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Faecal candida and diarrhoea 329
Table 1 Characteristics of diarrhoea and control patients Table 3 Age distribution of patients with faecal yeasts
Diarrhoea group (DG) n (%) Control group (CG) n (%) Diarrhoea group Control group
107 67
Bacteria
of an enteric pathogen was significantly associ-
C diYcile culture and/or 28 (26) 6 (9) ated with the identification of faecal yeasts
toxin (÷2 = 25.1, p < 0.005).
Campylobacter jejuni 4 (4) —
Viruses
There was no diVerence in the isolation of
Adenovirus 4 (4) —* yeasts between DG (n = 43, 39%) and CG
Rotavirus 20 (19) —* (n = 26, 35%) children. C albicans was the
Parasite
Giardia intestinalis 6 (6) 2 (3) most commonly identified yeast and was
Total 62 (58) 8 (12) isolated from 35 of 107 (35%) and 18 of 67
(27%) DG and CG children, respectively.
*Rotavirus/adenovirus testing not performed on non-diarrhoeal
stools. Other yeasts isolated included other candida
species (C parapsilosis, C guillermondii, C lipoly-
fying the colonies. C albicans was identified by tica, C humicola) as well as Torulopsis glabrata
the production of germ tubes and confirmed by (n = 2), Trichsporon beigelii (n = 1), and Rhodo-
the production of chlamydospores.16 Species torula glutinis (n = 1). All of the isolated yeast
identification of germ tube negative yeasts was species were grouped together in subsequent
carried out using the commercial API C20 analyses, and referred to collectively as yeasts.
AUX yeast kit (Blackaby Diagnostics, Aus- Table 3 shows the age distribution of patients
tralia). Yeast counts were determined by colony with yeasts in the stool. There was no
counting 48 hours after incubation. significant association between age and identi-
fication of faecal yeasts.
STATISTICAL ANALYSIS Table 4 shows the concentration of stool
The significance of diVerences between the yeasts. Patients with diarrhoea were more likely
DG and CG patients was determined using the to have higher concentrations of faecal yeasts
÷2 test for categorical variables and Student’s t than the CG patients. The CG children tended
test for continuous variables. Analyses are to have more counts of less than 10 000 yeasts
reported with all yeasts included together in per g of faeces (÷2 = 9.687, p = 0.017). The
one group. concentration of faecal yeasts was significantly
associated with use of antibiotics (÷2 = 12.515,
Results p < 0.005).
Stool samples were collected from 107 children Patients with yeasts in their stools were more
with diarrhoea and 67 children without diar- likely to have had recent antibiotic treatment
rhoea. Both groups were similar in age, race, than those without yeasts, although this was
and percentage weight for height (table 1). The not significant (48% v 35%, ÷2 = 2.74,
duration of diarrhoea in the DG patients p = 0.095). The density of candida was how-
ranged from less than one day to 480 days, with ever related to recent antibiotic use, with higher
a median of one day. The duration of diarrhoea concentrations of faecal candida more likely to
in DG patients with and without stool yeasts occur with recent antibiotic use (÷2 = 11.687,
was not significantly diVerent (median: one day p = 0.009).
in both groups). More of the DG children had Stool characteristics recorded included the
recent exposure to antibiotics than CG chil- presence of white blood cells (18 patients), red
dren (n = 51, 45% compared with n = 19, blood cells (two patients), fat globules (28
28%; p = 0.013). patients), lactose intolerance (17 patients), and
Enteric pathogens were isolated from the monosaccharide intolerance (six patients).
stools of 47 of 107 (44%) DG and seven of 67 None of these characteristics were associated
(10%) CG children (table 2). Twenty three of with the presence of stool yeasts.
66 patients with enteric yeasts also had other
pathogens isolated from their stools (18 from Discussion
DG and five from CG). There were five Yeasts and fungi, especially candida species, are
subjects in the DG in whom rotavirus and present in the faeces of healthy individuals.
another pathogen was isolated. Identification Candida colonises the oral cavity of up to three
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330 Forbes, Ee, Camer-Pesci, Ward
quarters of preterm infants within the first In contrast to these previous studies, our
week of life,17 18 and can be found in the study did not document an association be-
oropharyx of nearly 20% of healthy infants.19 tween faecal candida species and diarrhoea.
