium tuberculosis by their lower virulence and lack of human-to-human transmission. Another distinguishing feature is their resistance to almost all traditional anti-tuberculous medications and many antibiotics. Because such infections are encountered so infrequently, delays in reaching a microbiological diagnosis are not unusual. This inevitably compromises patient care. At present, there is no universally accepted treatment protocol. Management tends to be individualized, but cure may be possible with a prolonged course of appropriate anti-microbial therapy, removal of the implant, biopsy to confirm eradication of the organism, and finally, reimplantation of a new prosthesis. This paper presents the successful treatment of such an infection. Use of the combination of meropenem and moxifloxacin has not been previously reported in this setting. This case suggests that their in vivo activity is clinically effective against M. fortuitum peri-prosthetic infections when combined with surgical therapy. Crown Copyright © 2007 Published by Elsevier B.V. All rights reserved. Keywords: Total knee arthroplasty; Total knee arthroplasty infection; Mycobacterium fortuitum; Non-tuberculous mycobacteria
1. Introduction Mycobacterium fortuitum is a recognized cause of soft tissue infections, often associated with trauma, injection or surgery [1–4]. In contrast, only a few cases of M. fortuitum peri-prosthetic infections have been reported in the literature [5–10]. Of the three infected knee arthroplasties reported, only one successful reimplantation was noted [9]. In contrast, two-stage reimplantation in the setting of the more common bacterial peri-prosthetic infections fare better, with success rates of 90% in the short term [11] and of 77% at ten years [12]. Other issues arise in the management of this unusual infection. One such issue is the lack of a universally accepted anti-microbial guideline. Combination therapy for a total of 6 months is recommended [2], though previous authors have all reported differing ⁎ Corresponding author. Orthopaedics Department, Toowoomba Hospital, Pechey Street, Toowoomba, Queensland 4350, Australia. Tel.: +61 7 4616 6000. E-mail address: [email protected] (I. Cheung).
regimes. In this case, meropenem and moxifloxacin were used for 8 months pre-implantation followed by a further three months post-implantation. This prolonged duration and a conservative approach may well have contributed to the successful eradication of the mycobacterial infection. It also confirms that the newer quinolone, moxifloxacin, is an effective alternative when used in vivo. 2. Case report A 68-year-old man was transferred to our hospital with a proven prosthetic knee joint infection. He had undergone a total knee replacement in Chennai, India, 3 months ago. He started to develop an erythematous wound, a hot, swollen joint, a limp, and weight loss 9 weeks post-operatively, by which time he had returned to his Australian residence. Also noted was a sinus opening at the distal end of the surgical scar. On initial assessment, his white cell count was 6.1 × 109 cells per litre and C-reactive protein was 56 mg/L. A knee joint aspirate performed
0968-0160/$ - see front matter. Crown Copyright © 2007 Published by Elsevier B.V. All rights reserved. doi:10.1016/j.knee.2007.08.007
62
I. Cheung, A. Wilson / The Knee 15 (2008) 61–63
at the referring hospital demonstrated frank purulent material. Cephalexin and dicloxacillin were commenced as empiric therapy until cultures demonstrated non-tuberculous Mycobacterium on day 4–5. He was then transferred to our facilities. At our hospital, he underwent an initial surgical debridement. The draining sinus communicated with an abscess cavity that extended to the tibial component of the knee replacement. Extensive synovitis was noted, as were areas of osteolysis affecting the anterior tibia and lateral femoral condyle. Further specimens were sent for culture. The patient was then commenced on intravenous antibiotics (amikacin 1250 mg once daily and cefoxitin 2 g every 4 h). After 5 days, cefoxitin was changed to meropenem 1 g every 8 h because of lack of hospital supply. Cultures from the operative specimen confirmed M. fortuitum as the causative organism. He was taken back to theatre for removal of prosthesis and insertion of a cement spacer made with CMW2 (Depuy) and amikacin 2 g. Over the course of 2 weeks, the combination of meropenem 1 g every 8 h and moxifloxacin 400 mg every 8 h was settled upon. The latter was chosen because of its supposedly greater activity over older quinolones such as ciprofloxacin. Furthermore, given the low success rate reported in the literature, a conservative approach of 6 months' therapy was chosen pre-implantation (though this extended to eight months because of non-clinical delays in arranging operating time) and 3 months' therapy postimplantation. When clinical improvements were noted and C-reactive protein remained normal (b 5) on multiple samples, an open biopsy of the knee was performed. This suggested no further infection, and thus, implantation of a new prosthesis was performed. The combination of meropenem and moxifloxacin was continued for 3 more months as planned. On last review, the patient had no pain, no evidence of infection, and had a range of motion of 5–85°. 