Microbiology
- Gram-negative rod
- Facultative anaerobe
- Oxidase-negative, indole-positive
- Lactose fermenter
- Pink colonies on MacConkey
- Green metallic sheen on eosin methylene blue
- Motile (H antigen)
Reservoir & Spread
- Human colon (commensal)
- Can colonize vagina and urethra
- Routes
- Endogenous spread
- Fecal–oral
- Maternal flora during birth
- Enterohemorrhagic strains
- Cattle gut
- Undercooked beef, raw milk, unpasteurized juice, petting zoos
Identifying Pathogenic Strains
- Finding E. coli in stool alone means little (normal flora)
- Sorbitol-MacConkey agar
- Most E. coli ferment sorbitol → pink
- O157:H7 enterohemorrhagic strain does not → colorless
- Other tools
- Toxin immunoassay
- Serotyping
- DNA probes, PCR for virulence genes
Extraintestinal Disease
| Syndrome | Mechanism | Clues | Therapy |
|---|---|---|---|
| Urinary tract infection (most common cause overall) |
| Gram-negative rods, pyuria, ≥10⁵ CFU/mL clean-catch | Fluoroquinolone, TMP-SMX, or based on susceptibilities |
| Neonatal sepsis / meningitis (second leading cause) | K1 capsule (sialic-acid-like, poorly immunogenic) + endotoxin; maternal flora acquired at delivery | Blood/CSF culture, Gram-negative rods | Ceftriaxone/cefotaxime (± ampicillin) |
| Gram-negative sepsis | Endotoxin (lipid A) → TNF/IL-1 → shock, DIC | Gut translocation, indwelling lines, abdominal source | Third-generation cephalosporin, fluoroquinolone, carbapenem if resistant |
Diarrheagenic Pathotypes
| Type | Mechanism | Picture | Management |
|---|---|---|---|
| ETEC (enterotoxigenic) |
| Watery, non-inflammatory "traveler's" diarrhea | Rehydration; antibiotics (TMP-SMX, fluoroquinolone, rifaximin) may shorten illness |
| EPEC (enteropathogenic) |
| Watery diarrhea in infants, mainly low-resource settings | Supportive; antibiotics in severe cases |
| EIEC (enteroinvasive) |
| Inflammatory dysentery: fever, cramps, blood, leukocytes | Supportive; antibiotics in severe disease |
| EAEC (enteroaggregative) |
| Persistent watery diarrhea in children, travelers, HIV | Fluids; ciprofloxacin or rifaximin if needed |
| EHEC / STEC (Shiga-toxin producing) |
|
| Supportive care; avoid antibiotics (raise hemolytic-uremic syndrome risk) and antimotility drugs |
Hemolytic-uremic syndrome
Shiga toxin enters blood→
Renal microvascular endothelial injury→
Platelet-fibrin microthrombi→
Microangiopathic hemolytic anemia + thrombocytopenia + acute kidney injury
- Typically in children <5 years, 5–10 days after diarrhea
- Smear: schistocytes
- Coagulation studies normal (differs from DIC)
- Toxins that raise cAMP: cholera toxin, ETEC heat-labile toxin, anthrax edema factor, pertussis toxin (indirectly via Gᵢ).
- Shiga toxin and Shiga-like toxin inactivate the 60S ribosomal subunit.
- ETEC and cholera cause watery diarrhea; EIEC and Shigella cause inflammatory diarrhea.
- Bloody diarrhea without fever in a child, followed by anemia and renal failure, is STEC-HUS, so no antibiotics.
K. pneumoniae
Microbiology
- Large polysaccharide capsule → mucoid colonies
- Lactose fermenter (pink on MacConkey)
- Non-motile
- Indole-negative
- Oxidase-negative
- Reservoir: human gut and upper airway
- Endogenous spread
Virulence
- Capsule: blocks phagocytosis
- Endotoxin: fever, shock
- Hypervirulent strains cause liver abscess (esp. Asia)
Disease
| Syndrome | Features |
|---|---|
| Pneumonia |
|
| Urinary tract infection | Catheter-associated, hospital-acquired |
| Sepsis | Immunocompromised, nosocomial lines, bowel source |
| Liver abscess | Hypervirulent strains; can seed eye/CNS |
- Diagnosis: culture of sputum, urine, or blood
- Treatment
- Third-generation cephalosporin ± aminoglycoside
- ESBL producers: carbapenem
- Carbapenemase (KPC) producers: ceftazidime–avibactam and other newer agents
- Prevention: catheter care, antibiotic stewardship
Encapsulated Pathogens at a Glance
| Organism | Capsule note |
|---|---|
| S. pneumoniae | >90 serotypes; conjugate and polysaccharide vaccines |
| H. influenzae type b | Polyribosyl-ribitol phosphate; conjugate vaccine |
| N. meningitidis | Serogroup vaccines (A, C, W-135, Y, plus B protein vaccine) |
| K. pneumoniae | Mucoid; no vaccine |
| P. aeruginosa | Alginate slime |
| Salmonella Typhi | Vi capsule; Vi vaccine |
| E. coli K1 | Neonatal meningitis |
| Cryptococcus neoformans | Yeast with polysaccharide capsule |
- Encapsulated organisms
- Resist phagocytosis until opsonized by antibody
- Cause overwhelming sepsis after splenectomy
- Vaccinate asplenic patients against pneumococcus, H. influenzae b, meningococcus
K. granulomatis (Donovanosis)
- Formerly Calymmatobacterium granulomatis
- Sexually transmitted; tropical regions (India, Papua New Guinea, Africa, Brazil)
- Small nodule → painless, beefy-red, easily bleeding ulcer
- Large lesions can enlarge into the groin (pseudo-bubo)
- Diagnosis: Donovan bodies (intracellular safety-pin-like bacteria within macrophages) on Wright–Giemsa smear
- Not visible on Gram stain
- Treatment: doxycycline (or azithromycin)
- Painless beefy ulcer without prominent nodes suggests Donovanosis; painless ulcer with matted nodes suggests lymphogranuloma venereum.