The gut is colonised more slowly, with 11% of There are several explanations for this discrep-
preterm infants having positive faecal cultures ancy. Firstly, earlier studies did not include
for candida at 4 weeks of age.20 Up to a quarter control groups. Secondly, it is possible that
of healthy, non-hospitalised infants are re- candida may have a diVerent eVect in patients
ported to have candida in their faeces by 5 to who are malnourished. Malnutrition may
12 months of age.21 During childhood 12 to encourage proliferation of yeast species, and
16% of children carry candida in the stool, and the association with diarrhoea may be coinci-
the proportion increases to 80% in adult- dental.
hood.7 22 23 Hospitalised children appear to It is not surprising that recent antibiotic use
have higher carriage rates of candida than chil- was associated with higher candida counts,
dren in the community, and the proportion given that antibiotic therapy encourages prolif-
increases with duration of hospitalisation.22 24 eration of candida in the intestine.28–30 Our
This study confirms that yeasts, predomi- finding that the identification of another
nantly candida species, are common in the fae- pathogen was strongly associated with higher
ces of hospitalised patients in a paediatric hos- counts of faecal candida is also consistent with
pital. Candida species were identified in the other reports.12–14 26 31
stools of approximately 40% of all patients Despite previous reports to the contrary, we
studied. Although higher concentrations of have not confirmed an association between
candida were found in patients with diarrhoea faecal candida or other yeasts and diarrhoea.
it was not possible to prove a causative relation Faecal concentrations of candida were however
between the yeasts and diarrhoea. higher in patients with diarrhoea. While
candida did not contribute to diarrhoea in our
A number of reports have suggested that
population it is possible that in malnourished
candida might cause diarrhoea in adults and
children with chronic diarrhoea, candida spe-
children. Discontinuation of antibiotics and
cies may assume a significant role.
the use of nystatin in adults with persistent
diarrhoea and “heavy” faecal growth of yeasts
The assistance of the staV of the Microbiology Department at
resulted in a return to normal stool patterns Princess Margaret Hospital, Perth, Western Australia in
within days.8 10 Gupta and Ehrinpreis identified specimen processing, and ward nursing staV for their assistance
in specimen collection is gratefully acknowledged.
heavy faecal growth of candida in a group of
elderly, malnourished, and critically ill patients 1 Lambrechts T, Bryce J, Orinda V. Integrated management of
with diarrhoea, but were unable to find any childhood illness: a summary of first experiences. Bull World
Health Organ 1999;77:582–94.
other microbiological, inflammatory, or chemi- 2 Ahmed T, Ali M, Ullah MM, et al. Mortality in severely
cal cause for their symptoms.9 With anti- malnourished children with diarrhoea and use of a
standardised management protocol. Lancet 1999;353:
candida therapy, the diarrhoea resolved. Danna 1919–22.
et al reported resolution of antibiotic associated 3 Murray CJ, Lopez AD. Mortality by cause for eight regions
of the world: Global Burden of Disease Study. Lancet 1997;
diarrhoea in elderly patients with intestinal 349:1269–76.
overgrowth of candida, after treatment with 4 Biswas R, Lyon D, Nelson E, et al. Aetiology of acute diar-
rhoea in hospitalized children in Hong Kong. Trop Med Int
nystatin.10 Health 1996;1:679–83.
Bishop and Barnes identified C albicans in 5 Suwatano O. Acute diarrhea in under five-year-old children
admitted to King Mongkut Prachomklao Hospital, Petch-
the stools of one third of children with acute aburi Province. J Med Assoc Thai 1997;80:26–33.
gastroenteritis who were aged less than 1 year, 6 Warren NG, Shadomy JH. Yeasts of medical importance. In:
Balows A, Hausler WJ, Herrmann KL, et al, eds. Manual of
compared with just 15% of controls.25 They clinical microbiology. Washington, DC: American Society for
suggested that C albicans was an opportunistic Microbiology, 1991:617–29.
7 Cohen R, Roth FJ, Delgado E, et al. Fungal flora of the
pathogen, causing prolonged diarrhoea after human small and large intestine. N Engl J Med 1969;280:
mucosal injury by another pathogen.25 Fungal 638.
