Medically Important Bacteria

What the USMLE Requires You To Know

The type of major disease from presenting symptoms

•Determine the causal agent from case clues.

•No distinguishing clues given? Know most common agent(s).

•Epidemiologic clues, symptomatic clues, or organism information given? Know the specific agent.

•Be able to answer basic science questions about disease or organism, predis­ posing conditions, epidemiology, mechanisms of pathogenicity, complications, standard preventive measures, and major tests used in identification.

The basic science used as clues or tested directly

•Morphology (Gram reaction, basic morphology, motility, spore formation)

•Physiology (obligate aerobes/anaerobes; a few specific fermentations; oxi­ dase, urease, catalase, coagulase, superoxide dismutase, hemolysins; and how bacterial cells grow, divide, and die

•Bacterial structures (composition, function, and role in disease)

•Determinants of pathogenicity (toxins; factors aiding in invasiveness, pathoge­ nicity or immune evasion; and obligate and facultative intracellular pathogens)

•Epidemiology/transmission (arthropod vectors; and how each major disease is acquired)

•Laboratory diagnosis (serologic/skin tests: specific serology for syphilis; acid fast and Gram stains; specific media; and unusual growth requirements)

•Treatment (drug of choice and prophylaxis where regularly used)

Note

Nomenclature

Latin bacterial family names have "-aceae," e.g., Enterobacteriaceae.

Genus and species names are italicized and abbreviated, e.g., Enterobacteraero­

genes = E. aerogenes.

Note

Mnemonic

The 4 sisters "Ella" worship in the "Cyste­ ine" chapel:

•Francisella

•Bruce/la

•Legionella

•Pasteurella

0

2

Microaerophilic

Facultative

anaerobes

Obligate

anaerobes

Require low but not full oxygen tension

Will respire aerobically until oxygen is depleted and then ferment

•Lack superoxide dismutase

•Generally lack catalase

•Are fermenters

•Cannot use 02 as terminal electron acceptor

Campylobacter

Helicobacter

Most bacteria,

e.g., Enterobacteriaceae

Actinomyces*

Bacteroides

Clostridium

Section II • Microbiology

GRAM-STAINING REACTIONS

Table ll-2-9. Gram-Positive Bacteria

Coed

Staphylococcust

Streptococcust

Rods

Aerobic or facultative anaerobic

Bacillus

Listeria

Corynebacteriumt

Nocardia

Mycobacteriumt

Anaerobic

Clostridiumt

Actinomyces

Eubacterium

Propionibacterium

Lactobacillus

Note: Spore formers are Bacillus and Clostridium.

Table ll-2-10. Non-Gram-staining Bacteria*

Mycoplasmataceae

Mycoplasmat

Ureaplasma

*Note:

Poorlyvisible on traditional Gram stain: Mycobacte­ riumdoes not stain well with the Gram stain due to its waxy cell wall. It is considered gram-positive.

Most spirochetes, chlamydiae, and rickettsias are so thin that the color of the Gram stain cannot be seen. All have gram-negative cell walls.

Legionella (gram-negative) also does not stain well with the traditional Gram stain unless counterstain time is increased.

(tMarked organisms have high numbers of questions in the pool.)

Table ll-2-11. Gram-Negative Bacteria

Aerobic

Helical or curved (and microaerophilic)

Campylobacter

He/icobacter

Ehrlichia

Chlamydiaceae

Chlamydiat

Chlamydophila

Key Vignette Clues

S.epiderm idis

•Coagulase (-); gram (+) cocci

•Novobiocin sensitive

•Infections of catheters/shunts

S.·saprophyticus

•Coagulase (-), gram (+) cocci

•Novobiocin resistant

•"Honeymoon cystitis"

Key Vignette Clues

Staphylococcusaureus

•Coagulase (+), gram (+) cocci in clus· ters

•Gastroenteritis: 2-6 h onset, salty foods, custards

•Endocarditis: acute

•Toxic shock syndrome: desquamating rash, fever, hypotension

•Impetigo: bullous

•Pneumonia: nosocomial, typical, acute

•Osteomyelitis: #1 cause unless HbS mentioned

GENUS: STAPHYLOCOCCUS

Genus Features

•Gram-positive cocci in clusters

•Catalase positive (streptococci are catalase negative)

Species ofMedical Importance

•S. aureus

•S. epidermidis

•S. saprophyticus

Staphylococcus aureus

Distinguishing Features

•Small, yellow colonies on blood agar

•-hemolytic

•Coagulase positive (all other Staphylococcus species are negative)

•Ferments mannitol on mannitol salt agar

Reservoir

•Normal flora

-Nasal mucosa (25% of population are carriers)

-Skin

Transmission

•Hands

•Sneezing

•Surgical wounds

•Contaminated food

-Custard pastries

-Potato salad

-Canned meats

Predisposing Factors for Infection

•Surgery/wounds

•Foreign body (tampons, surgical packing, sutures)

•Severe neutropenia (<500/µL)

•Intravenous drug abuse

•Chronic granulomatous disease

•Cystic fibrosis

0 Superantigens

Diseases

Table 11·2·11f. Acute Suppurative Group A Streptococcal Infections*

*Also, cellulitis/necrotizing fasciitis, puerperal fever, lymphangitis, erysipelas

Key Vignette Clues

Group A Streptococcus

•Catalase (-), hemolytic, bacitracin sensitive, gram (+) cocci

•Pharyngitis: abrupt onset, tonsillar abscesses

•Scarlet fever: blanching, sandpaper rash, strawberrytongue

•Impetigo: honey-crusted lesions

LaboratoryDiagnosis

•The rapid strep test (ELISA-based) misses approximately 25% ofinfections. Culture allnegatives.

•Antibodies to streptolysin 0 (ASO) titer of>200 is significant for rheumatic fever.

Key Vignette Clues

•Rheumatic fever: after streptococcal pharyngitis, i ASO titer

•AGN: after streptococcal skin or throat infection, hypertension, edema, smoky urine

LaboratoryDiagnosis

•Gram stain of CSF

•PCR ofCSF

•Quellung reaction: positive (swelling ofthe capsulewith the addition of type-specific antiserum)

•Latex particle agglutination: test for capsular antigen in CSF

Treatment

•Bacterial pneumonia--macrolides

•Adultmeningitis---eftriaxoneC or cefotaxime.Vancomycin is added ifpenicil­ lin-resistant S. pneumoniae has been reportedin the community

•Otitis media and sinusitis in children--amoxicillin, erythromycin for aller­ gic individuals

Prevention

•Antibody to the capsule (over 80 different capsular serotypes) provides type-specific immunity

In a Nutshell

Typical Pneumonia

Bacterial pneumonia such as Streptococ­ cus pneumoniae elicits neutrophils; ara­ chidonic acid metabolites (acute inflam­ matory mediators) cause pain and fever. Pneumococcus produces a lobar pneu­ monia with a productive cough, grows on blood agar, and usually responds well to penicillin treatment.

