Microbiology
- Small Gram-positive rod
- Non-spore-forming
- β-hemolytic on blood agar
- Catalase-positive
- CAMP-positive
- Tumbling motility in liquid at room temperature
- Facultative intracellular parasite
- Grows at refrigerator temperature
- Cold enrichment aids isolation
Sources & Spread
- Reservoirs
- Animal GI and genital tracts
- Soil and plants
- Foods that carry it
- Unpasteurized dairy, soft cheese
- Deli meats, hot dogs
- Coleslaw, fruit, ice cream
- Routes
- Foodborne
- Vertical (mother → fetus/newborn)
Intracellular Life Cycle
Ingested cells invade gut epithelium→
Phagocytosed→
Listeriolysin O lyses phagosome→
Escapes into cytoplasm→
Actin tail propels cell-to-cell spread
- Cell-to-cell spread avoids antibodies
- Cell-mediated immunity is the key defense
- Listeriolysin O is a pore-forming hemolysin active in acidic phagosomes
Clinical Syndromes
| Host | Presentation |
|---|---|
| Healthy adult |
|
| Pregnancy |
|
| Early-onset neonatal |
|
| Late-onset neonatal |
|
| Immunocompromised, older adults |
|
Diagnosis & Management
- Diagnosis
- Blood or CSF culture
- Gram stain shows Gram-positive rods (can be mistaken for diphtheroids)
- CSF: neutrophils and/or lymphocytes, protein ↑
- Treatment
- Ampicillin; add gentamicin in severe or immunocompromised disease
- TMP-SMX if penicillin-allergic
- Prevention
- Pregnant and immunocompromised patients avoid unpasteurized dairy, deli meats, refrigerated pâtés
- Cephalosporins are inactive against Listeria, so empirical meningitis regimens in neonates and elders add ampicillin.
- Pregnant woman with fever after soft cheese → Listeria until proven otherwise.
Microbiology
- Club-shaped Gram-positive rods
- Arranged in V or L (Chinese-letter) patterns
- Aerobic, non-spore-forming, non-motile
- Metachromatic (volutin) granules
- Visible with methylene blue on Loeffler medium
- Grows black on tellurite agar
- Reservoir: human throat and nasopharynx
- Spread by respiratory droplets
Toxin Acquisition
Non-toxigenic strain+β-corynephage→Lysogeny → tox gene
- Only lysogenized strains cause diphtheria
- Other toxins carried by phages: botulinum, cholera, Shiga-like, erythrogenic strep toxins
- Organism stays at the surface (non-invasive)
- Toxin travels through blood
Toxin Mechanism
B subunit binds heparin-binding EGF-like receptor→
Endocytosis→
A subunit ADP-ribosylates eEF-2→
Translocation blocked→
Protein synthesis halts → cell death
- Same target as Pseudomonas exotoxin A
Clinical Picture
| Feature | Details |
|---|---|
| Pharyngitis | Sore throat, low fever, malaise |
| Pseudomembrane |
|
| Bull neck | Marked cervical lymphadenopathy and edema |
| Airway | Extension to larynx/trachea → obstruction |
| Myocarditis | Arrhythmia, heart failure; major cause of death |
| Neuropathy | Palatal and cranial nerve palsies, later peripheral polyneuropathy |
| Cutaneous form | Chronic non-healing ulcer |
Diagnosis & Management
- Diagnosis
- Culture on Loeffler and tellurite media
- Toxin testing: Elek immunodiffusion or PCR/ELISA
- Elek test principle
- Antitoxin strip on agar
- Toxin diffuses outward from toxigenic growth
- Precipitin lines form where toxin meets antitoxin
- Treatment
- Diphtheria antitoxin early (neutralizes only unbound toxin)
- Erythromycin or penicillin to eradicate organism
- Airway protection
- Prevention
- Formalin-inactivated toxoid in DTaP / Tdap / Td
- Boosters about every 10 years
- Pseudomembrane + bull neck + myocarditis in an unvaccinated patient is diphtheria.
- Diphtheria toxin and Pseudomonas exotoxin A both inactivate eEF-2.
