Problem-Based Microbiology

2008

(4) DiphtheriaCorynebaterium diphtheriae

• Recent emigrant w/ unknown immunizations

• Yellowish, leathery thick membrane in pharynx

• “Bull neck” – bilateral cervical adenopathy

• Gm+ clubs, non-motile, non-hemolytic, catalase+, aerobic

• Tellurite medium• Diptheria toxin

• Diphtheria A-B exotoxin affects Elongation Factor 2 blocking protein synthesis leading to cell necrosis

• Upper respiratory droplets, direct contact

• Tx: Diptheria antitoxin

(10) Bacterial pneumoniaKlebsiella pneumoniae

• Alcoholic, homeless• Thick, blood-tinged

sputum (currant jelly)• RUL infiltrate with

cavitary lesion (abscess)

• Gm- short plump bacilli• Lactase+, Urease+,

Indole-• Capsular polysacchride

(CPS), K antigen

• Most common Gm- pneumonia, nosocomial

• CPS are antiphagocytic, molecular mimicry with C3b and prevents alternative complement pathway, inflammation

• Aspiration pneunomia

• Tx: Piperacillin

(15) Post-Primary TuberculosisMycobacterium tuberculosis

• Recent emigrant• Fever, cough, night sweats,

weight loss• Chronic cough w/ blood-

tinged sputum• RUL infiltrates

• Acid-fast, long bacilli cord• Multinucleated giant cells• Cord Factor, phenolic

glycolipids (LAM)

• Infects macrophages (recognize LAM) inhibits phagolysosome fusion, cord factor damages PMNs, form granulomas w/ large multinucleated giant cells

• Airborne transmission

• Tx: Isoniazid+Rifampin+ Pyrazinamide+Ethambutol empirically, later INH+RIF only if susceptible

(17) HistoplasmosisHistoplasma capsulatum

• 5 workers demolish building near Ohio river

• Pigeon droppings• Multiple nodular

infiltrates, cavitary lesion in RML, popcorn calcification

• Mold in soil, yeast in humans

• Giemsa, Wright stains

• Yeasts grow in inactivated macrophages (histiocyte) causing granuloma formation, disseminate via lymph, cytokines

• Ohio/Mississippi river valleys, soil with bat/bird droppings

• Tx: Itraconazole (Amphotricin B if severe)

(18) BlastomycosisBlastomyces dermatitidis

• Tennessee landscaper• Painful R arm verrucous

skin lesion, pustular• Multiple nodular

cavitating lesions in LUL• Unresponsive to

cefuroxime/erythromycin

• White fluffy mold, large budding yeast in humans

• Neutrophils recruited forming suppurative/ granulomatous inflammation, focal microabscesses in papillary dermis

• SE US, wooded areas

• Tx: Itraconazole (Amphotericin B if severe)

(19) CoccidioidomycosisCoccidioides immitis

• Recently visited Arizona• Erythema nodosum on

back• Infiltrates in both lungs,

large cavity in RUL

• Branching septate hyphae mold in soil, non-budding spherules in humans forming endospores

• Spherule in terminal bronchiole causes chronic granulomatous inflammation, can disseminate to skin

• SW US, arid soil around rodent burrows

• Tx: Itraconazole (Amphotericin B if severe)

(22) Pneumocystis PneumoniaPneumocystis jiroveci

• Has AIDS with thrush• Bilateral air-space

consolidation with interstitial/alveolar markings “ground glass”

• Fungus, 5-8 um cysts containing intracystic sporozoites

• Giemsa, Silver, DFA stain

• Adhere to Type I pneumocytes, cysts rupture and fill alveoli, decrease surfactant secretion forming foamy exudate

• Immunocompromised

• Tx: TMP-SMX

(26) Secondary SyphilisTreponema pallidum

• Multiple sexual partners• Hx of painless ulcers on

vulva• Maculopapular rash on

palms and soles, pustular lesions and condylomata lata on face

• Spirochetes, obligate human pathogens

• Lipoproteins• RPR, VDRL tests

• Chancre, indurated painless ulcer, indicated in primary syphilis.

• Spread by lymph and blood leads to a maculopapular rash in secondary syphilis.