Section II • Microbiology

Key Vignette Clues

Viridans Streptococci

•Gram (+), catalase (-),ahemolytic, optochin resistant, bile insoluble

•Plaque and dental caries

•Subacute bacterial endocarditis-pre­ existing damage to the heart valves; follows dental work

• Vaccine

Pediatric (PCV, pneumococcal conjugate vaccine)

0Thirteen ofthe most common serotypes

° Conjugated to diphtheria toxoid

0Prevents invasive disease

Adult (PPV, pneumococcal polysaccharide vaccine)

023 ofthe most common capsular serotypes

0Recommended for alladults 65 years ofage andanyat-risk individuals

Viridans Streptococci (S. sanguis, S. mutans)

Distinguishing Features

•a hemolytic

•Optochin resistant

Reservoir-human oropharynx (normal flora)

Transmission--ndogenous

Pathogenesis--extrand (biofilm)-mediated adherence onto tooth enamel or damaged heart valve and to each other (vegetation); growth in vegetation protects organism from immune system.

Diseases

•Dental caries--S. mutans dextran-mediated adherence glues oral flora onto teeth, forming plaque and causing dental caries.

•Infective endocarditis (subacute)

-Malaise, fatigue, anorexia, night sweats, weight loss, splinterhemorrhages

-Predisposing conditions: damaged (or prosthetic) heart valve and dental work without prophylactic antibiotics or extremelypoor oral hygiene

Treatment-penicillinwithG aminoglycosides for endocarditis

Prevention-prophylactic antibiotics priorto dentalworkforindividualswith dam­ aged heartvalve

GENUS: ENTEROCOCCUS

Genus Features

•Catalase negative

•PYR+

Species ofMedical Importance

•Enterococcus faecalis

•Enterococcusfaecium

Enterococcus faeca/is/faecium

Distinguishing Features

•Group D gram-positive cocci in chains

•. PYRtestpositive

•Catalase-negative, varied hemolysis

•Hydrolyze esculin in 40% bile and 6.5%NaCl (bile esculin agar turns black)

Reservoir--human colon, urethra ± and female genitaltract

Transmission-endogenous

Pathogenesis

•Bile/salt tolerance allows survival in bowel and gall bladder.

•During medical procedures on GI or GU tract: E. faecalis bloodstream

previouslydamagedheartvalves endocarditis

Diseases

•Urinary and biliary tract infections

•Infective (subacute) endocarditis-in persons (often elderly) with damaged heart valves

Diagnosis

•Culture on blood agar

•Antibiotic sensitivities

Treatment

•Allstrains carry some drug resistance.

•Some vancomycin-resistant strains ofEnterococcusfaecium or E. faecalis have no reliably effective treatment. In general forlow-level resistance, use ampicillin, gentamicin, or streptomycin.

•VanAstrains have UDP-N-acetylmuramyl pentapeptide with the terminal

D-alanyl-D-alanine replacedwith D-alanyl-D-lactate, which functions in cell wall synthesis but does not bind to vancomycin.

Prevention--rophylacticuseofpenicillin andgentamicin inpatientswith damaged heartvalves prior to intestinalor urinarytract manipulations

Key Vignette Clues

Enterococcusfaecalis/faecium

•Gram (+), catalase (-), variable hemolysis, hydrolyzes esculin

•Urinary/biliary tract infections­ elderly males

•Subacute bacterial endocarditis­ elderly males, follows GI/GU surgery, preexisting heart valve damage

GENUS: BACILLUS

Genus Features

•Gram-positive rods

•Spore forming

•Aerobic

Species ofMedical Importance

•Bacillus anthracis

•Bacillus cereus

Bacillus anthracis

Distinguishing Features

•Large,boxcar-like, gram-positive, spore-fonning rods

•Capsuleispolypeptide (poly-D-glutamate)

•Potential biowarfare agent

Reservoir-animals, skins, soils

Transmission----ontact<:with infected animals or inhalation ofspores (bioterrorism)

Pathogenesis

•Capsule-polypeptide, antiphagocytic, immunogenic

•Anthraxtoxin includes 3 protein components:

Protective antigen (B component)-mediates entryofLF or EF into eukaryotic cells

Lethalfactor-killscells

- Edemafactor is an adenylate cyclase (calmodulin-activated like pertussis adenylate cyclase)

Diseases

•Cutaneous anthrax-papule -7 papule with vesicles (malignant pustules) -7 central necrosis (eschar) with erythematous border often with painful regional lymphadenopathy; fever in 50%

•Pulmonary (wool sorter's disease)

Life-threatening pneumonia; cough, fever, malaise, and ultimatelyfacial edema, dyspnea, diaphoresis, cyanosis, and shock with

orrhagic lymphadenitis

• Gastrointestinal anthrax Rare

Edema and blockage ofgastrointestinal tract can occur, vomiting and bloody diarrhea, high mortality

Diagnosis

•Gram stain and culture of blood, respiratory secretions or lesions

•Serology

•PCR

Treatment--ciprofloxacin or doxycycline. (Genes encoding resistance to penicillin and doxycycline have been transferred to B. anthracis.)

Key Vignette Clues

Bacillus anthracis

•Gram (+), spore forming, aerobic rods

•Contact with animal hides or postal worker; eschar or life-threatening pneumonia

Section II • Microbiology

Key Vignette Clues

Bacillus cereus

•Rapid-onset gastroenteritis

•Fried rice, Chinese restaurants

Prevention

•Toxoid vaccine (AVA, acellular vaccine adsorbed)

•Given to individuals in high risk occupations

Bacillus cereus

Distinguishing Feature--spores

Reservoir-found in nature

Transmission

•Foodborne

•Major association with fried rice from Chinese restaurants

•Associated with food kept warm, not hot (buffets)

Pathogenesis--two possible toxins:

•Emetic toxin: preformed fast (1-6 hours), similar to S. aureus with vomit­ ing and diarrhea; associated with fried rice

•Diarrheal toxin produced in vivo (meats, sauces): 18 hours, similar to E. coli; LT: increasing cAMP waterydiarrhea

Diseases

•Gastroenteritis -Nonbloody -± Vomiting

Diagnosis

•Clinical grounds

•Culture and Gram stain ofimplicated food

Treatment--self-limiting

GENUS: CLOSTRIDIUM

Genus Features

•Gram-positive rods

•Spore forming

•Anaerobic

Species ofMedical Importance

•Clostridium tetani

•Clostridium botulinum

•Clostridium perfringens

•Clostridium difficile

Clostridium tetani

DistinguishingFeatures

•Large gram-positive, spore-forming rods

•Anaerobes

•Produces tetanus toxin

Reservoir--soil

Transmission

•Puncture wounds/trauma (human bites)

•Requires low tissue oxygenation (Bi,)

Pathogenesis

•Spores germinate in the tissues, producingtetanustoxin (an exotoxin also called tetanospasmin).

