17.3 Infection, Sepsis & Multisystem Microbial Disease
Key Takeaways
- Gram stain, cell wall structure, and virulence factors (capsule, toxins, adhesins, biofilms) determine clinical syndromes and lab identification patterns.
- Endotoxin (LPS lipid A) from gram-negatives drives fever, shock, and DIC via cytokine storm; exotoxins are secreted proteins with specific enzymatic targets (e.g., diphtheria, cholera, tetanus, botulinum, superantigens).
- Sepsis and septic shock reflect dysregulated host response with vasodilatory shock, capillary leak, and often DIC; SIRS criteria are nonspecific physiologic thresholds.
- High-yield multisystem microbes include zoonoses, mycobacteria, dimorphic fungi, opportunistic pathogens mapped to immunodeficiency type, malaria lifecycle stages, and HIV CD4-stratified opportunistic infections.
- Live vaccines generally induce strong cellular and durable immunity but are contraindicated in significant immunocompromise; killed/subunit vaccines are safer in that setting but may need boosters.
17.3 Infection, Sepsis & Multisystem Microbial Disease
Quick Answer: Gram structure + virulence factors explain invasion. LPS (endotoxin) → cytokine shock/DIC; exotoxins are targeted enzymes/superantigens. Sepsis is dysregulated host response. Map zoonoses, mycobacteria, dimorphics, opportunists by immune hole, malaria stages, and HIV CD4 thresholds. Live vs killed vaccines guide contraindications.
Infection content on CBSE is mechanism- and pattern-based: structure predicts stain and toxin type; host defect predicts organism list; geography and vectors finish the vignette.
Bacterial Structure, Gram Stain, and Virulence
Gram-positive organisms have a thick peptidoglycan layer and stain purple; teichoic acids are common. Gram-negative organisms have a thin peptidoglycan layer plus outer membrane containing lipopolysaccharide (LPS) and stain pink. Acid-fast organisms (Mycobacterium) have mycolic acid walls that retain carbol fuchsin. Atypical bacteria (Mycoplasma—no cell wall; Chlamydia—obligate intracellular; Rickettsia—obligate intracellular) need special recognition.
Virulence factors to lock in:
- Capsule — antiphagocytic (S. pneumoniae, H. influenzae type b, N. meningitidis, K. pneumoniae, Cryptococcus).
- Adhesins / pili — mucosal colonization (E. coli P pili → pyelonephritis; N. gonorrhoeae pili).
- Biofilms — catheter and prosthetic infections (S. epidermidis, Pseudomonas).
- IgA protease — mucosal invaders (SHiN: S. pneumoniae, H. influenzae, Neisseria).
- Protein A — S. aureus binds Fc of IgG, impairs opsonization.
- M protein — S. pyogenes antiphagocytic; molecular mimicry → rheumatic fever.
- Spores — Clostridium, Bacillus survive harsh environments.
| Structure | Clinical link |
|---|---|
| Peptidoglycan | β-lactam target |
| LPS (gram-neg) | Endotoxin shock |
| Mycolic acids | Acid-fast; TB drugs |
| Capsule | Asplenia risk (encapsulated) |
| Spores | Hard to eradicate; soil/food |
Endotoxin vs Exotoxin
Endotoxin is LPS, especially lipid A, integral to gram-negative outer membranes. It is heat-stable, not actively secreted as a classic protein toxin, and released with bacterial lysis or blebbing. LPS binds TLR4–MD2–CD14 on macrophages → massive IL-1, TNF, IL-6 release → fever, vasodilation, increased permeability, septic shock, activation of coagulation → DIC, and neutrophil effects. Meningococcemia is a dramatic clinical package of endotoxin-driven purpura fulminans and adrenal hemorrhage (Waterhouse-Friderichsen).