• Neurosyphilis (teritiary)• Sexual, congenital spread

• Tx: Penicillin G (doxycycline if allergic)

(30) ChlamydiaChlamydia trachomatis

• Multiple sexual partners• Lower abd pain, vaginal

discharge, dysuria, cervical motion tenderness

• Pelvic Inflammatory Disease

• Gm- cell layers w/ LPS• Serotypes D-K most

common

• Most frequently reported STD in US

• Elementary bodies (EB) enter columnar epithelial cells of cervix becoming reticulate bodies (RB) which multiply and release EBs, inflammation

• Tx: Doxycycline (and cefoxitin for anerobes)

(31) TrichomoniasisTrichomonas vaginalis

• Sexually promiscuous• Yellow, foamy vaginal

discharge with foul odor• “Strawberry cervix”

• Motile, pear shaped• Human-only host• Fishy odor with KOH test• No stippled “clue cells”

• Inflammatory response (vaginitis) with PMNs present, direct damage causes microulcerations, increased vaginal pH

• Most men asymptomatic

• Tx: Metronidazole

(32) Candidiasis (Yeast Infection)Candida albicans

• Thick whitish vaginal discharge

• Vulvar itching• Denys sexual activity• Recent ATB use

• Yeast with pseudohyphae, produce chlamydospores

• Yeast cell cultivation in human serum yields distinctive germ tubes

• With disruption of normal flora, C. albicans overgrows on muco-cutaneous surfaces forming cottage cheese-like discharge

• Broad-spectrum ATB

• Tx: Topical antifungals (clotrimazole) or oral fluconazole

(33) HIV-1Human immunodeficiency virus type 1• Unprotected MSM• Diffuse maculopapular

rash on abdomen

• Retrovirus• gp120, gp41• ELISA + Western Blot

• gp120 binds to CD4 which allows it to bind to CXCR4 (T-cells) or CCR5 (T-cells/ Mφ) co-receptors.

• gp41 leads to fusion and cell entry

• Sex, IV Drug Use, Congenital spread

• Tx: Combination anti-retroviral therapy (HAART)

(35) SalmonellaSalmonella typhimurium

• Family has cramps, vomiting, diarrhea (bloody)

• Ate turkey and stuffing

• Gm- motile rods, facultative anaerobic, lactase-, oxidase-

• Stool cultures

• 2nd leading cause of food-borne disease

• Localized invasion results in influx of neutrophils, can cause bacteremia w/ LPS inducing sepsis

• Poultry, eggs, dairy

• Tx: NONE (self-limiting)

(38) E. Coli O157:H7Enterohemorrhagic Escherichia coli (EHEC)• Severe abdominal

cramps, watery turning into bloody diarrhea

• Ate pink hamburgers

• Gm- rod, Indole+, Lactase+, Sorbitol non-fermenting

• Stool cultures

• Most common cause of bloody diarrhea

• Attaches to brush border of intestinal epithelium

• Shiga-toxins cause endothelial damage leading to blood loss

• Ground beef, unpasteurized milk

• Tx: NONE (self-limiting)

(39) CholeraVibrio cholerae

• Traveled to Bangladesh• Profuse rice-water

diarrhea, vomiting, sweating, cramps

• Taking H2-blocker drug

• Gm-, comma-shaped• Motile, oxidase+,

faculatative anaerobe• Acid-sensitive• Cholera toxin (CTX)

• Pandemic due to O:1 biotype El Tor

• CTX activates adenyl cyclase cascade increasing cAMP, accumulate NaCl in lumen leading to dehydration

• Contaminated water/food

• Gulf coast US: shellfish

• Tx: Rehydration therapy (oral rehydration sol’n)

(42) C. difficile-associated diarrhea (CDAD)Clostridium difficile

• Frequent diarrhea• Erythematous, friable

colonic mucosa• Hx of broad spectrum

ATB treatment

• Gm+, spore-forming rod, strict anaerobe

• Toxin A, Toxin B• Stool sampled for toxin

(ELISA)

• Toxin B more potent, inactivate GTP-binding proteins causing break-up of actin filaments damaging cellular lining

• Exposure to broad-spectrum ATB (clindamycin, cephalo-sporin, ampicillin)