•Carried intra-axonally to CNS

•Binds to ganglioside receptors

•Blocks release ofinhibitorymediators (glycine and GABA) at spinal synapses

•Excitatory neurons are unopposed extreme muscle spasm

•One ofthe most toxic substances known

Disease-tetanus

•Risus sardonicus

•Opisthotonus

•Extreme muscle spasms

Key Vignette Clues

Clostridium tetani

•Dirty puncture wound

•Rigid paralysis

Section II • Microbiology

Key Vignette Clues

Clostridium botulinum

•Home-canned alkaline vegetables

•Floppy baby syndrome (infant with flaccid paralysis)

•Reversible flaccid paralysis

Disease(s)

Table ll-2-18. Forms of Botulism

Clostridium difficile

Reservoir-human colon/gastrointestinal tract

Transmission-endogenous

Pathogenesis

•ToxinA: enterotoxin damagingmucosaleadingtofluidincrease; granulocyte attractant

•Toxin B: cytotoxin: cytopathic

Disease(s)-antibiotic-associated (clindamycin, cephalosporins, arnoxicillin, arnpicillin) diarrhea, colitis, or pseudomembranous colitis (yellowplaques on colon)

Diagnosis

•Culture is not diagnostic because organism is part ofnormal flora

•Stool exam for toxin production

Treatment

•Severe disease--etronidazole:m use vancomycin only if no other drug avail­ able; to avoid selecting forvancomycin-resistant normal flora

•Mild disease-discontinue other antibiotic therapy

Prevention

•Caution in overprescribing broad-spectrum antibiotics (limited-spectrum drugs should be considered first)

•In the nursing home setting, patients who are symptomatic should be iso­ lated.

•Autoclave bed pans (treatment kills spores)

Key Vignette Clues

Clostridium difficile

•Hospitalized patient on antibiotics

•Develops colitis, diarrhea

Key Vignette Clues

Listeria monocytogenes

•Gram (+), 13 hemolytic bacilli, cold growth

•Facultative intracellular

•Foodborne (deli foods)

•Transplacental-­ granulomatosis infantiseptica

•Neonatal septicemia and meningitis (third most common cause)

•Meningitis in renal transplant or cancer patients (most common cause)

GENUS: LISTERIA

Genus Features

•Gram-positive, non-spore forming rods

•Facultative intracellular

•Tumbling motility

Species ofMedical Importance--Listeria monocytogenes

Listeria monocytogenes

Distinguishing Features

•Small gram-positive rods

•Beta hemolytic, nonspore-forming rod on blood agar

•Tumbling motility in broth; actin jet motility in cells

•Facultative intracellular parasite

•Cold growth

Reservoir

•Widespread: animals (gastrointestinal and genital tracts), unpasteurized milk products, plants, and soil

•Cold growth: soft cheeses, deli meats, cabbages (coleslaw), hotdogs

Transmission---foodborne, vertical, or across the placenta

Pathogenesis

•Listeriolysin 0, a -hemolysin: facilitates rapid egress from phagosome into cytoplasm, thus evading killingwhen lysosomal contents are dumped into phagosome; "jets" directly (by actin filament formation) from cytoplasm to another cell

•Immunologicimmaturitypredisposes to serious infection.

Disease(s)

• Listeriosis (human, peaks in summer)

Healthy adults and children: generally asymptomatic or diarrhea with low % carriage

Pregnant women: symptomatic carriage, septicemia characterized by fever and chills; can cross the placenta in septicemia.

• Neonatal disease

Early-onset: (granulomatosis infantisepticum) in utero transmission; sep­ sis with high mortality; disseminated granulomas with central necrosis

Late-onset: 2-3 weeks after birth from fecal exposure; meningitis with septicemia

• In immunocompromised patients

Septicemia and meningitis (most common clinical presentation)

Listeria meningitis-most common cause of meningitis in renal trans­ plantpatientsand adultswith cancer

Key Vignette Clues

Corynebacterium diphtheriae

•Gram (+), aerobic, non-spore forming rods

•Bull neck, myocarditis, nerve palsies

•Gray pseudomembrane airway obstruction

•Toxin produced by lysogeny

•Toxin ribosylates eEF-2; heart, nerve damage

GENUS: CORYNEBACTERIUM

Genus Features

•Gram-positive rods

•Non-spore forming

•Aerobic

Species ofMedical Importance

•Corynebacterium diphtheriae

•Diphtheroids (normal flora)

Corynebacterium diphtheriae

Distinguishing Features

•Gray-to-black colonies of dub-shaped gram-positive rods arranged in

V or L shapes on Gram stain

•Granules (volutin) produced on Loeffler coagulated serum medium stain metachromatically

•Aerobic, non-spore forming

•Toxin-producing strains have -prophage carrying genes for the toxin

(lysogeny, -corynephage). The phage from one patient with diphtheria can infect the normal nontoxigenic diphtheroid of another person and cause diphtheria.

Reservoir--throat and nasopharynx

Transmission--bacterium or phage via respiratory droplets

Pathogenesis

•Organism not invasive; colonizes epithelium of oropharynx or skin in cuta­ neous diphtheria

•Diphtheriatoxin (A-B component)-inhibitsprotein synthesis byadding

ADP-ribose to eEF-2

•Effect on oropharynx: Dirty graypseudomembrane (made up of dead cells and fibrin exudate, bacterial pigment)

•Extension intolarynx/trachea obstruction

•Effect of systemic circulation heart and nerve damage

Disease-diphtheria (sore throatwith pseudomembrane,bullneck,potential respira­ tory obstruction, myocarditis, cardiac dysfunction, recurrentlaryngeal nerve palsy, and lower limb polyneuritis)

Diagnosis

•Elek test to document toxin production (ELISA for toxin is now the frontline)

•Toxin produced by toxin-producing strains diffuses away from growth.

•Antitoxin diffuses away from the strip of filter paper.

•Precipitin lines form at zone of equivalence.

Key Vignette Clues

•Patient with mycetoma on jaw line or spread from IUD

•Sulfur granules in pus grow anaerobic, gram (+), non-acid fast branching rods

GENUS: ACTINOMYCES

Genus Characteristics

•Anaerobic

•Gram-positive branching rods

•Non-acid fast

Species ofMedical Importance--Actinomyces israelii

Actinomyces israelii

Distinguishing Features

•Anaerobic

•Branching rods

•Non-acid fast

Reservoir-human; normal flora ofgingival crevices and female genitaltract

Transmission--ndogenous

Pathogenesis--invasive growth in tissues with compromised oxygen supply

Disease--actinomycosis

•Generally not painful but veryinvasive, penetrating all tissues, including bone

•Tissue swelling drainingabscesses (sinus tracts) with "sulfur" granules

(hard yellow microcolonies) in exudate that can be used for microscopy or culture

•Only in tissues with low oxygenation (Eh)

Cervicofacial (lumpyjaw): dentaltrauma or poor oral hygiene Pelvic: from thoracic or sometimes IUDs

Abdominal: surgery or bowel trauma

Thoracic: aspiration with contiguous spread

CNS: solitarybrainabscess (Nocardia will produce multiple foci)

Diagnosis

•Identify gram-positive branching bacilli in "sulfur granules"

•Colonies resemble molar tooth

Treatment-ampicillin or penicillin G and surgical drainage

GENUS: NOCARDIA

Genus Features

•Gram-positive filaments breaking up into rods

•Aerobic

•Partiallyacid fast (some areas ofsmear willbe blue and some red)

Species ofMedical Importance

•N. asteroides

•N. brasiliensis

Nocardia asteroidesand Nocardia brasiliensis

Distinguishing Features

•Aerobic

•Gram-positive branching rods

•Partially acid fast

Reservoir---soil and dust

Transmission--airborne or traumatic transplantation

Pathogenesis

•No toxins or virulence factors known

•Immunosuppressionand cancerpredispose to pulmonary infection

Disease(s)

• Nocardiosis

Cavitarybronchopulmonarynocardiosis

-Mostly N. asteroides

-Can be acute, subacute, chronic

Symptoms: cough, fever, dyspnea, localized or diffuse pneumonia with cavitation

-May spread hematogenously to brain (brain abscesses)