Head-to-Head
| Feature | Actinomyces israelii | Nocardia (asteroides, brasiliensis) |
|---|---|---|
| Oxygen | Anaerobe | Strict aerobe |
| Shape | Branching filamentous Gram-positive rods | Branching filamentous Gram-positive rods |
| Acid-fast | No | Partially (modified stain) |
| Habitat | Human flora: gingival crevices, GI tract, female genital tract | Soil and dust |
| Acquisition | Endogenous, after mucosal breach | Inhalation or traumatic skin inoculation |
| Host | Often immunocompetent | Immunosuppressed (steroids, transplant, malignancy, HIV) |
| Virulence factors | None well defined | None well defined |
| Hallmark | Sulfur granules in draining sinus tracts | Cavitary lung disease; brain abscesses |
| Treatment | Penicillin (prolonged) + surgical drainage | TMP-SMX or sulfonamide (prolonged) |
Actinomycosis
- Invades tissue where oxygen is low
- Often after trauma, surgery, or devitalized tissue
- Chronic, slowly progressive, often painless mass
- Ignores tissue planes → crosses to bone
- Draining sinus tracts release yellow sulfur granules
- Granules are bacterial microcolonies
- Diagnosis: Gram-positive branching rods in granules, anaerobic culture
- Metronidazole is not effective (organism is Gram-positive, non-spore-forming anaerobe needing β-lactam)
| Form | Trigger |
|---|---|
| Cervicofacial ("lumpy jaw") | Dental extraction, trauma, poor oral hygiene |
| Thoracic | Aspiration, then contiguous spread |
| Abdominal | Bowel surgery, perforation (appendix common) |
| Pelvic | Long-term intrauterine device |
| CNS | Usually a single brain abscess |
Nocardiosis
- Pulmonary
- N. asteroides complex most often
- Cough, fever, dyspnea
- Nodules or cavitating pneumonia
- Hematogenous spread to brain → often multiple abscesses
- Cutaneous / subcutaneous
- N. brasiliensis most often
- Inoculation through skin injury
- Cellulitis → abscesses → draining mycetoma-like granules
- Diagnosis: sputum or pus culture; modified acid-fast stain positive; Gram stain beaded branching rods
- Single brain abscess with sulfur granules elsewhere suggests Actinomyces; multiple abscesses with cavitary lung disease suggests Nocardia.
- Actinomycosis is treated with a β-lactam, nocardiosis with a sulfonamide.
Mycobacteria: Genus Facts
- Acid-fast rods (mycolic-acid-rich waxy wall)
- Obligate aerobes (upper lung lobes favored in TB)
- Resist drying, many disinfectants, and alkali
- Sputum can be treated with NaOH to remove contaminants before culture
- Sensitive to ultraviolet light
- Slow-growing
Laboratory Identity
- Acid-fast stain positive
- Fluorescent auramine–rhodamine screening stain
- Sensitive; positives are confirmed
- Löwenstein–Jensen or Middlebrook medium
- Visible growth takes 3–6 weeks
- Liquid systems are faster
- Niacin production positive
- Catalase is heat-labile
- Negative on standard 68 °C test
- Serpentine cords in culture (cord factor)
- Serology is not used for diagnosis
Virulence Factors
| Factor | Effect |
|---|---|
| Intracellular survival | Lives inside macrophages; major driver of persistence |
| Sulfatides | Block phagosome–lysosome fusion |
| Cord factor (trehalose dimycolate) | Serpentine growth; inhibits neutrophil migration; disrupts mitochondrial function |
| Wax-D / mycolic acids / tuberculin protein | Drive delayed hypersensitivity and granuloma formation |
| Toxins | None (no exotoxin or endotoxin); damage comes from host immunity |
Natural History
Inhaled droplet nuclei→
Alveolar macrophage infection→
Ghon focus (subpleural, lower/mid lung)→
Spread to hilar nodes = Ghon complex→
Cell-mediated immunity forms caseating granuloma
| Stage | Features |
|---|---|
| Primary infection |
|
| Reactivation |
|
| Dissemination |
|
- Granuloma structure
- Central caseous necrosis
- Epithelioid macrophages, Langhans giant cells
- Rim of CD4 T cells (IFN-γ activates macrophages)
Diagnosis
| Test | Notes |
|---|---|
| Tuberculin skin test |
|
| Interferon-γ release assay |
|
| Sputum smear + culture | Confirms active pulmonary disease; culture allows susceptibility testing |
| Nucleic acid amplification | Rapid detection, can flag rifampin resistance |
| Chest imaging | Apical infiltrates, cavities, hilar adenopathy, miliary pattern |
- BCG vaccination can cause a false-positive skin test but not a false-positive release assay.
- Advanced HIV or sarcoidosis can cause false-negative skin tests (anergy).
Treatment of Active TB
Months 1–2→
RifampinIsoniazidPyrazinamideEthambutol→
Months 3–6→
RifampinIsoniazid
- Multiple drugs prevent selection of resistant mutants
- Resistant or MDR disease
- Use several previously unused agents
- Examples: fluoroquinolones, bedaquiline, aminoglycosides, cycloserine, thioamides
| Drug | Mechanism | Key toxicity |
|---|---|---|
| Rifampin | Inhibits bacterial DNA-dependent RNA polymerase | Hepatitis; orange body fluids; strong CYP450 induction |
| Isoniazid | Blocks mycolic acid synthesis (prodrug activated by KatG) | Hepatitis; peripheral neuropathy (give pyridoxine); lupus-like reaction; slow acetylators more affected |
| Pyrazinamide | Acts in acidic phagolysosomes | Hepatitis; hyperuricemia/gout |
| Ethambutol | Inhibits arabinosyl transferase (cell wall) | Optic neuritis (red-green color loss) |
Prevention
- Latent TB treatment
- Isoniazid for about 9 months (shorter rifamycin-based regimens also used)
- BCG vaccine
- Live attenuated M. bovis
- Mainly protects children against severe disseminated forms
- Not routine in the U.S.