3. Discussion Despite the high volume of arthroplasty performed, very few cases of peri-prosthetic M. fortuitum infections have occurred. To our knowledge this is the fourth case reported in the literature of an infected total knee arthroplasty. A similar number of M. fortuitum total hip arthroplasty infections have been described: one in the English literature [5] and four in the French [6,7]. M. fortuitum belongs to a group of organisms known as rapidly growing mycobacteria (RGM), equivalent to Runyon group IV in the classification scheme of non-tuberculous mycobacteria (NTM). Over 150 NTM species have been described, one-third of which demonstrating clinical significance. As a general rule, NTM are distinguished from Mycobacterium tuberculosis by their lower virulence and lack of human-to-human transmission, though as this case demonstrates, serious infections can still occur [13]. RGM are widely distributed in the environment: in natural water, tap water, and soil. Contaminated water, water-based solutions and ice are important sources for nosocomial infections [1]. Povidone–iodine (10%), saline and various injectable medications, EMG needles, haemodialysis units, continuous ambula-
tory peritoneal dialysis systems, and cooling solutions for cardioplegia have all been implicated in RGM infections [2,14]. Though epidemics and outbreaks are reported, the majority of cases occur sporadically. M. fortuitum, along with Mycobacterium chelonae and Mycobacterium abscessus, account for the majority of human diseases caused by RGM [2]. They are important causes of cutaneous, pulmonary and nosocomial infections. According to various authors, the M. fortuitum group accounts for 19–45% of non-tuberculous mycobacterial infections. In a study by Martin-Casabona et al. [15], data from 14 countries were collected between the years 1991–1996. Of the clinical specimens that demonstrated the presence of an NTM, M. fortuitum accounted for 2.1% (Belgium) to 53.9% (Iran) of the samples. The figure for India is unknown. Certainly, M. tuberculosis is more prevalent in India, and the proportion of mycobacterial infections attributable to NTM is considered low [16]. M. fortuitum infections often occur in the setting of trauma or local surgical procedures, such as post-injection abscesses and post-operative wound infections [1,3]. Outbreaks following cardiac surgery and mammaplasty have been well described. Infections with M. fortuitum rarely result in disseminated disease, though this can occur in immunocompromised hosts. They are also an infrequent cause of peri-prosthetic joint infections. Managing such infections can be challenging. Kalita et al. observed that atypical mycobacterial wound infections may not occur as an immediate post-operative complication [4]. Apparent healing occurs early before the scar breaks down, a sinus develops, and an infection declares itself. In the series of four M. fortuitum infections, symptoms developed an average of 5.4 weeks post-total knee arthroplasty (range 18 days to 9 weeks). Evident in all four cases were local symptoms and signs of infection: the patients presented with painful, red, hot, swollen knees. Purulent discharge drained from the wound in two cases. Three of the four patients demonstrated systemic symptoms of fever, chills or weight loss. Understandably, antibiotics for pyogenic infections were commenced as initial empiric therapy. In the present case, the patient was given cephalexin and dicloxacillin until NTM was seen in the knee joint aspirate cultures. Difficulties can arise in establishing a microbiological diagnosis. Five to 7 days may be required for colonies of RGM to become visible on culture, by which time, routine specimens may have been discarded already [8]. At times, a negative culture may be attributed to prior antibiotic therapy, and the differential diagnosis of a mycobacterial infection may not have been considered [9]. As M. fortuitum is resistant to almost all traditional anti-tuberculous medications and many antibiotics, delays in diagnosis result in prolonged morbidity, delay in treatment with appropriate chemotherapy and/or unnecessary use of ineffective anti-microbials. This potential difficulty is highlighted in a paper by Uslan et al. [3]. In their series of RGM skin and soft tissue infections, the median time between symptom onset and microbiological diagnosis was 86 days. Admittedly, the seriousness of periprosthetic infections will justify a more aggressive diagnostic process, the paper emphasizes the need for a high index of
I. Cheung, A. Wilson / The Knee 15 (2008) 61–63
suspicion in cases where a septic joint is clinically evident but routine cultures remain negative. In three peri-prosthetic infections reviewed in this paper, microbiological diagnosis was established within 18 days of symptom onset. In the fourth case, diagnosis took 14 months because mycobacteria were not considered [9]. Difficulties also arise in the treatment of these infections. Because of the small numbers of M. fortuitum peri-prosthetic infections, there are no standardized treatment protocols. Combined medical and surgical therapy will optimize outcome, but treatment remains individualized. At least 6 months of anti-microbial therapy is recommended for peri-prosthetic infections. In vitro studies suggest M. fortuitum is susceptible to agents such as amikacin, cefoxitin, imipenem and sulfonamides [1,14]. Thus, a combination of amikacin and cefoxitin (or imipenem) can be used for a minimum of 4 to 8 weeks for