•Cutaneous/subcutaneous nocardiosis

Mostly N. brasiliensis

Starts with traumatic implantation

Symptoms: cellulitiswith swelling drainingsubcutaneous abscesses with granules (mycetoma)

Diagnosis--cultureofsputum or pus from cutaneous lesion

Treatment---sulfonamides (high dose) or trimethoprim/sulfamethoxazole (TMP-SMX)

Key Vignette Clues

Nocardia asteroides and

Nocardia brasiliensis

•Gram (+) filamentous bacilli, aerobic, partially acid fast

•Cavitary bronchopulmonary disease, mycetomas

Key Vignette Clues

Mycobacterium tuberculosis

•High-risk patient (poverty, HIV+, IV drug user)

•Chronic cough, weight loss

•Ghan complex

•Auramine-rhodamine staining, acid fast bacilli in sputum

•Produce niacin, heat-sensitive catalase

•Positive DTH test (PPD)

•Facultative intracellular

GENUS: MYCOBACTERIUM

Genus Features

•Acid fast rods with a waxy cell wall

•Obligate aerobe

•Cell wall

Unique: high concentration oflipids containing long chain fatty acids called mycolic acids

Wall makes mycobacteriahighlyresistant to:

0Desiccation

0Manychemicals (including NaOH used to killother bacteria in sputa before neutralizing and culturing)

Peptidoglycan (trilayer)

Cytoplasmic membrane

Cytoplasm

Figure 11-2-7. Mycobacterial Cell Envelope

• Sensitive to UV

Species ofMedical Importance

•M. tuberculosis

•M. leprae

•M. avium-intracellulare

•M. kansasii

•M. scrofulaceum

•M. marinum

Mycobacterium tuberculosis

Distinguishing Features

•Auramine-rhodamine stainingbacilli (fluorescent apple green); no anti­ body involved (sensitive but not specific)

•Acid fast

•Aerobic, slow growing on Lowenstein-Jensen medium; new culture systems

(broths with palmitic acid) faster

•Produces niacin

•Produces a heat-sensitive catalase

Catalase negative at 68.0°C (standard catalase test)

Catalase active at body temperature

Transmission-respiratory droplets

Pathogenesis

•Facultative intracellular organism

•Sulfatides (sulfolipids in cell envelope)

-Inhibit phagosome-lysosome fusion, allowing intracellular survival (if fusion occurs, waxy nature of cell envelope reduces killingect)eff

•Cordfactor (trehalose dimycolate)

Causes serpentine growth in vitro

Inhibits leukocyte migration; disrupts mitochondrial respiration and oxidative phosphorylation

•Tuberculin (surface protein) along with mycolic acid ----delayed7 hypersensi­ tivity and cell-mediated immunity (CMI)

Granulomas and caseation mediated by CMI

No exotoxins or endotoxin; damage done by immune system

Disease(s)

• Primary pulmonary tuberculosis

Organisms replicate in naive alveolar macrophages, killing the macro­ phages until CMI is set up (Ghon focus)

Macrophages transport the bacilli to the regional lymph node (Ghon complex) and most people heal without disease

Organisms that are walled off within the Ghon complex remain viable unless treated

• Reactivational tuberculosis

Erosion of granulomas into airways (high oxygen) later in life under conditions of reduced T-cell immunity leads to mycobacterial replication and disease symptoms

Complex disease with the potential of infecting any organ system May disseminate (miliary TB)

Diagnosis

•Microscopy of sputum: screen with auramine-rhodamine stain (fluorescent apple-green); no antibody involved; very sensitive; if positive, confirm with acid fast stain

•PPD skin test (Mantoux): measure zoneofinduration at48-72hours; positive if:

:;:::5mm in HIV+ or anyone with recent TB exposure; AIDS patients have reduced ability to mount skin test.

:;:::10 mm in high-risk population: IV drug abusers, people living in pov­ erty, or immigrants from high TB area

:;:::15 mm in low-risk population

•Positive skintestindicates only exposurebutnot necessarilyactive disease.

•Quantiferon-TB Gold Test: measures interferon-gamma production when leukocytes exposed to TB antigens

•Slow-growing (3-6weeks) colonies on Lowenstein-Jensen mediUill (faster new systems)

•Organisms produce niacin and are catalase-negative (68°C).

•No serodiagnosis

Figure 11-2-8.

Cord Factor

Mycobacterium /eprae

Distinguishing Features

•Acid fast rods (seen in punch biopsy)

•Obligate intracellularparasite (cannot be cultured in vitro)

•Optimal growth at less than body temperature

Reservoir

•Human mucosa, skin, and nerves are only significant reservoirs

•Some infected armadillos in Texas and Louisiana

Transmission-nasal discharge from untreatedlepromatous leprosy patients

Pathogenesis

•Obligateintracellular parasite

•Cooler parts of body, e.g., skin, mucous membranes, and peripheral nerves

Disease(s)-leprosy: a continuum ofdisease, which usually starts out with an indeter­ minate stage called "borderline"

Diagnosis

•Punchbiopsyornasal scrapings; acidfast stain

•Leprominskintestis positive in the tuberculoid but not in the lepromatous

form

• No cultures

Treatment-multiple-drug therapy with dapsone and rifampin, with clofazirnine added for lepromatous

Prevention-dapsone for close family contacts

Note

•M. tuberculosis in HIV patient with normal count or low CD4 count (dis­ seminated)

•MAI only in late HIV patient with low CD4 count

Key Vignette Clues

Leprosy

•Acid fast bacilli in punch biopsy

•Immigrant patient with sensory loss in extremities

MEDICAL 245

Neisseria gonorrhoeae

Distinguishing Features

• Gram-negative, kidney bean-shaped diplococci

Reservoir-human genital tract

Transmission

•Sexual contact, birth

•Sensitive to drying and cold

Pathogenesis

•Pili

-Attachment to mucosa! surfaces

-Inhibitphagocytic uptake

-Antigenic (immunogenic) variation: >1 million variants

•Outer membrane proteins

-OMP I: structural, antigen used in serotyping

-Opa proteins (opacity): antigenicvariation, adherence

-IgA protease: aids in colonization and cellular uptake

•Organism invadesmucosalsurfaces andcauses inflammation.

Disease--gonorrhea

•Male: urethritis, proctitis

•Female: endocervicitis, PID (contiguous spread), arthritis, proctitis

•Infants: ophthalmia (rapidly leads to blindness ifuntreated)

Key Vignette Clues

Neisseria gonorrhoeae

•Sexually active patient

•Urethral/vaginal discharge (leukor- rhea)

•Arthritis possible

•Neonatal ophthalmia

•Gram (-) diplococcus in neutrophils

GRAM-NEGATIVE BACILLI

GENUS: PSEUDOMONAS

Genus Features

•Gram-negative rod

•Oxidase-positive

•Aerobic (nonfermenting)

Species ofMedical Importance-Pseudomonas aeruginosa

Pseudomonas aeruginosa

Distinguishing Features

•Oxidase-positive, Gram-negative rods, nonfermenting

•Pigments: pyocyanin (blue-green) and fluorescein

•Grape-like odor

•Slime layer

•Non-lactose-fermenting colonies on EMB or MacConkey

Reservoir-ubiquitous in water

Transmission-water aerosols, rawvegetables, flowers

Pathogenesis

•Endotoxin causes inflammation in tissues and gram-negative shock in sep­ ticemia.

