ENTEROTOXIGENIC CLOSTRIDIUM PERFRINGENS: A POSSIBLE CAUSE OF ANTIBIOTIC-ASSOCIATED DIARRHOEA

doi:10.1016/S0140-6736(84)90359-3

The Lancet

Volume 323, Issue 8372, 11 February 1984, Pages 305-307

https://doi.org/10.1016/S0140-6736(84)90359-3 Get rights and content

Abstract

Free Clostridium perfringens enterotoxin was detected in the stools of 11 patients with diarrhoea. All had high faecal counts of enterotoxigenic strains of C perfringens, mostly of serotypes not commonly associated with food poisoning. 10 of these 11 patients had severe or prolonged diarrhoea which had developed after antibiotic treatment. Enterotoxigenic C perfringens appears to be one of the causes of antibiotic-associated diarrhoea.

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Cited by (122)

Prevalence of Clostridium perfringens toxinotypes in antibiotic-associated diarrheal (AAD) patients in Iranian hospitals; can toxinotype D serve as a possible zoonotic agent for humans?
2023, Acta Tropica
While Clostridium perfringens (C. perfringens) toxinotype F is known as the cause of 15% of antibiotic-associated diarrhea (AAD) and sporadic diarrhea (SD) cases, the association of the other C. perfringens toxinotypes with AAD/SD is not investigated. Therefore, the incidence of C. perfringens-associated diarrhea was investigated in hospitalized patients in six Iranian hospitals. A total of 151 stool specimens from AAD/SD patients were investigated for C. perfringens strains and the isolates were analyzed for the major (cpa, cpb, etx, and iap) and minor (cpe, cpb₂, netb, PFO, and tpeL) toxin genes by PCR. C. perfringens isolation ratio was 28.5% (43 of 151 patients). C. perfringens isolation rates were not significant between different gender and age groups (p > 0.05), whereas it was significant between different wards and hospitals (p < 0.01). The cpa gene was detected in all C. perfringens isolates (n = 116). After that, the highest prevalence belonged to tpeL (87.1%), followed by pfo (84.5%), cpb₂ (69.8%), cpe (55.2%), etx (12.9%), and netb (1.7%) genes. Based on these gene profiles, 35 (30.2%), 64 (55.2%), 15 (12.9%), and two (1.7%) isolates belonged to toxinotypes A, F, D, and G, respectively, and the other toxinotypes were not detected. This study persists in considering toxinotype F in Iranian AAD patients as it was the dominant C. perfringens toxinotype. Remarkably, the isolation of toxinotype D suggests it as a potential trigger in C. perfringens-associated AAD for the first time and highlights it as a possible zoonotic agent for humans.
Involvement of Bacteria Other Than Clostridium difficile in Antibiotic-Associated Diarrhoea
2016, Trends in Microbiology
Citation Excerpt :
difficile AAD, many diseases associated with a concurrent C. difficile infection have also been identified in C. perfringens, S. aureus, and K. oxytoca AAD cases. These diseases include diabetes, kidney disease, pancreatitis, other infections, and cancer [4,6–8,11,13,23,30,32]. Inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) is associated with increased C. difficile infection risk [49].
Antibiotic-associated diarrhoea (AAD) is a common and unintended consequence of antibiotic use. Clostridium difficile is the most common infectious aetiology of AAD; however, only approximately 25% of all AAD cases are associated with C. difficile infection, with the aetiology in the majority of cases remaining undetermined. Numerous other bacterial infectious agents have been implicated in AAD, including Clostridium perfringens, Staphylococcus aureus, and Klebsiella oxytoca. AAD is a complex disease that is influenced by the host, the infectious agent involved, and numerous clinical factors, including antibiotic treatment regimes. This review re-examines AAD and presents current perspectives on this disease, with a particular focus on the current understanding of bacterial causes other than C. difficile and the virulence factors involved in pathogenesis.
New amino acid germinants for spores of the enterotoxigenic Clostridium perfringens type A isolates
2014, Food Microbiology
Citation Excerpt :
