![[Feedback]](/icons/banner/feedbackACT.gif)
![[For Subscribers]](/icons/banner/subscriberACT.gif)
![[Archive]](/icons/banner/archiveACT.gif)
![[Search]](/icons/banner/searchACT.gif)
![[Contents]](/icons/banner/tocACT.gif)
Previous Article | Next Article 
Journal of Clinical Microbiology, February 2001, p. 720-724, Vol. 39, No. 2
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.2.720-724.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Peritonitis Due to Thermoascus
taitungiacus (Anamorph Paecilomyces
taitungiacus)
Asher
Korzets,1,2
Miriam
Weinberger,2,3,*
Avry
Chagnac,1,2
Anna
Goldschmied-Reouven,2,4
Michael
G.
Rinaldi,5,6 and
Deanna A.
Sutton6
Department of Nephrology, Golda
Campus,1 and Department of Internal
Medicine C & Infectious Diseases, Beilinson
Campus,3 Rabin Medical Center, Petach-Tikva,
Mycology Unit, Chaim Sheba Medical Center,
Tel-Hashomer,4 and The Sackler School of
Medicine, Tel-Aviv University, Ramat-Aviv,2
Israel, and Audie L. Murphy Division, South Texas Veterans
Health Care System,5 and Fungus Testing
Laboratory, Department of Pathology, University of Texas Health
Science Center,6 San Antonio, Texas
Received 21 August 2000/Returned for modification 19 September
2000/Accepted 1 December 2000
 |
ABSTRACT |
The first case of human disease due to the thermophilic ascomycete
Thermoascus taitungiacus (the teleomorph of
Paecilomyces taitungiacus) is presented. T. taitungiacus was recovered from four dialysate fluid specimens of
a 57-year-old patient undergoing chronic peritoneal dialysis.
Identification was based upon cylindrical conidia, reddish orange
nonostiolate ascomata, lack of growth at 20°C, thermotolerance, and
ascospores that appeared pale yellow, elliptical, thick walled, and
predominately echinulate by light microscopy but irregularly verrucose
by scanning electron microscopy.
| |
TEXT |
Paecilomyces species are
found worldwide in soil, water, and decaying vegetation (13,
29) and are microscopically similar to Penicillium
and some Aspergillus species. While they are uncommon human
pathogens, they have been associated with serious infections in both
immunosuppressed and immunocompetent patients, especially those with
defects in the anatomic barriers or with a foreign body. Five species
in the genus Paecilomyces have been reported to cause
infection, including Paecilomyces variotii, Paecilomyces lilacinus, Paecilomyces marquandii, Paecilomyces viridis, and Paecilomyces javanicus (13). The most commonly
reported infections are keratitis, endophthalmitis, and cutaneous
infections. Fungemia, prosthetic valve endocarditis, lung infections,
sinusitis, and peritonitis are less frequently reported (11, 20,
23, 24, 26, 29). Thermoascus crustaceus has been
reported from monocyte cultures of patients with AIDS
(14). We report what we believe to be the first case of
human mycosis due to the ascomycetous fungus Thermoascus
taitungiacus causing peritonitis in a patient undergoing chronic
peritoneal dialysis (CPD).
Case report.
A 57-year-old man presented on 25 October 1998 with a 5-day history of abdominal pain. Since 1994 the patient had been
treated with CPD for end-stage renal failure due to chronic
glomerulonephritis and malignant hypertension. He had had two episodes
of bacterial peritonitis in 1996. Physical examination on admission
revealed diffuse abdominal tenderness compatible with peritonitis.
Empirical intraperitoneal treatment with cefazolin, 0.5 g/2 liters, and aztreonam, 0.6 g/2 liters, was started following a cell count of the
turbid dialysate effluent that revealed 250 white blood cells/mm3 (35% neutrophils, 10% lymphocytes, and 55%
monocytes). Three additional dialysate fluids were collected on October
27 and 29 and November 1. Each was plated onto blood, MacConkey,
chocolate, and Sabouraud dextrose agar (SDA) plates (Hy
Laboratories, Rehovot, Israel), as well as Löwenstein-Jensen
medium agar tubes (Heipha Diagnostika, Heidelberg, Germany), and
incubated at 35°C. All bacterial cultures were negative, but by early
November a tan-colored mould grew in pure culture on the Sabouraud agar
plates from the four separate dialysate fluid specimens. Intravenous
amphotericin B (40 mg/day) was started, and the indwelling Tenckhoff
catheter was removed. Hemodialysis was thereafter maintained via a
temporary central vein catheter.
