invasive candidiasis ( ic ) is a serious infection associated with a high mortality rate and limited definitive diagnostic signs .
colonization is a key component of ic pathogenesis , yet the significance of gastrointestinal candida colonization as a predictor of ic remains controversial . although yeast are normal bowel flora and recovery of low numbers in stool cultures is common , some hospitalized patients exhibit large numbers of yeast in stools obtained for enteric pathogen screening .
hospitalized patients undergoing evaluation for a possible inflammatory etiology of diarrhea may heighten concern that heavy yeast colonization of the gastrointestinal tract could progress to ic . clinicians
question whether prophylaxis of ic is warranted in such cases , and clinical microbiologists question whether the reporting of heavy yeast carriage is necessary .
the study objective was to determine if a relationship exists between ic and recovery of large numbers of yeast from stool cultured for enteric pathogens .
all inpatients at a 689-bed academic medical center from january 2004july 2008 with an enteric pathogen stool culture revealing yeast were eligible for inclusion .
only stools with moderate to many yeast detected ( growth in two or more quadrants of an isolation streak from the original stool on sheep blood agar ) were evaluated .
sheep blood agar , incubated for 72 hours , was included as a primary medium to screen for aeromonas hydrophila and recognize patients that lack stool flora .
each case patient , included only once , was matched by age , gender , and admission date in a 1:3 ratio to subjects with enteric pathogen stool cultures negative for yeast in a retrospective matched case - control study .
subjects with ic prior to the index stool and those who received systemic antifungals within 30 days after the index stool were excluded .
the primary outcome was development of ic , identified from an institutional database of patients diagnosed with ic and defined by a positive culture from blood , intra - abdominal abscess , peritoneal fluid , or cerebrospinal fluid indicative of ic .
a retrospective chart review was done to collect the following : demographics ; admission/ discharge dates ; culture / susceptibility results ; presence and date of ic ; antimicrobial , immunosuppressant , and chemotherapy regimens ; mechanical ventilation ; catheterizations ( intravascular and urinary ) ; hemodialysis ; and parenteral nutrition received during hospitalization , as well as internal prosthetic devices and surgical procedures performed within 30 days prior to index stool .
wilcoxon rank sum and chi - square or fisher s exact tests were used for continuous and categorical variables , respectively .
115 unique subjects had a stool culture that revealed moderate to many yeast out of 2373 total unique stool cultures performed among hospitalized patients during the study period .
fifty - seven subjects were excluded [ developed ic prior to index stool ( n=1 ) , received systemic antifungals after index stool ( n=40 ) , and outpatient status at time of culture ( n=16 ) ] .
the remaining cases ( n=58 ) were matched to 174 controls in a 1:3 ratio .
no significant differences were detected between cases and controls for age , gender , and ethnicity , ( data not shown ) but antimicrobial use was significantly more common in cases versus controls ( 95% vs. 73% , p=0.0005 ) .
the length of hospitalization was significantly longer ( median , 2.5 days longer ) for cases ( p=0.002 ) . 

table 1patient characteristics comparing patients with gastrointestinal yeast colonization to those without colonization.patient characteristicyeast in stool cultureppositive(n=58)n ( % ) negative(n=174)n ( % ) received antimicrobials55 ( 94.8)127 ( 72.9)0.0005received immunosuppressants24 ( 41.4)63 ( 36.2)0.481received chemotherapy0 ( 0)2 ( 1.1)0.99medical prosthetic devices12 ( 20.7)20 ( 11.5)0.08surgical procedures19 ( 32.8)41 ( 23.6)0.166mechanical ventilation11 ( 19)20 ( 11.5)0.148intravascular catheterization44 ( 75.9)113 ( 65)0.12hemodialysis4 ( 6.9)12 ( 7.5)0.99parenteral nutrition8 ( 13.8)28 ( 16.1)0.68total length of hospitalization [ median ( range)]8.5 ( 1 , 116)6.0 ( 1 , 231)0 , 002aduring hospitalization;bwithin 30 days of index stool culture . 
  during hospitalization ; within 30 days of index stool culture . one control subject developed ic .
other studies investigating candidal colonization and systemic disease have neither focused on incidental demonstration of heavy gastrointestinal colonization from an enteric pathogen culture nor firmly concluded a correlation between colonization and subsequent ic .
magill et al . investigated whether colonization site impacted the likelihood of developing ic in 182 surgical intensive care unit ( sicu ) patients .
no sites ( urine , oropharynx , trachea , gastric aspirate , or rectum / ostomy ) were associated with a high positive predictive value for ic .
conversely , all patients with negative rectum / ostomy , urine , and tracheal aspirate cultures remained without ic .
the high negative predictive values for these cultures suggest a limited strategy to identify patients who are unlikely to benefit from antifungal prophylaxis .
blumberg et al . assessed risk factors for candidemia in a multicenter , prospective cohort involving sicu patients ( n=4276 ) .
recovery of candida from rectum and urine samples was not associated with a significant risk of developing candidemia .
the authors concluded urinary or rectal colonization alone did not predict patient populations for antifungal prophylaxis . while these findings , in addition to the present study , suggest that rectal / gastrointestinal colonization alone does not predict ic , another study suggested that gastrointestinal colonization was the source for c. albicans candidemia .
however , surveillance cultures were obtained after candidemia documentation , and thus , whether gastrointestinal tract colonization preceded candidemia was not elucidated .
other investigators have incorporated colonization as one of many risk factors to be included in rules to help predict whether a given patient is likely to develop ic .
these studies have focused on patients at high risk for ic and have included colonization sites other than the gastrointestinal tract .
additionally , the ability to include colonization with yeast in such a clinical prediction rule requires routine surveillance cultures , which are not performed at our institution .
these studies demonstrate that the predictive value of colonization for invasive candidiasis is variable . in our study , the only case of ic occurred in a control subject who did not have heavy gastrointestinal colonization with yeast .
thus , if a negative gastrointestinal culture had been used to decide upon prophylactic therapy , this patient would not have received prophylaxis .
this matched case - control study was intended to investigate the significance of incidental demonstration of substantial gastrointestinal yeast colonization as a predictor of ic .
although conducted in a general population not selected as high risk for ic , many risk factors were present in both cases and controls ( table 1 ) . since cultures collected for detection of enteric pathogens were used , these observations may not be applicable to other situations .
furthermore , only patients who had an enteric stool specimen submitted for analysis were included in the study , and thus , these results may not be generalizable to the majority of patients who do not have stool specimens collected .
other limitations include the retrospective , single - centered study design , small sample size , and lack of data regarding intensive care unit days .
additionally , a significant difference was found in length of hospital stay between cases and controls , suggesting more time in the hospital may increase the probability of colonization .
 a matched case - control study was conducted to investigate gastrointestinal colonization with yeast as a predictor of invasive candidiasis ( ic ) in patients who underwent an enteric pathogen test . 
 no significant association was detected between gastrointestinal colonization and ic . 
 however , gastrointestinal colonization with yeast was associated with increased antimicrobial exposure and median length of hospitalization . 
Introduction