It can be classified into five toxinotypes (A–E) based on production of four major toxins (α, β, ε, and ι toxins) (McClane, 2007). Another important toxin produced by C. perfringens type A is C. perfringens enterotoxin (CPE), which is the major virulence factor responsible for C. perfringens type A food poisoning (FP) and non-food borne (NFB) gastrointestinal (GI) diseases (Abrahao et al., 2001; Asha and Wilcox, 2002; Borriello et al., 1984; Kobayashi et al., 2008; Mpamugo et al., 1995). Even though only a small group (less than 5%) of the global population of C. perfringens can produce CPE, C. perfringens type A FP still currently ranks as the third most commonly reported foodborne disease outbreaks in the United States and the cost of illness was estimated to be about $309.4 millions annually (Brown, 2000; Buzby and Roberts, 1997; Hoffmann et al., 2012; Lindström et al., 2011; Lynch et al., 2006; McClane, 2007; Scallan et al., 2011; Xiao et al., 2012).
Clostridium perfringens spore germination plays a critical role in the pathogenesis of C. perfringens-associated food poisoning (FP) and non-food-borne (NFB) gastrointestinal diseases. Germination is initiated when bacterial spores sense specific nutrient germinants (such as amino acids) through germinant receptors (GRs). In this study, we aimed to identify and characterize amino acid germinants for spores of enterotoxigenic C. perfringens type A. The polar, uncharged amino acids at pH 6.0 efficiently induced germination of C. perfringens spores; l-asparagine, l-cysteine, l-serine, and l-threonine triggered germination of spores of most FP and NFB isolates; whereas, l-glutamine was a unique germinant for FP spores. For cysteine- or glutamine-induced germination, gerKC spores (spores of a gerKC mutant derivative of FP strain SM101) germinated to a significantly lower extent and released less DPA than wild type spores; however, a less defective germination phenotype was observed in gerAA or gerKB spores. The germination defects in gerKC spores were partially restored by complementing the gerKC mutant with a recombinant plasmid carrying wild-type gerKA-KC, indicating that GerKC is an essential GR protein. The gerKA, gerKC, and gerKB spores germinated significantly slower with l-serine and l-threonine than their parental strain, suggesting the requirement for these GR proteins for normal germination of C. perfringens spores. In summary, these results indicate that the polar, uncharged amino acids at pH 6.0 are effective germinants for spores of C. perfringens type A and that GerKC is the main GR protein for germination of spores of FP strain SM101 with l-cysteine, l-glutamine, and l-asparagine.
Enterotoxigenic Clostridium perfringens infection and pediatric patients with inflammatory bowel disease
2014, Journal of Crohn's and Colitis
Citation Excerpt :
Experimental diarrhea can be induced in healthy volunteers by the oral administration of CPE, which confirmed its role in the development of infection.16 Similar to C. difficile, C. perfringens was also identified as a cause of AAD, sporadic diarrhea and nosocomial diarrhea.17–19 Evidence of CPE was found in up to 15% of AAD cases20 and 31% of sporadic (in the absence of antibiotic treatment) diarrhea cases.18
Clostridium difficile is the major cause of antibiotic-associated diarrhea and is the most well known bacterial pathogen associated with inflammatory bowel disease (IBD). Enterotoxigenic Clostridium perfringens has also been detected in up to 15% of antibiotic-associated diarrhea cases, and it has not been found in healthy people. The aim of this study was to investigate the prevalence of C. perfringens infection in pediatric patients with IBD.
This was a prospective, controlled study evaluating pediatric IBD patients in the Department of Pediatric Gastroenterology and Nutrition in Warsaw, Poland. All of the patients were diagnosed according to the Porto criteria. There were two control groups: (1) non-IBD patients that were suspected for bacterial diarrhea and (2) healthy children. Stool samples were collected on the day of admission. C. perfringens infection diagnosis was based on a positive stool enzyme immunoassay (C. perfringens enterotoxin test kit TechLab).
91 fecal specimens from patients with IBD were collected. The average patient age was 11.7 years in IBD group, 7.4 years in non-IBD patients with diarrhea, and 7.4 years in healthy children. The prevalence of C. perfringens infection was 9% (8/91; CI 95% 4.6–16.4). There were more Crohn's patients (6/8) in the C. perfringens positive group. There was no C. perfringens infection in the two control groups.