Amphotericin B was discontinued after 2 weeks of therapy due to
intolerance (severe and repeated vomiting), liver toxicity (elevated
serum alkaline phosphatase levels), and the development of a deep vein
thrombosis of the upper limb. Oral ketoconazole (200 mg/day) was then
given for 2 weeks but was stopped due to the appearance of fever, the
accumulation of ascitic fluids, and worsening abdominal pain. The
patient became severely catabolic with an accompanying weight loss of 5 kg and hypoalbuminemia of 24 g/liter. Amphotericin B therapy was
restarted on December 6 and was given thrice weekly at the end of each
hemodialysis session together with intradialytic parenteral nutrition.
Fever abated and abdominal pain improved; however, no improvement was
seen in either the ascitic fluid volume or the ascitic white cell
count. On 20 January 1999, oral itraconazole (400 mg/day) was
substituted for amphotericin B, resulting in a gradual decrease in the
accumulation of ascitic fluid and complete disappearance of the
abdominal pain. The patient started to gain weight, and his serum
albumin level increased to 37 g/liter. Itraconazole was discontinued
after 5 months of therapy. Repeated dialysate fluid cultures since
November 1 were all sterile.
In July 1999, one month after the discontinuation of itraconazole
therapy, an enlarging right kidney mass, diagnosed histologically as
renal cell carcinoma, was removed at nephrectomy. Two years later the
patient is doing well on hemodialysis and remains asymptomatic.
Mycologic studies.
The mould isolated from
the peritoneal fluids was initially identified as a
Paecilomyces species at the Mycology Unit, Chaim Sheba
Medical Center, Tel-Hashomer, Israel. It was then referred to the
Fungus Testing Laboratory, Department of Pathology, University of Texas
Health Science Center at San Antonio, San Antonio, Texas, where the
final identification of T. taitungiacus was made and susceptibility tests were performed. The isolate was accessioned as
UTHSC R-3084, subcultured onto in-house-made (21) potato flakes agar (PFA) and SDA (Remel, Lenexa, Kans.), and incubated at 25, 35, and 42°C. A slide culture was also prepared on PFA and incubated
at 25°C. Growth of the isolate on PFA (Fig.
1A) and SDA revealed colonies that were
initially flat and buff colored but that quickly (within 6 days) became
yellowish orange with a brownish yellow reverse. Sparse conidial
structures of the Paecilomyces anamorph were evident between
3 and 4 days at 25°C on PFA. Conidia were initially cylindrical to
rectangular, approximately 7 to 7.8 by 2.9 to 3.9 µm, and then became
elliptical to subglobose (Fig. 1C). With the formation of a
Paecilomyces anamorph, additional subcultures onto Czapek
Dox and malt extract agar (MEA) (Remel) at 35°C were made in an
attempt to induce ascospore formation. Colonies on MEA became reddish
orange and granular to crust-like with a brownish orange reverse (Fig.
1B). Globose, nonostiolate ascomata occurred within 7 days on Czapek
Dox agar (Fig. 1D) and contained asci that were approximately 15.6 by
11.7 µm (Fig. 1E). Ascospores were elliptical, pale yellow, thick
walled, approximately 4 to 5 by 6.8 µm, and predominately echinulate
by light microscopy (Fig. 1F). Ascospores were subsequently examined by
scanning electron microscopy (SEM). Briefly, stubs were mounted with
Spot-O-Glue Avery labels (Diamond Bar, Calif.) and touched to the
fungal culture. Preparations were coated with gold-palladium using a
Denton Bench Top Turbo III vacuum evaporator (Morristown, N.J.)
and were examined with a LEO 435 VP digital scanning electron
microscope (Thornwood, N.Y.). When viewed by scanning electron
microscope, ascospores appeared irregularly verrucose (Fig. 1G).