Shigella
Facts
- Gram-negative rod
- Non-motile (no H antigen)
- Non-lactose fermenter
- H₂S-negative
- Reservoir: humans only (no animal reservoir)
- Fecal–oral, person to person (day care, crowding, poor sanitation, men who have sex with men)
- Very low infectious dose (about 10–100 organisms)
- Acid-resistant, survives stomach
Species
- S. sonnei – most common in the U.S., mildest
- S. flexneri
- S. boydii
- S. dysenteriae type 1 – most severe, makes Shiga toxin
Pathogenesis
Cross M cells→
Taken up by macrophages → escape, trigger apoptosis→
Enter colonocytes from basolateral side→
Actin tails spread cell to cell→
Shallow ulcers, inflammation, rare bacteremia
- Shiga toxin (S. dysenteriae type 1)
- Cleaves 28S rRNA of the 60S subunit → protein synthesis stops
- Enterotoxic, cytotoxic (and neurotoxic in animals)
- Can cause HUS
Clinical
- Incubation 1–4 days
- Fever, lower abdominal cramps, tenesmus
- Watery stool first → bloody mucoid stool (dysentery)
- Stool: many neutrophils
- Complications: HUS, reactive arthritis (HLA-B27)
- Diagnosis: stool culture on selective media (MacConkey, Hektoen, XLD)
- Treatment
- Fluid and electrolyte replacement
- Antibiotics for severe disease (fluoroquinolone, azithromycin, ceftriaxone; resistance via plasmid enzymes is common, including ampicillin)
- Avoid antimotility drugs
- Prevention: sanitation, clean water, handwashing
Invasive vs Toxin-Mediated Diarrhea
| Type | Stool | Examples |
|---|---|---|
| Invasive / inflammatory | Neutrophils, often blood; fever | Shigella, non-typhoidal Salmonella, Campylobacter, EIEC, Yersinia |
| Toxin-mediated / secretory | Watery, no blood or few cells | ETEC, V. cholerae, C. perfringens, B. cereus, S. aureus (preformed) |
| Cytotoxin / hemorrhagic | Bloody, little fever | EHEC |
Aeromonas
- Oxidase-positive, flagellated, glucose-fermenting Gram-negative rod (not an Enterobacterium)
- Aquatic habitat; contaminated water, seafood
- Diarrhea resembling shigellosis (can be bloody)
- Wound infection after freshwater exposure; leech therapy complication
- Treatment: fluoroquinolone, third-generation cephalosporin, or TMP-SMX
- Shigella ulcers are shallow and rarely reach the bloodstream.
- Non-motile, non-lactose-fermenting, H₂S-negative colonies are Shigella.
Y. pestis (Plague)
Features
- Small Gram-negative coccobacillus
- Bipolar ("safety-pin") staining with Wright, Giemsa, or Wayson stains
- Facultative intracellular
- Zoonosis; bioweapon potential
- Reservoir: wild rodents (prairie dogs, ground squirrels) in the U.S. Southwest
- Vector: rodent fleas (Xenopsylla)
Virulence
- Flea gut blockage by biofilm → regurgitation into bite
- F1 capsular antigen: antiphagocytic
- Type III secretion (Yop proteins): disable phagocytes and cytokine signaling
- V and W antigens, endotoxin, plasminogen-activating protease
| Form | Course |
|---|---|
| Bubonic |
|
| Septicemic | Shock, DIC, purpura, gangrene of digits |
| Pneumonic |
|
- Diagnosis: smear and fluorescent antibody, serology; cultures are hazardous (alert lab)
- Treatment: streptomycin or gentamicin (doxycycline, fluoroquinolone alternatives); start empirically
- Prevention: rodent and flea control, avoid sick animals, prophylactic doxycycline after exposure, respiratory isolation
Y. enterocolitica
- Gram-negative rod, non-lactose fermenter
- Motile at 25 °C, non-motile at 37 °C
- Grows at refrigerator temperature (cold enrichment helps isolation)
- Zoonotic: pigs, rodents
- Sources: pork (chitterlings), unpasteurized milk
- More common in colder regions
- Enterotoxin and invasion of terminal ileum
- Mesenteric lymphadenitis
- Presentations
- Young children: febrile enterocolitis, bloody stool
- Older children/young adults: pseudoappendicitis (right lower quadrant pain, no appendicitis at surgery); also Y. pseudotuberculosis
- Adults: reactive arthritis, erythema nodosum
- Transfusion-related sepsis (organism thrives in refrigerated blood with iron)
- Diagnosis: stool culture with cold enrichment, CIN agar
- Treatment: supportive; fluoroquinolone or cephalosporin in immunocompromised or severe disease
- Enterocolitis mimicking appendicitis plus pork or raw milk exposure points to Yersinia enterocolitica.
