BRIEF REPORT
ceived PD treatment during the period of January 1991 through
Fungal Peritonitis Complicating
Peritoneal Dialysis during an 11-Year
Period: Report of 46 Cases
Evangelia Bibashi,1 Dimitrios Memmos,2 Elizabeth Kokolina,2
Dimitrios Tsakiris,2 Danai Sofianou,1 and Menelaos Papadimitriou2
Departments of 1Microbiology and 2Nephrology, Aristotle University,
Hippokration General Hospital, Thessaloniki, Greece
The incidence of fungal peritonitis (FP) and the fungi that
caused FP were evaluated in 422 patients treated with peri-
toneal dialysis. During an 11-year period, 804 episodes of
peritonitis occurred, 46 (5.7%) of which were caused by
fungi. Treatment was successful for 39 patients. Early diag-
nosis of FP and prompt therapy decreases morbidity and
mortality.
In recent years, the frequency of bacterial peritonitis in patients
with end-stage renal disease treated by peritoneal dialysis (PD)
has been reduced because of improvements in dialysis equip-
ment and a better approach to treatment. Nevertheless, fungal
peritonitis (FP) remains a serious complication associated with
high rates of morbidity and mortality. The reported incidence
of FP is 2%–10.2% [1], the mortality rate is 5%–25%, and 40%
of patients with an episode of FP are switched to hemodialysis
[2–4]. The most common cause of FP is Candida species, with
Candida albicans predominating [1–3]. Fungi enter the peri-
toneal cavity intraluminally or periluminally; very rarely, they
enter via the vaginal route [1]. Clinically, FP cannot be differ-
entiated from bacterial peritonitis, except by Gram stain and
culture of dialysate specimens. The treatment of FP is difficult
because the fungi form a biofilm on the surface of the silastic
catheters that reduces the penetration of antifungal agents. In
this study, the incidence of FP and the organisms that most
commonly cause FP were evaluated in 422 patients who re-
Received 7 October 2002; accepted 2 December 2002; electronically published 18 March
2003.
Presented in part: 8th Congress of the European Confederation of Medical Mycology,
Budapest, Hungary, August 2002 (poster PO3 02).
Reprints or correspondence: Dr. Evangelia Bibashi, Dept. of Microbiology, Hippokration
General Hospital, 49, Konstantinoupoleos St., Thessaloniki 54642, Greece (bibashi@med.
auth.gr).
Clinical Infectious Diseases 2003; 36:927–31
 2003 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2003/3607-0017$15.00
December 2001.
Patients and methods. The frequency, diagnosis, and
treatment of FP during an 11-year period (January 1991
through December 2001) were retrospectively studied in 422
patients with end-stage renal failure treated by PD (405 were
treated with continuous ambulatory PD, and 17 were treated
with automated PD). The diagnosis of peritonitis was based
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on clinical manifestations (abdominal pain, nausea, and fever)
and a cloudy appearance of the dialysis effluent (DE), with a
WBC count of 1100 cells/mm3 (with neutrophil predomi-
nance). Diagnosis was confirmed by the isolation of the same
fungus from 11 DE sample. The processing of the DE sample
included a leukocyte count, centrifugation of cloudy DE, and
Gram and Giemsa staining of the pellet (i.e., the sediment of
peritoneal dialysis effluent). For bacterial culture, DE samples
were inoculated onto blood agar and MacConkey agar, and
5 mL of DE was added to double-concentration thioglycollate
broth. For fungal culture, DE samples were inoculated onto
Sabouraud dextrose agar. All incubation was performed at
37C for 7 days.
For the identification of C. albicans, a screening test of the
germination tube was initially performed. If the result was neg-
ative (for C. albicans), the Api-System CAUX20 or Api-System
ID 32C (bioMérieux) was used. Molds were identified on the
basis of their macroscopic and microscopic appearances after
culture on Sabouraud dextrose agar and potato dextrose agar,
which induces sporulation.
Susceptibility testing of all isolated Candida species to the
antifungal drugs 5-fluorocytosine, amphotericin B, nystatin,
miconazole, econazole, and ketoconazole was performed first
by the method of Drouhet and Dupont [5] (i.e., the antifungal
drug was absorbed in paper disks that were put onto a semi-
synthetic medium [Pasteur]), and second by determination of
the MIC with use of the commercially available ATB-fungus
test (bioMérieux). In addition, 30 isolates of Candida species
underwent susceptibility testing by the National Committee for
Clinical Laboratory Standards (NCCLS) M27-A method, with
some modification [6]. The isolates were tested for suscepti-
bility to amphotericin B, fluconazole, 5-fluorocytosine, itra-
conazole, ketoconazole, and voriconazole.
The treatment of FP included administration of amphoter-
icin B (20–25 mg iv q.d.) and 5-fluorocytosine (50 mg in every
2-L PD bag) for 14 days, followed by administration of flu-
conazole (100 mg po q.d.) for 1 month. If there was no clinical
improvement, the PD catheter was removed on the fifth to
BRIEF REPORT • CID 2003:36 (1 April) • 927
seventh day of treatment, intraperitoneal administration of 5- Table 1. Species of fungi isolated during 46
fluorocytosine was stopped, and the patient was treated by episodes of peritoneal dialysis peritonitis.
hemodialysis for 4–6 weeks. After this period, a new catheter
No. (%) of
was inserted in patients who recommenced PD treatment. episodes
Results. During the 11-year study period, 804 episodes of Fungus (n p 46)
peritonitis were observed. In 46 of these episodes, which oc- Candida species
curred in 44 patients (23 men and 21 women), fungi were All 41 (89.1)
identified as etiological agents. Two female patients each had Candida albicans 17 (36.9)
2 episodes of FP. At the time of diagnosis of FP, the mean age Candida parapsilosis 11 (23.9)
of the 44 patients was 59.4 years (range, 3–80 years), and the Candida tropicalis 5 (10.8)
mean duration of PD (SD) was 34.8  30.4 months (range, Candida guilliermondii 4 (8.7)
0.5–96 months). Candida pseudotropicalis 1 (2.2)
The primary renal disease leading to end-stage renal failure Candida pulcherrima 1 (2.2)