- Airborne infection control
- Negative-pressure rooms, N95 masks
- Ultraviolet germicidal light, HEPA filtration
Non-Tuberculous Mycobacteria
- Environmental organisms (water, soil)
- Not transmitted person-to-person
| Organism | Disease | Source / setting | Therapy |
|---|---|---|---|
| M. avium-intracellulare | Disseminated infection; lung disease | Advanced HIV (CD4 <50/µL), chronic lung disease, cancer | Macrolide + ethambutol; macrolide prophylaxis at CD4 <50 |
| M. kansasii | TB-like cavitary lung disease | Chronic lung disease | Multidrug regimen incl. rifampin, isoniazid, ethambutol |
| M. marinum | Skin granulomas ("aquarium" granuloma) | Abrasions exposed to fish tanks, pools, marine water; cooler skin | Multidrug regimen (e.g., rifampin + ethambutol, or a macrolide) |
| M. ulcerans | Painless necrotizing skin ulcer (Buruli ulcer) | Tropical wetlands, Africa; wound contamination; mycolactone toxin | Rifampin-based combination; surgery for large lesions |
- Disseminated mycobacterial disease at normal-to-moderately low CD4 counts is usually M. tuberculosis.
- M. avium-intracellulare disseminates only with profound CD4 depletion.
M. leprae
Microbiology
- Acid-fast rods
- Obligate intracellular
- Cannot be grown in artificial culture
- Grows in armadillo footpads / mouse footpads
- Prefers cooler tissue (skin, nasal mucosa, peripheral nerves, testes)
- Very slow doubling; long incubation (years)
Reservoir / transmission
- Humans (untreated lepromatous patients shed from nasal secretions)
- Nine-banded armadillos in the southern U.S. also carry it
- Prolonged close contact needed
Spectrum of Disease
| Feature | Tuberculoid | Lepromatous |
|---|---|---|
| Immune response | Strong cell-mediated, Th1-type | Weak cell-mediated, Th2-type with antibody |
| Lepromin skin test | Positive | Negative |
| Bacterial load | Few organisms | Very many; macrophages become foam cells |
| Skin lesions | Few, well-defined anesthetic plaques or macules | Numerous symmetric nodules and plaques; leonine face, loss of eyebrows |
| Nerves | Asymmetric enlarged nerves, early sensory loss | Diffuse symmetric neuropathy |
| Source of damage | Immune-mediated (granuloma) | Bacterial overgrowth |
| Prognosis / infectivity | Milder, low infectivity | Severe, highly infectious |
- Borderline forms lie between the two poles
- Sensory loss → painless burns and injuries → deformity
- Diagnosis
- Skin or nerve punch biopsy with acid-fast stain
- Nasal scrapings
- Culture not possible
- Treatment
- Tuberculoid: dapsone + rifampin
- Lepromatous: dapsone + rifampin + clofazimine
- Dapsone adverse effects
- Hemolysis in G6PD deficiency
- Methemoglobinemia
- Leprosy cannot be cultured on artificial media, so acid-fast biopsy is the diagnostic key.
- Painless skin patches with numbness in a patient from an endemic region point to leprosy.
