Colorectal neoplasm in cases of Clostridium septicum and Streptococcus gallolyticus subsp. gallolyticus bacteraemia

Published:February 21, 2017DOI:


      • C. septicum and S. gallolyticus bacteremia were linked to occult colon neoplasms.
      • C. septicum and S. gallolyticus might play a distinct role in the carcinogenesis.
      • Colonic examination is mandatory in C. septicum and S. gallolyticus bacteremia.



      Bacteremia with Clostridium septicum (CS) and Streptococcus gallolyticus subsp. gallolyticus (SGG) have both been associated with colorectal neoplasms (CRN) and colonoscopic examination is advised, however the differences and similarities in colorectal findings are not well known.


      This is a multicenter, comparative study of patients with CS bacteremia [44 of 664 cases (6.6%) of Clostridium spp.] and SGG bacteremia [257 of 596 cases (44.2%) of S. bovis group], carried out in three hospitals from Spain. Clinical findings related to bacteremia and associated CRN were collected.


      The main sources of infection were abdominal (77.7%) for CS bacteremia and endovascular (75%) for SGG bacteremia. CS bacteremia was more often associated with malignancies, (72.6% vs. 19.4%) and neutropenia (29.5% vs. 3.1%), and was more acute, with shock at presentation (63.6% vs. 3.9%) and higher 30-day mortality (47.7% vs. 9.7%) compared to SGG (P < 0.05 for all).
      Both, patients with CS and SGG bacteremia often had concomitant CRN (43.1% vs. 49.8%) and most of them presented as occult CRN (73.7% vs. 91.4%; P = 0.02). CS cases more often had invasive carcinomas (94.7% vs. 19.5%), location of CRN in the right colon (73.7% vs. 23.4%), larger tumor size (median 7 vs. 1.5 cm), and a higher overall CRN related mortality rate (68.4% vs. 7.8%) compared to SGG cases (P < 0.05 for all).


      Both, CS and SGG bacteremia are associated with occult CRN. CS cases more often had advanced carcinomas than SGG cases, suggesting a distinct temporal association with CRN.


