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A Cluster of Rapidly Growing Mycobacterial Peritoneal Dialysis Catheter Exit-Site Infections
CASE REPORT A Cluster of Rapidly Growing Mycobacterial Peritoneal Dialysis Catheter Exit-Site Infections Kai-Chung Tse, MRCP,1 Sing-Leung Lui, MD, FRCP (Edin),2 Vincent Chi-Chung Cheng, MRCP,1 Terence Pok-Siu Yip, MRCP,2 and Wai Kei Lo, FRCP2 In this case series, a cluster of 5 consecutive peritoneal dialysis patients with atypical mycobacterial exit-site infections in a single center within 20 months are described. Clinical features, treatment, and outcomes are discussed. Most patients had been treated with prolonged systemic antibiotic therapy for recurrent bacterial exit-site infections in the preceding months, and all had used topical gentamicin ointment for exit-site infection treatment or prophylaxis. It is postulated that this might have predisposed them to atypical mycobacterial exit-site infection as a result of selection pressure on uncommon organisms. Am J Kidney Dis 50:E1-E5. © 2007 by the National Kidney Foundation, Inc. INDEX WORDS: Atypical mycobacteria; exit-site infection; peritoneal dialysis; gentamicin.
E
xit-site infection (ESI) is a common problem in patients on long-term peritoneal dialysis (PD) therapy. Although causative organisms in the majority of cases are pyogenic bacteria, such uncommon organisms as rapidly growing mycobacteria sometimes may be seen presenting as ESIs refractory to treatment with antibiotics and occur usually as isolated cases.1-3 However, we recently encountered a cluster of atypical mycobacterial ESIs in PD patients since 2005 in our dialysis center. Clinical features and outcomes for these patients are described and potential common risk factors also are investigated. CASE REPORT Patient 1 A 40-year-old man with immunoglobulin A nephropathy had been on continuous ambulatory PD (CAPD) since 1995. He experienced recurrent bacterial ESIs since March 2004 and was given different courses of antibiotic treatment. Topical gentamicin ointment was started on December 10, 2004. He presented with a breakthrough Pseudomonas aeruginosa ESI in January 2005 that required Tenckhoff catheter removal on March 1, 2005. An exit-site swab obtained just before Tenckhoff catheter removal subsequently grew Mycobacterium chelonae. Gentamicin ointment was stopped. He was started on intravenous (IV) amikacin and oral clarithromycin therapy for 6 weeks. The old exit site healed well. Tenckhoff catheter reinsertion failed, and he was maintained on long-term hemodialysis therapy.
Patient 2 A 76-year-old woman with lupus nephritis had been on CAPD therapy since 1999. Her course of CAPD was complicated by recurrent bacterial ESIs and peritonitis caused by
gram-negative bacteria, and the last episode of ESI was caused by P aeruginosa in July 2005. She was started on treatment with topical gentamicin ointment for the exit site since then. She presented with a resistant Escherichia coli and Klebsiella species ESI with granuloma in March 2006 despite treatment with IV amikacin. Debridement was performed and IV ceftriaxone was administered for 1 more week. An exit-site bacterial culture obtained on the day of debridment grew M chelonae after 5 days. The Tenckhoff catheter therefore was removed. External and internal cuff granulation tissue sent for histological examination confirmed granulomatous inflammation, and Ziehl-Neelsen stain showed acid-fast bacilli (Fig 1). IV amikacin for 2 weeks, followed by oral clarithromycin for 8 weeks, was administered. The Tenckhoff catheter was reinserted on the contralateral side 12 weeks after removal, and the patient resumed CAPD therapy without problems.
Patient 3 A 71-year-old man with diabetic nephropathy had been on CAPD therapy since April 2004. He experienced recurrent bacterial ESIs since October 2005 that were treated with prolonged antibiotic therapy and topical gentamicin ointment. The last episode of ESI was caused by Burkholderia cepacia, which eventually required trimming of the external cuff in January 2006. He presented with an ESI again on May 15, 2006, and treatment with oral levofloxacin and topical gentamicin ointment was resumed since then. All exit-site culture results were negative. The infection was
From the 1Department of Microbiology, Queen Mary Hospital; and 2Renal Unit, Tung Wah Hospital, Hong Kong. Received January 16, 2007. Accepted in revised form April 17, 2007. Address correspondence to Wai Kei Lo, FRCP, Department of Medicine, Tung Wah Hospital, 12, Po Yan St, Hong Kong. E-mail: [email protected] © 2007 by the National Kidney Foundation, Inc. 0272-6386/07/5001-0024$32.00/0 doi:10.1053/j.ajkd.2007.04.017
American Journal of Kidney Diseases, Vol 50, No 1 (July), 2007: E1-E5
e1
e2
Tse et al
Figure 1. Numerous acidfast bacilli among the purulent exudate from a biopsy specimen from around the internal cuff during Tenckhoff catheter removal. (Ziehl Neelsen stain; original magnification ⫻40.)