8 Kane JG, Chreteun JH, Garagusi VF. Diarrhoea caused by
mycelia in the stools were reported as a marker Candida. Lancet 1976;i:335–6.
of invasive enteric candida in a group of 9 Gupta TP, Ehrinpreis MN. Candida-associated diarrhea in
hospitalized patients. Gastroenterology 1990;98:780–5.
patients, some of who had persistent diarrhoea 10 Danna PL, Urban C, Bellin E, Rahal JJ. Role of candida in
following other infections.26 In these patients pathogenesis of antibiotic-associated diarrhoea in elderly
inpatients. Lancet 1991;337:511–14.
there was resolution of the diarrhoea after 11 Gracey M, Suharjono M, Sunoto M, Stone D. Microbial
treatment with nystatin. In a group of Nigerian contamination of the gut: another feature of malnutrition.
Am J Clin Nutr 1973;26:1170–4.
children, 77% had fungi isolated from the 12 Heyworth B, Brown J. Jejunal microflora in malnourished
stools, and candida, the predominant isolate, Gambian children. Arch Dis Child 1975;50:27–33.
13 Enweani IB, Obi CL, Jokpeyibo M. Prevalence of Candida
was strongly associated with diarrhoea.13 In a species in Nigerian children with diarrhoea. J Diarrhoeal
large Indian study fungal proliferation was Dis Res 1994;12:133–5.
14 Chaudhury A, Nath G, Shukla B, et al. Diarrhoea associated
noted in the stools of 55% of children and with Candida spp: incidence and seasonal variation. J
adults with acute and chronic diarrhoea.27 The Diarrhoeal Dis Res 1996;14:110–12.
15 Ponnuvel KM, Rajkumar R, Menon T, Sankaranarayanan
prevalence of faecal fungi in children peaked at VS. Role of Candida in indirect pathogenesis of antibiotic
the same time as the peak prevalence of bacte- associated diarrhoea in infants. Mycopathologia 1996;135:
145–7.
rial diarrhoea. A subsequent study in India 16 Odds FC, Kibbler CC, Walker E, et al. Carriage of Candida
reported candida as the sole pathogen in 15% species and C albicans biotypes in patients undergoing
chemotherapy or bone marrow transplantation for haema-
of diarrhoeal stool specimens.14 Prevalence was tological disease. J Clin Pathol 1989;42:1259–66.
highest among infants aged 0–12 months, with 17 Rotimi VO, Olowe SA, Ahmed I. The development of bac-
terial flora of premature neonates. J Hyg (Lond) 1985;94:
a summer peak in prevalence. Several authors 309–18.
have reported small intestinal overgrowth with 18 Pappu-Katikaneni L, Rao K, Banister E. Gastrointestinal
colonization with yeast species and Candida septicemia in
candida in malnourished children.11 12 very low birth weight infants. Mycoses 1990;33:20–3.
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Faecal candida and diarrhoea 331
19 Dixon PN, Warin RP, English MP. Role of Candida albicans Here again the principle applies that “coinci-
infection in napkin rashes. BMJ 1969;2:23–7.
20 Ormala T, Korppi M, Katila ML, et al. Fungal gut coloniza- dence is no proof of causality”.2 The associ-
tion with Candida or Pityrosporum sp. and serum Candida ation between antibiotic usage and diarrhoea is
antigen in preterm neonates with very low birth weights.
Scand J Infect Dis 1992;24:781–5. no surprise, and the link between antibiotic
21 Pederson G. Yeast flora in mother and child. A mycological- usage and faecal candida has been well
clinical study of women followed up during pregnacy, the
puerperium and 5–12 months after delivery, and their chil- documented. This, of course, is no proof that
dren on the 7th day of life and 5–12 months. Nord Med antibiotic associated diarrhoea is caused by
1969;81:207.
22 Pan N-C, Pan I-H. Prevalence rate of Candida species in candida. Nevertheless, there are anecdotal
stool of children in Taipei. J Formosan Med Assoc 1964;63: reports of successful treatment of this condi-
396.
23 Gorbach SL. Studies of intestinal microflora. I. EVects of tion with nystatin.
diet, age and periodic sampling on numbers of faecal Patients infected with human immuno-
micro-organisms in man. Gastroenterology 1967;53:845–54.
24 Marks M, Marks S, Brazeau M. Yeast colonization in hospi- deficiency virus often suVer from diarrhoea. C
talised and nonhospitalised children. J Pediatr 1975;87: albicans is commonly isolated from the stool in
524–7.