View larger version (57K):
[in this window]
[in a new window]
|
FIG. 1.
Macroscopic and microscopic features of T. taitungiacus (anamorph P. taitungiacus). (A) Colonial
morphology of T. taitungiacus after 7 days of incubation at
35°C on PFA. Magnification, ×920. (B) Colonial morphology of
T. taitungiacus after 7 days of incubation at 35°C on
Czapek Dox and malt extract agar. Magnification, ×920. (C) P. taitungiacus anamorph from slide culture on PFA after 7 days of
incubation at 25°C on PFA. Magnification, ×920. (D) Nonostiolate
ascoma of T. taitungiacus. Magnification, ×230. (E) Asci
containing ascospores of T. taitungiacus. Magnification,
×920. (F) Predominately echinulate ascospores of T. taitungiacus viewed by light microscopy. Magnification, ×920. (G)
Irregularly verrucose ascospores of T. taitungiacus viewed
by scanning electron microscopy. Magnification, ×3,000.
|
|
Temperature studies were also performed by inoculating five plates of
MEA (Remel) in triplicate with a 1-mm portion of the case isolate.
Plates were incubated at 18 to 20, 25, 30, 35, and 42°C for 6 days,
and zone sizes were measured with calipers. Temperature studies
performed on day 6 indicated mean colony diameters at 20, 25, 30, 35, and 42°C of 0, 16, 85, 85, and 60 mm, respectively. The most abundant
ascocarp formation occurred at 30 and 35°C, while maximum conidial
production occurred at 42°C.
Susceptibility studies.
The case isolate and the P. variotii control strain UTHSC 90-459 were evaluated for in vitro
antifungal susceptibility by the National Committee for Clinical
Laboratory Standards broth macrodilution method M27-A (19)
modified for mould testing (9, 10). Results indicated 24- and 48-h MICs of amphotericin B of 0.25 µg/ml. Itraconazole 24- and
48-h MICs were <0.015 and 0.06 µg/ml, respectively. Based upon
achievable drug concentrations using standard dosing regimens, the
isolate appeared susceptible, in vitro, to both antifungal agents tested.
Paecilomyces species lacking known teleomorphs that have
been cited as human etiologic agents include P. variotii, P. lilacinus, P. marquandii, P. viridis, and P. javanicus
(13). Homothallic Paecilomyces species are
reported by their teleomorph name, Thermoascus (2, 5,
14, 25, 27, 28). As the name implies, these are thermophilic or
at least thermotolerant fungi. Their identification in clinical
laboratories is based upon growth characteristics, temperature studies,
and the microscopic morphology of both the anamorph and teleomorph
forms, i.e., conidiogenous cells and conidia in the genus
Paecilomyces, and ascomata, asci, and ascospores in the
genus Thermoascus. The case isolate was initially identified in San Antonio as T. crustaceus based upon its yellow-orange
to reddish orange colonies, the Paecilomyces anamorph
displaying cylindrical to rectangular-shaped conidia, growth at 25, 30, 35, and 42°C, and nonostiolate, reddish yellow ascomata producing thick-walled, slightly roughened ascospores as viewed by light microscopy. Ascospores measured 6.5 to 8 by 4.5 to 5 µm. However, in
preparation for submission of this paper, SEM studies of the ascospores
did not match those reported for T. crustaceus in that they
were irregularly verrucose (Fig. 1G) rather than finely echinulate. Recently, Chen and Chen (5) reported a new thermophilic
species of Thermoascus that failed to grow at 20°C and
produced ascospores that were echinulate by light microscopy but
irregularly verrucose by SEM. The irregularly verrucose ascospores in
the case isolate matched those described by Chen and Chen
(5) for T. taitungiacus. An identification of
T. crustaceus was eliminated due to the ascospore morphology
and lack of growth at 20°C (5). Other
Thermoascus species excluded from consideration were
Thermoascus aegyptiacus with slightly verrucose
ascospores and no growth at 20°C (27), Thermoascus
aurantiacus that frequently lacks an anamorphic state, has
minutely verrucose ascospores, and fails to grow at 30°C (5, 28), and Thermoascus thermophilus with nearly smooth
ascospores and a Polypaecilium anamorph (2).