relapsing in nature, and a repeated exit-site bacterial culture finally grew Mycobacterium fortuitum. Treatment with gentamicin ointment was stopped. Oral ciprofloxacin and clarithromycin were administered for 8 weeks with clinical response. CAPD was continued without relapse of the ESI 8 weeks after completion of antibiotics.
Patient 4 A 64-year-old man with renal failure caused by kidney stones had been on CAPD therapy since June 2006. An ESI
Figure 2. Gram stain of pus from the exit site shows grampositive rods mimicking diptheroids, subsequently found to be rapidly growing mycobacteria.
caused by diptheroid was noted 2 months later (Fig 2), but was refractory to treatment despite topical gentamicin and IV vancomycin. An atypical mycobacterial infection was suspected. Topical gentamicin treatment was stopped. While waiting for acid-fast bacilli culture results, there was an evolving tunnel-tract infection that required urgent Tenckhoff catheter removal. The exit-site acid-fast bacilli culture finally confirmed M fortuitum infection postoperatively. IV amikacin and imipenem were administered for 3 weeks and streamlined to oral ciprofloxacin and IV amikacin for 3 more
A Cluster of Atypical Mycobacterial Exit-Site Infections
e3
Table 1. Characteristics and Outcomes of 5 Patients With Atypical Mycobacterial ESI Patient No. 1 Date of first ESI manifestation Treatment of ESI before identification of atypical mycobacterium Duration of gentamicin ointment application Date of first positive culture for atypical mycobacterium Organism Antibiotic treatment for atypical mycobacterial ESI
Tenckhoff catheter removal Technique outcome
2
3
4
5
January 2005
March 2006
May 2006
July 2006
September 2006
Oral levofloxacin ⫻ 4 wk
Oral levofloxacin ⫻ 4 wk
IV vancomycin ⫻ 3 wk
Oral cephalexin ⫻ 2 wk
10 wk
IV amikacin ⫻ 2 wk, IV cefriaxone ⫻ 1 wk 32 wk
10 wk
10 d
7 wk
Februay 25, 2005
March 28, 2006
June 24, 2006
July 31, 2006
October 13, 2006
M chelone IV amikacin & oral clarithromycin ⫻ 6 wk
M chelone IV amikacin & oral clarithromycin ⫻ 10 wk
M fortuitum Oral clarithromycin & ciprofloxacin ⫻ 8 wk
M fortuitum No
Yes
Yes
No
M fortuitum IV amikacin & imipenem ⫻ 3 wk, IV amikacin & oral ciprofloxacin ⫻ 3 wk Yes
HD
CAPD
CAPD
CAPD
CAPD
No
Abbreviations: ESI, exit-site infection; IV, intravenous; HD, hemodialysis; CAPD, continuous ambulatory peritoneal dialysis.
weeks, with good clinical response. The Tenckhoff catheter was reinserted on the contralateral side 10 weeks later, and CAPD therapy was resumed without problems.
Patient 5 A 58-year-old man with renal failure caused by diabetic nephropathy had been on CAPD therapy since March 2003. He was administered prophylactic gentamicin ointment for exit-site care. There was no history of ESI. He presented with a refractory culture-negative ESI in October 2006; a repeated swab culture finally grew mycobacterium pending exact identification. Topical gentamicin therapy was stopped. However, the exit site showed spontaneous improvement while waiting for the formal identity of acid-fast bacilli, which finally was determined to be M fortuitum. No specific treatment was given. After observation for 10 weeks, there were still no signs or symptoms of ESI. Clinical presentations, treatment, and outcomes of atypical mycobacterial ESIs for all patients are listed in Table 1.