Shared Features
- Gram-negative, kidney-bean-shaped diplococci
- Oxidase-positive
- Catalase-positive
- Aerobic
- Endotoxin is lipooligosaccharide (LOS)
- Secrete IgA protease
- Grow on chocolate agar in CO₂ (selective Thayer–Martin for pathogens)
Comparison
| Feature | N. meningitidis | N. gonorrhoeae |
|---|---|---|
| Capsule | Yes (polysaccharide) | No |
| Vaccine | Yes | No (antigenic variation) |
| Maltose fermentation | Yes | No |
| Glucose fermentation | Yes | Yes |
| Entry | Respiratory | Genital, perinatal |
| β-lactamase | Rare | Common (plasmid) |
| Reservoir | Human nasopharynx (5–10% carriers) | Human genital tract |
N. meningitidis
- Virulence
- Capsule: antiphagocytic; serogroups A, B, C, W-135, Y
- Serogroup B capsule is poorly immunogenic (sialic-acid mimicry of host)
- LOS endotoxin: fever, shock, DIC
- Pili and outer-membrane proteins: attachment and invasion
- IgA protease: mucosal colonization
- Host risk
- Late complement (C5–C9) deficiency → recurrent neisserial infection
- Asplenia
- Crowded living (dormitories, barracks)
- Disease
- Meningitis: abrupt fever, headache, neck stiffness
- Meningococcemia: petechial/purpuric rash, rapid shock
- Waterhouse–Friderichsen syndrome: adrenal hemorrhage, DIC, collapse
- Diagnosis
- Gram-negative diplococci in CSF
- Culture, PCR, antigen tests
- Treatment: ceftriaxone or cefotaxime (add ampicillin in neonates; add vancomycin in some settings)
- Prevention
- Conjugate vaccine (A, C, W-135, Y) and separate recombinant protein vaccine for serogroup B
- Close-contact prophylaxis: rifampin, ciprofloxacin, or ceftriaxone
N. gonorrhoeae
- Virulence
- Pili: attachment, resist phagocytosis, enormous antigenic variation
- Opa proteins: tight adherence
- Porins, LOS, IgA protease
- Fragile outside the body (drying, cold)
| Setting | Presentation |
|---|---|
| Male | Purulent urethral discharge, dysuria; epididymitis; proctitis |
| Female | Often silent; cervicitis; pelvic inflammatory disease (infertility, ectopic pregnancy, perihepatitis) |
| Neonate | Conjunctivitis within days of birth → blindness if untreated |
| Disseminated | Fever, migratory arthralgias, tenosynovitis, pustular skin lesions, septic arthritis |
| Other | Pharyngitis, anorectal infection |
- Diagnosis
- Urethral smear: intracellular Gram-negative diplococci in neutrophils
- Nucleic acid amplification test (standard)
- Culture on Thayer–Martin: oxidase-positive, maltose-negative
- Treatment
- Ceftriaxone (penicillin resistance common)
- Also cover co-infecting Chlamydia trachomatis (doxycycline or azithromycin)
- Prevention
- Condoms, partner treatment
- Neonatal ocular prophylaxis (erythromycin ointment)
- Recurrent infection is common (no lasting immunity)
Moraxella catarrhalis
- Gram-negative diplococcus
- Normal upper-airway colonizer
- Spread by droplets
- Diseases
- Otitis media and sinusitis
- Bronchitis / pneumonia in elderly and COPD patients
- Most strains produce β-lactamase
- Treat with amoxicillin–clavulanate, second/third-generation cephalosporin, or TMP-SMX
- The oxidase test turns colonies dark with reagent; Enterobacteriaceae are the main oxidase-negative Gram-negative rods.
- Maltose-positive diplococci are meningococci; maltose-negative are gonococci.
Pseudomonas aeruginosa
Identification
- Gram-negative rod
- Oxidase-positive, catalase-positive
- Strict aerobe; non-fermenter
- Non-lactose fermenter (pale colonies)
- Pigments
- Pyocyanin (blue-green)
- Pyoverdin (fluorescent yellow-green)
- Sweet grape-like odor
- Mucoid alginate slime and biofilm
Ecology / spread
- Water-loving; thrives in moist hospital sites
- Respirators, humidifiers, sink drains
- Hot tubs, contaminated contact-lens solutions
- Transient gut carriage in a minority of people
- Raw produce and flowers can carry it
Virulence
| Factor | Role |
|---|---|
| Exotoxin A | ADP-ribosylates eEF-2 → halts protein synthesis (liver is a prime target) |
| Endotoxin | Sepsis and shock |
| Alginate capsule / biofilm | Microcolonies in CF lung; resists phagocytosis and antibiotics |
| Elastase, phospholipase, pyocyanin | Tissue destruction, oxidative injury |
Clinical settings
| Host / exposure | Disease |
|---|---|
| Burn patients | Colonization of eschar → wound infection with blue-green pus → sepsis |
| Neutropenia | Pneumonia, bacteremia, ecthyma gangrenosum (necrotic black-centered skin lesions) |
| Cystic fibrosis | Chronic mucoid-strain lung infection, recurrent exacerbations |
| Chronic granulomatous disease | Catalase-positive organisms evade killing; pneumonia, sepsis |
| Diabetes | Malignant (necrotizing) otitis externa; foot osteomyelitis |
| Swimmers | Otitis externa, hot-tub folliculitis |
| Contact-lens wearers | Corneal ulcer |
| Catheterized patients | Urinary tract infection |
| Ventilated patients | Nosocomial pneumonia |
Management
- Intrinsically drug-resistant
- Porin changes, efflux pumps, β-lactamases
- Susceptibility testing is essential
- Therapy: antipseudomonal β-lactam (piperacillin–tazobactam, ceftazidime, cefepime, carbapenem) ± aminoglycoside or fluoroquinolone
- Prevention: sanitize water-related equipment, hand hygiene, early catheter removal
Other Non-fermenters
| Organism | Features | Disease | Treatment |
|---|---|---|---|
| Burkholderia cepacia | Oxidase-positive, catalase-positive; spreads patient to patient | Pneumonia in CF; infection in CGD | TMP-SMX |
| Acinetobacter baumannii | Oxidase-negative; biofilm; highly resistant | Ventilator pneumonia, wound infection (including combat-related) | Carbapenem, polymyxin (often multidrug-resistant) |
- Blue-green pus or grape-like smell plus a burn wound is Pseudomonas.
