19
Peritonitis Due to Rhizopus in a Patient Undergoing Continuous Ambulatory Peritoneal Dialysis Mary H. Branton, Steven C. Johnson, John D. Brooke, and James A. Hasbargen
From the Nephrology and Infectious Disease Services, Department of Medicine, Walter Reed Army Medical Center, Washington, D.C.; and the Department of Pathologyand Nephrology Service, Department of Medicine, Fitzsimons Army Medical Center, Aurora, Colorado
Continuous ambulatory peritoneal dialysis (CAPD) has become a popular technique for the management of end-stage renal disease. The primary complication that occurs with this method of dialysis is peritonitis, which is observed in most treatment centers at a rate of one episode per patient-year [1]. Although most cases of peritonitis that are associated with CAPD are due to bacterial infections, fungi are implicated in up to 15% of cases [2]. Fungal peritonitis may lead to significant morbidity and mortality. Removal of the dialysis catheter is frequently required for treatment of patients with fungal peritonitis; in addition, complications, such as intraabdominal abscesses, peritoneal adhesions, or peritoneal sclerosis, may make continuation of peritoneal dialysis untenable [3]. Fungal peritonitis is most often caused by Candida species; however, infections due to spore-forming molds, such as Aspergillus, have been reported [4]. We report a case of fungal peritonitis caused by a Rhizopus species; findings at autopsy and potential pathophysiologic mechanisms are discussed.
Case Summary A 61-year-old man developed end-stage renal disease secondary to diabetes mellitus and hypertension and began undergoing CAPD in February 1983. He experienced six
Received for publication 17October 1989and in revised form 22 March 1990. The assertionscontainedherein are the opinionsof the authors and should not be construedas official or as reflecting the viewsof the U.S. Department of the Army or the U.S. Department of Defense. Please address requests for reprints to Dr. StevenC. Johnson, Infectious Disease Service, Walter Reed Army Medical Center, Washington, D.C., 20307-5001. Reviewsof Infectious Diseases 1991;13:19-21 This article is in the public domain.
episodes of peritonitis in 1984 and 1985, all of which were caused by coagulase-negative staphylococci, except for one occasion when cultures also yielded Pseudomonas aeruginosa. His episodes of peritonitis were attributed to his poor aseptic technique during the use of the equipment for dialysis; the use of this technique was affected by worsening vision. The patient was trained regarding the use of an ultraviolet exchange device (UVXD, Travenol Laboratories, Deerfield, m.) in July 1985 in an attempt to minimize the number of further episodes of peritonitis. In May 1986, the patient found that his Tenckhoff catheter was clogged and therefore could not infuse dialysate solution. At that time, he was afebrile, and there was no evidence of a catheter site infection. The effluent was cloudy, and analysis revealed a white blood cell (WBC) count of 3,800/mm3 , with 78 % polymorphonuclear leukocytes, 2 % lymphocytes, and 20 % mononuclear cells. The gram stain of the fluid was negative. The patient was neither acidemic nor hyperglycemic. Intraperitoneal therapy with cefazolin and gentamicin was initiated. However, he did not improve, and cultures of the peritoneal fluid repeatedly yielded a fungus of the genus Rhizopus (the isolates were not speciated). The patient had not been treated with deferoxamine; the level of serum aluminum was 36 p.glmL, and the levels of serum iron and serum ferritin were normal, as was the iron-binding capacity. The patient was admitted to the hospital, and therapy with intraperitoneal amphotericin B was initiated. At this time, he had a fever of 101OF and diffuse abdominal tenderness, and his peripheral WBC count was 10,500/mm3 , with 5% eosinophils. The Tenckhoff catheter was removed, hemodialysis was initiated, and intravenous therapy with amphotericin B was initiated. Computed tomography of the abdomen revealed no evidence of abscess, but an indium-labeled WBC scan revealed local uptake in the abdominal wall. The patient's clinical response to therapy was rapid, and his temperature and abdominal pain decreased; however, he died of a myocardial
Downloaded from http://cid.oxfordjournals.org/ at The University of British Colombia Library on June 22, 2015
A 61-year-oldman who had end-stage renal disease secondary to diabetes mellitus and hypertension developed peritonitis due to infection with Rhizopus as a complication of receiving continuous ambulatory peritoneal dialysis (CAPD). At the onset of infection, the patient was neither acidemic nor hyperglycemic; in addition, deferoxamine had not beenadministered and Elastoplast dressings had not been applied. The infection occurred after the technique for disinfection of the catheter used for CAPD had been changed. The catheter was removed, and therapy with amphotericin B was initiated. Although the patient died of apparently unrelated causes, an autopsy revealedactive fungal infection with multiple abscessesand superficial invasion of the ileal wall.