- Patients with iron overload (hemochromatosis, deferoxamine therapy) are prone to Yersinia and Vibrio vulnificus sepsis.
P. mirabilis / P. vulgaris
- Gram-negative rod, non-lactose fermenter
- Strongly motile
- Swarming waves on agar
- H₂S-positive
- Urease-positive (rapid)
- Oxidase-negative
- Habitat: human gut, soil, water
- Endogenous spread
Pathogenesis
Motile, ascends urethra→
Urease splits urea → ammonia→
Alkaline urine→
Struvite (staghorn) stones
- Stones shelter bacteria → recurrent infection
- Endotoxin → urosepsis
- Disease
- Urinary tract infection, catheter-associated
- Pyelonephritis, urosepsis
- Wound infection
- Diagnosis: urine/blood culture; swarming non-lactose fermenter with urease
- Treatment
- Fluoroquinolone, TMP-SMX, or third-generation cephalosporin
- Remove stones and catheters (infection persists otherwise)
- Prevention: early catheter removal
- Historical test
- Weil–Felix: antibodies to rickettsiae cross-react with Proteus vulgaris OX antigens; no longer used
| Other urease-positive organisms | Setting |
|---|---|
| H. pylori | Stomach; gastritis, ulcer |
| Ureaplasma | Urethritis, stones |
| Klebsiella (variable) | Urinary stones |
| Cryptococcus, Nocardia | Non-enteric urease producers |
- Alkaline urine with struvite stones and a swarming organism is Proteus.
Genus Features
- Gram-negative rod, facultative anaerobe
- Motile, non-lactose fermenter
- H₂S-positive (black on Hektoen / SS agar)
- Over 2,400 serotypes (O, H, Vi antigens)
- Acid-sensitive → gastric acid is a defense
- Antacids, PPIs, gastrectomy lower the infectious dose
- Intracellular survival in macrophages (type III secretion)
Typhoidal vs Non-typhoidal
| Feature | Typhoidal (S. Typhi, Paratyphi) | Non-typhoidal (Enteritidis, Typhimurium, others) |
|---|---|---|
| Reservoir | Humans only; chronic carriers (gallbladder) | Poultry, eggs, cattle, reptiles, pets |
| Capsule (Vi) | Present for Typhi | Absent |
| Infectious dose | Low (about 10³) | High (about 10⁵ or more) |
| Syndrome | Enteric (typhoid) fever | Gastroenteritis; bacteremia in vulnerable hosts |
| Diarrhea | Often constipation first | Prominent |
| Antibiotics | Always treated | Not for uncomplicated gastroenteritis |
Enteric (Typhoid) Fever
Ingestion→
Invade M cells, ileum/Peyer patches→
Engulfed by macrophages→
Mesenteric nodes → blood→
Liver, spleen, bone marrow, gallbladder seeding
| Week | Features |
|---|---|
| 1 | Stepwise rising fever, headache, malaise, constipation; relative bradycardia; blood cultures usually positive |
| 2 | Sustained high fever, rose spots on trunk (blanching pink macules), hepatosplenomegaly, "pea-soup" diarrhea, leukopenia |
| 3 | Peyer-patch necrosis → intestinal bleeding or perforation; stool cultures positive |
| 4+ | Recovery or complications; chronic gallbladder carriage in some |
- Other complications
- Cholecystitis, osteomyelitis, endocarditis, meningitis, pneumonia
- Diagnosis
- Cultures: blood (early), bone marrow (most sensitive), stool, urine
- Widal test (O and H agglutinins) is historical and unreliable
- Treatment: ceftriaxone, azithromycin, or fluoroquinolone (resistance patterns vary by region)
- Carrier state: prolonged antibiotic, cholecystectomy if gallstones
- Prevention
- Sanitation and food/water safety
- Live oral Ty21a vaccine
- Parenteral Vi capsular polysaccharide vaccine
Non-typhoidal Salmonella
- Sources: poultry, eggs, produce, peanut butter, pet reptiles and turtles
- Invasion of ileocolonic mucosa → inflammation → prostaglandins → ↑cAMP → diarrhea
- Gastroenteritis
- Incubation 6–48 hours
- Nausea, vomiting, fever, cramps, loose stools (sometimes bloody)
- Self-limited in about a week
- No antibiotics for uncomplicated cases
- May prolong carriage
- Treat invasive disease or high-risk hosts
- Infants, elderly, immunocompromised, valvular/vascular disease, sickle cell disease
- Ceftriaxone, fluoroquinolone, or TMP-SMX
- Bacteremia (e.g., S. Choleraesuis, Dublin) → endocarditis, mycotic aneurysm, arthritis (~10%)
Special host associations
| Host | Why |
|---|---|
| Sickle cell disease | Functional asplenia and bone infarcts → Salmonella osteomyelitis (leading cause alongside S. aureus) |
| HIV / low CD4 | Recurrent non-typhoidal bacteremia |
| Reduced gastric acid | Lower infectious dose |
| Reactive arthritis | HLA-B27 patients, after enteric infection |
- Salmonella and Shigella are both non-lactose fermenters; Salmonella is motile and H₂S-positive, Shigella is neither.