• Tx: Metronidazole

(46) Amebic DysenteryEntamoeba histolytica

• Traveled to India• Intermittent diarrhea

with blood and mucus• Multiple small

hemorrhagic areas with ulcers in sigmoid colon

• Trophozoite in host and infective cyst in feces

• Cyst transforms in small intestine and migrate to large intestine, invading colon causing cell and PMN lysis, can cause flask-shaped ulcers

• Fecal-oral transmission

• Tx: Metronidazole and Paromomycin

(47) GiardiasisGiardia lamblia

• Backpacking in Rockies• Watery diarrhea turning

greasy and foul smelling

• Trophozoite pear-shaped, face-like appearance, cysts in stool

• Stool antigen test

• Trophozoites attach to brush border causing villus atrophy resulting in diarrhea

• Beavers, dog feces contaminated water

• Tx: Metronidazole

(48) CryptosporidiosisCryptosporidium parvum

• Untreated AIDS• Chronic watery diarrhea

• Acid-fast, intracellular, extracytoplasmic coccidian oocysts

• Ziehl-Neelsen staining

• Oocysts release sporozoites infecting the jejunum between microvilli, impairing adsorption resulting in water loss

• Water-borne transmission

• Tx: IV rehydration, restore HAART

(49) AscariasisAscaris lumbricoides

• Originally from Mexico• Poor appetite, abd pain• Eosinophilia• Intestinal obstruction• Nematode eggs in stool

• Largest human roundworm

• Eggs have “bumpy coat”

• Larvae hatch, invade intestinal mucosa, travel through portal and systemic circulation to lungs and alveolar walls (Loeffler syndrome). Larvae are reswallowed.

• Tropical regions, soil, produce, children 3-8 yo

• Tx: Mebendazole

(50) StrongyloidiasisStrongyloides stercoralis

• Traveled to El Salvador• 3w worsening diarrhea,

abd pain, fevers• Eosinophilia• Maculopapular rash on

groin and buttocks

• Rhabditiform larvae with prominent genital primordium

• Filariform larvae penetrate skin and migrate to lungs where they are reswallowed into the jejunum causing GI symptoms and can reinfect peri-anally.

• Humid tropical regions, direct contact with soil (walking barefoot)

• Tx: Ivermectin

(51) Hydatid Cyst DiseaseEchinococcus granulosus

• Emigrated from Argentina raising sheepdogs

• Fever, chills, jaundice, upper abd pain

• Liver has large multi-loculated cyst with bile duct dilation

• Tapeworm, 3 proglottids• Hydatid cysts

• Oncospheres invade and develop into cysts in liver, lung, brain, etc. Can lead to biliary duct dilation and jaundice, hydatid cysts cause abd pain

• Dog feces

• Tx: Surgery, Albendazole

(52) SchistosomiasisSchistosoma mansoni

• Recent immigrant from Kenya

• Eosinophilia• Hepatosplenomegaly w/

portal HTN• Vomiting w/ blood

• Blood trematode• Egg w/ lateral spine

• Cercariae penetrate skin and migrate to veins, eggs migrate but some are trapped and die in tissue causing granulomatous rxn in liver and spleen.

• Infected snails in open water

• Tx: Praziquantel

(53) Hepatitis AHepatitis A Virus (HAV)

• Fever, jaundice, dark yellow urine, pale stools

• Sight of food triggers nausea

• High ALT and AST

• Picorna – ssRNA+ icosahedral capsid

• Hepatitis panel serology

• Replicates in liver, CTL response, viremia, and eventually cleared

• Worldwide: Poor sanitation, US: Shellfish

• Tx: NONE (self-limiting)

(58) MeningitisListeria monocytogenes

• Headache, confusion, no nuchal rigidity

• Hx: Steroid use for RA• MRI show meningeal

enhancement

• Gm+, intracellular small rods, grow at 4⁰C, β-hemolysis, tumbling motility, ferment glucose.

• Internalin, listeriolysin O, phospholipases

• Internalin induces host cells to engulf. Phospholipases allows it to escape phagosomes, spread via pseudopods. Killed by T cell-mediated activation of Mφ.

• Meningitis in newborns• Processed meat, soft

cheeses

• Tx: Ampicillin + Aminoglycoside

(67) OsteomyelitisStaphylococcus aureus

• Spreading painful, warm, tender, necrotic-appearing boils on L leg with fever.