- Pseudomonas and Acinetobacter differ by oxidase: positive vs negative.
Legionella pneumophila
Lab behavior
- Gram-negative rod
- Stains poorly with Gram stain
- Silver stain (Dieterle) shows organisms
- Fastidious
- Needs iron and cysteine
- Grows on buffered charcoal yeast extract agar
- Facultative intracellular (alveolar macrophages)
Epidemiology
- Reservoir: fresh water, amoebae, building water systems
- Spread by aerosols (cooling towers, showers, whirlpools, fountains)
- No person-to-person spread
- Risk groups
- Smokers, age >55
- Heavy alcohol use
- Chronic lung disease
- Immunosuppression (e.g., transplant)
Disease
- Legionnaires disease
- Pneumonia (an "atypical" pattern)
- High fever, cough, dyspnea
- Hyponatremia
- Confusion and other neurologic signs
- Watery diarrhea (organism is not in the gut)
- Elevated liver enzymes
- Pontiac fever
- Self-limited flu-like illness
- No pneumonia; no deaths
Diagnosis & therapy
- Urinary antigen (detects serogroup 1)
- Culture on charcoal yeast agar; direct fluorescent antibody; PCR
- Treat with a drug that penetrates cells
- Fluoroquinolone (e.g., levofloxacin) or azithromycin
- β-lactams and aminoglycosides do not work
- Prevention: disinfect and maintain water systems
Francisella tularensis
- Small Gram-negative coccobacillus
- Facultative intracellular (reticuloendothelial cells), granulomatous reaction
- Zoonosis; potential bioweapon
- Reservoirs: rabbits, hares, rodents, deer; ticks (Dermacentor)
- Endemic across the U.S., especially central states (Arkansas, Missouri)
- Culture is a laboratory hazard
- Needs cysteine-enriched media
| Form | Route | Picture |
|---|---|---|
| Ulceroglandular (commonest) | Tick bite or handling infected rabbit tissue | Fever, skin ulcer at inoculation site, tender regional lymph nodes |
| Pneumonic | Aerosols (skinning animals, lab, bioterror) | Atypical pneumonia |
| Oculoglandular | Splash to eye | Conjunctivitis with nodes |
| Typhoidal / oropharyngeal | Contaminated meat or water | Systemic febrile illness, GI symptoms |
- Diagnosis: serology, direct fluorescent antibody, PCR
- Treatment: streptomycin (gentamicin an alternative)
- Prevention: tick protection, gloves when handling wild game, live attenuated vaccine for high-risk workers
Bordetella pertussis
- Small encapsulated Gram-negative coccobacillus; strict aerobe
- Exclusive human pathogen; droplet spread
- Stays on the mucosal surface of ciliated respiratory epithelium (non-invasive)
Virulence
| Factor | Role |
|---|---|
| Filamentous hemagglutinin, pertactin | Adhesins to ciliated cells |
| Pertussis toxin (A-B) |
|
| Adenylate cyclase toxin | Raises cAMP in phagocytes; impairs killing; local edema |
| Tracheal cytotoxin | Destroys ciliated cells → impaired mucociliary clearance |
| Endotoxin | Local inflammation |
Clinical stages
Incubation 7–10 d→
Catarrhal 1–2 wk→
Paroxysmal 2–4 wk→
Convalescent ≥3–4 wk
| Stage | Features | Culture yield |
|---|---|---|
| Incubation | No symptoms | — |
| Catarrhal | Rhinorrhea, sneezing, low fever, anorexia; most contagious | Highest |
| Paroxysmal | Repeated cough bursts ending in inspiratory whoop, post-tussive vomiting, marked lymphocytosis | Falling |
| Convalescent | Cough gradually fades; complications (pneumonia, seizures, encephalopathy) | Low |
- Diagnosis
- PCR on nasopharyngeal swab (best)
- Culture on Bordet–Gengou or Regan–Lowe medium
- Direct fluorescent antibody; serology later
- Treatment
- Macrolide (azithromycin/erythromycin)
- Early therapy shortens contagiousness more than symptoms
- Treat household contacts
- Infants <6 months often hospitalized
- Prevention
- Acellular vaccine (pertussis toxoid, filamentous hemagglutinin, ± pertactin) in DTaP / Tdap
- Immunity wanes over 5–10 years; adults become reservoirs
- Newborns have little maternal protection → vaccinate during pregnancy
- Persistent cough longer than 2 weeks in a vaccinated adult can still be pertussis.