Exotoxins are secreted proteins (usually from gram-positives, some gram-negatives), often heat-labile, highly antigenic, and sometimes convertible to toxoids for vaccines (diphtheria, tetanus).
| Exotoxin example | Mechanism | Disease |
|---|---|---|
| Corynebacterium diphtheriae toxin | ADP-ribosylation of EF-2 | Pseudomembranous pharyngitis, myocarditis |
| Pseudomonas exotoxin A | ADP-ribosylation of EF-2 | Similar biochemical motif |
| Shiga / Shiga-like (EHEC) | Removes adenine from rRNA (60S) | Dysentery; HUS |
| ETEC LT / cholera toxin | ADP-ribosylation → ↑cAMP | Watery diarrhea |
| ETEC ST | ↑cGMP | Watery diarrhea |
| Pertussis toxin | Inhibits Gi → ↑cAMP | Whooping cough |
| Tetanospasmin | Cleaves SNARE → blocks inhibitory glycine/GABA release | Spastic paralysis |
| Botulinum toxin | Cleaves SNARE → blocks ACh at NMJ | Flaccid paralysis |
| Clostridial α-toxin (perfringens) | Lecithinase | Gas gangrene |
| Superantigens (TSST-1, SpeA/C) | Polyclonal MHC II–TCR bridging | Toxic shock, cytokine storm |
Superantigens differ from classic antigen processing: massive non-specific T-cell activation produces shock resembling endotoxin crisis but with a gram-positive toxin source (S. aureus TSST-1; S. pyogenes Spe).
Sepsis, SIRS, and Septic Shock
SIRS (systemic inflammatory response syndrome) is a clinical pattern: abnormal temperature, heart rate, respiratory rate/PaCO2, and WBC—triggered by infection or sterile inflammation (pancreatitis, burns, trauma).
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset with profound circulatory and cellular/metabolic abnormalities—classically vasodilatory (distributive) shock with relative hypovolemia from leak, myocardial depression, and microthrombi. Lactate rises with hypoperfusion.
Mechanism chain: pathogen patterns → innate activation → cytokine storm → endothelial injury → tissue factor exposure → DIC → consumption coagulopathy and bleeding risk alongside microvascular thrombosis. ARDS, AKI, and multiorgan failure follow. Treatment principles (fluids, early antibiotics, source control, pressors) are clinical, but CBSE emphasizes the LPS/cytokine/DIC pathophysiology.
Zoonoses (High-Yield)
| Organism | Reservoir / vector | Classic clue |
|---|---|---|
| Borrelia burgdorferi | Ixodes tick (mouse/deer) | Erythema migrans; Lyme stages |
| Rickettsia rickettsii | Dermacentor tick | Rocky Mountain spotted fever; rash wrists/ankles |
| Yersinia pestis | Fleas / rodents | Bubonic plague; bipolar “safety pin” |
| Francisella tularensis | Ticks / rabbits | Ulceroglandular tularemia |
| Brucella | Unpasteurized dairy / cattle/goats | Undulant fever; night sweats |
| Leptospira | Animal urine / water | Weil disease; conjunctival suffusion |
| Bacillus anthracis | Spores / herbivores | Black eschar; woolsorter’s lung |
| Coxiella burnetii | Aerosols / parturient animals | Q fever; culture-negative endocarditis |
| Pasteurella multocida | Cat/dog bite | Rapid cellulitis |
| Bartonella henselae | Cats | Cat-scratch disease; bacillary angiomatosis in AIDS |
| Chlamydia psittaci | Birds | Psittacosis pneumonia |
Mycobacteria and Dimorphic Fungi
Mycobacterium tuberculosis: airborne; primary Ghon complex; reactivation at apices; caseating granulomas; acid-fast; cord factor and intracellular survival in macrophages. Disseminated (miliary) disease in immunocompromised. M. avium complex disseminates at very low CD4 counts. M. leprae prefers cool skin/nerves; tuberculoid (strong Th1) vs lepromatous (weak cell-mediated) poles.
Dimorphic fungi grow as mold in the environment (cold) and yeast (or spherules) in tissue (heat):
| Fungus | Geography / clue | Tissue form |
|---|---|---|
| Histoplasma | Ohio/Mississippi valleys; bird/bat droppings | Small intracellular yeasts |
| Blastomyces | Similar rivers; broad-based budding | Broad-based budding yeast |
| Coccidioides | Southwest deserts | Spherules filled with endospores |
| Paracoccidioides | Latin America | “Pilot wheel” multiple buds |
Opportunistic molds/yeasts: Candida (thrush, esophagitis, disseminated), Aspergillus (invasive in neutropenia; septate 45° hyphae), Mucor/Rhizopus (DKA, ketoacidosis; right-angle nonseptate; rhinocerebral), Cryptococcus (pigeon droppings; India ink/mucicarmine capsule; meningitis in AIDS), Pneumocystis jirovecii (interstitial pneumonia at CD4 <200).
