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Host and Defense > Week 13 > Flashcards

Week 13 Flashcards

1
Q

Fungi have a cell wall composed of ___ and a cell membrane composed of ___

A

Chitin

Ergosterol (acts like cholesterol in human membranes, note that bacterial membranes do not have sterols)

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2
Q

True or false… antibacterial agents can also be used to target some fungal infections

A

False

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3
Q

____ is the leading cause of death in immunocompromised patients, patients with asthma, patients with cystic fibrosis, mainly due to hypersensitivity reactions to antigens to _____

A

Pulmonary aspergillosis

Aspergillus fumigatus

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4
Q

What are four different targets of antifungals?

A

Components of fungal cell membrane

Cell wall synthesis

Nucleic acid synthesis

Microtuble function

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5
Q

What three types of antifungal drugs interact with or inhibit ergosterol synthesis?

A

Amphotericin B

Azoles

Echinocandins

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6
Q

What two drugs bind to ergosterol in fungal membranes to disrupt membrane function and permeability? Describe their mechanism in more detail.

A

Amphotericin B

Nystatin

Bind to plasma membrane ergosterol and damages the membrane by forming pores which cause leakage of potassium ions.

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7
Q

What two drugs inhibit 14-alpha-sterol dymethylase, to prevent ergosterol synthesis, and lead to the accumulation of 14-alpha-methylsterols?

A

Itraconazole

Fluconazole

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8
Q

What two drugs inhibit squalene epoxidase to prevent ergosterol synthesis?

A

Naftifine

Terbinafine

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9
Q

What drug inhibits fungal cell wall synthesis by inhibitin glucan synthesis?

A

Echinocandins (caspofungin)

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10
Q

Is amphotericin B broad spectrum or narrow spectrum? What are its clinical uses?

A

Broad

However, due to its extensive side effects, it is only reserved for severe infections.

First line therapy for invasive, life threatening, systemic and localized candidemia

Effective for aspergillus infections

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11
Q

True or false… amphotericin is absorbed well orally

A

False. It is only administered parenteral (in hospital setting)

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12
Q

What are the adverse effects of amphotericin b?

A

Highly toxic chronic reactions.

Immediate reactions include fever, chills, muscle spasms, etc. but can be avoided by slow infusion, decrease daily dose, premedication

Slower reactions are most detrimental for renal toxicity and may also cause neurotoxicity, as well as other side effects

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13
Q

Nystatin’s mechanism is similar to amphotericin b. How is it administered? What are its clinical uses? What are some adverse effects?

A

Topical administration only

Treatment for oral thrush (candida albicans) and vaginal candidiasis

Adverse effects: higher systemic toxicity than amphotericin B (why its only administered topically). Disulfuram-like reactions

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14
Q

What is the spectrum of azoles?

A

Antibacterial
Antiprotozoal
Antihelminthic
Antifungal

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15
Q

Describe the classification system of azoles.

A

Based on the number of nitrogen atoms attached to the ring

Imidazoles (2)

Triazoles (3)

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16
Q

What is the mechanism of azoles?

A

Inhibit ergosterol synthesis

It does this by blocking ianosine 14a-demethylase, a fungal CYP-450-dependent enzyme that converts ianosterol to ergosterol

This will ultimately increase membrane fluidity, increase permeability, and inhibit fungal cell growth/replication

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17
Q

How are azoles administer? What is their clinical use? What are its contraindications?

A

Administered topically or systemically

Used for superficial fungal infections or systemic infections

Contraindicated in pregnancy, during lactation, or in patients with hepatic dysfunction

-it will also inhibit human gonadal steroid synthesis causing decreased testosterone

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18
Q

What is the most commonly prescribed systemic antifungal? It is the drug of choice for ____ but does not treat _____. It is contraindicated in ___ patients

A

Flucanazole

Candidiasis albicans (also used to treat fungal cryptococcal meningitis in AIDs patients

Aspergillus

Pregnant

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19
Q

What azole was the first azole and is used for systemic and topical therapy?