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was diabetic nephropathy in 9 patients, chronic interstitial ne-
phritis in 8 patients, chronic glomerulonephritis in 6 patients,
polycystic kidney disease in 7 patients, amyloidosis in 4 patients,
and nephrosclerosis in 4 patients. The disease was unknown
for the remaining 6 patients.
At admission to the hospital, all patients had clinical signs
and symptoms of peritonitis and cloudy DE samples. At pre-
sentation, the signs and symptoms of FP were not different
from those of bacterial peritonitis. WBC counts were 150–9000
cells/mm3, with neutrophil predominance. Gram staining of
DE samples revealed budding yeasts or hyphae for 9 (19.6%)
of 46 episodes in which the presence of fungi was confirmed
by culture. In the remaining 37 episodes, the results of Gram
staining were negative, and dialysate cultures revealed fungi
after a mean period of 1.5 days (range, 1–5 days).
Among the causative organisms (table 1), various Candida
species accounted for 89.1% of all episodes of FP, with C.
albicans being by far the most common isolate. Filamentous
fungi were identified in 4 cases of FP, the details of which have
been published elsewhere [7, 8]. Aspergillus niger was identified
in a 37-year-old woman shortly after the initiation of PD be-
cause of rejection of a kidney transplant. Atypical Paecilomyces
variotii was isolated from a 65-year-old woman with FP. The
remaining 2 filamentous fungi that caused FP in 2 women (ages,
76 and 57 years old) were Fusarium solani and Acremonium
strictum, respectively. In 15 patients, FP followed an episode of
bacterial peritonitis that was treated with antibiotics.
All isolates tested by methods 1 and 2 were susceptible to
the antifungal drugs amphotericin B, 5-fluorocytosine, nystatin,
miconazole, econazole, and ketoconazole. The results yielded
using the NCCLS M27-A method are presented in table 2. All
blood culture results were negative, and there was no evidence
of disseminated fungal disease.
Treatment was successful in 39 (88.6%) of 44 patients. The
PD catheter was removed on the fifth to seventh day after the
initiation of the therapy in 40 episodes (87%). After treatment,
17 patients (38.6%) recovered from infection and continued
Other Candida species 2 (4.3)
Other fungus
All 5 (10.9)
Rhodotorula pilimanae 1 (2.2)
Aspergillus niger 1 (2.2)
Paecilomyces variotii 1 (2.2)
Fusarium solani 1 (2.2)
Acremonium strictum 1 (2.2)
PD, 20 (45.5%) switched to hemodialysis, and 7 (15.9%) died.
Our results, as well as the results from other reports [2, 3,
9–14], are shown in table 3.
Discussion. FP is a serious complication of treatment
with PD, with high rates of morbidity and mortality. The
incidence of FP (5.7% of episodes of peritonitis) at our health
care center is within the range of the reported incidence of
2%–10.2% [1–3, 9–15]. The duration of PD treatment before
the diagnosis of FP in our patients (0.5–96 months) is also
similar to the reported ranges of 1–72 months [3] and 2–69
months [2].
In patients undergoing PD, many factors are present that are
liable to favor the occurrence of FP, including rupture of the
cutaneous barrier, as a result of the presence of the catheter,
and reduced cellular immunity during chronic end-stage renal
disease. The relative rarity of fungal infection suggests that other
factors are also involved, but neither age nor sex seems to be
implicated. On the other hand, 34% of the patients with FP
in this study had a recent episode of bacterial peritonitis and
had received antibiotics. It seems that hospitalization, recent
episodes of bacterial peritonitis, and the administration of an-
tibiotics are involved in the pathogenesis of FP [9, 16]. The
role of diabetes has been variously evaluated in different series
[3, 16], but, in most studies, it does not seem to predispose
patients to FP.
Our results confirm the absence of specificity of clinical
manifestations and cell counts in DE in our patients with FP
[9, 10, 17]. On the other hand, Gram staining of centrifuged