- Pea-soup diarrhea, rose spots, and travel to an endemic region point to typhoid.
Gardnerella vaginalis and Bacterial Vaginosis
Organism
- Gram-variable pleomorphic rod
- Gram-positive-type wall but stains pink
- Facultative anaerobe
- Catalase-negative, oxidase-negative
- Normal vaginal-flora member
Pathogenesis
↓ Lactobacillus→
↑ vaginal pH→
Overgrowth of Gardnerella + anaerobes (Mobiluncus, Prevotella, Bacteroides)
- Triggers: douching, new or multiple partners, antibiotics
- Polymicrobial biofilm
- Presentation
- Thin, gray-white, homogeneous discharge
- Fishy odor
- Little inflammation (no itching or burning typically)
- Diagnosis (any three of four findings)
- Vaginal pH >4.5
- Clue cells: squamous cells studded with bacteria
- Positive whiff test: KOH releases amines
- Thin homogeneous discharge
- Treatment: metronidazole or clindamycin (oral or vaginal)
- Complications: preterm birth, postoperative infection, higher HIV acquisition risk
| Cause of vaginitis | Discharge | pH | Microscopy |
|---|---|---|---|
| Bacterial vaginosis | Thin gray, fishy | >4.5 | Clue cells |
| Trichomoniasis | Frothy yellow-green, malodorous | >4.5 | Motile trophozoites |
| Candidiasis | Thick white, curd-like | Normal (≤4.5) | Pseudohyphae/budding yeast |
Bacteroides fragilis
- Obligate anaerobic Gram-negative rod
- Most abundant colonic anaerobe among clinically important species
- Resistant to bile
- Virulence
- Polysaccharide capsule: antiphagocytic, promotes abscess formation
- Modified lipopolysaccharide with weak endotoxin activity
- β-lactamase
- Source: gut flora spilling after trauma, surgery, perforation, cancer, or ischemia
- Disease
- Intra-abdominal, pelvic, and liver abscesses
- Peritonitis (usually mixed with aerobes such as E. coli)
- Bacteremia
- Diagnosis: anaerobic culture, gas-liquid chromatography; Gram stain of pus often shows mixed flora
- Treatment
- Drain the abscess (essential)
- Metronidazole, carbapenem, or β-lactam/β-lactamase inhibitor; cefoxitin
- Clindamycin resistance is increasing
- Prevention: perioperative prophylaxis for bowel and biliary surgery
Porphyromonas, Prevotella, Fusobacterium
| Organism | Notes |
|---|---|
| Porphyromonas gingivalis | Gingipain proteases and adhesins; degrade IgG and cytokines; periodontitis |
| Prevotella | Oral/vaginal anaerobe; aspiration pneumonia, lung abscess, brain abscess, polymicrobial infections |
| Fusobacterium | Slender pointed rods; periodontal infection, lung abscess, Lemierre syndrome (jugular vein septic thrombophlebitis) |
- Normal oral flora; endogenous spread
- Treatment: metronidazole, clindamycin, or β-lactam/inhibitor; drain pus
- Aspiration pneumonia
- Dependent lung segments, foul-smelling sputum, cavitation
- Risk: alcohol use, seizures, dysphagia
- Aminoglycosides do not work against anaerobes, so an abdominal abscess needs anaerobic coverage plus drainage.
- Foul-smelling pus signals an anaerobic infection.