A

Ketoconazole

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20
Q

What azole requires low pH for absorption and is more toxic than fluconazole?

A

Itraconazole

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21
Q

What azole is administer topically only? It is used to treat Vulcan-vaginal candidiasis, oral candidiasis, and athletes foot.

A

Clotrimazole and miconazole

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22
Q

What drug is the first line treatment for aspergillus infections?

A

Vorconizole (an azole)

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23
Q

Ketoconozale and ____ should never be given together. Why?

A

Amphotericin B

Kentonazole decreases ergosterol in the fungal membrane and thus reduces the fungicidal action of amphotericin B

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24
Q

Amphotericin B is syndergistic with ____

A

Flucytosine

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25
Q

What is the mechanism of flucytosine? What is the spectrum of flucytosine? What is its clinical use? What are some adverse effects?

A

Inhibits thymidylate synthetase which inhibits DNA and RNA synthesis in fungi

Specturm: narrow, used for systemic fungal infections

Clinical use: synergistic with amphotericin B for cryptococcal meningitis

Adverse effects: bone marrow suppression

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26
Q

What drugs are considered the penicillins of antifungal drugs? Name one drug of this class.

A

Echinocandins

Caspofungin

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27
Q

What is the mechanism of echinocandins (caspofungin). What are some clinical uses and side effects?

A

Blocks cell wall synthesis and maintenance by inhibition of the enzyme 1,3-b glucan synthase.

Clinical uses: fungicidal against some candida species. Fungistatic against aspergillus. Used in azole resistant candida or as a second line agent for refractory aspergillus

Side effects: avoid in pregnancy (embryotoxic).

Note that this is administered via IV

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28
Q

True or false… caspofungin is involved in blocking B-glucan synthase to inhibit fungi cell wall synthesis.

It is generally safe except for in pregnancy

A

True

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29
Q

What is the mechanism of griseofulvin? What are its clinical uses? True or false… it is effective topically. What are some adverse effects?

A

Disrupts microtubule function, inhibiting fungal mitosis.

Inhibits growth of dermatophytes (infections of hair, skin, nails)

False. But it has entirely local effects as it accumulates in the hair and nails.

Adverse effects: teratogenic, carcinogenic, severe headaches

Note that this drug has multiple drug interactions (increases metabolism of Warfin)

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30
Q

The use of griseofulvin to treat onychomycosis has mostly been replace by ____. Describe its mechanism and clinical use and adverse effects

A

Terbinafine

Mechanism: inhibits squalene epoxidase to inhibit ergosterol synthesis, which disrupts cell membrane permeability

Clinical use: concentrated in keratin. Treats dermatophytes

Adverse effects: hepatotoxicity

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31
Q

What two drugs are topical antifungals used for localized candidiasis in patients with normal immune function?

A

Nystatin

Clotrimazole

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32
Q

What are two systemic antifungals that are used for disseminated disease and in immunocompromised patients?

A

Fluconazole tablets

Itraconazole tablets

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33
Q

True or false… azoles inhibit CYP-450 function

A

True

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34
Q

What is bacteriuria?

A

Bacteria in urine

Often colonization, not infection

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35
Q

What is acute cystitis?

A

Bacterial infection of the bladder

Infection (and symptoms) confined to lower urinary tract

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36
Q

What is acute pyelonephritis?

A

Bacterial infection of the upper urinary tract (ureters, renal pelvis, kidney parenchyma)

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37
Q

In order for a patient to have an uncomplicated UTI, what criteria should be met?

A

Not pregnant

Normal urinary anatomy

No co-morbidities (healthy, outpatient)

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38
Q

If a patient has any of these criteria, they are considered to have a complicated UTI. What are the criteria? (6 things)

A

Pregnant

Male gender

Abnormal urinary anatomy

Diabetes mellitus

Immune compromise

Indwelling bladder catheter

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39
Q

True or false.. UTI is one of the most common bacterial infection seen in outpatient setting

A

True

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40
Q

True or false… by age 18, half of women have had at least one UTI. (Cystitis more common than pyelonephritis)

A

False. By age 32

41
Q

UTIs develop in ___% of patients with indwelling urinary catheters

A

10

42
Q

In healthy individuals, in the absence of infection, which bacteria typically colonize the lower urinary tract?