ADDITIONAL INVESTIGATIONS FOR CLUSTERING OF ATYPICAL MYCOBACTERIAL ESIS
In view of the unusual clustering of these patients, additional investigations were launched to exclude potential predisposing factors. Patients were specifically asked about their bathing practice and routine exit-site care. There was no change in the routine practice of exit-site care, outpatient clinic setting, or recent renovation. No patient had kept plants or pets at home. There
was no overlapping in the hospitalization period. Gentamicin ointments used by patients 1 and 5 were sterile on culture, suggesting that the possibility of direct inoculation by a contaminated ointment leading to ESI was unlikely. DISCUSSION
Rapidly growing mycobacteria are classified as atypical mycobacteria or nontuberculous mycobacteria. They may be isolated from soil, dust, water, terrestrial and aquatic animals, hospital environments, and contaminated reagents and pharmaceuticals.4,5 In long-term dialysis patients, most reported cases of atypical mycobacterial infections are related to ESIs and peritonitis,1-3,6-12 although other uncommon sites of infections, including cutaneous infection,13,14 septic arthritis,15 synovitis, and spondylitis, also were reported.16 M fortuitum and M chelonae are the most commonly encountered atypical mycobacteria in clincial practice, but other strains of aytpical mycobacteria, including Mycobacterium xenopi, Mycobacterium intracellulare, Mycobacterium gordonae, Mycobacterium kansasii, and Mycobacterium gastri, were reported to cause infections in dialysis patients.15-20 From a microbiological point of view, rapidly growing mycobacteria can be picked up by using Gram
e4
stain and sometimes may be mistaken as diptheroids. However, they will produce visible colonies at around 1 week of incubation, even in such routine culture plates as blood and chocolate agar. Ziehl-Neelsen stain is useful to differentiate mycobacteria from bacteria. For slow-growing mycobacteria, Ziehl-Neelsen stain and mycobacterial culture are essential for microbiological documentation. Therefore, prolonged incubation of routine bacterial culture plates and request for mycobacterial culture should be performed if atypical mycobacterial ESI is clinically suspected. The usual presenting features of atypical mycobacterial ESI from our series include an initially refractory bacterial ESI, bacterial ESI caused by apparently nonvirulent organisms, or culture-negative ESI before the final identification of atypical mycobacterium. In our dialysis center, patients were taught by the dialysis nurse during CAPD training about direct showering with antiseptic soap for cleansing of the exit site and dressing with chlorhexidine gluconate or normal or 5% saline when there was a clinical or equivocal ESI. Systemic antibiotics were used for ESI treatment according to International Society of Peritoneal Dialyis guidelines. There were 121 episodes of ESI in 2006 amounting to an ESI rate of 0.68 episodes/patientmonth. Topical gentamicin was available since December 2004 in our center, and to date, 110 patients had used prophylactic gentamicin ointment in the same period, with 5 cases of atypical mycobacterial ESI described in the present case series. No definite underlying epidemiological links were identified, and the exact environmental source from which patients contracted the infection remains unknown. However, most of our patients had prolonged exposure to systemic antibiotics for management of ESI. Because we did not encounter atypical mycobacterial ESIs in the past with patients administered multiple courses of antibiotics, we postulate that a high topical concentration of gentamicin might have resulted in selection pressure favoring the growth of atypical organisms. In this respect, it is interesting to note that stopping treatment with topical gentamicin ointment in our last patient resulted in spontaneous resolution of the infection, presumably because of removal of selection pressure and clearance of the infection by the pa-
Tse et al
tient’s own defense mechanisms. In addition, the growth of these ubiquitous environmental organisms may be enhanced further in areas where there is an overall warmer climate and increased humidity, as in our locality. This also may explain the absence of reported atypical mycobacterial ESIs in the previous study using prophylactic gentamicin application in PD patients in the United States.21 Our findings, although observational in nature, should alarm about the use of long-term gentamicin ointment for exit sites because of the possibility of inducing atypical mycobacterial ESIs in warm and humid localities. In particular, use of prophylactic gentamicin ointment in patients with a history of recurrent ESI should be reconsidered and best avoided. Concerning antibiotic treatment, a combination of 2 antibiotics, including the macrolide, quinolone, imipenem, and aminoglycoside groups, depending on the in vitro susceptibility profile, for 6 to 10 weeks was recommended. Tenckhoff catheter removal is not mandatory, but should be considered in refractory cases. Outcomes in terms of patient and PD technique survival generally are good with proper management. In conclusion, ESI caused by atypical mycobacteria is an uncommon condition in PD patients, but an increasing incidence of these infections may be seen with prolonged systemic antibiotic and topical gentamicin use. Specific antibiotic therapy is required for most cases, whereas adjuvant surgical interventions may be needed in selected patients to achieve an optimal clinical outcome. ACKNOWLEDGEMENTS Support: None. Financial Disclosure: None.