Spirochete Essentials
- Thin, coiled, motile bacteria
- Motion by axial filaments (periplasmic flagella)
- Gram-negative-type envelope but too thin for ordinary Gram staining
- Genera: Treponema, Borrelia, Leptospira
- Seen by dark-field microscopy, silver stain, or fluorescent antibody
T. pallidum subsp. pallidum
- Cannot be cultured in vitro; obligate human pathogen (extracellular)
- Sexual transmission (through microabrasions) or transplacental
- Mother to fetus at any stage; highest risk with early syphilis
- Pathology: endarteritis (perivascular plasma cell/lymphocytic infiltrate) → ulcer, rash, gumma
- Chronic course with periods of latency
Stages
| Stage | Timing | Features | Testing |
|---|---|---|---|
| Primary | About 3 weeks (10 days–3 months) after exposure |
| Dark-field or fluorescent microscopy of lesion; nontreponemal tests may still be negative (~25–50%) |
| Secondary | Weeks to months later |
| Both serologic types positive |
| Latent | Early (<1 year) vs late | No symptoms | Serology only |
| Tertiary | Years later (about 30% of untreated) |
| Treponemal tests positive; nontreponemal may be low or negative |
| Congenital | Maternal infection transmitted across the placenta |
| Infant titer higher than mother's or persisting beyond ~3 months |
- Neurosyphilis can occur at any stage (meningitis, meningovascular disease, tabes, paresis)
- Ocular and otic syphilis possible at any stage
Serology
| Feature | Nontreponemal (VDRL, RPR) | Treponemal (FTA-ABS, TP-PA, MHA-TP, EIA) |
|---|---|---|
| Antigen | Cardiolipin–lecithin–cholesterol (lipid released from damaged cells and treponemes) | Treponemal proteins |
| Antibody | Reagin (nonspecific) | Specific to treponemes |
| Use | Screening; titers track treatment response and reinfection | Confirmation |
| Time course | Titer falls with treatment; may revert negative | Usually positive for life |
| False positives | Lupus and antiphospholipid syndrome, pregnancy, viral infections (e.g., mononucleosis, hepatitis), injection drug use, aging | Other treponemal diseases (yaws, pinta, bejel); Lyme disease (less often) |
| Prozone effect | Very high antibody levels can cause false-negative until diluted | — |
- Typical algorithm: screening test → confirmatory test of the other type
- CSF VDRL for neurosyphilis (specific, insensitive)
Treatment & Prevention
- Penicillin G is the drug of choice (no resistance)
- Primary, secondary, early latent: single dose of benzathine penicillin G (intramuscular)
- Late latent / tertiary: weekly benzathine penicillin for 3 doses
- Neurosyphilis, ocular syphilis, congenital syphilis: intravenous aqueous penicillin G
- Penicillin-allergic pregnant women are desensitized and treated with penicillin
- Jarisch–Herxheimer reaction
- Within hours of first dose (usually 24 h)
- Fever, chills, myalgia, hypotension, worsening rash
- Release of endotoxin-like lipoproteins and cytokines from dying spirochetes
- Not an allergy; supportive care; can follow therapy of any spirochetal disease
- Prevention: screening, partner treatment, condoms, prenatal screening
- No vaccine
- Painless chancre = syphilis; painful genital ulcer = chancroid or herpes.
- Aortitis with a tree-bark appearance of the aorta indicates tertiary syphilis.
- Treponemal antibody tests detect infection earliest and stay positive after cure.
Borrelia: Genus Features
- Large, loosely coiled spirochetes
- Microaerophilic, difficult to culture
- Visible with Giemsa or Wright stain on blood smear (relapsing fever)
- Transmitted by arthropods
Borrelia burgdorferi (Lyme Disease)
Ecology
- Vector: Ixodes (deer) ticks
- I. scapularis: Northeast and upper Midwest
- I. pacificus: Pacific coast
- Reservoirs: white-footed mice (nymphs feed), white-tailed deer (adult ticks)
- Peak: late spring through summer (nymph season)
- Tick must feed for roughly 36–48 hours to transmit
- Most common vector-borne disease in the U.S.
Pathogenesis
- Spreads locally in skin, then hematogenously
- Heart, joints, nervous system targeted
- Antigenic variation of surface lipoproteins (OspC, VlsE) aids evasion
- Late arthritis is immune-mediated (immune complexes, cytokines)
| Stage | Timing | Features |
|---|---|---|
| Early localized | 3 days–1 month | Erythema migrans (expanding annular rash, often central clearing, "bull's-eye"), fever, fatigue, myalgias |
| Early disseminated | Weeks to months |
|
| Late | Months to years | Oligoarticular arthritis (large joints, especially the knee), chronic acrodermatitis, encephalopathy |
- Diagnosis
- Erythema migrans in an endemic area is diagnosed clinically (no test needed)
- Otherwise two-tier serology: ELISA/immunoassay then Western blot (IgM and IgG)
- Serology is often negative early
- Treatment
- Early localized: doxycycline (all ages, short course), amoxicillin, or cefuroxime
- Neurologic or high-grade AV block: ceftriaxone
- Arthritis: doxycycline or amoxicillin (ceftriaxone if refractory)
- Prevention: protective clothing, repellents, tick checks, prompt removal
- Single-dose doxycycline prophylaxis in selected high-risk bites
- Vaccine not currently used in the U.S.