A

None. The urinary tract is normally sterile in young, healthy patients

43
Q

85% of bacteria that cause UTIs are _____

A

Gram negative colonizers of GI tract

E. Coli (predominant pathogen of UTIs)

May also be proteus mirabilis, klebsiella pneumoniae, staphylococcus saprophyticus

44
Q

Describe the pathogenesis of UTIs

A

GI pathogens colonize the peri-urethral mucosa

The bacteria ascend through urethra to bladder (more common in women because the urethra is much shorter, also male prostatic fluid has anti-bacterial properties)

Infection may continue to ascend to the ureters and kidney

45
Q

True or false.. most untreated lower UTIs will progress to pyelonephritis

A

False

46
Q

What are some virulence factors of uropathogenic E.coli?

A 
Pili
Flagella
Adhesins
Siderophores
Toxins
Polysaccharide coating
47
Q

What are the symptoms of cystitis?

A

Increased frequency of urination

Increased urgency of urination

Pain or burning with urination

Suprapubic pain

48
Q

What are some symptoms pyelonephritis?

A

*fever or chills

Flank or Costco-vertebral angle pain

Nausea/vomiting

May also have symptoms of cystitis

49
Q

What is the gold standard for diagnosis of a UTI?

A

SYMPTOMS + urine culture demonstrating >10^5 colony-forming units of uropathogenic bacteria per ml

50
Q

True or false… a positive urine culture alone is indicative of a UTI

A

False. A positive urine culture without symptoms is indicative of an asymptomatic bacteruria

-note that this is an important distinction to be made because it will determine if antibiotics are prescribed or not

51
Q

What are some indications of a normal urinalysis?

A

Specific gravity (urine density/water density) = ~1.01

Negative urine nitrite (metabolic product of bacteria)

RBC/WBC count should be less than 5

52
Q

What are some indications of an abnormal urinalysis?

A

Cloudy urine with an increased specific gravity

Positive nitrite (indicates nitrogen-metabolising bacteria)

Hematuria and pyuria present (increased WBCs and RBCs

53
Q

What are the four roles of urinalysis?

A

Utility for UTI diagnosis is to RULE OUT UTI based on absence of pyuria (<10 WBC or negative leukocyte esterase)

*UA is not necessary when symptoms are present or absent

Pyuria alone is not an indication for antibiotics. Doesn’t indicate if UTI or asymptomatic bacteruria (same for nitrite positive)

54
Q

True or false… pyuria is common in patients with asymptomatic bacteruria. Thus, pyuria in patients with asymptomatic bacteriuria is NOT an indication for antibiotic therapy. It may be caused by STDs, catheter in place, or interstitial nephritis

A

True

55
Q

True or false… antibiotics are generally needed in order to resolve uncomplicated cystitis, otherwise they will continue to persist.

A

False. Cystitis generally resolved without antibiotics; they are used to provide symptom relief

56
Q

Name three drugs that can be used to treat uncomplicated cystitis.

A

Nitrofurantoin

Trimethoprim-sulfa methoxazole

Fosfomycin

-note that all of these drugs can be taken orally

57
Q

Name three drugs that are used to treat uncomplicated pyelonephritis

A

Fluoroquinolones

Trimethoprim-sulfa methoxazole

B-lactams

  • note that if the patient is unstable, they should be admitted to the hospital for IV antibiotics
58
Q

Broad spectrum antibiotics have side effects of killing normal GI flora, thus the newer trend is to prescribe narrower antibiotics for UTIs. Name two bacteria that are growing restitant to antibiotics in UTIs

A

E.coli resistance to amoxicillin

Most UTI bacteira resistant to fluoroquinolone

59
Q

Asymptomatic bacteriuria is a positive urine culture without symptoms. Usually you do not prescribe antibiotics, unless…. (4 things)

A

Pregnant

Pre-urology procedure

Renal transplant

Neutropenia

60
Q

True or false… antibiotics do not decrease ASB or prevent subsequent development of UTI

A

True

61
Q

What are the main consequences of over-testing and treatment of UTIs?