Our pilot data add evidence to the hypothesis that Clostridia other than C. difficile may play a significant role in the clinical course of IBD. However, further studies are needed to confirm this.
Predisposing factors and prevention of Clostridium perfringens-associated enteritis
2013, Comparative Immunology, Microbiology and Infectious Diseases
Clostridium perfringens is one of the major causes of intestinal disease in humans and animals. Its pathogenicity is contributed to by the production of a variety of toxins. In addition, predisposing environmental factors are important for the induction of C. perfringens-associated enteritis as shown by infection models. Environmental contamination, gastric and intestinal pH, intestinal microflora, nutrition, concurrent infections, and medical interventions may influence the intestinal colonization, growth, and toxin production by C. perfringens. Prevention of C. perfringens-associated enteritis may be mediated by the use of feed additives like probiotics, prebiotics, organic acids, essential oils, bacteriophages, lysozymes, bacteriocins, and antimicrobial peptides. Here we summarize and discuss published data on the influence of different environmental predisposing factors and preventive measures. Further research should focus on feed composition and feed additives in order to prevent C. perfringens-associated enteritis.
Novel insights into the epidemiology of Clostridium perfringens type A food poisoning
2011, Food Microbiology
Citation Excerpt :
While all toxin types have been reported to cause diseases in certain animals, such as types B and D in small ruminants and type A in poultry, type A and C strains alone have been associated with human diseases. These include food poisoning (Knox and MacDonald, 1943), antibiotic-associated diarrhea (AAD, Borriello et al., 1984), sporadic diarrhea (SD, Brett et al., 1992), and sudden infant death syndrome (SIDS, Murrell et al., 1987) that are caused by CPE, and gas gangrene due to alpha toxin (Simonds, 1917) and human necrotic enteritis, also called pig bel, due to beta toxin (Murrell and Roth, 1963). Recent work has depicted that CPE, encoded by the gene cpe, is produced by less than 5% of all C. perfringens strains (Smedley et al., 2004).
Clostridium perfringens food poisoning ranks among the most common gastrointestinal diseases in developed countries. The disease is caused by C. perfringens enterotoxin (CPE) encoded by cpe and produced by less than 5% of C. perfringens type A strains. Molecular epidemiological research in the past 15 years has focused on the reservoirs and routes of cpe-positive C. perfringens aiming to clarify the role and epidemiology of chromosomal and plasmid-borne cpe-carrying strains. This literature review highlights novel aspects in the epidemiology of CPE-mediated diseases. We suggest that (1) chromosomal and plasmid-borne cpe-carrying C. perfringens strains are genetically and epidemiologically distinct and have adapted to different environments; (2) not only chromosomal but also plasmid-borne cpe-carrying C. perfringens strains cause food poisonings; (3) other CPE-mediated diseases, such as antibiotic-associated and sporadic diarrhea, associated with plasmid-borne cpe-positive strains, may be food-related; (4) the role of animals as the main reservoir of cpe-positive C. perfringens needs to be reconsidered; (5) humans serve as an important reservoir of cpe-positive C. perfringens, introducing a contamination risk into foods through handling; and (6) the current standard procedures to diagnose C. perfringens food poisoning fail to detect and isolate many C. perfringens strains, distorting the epidemiological understanding of C. perfringens food poisoning.

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ENTEROTOXIGENIC CLOSTRIDIUM PERFRINGENS: A POSSIBLE CAUSE OF ANTIBIOTIC-ASSOCIATED DIARRHOEA

Abstract

Lancet

Lancet

FEMS Microbiol Lett

J Infect

Randomised controlled trial of vancomycin for pseudomembranous colitis and post-operative diarrhoea

Br Med J

The aetiology of acute diarrhoea in adults

Gut

Acute right-sided hemorrhagic colitis associated with oral administration of ampicillin

Dig Dis Sci

Transport and storage of faeces for bacteriological examination

J Appl Bact

Applications of an ELISA technique for the detection of Clostridium perfringens enterotoxin

J Appl Bact