REFERENCES 1. Gourtzelis N, Margassery S, Bastani B: Successful treatment of severe Mycobacterium fortuitum exit-site infection with preservation of the Tenckhoff catheter. Perit Dial Int 25:607-608, 2005 2. Siu YP, Leung KT, Tong MK, Lee MK: Mycobacterium chelone exit site infection in a patient on peritoneal dialysis. Clin Nephrol 63:321-324, 2005 3. Gehr TW, Walters BA: Catheter-related Mycobacterium chelonei infection in a CAPD patient. Perit Dial Int 14:278-279, 1994 4. Goslee S, Wolinsky E: Water as a source of potentially pathogenic mycobacteria. Am Rev Respir Dis 113:287-292, 1976
A Cluster of Atypical Mycobacterial Exit-Site Infections 5. Gruft H, Falkinham JO III, Parker BC: Recent experience in the epidemiology of disease caused by atypical mycobacteria. Rev Infect Dis 3:990-996, 1981 6. Kleinpeter MA, Krane NK: Treatment of mycobacterial exit-site infections in patients on continuous ambulatory peritoneal dialysis. Adv Perit Dial 17:172-175, 2001 7. Tang S, Tang AW, Lam WO, Cheng YY, Ho YW: Successful treatment of Mycobacterium fortuitum peritonitis without Tenckhoff catheter removal in CAPD. Perit Dial Int 23:304-305, 2003 8. Youmbissi JT, Malik QT, Ajit SK, al Khursany IA, Rafi A, Karkar A: Non tuberculous mycobacterium peritonitis in continuous ambulatory peritoneal dialysis. J Nephrol 14:132135, 2001 9. Hevia C, Bajo MA, Sanchez-Tomero JA, et al: Peritoneal catheter exit-site infections caused by rapidly-growing atypical mycobacteria. Nephrol Dial Transplant 15:14581460, 2000 10. Vera G, Lew SQ: Mycobacterium fortuitum peritonitis in two patients receiving continuous ambulatory peritoneal dialysis. Am J Nephrol 19:586-589, 1999 11. Choi CW, Cha DR, Kwon YJ, Cho WY, Pyo HJ, Kim HK: Mycobacterium fortuitum peritonitis associated with continuous ambulatory peritoneal dialysis. Korean J Intern Med 8:25-27, 1993 12. Woods GL, Hall GS, Schreiber MJ: Mycobacterium fortuitum peritonitis associated with continuous ambulatory peritoneal dialysis. J Clin Microbiol 23:786-788, 1986 13. Drouineau O, Rivault O, Le Roy F, Martin-Passos E, Young P, Godin M: Cutaneous infection due to Mycobacterium chelone in a hemodialysed patient. Nephrol Ther 2:136139, 2006 Epub May 19, 2006
e5 14. Kolivras A, De Berdt PA, Theunis A, et al: Cutaneous Mycobacterium chelone infection extending distally in a hemodialysed patient. Dermatology 204:341-343, 2002 15. Kelly M, Thibert L, Sinave C: Septic arthritis in the knee due to Mycobacterium xenopi in a patient undergoing hemodialysis. Clin Infect Dis 29:1342-1343, 1999 16. Otaki Y, Nakanishi T, Nanami M, et al: A rare combination of sites of involvement by Mycobacterium intracellulare in a hemodilaysis patient: Multifocal synovitis, spondylitis, and multiple skin lesions. Nephron 92:730734, 2002 16. Harro C, Braden GL, Morris AB, Lipkowitz GS, Madden RL: Failure to cure Mycobacterium gordonae peritonitis associated with continuous ambulatory peritoneal dialysis. Clin Infect Dis 24:955-957, 1997 17. Giladi M, Lee BE, Berlin OG, Panosian CB: Peritonitis caused by Mycobacterium kansasii in a patient undergoing continuous ambulatory peritoneal dialysis. Am J Kidney Dis 19:597-599, 1992 18. London RD, Damsker B, Neibart EP, Knorr B, Bottone BJ: Mycobacterium gordonae: An unusual peritoneal pathogen in a patient undergoing continous ambulatory peritoneal dilaysis. Am J Med 85:703-704, 1988 19. Linton IM, Leahy SI, Thomas GW: Mycobacterium gastri peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis. Aust NZ J Med 16:224-225, 1986 20. Bernardini J, Bender F, Florio T, et al: Randomized, double-blind trial of antibiotic exit site cream for prevention of exit site infection in peritoneal dialysis patients. J Am Soc Nephrol 16:539-545, 2005 Epub December 29, 2004
E