•Pseudomonas exotoxin A ADP ribosylates eEF-2,inhibiting protein syn­ thesis (like diphtheria toxin)

•Liver is the primary target.

•Capsule/slime layer: allows formation ofpulmonary microcolonies; diffi­ cult to removeby phagocytosis

Disease(s)

• Healthy people

- Transient gastrointestinal tract colonization: loose stools (10% population) Hot tub folliculitis

-Eye ulcers: trauma, coma, or prolonged contact wear

•Burn patients

-Gastrointestinal tract colonization skin colonization ofeschar cellulitis (blue-green pus) septicemia

•Neutropenic patients

-Pneumonia and septicemias---often superinfections (infections while on antibiotics)

•Chronicgranulomatous disease (CGD)

-Pneumonias, septicemias (Pseudomonas is catalase positive)

Key Vignette Clues

Pseudomonas

•Gram (-), oxidase (+), aerobic bacillus

•Blue-green pigments, fruity odor

•Burn infections-blue-green pus, fruity odor

•Typical pneumonia-CGD or CF

•UTl-catheterized patients

Note

Pseudomonas Medical Ecology

Pseudomonas aeruginosa is a ubiquitous water and soil organism that grows to very high numbers overnight in standing water (distilled or tap).

Sources for infections include:

•Rawvegetables, respirators, humidi­ fiers, sink drains, faucet aerators, cut and potted flowers, and, if not properly maintained, whirlpools.

•Transient colonization of colons of about 10% of people. Bacteria get on skin from fecal organisms. Requires exquisitely careful housekeeping and restricted diets in burn units.

Section II • Microbiology

Note

Drug Resistance in P. aeruginosa

Susceptibilities important.

Drug resistance very common:

Intrinsic resistance (missing high affin­ ity porin some drugs enter through); Plasmid-mediated 13-lactamases and acetylating enzymes.

•Septicemias

-Fever, shock ± skin lesions (black, necrotic center, erythematous margin, ecthyma gangrenosum)

•Catheterized patients

-Urinary tract infections (UTis)

•Cystic fibrosis

Early pulmonary colonization, recurrent pneumonias; always high slime­ producing strains

Diagnosis-Gram stain and culture

Treatment-antipseudomonal penicillin and an aminoglycoside

Prevention

•Pasteurization or disinfection of water-related equipment, hand washing; prompt removal of catheters

•No flowers or raw vegetables in burn units

GENUS: LEG/ONELLA

Genus Features

•Weakly gram-negative

•Pleomorphic rods requiring cysteine and iron

•Water organisms

Species of Medical Importance-Legionella pneumophila

Legionella pneumophi/a

Distinguishing Features

•Stain poorlywith standard Gram stain; gram-negative

•Fastidious requiring increased iron and cysteine for laboratory culture (CYE, charcoal yeast extract)

•Facultative intracellular

Reservoir-rivers/streams/amebae; air-conditioning water cooling tanks

Transmission

•Aerosols from contaminated air-conditioning

•No human-to-human transmission

Predisposing Factors

•Smokers over 55 years with high alcohol intake

•Irnmunosuppressed patients, e.g., renal transplant patients

Pathogenesis

•Facultative intracellular pathogen

•Endotoxin

Disease(s)

• Legionnaires disease ("atypical pneumonia")

Associated with air-conditioning systems, now routinely decontaminated Pneumonia

Mental confusion

Diarrhea (no Legionella in gastrointestinal tract)

• Pontiac fever Pneumonitis No fatalities

Diagnosis

•Diagnosis: DFA (direct fluorescent antibody) on biopsy, (+) by Dieterle sil­ ver stain

•Antigen urine test for one serogroup only

•Fourfold increase in antibody

Treatment

•Fluoroquinolone or azithromycin or erythromycin with rifampin for immunocompromised patients

•Drug must penetrate human cells.

Prevention-routine decontamination of air-conditioner cooling tanks

Key Vignette Clues

Legionella pneumophila

•Elderly smoker, heavy drinker, or im­ munosuppressed

•Exposure to aerosols ofwater

•Atypical pneumonia

Section II • Microbiology

Key Vignette Clues

Francisella tularensis

•Hunter with ulceroglandular disease, atypical pneumonia, or gastrointesti­ nal disease

•Arkansas/Missouri

•Exposure to rabbits, deer, ticks

GENUS: FRANC/SELLA

Genus Features

•Gram-negative small rods

•Facultative intracellular pathogen

Species of Medical Importance-Francisella tularensis

Francise/la tularensis

Distinguishing Features

•Small gram-negative rod

•Potential biowarfare agent

•Zoonosis

Reservoir-many species ofwild animals, especially rabbits, deer, and rodents

Transmission

• Tickbite (Dermacentor) ulceroglandular disease, characterized by fever, ulcer at bite site, and regional lymph node enlargement and necrosis

•Traumatic implantation while skinning rabbits ulceroglandular disease

•Aerosols (skinning rabbits) pneumonia

•Ingestion (of undercooked, infected meat or contaminated water) produces

typhoidal tularemia.

Pathogenesis

•Facultative intracellular pathogen (localizes in reticuloendothelial cells)

•Granulomatous response

Disease

•Tularemia

-Endemic in every state of the U.S.

-Highest in Arkansas and Missouri

Diagnosis

•Serodiagnosis; culture is hazardous.

•DFA

Treatment-streptomycin

Prevention

•Protect against tick bites, gloves while butchering rabbits

•Live, attenuated vaccine for persons in high risk

GENUS: BORDETELLA

Genus Features

•Gram-negative small rods

•Strict aerobes

Species ofMedical Importance-Bordetella pertussis

Key Vignette Clues

Bordetel/a pertussis

•Unvaccinated child (immigrant family or religious objections)

•Cough with inspiratory "whoop"

Bordetella pertussis

Distinguishing Features

•Small gram-negative, aerobic rods

•Encapsulated organism

Reservoir-human (vaccinated)

Transmission-respiratory droplets

Pathogenesis

•B. pertussis is a mucosa! surface pathogen.

•Attachmentto nasopharyngeal ciliated epithelial cells is via:

-Filamentous hemagglutinin

-Pertussis toxin (on outer membrane) aids in attachment.

•Toxins damage respiratory epithelium.

Adenylate cyclase toxin: impairs leukocyte chemotaxis inhibits phago­ cytosis and causes local edema

Tracheal cytotoxin: interferes with ciliary action; kills ciliated cells Endotoxin

Pertussis toxin (A and B component, OM protein toxin): ADP ribosyl­ ation of Gi (inhibiting negative regulator of adenylate cyclase) interferes with transfer of signals from cell surface to intracellular mediator system.

0Lymphocytosis promotion

0Islet-activation hypoglycemia

0Blocks immune effector cells

0Increased histamine sensitivity

In a Nutshell

B. pertussis Immunity

•Vaccine immunity lasts 5-10 years (and is primarily lgA)

•Babies born with little immunity.

•Vaccinated humans >10 yrs serve as reservoir.

•12-20% of afebrile adults with cough >2 weeks have pertussis.

•Immunity to actual pertussis is life long.

