SEARCH RESULTS FOR: Fluoroquinolones

clostridium-difficile-infection-pathogenesis-and-clinical-findings

Clostridium difficile (C. diff) Infection Authors: Ryan Brenneis, Sravya Kakumanu Reviewers: Yoyo Chan, Sean Doherty, Vina Fan, Ben Campbell, Dr. Steve Vaughan*, Dr. Sylvain Coderre* * MD at time of publication Community exposure Infected close contacts Nosocomial exposure (most common) Poor hand hygiene and sanitization of surfaces and medical equipment Nosocomial risk factors Any antibiotic use (Especially clindamycin, fluoroquinolones, penicillins, cephalosporins) ↑ Antibiotic resistant strains Presence of pre-disposing risk factors (Note: do not need to be present for infection) Recent GI surgery Chemotherapy that has antimicrobial and immunosuppressive effects Usage of medications that reduce stomach acid (↑ pH) ↑ C. diff spores on surfaces and personnel Contact exposure Environmental exposure to C. diff carriers Inoculation of GI tract Disruption of normal gut microbiome allowing C. diff overgrowth Comorbidities (>65 years old, cirrhosis, inflammatory bowel disease, enteral feeding, obesity) via fecal-oral route Clostridium difficile Infection of GI Tract Spores unaffected by antibiotics germinate post-antibiotic treatment Infection recurrence Pseudomembranous colitis on endoscopy (colonic ulcerations potentially seen with severe infection) Hypotension Acute kidney injury Release of C. diff toxin A and B inactivates Rho and Ras GTPases in colonic epithelial cells (colonocytes) (Rho and Ras GTPases control cytoskeletal dynamics and gene expression) Cytoskeletal disorganization and arrest of RNA synthesis causes necrosis of colonocytes and triggers host immune response Neutrophil chemotaxis and activation ↑ Inflammation of colon Disruption of tight junctions between colonocytes Release of fluid into intestinal lumen and inability of colon to reabsorb it Toxic megacolon Bowel perforation Bloody stool (<10% of patients) Abdominal cramps Large bowel dilation from muscle paralysis Inflammation and destruction of underlying smooth muscle Breakdown of colonocyte cell membranes Inflammation of visceral peritoneum Volume depletion Watery diarrhea: ↑ frequency, small volume Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 30, 2019, updated May 16, 2022 on www.thecalgaryguide.com

Fluoroquinolones

Inhibition of cardiac voltage-gated potassium channels Delayed cardiac repolarization Fluoroquinolones: Mechanism of action & side effects Fluoroquinolones (FQs) Bactericidal antibiotics that inhibit bacterial DNA synthesis. Coverage depends on specific agent but includes gram-negatives (e.g., E. coli, H. influenzae), atypicals (e.g., Legionella, Mycoplasma), anaerobes & selected gram-positives (e.g., Streptococcus) High affinity for connective tissue FQ metabolism forms toxic metabolites & free radicals ↑ Concentration of FQ in tendons & connective tissue Toxic metabolites & free radicals accumulate in nerve tissue (mechanism poorly understood) ↑ Metalloprotease (MMP) activity & magnesium chelation (mechanism poorly understood) ↑ Inflammation & oxidative stress causes neuronal dysfunction & cell death Tendinopathy & tendon rupture Peripheral neuropathy (pain, numbness, weakness, tingling) Fluoroquinolones can cross placental membrane Collagenolytic effect of ↑ MMP-9 & MMP-2 disrupts aortic wall (mechanism poorly understood) Cartilage & bone toxicity in fetus Aortic dissection** & aortic aneurysm** **See corresponding Calgary Guide slide Pathophysiology FQ targets bacterial enzymes DNA gyrase & topoisomerase IV Structural similarity to gamma-aminobutyric acid (GABA) Broad-spectrum antibiotic FQ-DNA-enzyme complexes form & become irreversibly bound DNA replication fork movement is blocked causing DNA strand breakage DNA replication inhibition & bacterial cell death Bacterial clearance on microbiological culture Legend: Possible GABA antagonist (mechanism unclear) GABA binds less effectively to neurons in central nervous system (CNS) & exerts a weaker inhibitory effect ↑ Neuronal excitability & CNS stimulation ↓ Microbiome diversity ↑ Antibiotic- resistant strains ↑ Pathogenic & ↓ protective bacteria (gut dysbiosis) Gastritis (inflammation of the stomach lining) Clostridium difficile overgrowth & infection ↓ Seizure threshold Headache Insomnia Confusion Mechanism Sign/Symptom/Lab Finding Published Jun 22, 2025 on www.thecalgaryguide.com QT interval prolongation Torsades de Pointes** Blockage of ATP- sensitive potassium channels in pancreatic β cells ↑ β-cell membrane depolarization ↑ Insulin secretion Hypoglycemia** Authors: Ben Jackson Reviewers: Rafael Sanguinetti Luiza Radu Emily J. Doucette Meagan Deviaene* * MD at time of publication Complications