Features of thermophilic Thermoascus species are displayed
in Table 1. The etymology for the species
name T. taitungiacus comes from the region Taitung in
Taiwan, where the organism was isolated from field soils
(5). The recovery of this organism from Israel broadens
the geographic region for this new species. T. taitungiacus
has not been previously associated with human disease.
Laboratory contamination is unlikely in the case presented, as T. taitungiacus was isolated in pure growth from four different dialysate fluids over a period of 8 days. Moreover, our patient had
clinical and laboratory evidence of CPD-associated peritonitis and
considerable morbidity due to a protracted symptomatic disease course
and the development of a hypercatabolic state. In addition to Tenckhoff
catheter removal, he required an extended period of systemic antifungal
therapy and parenteral alimentation. Paecilomyces and
Thermoascus species are a rare cause of fungal peritonitis (E. Bibashi, L. Sigler, E. Mitsopoulos, E. Roilides, M. Rinaldi, D. Sutton, D. Tsakiris, and M. Papadimitriou, Abstr. 13th Congr. Int. Soc.
Hum. Anim. Mycol., abstr. P142, 1997). The first case was reported in
1990 by Lye (16). Since then only 14 additional cases have
been published, 13 of which were identified as P. variotii (1, 3, 6, 8, 12, 15-18, 22). Paecilomyces
peritonitis is associated with substantial morbidity. Ten of 14 reported patients had to be removed from CPD and were placed on
hemodialysis (1, 6, 8, 12, 16-18); however, no fatalities
were associated with Paecilomyces peritonitis. This stands
in contrast with the high mortality rate (up to one-third of cases)
reported in CPD-related peritonitis due to other fungi
(4). The optimal approach for the treatment of
Paecilomyces peritonitis is difficult to derive from the
published data. Removal of the Tenckhoff catheter was the rule in the
majority of the patients (1, 3, 6, 8, 12, 16-18);
however, the antifungal regimens differed widely among the patients,
even within the same center (17). Of note, one patient did
not receive any antifungal therapy (18), while another
received fluconazole despite the fact that his Paecilomyces isolate appeared resistant, in vitro, to the drug (8). All eight tested Paecilomyces isolates from the reported cases
appeared susceptible, in vitro, to itraconazole (1, 3, 12,
17; Bibashi et al., Abstr. 13th Congr. Int. Soc. Hum. Anim.
Mycol.). Eight of nine tested isolates were susceptible to amphotericin B (1, 8, 12, 17, 18, 22; Bibashi et al., Abstr. 13th
Congr. Int. Soc. Hum. Anim. Mycol.), five of five to flucytosine (1, 3, 17), and only two of ten to fluconazole (1, 3, 8, 12, 17, 22; Bibashi et al., Abstr. 13th Congr. Int. Soc.
Hum. Anim. Mycol.). T. taitungiacus can be added to an
enlarging list of opportunistic filamentous fungi associated with human
infection in general and CPD-associated peritonitis in particular.
Further case studies are required to elucidate the clinical course of
infection and the optimal treatment strategies.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Internal
Medicine C & Infectious Diseases, Rabin Medical Center, Beilinson
Campus, Petach-Tikva 49100, Israel. Phone: 972-3-9378210. Fax:
972-3-9221605.
| |
REFERENCES |
| 1.
|
Alscher, D. M.,
E. Pfinder-Nohe,
D. Rumpf,
C. Pauli-Magnus,
C. Knabbe,
U. Kuhlmann, and T. Mettang.
1998.
Moulds in containers with biological wastes as a possible source of peritonitis in two patients on peritoneal dialysis.
Perit. Dial. Int.
18:643-646[Medline].
|
| 2.
|
Apinis, A. E.
1967.
Dactylomyces and Thermoascus.
Trans. Brit. Mycol. Soc.