•New vaccines (DTaP)

•Acellular

•Components:

-lmmunogens vary by manufacturer

-Pertussis toxoid

-Filamentous hemagglutinin

-Pertactin (OMP)

1 other

GENUS: BRUCELLA

Genus Features

•Gram-negative rods, aerobic

•Zoonosis

•Facultative intracellular pathogen

•Potential biowarfare agent

Species of Medical Importance

•Brucella abortus: cattle

•Brucella melitensis: goats

•Brucella suis: pigs

Brucella Species

Distinguishing Features

•Small gram-negative rods, aerobic

•Facultative intracellular

•Serological confirmation of disease most common

•Culture is hazardous.

•Potential biowarfare agent

Reservoir-domestic livestock

Transmission

• Unpasteurized dairyproducts (California and Texas highest number of cases; most associated with travel to Mexico)

• Direct contact with the animal, work in slaughterhouse

Pathogenesis

•Endotoxin

•Facultative intracellular parasite (localizes in cells of the RES, reticuloen­ dothelial system) septicemia

•Granulomatous response with central necrosis

Disease

•Brucellosis (undulant fever)

Acute septicemias

Fever 100-104°F (often in evening)

-Influenza-like symptoms, including arthralgias, anorexia, myalgia, back pain

-Sweating (profuse) Hepatomegaly

•Undulant form

-Milder, often a result of incomplete treatment

•Chronic form (disease for more than one year)

Usually B. melitensis

-Usually in older people (veterinarians) Cyclic bouts of depression and sweating

Key Vignette Clues

Bruce/la

•Patient with acute septicemia

•Exposure to animals or unpasteurized dairy

•California/Texas or travel to Mexico

Note

Zoonotic Organisms

•Bruce/la

•Bacillus anthracis

•Listeria monocytogenes

•Salmonella enteritidis

•Campylobacter

•Chlamydophila psittaci

•Francisella tularensis

•Yersinia pestis

GENUS: CAMPYLOBACTER

Genus Features

•Gram-negative curved rods with polar flagella ("gulls' wings")

•Oxidase-positive

Figure 11-2-9.

Campylobacter

Species ofMedical Importance-Campylobacterjejuni

Campylobacterjejuni

Distinguishing Features--microaerophilic, grows well at 42.0°C on selective media (Campy medium or Skirrow agar)

Reservoir-intestinal tracts ofhumans, cattle, sheep, dogs, cats, poultry

Transmission-fecal-oral, primarily from poultry

Pathogenesis

•Low infectious dose (as few as 500)

•Invades mucosa of the colon, destroying mucosal surfaces; blood and pus in

stools (inflammatory diarrhea)

• Rarely penetrates to cause septicemia

Disease

• Gastroenteritis

Common cause of infectious diarrhea worldwide

In U.S., Campylobacter enteritis > (Salmonella plus Shigella)

-Ten or more stools/day, may be frankly bloody

-Abdominal pain, fever, malaise, nausea, and vomiting Generally self-limiting in 3-5 days but may last longer

-Complications

0Guillain-Barre syndrome (GBS) -7 30% of the GBS in the U.S. Serotype 0:19, antigenic cross-reactivity between Campylobacter

oligosaccharides and glycosphingolipids on neural tissues

0Reactive arthritis

Diagnosis

• Culture on Campylobacter or Skirrow agar at 42°C

Treatment

•Mostly supportive via fluid and electrolyte replacement

•Erythromycin, fluoroquinolones, penicillin resistant

Key Vignette Clues

Campy/obacterjejuni

•Patient with inflammatory diarrhea

•Gram (-), curved rod, microaerophilic, oxidase (+), grows at 42°(

Section II • Microbiology

Key Vignette Clues

Helicobacterpylori

•Patient with gastritis, ulcers, stomach cancer

•Gram (-), helical bacilli, oxidase (+), microaerophilic, urease (+)

GENUS: HELICOBACTER

Genus Features

•Gram-negative spiral gastric bacilli with flagella

•Microaerophilic, 37.0°C growth (Campy medium or Skirrow agar); oxidase positive

Species of Medical Importance-Helicobacterpylori

Helicobacterpylori

Distinguishing Feature--urease positive

Reservoir-humans

Transmission

•Fecal-oral

•Oral-oral

Pathogenesis

•Motile

•Urease-positive: ammonium cloud neutralizes stomach acid, allowing sur­

vival in stomach acid during transit to border.

• Mucinase aids in penetration of mucous layer (rapid shift down to neutral as it penetrates).

•Invasive into stomach lining where pH is neutral

•Inflammation is prominent.

•Two biotypes (I and II); type I produces vacuolating cytotoxin.

Diseases

•Chronic gastritis and duodenal ulcers

-Associated with several forms of stomach cancer (gastric adenocarcino­ ma, gastric mucosa-associated lymphoid tissue lymphoma [MALT-oma] , B-cell lymphomas)

-Now classed by WHO as type I carcinogen

Diagnosis

•Biopsy with culture; histology with Giemsa or silver stain

•Breath test: 13C-urea swallowed; ammonia+13C-C02 exhaled

•Serology

Treatment

• Myriad of regimens

Omeprazole + amoxicillin + clarithromycin is one example of triple therapy.

Treat for 10-14 days.

Quadruple therapy is used in areas where clarithromycin resistance is

15%, e.g., PPI + bismuth + 2 antibiotics (metronidazole + tetracycline)

GENUS: VIBRIO

Genus Features

•Gram-negative curved rod with polar flagella

•Oxidase positive

•Vibrionaceae

•Growth on alkaline, but not acidic, media (TCBS, thiosulfate citrate bile salt sucrose medium)

Species of Medical Importance

•Vibrio cholerae

•Vibrio parahaemolyticus

•Vibrio vulnificus

Vibrio cholerae

Distinguishing Features

•Vibrio cholerae 01 is divided into biotypes El Tor (predominant now) and Cholerae (classic).

•Vibrio cholerae 0139 also produces cholera toxin.

•"Shooting star" motility inactivated by specific serum

Reservoir

•Human colon; no vertebrate animal carriers (copepods or shellfish may be contaminated bywater contamination)

•Human carriage maypersist after untreated infection for months after infection; permanent carrier state is rare.

Transmission

•Fecal-oral spread; sensitive to stomach acid

•Requires high dose (> 107 organisms), ifstomach acid is normal

Pathogenesis

• Motility, mucinase, and toxin coregulated pili (TCP) aid in attachment to the intestinal mucosa.

• Cholera enterotoxin (choleragen) similar to E. coli LT; ADP ribosylates (G5 alpha) activating adenylate cyclase --7 increased cAMP --7 efflux of c1-and H20 (persistent activation of adenylate cyclase)

Disease

• Cholera

Rice water stools, tremendous fluid loss

Hypovolemic shock ifnot treated

Diagnosis

•Culture stool on TCBS

•Oxidase positive

Key Vignette Clues

Vibrio cholerae

•Patient with noninflammatory diarrhea

•Rice-water stool

•Dehydration

•Travel to endemic area

•Gram (-) curved rods, polar flagellae, oxidase (+)

•Alkaline growth

Note

E.coli identification from stool

•Isolation of £. coli from feces is not by itself significant.

•Sorbitol MacConkey screen

•Most E. coli ferment sorbitol.

