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