- Marked lymphocytosis in pertussis arises from toxin-blocked lymphocyte trafficking, not infection of lymphocytes.
Brucella species
Features
- Small Gram-negative coccobacilli; aerobic
- Facultative intracellular (reticuloendothelial system)
- Zoonosis; potential bioweapon
- Culture is a laboratory hazard
- Endotoxin plus granulomatous response
Acquisition
- Unpasteurized dairy (soft cheese, goat milk), often linked to Mexico travel
- Direct animal contact (slaughterhouse, veterinary, farm work)
- Species–host pairs
- B. abortus – cattle
- B. melitensis – goats and sheep
- B. suis – pigs
- B. canis – dogs
- Brucellosis ("undulant fever")
- Evening fever spikes that come and go
- Drenching sweats
- Arthralgia, myalgia, back pain
- Hepatosplenomegaly
- Complications: sacroiliitis, spondylitis, epididymo-orchitis, endocarditis
- Diagnosis: serum agglutination titer rise (≥1:160 supportive), blood culture with lab alert
- Treatment: doxycycline + rifampin for at least 6 weeks (children: rifampin + TMP-SMX)
- Prevention: vaccinate livestock, pasteurize milk
Zoonotic Bacteria Worth Grouping
| Organism | Typical animal link |
|---|---|
| Brucella | Livestock, unpasteurized dairy |
| Bacillus anthracis | Herbivores, hides, wool |
| Listeria monocytogenes | Contaminated food from animals |
| Salmonella (non-typhoidal) | Poultry, eggs, reptiles |
| Campylobacter | Poultry |
| Chlamydophila psittaci | Birds |
| Francisella tularensis | Rabbits, ticks |
| Yersinia pestis | Rodents, fleas |
Haemophilus influenzae
Microbiology
- Small pleomorphic Gram-negative coccobacillus
- Needs two blood-derived factors
- Factor X (hemin)
- Factor V (NAD)
- Grows on chocolate agar (both factors present)
- On blood agar, grows only as satellite colonies near S. aureus (which releases V factor)
- Reservoir: human nasopharynx
- Spread: respiratory droplets
Virulence
- Type b polysaccharide capsule (polyribosyl-ribitol phosphate) – dominant factor
- Most invasive disease is type b
- IgA protease (colonization)
- Non-typeable (unencapsulated) strains → mucosal disease
| Disease | Notes |
|---|---|
| Meningitis | Unvaccinated infants and toddlers, after maternal antibody wanes (about 3 months to 2 years) |
| Epiglottitis | Fever, drooling, muffled voice, stridor; "thumbprint" sign; airway emergency |
| Pneumonia, bacteremia | Young unvaccinated children; adults with chronic lung disease |
| Otitis media, sinusitis | Mostly non-typeable strains |
| COPD exacerbation | Non-typeable strains in smokers |
- Diagnosis: culture on chocolate agar, PCR, capsular antigen (latex agglutination) in CSF
- Treatment
- Meningitis: ceftriaxone or cefotaxime
- Respiratory/ENT disease: amoxicillin–clavulanate (β-lactamase common)
- Prevention
- Conjugate vaccine: capsule linked to a carrier protein → T-cell-dependent response
- Doses at 2, 4, 6 months with booster at 12–15 months
- Rifampin prophylaxis for unvaccinated close contacts under 2 years (and household contacts)
- Vaccine covers type b only; non-typeable strains still cause ear and sinus disease.
- Pure polysaccharide vaccines generate poor infant responses, which is why conjugation is needed.
