gram-negative rods

Gram-negative rods possess a cell wall structure distinct from gram-positive organisms: a thin peptidoglycan layer sandwiched between an inner (cytoplasmic) membrane and an outer membrane. The outer membrane contains lipopolysaccharide (LPS), whose lipid A component is endotoxin—responsible for fever, septic shock, DIC, and activation of TLR4/innate immune pathways. Because of the outer membrane, GNRs resist crystal violet retention and stain pink/red with the counterstain (safranin) in Gram staining.

Clinically, GNRs are subdivided using key lab tests: - Lactose fermenters (pink colonies on MacConkey agar): E. coli, Klebsiella, Enterobacter, Citrobacter ("fast fermenters": E. coli, Klebsiella; "slow fermenters": Citrobacter, Serratia) - Non-lactose fermenters: Shigella, Salmonella, Proteus, Pseudomonas - Oxidase-positive: Pseudomonas aeruginosa, Neisseria (though Neisseria is a diplococcus, not rod), Vibrio, Campylobacter - Oxidase-negative: Enterobacteriaceae (E. coli, Klebsiella, etc.)

High-yield associations: - E. coli: #1 cause of UTIs, neonatal meningitis, traveler's diarrhea (ETEC), HUS (EHEC O157:H7) - Klebsiella pneumoniae: aspiration pneumonia in alcoholics, "currant jelly" sputum, thick mucoid capsule - Pseudomonas aeruginosa: burn wound infections, cystic fibrosis pneumonia, hot tub folliculitis, ecthyma gangrenosum, produces pyocyanin (blue-green pigment) - Proteus mirabilis: urease-positive, struvite kidney stones, motile with swarming pattern - Salmonella vs Shigella: Salmonella has flagella (motile), can invade bloodstream, animal reservoir; Shigella is non-motile, human-only reservoir, more virulent (lower infectious dose), produces Shiga toxin - Vibrio cholerae: comma-shaped, cholera toxin causes secretory diarrhea via Gs activation - Campylobacter jejuni: leading cause of bacterial diarrhea, associated with Guillain-Barré syndrome - Bacteroides fragilis: anaerobic GNR, foul-smelling abscesses, intra-abdominal infections

Treatment considerations: GNRs are frequently associated with antibiotic resistance mechanisms (ESBLs, carbapenemases) making them clinically significant in hospital-acquired infections. Empiric coverage often includes fluoroquinolones, aminoglycosides, third/fourth-generation cephalosporins, or carbapenems depending on resistance patterns and clinical context.

Endotoxin (LPS) is a key USMLE topic—unlike exotoxins, it is not actively secreted, is heat-stable, and stimulates macrophages via CD14/TLR4 to release TNF-alpha, IL-1, and IL-6, contributing to septic shock pathophysiology.