20
Branton et aI.
RID 1991;13 (January-February)
A
B
Figure 1. A, A segment of the ileum at autopsy that demonstrates a fungal abscess on the serosal surface. B, Hematoxylin-eosin stain ofoneoftheabscesses thatdemonstrates hyphal elements that aretypical ofa Rhizopus species and necrotic debris as well asanassociated inflammatory response (x 400).
infarction 1 month after initiation of therapy. At the time of his death, he had received a total of 500 mgofamphotericin B. Autopsy revealed diffusefibrinous peritonitisas wellas abscesses located at the site of the Tenckhoff catheter, in the left lower quadrant, and on the serosal surface of the ileum (figure lA). On histologic examination, the abscesses containedlarge,ribbon-shaped aseptatehyphae thatbranchedperpendicularly, whichis typical of an infectiondue to Rhizopus (figure lB). Superficial invasionof the ileal wall was noted. Discussion
Rhizopus is an organism that belongs to the class Zygomycetes and family Mucoraceae and is commonly found in the soil. Diabeticpatientswho haveketoacidosisare particularly susceptible to infection due to these fungi. Given the high proportionof diabetics in the populationwhoundergoCAPD, the properties of peritoneal dialysatesolution that make it an ideal culture medium(high levelof glucoseand lowpH), and theubiquitous distribution of Rhizopus organisms, it is remarkable that these fungi have not been reported more frequently as pathogensof peritonitis. Polo and his colleagues recently described a patient who underwent CAPD and who developed peritonitis due to infection with Rhizopus and died [5]. This patient, like our patient, did not have ketoacidosis or any history of other clinicalmeansof exposurethat havebeen associated withinfection due to Rhizopus; suchmeansinclude the use of Elastoplast dressings [6] or chelation therapy with deferoxamine [7]. The findings at autopsy for our patient
confirm the pathogenic potential of these fungi for causing peritonitis in patients who undergo CAPD. A matter of concern for our patient was the development of fungal peritonitis after a change in the technique used to disinfect the catheter. The principle study that addresses the effectiveness of ultravioletsterilizationof the catheter against fungi in this setting was performed with use of a unicellular, non-spore-formingorganism (Candida aLbicans) as the indicator species, but other fungi were not used to test the device in this study [8]. The multicellular structure of Rhizopus as well as its propensity to form spores might make it resistant to disinfection with use of ultraviolet light. When Luyet exposed the spores of Rhizopus nigricans tRhizopus stoLonifer) to ultraviolet light at 254 nm (the wavelength of the UVXD used by our patient), he noted that as much as six times the energy used to kill yeasts was needed to kill these fungi [9]. The relative radioresistanceof older spores of Rhitopus [10], the effect of inoculum size, and variations in sensitivity to ultraviolet light among Rhizopus species could allow some spores to escape death. From 1987to 1989, the manufacturer of the UVXD (Baxter Healthcare, RoundLake, Ill.) received only one report of an episodeof fungalperitonitis in a patient who used this device (CliffordHolmes, personal communication). Since the mode of disinfection of catheters is not recorded in most published reports of fungal peritonitis, including the case reported by Polo et al. [5], a more definite association between the technique used for disinfection and fungal infection cannot be made. Regardless of the pathophysiologic mechanisms, this case
Downloaded from http://cid.oxfordjournals.org/ at The University of British Colombia Library on June 22, 2015
, I
RID 1991;13 (January-February)
Peritonitis Due to Rhizopus
and the previously reported one attest to the serious pathogenic potential of these fungi for causing peritonitis in patients who undergo CAPD. Acknowledgment The authors thank Barbara Hasbargen for her care and assistance in the management of this patient.