25 Bishop RF, Barnes GL, Townley RRW. Microbial flora of these patients, but is just one of many possible
stomach and small intestine in infantile gastroenteritis. agents that might be responsible for the
Acta Paediatr Scand 1974;63:418–22.
26 Kozinn P, Taschdjian C. Enteric candidiasis. Diagnosis and diarrhoea.
clinical considerations. Pediatrics 1962;30:71–85. As the authors indicate, studies from Paki-
27 Talwar P, Chakrabarti A, Chawla A, et al. Fungal diarrhoea:
association of diVerent fungi and seasonal variation in their stan and Nigeria have revealed increased
incidence. Mycopathologia 1990;110:101–15. carriage of Candida spp. in the stools of
28 Samonis G, Anaissie EJ, Rosenbaum B, Bodey GP. A model
of sustained gastrointestinal colonization by Candida albi- malnourished children with diarrhoea. This
cans in healthy adult mice. Infect Immun 1990;58:1514–17. does not confirm an aetiological role for
29 Samonis G, Gikas A, Anaissie EJ, et al. Prospective
evaluation of eVects of broad-spectrum antibiotics on candida, even in those populations. Candida
gastrointestinal yeast colonization of humans. Antimicrob spp. are frequently identified in the absence of
Agents Chemother 1993;37:51–3.
30 Guggenbichler JP, Kofler J, Allerberger F. The influence of diarrhoea as the present study confirms.
third-generation cephalosporins on the aerobic intestinal If “coincidence is not causality”, neither
flora. Infection 1985;13(suppl 1):S137–9.
31 Househam K, Mann M, Mitchell J, Bowie M. Duodenal does the failure of this study to show a signifi-
microflora in infants with acute diarrheal disease. J Pediatr cant association with diarrhoea disprove the
Gastroenterol Nutr 1986;5:721–5.
role of yeasts as potential pathogens. There
Commentary may be specific clinical circumstances in which
Does candida cause diarrhoea? they can be responsible for diarrhoea. In addi-
Despite significant progress over the years, tion, there are more than 80 candida species, as
no causative agent can be identified in a well as other yeast species, and these may vary
substantial proportion of infants and children in their pathogenicity. Even within species cer-
with acute diarrhoea. In one study of over 4600 tain strains may have diVerent properties.
such children in Australia, no known enteric Using restriction enzyme analysis and a C albi-
pathogen was found in 44% of cases.1 The cans specific DNA probe, Mathaba et al
search for possible pathogens goes on. In this recently identified specific genetically distinct
study the authors asked whether Candida spp. strains that may be associated with diarrhoea.3
or other yeasts might be an important and Increased levels of secretory proteinase pro-
unrecognised cause of diarrhoea. duction were noted in isolates from patients
They analysed stool specimens from well with diarrhoea. Variation in adherence proper-
nourished children in a tertiary referral hospi- ties was shown in diVerent isolates, and they
tal in Western Australia. These included reported that reduced and increased adherence
children admitted with diarrhoea, children who were associated with acute and chronic diar-
developed diarrhoea while in hospital, and rhoea respectively.
children without diarrhoea who were in hospi- The role of candida and other yeast species
tal with various other disorders (disease as enteric pathogens may yet prove to be a
controls). Although some of the subjects had complex one.
chronic diarrhoea (the duration ranged from M STEPHEN MURPHY
less than 24 hours to 480 days), the median Institute of Child Health, Clinical Research Block,
duration was just one day. Yeasts (most often C Whittall Street, Birmingham B4 6NH, UK
albicans) were identified in stool samples from
1 Barnes GL, Uren E, Stevens KB, Bishop RF. Etiology of
39% of those with diarrhoea and 35% of the acute gastroenteritis in hospitalized children in Melbourne,
controls (no significant diVerence). Higher Australia, from April 1980 to March 1993. J Clin Microbiol
1998;36:133–8.
yeast concentrations were reported in those 2 Heininger U. Coincidence is not causality—a principle
with diarrhoea and in those with a history of which needs regular rediscovery. Arch Dis Child 2000;83:
355.
recent antibiotic treatment. However, there 3 Mathaba LT, Paxman AE, Ward PB, Warmington JR.
was a higher incidence of antibiotic exposure in Genetically distinct strains of Candida albicans with
those with diarrhoea, and this may have elevated secretory proteinase production are associated
with diarrhoea in hospitalised patients. J Gastroenterol
explained that diVerence in concentration. Hepatol 2000;15:53–60.
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