Haemophilus ducreyi (Chancroid)
- Spread by sexual contact
- Lesion
- Painful, soft, ragged genital ulcer
- Purulent base, tender inguinal nodes (possible suppurating bubo)
- Contrast with syphilis: painless, indurated, clean-based ulcer
- Open ulcers raise HIV transmission risk
- Diagnosis: Gram stain with chains/"school of fish" arrangement, culture, PCR
- Treatment: azithromycin, ceftriaxone, ciprofloxacin, or erythromycin
Pasteurella multocida
- Small Gram-negative coccobacillus; facultative anaerobe
- Normal oral flora of cats and dogs
- Cat bite or scratch → rapid cellulitis within 24 h
- Pain, swelling, lymphangitis
- Risk of septic arthritis/osteomyelitis
- Pathogenic factors: capsule, endotoxin
- Treatment and bite prophylaxis: amoxicillin–clavulanate
- Penicillin is also active
Other Bite- and Contact-Associated Bacteria
| Organism | Features | Source | Disease | Therapy |
|---|---|---|---|---|
| Eikenella corrodens | Gram-negative rod; pits agar; bleach-like odor | Human mouth; human bites, clenched-fist injuries | Cellulitis, joint and bone infection | Amoxicillin–clavulanate; third-generation cephalosporin; fluoroquinolone |
| Capnocytophaga canimorsus | Thin, filamentous Gram-negative rod | Dog mouth; bites and licks | Overwhelming sepsis in asplenic or alcoholic patients | Amoxicillin–clavulanate, third-generation cephalosporin |
| Bartonella henselae | Small Gram-negative rod; warthin-starry silver stain | Cats (kittens), fleas; scratches | Cat-scratch disease (tender regional nodes); bacillary angiomatosis in advanced HIV | Azithromycin; doxycycline for angiomatosis |
Slow-Growing Oral Gram-negative Endocarditis Group
- Members
- Aggregatibacter aphrophilus (formerly H. aphrophilus)
- Aggregatibacter actinomycetemcomitans
- Cardiobacterium hominis
- Eikenella corrodens
- Kingella kingae
- Fastidious Gram-negative rods, part of normal oral flora
- Cause roughly 5–10% of infective endocarditis
- Subacute course
- Leading cause of Gram-negative endocarditis outside injection drug use
- Slow growth in blood culture → delayed diagnosis (prolonged incubation helps)
- Treatment: third-generation cephalosporin (or fluoroquinolone)
Quick Comparison
| Feature | Campylobacter jejuni | Helicobacter pylori | Vibrio cholerae |
|---|---|---|---|
| Shape | Curved/comma, polar flagellum | Spiral, multiple polar flagella | Comma-shaped, single polar flagellum |
| Oxygen | Microaerophilic | Microaerophilic | Aerobic/facultative |
| Oxidase | + | + | + |
| Special feature | Grows at 42 °C | Urease-positive | Grows in alkaline media |
| Medium | Campylobacter / Skirrow agar at 42 °C | Selective microaerophilic media | TCBS, alkaline peptone water |
| Site | Colon (invasive) | Stomach mucus layer | Small bowel lumen (non-invasive) |
Campylobacter jejuni
- Reservoir: GI tract of poultry, cattle, sheep, pets
- Spread: fecal–oral, undercooked poultry, unpasteurized milk
- Low infectious dose (hundreds of organisms)
- Invades colonic mucosa → inflammatory diarrhea
- Fever, cramps, many stools per day, may be bloody
- Usually settles in about a week
- Leading bacterial cause of diarrhea in many countries
- Post-infectious complications
- Guillain–Barré syndrome (cross-reactive lipooligosaccharide with neural gangliosides)
- Reactive arthritis (HLA-B27)
- Diagnosis: stool culture at 42 °C, microaerophilic
- Treatment: fluids; azithromycin (or fluoroquinolone) for severe disease; penicillins ineffective
Helicobacter pylori
Fecal–oral / oral–oral→
Urease makes ammonia buffer→
Flagella and mucinase cross mucus→
Colonizes antrum surface, chronic inflammation
- Virulence
- Urease (acid neutralization)
- Motility, mucinase
- Vacuolating cytotoxin (VacA) and CagA in virulent strains
- Diseases
- Chronic gastritis (nearly universal with infection)
- Duodenal ulcer (antral predominance → ↑acid)
- Gastric ulcer
- Gastric adenocarcinoma (chronic atrophic gastritis)
- MALT lymphoma (can regress after eradication)
- Classified as a definite human carcinogen
- Diagnosis
- Urea breath test (¹³C- or ¹⁴C-urea)
- Stool antigen test
- Biopsy: rapid urease test, histology (Giemsa/silver), culture
- Serology shows exposure only
- Treatment (10–14 days)
- Triple therapy: proton-pump inhibitor + clarithromycin + amoxicillin (or metronidazole)
- Bismuth quadruple therapy where clarithromycin resistance is high
- Stop PPIs about 2 weeks before breath/stool testing to avoid false negatives
Vibrio
- Genus traits
- Gram-negative curved rods, polar flagella
- Oxidase-positive
- Salt-loving; tolerate alkaline pH
V. cholerae
- Reservoir: humans and aquatic environment (copepods, shellfish); no animal-to-human chain
- Spread: contaminated water, undercooked seafood; poor sanitation
- Large inoculum needed, especially with normal gastric acid
- Colonization: motility, mucinase, toxin-coregulated pili
Cholera toxin B binds GM1→
A subunit ADP-ribosylates Gₛα→
Adenylate cyclase stuck on→
↑cAMP→
Cl⁻ and water secretion → rice-water diarrhea
- Same mechanism class as heat-labile E. coli toxin
- Disease
- Profuse watery "rice-water" stool (up to liters per hour)
- Dehydration, hypokalemia, metabolic acidosis, hypovolemic shock
- No blood or inflammatory cells
- Diagnosis: stool culture on TCBS (yellow colonies, sucrose fermented)
- Treatment
- Aggressive oral/IV rehydration (cornerstone)
- Doxycycline or azithromycin shortens illness and shedding
- Prevention: sanitation, safe water, oral vaccine in endemic settings
Other pathogenic Vibrio species
| Species | Source | Syndrome | Treatment |
|---|---|---|---|
| V. parahaemolyticus | Raw or undercooked seafood | Watery diarrhea, cramps | Self-limited; supportive |
| V. vulnificus | Raw oysters; wounds exposed to warm brackish water | Gastroenteritis; rapidly spreading cellulitis with bullae; sepsis (high risk with liver disease or iron overload) | Doxycycline + third-generation cephalosporin; urgent debridement |
- Curved oxidase-positive rod with rice-water diarrhea is V. cholerae; with bloody diarrhea after poultry, Campylobacter.