xit-site infection (ESI) is a common problem in patients on long-term peritoneal dialysis (PD) therapy. Although causative organisms in the majority of cases are pyogenic bacteria, such uncommon organisms as rapidly growing mycobacteria sometimes may be seen presenting as ESIs refractory to treatment with antibiotics and occur usually as isolated cases.1-3 However, we recently encountered a cluster of atypical mycobacterial ESIs in PD patients since 2005 in our dialysis center. Clinical features and outcomes for these patients are described and potential common risk factors also are investigated. CASE REPORT Patient 1 A 40-year-old man with immunoglobulin A nephropathy had been on continuous ambulatory PD (CAPD) since 1995. He experienced recurrent bacterial ESIs since March 2004 and was given different courses of antibiotic treatment. Topical gentamicin ointment was started on December 10, 2004. He presented with a breakthrough Pseudomonas aeruginosa ESI in January 2005 that required Tenckhoff catheter removal on March 1, 2005. An exit-site swab obtained just before Tenckhoff catheter removal subsequently grew Mycobacterium chelonae. Gentamicin ointment was stopped. He was started on intravenous (IV) amikacin and oral clarithromycin therapy for 6 weeks. The old exit site healed well. Tenckhoff catheter reinsertion failed, and he was maintained on long-term hemodialysis therapy.
Patient 2 A 76-year-old woman with lupus nephritis had been on CAPD therapy since 1999. Her course of CAPD was complicated by recurrent bacterial ESIs and peritonitis caused by
gram-negative bacteria, and the last episode of ESI was caused by P aeruginosa in July 2005. She was started on treatment with topical gentamicin ointment for the exit site since then. She presented with a resistant Escherichia coli and Klebsiella species ESI with granuloma in March 2006 despite treatment with IV amikacin. Debridement was performed and IV ceftriaxone was administered for 1 more week. An exit-site bacterial culture obtained on the day of debridment grew M chelonae after 5 days. The Tenckhoff catheter therefore was removed. External and internal cuff granulation tissue sent for histological examination confirmed granulomatous inflammation, and Ziehl-Neelsen stain showed acid-fast bacilli (Fig 1). IV amikacin for 2 weeks, followed by oral clarithromycin for 8 weeks, was administered. The Tenckhoff catheter was reinserted on the contralateral side 12 weeks after removal, and the patient resumed CAPD therapy without problems.
Patient 3 A 71-year-old man with diabetic nephropathy had been on CAPD therapy since April 2004. He experienced recurrent bacterial ESIs since October 2005 that were treated with prolonged antibiotic therapy and topical gentamicin ointment. The last episode of ESI was caused by Burkholderia cepacia, which eventually required trimming of the external cuff in January 2006. He presented with an ESI again on May 15, 2006, and treatment with oral levofloxacin and topical gentamicin ointment was resumed since then. All exit-site culture results were negative. The infection was
From the 1Department of Microbiology, Queen Mary Hospital; and 2Renal Unit, Tung Wah Hospital, Hong Kong. Received January 16, 2007. Accepted in revised form April 17, 2007. Address correspondence to Wai Kei Lo, FRCP, Department of Medicine, Tung Wah Hospital, 12, Po Yan St, Hong Kong. E-mail: [email protected] © 2007 by the National Kidney Foundation, Inc. 0272-6386/07/5001-0024$32.00/0 doi:10.1053/j.ajkd.2007.04.017
American Journal of Kidney Diseases, Vol 50, No 1 (July), 2007: E1-E5
e1
e2
Tse et al
Figure 1. Numerous acidfast bacilli among the purulent exudate from a biopsy specimen from around the internal cuff during Tenckhoff catheter removal. (Ziehl Neelsen stain; original magnification ⫻40.)
relapsing in nature, and a repeated exit-site bacterial culture finally grew Mycobacterium fortuitum. Treatment with gentamicin ointment was stopped. Oral ciprofloxacin and clarithromycin were administered for 8 weeks with clinical response. CAPD was continued without relapse of the ESI 8 weeks after completion of antibiotics.