References 1. Vas SI. Infections of continuous ambulatory peritoneal dialysis catheters. Infect Dis Clin North Am 1989;3:301-28
4. Arfania D, Everett ED, Nolph KD, Rubin J. Uncommon causes of peritonitis in patients undergoing peritoneal dialysis. Arch Intern Med 1981;141:61-4 5. Polo JR, Luno J, Menarguez C, Gallego E, Robles R, Hernandez P. Peritoneal mucormycosis in a patient receiving continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1989;13:237-9 6. Gartenberg G, Bottone EJ, Keusch GT, Weitzman I. Hospital-acquired mucormycosis (Rhizopus rhizopodiformis) of skin and subcutaneous tissue. Epidemiology, mycology and treatment. N Engl J Med 1978; 299:1115-8 7. Windus DW, Stokes TJ, Julian BA, Fenves AZ. Fatal Rhizopus infections in hemodialysis patients receiving deferoxamine. Ann Intern Med 1987;107:678-80 8. Holmes CJ, Miyake C, Kubey W. In-vitro evaluation of an ultraviolet germicidal connection system for CAPD. Peritoneal Dialysis Bulletin Oct-Dec 1984;4:215-8 9. Luyet BJ. The effects of ultra-violet, X-, and cathode rays on the spores of Mucoraceae. Radiology 1932;18:1019-22 10. Dimond A, Duggar BM. Some lethal effects of ultra-violet radiation on fungus spores. Proc Nat! Acad Sci USA 1941;27:459-68
Downloaded from http://cid.oxfordjournals.org/ at The University of British Colombia Library on June 22, 2015
2. Kerr CM, Perfect JR, Craven PC, Jorgensen JH, Drutz DJ, Shelburne JD, Gallis HA, Gutman RA. Fungal peritonitis in patients on continuous ambulatory peritoneal dialysis. Ann Intern Med 1983;99:334-7 3. Eisenberg ES, Leviton I, Soeiro R. Fungal peritonitis in patients receiving peritoneal dialysis: experience with 11 patients and review of the literature. Rev Infect Dis 1986;8:309-21
21
Peritonitis Due to Rhizopus in a Patient Undergoing Continuous Ambulatory Peritoneal Dialysis Mary H. Branton, Steven C. Johnson, John D. Brooke, and James A. Hasbargen
From the Nephrology and Infectious Disease Services, Department of Medicine, Walter Reed Army Medical Center, Washington, D.C.; and the Department of Pathologyand Nephrology Service, Department of Medicine, Fitzsimons Army Medical Center, Aurora, Colorado
Continuous ambulatory peritoneal dialysis (CAPD) has become a popular technique for the management of end-stage renal disease. The primary complication that occurs with this method of dialysis is peritonitis, which is observed in most treatment centers at a rate of one episode per patient-year [1]. Although most cases of peritonitis that are associated with CAPD are due to bacterial infections, fungi are implicated in up to 15% of cases [2]. Fungal peritonitis may lead to significant morbidity and mortality. Removal of the dialysis catheter is frequently required for treatment of patients with fungal peritonitis; in addition, complications, such as intraabdominal abscesses, peritoneal adhesions, or peritoneal sclerosis, may make continuation of peritoneal dialysis untenable [3]. Fungal peritonitis is most often caused by Candida species; however, infections due to spore-forming molds, such as Aspergillus, have been reported [4]. We report a case of fungal peritonitis caused by a Rhizopus species; findings at autopsy and potential pathophysiologic mechanisms are discussed.
Case Summary A 61-year-old man developed end-stage renal disease secondary to diabetes mellitus and hypertension and began undergoing CAPD in February 1983. He experienced six
Received for publication 17October 1989and in revised form 22 March 1990. The assertionscontainedherein are the opinionsof the authors and should not be construedas official or as reflecting the viewsof the U.S. Department of the Army or the U.S. Department of Defense. Please address requests for reprints to Dr. StevenC. Johnson, Infectious Disease Service, Walter Reed Army Medical Center, Washington, D.C., 20307-5001. Reviewsof Infectious Diseases 1991;13:19-21 This article is in the public domain.