928 • CID 2003:36 (1 April) • BRIEF REPORT

 Table 2. Results of susceptibility tests conducted using the National
Committee for Clinical Laboratory Standards M27-A method.

MIC MIC50 MIC90

Organism (no. of isolates after 48 h, after 24/48 h, after 24/48 h,
tested), antifungal agent mg/mL mg/mL mg/mL
Candida albicans (15)
Amphotericin B 1 1/1 1/1
Fluconazole 0.25–64 0.25/1 0.25/64
5-Fluorocytosine 0.063–0.25 0.125/0.25 0.125/0.25
Itraconazole 0.031–32 0.031/0.063 0.031/2
Ketoconazole 0.031–16 0.031/0.063 0.031/16
Voriconazole 0.031–4 0.031/0.125 0.063/4
Candida parapsilosis (11)

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Amphotericin B 1 1/1 1/1
Fluconazole 0.5–2 0.5/1 1/2
5-Fluorocytosine 0.063–1 0.063/0.125 0.125/0.25
Itraconazole 0.125–0.25 0.063/0.25 0.125/0.25
Ketoconazole 0.031–0.25 0.031/0.063 0.063/0.125
Voriconazole 0.031–0.063 0.031/0.031 0.031/0.063
Candida tropicalis (4)
Amphotericin B 1 1/1 —
Fluconazole 1–64 0.5/64 —
5-Fluorocytosine 0.063–0.5 0.063/0.25 —
Itraconazole 0.125–4 0.063/0.25 —
Ketoconazole 0.125–8 0.063/8 —
Voriconazole 0.25–4 0.063/4 —

DE specimens was definitely a useful test, because it permitted of fungus from DE culture confirmed the diagnosis of FP.
the detection of budding yeasts or pseudohyphae in 19.6% The most common fungus was Candida species, a yeast that
of episodes of FP. The proportion of positive test results re- grows easily on medium used for culture of bacteria, such as
ported by other authors was 10%–50% [3, 9]. The isolation blood agar. It does not seem necessary, for routine purposes,

Table 3. Total number of episodes of peritoneal dialysis (PD)–associated fungal peritonitis (FP),
by fungal agent (Candida albicans [CA] and non-albicans species of Candida [CNA]), and the outcome
of FP.