Patient 4 A 64-year-old man with renal failure caused by kidney stones had been on CAPD therapy since June 2006. An ESI
Figure 2. Gram stain of pus from the exit site shows grampositive rods mimicking diptheroids, subsequently found to be rapidly growing mycobacteria.
caused by diptheroid was noted 2 months later (Fig 2), but was refractory to treatment despite topical gentamicin and IV vancomycin. An atypical mycobacterial infection was suspected. Topical gentamicin treatment was stopped. While waiting for acid-fast bacilli culture results, there was an evolving tunnel-tract infection that required urgent Tenckhoff catheter removal. The exit-site acid-fast bacilli culture finally confirmed M fortuitum infection postoperatively. IV amikacin and imipenem were administered for 3 weeks and streamlined to oral ciprofloxacin and IV amikacin for 3 more
A Cluster of Atypical Mycobacterial Exit-Site Infections
e3
Table 1. Characteristics and Outcomes of 5 Patients With Atypical Mycobacterial ESI Patient No. 1 Date of first ESI manifestation Treatment of ESI before identification of atypical mycobacterium Duration of gentamicin ointment application Date of first positive culture for atypical mycobacterium Organism Antibiotic treatment for atypical mycobacterial ESI
Tenckhoff catheter removal Technique outcome
2
3
4
5
January 2005
March 2006
May 2006
July 2006
September 2006
Oral levofloxacin ⫻ 4 wk
Oral levofloxacin ⫻ 4 wk
IV vancomycin ⫻ 3 wk
Oral cephalexin ⫻ 2 wk
10 wk
IV amikacin ⫻ 2 wk, IV cefriaxone ⫻ 1 wk 32 wk
10 wk
10 d
7 wk
Februay 25, 2005
March 28, 2006
June 24, 2006
July 31, 2006
October 13, 2006
M chelone IV amikacin & oral clarithromycin ⫻ 6 wk
M chelone IV amikacin & oral clarithromycin ⫻ 10 wk
M fortuitum Oral clarithromycin & ciprofloxacin ⫻ 8 wk
M fortuitum No
Yes
Yes
No
M fortuitum IV amikacin & imipenem ⫻ 3 wk, IV amikacin & oral ciprofloxacin ⫻ 3 wk Yes
HD
CAPD
CAPD
CAPD
CAPD
No
Abbreviations: ESI, exit-site infection; IV, intravenous; HD, hemodialysis; CAPD, continuous ambulatory peritoneal dialysis.
weeks, with good clinical response. The Tenckhoff catheter was reinserted on the contralateral side 10 weeks later, and CAPD therapy was resumed without problems.
Patient 5 A 58-year-old man with renal failure caused by diabetic nephropathy had been on CAPD therapy since March 2003. He was administered prophylactic gentamicin ointment for exit-site care. There was no history of ESI. He presented with a refractory culture-negative ESI in October 2006; a repeated swab culture finally grew mycobacterium pending exact identification. Topical gentamicin therapy was stopped. However, the exit site showed spontaneous improvement while waiting for the formal identity of acid-fast bacilli, which finally was determined to be M fortuitum. No specific treatment was given. After observation for 10 weeks, there were still no signs or symptoms of ESI. Clinical presentations, treatment, and outcomes of atypical mycobacterial ESIs for all patients are listed in Table 1.