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        • Brenner H.
        • Kloor M.
        • Pox C.P.
        Colorectal cancer.
        Lancet. 2014; 383: 1490-1502
        • Dejea C.
        • Wick E.
        • Sears C.L.
        Bacterial oncogenesis in the colon.
        Future Microbiol. 2013; 8: 445-460
        • Taketo M.M.
        • Edelmann W.
        Mouse models of colon cancer.
        Gastroenterology. 2009; 136: 780-798
        • Boleij A.
        • Tjalsma H.
        Gut bacteria in health and disease: a survey on the interface between intestinal microbiology and colorectal cancer.
        Biol Rev Camb Philos Soc. 2012; 87: 701-730
        • Louis P.
        • Hold G.L.
        • Flint H.J.
        The gut microbiota, bacterial metabolites and colorectal cancer.
        Nat Rev Microbiol. 2014; 12: 661-672
        • Tjalsma H.
        • Boleij A.
        • Marchesi J.R.
        • Dutilh B.E.
        A bacterial driver-passenger model for colorectal-cancer: beyond the usual suspects.
        Nat Rev Microbiol. 2012; 10: 575-582
        • Beeching N.
        • Christmas T.I.
        • Ellis-Pegler R.B.
        • Nicholson G.I.
        Streptococcus bovis bacteraemia requires rigorous exclusion of colonic neoplasia, and endocarditis.
        Q J Med. 1985; 56: 439-450
        • Tripodi M.F.
        • Adinolfi L.E.
        • Ragone E.
        • et al.
        Streptococcus bovis endocarditis and its association with chronic liver disease: an underestimated risk factor.
        Clin Infect Dis. 2004; 38: 1394-1400
        • Kornbluth A.A.
        • Danzig J.B.
        • Bernstein L.H.
        Clostridium septicum infection and associated malignancy. Report of 2 cases and review of the literature.
        Medicine (Baltimore). 1989; 68: 30-37
        • Koransky J.R.
        • Stargel M.D.
        • Dowell Jr., V.R.
        Clostridium septicum bacteremia. Its clinical significance.
        Am J Med. 1979; 66: 63-66
        • Corredoira J.
        • García-Garrote F.
        • Rabuñal R.
        • et al.
        Association between bacteraemia due to Streptococcus gallolyticus subsp. gallolyticus (S. bovis I) and colorectal neoplasia: a case-control study.
        Clin Infect Dis. 2012; 55: 491-496
        • Katlic M.R.
        • Derkac W.M.
        • Coleman W.S.
        Clostridium septicum infection and malignancy.
        Ann Surg. 1981; 193: 361-364
        • Boleij A.
        • van Gelder M.
        • Swinkels D.
        • Tjalsma H.
        Clinical importance of Streptococcus gallolyticus infection among colorectal cancer patients: systematic review and meta-analysis.
        Clin Infect Dis. 2011; 53: 870-878
        • Weinstein M.P.
        • Towns M.L.
        • Quartey S.M.
        • et al.
        The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults.
        Clin Infect Dis. 1997; 24: 584-602
        • Li J.S.
        • Sexton D.J.
        • Mick N.
        • et al.
        Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis.
        Clin Infect Dis. 2000; 30: 633-638
        • Microbiological Clinical and Laboratory Standards Institute
        Performance Standards for Antimicrobial Susceptibility Testing: Twenty-fourth Informational Supplement M100-S24.
        CLSI, Wayne, PA, USA2014
        • Beck M.
        • Frodl R.
        • Funke G.
        Comprehensive study of strains previously designated Streptococcus bovis consecutively isolated from human blood cultures and emended description of Streptococcus gallolyticus and Streptococcus infantarius subsp. coli.
        J Clin Microbiol. 2008; 46: 2966-2972
        • Poyart C.
        • Quesne G.
        • Trieu-Cuot P.
        Taxonomic dissection of the Streptococcus Bovis group by analysis of manganese-dependent superoxide dismutase gene (sodA) sequences: reclassification of `Streptococcus infantarius subsp. coli´ as Streptococcus lutetiensis sp. nov. and of Streptococcus bovis biotype II.2 as Streptococcus pasteurianus sp. nov.
        Int J Syst Evol Microbiol. 2002; 52: 1247-1255
        • Kudsk K.A.
        Occult gastrointestinal malignancies producing metastatic Clostridium septicum infections in diabetic patients.
        Surgery. 1992; 112: 765-770
        • Corredoira J.
        • Grau I.
        • Garcia-Rodriguez J.F.
        • et al.
        The clinical epidemiology and malignancies associated with Streptococcus bovis biotypes in 506 cases of bloodstream infections.
        J Infect. 2015; 71: 317-325
        • Larson C.M.
        • Bubrick M.P.
        • Jacobs D.M.
        • West M.A.
        Malignancy, mortality, and medicosurgical management of Clostridium septicum infection.
        Surgery. 1995; 118: 592-597
        • Seder C.W.
        • Kramer M.
        • Long G.
        • Uzieblo M.R.
        • Shanley C.J.
        • Bove P.
        Clostridium septicum aortitis: report of two cases and review of the literature.
        J Vasc Surg. 2009; 49: 1304-1309
        • Ridgway E.J.
        • Grech E.D.
        Clostridial endocarditis: report of a case caused by Clostridium septicum and review of the literature.
        J Infect. 1993; 26: 309-313
        • Cohen C.A.