- Co-infection with Anaplasma and Babesia possible (same tick)
Relapsing Fever
| Feature | B. recurrentis | B. hermsii and other species |
|---|---|---|
| Vector | Body louse (crushed louse contaminates skin) | Soft ticks (Ornithodoros) from rodents |
| Pattern | Epidemic, crowding, poverty, war | Sporadic; cabins and camping in western U.S. mountains |
| Mechanism | Antigenic variation → each new variant escapes antibody → recurrent fever bouts | |
| Clinical | Febrile episodes of several days alternating with afebrile intervals; headache, myalgia, rash | |
| Diagnosis | Spirochetes on peripheral blood smear during fever | |
| Treatment | Doxycycline (erythromycin in children and pregnancy); Jarisch–Herxheimer reaction common | |
Leptospira interrogans
- Tightly coiled spirochete with hooked ends
- Visible by dark-field microscopy
- Aerobic; culture possible but slow (special media)
- Zoonosis; reservoirs: rats, livestock, dogs, wildlife
- Shed in urine
- Transmission: contact with urine-contaminated fresh water or soil
- Enters through skin abrasions or mucous membranes
- Risk: sewer workers, farmers, flood exposure, swimmers/kayakers, adventure races
- Highest U.S. incidence in Hawaii
- Pathogenesis: vasculitis and tissue injury; no classic toxin
Phase 1: leptospiremic (abrupt fever, headache, myalgia, conjunctival suffusion)→
Brief improvement→
Phase 2: immune (aseptic meningitis, uveitis, ± severe disease)
- Severe form (Weil disease)
- Jaundice
- Acute kidney injury
- Hemorrhage (including pulmonary hemorrhage)
- Elevated bilirubin with only mild transaminase rise
- Diagnosis: serology (microscopic agglutination test), PCR; culture of blood/CSF/urine in specialized labs
- Treatment: penicillin G or doxycycline (ceftriaxone for severe disease); Jarisch–Herxheimer reaction can occur
- Prevention: doxycycline prophylaxis for brief high-risk exposure; vaccinate livestock and pets; rodent control
- Doxycycline-treated Lyme disease can be given even to children for short courses.
- Flu-like illness plus conjunctival suffusion after fresh-water exposure suggests leptospirosis.
Comparison with Typical Bacteria
| Property | Typical bacteria | Chlamydiaceae | Rickettsiaceae | Mycoplasmataceae |
|---|---|---|---|---|
| Obligate intracellular | Mostly no | Yes | Yes | No (extracellular, surface-attached) |
| Own ATP production | Full | None (energy parasites) | Limited | Full |
| Peptidoglycan | Normal | Unusual (lacks muramic acid) | Present | None |
| Gram stain | Usually works | Not useful | Poor (Giemsa, Gimenez) | Not visible |
| Culture | Artificial media | Cell culture | Cell culture | Cell-free media with sterols |
Chlamydiaceae: Biology
Elementary body (infectious, extracellular, dense)→
Enters epithelial cell (endosome that avoids lysosome fusion)→
Transforms to reticulate body→
Binary fission in inclusion→
Reorganizes to elementary bodies → cell lysis
- Reticulate body = metabolically active, replicating, non-infectious
- Not visible on Gram stain; inclusions seen with Giemsa, iodine, or immunofluorescence
- Grown in cell culture or embryonated eggs
- Species of importance: Chlamydia trachomatis, Chlamydophila pneumoniae, Chlamydophila psittaci
Chlamydia trachomatis
- Infects squamocolumnar epithelium of mucosal surfaces
- Reservoir: human genital tract and eyes
- Spread: sexual contact, birth, hand/fly-borne eye contact (trachoma)
| Serovars | Disease | Details |
|---|---|---|
| D–K | Genital and neonatal disease |
|
| L1, L2, L3 | Lymphogranuloma venereum |
|
| A, B, Ba, C | Trachoma |
|
- Diagnosis
- Nucleic acid amplification test (first-line, urine or swab)
- Inclusions in scrapings (Giemsa); direct fluorescent antibody
- Treatment
- Doxycycline or azithromycin
- LGV: longer doxycycline course
- Pregnancy: azithromycin
- Neonates: oral erythromycin (or azithromycin) for conjunctivitis to prevent pneumonia
- Prevention: screening of young sexually active women, partner treatment, condoms, prenatal screening
- Often treated together with gonorrhea (co-infection common)
Chlamydophila (Chlamydia) Species
| Feature | C. pneumoniae | C. psittaci |
|---|---|---|
| Reservoir | Humans | Birds (parrots, parakeets, pigeons, poultry) |
| Transmission | Respiratory droplets | Inhaled dried bird droppings and secretions |
| Disease | Atypical "walking" pneumonia (mild), pharyngitis, bronchitis, sinusitis; hoarseness | Psittacosis (ornithosis): atypical pneumonia, high fever, headache, hepatosplenomegaly, hepatitis |
| Notes | Possible link to atherosclerosis (unproven) | Occupational: bird owners, pet-shop and poultry workers |
| Diagnosis | Serology (microimmunofluorescence), PCR | Serology (complement fixation), PCR |
| Cold agglutinins | Negative | Negative |
| Treatment | Macrolide or doxycycline | Doxycycline |
| Prevention | None | Avoid infected birds; quarantine imports |
- Urethritis with a negative Gram stain for diplococci suggests Chlamydia.
- Conjunctivitis in the first week of life suggests gonococcus; 5–14 days suggests chlamydia.
- Atypical pneumonia after exposure to birds is C. psittaci.