ADDITIONAL INVESTIGATIONS FOR CLUSTERING OF ATYPICAL MYCOBACTERIAL ESIS
In view of the unusual clustering of these patients, additional investigations were launched to exclude potential predisposing factors. Patients were specifically asked about their bathing practice and routine exit-site care. There was no change in the routine practice of exit-site care, outpatient clinic setting, or recent renovation. No patient had kept plants or pets at home. There
was no overlapping in the hospitalization period. Gentamicin ointments used by patients 1 and 5 were sterile on culture, suggesting that the possibility of direct inoculation by a contaminated ointment leading to ESI was unlikely. DISCUSSION
Rapidly growing mycobacteria are classified as atypical mycobacteria or nontuberculous mycobacteria. They may be isolated from soil, dust, water, terrestrial and aquatic animals, hospital environments, and contaminated reagents and pharmaceuticals.4,5 In long-term dialysis patients, most reported cases of atypical mycobacterial infections are related to ESIs and peritonitis,1-3,6-12 although other uncommon sites of infections, including cutaneous infection,13,14 septic arthritis,15 synovitis, and spondylitis, also were reported.16 M fortuitum and M chelonae are the most commonly encountered atypical mycobacteria in clincial practice, but other strains of aytpical mycobacteria, including Mycobacterium xenopi, Mycobacterium intracellulare, Mycobacterium gordonae, Mycobacterium kansasii, and Mycobacterium gastri, were reported to cause infections in dialysis patients.15-20 From a microbiological point of view, rapidly growing mycobacteria can be picked up by using Gram
e4
stain and sometimes may be mistaken as diptheroids. However, they will produce visible colonies at around 1 week of incubation, even in such routine culture plates as blood and chocolate agar. Ziehl-Neelsen stain is useful to differentiate mycobacteria from bacteria. For slow-growing mycobacteria, Ziehl-Neelsen stain and mycobacterial culture are essential for microbiological documentation. Therefore, prolonged incubation of routine bacterial culture plates and request for mycobacterial culture should be performed if atypical mycobacterial ESI is clinically suspected. The usual presenting features of atypical mycobacterial ESI from our series include an initially refractory bacterial ESI, bacterial ESI caused by apparently nonvirulent organisms, or culture-negative ESI before the final identification of atypical mycobacterium. In our dialysis center, patients were taught by the dialysis nurse during CAPD training about direct showering with antiseptic soap for cleansing of the exit site and dressing with chlorhexidine gluconate or normal or 5% saline when there was a clinical or equivocal ESI. Systemic antibiotics were used for ESI treatment according to International Society of Peritoneal Dialyis guidelines. There were 121 episodes of ESI in 2006 amounting to an ESI rate of 0.68 episodes/patientmonth. Topical gentamicin was available since December 2004 in our center, and to date, 110 patients had used prophylactic gentamicin ointment in the same period, with 5 cases of atypical mycobacterial ESI described in the present case series. No definite underlying epidemiological links were identified, and the exact environmental source from which patients contracted the infection remains unknown. However, most of our patients had prolonged exposure to systemic antibiotics for management of ESI. Because we did not encounter atypical mycobacterial ESIs in the past with patients administered multiple courses of antibiotics, we postulate that a high topical concentration of gentamicin might have resulted in selection pressure favoring the growth of atypical organisms. In this respect, it is interesting to note that stopping treatment with topical gentamicin ointment in our last patient resulted in spontaneous resolution of the infection, presumably because of removal of selection pressure and clearance of the infection by the pa-
Tse et al
tient’s own defense mechanisms. In addition, the growth of these ubiquitous environmental organisms may be enhanced further in areas where there is an overall warmer climate and increased humidity, as in our locality. This also may explain the absence of reported atypical mycobacterial ESIs in the previous study using prophylactic gentamicin application in PD patients in the United States.21 Our findings, although observational in nature, should alarm about the use of long-term gentamicin ointment for exit sites because of the possibility of inducing atypical mycobacterial ESIs in warm and humid localities. In particular, use of prophylactic gentamicin ointment in patients with a history of recurrent ESI should be reconsidered and best avoided. Concerning antibiotic treatment, a combination of 2 antibiotics, including the macrolide, quinolone, imipenem, and aminoglycoside groups, depending on the in vitro susceptibility profile, for 6 to 10 weeks was recommended. Tenckhoff catheter removal is not mandatory, but should be considered in refractory cases. Outcomes in terms of patient and PD technique survival generally are good with proper management. In conclusion, ESI caused by atypical mycobacteria is an uncommon condition in PD patients, but an increasing incidence of these infections may be seen with prolonged systemic antibiotic and topical gentamicin use. Specific antibiotic therapy is required for most cases, whereas adjuvant surgical interventions may be needed in selected patients to achieve an optimal clinical outcome. ACKNOWLEDGEMENTS Support: None. Financial Disclosure: None.
