Impact of clinical awareness and diagnostic tests on the underdiagnosis of Clostridium difficile infection

Abstract

A multicenter study of Clostridium difficile infection (CDI) performed during 2008 in Spain revealed that two of every three episodes went undiagnosed or were misdiagnosed owing to nonsensitive diagnostic tests or lack of clinical suspicion and request. Since then, efforts have been made to improve the diagnostic tests used by laboratories and to increase the awareness of this disease among both clinicians and microbiologists. Our objective was to evaluate the impact of these efforts by assessing the current magnitude of underdiagnosis of CDI in Spain using two point-prevalence studies performed on one day each in January and July of 2013. A total of 111 Spanish laboratories selected all unformed stool specimens received for microbiological diagnosis on these days, and toxigenic culture was performed at a central reference laboratory. Toxigenic isolates were characterized both pheno- and genotypically. The reference laboratory detected 103 episodes of CDI in patients aged 2 years or more. Half (50.5 %) of the episodes were not diagnosed in the participating laboratories, owing to insensitive diagnostic tests (15.5 %) or the lack of clinical suspicion and request (35.0 %). The main ribotypes were 014, 078/126, 001/072, and 106. Ribotype 027 caused 2.9 % of all cases. Despite all the interventions undertaken, CDI remains a highly neglected disease because of the lack of sensitive diagnostic tests in some institutions and, especially, the absence of clinical suspicion, mainly in patients with community-associated CDI. Toxigenic C. difficile should be routinely sought in unformed stools sent for microbiological diagnosis, regardless of their origin.

Incorrect diagnosis of Clostridium difficile infection in a university hospital in Japan

“…They detected toxigenic isolates in 45 specimens from 730 patients, and concluded that two out of every three episodes were underdiagnosed or were misdiagnosed, owing to insensitive diagnostic tests (19.0%) or lack of clinical suspicion and request (47.6%). Furthermore, a subsequent Spanish study showed that half of CDI episodes were not diagnosed despite various interventions were undertaken [18]. Similar findings are presented here, with 69.0% of CDI cases undiagnosed owing to negative C. difficile toxin assay results (44.9%) or a lack of clinical suspicions (24.1%).…”

Prevalence and molecular epidemiology of Clostridium difficile infection in Thailand

“…Compared to other publications in the Asian region that involved direct stool culture and toxin gene detection by a PCR-based technique, the prevalence of toxigenic C. difficile in Thailand (9.2%) appeared to be lower than that reported in 2015 for China (19.2%, 80/416) [17] and similar to that reported in 2015 for India (10.9%, 121/1110) [18]. These figures are all higher than those reported in 2015 for Spain (6.0%, 108/1800) [19] and Australia (6.4% to 7.2%) [11], [20]. Many studies conducted in Asia have investigated the prevalence of toxigenic C. difficile using direct detection of preformed toxins in stool.…”

“…An earlier study investigating the molecular epidemiology of C. difficile collected between 2006 and 2008 from inpatients at Siriraj Hospital also reported RTs 017 (41.5%) and 014/020 group (20.7%) among the top RTs [9]. Additionally, RT 014/020 group was reported to be highly prevalent among humans in Australia [20], Korea [25], Europe [19], [26] and North America [27]. In contrast, RT 046, which was previously reported as the third most common RT at Siriraj Hospital (6/53), was not found [9].…”

Variability in testing policies and impact on reported Clostridium difficile infection rates: results from the pilot Longitudinal European Clostridium difficile Infection Diagnosis surveillance study (LuCID)

“…Sub-optimal CDI diagnosis is still prevalent within Europe [8, 14, 15], despite guidelines having been issued in 2009 [1]. Only 64 % of the 60 hospitals in the present study used recommended laboratory testing algorithms [1].…”

“…In addition to testing methodology, diagnostic intensity (mostly driven by CDI awareness) is a key determinant of reported rates [8, 14, 15]. In 2012, only ∼40 % of 482 hospitals across Europe were using recommended laboratory methods to diagnose CDI [8].…”