• Bone scan shows intense uptake in femur

• Gm+ cocci, clusters, catalase+, coagulase+, β-hemolytic

• Protein A, hemolysins, hyaluronidase, leukocidin

• Most common cause of skin infections

• Fibronectin-binding protein causes colonization in skin breaks that invade the mucosal barriers, makes pyogenic exudate, spreads locally or hematogenously to the bone (osteomyelitis)

• Human nasal carrier

• Tx: Nafcillin (Vancomycin if MRSA)

(68) Necrotizing FascitisStreptococcus pyogenes

• Severe pain, swelling in L thigh, purplish becoming rapidly grayish

• Gm+ cocci in chains, β-hemolysis, facultative anaerobic, catalase-, bacitracin-sensitive

• Hyaluronic acid, M-protein, LTA, hemolysin O and S, enzymes

• LTA-M protein binds to epidermis and resist phagocytosis, spread into subcutaneous tissue, dermis, and fascia via hyaluronidase prompting pyogenic inflammation.

• Direct contact, types M1 or M3 common for skin

• Tx: Surgery, Penicillin G (clindamycin if allergic)

(69) Gas GangreneClostridium perfringens

• Severe pain at colon carcinoma surgery site

• Discolored skin, hemorrhagic bullae, serosanguineous (thin brownish) discharge, extensive gas in soft tissue

• Gm+ box-shaped rods, anaerobic, catalase-, double β-hemolysis, deep tissues

• Nagler rxn (+ lecithinase)

• Bowel surgery allows anaerobes access to tissue and flourish with facultative anerobes. Α-toxin has phospholipase C activity on cell membranes, other enzymes produce gas, muscle turns black and gangrenous

• Normal human colon flora

• Tx: Surgery, Penicillin, Clindamycin

(71) Ringworm (tinea capitis)Microsporum canis

• Raised lesions with center nodules and peripherial scaling on head.

• Received dog recently

• Monomorphic fungi, spindle-shaped macro-conidia, white mold

• Wood’s light (UV) on hair• Keratinases, proteinases

• Only found in dead layer of epidermis, keratinases allow invasion of keratinized tissue, snake-like, annular, nodular, vesicular lesions.

• Found on cats and dogs

• Tx: Griseofulvin (concentrates in keratin), OTC drugs

(72) SporotrichosisSporothrix schenckii

• Multiple mildly painful erythematous lesions starting from thumb to elbow with lymphangitic streaking.

• Thumb has dry, shallow, ulcerated lesion

• Fungal dark-pigmented mold in soil, cigar-shaped yeasts in tissue, florally arranged microconidia

• Sabouraud dextrose agar

• “Rose handler’s disease”• Spores enter punctured skin

and form smooth/verru-cose painless nodules, spread via lymph forming chains of nodules or suppurating granulomas (plasma cells, neutrophils)

• Sphagnum moss, hay, thorny plants

• Tx: Itraconazole

(76) Native-Valve EndocarditisViridans streptococci

• Night sweats, “splinter hemorrhage” in fingernail, conjunctival petechiae

• Hx: Heart murmur• Hx: Wisdom tooth removal

w/ no ATB• Echo shows 8mm mobile

vegetation on bicuspid aortic valve

• Gm+ cocci in chains, α-hemolytic, optochin-resistant

• Results from transient bacteremia with preexisting valve abnormality. Minor trauma from turbulence leads to deposition of fibrin and platelets, binding bacteria forming micro-colonies leading to Janeway lesions, Osler nodes, Roth spots, splinter hemorrhages

• Normal oral/GI flora

• Tx: Bactericidal ATB (Penicillin G)

(77) PneumonitisCytomegalovirus (CMV)

• Moderate respiratory distress, bilateral interstitial infiltrates

• Received allogeneic bone marrow transplant, taking Bactrim

• Β-herpesvirus, dsDNA with capsid and env, can progress to latency

• Giant cells (cytomegalic) with intracellular inclusions (with halo “Owl’s eye”)

• Most common cause of post-transplant infection

• Multiplies in nucleus, enters latent state in leukocytes/ lymphocytes, can cause interstitial pneumonia on reactivation (spreading to pneumocytes)

• Close contact with body fluids (saliva)

• Tx: Ganciclovir (Foscarnet if resistant)