Group Properties
- Tiny Gram-negative-type coccobacilli, obligate intracellular
- Limited ATP production → depend on host cell
- Poorly stain with Gram; use Giemsa, Gimenez, or immunostains
- Most spread by arthropod bites; infect endothelium (rickettsiae) or white cells (ehrlichiae)
- Doxycycline is first-line for nearly all
- Start therapy on clinical suspicion; do not wait for serology
Rickettsial Diseases Compared
| Disease | Organism | Vector | Reservoir | Rash / notes |
|---|---|---|---|---|
| Rocky Mountain spotted fever | R. rickettsii | Hard ticks (Dermacentor) | Ticks, dogs, rodents | Starts at wrists/ankles, moves centrally (centripetal); includes palms and soles; petechial |
| Epidemic typhus | R. prowazekii | Human body louse | Humans (and flying squirrels in the U.S.) | Begins on trunk and spreads outward (centrifugal), sparing palms/soles; Brill–Zinsser recrudescence years later |
| Endemic (murine) typhus | R. typhi | Rat flea | Rodents | Milder; truncal rash; Texas, California, tropics |
| Scrub typhus | Orientia tsutsugamushi | Chigger mites | Rodents | Eschar at bite site; Asia–Pacific |
| Ehrlichiosis (monocytic) | E. chaffeensis | Lone star tick (Amblyomma) | Deer, small mammals | Usually no rash |
| Anaplasmosis (granulocytic) | A. phagocytophilum | Ixodes tick | Deer, mice | No rash; same ticks as Lyme |
| Q fever | Coxiella burnetii | No vector (aerosol) | Sheep, goats, cattle | No rash |
Rocky Mountain Spotted Fever
- Despite the name, most cases are in the south-central and southeastern U.S. (e.g., Oklahoma, Tennessee, the Carolinas)
- Season: spring and summer; incubation about 2–12 days
- Pathogenesis: invades endothelial cells → vasculitis → leaky capillaries
- Brain, lungs, skin, kidney, GI tract
- Disseminated vascular injury → edema, hypotension
- Presentation
- Fever, severe headache, myalgias
- Nausea, vomiting, abdominal pain
- Rash by day 2–5: macules → petechiae, wrists and ankles first, then trunk, palms, soles
- Possible confusion, hyponatremia, thrombocytopenia, elevated transaminases
- Diagnosis
- Clinical (exposure + fever + rash)
- Immunofluorescence antibody titers (fourfold rise), skin-biopsy immunostain, PCR
- Weil–Felix is obsolete (cross-reactivity with Proteus OX antigens)
- Treatment: doxycycline, including in young children
- Chloramphenicol only in pregnancy with allergy (limited use)
- Prevention: tick avoidance, repellents, prompt removal; no vaccine
- Delaying doxycycline for serologic confirmation risks death in spotted fever.
- Rash that starts peripherally and moves inward suggests spotted fever; rash that starts centrally suggests epidemic typhus.
Ehrlichiosis and Anaplasmosis
- Obligate intracellular in white blood cells
- Ehrlichia: monocytes/macrophages
- Anaplasma: neutrophils
- Presentation: flu-like illness, headache, myalgia; usually no rash
- Laboratory: leukopenia, thrombocytopenia, elevated liver enzymes
- Morulae: mulberry-like cytoplasmic inclusions in infected cells on Giemsa-stained blood smear
- Diagnosis: blood smear, PCR, serology
- Treatment: doxycycline, started empirically
- Prevention: avoid ticks; no vaccine
Coxiella burnetii (Q Fever)
- Obligate intracellular; lives in acidic phagolysosomes
- Spore-like, hardy form survives environmentally
- Reservoirs: sheep, goats, cattle
- High organism load in placenta, birth fluids, milk
- Spread: inhalation of dried aerosolized birth products, dust (farmers, vets, abattoir workers); raw milk
- Not tick- or arthropod-transmitted in practice
- Disease
- Acute: flu-like illness, atypical pneumonia, granulomatous hepatitis
- Chronic: culture-negative endocarditis (valvulopathy)
- Diagnosis: serology
- Phase II antibodies for acute disease
- Phase I antibodies high in chronic disease
- Treatment: doxycycline (long-term combination therapy for endocarditis)
- Possible bioterrorism agent
- The only rickettsia-like pathogen lacking an arthropod vector and rash is Coxiella.
- Culture-negative endocarditis in a farm worker suggests Q fever.
