Thread by @dhess_09

(1/10) 71 yo F with HTN and ESRD on HD presents to the ED w/ fever 🌡 + back pain, 🧫 BCx + Clostridium septicum. Which test should be considered? 🧐

(2/10) Clostridium septicum [motile, gram +, anaerobic, spore-forming rod] is rare in the GI tract. In colorectal tumor: anaerobic glycolysis = acidic and hypoxic environment ↑ C. septicum spore germination + tumors break down mucosal barrier and ↑ C. septicum blood entry

(3/10) Infxn mortality rates are high (60-79%)

Early diagnosis🩸and aggressive treatment💊of C. septicum are essential.

Colonoscopy is recommended to evaluate for malignancy. What is another gram + organism associated with colon CA?

pubmed.ncbi.nlm.nih.gov/11736823/

(4/10) Streptococcus gallolyticus subspecies gallolyticus (Sgg), formerly S. bovis biotype I, is a Group D Strep associated with early adenomas. In pre-neoplastic epithelium, Sgg kills related commensals → local microbial imbalance → potential ↑ colorectal CA risk

(5/10) High Sgg colonization in pre-malignant epithelium → inflammatory responses (IL-1, COX-2, IL-8) → ↑ cell proliferation → ↑ 𝛃-catenin levels + oncogenic targets (c-Myc and cyclin D) → ↑ pre-malignant to malignant epithelium.
ncbi.nlm.nih.gov/pmc/articles/P…

(6/10) Colonization with Sgg occurs if pre-malignant conditions exist, thus, Sgg is not the cause of colorectal CA, but an accelerating factor. Always obtain a colonoscopy for patients with Sgg isolates!

(7/10) Salmonella typhi [rod-shaped, gram-negative anaerobe] causative of typhoid or enteric fever can colonize the gallbladder & cause asymptomatic chronic infection→ gallbladder CA. Carcinogenic S. typhi typhoid toxins damage DNA & alter the infected cells cycle.

(8/10) Salmonella typhi PltB subunits bind host cell surface receptor → endocytosis → endosome-mediated delivery of toxin to Golgi complex → entry of toxin into ER + release of CdtB component of holotoxin → entry of CdtB into nucleus + induction of DNA damage.

(9/10) Gallstones = ideal substrate for S. typhi strains that form biofilms → bacterial cells detach from gallstones → release of carcinogens→ induced genomic instability → chronic inflammation → onset of gallbladder CA.
mdpi.com/1422-0067/18/9…

(10/10) Let’s recap:
✅Bacteria are linked to cancer through several mechanisms
✅Colonoscopy recommended with isolation of C. septicum or S. gallolyticus!
✅S. typhi chronic infection is linked with the development of gallbladder cancer
✅Check it out!⤵️
ncbi.nlm.nih.gov/pmc/articles/P…

#AntimicrobialStewardship #TwitteRx #OncoPharm @MsSmallsO @Stevens_AK @MikhailaPharmD