•Most EHEC do not (colorless)

Animal models and tissue culture assays may be used, but other methods of dif­ ferentiating pathogenic

E. coli from normal flora are more com­ monly:

•Immunoassay looking for specific protein antigens (on or excreted by the bacterium)

•Serotyping since certain serotypes are more often pathogenic

•DNA probes for specific genes in a culture

•PCR on clinical specimen

Mnemonic

Toxins icAMP

c = cholera A = anthrax

= E . coli LT P = pertussis

Mnemonic

PITcH

GENUS: ESCHERICHIA

Genus Features

•Gram-negative rods

•Enterobacteriaceae

•Ferinents lactose

Species ofMedical Intportance-Escherichia coli

Escherichia coli

Distinguishing Features

•Gram-negative rod

•Facultative anaerobic, oxidase negative

•E. coli is a lactose ferinenter: colonies with iridescent green sheen on EMB

Reservoir

•HUinan colon; may colonize vagina or urethra

•Contaminated crops where human fecal fertilizer is used

•Enteroheinorrhagic strains: bovine feces

Transmission

•Endogenous

•Fecal-oral

•Maternal fecal flora

•Enterohemorrhagic strains: bovine fecal contamination (raw or under­ cooked beef, milk, apple juice from fallen apples)

Pathogenesis-listed under specific diseases

Transmission

UTI (most common cause)

Endogenous fecal flora contaminate and ascend

EPEC (second most common infantile diarrhea)

Fecal/oral

EIEC

Fecal/oral

Adherence to M cells rearrangement of actin and effacement of brush border microvilli

Invades large bowel

Inflammatory diarrhea; similar to shigel- losis, induces formation of actin jet trails

Inflammatorydiarrhea, blood, pus, fever, abdominal pain

EHEC (VTEC}-0157:H7 most common

Bovine feces, petting zoos

Verotoxin-Shigella-like toxins 1 and 2, J, protein synthesis by interfering with 605 ribosomal subunit

EAEC

Fecal/oral

DAEC

Fecal/oral

Key Vignette Clues

Klebsiella pneumoniae

•Elderly patient with typical pneumo­ nia: currant-jelly sputum

•UTI (catheter associated)

•Septicemia: immunocompromised or nosocomial

•Gram (-) bacilli,

oxidase (-), encapsulated, lactose fermenters

In a Nutshell

Comparative Microbiology:

Major encapsulated organisms

ome illers Have eretty Nice Capsules:

Strep pneumoniae

Klebsiella pneumoniae

f!aemophi/us influenzae Type b (a-d)

f!seudomonas aeruginosa

f!eisseria meningitidis

£ryptococcus neoformans (the yeast)

(Not a complete list, just the big ones.)

264 MEDICAL

GENUS: KLEBSIELLA

Genus Features

•Gram-negative rods

•Enterobacteriaceae

•Major capsule

Species ofMedical hnportance

• Klebsiella pneumoniae

K/ebsiella pneumoniae

Distinguishing Features

•Gram-negative rods with large polysaccharide capsule

•Mucoid, lactose-fermenting colonies on MacConkey agar

•Oxidase negative

Reservoir-human colon and upper respiratory tract

Transmission-endogenous

Pathogenesis

•Capsule: impedes phagocytosis

•Endotoxin: causes fever, inflammation, and shock (septicemia)

Disease(s)

• Pneumonia

Community-acquired, most often in older males; most commonly in patients with either chronic lung disease, alcoholism, or diabetes (but this is not the most common cause ofpneumonia in alcoholics;

S. pneumoniae is.)

Endogenous; assumed to reach lungs by inhalation ofrespiratory drop­ lets from upper respiratory tract

Frequent abscesses make it hard to treat; fatalityrate high

Sputum is generallythickand bloody (currantjelly) but not foul smelling as in anaerobic aspiration pneumonia.

•Urinary tract infections-catheter-related (nosocomial) from fecal con­ tamination ofcatheters

•Septicemia-in immunocompromised patients, may originate from bowel defects or invasion of IV lines

Diagnosis

•Culture ofsputum or clean catch urine sample

•Lactose fermenter

Treatment

•Third-generation cephalosporin with or without an aminoglycoside

•Fluoroquinolones may also be used.

Preventio ood catheter care,limit use

GENUS: SHIGELLA

Genus Features

•Gram-negative rod

•Enterobacteriaceae

•Non-lactose fermenters (colorless colonies on EMB or MacConkey)

•Nonmotile

Species ofMedical Importance

•Shigella sonnei (most common in U.S.)

•Shigella flexneri

•Shigella dysenteriae (most severe disease)

•Shigella boydii

Shigella Species

Distinguishing Features

•Gram-negative rods, nonmotile

•Identified by biochemical reactions or by serology with anti-0 antibody in agglutination test

Reservoir-human colon only (no animal carriers)

Transmission--fecal-spread,oral person to person

Pathogenesis

•Endotoxin triggers inflammation.

•No H antigens

•Shigellae invade M cells (membrane ruffling and macropinocytosis), get into the cytoplasm, replicate, and then polymerize actinjet trails to go lat­ erallywithout going back out into the extracellular milieu. This produces veryshallowulcers and rarely causes invasion of blood vessels.

•Shiga toxin:

Produced by S. dysenteriae, type 1

-Three activities: neurotoxic, cytotoxic, enterotoxic

AB componenttoxin is internalized in human cells; inhibits protein synthesis by clipping 60S ribosomal subunit

Disease(s)

• Enterocolitis/shigellosis (most severe form is dysentery)

Few organisms required to start infection ( 1-10) (extremely acid resistant)

-1-4 day incubation

-Organisms invade, producing bloody diarrhea.

Fever (generally >10l.0°F); lower abdominal cramps; tenesmus; diar­ rhea first watery, then bloody; invasive but rarely causes septicemia; shallow ulcers

Severity depends on the age of patient and the strain; S. dysenteriae type 1 with toxin most severe

Diagnosis-isolation from stool during illness and culture on selective media

Note

Comparative Microbiology

•Invasive bacteria: PMN in stool: Shi· gel/a, Salmonella, Campylobacter, EIEC.

•Toxigenic bacteria: ETEC, V. cholera, Cl. perfringens, EHEC.

Key·Vignette Clues

Shigella

•Patient with acute bloody diarrhea and fever

•Gram (-) bacilli, which are nonmotile, nonlactose fermenters, do not produce H2S

GENUS: YERSINIA

Genus Features

•Gram-negative rods

•Enterobacteriaceae

Species of Medical Importance

•Yersinia pestis

•Yersinia enterocolitica

Yersinia pestis

Distinguishing Features

•Small gram-negative rods with bipolar staining

•Facultative intracellular parasite

•Coagulase positive

Reservoir

•Zoonosis

•U.S. desert southwest: rodents (e.g., prairie dogs, chipmunks, squirrels)

•Potential biowarfare agent

Transmission

•Wild rodents flea bite ---sylvatic7 plague

•Human-to-human transmission by respiratory droplets

Pathogenesis

•Coagulase-contaminated mouth parts of flea

•Endotoxin and exotoxin

•Envelope antigen (F-1) inhibits phagocytosis.

•Type III secretion system suppresses cytokine production and resists phago­ cytic killing

Disease(s)

•Bubonic plague

-Flea bites infected animal and then later uninfected human

-Symptoms

0 Rapidly increasing fever

0 Regional buboes

° Conjunctivitis

0 Leads to septicemia and death if untreated

•Pneumonic plague

-Arises from septic pulmonary emboli in bubonic plague or inhalation of organisms from infected individual

-Highly contagious!