REFERENCES 1. Gourtzelis N, Margassery S, Bastani B: Successful treatment of severe Mycobacterium fortuitum exit-site infection with preservation of the Tenckhoff catheter. Perit Dial Int 25:607-608, 2005 2. Siu YP, Leung KT, Tong MK, Lee MK: Mycobacterium chelone exit site infection in a patient on peritoneal dialysis. Clin Nephrol 63:321-324, 2005 3. Gehr TW, Walters BA: Catheter-related Mycobacterium chelonei infection in a CAPD patient. Perit Dial Int 14:278-279, 1994 4. Goslee S, Wolinsky E: Water as a source of potentially pathogenic mycobacteria. Am Rev Respir Dis 113:287-292, 1976
A Cluster of Atypical Mycobacterial Exit-Site Infections 5. Gruft H, Falkinham JO III, Parker BC: Recent experience in the epidemiology of disease caused by atypical mycobacteria. Rev Infect Dis 3:990-996, 1981 6. Kleinpeter MA, Krane NK: Treatment of mycobacterial exit-site infections in patients on continuous ambulatory peritoneal dialysis. Adv Perit Dial 17:172-175, 2001 7. Tang S, Tang AW, Lam WO, Cheng YY, Ho YW: Successful treatment of Mycobacterium fortuitum peritonitis without Tenckhoff catheter removal in CAPD. Perit Dial Int 23:304-305, 2003 8. Youmbissi JT, Malik QT, Ajit SK, al Khursany IA, Rafi A, Karkar A: Non tuberculous mycobacterium peritonitis in continuous ambulatory peritoneal dialysis. J Nephrol 14:132135, 2001 9. Hevia C, Bajo MA, Sanchez-Tomero JA, et al: Peritoneal catheter exit-site infections caused by rapidly-growing atypical mycobacteria. Nephrol Dial Transplant 15:14581460, 2000 10. Vera G, Lew SQ: Mycobacterium fortuitum peritonitis in two patients receiving continuous ambulatory peritoneal dialysis. Am J Nephrol 19:586-589, 1999 11. Choi CW, Cha DR, Kwon YJ, Cho WY, Pyo HJ, Kim HK: Mycobacterium fortuitum peritonitis associated with continuous ambulatory peritoneal dialysis. Korean J Intern Med 8:25-27, 1993 12. Woods GL, Hall GS, Schreiber MJ: Mycobacterium fortuitum peritonitis associated with continuous ambulatory peritoneal dialysis. J Clin Microbiol 23:786-788, 1986 13. Drouineau O, Rivault O, Le Roy F, Martin-Passos E, Young P, Godin M: Cutaneous infection due to Mycobacterium chelone in a hemodialysed patient. Nephrol Ther 2:136139, 2006 Epub May 19, 2006
e5 14. Kolivras A, De Berdt PA, Theunis A, et al: Cutaneous Mycobacterium chelone infection extending distally in a hemodialysed patient. Dermatology 204:341-343, 2002 15. Kelly M, Thibert L, Sinave C: Septic arthritis in the knee due to Mycobacterium xenopi in a patient undergoing hemodialysis. Clin Infect Dis 29:1342-1343, 1999 16. Otaki Y, Nakanishi T, Nanami M, et al: A rare combination of sites of involvement by Mycobacterium intracellulare in a hemodilaysis patient: Multifocal synovitis, spondylitis, and multiple skin lesions. Nephron 92:730734, 2002 16. Harro C, Braden GL, Morris AB, Lipkowitz GS, Madden RL: Failure to cure Mycobacterium gordonae peritonitis associated with continuous ambulatory peritoneal dialysis. Clin Infect Dis 24:955-957, 1997 17. Giladi M, Lee BE, Berlin OG, Panosian CB: Peritonitis caused by Mycobacterium kansasii in a patient undergoing continuous ambulatory peritoneal dialysis. Am J Kidney Dis 19:597-599, 1992 18. London RD, Damsker B, Neibart EP, Knorr B, Bottone BJ: Mycobacterium gordonae: An unusual peritoneal pathogen in a patient undergoing continous ambulatory peritoneal dilaysis. Am J Med 85:703-704, 1988 19. Linton IM, Leahy SI, Thomas GW: Mycobacterium gastri peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis. Aust NZ J Med 16:224-225, 1986 20. Bernardini J, Bender F, Florio T, et al: Randomized, double-blind trial of antibiotic exit site cream for prevention of exit site infection in peritoneal dialysis patients. J Am Soc Nephrol 16:539-545, 2005 Epub December 29, 2004