episodes of peritonitis in 1984 and 1985, all of which were caused by coagulase-negative staphylococci, except for one occasion when cultures also yielded Pseudomonas aeruginosa. His episodes of peritonitis were attributed to his poor aseptic technique during the use of the equipment for dialysis; the use of this technique was affected by worsening vision. The patient was trained regarding the use of an ultraviolet exchange device (UVXD, Travenol Laboratories, Deerfield, m.) in July 1985 in an attempt to minimize the number of further episodes of peritonitis. In May 1986, the patient found that his Tenckhoff catheter was clogged and therefore could not infuse dialysate solution. At that time, he was afebrile, and there was no evidence of a catheter site infection. The effluent was cloudy, and analysis revealed a white blood cell (WBC) count of 3,800/mm3 , with 78 % polymorphonuclear leukocytes, 2 % lymphocytes, and 20 % mononuclear cells. The gram stain of the fluid was negative. The patient was neither acidemic nor hyperglycemic. Intraperitoneal therapy with cefazolin and gentamicin was initiated. However, he did not improve, and cultures of the peritoneal fluid repeatedly yielded a fungus of the genus Rhizopus (the isolates were not speciated). The patient had not been treated with deferoxamine; the level of serum aluminum was 36 p.glmL, and the levels of serum iron and serum ferritin were normal, as was the iron-binding capacity. The patient was admitted to the hospital, and therapy with intraperitoneal amphotericin B was initiated. At this time, he had a fever of 101OF and diffuse abdominal tenderness, and his peripheral WBC count was 10,500/mm3 , with 5% eosinophils. The Tenckhoff catheter was removed, hemodialysis was initiated, and intravenous therapy with amphotericin B was initiated. Computed tomography of the abdomen revealed no evidence of abscess, but an indium-labeled WBC scan revealed local uptake in the abdominal wall. The patient's clinical response to therapy was rapid, and his temperature and abdominal pain decreased; however, he died of a myocardial
Downloaded from http://cid.oxfordjournals.org/ at The University of British Colombia Library on June 22, 2015
A 61-year-oldman who had end-stage renal disease secondary to diabetes mellitus and hypertension developed peritonitis due to infection with Rhizopus as a complication of receiving continuous ambulatory peritoneal dialysis (CAPD). At the onset of infection, the patient was neither acidemic nor hyperglycemic; in addition, deferoxamine had not beenadministered and Elastoplast dressings had not been applied. The infection occurred after the technique for disinfection of the catheter used for CAPD had been changed. The catheter was removed, and therapy with amphotericin B was initiated. Although the patient died of apparently unrelated causes, an autopsy revealedactive fungal infection with multiple abscessesand superficial invasion of the ileal wall.
20
Branton et aI.
RID 1991;13 (January-February)
A
B
Figure 1. A, A segment of the ileum at autopsy that demonstrates a fungal abscess on the serosal surface. B, Hematoxylin-eosin stain ofoneoftheabscesses thatdemonstrates hyphal elements that aretypical ofa Rhizopus species and necrotic debris as well asanassociated inflammatory response (x 400).
