Microbiology 13

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the natural habitat of most fungi is the environment. name an important exception.: candida albicans, part of normal human flora
infection with certain systemic fungi such as Histoplasma and Coccidioides elicits what type of response?: a granulomatous host defense response composed of macs and helper T cells
infection with Aspergillus, Mucor, and Sporothrix elicits what type of response?: a pyogenic response composed of neutrophils
aspergillus: dimorphic?: NO, exist only as molds
Would you see budding yeasts in mucormycosis?: NO, these are always hyphal
what are the three most important intestinal protozoa?: (1) Entamoeba histolytica

(2) Giardia lamblia (flagellate)

(3) Cryptosporidium
what is the most important protozoan of the urogenital tract?: Trichomonas vaginalis
what two main things does Entamoeba histolytica cause?: amebic dysentery and liver abscess
Does T. vaginalis have a trophozoite form?: YES, in fact it exists only as a trophozoite

Note: since the organism is transmitted by sexual contact, there is no need for a durable cyst form
desc basics of life cycle of Plasmodium: two phases:

(1) sexual cycle (sporogony), which occurs primarily in mosquitoes

(2) asexual cycle (schizogony), which occurs in humans
most of the pathologic findings of malaria result from what?: destruction of RBCs
the life cycle of which protozoa involves the sandfly as the vector? what are the primary cells that are infected?: Leishmania

cells of the reticuloendothelial system
Visceral Leishmaniasis - aka - symptomatology: kala-azar

fever, anemia, emaciation, splenomegaly, and hepatosplenomegaly
what are the agents of filariasis?: Wuchereria bacrofti, Brugia malayi
Filiariasis - Identification: adult worms in lymphatics, and the microfilariae (deposited by female worms are found in the blood and lymph)

man infected through the bite of the female mosquitoes harbouring larvae
acute filariasis symptoms: fever, eosinophilia, lymphangitis, and lymphadenitis
chronic filiariasis symptoms: "elephantitis"

obstruction of the lymphatics and hypertrophy of the skin and subcutaneous tissue of the limbs, genitalia, or breasts
Onchocerciasis - causative agent: Onchocerca volvulus
Onchocerciasis: A chronic disease with fibrous nodules in the skin and subcutaneous tissue in which the adult worms reside

transmitted by bite of "black flies", Simulium
Schistosomiasis - causative agents: schistosoma mansoni, S. japonicum, S. hematobium
Schistosomiasis: blood-fluke disease in which adult male and female worms live in the veins of man; larvae undergo maturation within the liver then migrate to veins

worms growing in liver may produce acute hepatitis; also dysentery, hematuria, and cystitis possible
Antiamebic drugs - DOC for Asymptomatic cyst passer: DOC: Iodoquinol (Yodoxin) or Paromomycin (Humatin)
Antiamebic drugs - DOC for Mild to Moderate disease: DOC: Metro
Antiamebic drugs - DOC for Severe disease: DOC: Metro
Antiamebic drugs - DOC for Hepatic (systemic) amebiasis: DOC: Metro
For the antiamebic drugs, for which three groups are the DOC the same?: for Mild/Moderate, Severe, and Systemic (Hepatic)

(DOC: Metro)
what is the chemical class of Metronidazole?: Nitroimidazole
what is the mechanism of action of metronidazole?: accepts e- from e-transport proteins, diverting them from normal energy-yielding pathways
four pontential adverse effects of metronidazole: (1) NS: headache, dizziness

ride the metro, get a headache and get dizzy

(2) mouth: metallic taste, dryness

DON'T LICK THE METRO

(3) antabuse-like rxn with ethanol

DON'T DRINK ON THE METRO

(4) concern over possible developmental effects (avoid in 1st trimester)
name 6 therapeutic uses for metronidazole: (1) amebiasis

(2) trichomonas vaginal infections

(3) giardia

(4) C. difficile or tetani, Bacteroides

(5) Gardnerella bacterial vaginosis

(6) Rosacea -- used as a topical cream
Iodoquinol - aka - pharmacokinetics - adverse effects - use: Iodoquinol
- aka: Yodoxin
- pharmacokinetics: oral, not well absorbed
- adverse effects: rashes and itching, slight thyroid enlargement
- use: intestinal amebiasis
Chloroquine: - terminates clinical attacks of P. vivax and falciparum

- effective suppressant against vivax

- most adverse effects involve eye
Primaquine: - strong effect on tissue stages (malaria); can produce a cure of vivax

- causes hemolytic anemia in persons with G-6-PD deficiency
Pyrimethamine (Daraprim): - active suppressant drug; also potent action against gametocytes

- useful against chloroquine-resistant falciparum strains
Quinine: - older drug; was considered obsolete but now used again against resistant strains

- causes cinchonism (headache, tinnitus)
Mefloquine (Lariam): - chemically related to quinine