KeyVignette Clues

Yersiniapestis

•Patient with high fever, buboes, con­ junctivitis, pneumonia

•Exposure to small rodents, desert Southwest

Section II • Microbiology

Key Vignette Clues

Yersinia enterocolitica

•Patient with inflammatory diarrhea or pseudoappendicitis

•Cold climates

•Unpasteurized milk, pork

•Gram (-) bacilli, non-lactose fermen­ ters, non-H2S producers

Diagnosis

•Clinical specimens and cultures are hazardous.

•Serodiagnosis or direct immunotluorescence

•"Safety pin'' staining

Treatment-aminoglycosides

Prevention

•Animal control; avoid sick and dead animals.

•Killed vaccine (military)

Yersinia enterocolitica

Distinguishing Features

•Motile at 25.0°C, nonmotile at 37.0°C

•Cold growth

Reservoir-zoonotic

Transmission

•Unpasteurized milk, pork

•Prominent in northern climates (Michigan, Scandinavia)

Pathogenesis

•Enterotoxin, endotoxin

•Multiplies in the cold

Disease(s)

•Enterocolitis

- Presentations mayvarywith age

0Very young: febrile diarrhea (blood and pus)

0Older kids/young adults: pseudoappendicitis (also caused by Yersinia pseudotuberculosis)

0Adults: enterocolitis with postinfective sequelae like reactive arthritis

•Blood transfusion-associated infections

Diagnosis-stool culture, 25°C, cold enrichment

Treatment

•Usually supportive care

•For immunocompromised: fluoroquinolones or third-generation cephalo­ sporins

GENUS: PROTEUS

Genus Features

•Gram-negative rod

•Enterobacteriaceae

•Peritrichous flagella/highly motile/"swarming motility"

•Non-lactose-fermenting

•Urease positive

Species of Medical Importance

•Proteus mirabilis (90% ofinfections)

•Proteus vulgaris

Proteus mirabilis/Proteus vulgaris

Distinguishing Features

•Gram-negative rods

•Highly motile; "swarming" motility on surface ofblood agar

•Urease produced

•Facultative anaerobe (Enterobacteriaceae), oxidase negative

Reservoir-human colon and environment (water and soil)

Transmission-endogenous

Pathogenesis

•Urease raises urine pH to cause kidney stones (staghorn renal calculi).

•Motility may aid entry into bladder.

•Endotoxin causes fever and shock when septicemia occurs.

Disease(s)

•Urinarytract infections

•Septicemia

Diagnosis-culture ofblood or urine for lactose-negative organismswith swarming motility.

Treatment

•Fluoroquinolones, TMP-SMX, or third-generation cephalosporin for uncomplicated UTis

•Remove stones, if present.

Prevention-promptly remove urinarytract catheters.

Key Vignette Clues

Proteus mirabilis/Proteus vulgaris

•Patient with UTI or septicemia

•Swarming motility

•Staghorn renal calculi (struvite stones)

•Gram (-), non-lactose fermenting, ure­ ase (+)

Note

Weil-Felix test: antigens of OX strains of Proteus vulgaris cross-react with rickett­ sial organisms.

Section II • Microbiology

Key Vignette Clues

Salmonella enterica subsp. typhi

•Patient with fever, abdominal pain

•Travel to endemic area

•Gram (-), encapsulated, nonlactose fermenter, produces H25 gas

•Wida! test

GENUS: SALMONELLA

Genus Features

•Gram-negative rods (Enterobacteriaceae)

•Non-lactose fermenters

•Motile

•More than 2,400 serotypes ofsalmonellae

•Salmonellae are named by genus (Salmonella), species (enterica), and sub­ species (e.g., typhi or enteritidis).

Species ofMedical Importance

•S. enterica subsp. typhi

•S. enterica subsp. enteritidis

•S. enterica subsp. typhimurium

•S. enterica subsp. choleraesuis

•S. enterica subsp. paratyphi

•S. enterica subsp. dublin

Salmonella entericaSubsp. typhi

Distinguishing Features

•Gram-negative rods, highly motile with the Vi capsule

•Facultative anaerobe, non-lactose fermenting

•Produces H2S

•Species identification with biochemical reactions

•Sensitive to acid

Reservoir

• Humans only; no animal reservoirs

Transmission

•Fecal-oral route from human carriers (gall bladder)

•Decreased stomach acid or impairment ofmononuclear cells such as in sickle cell disease predisposes to Salmonella infections

Pathogenesis and Disease

•Typhoid fever (enteric fever), S. typhi (milder form: paratyphoid fever; S. paratyphi)

-Organism ingested (requires large number ifstomach acid is normal)

-Infection begins in ileocecal region; constipation common

-Host cell membranes "ruffle" from Salmonella contact.

Salmonella reach basolateral side ofM cells, then mesenteric lymph nodes and blood (transient l' septicemia)

-At 1 week: patients have 80% positive blood cultures; 25% have rose spots (trunk/abdomen)

Liver and spleen are infected with additional release ofbacteria to bloodstream signs ofsepticemia (mainly fever).

Salmonella entericaSubspecies Other Than typhi (S. enteritidis, S. typhimurium)

Distinguishing Features

•Facultative gram-negative rods, non-lactose-fermenting on EMB, MacConkey medium

•Produces H2S, motile (unlike Shigella)

•Speciated with biochemical reactions and serotyped with 0, H, and Vi anti­ gens

•Antibodies to 0, Vi, and H antigens in patient's serum can be detected by agglutination (Widal test)

Reservoir-enteric tracts ofhumans and domestic animals, e.g., chickens and turtles

Transmission

•Largely through chicken products (raw chicken and eggs) in the kitchen

•Reptile pets--snakes, turtles

Pathogenesis

•Sensitive to stomach acid (infectious dose 105 organisms)

•Lowered stomach acidity (antacids or gastrectomy) increases risk.

•Endotoxin in cell wall; no exotoxin

Key Vignette Clues

Salmonella enterica Subspecies Other Than typhi

•Enterocolitis-inflammatory, follows ingestion of poultry products or han­ dling pet reptiles

•Septicemia-very young or elderly

•Osteomyelitis-sickle cell disease

•Gram (-) bacillus, motile, non-lactose fermenter, produces H2S

•Wida! test

GENUS: HAEMOPHILUS

Genus Features

•Gram-negative, pleomorphic rod

•Requires growth factors factors X (hemin) and V (NAD) for growth on nutrient or blood agar (BA)

•Grows near S. aureus on BA = "satellite" phenomenon

•Chocolate agar provides both X andV factors.

Species of Medical Importance

•Haemophilus influenzae

•Haemophilus ducreyi

Haemophilus influenzae

Distinguishing Features

•Encapsulated, gram-negative rod; 95% ofinvasive disease caused by capsular type b

•Fastidious: requires factors X andV

Reservoir-human nasopharynx

Transmission-respiratory droplets, shared toys

Pathogenesis

•Polysaccharide capsule (type b capsule is polyribitol phosphate) most importantvirulence factor

•Capsule importantin diagnosis; antigen screen on CSF (e.g.,latexparticle agglutination); serotype all isolates by quellung.

•IgA protease is a mucosal colonizing factor.

Diseases

•Meningitis