No. of episodes of FP, by patient group and fungal agent

Patient had Patient
All catheter removed resumed PD Patient died
Study Total CA CNA Total CA CNA Total CA CNA Total CA CNA
[9] 11 4 4 11 4 4 0 0 0 3 1 1
[10] 27 NS NS 23 NS NS 9 NS NS 6 NS NS
[2] 38 13 11 38 NS NS 23 NS NS 5 NS NS
[3] 20 6 9 13 NS NS 5 NS NS 5 NS NS
[11] 6 1 4 6 1 4 0 0 0 2 1 1
[12] 55 NS NS 47 NS NS 27 NS NS 11 NS NS
[13] 16 1 5 12 1 4 3 0 2 5 0 2
[14] 34 NS NS 32 NS NS 10 NS NS 9 NS NS
Present study 46 17 24 40 14 21 17 6 8 7 2 5

NOTE. NS, not specified.

BRIEF REPORT • CID 2003:36 (1 April) • 929

to grow cultures on specific fungal media, as suggested by
Rubin et al. [18]. The most common species of Candida to
have caused FP in our patients were C. albicans (36.9%) and
Candida parapsilosis (23.9%), as has also been reported by
others [2, 16, 18, 19].
Although filamentous fungi rarely invade the PD catheter
and cause FP [18], they were isolated in 4 episodes of FP. To
our knowledge, the patient with FP caused by A. niger was the
only one to have survived of 7 reported patients with PD caused
by Aspergillus species [7, 20]. In the relevant literature, there
are 13 reported cases involving P. variotii [8, 21], 12 cases
involving Fusarium species (one of which was due to F. solani)
[8, 22], and 2 cases involving Acremonium species (one of which
was due to Acremonium kiliense, and the other of which was
due to A. strictum) [23, 24].
Susceptibility testing revealed that amphotericin B was the only
antifungal agent to which all recovered organisms were suscep-
tible. On the other hand, 4 of 15 isolates of C. albicans with a
high MIC of fluconazole had high MICs of other azoles, too.
With regard to treatment of FP, most authors agree that
removal of the PD catheter is not adequate and that admin-
istration of antifungal agents is imperative. In this study, the
PD catheter was removed during 40 (87%) of 46 episodes of
FP, which is higher than the rate described in most reports
[2, 17]. This may have contributed to the low percentage of
deaths in our study (15.9%), which is comparable to the
incidence of 17%–24% reported elsewhere [9, 10], although
even higher mortality rates have been reported by some au-
thors [3, 15, 18].
In conclusion, FP is a serious complication of PD leading
to loss of ultrafiltration and discontinuation of PD treatment.
The most frequently isolated fungi are C. albicans and C. para-
psilosis; filamentous fungi are found only rarely. The Api-System
CAUX20 and Api-System ID 32C methods seem to be simple
means for yeast identification. The ATB-fungus method for
antifungal susceptibility testing is simple, and the result is ready
in 24 h. Treatment requires administration of antifungal agents,
especially amphotericin B, to which organisms are still suscep-
tible, and early removal of the peritoneal catheter. The prompt
diagnosis of FP and the early institution of therapy decrease
the rates of morbidity and mortality.
Acknowledgments
We thank Lynne Sigler, curator and professor at the Uni-
versity of Alberta Microfungus Collection and Herbarium (Ed-
monton, Alberta, Canada), for the identification of Paecilomyces
variotii and Acremonium strictum. We thank the Department
of Medical Microbiology, University Medical Center Nijmegen,
The Netherlands, for technical support regarding the suscep-
930 • CID 2003:36 (1 April) • BRIEF REPORT
tibility testing by the National Committee for Clinical Labo-
ratory Standards method.
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