- Cirrhosis plus raw oyster plus bullous cellulitis is V. vulnificus.
Shared Properties
- Gram-negative rods
- Facultative anaerobes
- Ferment glucose
- Reduce nitrate to nitrite
- Oxidase-negative
- Catalase-positive
- All produce endotoxin (LPS)
- Some add exotoxins
Antigen Systems
| Antigen | Location | Note |
|---|---|---|
| O | Outer-membrane LPS side chains | Basis of serotyping; part of endotoxin |
| H | Flagella | Motile species only |
| K | Capsule polysaccharide | Antiphagocytic (e.g., E. coli K1 in neonatal meningitis) |
| Vi | Capsule of Salmonella Typhi | Virulence antigen; basis of Vi vaccine |
Laboratory Sorting
- Grow on blood agar
- Selective/differential plates (MacConkey, eosin methylene blue) separate lactose use
- Lactose fermenters → pink/colored colonies
- Non-lactose fermenters → colorless colonies
Gram-negative Rod Identification Pathway
Gram-negative rod→ oxidase
Oxidase +→Non-fermenter: PseudomonasCurved: Campylobacter (42 °C), Vibrio (TCBS)
Oxidase −→Enterobacteriaceae→ lactose
Lactose +→ indole+ → E. coli− → Klebsiella (and Enterobacter, Citrobacter)
Lactose −→ H₂S / motility
H₂S +→ urease+ → Proteus− → Salmonella
H₂S −→Non-motile → ShigellaBipolar staining, motile at 25 °C → Yersinia
- Identification schemes simplify: Citrobacter, Enterobacter, and Serratia also appear in hospital infections and need full biochemical testing.
- Most Gram-negative rods other than Enterobacteriaceae are oxidase-positive.
- Oxidase-negative, lactose-fermenting, indole-positive rod is E. coli.
- Non-lactose-fermenting, H₂S-positive, urease-negative rod is Salmonella.
| Clue | Think |
|---|---|
| Pregnant woman, fever, soft cheese; newborn sepsis; tumbling motility | Listeria |
| Gray pseudomembrane, bull neck, myocarditis | C. diphtheriae |
| Sulfur granules, lumpy jaw, IUD | Actinomyces |
| Cavitary lung disease plus brain abscesses in immunosuppressed host | Nocardia |
| Night sweats, apical cavity, caseating granulomas | M. tuberculosis |
| AIDS, CD4 <50, disseminated acid-fast disease | M. avium-intracellulare |
| Fish-tank skin lesion | M. marinum |
| Hypoesthetic skin patches, armadillo, cannot be cultured | M. leprae |
| Young adult, petechiae, adrenal hemorrhage, maltose-positive diplococci | N. meningitidis |
| Urethral pus, intracellular diplococci, maltose-negative | N. gonorrhoeae |
| COPD, otitis, β-lactamase-positive diplococci | M. catarrhalis |
| Burn wound, blue-green pus, grape smell; CF lung | P. aeruginosa |
| Pneumonia, hyponatremia, diarrhea, air-conditioning/water exposure | Legionella |
| Hunter, rabbit, tick, skin ulcer with nodes | F. tularensis |
| Whooping cough, marked lymphocytosis | B. pertussis |
| Undulant fever after raw dairy or slaughterhouse work | Brucella |
| Epiglottitis or meningitis in an unvaccinated child; X and V factors | H. influenzae type b |
| Painful genital ulcer, soft edges | H. ducreyi |
| Rapid cellulitis after cat bite | Pasteurella |
| Bloody diarrhea after poultry, later paralysis | Campylobacter |
| Gastritis, duodenal ulcer, urease-positive spiral rod | H. pylori |
| Rice-water stool, traveler, TCBS growth | V. cholerae |
| Raw oysters, liver disease, hemorrhagic bullae | V. vulnificus |
- ADP-ribosylation toxins: diphtheria and Pseudomonas (eEF-2), cholera (Gₛ), pertussis (Gᵢ).
- Facultative intracellular rods: Listeria, Mycobacterium, Brucella, Francisella, Legionella.
- Vaccines against polysaccharide capsules work best as protein conjugates (H. influenzae b, pneumococcus, meningococcus).