A

Its hard to ignore a positive test, leading to unnecessary prescriptions and missing the true diagnosis

Also will increase risk of developing resistant organisms

62
Q

A patient is admitted with an indwelling catheter. Urine culture reveals >10^5 cfu e.coli. There are no urinary symptoms and the patient feels well. What is the best management?

A

Remove catheter if possible, no further treatment

63
Q

What are some symptoms of a catheter-associated UTI?

A

Usually lack typical UTI symptoms

New fever with no other source

CVA tenderness, flank pain, pelvic discomfort

64
Q

Explain the diagnosis of a catheter associated UTI

A

Presence of inflammation on urinalysis doesn’t correlate with infection, however absence of pyuria rules out CA-UTI

Urine culture with >10^5 cfu bacteria

UA/culture must be interpreted based on clinical scenario

65
Q

What is the treatment for a catheter-associated UTI?

A

Remove catheter whenever possible

Replace catheters that have been in for more than 2 weeks if still indicated

Antibiotic duration is 7 days if prompt response. Or 3 days if catheter removed in female patient with no evidence of associate pyelonephritis

66
Q

What are anaerobes?

A

Do not require oxygen for life and reproduction and oxygen direct toxic effect may prohibit their growth

67
Q

Name three toxic byproducts of oxygen

A

Superoxide

Hydrogen peroxide

Hydroxyl radical

68
Q

Explain why anaerobes are party animals

A

They tend to grow in mixtures of organisms. This is because other bacteria tend to lower the redox potential of oxygen and provide favorable conditions for the growth of anaerobes.

Volatile and foul-smelling metabolic byproducts of other anaerobes contribute to his balanced environ,ent

69
Q

What genus of anaerobes are typically exogenous?

A

Clostridium

70
Q

True or false…. most anaerobic infections are seeded from normal endogenous flora.

A

True

71
Q

What parts of the body have anaerobes as part of the normal flora?

A

Mouth

Vagina

Bowels

Skin (deep in pores)

72
Q

Some anaerobic species are characteristic of the site they are from, without much crossover. Name the anaerobes of the mouth, skin, vagina, and colon

A 
Mouth 
Fusobacterium 
Veilonella 
Actinomyces 
Porphyromonas 
Prevotella

Skin
Proprionibacterium

Vagina
Lactobacillus
Prevotella bivia

Colon
Bacteriodes fragilis

73
Q

What are predisposing factors for an anaerobic infection?

A

Trauma to mucous membranes or skin

Vascular stasis

Tissue necrosis

Decrease of redox potential (cutting off blood supply)

74
Q

True or false… anaerobes typically require longer incubation periods in the laboratory

A

True

75
Q

Name three anaerobic non-spore forming gram positive rods

A

Actinomyces

Proprionibacterium

Mobiluncus

76
Q

Describe actinomyces species

A

Chronic, granulomatous, infectious disease with sinus tracts and fistulae, which erupt to the surface and drain pus containing sulfur granules.

77
Q

Describe proionibacterium species

A

Normal skin and and respiratory flora. Scope of infection similar to coagulase negative staphylococcus species

P. Acnes is often found in acne pustules

78
Q

Describe mobiluncus species

A

Act synergistically with organisms including gardenella vaginosis to cause bacterial vaginosis

79
Q

Name two gram positive cocci anaerobic groups. Describe them

A

Peptostreptococcus species. - usually found in abscess that arise from misplaced oral flora. Brain or deep lung abscess

Anaerobic and microaerophillic streptococcus species. - habitat and appearance similar to peptostreptococcus species. Note that these species do not respond to the classic anaerobe drug metronidazole.