50:573-582.
|
| 3.
|
Chan, T. H.,
A. Koehler, and P. K. Li.
1996.
Paecilomyces variotii peritonitis in patients on continuous ambulatory peritoneal dialysis.
Am. J. Kidney Dis.
27:138-142[Medline].
|
| 4.
|
Chan, T. M.,
C. Y. Chan,
S. W. Cheng,
W. K. Lo,
C. Y. Lo, and I. K. Cheng.
1994.
Treatment of fungal peritonitis complicating continuous ambulatory peritoneal dialysis with oral fluconazole: a series of 21 patients.
Nephrol. Dial. Transplant.
9:539-542[Abstract/Free Full Text].
|
| 5.
|
Chen, K.-Y., and Z.-C. Chen.
1996.
A new species of Thermoascus with a Paecilomyces anamorph and other thermophilic Thermoascus species from Taiwan.
Mycotaxon
60:225-240.
|
| 6.
|
Crompton, C. H.,
J. W. Balfe,
R. C. Summerbell, and M. M. Silver.
1991.
Peritonitis with Paecilomyces complicating peritoneal dialysis.
Pediatr. Infect. Dis. J.
10:869-871[Medline].
|
| 7.
|
Eisenberg, E. S.,
I. Leviton, and R. Soeiro.
1986.
Fungal peritonitis in patients receiving peritoneal dialysis: experience with 11 patients and review of the literature.
Rev. Infect. Dis.
8:309-321[Medline].
|
| 8.
|
Eisinger, R. P., and M. P. Weinstein.
1991.
A bold mold? Paecilomyces variotii peritonitis during continuous ambulatory peritoneal dialysis.
Am. J. Kidney Dis.
18:606-608[Medline].
|
| 9.
|
Espinel-Ingroff, A.,
M. Bartlett,
R. Bowden,
N. X. Chin,
C. Cooper, Jr.,
A. Fothergill,
M. R. McGinnis,
P. Menezes,
S. A. Messer,
P. W. Nelson,
F. C. Odds,
L. Pasarell,
J. Peter,
M. A. Pfaller,
J. H. Rex,
M. G. Rinaldi,
G. S. Shankland,
T. J. Walsh, and I. Weitzman.
1997.
Multicenter evaluation of proposed standardized procedure for antifungal susceptibility testing of filamentous fungi.
J. Clin. Microbiol.
35:139-143[Abstract].
|
| 10.
|
Espinel-Ingroff, A.,
K. Dawson,
M. Pfaller,
E. Anaissie,
B. Breslin,
D. Dixon,
A. Fothergill,
V. Paetznick,
J. Peter,
M. Rinaldi, and T. J. Walsh.
1995.
Comparative and collaborative evaluation of standardization of antifungal susceptibility testing for filamentous fungi.
Antimicrob. Agents Chemother.
39:314-319[Abstract/Free Full Text].
|
| 11.
|
Gucalp, R.,
P. Carlisle,
P. Gialanella,
S. Mitsudo,
J. McKitrick, and J. Dutcher.
1996.
Paecilomyces sinusitis in an immunocompromised adult patient: case report and review.
Clin. Infect. Dis.
23:391-393[Medline].
|
| 12.
|
Kovac, D.,
J. Lindic,
T. Lejko-Zupanc,
A. F. Bren,
B. Knap,
M. Lesnik,
A. Gucek, and D. Ferluga.
1998.
Treatment of severe Paecilomyces variotii peritonitis in a patient on continuous ambulatory peritoneal dialysis.
Nephrol. Dial. Transplant.
13:2943-2946[Abstract/Free Full Text].
|
| 13.
|
Kwon-Chung, K. J., and J. E. Bennet (ed.).
1992.
Medical mycology.
Lea & Febiger, Philadelphia, Pa.
|
| 14.
|
Kwon-Chung, K. J.,
T. Folks, and K. W. Sell.
1984.
Unusual isolates of Thermoascus crustaceus from three monocyte cultures of AIDS patients.
Mycologia
76:375-379.
|
| 15.
|
Liu, K.,
D. N. Howell,
J. R. Perfect, and W. A. Schell.
1998.