susceptible isolates, and adjusted according to the organism's specific sensitivities. After a minimum of 12 weeks of cefoxitin or imipenem, oral therapy can be commenced to make up a total of 6 months of antibiotics [2]. Alternatively, a quinolone, such as ciprofloxacin or ofloxacin, can be used as part of combination therapy. In contrast, quinolone monotherapy is associated with acquired resistance among RGM and thus should be avoided. Likewise, even though 80% of M. fortuitum isolates is susceptible to clarithromycin, its use is also cautioned against because of the ubiquitous occurrence of a macrolide resistance gene, erm(39) [17]. Newer alternatives such as moxifloxacin (an 8-methoxyfluoroquinolone) may demonstrate greater activity against M. fortuitum than older quinolones, such as ciprofloxacin. As mentioned, since most cases are sporadic, there are no controlled trials comparing different therapeutic regimes. The anti-microbial therapy used in the four cases differed from each other. In the case reported here, combination therapy with meropenem and moxifloxacin for 8 months proved effective. Although anti-microbial therapy can suppress the symptoms and signs of infection, cure requires prosthesis removal. This was performed in all four cases of infected total knee arthroplasties, including ours. Once cure is obtained, reimplantation of new prostheses can be attempted. This was done in three of the four cases (arthrodesis was performed in the remaining case). In Saccente's [9] and in our experience, the patient improved following revision surgery and demonstrated a satisfactory outcome in the early follow up period. Unfortunately, in the third case, a chronic infection persisted, and because of unsatisfactory knee function, the patient opted for removal of prosthesis and arthrodesis of the knee joint. In this instance, intra-operative cultures were positive for M. fortuitum two weeks after implantation [10]. In light of this long incubation period, it may be prudent to perform an open biopsy as a separate procedure and only embark on a second stage revision after a negative culture is confirmed. 4. Conclusion M. fortuitum infection following arthroplasties is an uncommon occurrence. Difficulties can arise in establishing
63
the causative organism in a timely manner. A high index of suspicion is needed if clinical response to the usual antimicrobial agents is not satisfactory. Effective treatment requires a long duration of antibiotic therapy, removal of prosthesis, open biopsy to confirm absence of the causative pathogen, and if suitable, reimplantation of a new prosthesis. This paper suggests that the in vivo activity of meropenem and moxifloxacin is clinically effective against M. fortuitum peri-prosthetic infections when combined with surgical therapy. References [1] Brown-Elliott BA, Wallace RJ. Clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria. Clin Microbiol Rev 2002;15:716–46. [2] McFarland EJ, Kuritzkes DR. Clinical features and treatment of infection due to Mycobacterium fortuitum/chelonae complex. Curr Clin Top Infect Dis 1993;13:188–202. [3] Uslan DZ, Kowalski TJ, Wengenack NL, Virk A, Wilson JW. Skin and soft tissue infections due to rapidly growing mycobacteria: comparison of clinical features, treatment, and susceptibility. Arch Dermatol 2006;142: 1287–92. [4] Kalita JB, Rahman H, Baruah KC. Delayed post-operative wound infections due to non-tuberculous Mycobacterium. Indian J Med Res 2005;122: 535–9. [5] Booth JE, Jacobson JA, Kurrus TA, Edwards TW. Infection of prosthetic arthroplasty by Mycobacterium fortuitum. Two case reports. J Bone Joint Surg Am 1979;61:300–2. [6] Delrieu F, Slaoui O, Evrard J, Amor B, Postel M, Kerboull M. Mycobacterial infection of the hip following total prosthesis. Study of 6 cases. Rev Rhum Mal Osteoartic 1986;53:113–8. [7] Badelon O, David H, Meyer L, Radault A, Zucman J. Mycobacterium fortuitum infection after total hip prosthesis. A report of 3 cases. Rev Chir Orthop Reparatrice Appar Mot 1979;65:39–43. [8] Horadam VW, Smilack JD, Smith EC. Mycobacterium fortuitum infection after total hip replacement. South Med J 1982;75:244–6. [9] Saccente M. Mycobacterium fortuitum group periprosthetic joint infection. Scand J Infect Dis 2006;38:737–9. [10] Herold RC, Lotke PA, MacGregor RR. Prosthetic joint infections secondary to rapidly growing Mycobacterium fortuitum. Clin Orthop Relat Res 1987;216:183–6. [11] Windsor RE, Bono JV. Infected total knee replacements. J Am Acad Orthop Surg 1994;2:44–53. [12] Haleem AA, Berry DJ, Hanssen AD. Mid-term to long-term followup of two-stage reimplantation for infected total knee arthroplasty. Clin Orthop Relat Res 2004;428:35–9. [13] Tortoli E. The new mycobacteria: an update. FEMS Immunol Med Microbiol 2006;48:159–78. [14] Brown TH. The rapidly growing mycobacteria-Mycobacterium fortuitum and Mycobacterium chelonei. Infect Control 1985;6:283–8. [15] Martin-Casabona N, Bahrmand AR, Bennedsen J, Thomsen VO, Curcio M, Fauville-Dufaux M, et al. Non-tuberculous mycobacteria: patterns of isolation. A multi-country retrospective survey. Int J Tuberc Lung Dis 2004;8:1186–93. [16] Katoch VM. Infections due to non-tuberculous mycobacteria (NTM). Indian J Med Res 2004;120:290–304. [17] Nash KA, Zhang Y, Brown-Elliott BA, Wallace RJ. Molecular basis of intrinsic macrolide resistance in clinical isolates of Mycobacterium fortuitum. J Antimicrob Chemother 2005;55:170–7.