80
Q

Name one anaerobic gram negative cocci group and describe it

A

Veillonella - th only anaerobic genus of gram negative cocci usually implicated as pathogenic. Found in mixed infections of oral origin

81
Q

Name three gram negative anaerobic rods and describe them.

A

Bacteriodes- the bacteriodes fragilis group account for about 70% of clinically significant anaerobic bactermias. Bacteriodes fragalis out number E. coli 1000:

Prevotella and porphyromonas - former pigmented bacteriodes species. Common in mouth flora and dental abscesses

Fusobacterium - also mouth associated. Can be mixed with actinomyces. So if you find fusobacterium, you want to do screening to look for actinomyces as well

82
Q

What is the treatment for anaerobes?

A

Create an environment in which anaerobes cannot proliferate. Useful measures include removing dead tissue (debridement), draining pus, eliminating obstructions, etc.

Arrest the spread of anaerobes into healthy tissue

Neutralize toxins

83
Q

What are the five stages of biofilm formation?

A

Attachment

Irreversible binding

Layering/maturation

Ultimate thickness/maturation

Dispersion

84
Q

Describe the attachment phase of biofilm formation

A

Occurs in seconds

Reversible binding
Logarithmic growth
Pili and bacterial adhesion molecules
Changes in gene expression (decrease flagella, increase adhesion molecules)

85
Q

Describe the irreversible binding phase of biofilm formation

A

Occurs in minutes

Exopolysaccharides trap nutrients and planktonic bacteria

Cells are sessile

86
Q

Describe the difference between the layering and ultimate thickness phases in biofilm formation

A

Layering - greater than 10 um thickness

Ultimate thickness - greater than 100 um thickness. Some cells released from substrate, but trapped in the EPS

87
Q

Describe the dispersion phase of biofilm formation

A

Occurs in several days

Cells leaving
As nutrition become scarce, there are changes in gene expression
Cells again become planktonic

88
Q

What are three purposes of fluid-filled channels in biofilms?

A

Exchange nutrients

Dispose of wastes

Some motile organisms

89
Q

What are the three layers of mature biofilm? Describe them.

A

Outer - most exposure to nutrients. Most active organisms. Some become planktonic.

Intermediate - metabolism is down-regulated, but still using nutrients and exchanging genes

Innermost - attached, earliest and least active, includes the persister cells

90
Q

What are planktonic cells?

A

Free living.

The can begin biofilm formation and leave the biofilm at any time

91
Q

What are sessile cells?

A

Attached/ participating in the biofilm community

92
Q

What are persister cells?

A

Located bottom of the heap

Metabolically inert

Present in all biofilms

Potential for maintenance of gene pool

Resist environmental stress, including antibiotics

Possibly able to disable apoptosis

93
Q

What are some advantages to living in a biofilm?

A

Protection from host defenses

Physical barrier to PMNs

Potential to out-compete normal biota

Gene transfer (ability to spread resistance in community)

Provide protective enzymes

Perform as organic polymers

94
Q

True or false… as a biofilm forms, streamers of cells extend from the surface and break away to form new biofilms elsewhere. Disaggregation can transmit already up-regulated resistant aggregates of organisms to other body sites

A

True

95
Q

What are the primary colonizers of dental plaque?

A

Streptococcus mutans and actinomyces

Pili and adhesion molecules

Glucan polymer glycocalyx (EPS)

96
Q

What are the bridge bacteria in dental plaque?

A

Glucan-binding proteins

Fusobacterium

Cant bind to pellicle, but can bind to primary colonizers

97
Q

What are the late colonizers of dental plaque?

A

Streptococcus salivarius, proprionibacterium, prevotella, veillonella, selenomonas

Generally considered non-pathogenic

98
Q

True or false… dental plaque is mostly comprised of gram-negative organisms

A

False.. mostly gram positive

99
Q

Name four dental pathogens associated with plaque

A

Porphyromonas gingivalis

Bacteroides forsythia

Aggregatibacter actinomycetemcomitans

Treponema denticola (spirochete)

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