- used for chloroquine-resistant falciparum

- major agent for malaria prophylaxis

- high incidence of NS toxicity
what is the treatment of choice for PCP?: Pneuomocystis Carinii Pneumonia (PCP)

treatment of choice is trimethoprim-sulfamethoxazole (Bactrim, Septra)
Pentamidine (Pentam): - used for PCP

- administration: aerosol (prophylaxis), IV (treatment)

- adverse effects: cough (aerosol), hypotension, hypoglycemia, pancreatitis
Tichomonas vaginalis - DOC: Metro
Giardia lamblia - DOC: Metro
Balantidium coli - DOC: Tetracycline
Toxoplasma gondii - DOC: Pyrimethamine + Sulfadiazine
T. cruzi - DOC: Nifurtimox
T. gambiense or T. rhodesiense - DOC: DOC: Suramin or Eflornithine Melarsoprol (for late disease with CNS involvement)
Leishmania - DOC: Stibogluconate (Pentostam)
properties (2) of an ideal anthelmintic drug: (1) highly toxic to worm in intestine

(2) NOT absorbed from GI tract
Mebendazole (Vermox) - MOA - pharmacokinetics - uses: - MOA: inhibits microtubule synth and impairs glucose uptake

- pharmacokinetics: poorly absorbed

- uses: roundworm, hookworm, pinworm, whipworm
Pyrantel pamoate (Antiminth, Pin-X) - MOA - pharmacokinetics - adverse effects - uses: - MOA: inhibition of cholinesterase, depolarizing neuromuscular blockage and paralysis

- pharmacokinetics: poorly absorbed

- adverse effects: N&V, abdominal pain

- uses: roundworm, hookworm, pinworm
Thiabendazole (Mintezol) - pharmacokinetics - adverse effects - uses: - pharmacokinetics: absorbed and metabolized

- adverse effects: dizziness, N&V

- uses: threadworm, alternate for whipworm and hookworm
Praziquantel (Biltricide) - MOA - Pharmacokinetics - Adverse effects - Uses: - MOA: alters cell membrane permeability

- Pharmacokinetics: absorbed and metabolized

- Adverse effects: dizziness, headache, and abdominal pain

- Uses: all forms of tapeworm and schistosomiasis
Ascaris (roundworm) - DOC: Mebendazole (Vermox) or Pyrantel pamoate
Tichuris (whipworm) - DOC: Mebendazole
Anclostoma duodenale (hookworm) - DOC: Mebendazole or Pyrantel pamoate
Necator americanus (hookworm) - DOC: Mebendazole or Pyrantel pamoate
Strongyloides (threadworm) - DOC: Thiabendazole (Mintezol)
Enterobius (pinworm) - DOC: Pyrantel pamoate or Mebendazole
Taenia saginata (beef tapeworm) - DOC: Praziquantel (Biltricide)
Diphyllobothrium latum (fish tapeworm) - DOC: Praziquantel
Taenia solium (pork tapeworm) - DOC: Praziquantel
Hymenolepsis nana (dwarf tapeworm) - DOC: Praziquantel
What are the DOCs for Schisosma haematobium / S. japonicum / S. mansoni / S. mekongi: Remember, DOC for all is Praziquantel
kid has itchiness, restlessness? what test? what do you suspect?: scotch tape test

Enterobius vermicularis (Intestinal Pinworm)
for Ancylostomiasis (Necator americanus) what is the infective form?: (OTE) larvae
which disease / agent associated with "river blindness" / back flies: onchocerciasis / onchocerca volvulus
how is metronidazole administered?: orally

one exception: topical cream for rosacea
Which gram(-) diplococci is a big cause of bacterial meningitis, especially in the 2-18 age group?: N. meningitidis
which bacterium causes meningitis in infants?: Group B streptococcus
which bacterium causes meningitis often in people of age group 19-59?: S. pneumoniae
polyenes: bind to ergosterol in the fungal cell membrane and alter membrane permeability
azoles: (imidazoles and triazoles)

interfere with synthesis of membrane ergosterol by inhibiting a demethylase, leading to altered membrane permeability
allylamines: interfere with the synthesis of lanosterol, a precursor of ergosterol, by inhibiting squalene epixodiase
what are the three major categories of fungal infections?: (1) systemic mycoses

(2) candidiasis - superficial infections involving the GI tract, skin, mucous membranes

(3) dermatophytic infections e.g. ringworm of skin, scalp, nails
what class of drug is Amphotericin B?: a polyene antibiotic (used against systemic mycoses)
Amphotericin B - MOA: a polyene

binds to ergosterol in the fungal cell membrane leading to altered permeability, loss of macromolecules and ions and irreversible damage to cell
adverse effects of amphotericin B: very toxic: renal, fever/chills, hypokalemia, anemia, shock
therapeutic uses of amphotericin: DOC or co-DOC for most rapidly progressing or severe mycoses including aspergillos, blastomycosis, candidiasis, coccidioidomycosis, cyptococcosis, histoplasmosis, paracoccidioidomycosis
chemical class of Ketoconazole: imidazole
Ketoconazole - MOA: imidazoles block the synth of fungal cell membrane lipids, especially ergosterol
comment on the distribution of Ketoconazole: 99% protein bound (none in CSF)
comment on the adverse effects of Ketoconazole: - inhib testosterone synth