Family Features
- Smallest free-living bacteria
- No cell wall (no peptidoglycan)
- Not seen on Gram stain
- Intrinsically resistant to β-lactams and vancomycin
- Pleomorphic, flexible
- Membrane contains sterols
- Cannot make cholesterol → needs it from the medium or host
- Culture: special sterol-containing agar
- "Fried-egg" colonies after days to weeks
- Genera: Mycoplasma, Ureaplasma
Mycoplasma pneumoniae
Epidemiology
- Reservoir: human respiratory tract
- Droplet spread with prolonged close contact
- Schools, college dorms, military barracks, families
- Peaks in older children and young adults
- Outbreaks every few years
Pathogenesis
- Extracellular surface parasite (non-invasive)
- P1 adhesin binds respiratory epithelium (sialylated receptors)
- Impairs ciliary activity
- Hydrogen peroxide and superoxide damage the epithelium
- Host inflammatory response drives symptoms (IL-1, IL-6, TNF-α)
Droplets→
P1 attachment→
Ciliostasis + oxidative injury→
Persistent dry cough, atypical pneumonia
- Disease
- Pharyngitis, tracheobronchitis
- "Walking" pneumonia: gradual onset, low-grade fever, headache, malaise
- Prominent dry hacking cough, little sputum
- Chest X-ray looks worse than the exam (patchy/interstitial infiltrate)
- Most common non-viral atypical pneumonia in young adults
- Extrapulmonary
- Cold-agglutinin autoimmune hemolytic anemia (IgM against the I antigen on red cells)
- Erythema multiforme / Stevens–Johnson syndrome, bullous myringitis
- Neurologic complications (rare)
- Diagnosis
- Mostly clinical
- PCR on respiratory specimens; serology
- Cold agglutinin titer: positive in only part of cases (about 50–65%), nonspecific
- Culture on sterol-rich medium is slow (up to about 10 days)
- Treatment: macrolide (azithromycin), doxycycline, or respiratory fluoroquinolone
- Penicillins and cephalosporins are useless (no wall)
- Prevention: none
Ureaplasma urealyticum
- Wall-less, urease-positive; part of genitourinary flora in many adults
- Associated conditions
- Non-gonococcal urethritis
- Prostatitis
- Struvite/alkaline stones (urease)
- Chorioamnionitis, preterm birth, neonatal pneumonia
- Diagnosis: PCR; special culture
- Treatment: doxycycline or azithromycin (macrolides alternative)
Atypical Pneumonia: Quick Comparison
| Cause | Setting | Distinguishing clue | Therapy |
|---|---|---|---|
| M. pneumoniae | Young adults, dorms, barracks | Cold agglutinins, fried-egg colonies, rash/hemolysis | Macrolide, doxycycline |
| C. pneumoniae | Teens/young adults | Hoarseness, mild illness; negative cold agglutinins | Macrolide, doxycycline |
| C. psittaci | Bird exposure | Hepatosplenomegaly, high fever | Doxycycline |
| Legionella | Older smokers, water aerosols | Hyponatremia, diarrhea, confusion | Fluoroquinolone, azithromycin |
| Coxiella | Livestock exposure | Hepatitis, culture-negative endocarditis | Doxycycline |
- Pneumonia that does not respond to penicillin or cephalosporin with a normal Gram stain of sputum suggests a wall-less or intracellular organism.
- Positive cold agglutinins support but do not prove Mycoplasma.
| Clue | Think |
|---|---|
| Cystitis; pink colonies, metallic sheen on EMB | E. coli |
| Bloody diarrhea, no fever, then hemolysis and renal failure; sorbitol-negative | EHEC O157:H7 |
| Traveler's watery diarrhea | ETEC |
| Alcoholic, currant-jelly sputum, mucoid lactose fermenter | K. pneumoniae |
| Beefy painless genital ulcer, Donovan bodies | K. granulomatis |
| Dysentery in a child at day care; non-motile, H₂S-negative | Shigella |
| Bubo after rodent flea exposure; safety-pin bacilli | Y. pestis |
| Pseudoappendicitis, pork or milk, cold enrichment | Y. enterocolitica |
| Staghorn stones, alkaline urine, swarming | Proteus |
| Fever, rose spots, relative bradycardia, travel | S. Typhi |
| Sickle cell disease and osteomyelitis | Salmonella |
| Poultry or turtle exposure, diarrhea, H₂S-positive motile rod | Non-typhoidal Salmonella |
| Thin gray discharge, clue cells, whiff test | Gardnerella (bacterial vaginosis) |
| Foul abdominal abscess after surgery or perforation | B. fragilis |
| Painless chancre; copper rash on palms and soles; gumma | T. pallidum |
| Bull's-eye rash, facial palsy, AV block, knee arthritis | B. burgdorferi |
| Recurrent fever episodes, cabin stay, spirochetes on blood smear | Relapsing fever Borrelia |
| Flooded-water exposure, jaundice, kidney failure, Hawaii | Leptospira |
| Urethritis, no organisms on Gram stain; neonatal afebrile pneumonia | C. trachomatis |
| Chronic follicular conjunctivitis, scarring | Trachoma (serovars A–C) |
| Parrot exposure, atypical pneumonia | C. psittaci |
| Fever, wrist/ankle petechial rash that moves inward, tick | R. rickettsii |
| Flu-like illness, no rash, low WBC and platelets, morulae | Ehrlichia / Anaplasma |
| Sheep or goat birthing, hepatitis, culture-negative endocarditis | C. burnetii |
| Dorm outbreak, dry cough, cold agglutinins | M. pneumoniae |
- Doxycycline covers most tick-borne and obligate intracellular pathogens (rickettsiae, ehrlichiae, anaplasma, Lyme, Chlamydia, Coxiella).
- Antibiotics worsen or fail to help in EHEC infection and uncomplicated non-typhoidal salmonellosis.
- Jarisch–Herxheimer reaction follows spirochete treatment, not just syphilis.
- Wall-less organisms are naturally resistant to every drug that attacks peptidoglycan.