(78) Lyme Disease (LD)Borrelia burgdorferi

• Home in wooded CT• Multiple tick bites• Rash under armpit with

central clearing• Myalgia, arthralgia, fever

• Spirochete, motile• OspA, OspB• ELISA + Western Blot

• Ticks inoculate host, spread outwards and trigger inflammatory cytokines, can cause auto-immune Abs

• Black-legged deer-ticks• US: NE, MN, WI, Pacific

• Tx: Doxycycline

(79) MalariaPlasmodium falciparum

• Immigrated from W Africa• Intense periodic fevers,

drenched in sweat• Hepatosplenomegaly• Generalized seizure

• Protozoa with 4 stages: ring (around central vacuole), trophozoite (Schuffner dots), schizont (chromatin dots), gametocyte (crescent-shaped).

• Thick/thin film blood smear

• Sporozoites infect liver cells, mature and invate RBCs (Duffy Ag) and feed on Hg leading to anemia, thrombocytopenia, hypoglycemia, lactic acidosis. Can persist in liver

• Mosquitos

• Tx: Chloroquine (Primaquine for liver infections, mefloquine if resistant, exchange transfusion if severe)

(81) LeptospirosisLeptospira interrogans

• Recently returned from boating trip in August

• High fever, myalgia, severe HA, photophobia

• Swollen conjunctiva

• Spirochetes, long, thin, motile with hooked ends

• ELISA, microagglutination test (MAT)

• Hooked ends and flagella allows burrowing into tissues leading to bacteremia followed by inflammatory and immune response which can lead to jaundice

• Rat or livestock urine

• Tx: Oral doxycycline (IV penicillin if severe)

(82) PasteurellosisPasteurella multocida

• R hand and axilla was swollen and tender

• Hx: Bitten by cat

• Gm- short rods, oxidase+, encapsulated

• Chocolate agar• Bipolar staining

• Polymicrobic, capsule and endotoxin trigger inflammation with purulent drainage

• Cats (sometimes dogs)

• Tx: Penicillin G

(84) SmallpoxVariola major

• Papulovesicular lesions on face and extremities at same stage of development, bumpy lesions filled with opaque fluid

• Already had chickenpox

• Herpes, linear dsDNA, dumbbell-shaped core

• Eradicated worldwide• After week-long

incubation, flu-like symptoms, maculo-papular rash on face, palms, soles.

• Bioterrorism agent

• Tx: NONE (self-limiting)

(85) PlagueYersinia pestis

• Lives in Arizona• Painful L groin mass, firm

and tender• Small hemorrhages on skin

of R leg

• Gm- “safety-pin” shaped, nonmotile, oxidase-, ferment glucose, reduce nitrates

• F1 glycoprotein, protease, coagulase, exotoxin

• Wright stain

• F1 avoids phagocytosis and multiplies in Mφ, spread to lymph nodes forming “buboes” and can cause bacteremia, widespread petechial lesions from vascular necrosis if systemic

• Rodents, carnivores, cats, dogs are animal reservoirs

• Flea vectors

• Tx: Streptomycin

(88) Hantavirus Pulmonary Syndrome (HPS)

Sin Nombre Virus• Fever, malaise, muscle

aches, hypotension, SOB• Camping in rural NM with

deer mice• Bilateral interstitial

infiltrates with hilar indistinctness

• Left-shift (22% bands)

• Bunyavirus, spherical, circular ssRNA-, triple-segmented

• Serology, RT-PCR

• Attach to cells at b3 integrin receptor, replicate in cytoplasm, initiate TNF, IL-2 response. Activated CD8 T-cells produce holes in infected pneumocytes leading to bilateral infiltrates, left-shift, thrombocytopenia, pulmonary edema, hemoconcentration

• Rodent urine or droppings

• Tx: Supportive care

(91) Severe Acute Respiratory Syndrome (SARS)SARS Coronavirus

• Mild SOB, hypoxia• Hx: Care of patient with

severe respiratory illness• Bilateral lower lobe

interstitial infiltrates

• Coronavirus, ssRNA+, enveloped with club-shaped peplomers, nonsegmented

• Infection leads to diffuse alveolar damage (DAD), multinucleated giant cells with no viral inclusions, squamous metaplasia, increased fibrosis

• Respiratory droplets

• Tx: Supportive Care