infarction 1 month after initiation of therapy. At the time of his death, he had received a total of 500 mgofamphotericin B. Autopsy revealed diffusefibrinous peritonitisas wellas abscesses located at the site of the Tenckhoff catheter, in the left lower quadrant, and on the serosal surface of the ileum (figure lA). On histologic examination, the abscesses containedlarge,ribbon-shaped aseptatehyphae thatbranchedperpendicularly, whichis typical of an infectiondue to Rhizopus (figure lB). Superficial invasionof the ileal wall was noted. Discussion
Rhizopus is an organism that belongs to the class Zygomycetes and family Mucoraceae and is commonly found in the soil. Diabeticpatientswho haveketoacidosisare particularly susceptible to infection due to these fungi. Given the high proportionof diabetics in the populationwhoundergoCAPD, the properties of peritoneal dialysatesolution that make it an ideal culture medium(high levelof glucoseand lowpH), and theubiquitous distribution of Rhizopus organisms, it is remarkable that these fungi have not been reported more frequently as pathogensof peritonitis. Polo and his colleagues recently described a patient who underwent CAPD and who developed peritonitis due to infection with Rhizopus and died [5]. This patient, like our patient, did not have ketoacidosis or any history of other clinicalmeansof exposurethat havebeen associated withinfection due to Rhizopus; suchmeansinclude the use of Elastoplast dressings [6] or chelation therapy with deferoxamine [7]. The findings at autopsy for our patient
confirm the pathogenic potential of these fungi for causing peritonitis in patients who undergo CAPD. A matter of concern for our patient was the development of fungal peritonitis after a change in the technique used to disinfect the catheter. The principle study that addresses the effectiveness of ultravioletsterilizationof the catheter against fungi in this setting was performed with use of a unicellular, non-spore-formingorganism (Candida aLbicans) as the indicator species, but other fungi were not used to test the device in this study [8]. The multicellular structure of Rhizopus as well as its propensity to form spores might make it resistant to disinfection with use of ultraviolet light. When Luyet exposed the spores of Rhizopus nigricans tRhizopus stoLonifer) to ultraviolet light at 254 nm (the wavelength of the UVXD used by our patient), he noted that as much as six times the energy used to kill yeasts was needed to kill these fungi [9]. The relative radioresistanceof older spores of Rhitopus [10], the effect of inoculum size, and variations in sensitivity to ultraviolet light among Rhizopus species could allow some spores to escape death. From 1987to 1989, the manufacturer of the UVXD (Baxter Healthcare, RoundLake, Ill.) received only one report of an episodeof fungalperitonitis in a patient who used this device (CliffordHolmes, personal communication). Since the mode of disinfection of catheters is not recorded in most published reports of fungal peritonitis, including the case reported by Polo et al. [5], a more definite association between the technique used for disinfection and fungal infection cannot be made. Regardless of the pathophysiologic mechanisms, this case
Downloaded from http://cid.oxfordjournals.org/ at The University of British Colombia Library on June 22, 2015
, I
RID 1991;13 (January-February)
Peritonitis Due to Rhizopus
and the previously reported one attest to the serious pathogenic potential of these fungi for causing peritonitis in patients who undergo CAPD. Acknowledgment The authors thank Barbara Hasbargen for her care and assistance in the management of this patient.
References 1. Vas SI. Infections of continuous ambulatory peritoneal dialysis catheters. Infect Dis Clin North Am 1989;3:301-28
4. Arfania D, Everett ED, Nolph KD, Rubin J. Uncommon causes of peritonitis in patients undergoing peritoneal dialysis. Arch Intern Med 1981;141:61-4 5. Polo JR, Luno J, Menarguez C, Gallego E, Robles R, Hernandez P. Peritoneal mucormycosis in a patient receiving continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1989;13:237-9 6. Gartenberg G, Bottone EJ, Keusch GT, Weitzman I. Hospital-acquired mucormycosis (Rhizopus rhizopodiformis) of skin and subcutaneous tissue. Epidemiology, mycology and treatment. N Engl J Med 1978; 299:1115-8 7. Windus DW, Stokes TJ, Julian BA, Fenves AZ. Fatal Rhizopus infections in hemodialysis patients receiving deferoxamine. Ann Intern Med 1987;107:678-80 8. Holmes CJ, Miyake C, Kubey W. In-vitro evaluation of an ultraviolet germicidal connection system for CAPD. Peritoneal Dialysis Bulletin Oct-Dec 1984;4:215-8 9. Luyet BJ. The effects of ultra-violet, X-, and cathode rays on the spores of Mucoraceae. Radiology 1932;18:1019-22 10. Dimond A, Duggar BM. Some lethal effects of ultra-violet radiation on fungus spores. Proc Nat! Acad Sci USA 1941;27:459-68
Downloaded from http://cid.oxfordjournals.org/ at The University of British Colombia Library on June 22, 2015
2. Kerr CM, Perfect JR, Craven PC, Jorgensen JH, Drutz DJ, Shelburne JD, Gallis HA, Gutman RA. Fungal peritonitis in patients on continuous ambulatory peritoneal dialysis. Ann Intern Med 1983;99:334-7 3. Eisenberg ES, Leviton I, Soeiro R. Fungal peritonitis in patients receiving peritoneal dialysis: experience with 11 patients and review of the literature. Rev Infect Dis 1986;8:309-21
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