        • Almeder L.M.
        • Israni A.
        • Maslow J.N.
        Clostridium septicum endocarditis complicated by aortic-ring abscess and aortitis.
        Clin Infect Dis. 1998; 26: 495-496
        • Hermsen J.L.
        • Schurr M.J.
        • Kudsk K.A.
        • Faucher L.D.
        Phenotyping Clostridium septicum infection: a surgeon's infectious disease.
        J Surg Res. 2008; 148: 67-76
        • Corredoira J.
        • García-País M.J.
        • Coira A.
        • et al.
        Differences between endocarditis caused by Streptococcus bovis and Enterococcus spp. and their association with colorectal cancer.
        Eur J Clin Microbiol Infect Dis. 2015; 34: 1657-1665
        • zur Hausen H.
        Streptococcus bovis: causal or incidental involvement in cancer of the colon?.
        Int J Cancer. 2006; 119: xi-xii
        • Wentling G.K.
        • Metzger P.P.
        • Dozois E.J.
        • Chua H.K.
        • Krishna M.
        Unusual bacterial infections and colorectal carcinoma. Streptococcus bovis and Clostridium septicum: report of three cases.
        Dis Colon Rectum. 2006; 49: 1223-1227
        • Abdulamir A.S.
        • Hafidh R.R.
        • Mahdi L.K.
        • Al-Jeboori T.
        • Abubaker F.
        Investigation into the controversial association of Streptococcus gallolyticus with colorectal cancer and adenoma.
        BMC Cancer. 2009; 9: 403
        • Boleij A.
        • Tjalsma H.
        The itinerary of Streptococcus gallolyticus infection in patients with colonic malignant disease.
        Lancet Infect Dis. 2013; 13: 719-724
        • Sears C.L.
        • Garrett W.S.
        Microbes, microbiota, and colon cancer.
        Cell Host Microbe. 2014 Mar 12; 15: 317-328
        • Sears C.L.
        • Pardoll D.M.
        Perspective: alpha-bugs, their microbial partners, and the link to colon cancer.
        J Infect Dis. 2011; 203: 306-311
        • Housseau F.
        • Sears C.L.
        Enterotoxigenic Bacteroides fragilis (ETBF)-mediated colitis in Min (Apc±) mice: a human commensal-based murine model of colon carcinogenesis.
        Cell Cycle. 2010; 9: 3-5
        • Nougayrède J.P.
        • Homburg S.
        • Taieb F.
        • et al.
        Escherichia coli induces DNA double-strand breaks in eukaryotic cells.
        Science. 2006; 313: 848-851
        • Wang X.
        • Huycke M.M.
        Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells.
        Gastroenterology. 2007; 132: 551-561
        • Kang H.Y.
        • Kim N.
        • Park Y.S.
        • et al.
        Progression of atrophic gastritis and intestinal metaplasia drives Helicobacter pylori out of the gastric mucosa.
        Dig Dis Sci. 2006; 51: 2310-2315
        • Boleij A.
        • Muytjens C.M.
        • Bukhari S.I.
        • et al.
        Novel clues on the specific association of Streptococcus gallolyticus subsp. gallolyticus with colorectal cancer.
        J Infect Dis. 2011; 203: 1101-1109
        • Danne C.
        • Entenza J.M.
        • Mallet A.
        • et al.
        Molecular characterization of a Streptococcus gallolyticus genomic island encoding a pilus involved in endocarditis.
        J Infect Dis. 2011; 204: 1960-1970
        • Sillanpää J.
        • Nallapareddy S.R.
        • Qin X.
        • et al.
        A collagen-binding adhesin, Acb, and ten other putative MSCRAMM and pilus family proteins of Streptococcus gallolyticus subsp. gallolyticus (Streptococcus bovis group, biotype I).
        J Bacteriol. 2009; 191: 6643-6653
        • Martins M.
        • Aymeric L.
        • du Merle L.
        • et al.
        Streptococcus gallolyticus Pil3 pilus is required for adhesion to colonic mucus and for colonization of mouse distal Colon.
        J Infect Dis. 2015; 212: 1646-1655
        • Martins M.
        • Porrini C.
        • du Merle L.
        • et al.
        The Pil3 pilus of Streptococcus gallolyticus binds to intestinal mucins and to fibrinogen.
        Gut Microbes. 2016; 22: 1-7
        • Ellmerich S.
        • Scholler M.
        • Duranton B.
        • et al.
        Promotion of intestinal carcinogenesis by Streptococcus bovis.
        Carcinogenesis. 2000; 21: 753-756
        • Abdulamir A.S.
        • Hafidh R.R.
        • Bakar F.A.
        Molecular detection, quantification, and isolation of Streptococcus gallolyticus bacteria colonizing colorectal tumors; inflammation-driven potential of carcinogenesis via IL-1, COX-2, and IL-8.
        Mol Cancer. 2010; 9: 249
        • zur Hausen H.
        Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer.
        Int J Cancer. 2012; 130: 2475-2483
        • Sears C.L.
        • Geis A.L.
        • Housseau F.
        Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis.
        J Clin Invest. 2014; 124: 4166-4172
        • Marchesi J.R.
        • Dutilh B.E.
        • Hall N.
        • et al.
        Towards the human colorectal cancer microbiome.
        PLoS One. 2011; 6e20447
        • Corredoira J.
        • Rabuñal R.
        • Alonso Mª.P.
        Streptococcus bovis: 100 years of an intriguing pathogen.
        Clin Microbiol Newsl. 2017; 39: 1-9