Opportunistic Infections by Immunodeficiency Type
| Host defect | Typical pathogens |
|---|---|
| Neutropenia | Extracellular bacteria, Aspergillus, Candida |
| Asplenia | Encapsulated (SHiN), Salmonella |
| Humoral deficiency | Pyogenic bacteria, enteroviruses, Giardia |
| C5–C9 (MAC) | Neisseria |
| CGD | Catalase-positive (Staph, Burkholderia, Aspergillus, Serratia, Nocardia) |
| T-cell / AIDS | PCP, CMV, MAC, Crypto, Toxoplasma, JC (PML), TB, Candida mucosal |
| C3 deficiency | Severe pyogenic infections |
| C1-INH | Hereditary angioedema (not infection-primary) |
Malaria Life Cycle (High-Yield)
Plasmodium is transmitted by Anopheles mosquito injecting sporozoites → liver schizonts (exoerythrocytic) → merozoites invade RBCs → cyclic trophozoites/schizonts → RBC rupture (fever periodicity) → gametocytes taken up by mosquito. P. vivax/ovale form hypnozoites in liver → relapse (need primaquine when G6PD allows). P. falciparum is most severe: sequesters in microvasculature, cerebral malaria, blackwater fever; banana gametocytes. Blood smear remains diagnostic gold standard conceptually.
HIV Pathogenesis and Opportunistic Map
HIV is a retrovirus using gp120 (CD4 + CCR5/CXCR4 co-receptor binding) and gp41 (fusion). Reverse transcriptase, integrase, and protease are drug targets. Infection depletes CD4+ T cells by direct killing, pyroptosis, and immune clearance, progressive immunodeficiency, and chronic immune activation.
Approximate CD4 correlates (classic teaching thresholds):
| CD4 (cells/µL) | Risks |
|---|---|
| >500 | Acute seroconversion illness possible; otherwise near-normal opportunistic risk |
| <500 | Oral hairy leukoplakia, Candida thrush begin to rise; TB risk elevated |
| <200 | AIDS-defining risk: PCP, progressive multifocal risk cluster |
| <100 | Toxoplasma encephalitis, Cryptococcus, Candida esophagitis more common |
| <50 | MAC, CMV retinitis |
HIV also associates with malignancies: Kaposi sarcoma (HHV-8), non-Hodgkin lymphoma, cervical/anal HPV-related cancers.
Vaccines: Live vs Killed Concepts
Live attenuated vaccines (MMR, varicella, yellow fever, oral polio/Sabin, intranasal influenza in some formulations, rotavirus, BCG where used) replicate limitedly → strong cellular and humoral responses, often lifelong; contraindicated in pregnancy and significant T-cell immunocompromise (risk of vaccine-strain disease). Household caveats exist for some live vaccines around severely immunocompromised contacts.
Killed/inactivated (injected polio/Salk, rabies, hepatitis A, intramuscular influenza) and subunit/toxoid/conjugate (HBV surface antigen, acellular pertussis, tetanus/diphtheria toxoids, pneumococcal/meningococcal/Hib conjugates) cannot cause disease from replication; safer in immunocompromise but may need boosters; conjugates recruit T-cell help for polysaccharide antigens in infants.
Passive immunization (IVIG, antitoxins, monoclonal antibodies) provides immediate but temporary protection.
Integration for CBSE Vignettes
Sort the stem: structure/toxin, host defect, vector/geography, or HIV stage. A neutropenic patient with invasive mold → Aspergillus. DKA with black eschar on face → Mucor. Farmer with undulant fever → Brucella. Banana gametocyte → falciparum. CD4 40 with diarrhea and marrow → MAC until proven otherwise. That sorting skill is the multisystem micro exam strategy.
Which statement best distinguishes endotoxin from a classic AB exotoxin?
A patient with untreated HIV has a CD4 count of 45 cells/µL and presents with fevers and cytopenias. Which opportunistic pathogen is most classically associated with this CD4 range?
Why are live attenuated vaccines generally avoided in patients with significant T-cell immunodeficiency?