- inc hepatic transaminases
therapeutic uses of Ketoconazole: blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis
what is the chemical class of Fluconazole?: triazole
therapeutic uses of Fluconazole: candidiasis, cryptococcosis, very useful in immunosuppressed patients
what chemical class is Itraconazole?: triazole
Itraconazole interactions: slows hepatic metabolism and inc activity of many drugs
therapeutic uses for Itraconazole: histoplasmosis, blastomycosis, paracoccidioidmycosis, sporotrichosis
voriconazole chemical class: triazole
therapeutic uses for voriconazole: invasive aspergillos, scedosporium apiospermum
Terbinafine (Lamisil) - chemical class: synthetic allylamine
Terbinafine MOA: inhibits the enzyme squalene epoxidase, thus inhibiting synth of ergosterol and causing toxic concentrations of squalene to accumulate in the fungal cell
therapeutic uses of Terbinafine: dermatophytic infections of toenails and fingernails (onychomycosis)
Caspofungin - what class?: lipopeptide echinocandin
Caspofungin - MOA: inhibits synth of glucan, a component of the fungal cell wall
Caspofungin - admin - therapeutic uses: IV

aspergillos and severe candida infections
Griseofulvin - MOA: binds to microtubules, disrupting the mitotic spindle and inhibiting cell division
Griseofulvin - Pharmacokinetics: first agent used systemically (oral administration) for the treatment of superficial dermatophytic infectionss. Absorption is aided by microsize particle preparations and high-fat foods.
Griseofulvin - therapeutic uses: topical for ringworm of scalp and nails
Miconazole: a broad spectrum antifungal drug useful for: vaginal candidiasis, tinea
Clotrimazole: a broad-spectrum antifungal drug used for: candidiasis and tinea
what are two good drugs to remember for motion sickness?: meclizine, scopolamine
when traveling, if you have diarrhea with no fever, no vomiting, no blood / cramps, what should you give?: Loperamide (Immodium)

then if symptoms get worse start antibiotics
If traveling and you get diarrhea with fever, what should you give?: Ciprofloxin
ciprofloxin adverse effects: photosensitivity, potentiates effects of caffeine, theophylline
How long after Hep A immunization is vaccine effective?: 2-4 weeks
name four good prophylaxis treatments for malaria: (1) chloroquine

(2) mefloquine

(3) doxycycline

(4) Malarone
Haiti, Dominican Republic, Central America north of the Panama canal, Parts of the Middle East, Northern China - Chloroquine-sensitive or resistant areas?: sensitive
Is chloroquine safe in pregnancy and infancy?: YES
what anti-malarial drugs should you consider in chloroquine-resistant areas?: mefloquine, doxycycline, malarone, primaquine
what are the side effects of mefloquine?: insomnia, bad dreams, dizziness, headache, irritability, GI symptoms
Doxycycline - side effects - contraindications: photosensitivity, GI symptoms, vaginal yeast infections

not recommended for pregnant women or children
which anti-malarial drug causes hemolysis if G-6-P deficient?: Primaquine
is Primaquine OK for everyone?: not good for pregnant or for breast feeding mothers
Elderly patients with pneumonia -- most likely causes (community / long-term-care / hospital)?: Community -- Strep Pneumo

Long Term -- Polymicrobial

Hospital -- Gram(-) -- Pseudomonas
bladder catheter / UTI - likely cause M/F: Females -- gram(-) Rods (E. coli)

Males -- Gram(+) Enterococci OR Gram(-)
elderly patient with bacteria in the urine but no symptoms - should they be treated? - risk for complications?: NO

but lookout for possible bacteremia
complications of bacteremia in older patients?: E. coli --> UTI

S. aureus --> common in hospital, metastases possible
After course of broad spectrum antibiotics, diarrhea is common, particularly for older patients; what may cause this diarrhea?: C. difficile
pathogens involved in dural sinuses and salivary glands?: dural sinuses --> nasogastric tube (maybe S. aureus)

salivary glands --> polymicrobial anaerobes
common intra-abdominal infections in elderly (3): gall-bladder, appendix, diverticulitis
What is the most serious of the "atypical" pneumonia causes?: Legionella
why is tuberculosis more common in the elderly?: cilia beat slower, cough less

related to defects in T cell and macs
how to prevent / test for TB different in elderly?: two-step PPD testing

quarantines
In the elderly are viral respiratory infections (i.e. common cold) common?: NO
where can you get extra-pulmonary tuberculosis?: bone = Pott's

genitourinary
major treatment for most rapidly progressing or severe systemic mycoses?: Amphotericin B

but don't use it if it's not -- very toxic!
Fluconazole distribution: unique in that it has good distribution, including to the CNS -- could e.g. use this for crypotococcal meningitis

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