Morphologic criteria for the preliminary identification of Fusarium, Paecilomyces, and Acremonium species by histopathology.
Am. J. Clin. Pathol.
109:45-54[Medline].
|
| 16.
|
Lye, W. C.
1990.
Paecilomyces peritonitis in a patient on continuous ambulatory peritoneal dialysis.
Nephrol. Dial. Transplant.
5:1053-1054.
|
| 17.
|
Marzec, A.,
L. G. Heron,
R. C. Pritchard,
R. H. Butcher,
H. R. Powell,
A. P. Disney, and F. A. Tosolini.
1993.
Paecilomyces variotii in peritoneal dialysate.
J. Clin. Microbiol.
31:2392-2395[Abstract/Free Full Text].
|
| 18.
|
Nankivell, B. J.,
D. Pacey, and D. L. Gordon.
1991.
Peritoneal eosinophilia associated with Paecilomyces variotii infection in continuous ambulatory peritoneal dialysis.
Am. J. Kidney Dis.
18:603-605[Medline].
|
| 19.
|
National Committee for Clinical Laboratory Standards.
1997.
Reference methods for broth dilution antifungal susceptibility testing of yeasts. Approved standard M27-A.
National Committee for Clinical Laboratory Standards, Wayne, Pa.
|
| 20.
|
Orth, B.,
R. Frei,
P. H. Itin,
M. G. Rinald,
B. Speck,
A. Gratwohl, and A. F. Widmer.
1996.
Outbreak of invasive mycoses caused by Paecilomyces lilacinus from a contaminated skin lotion.
Ann. Intern. Med.
125:799-806[Abstract/Free Full Text].
|
| 21.
|
Rinaldi, M. G.
1982.
Use of potato flakes agar in clinical mycology.
J. Clin. Microbiol.
15:1159-1160[Abstract/Free Full Text].
|
| 22.
|
Rinaldi, S.,
E. Fiscarelli, and G. Rizzoni.
2000.
Paecilomyces variotii peritonitis in an infant on automated peritoneal dialysis.
Pediatr. Nephrol.
14:365-366[CrossRef][Medline].
|
| 23.
|
Rodrigues, M. M., and D. MacLeod.
1975.
Exogenous fungal endophthalmitis caused by Paecilomyces.
Am. J. Ophthalmol.
79:687-690[Medline].
|
| 24.
|
Saberhagen, C.,
S. A. Klotz,
W. Bartholomew,
D. Drews, and A. Dixon.
1997.
Infection due to Paecilomyces lilacinus: a challenging clinical identification.
Clin. Infect. Dis.
25:1411-1413[Medline].
|
| 25.
|
Stolk, A. C.
1965.
Thermophilic species of Talaromyces Benjamin and Thermoascus Miehe.
Antonie Leeuwenhoek
31:262-276.
|
| 26.
|
Tan, T. Q.,
A. K. Ogden,
J. Tillman,
G. J. Demmler, and M. G. Rinaldi.
1992.
Paecilomyces lilacinus catheter-related fungemia in an immunocompromised pediatric patient.
J. Clin. Microbiol.
30:2479-2483[Abstract/Free Full Text].
|
| 27.
|
Ueda, S., and S.-I. Udagawa.
1983.
Thermoascus aegyptiacus, a new thermophilic ascomycete.
Trans. Mycol. Soc. Japan
24:135-142.
|
| 28.
|
Upadhyay, M. M.,
M. S. Framelo,
S. O. Goetz, and M. A. Melan.
1984.
A new variety of a thermophilic mold, Thermoascus aurantiacus var. levisporus.
Mycopathologia
87:71-80[CrossRef].
|
| 29.
|
Williamson, P. R.,
K. J. Kwon-Chung, and J. I. Gallin.
1992.
Successful treatment of Paecilomyces variotii infection in a patient with chronic granulomatous disease and a review of Paecilomyces species infections.
Clin. Infect. Dis.
14:1023-1026[Medline].
|
Journal of Clinical Microbiology, February 2001, p. 720-724, Vol. 39, No. 2
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.2.720-724.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Top
Abstract
Text
