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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
What is the mechanism of flucytosine? What is the spectrum of flucytosine? What is its clinical use? What are some adverse effects?
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
26
What drugs are considered the penicillins of antifungal drugs? Name one drug of this class.
Echinocandins Caspofungin
27
What is the mechanism of echinocandins (caspofungin). What are some clinical uses and side effects?
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
28
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
True
29
What is the mechanism of griseofulvin? What are its clinical uses? True or false... it is effective topically. What are some adverse effects?
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)
30
The use of griseofulvin to treat onychomycosis has mostly been replace by ____. Describe its mechanism and clinical use and adverse effects
Terbinafine Mechanism: inhibits squalene epoxidase to inhibit ergosterol synthesis, which disrupts cell membrane permeability Clinical use: concentrated in keratin. Treats dermatophytes Adverse effects: hepatotoxicity
31
What two drugs are topical antifungals used for localized candidiasis in patients with normal immune function?
Nystatin Clotrimazole
32
What are two systemic antifungals that are used for disseminated disease and in immunocompromised patients?
Fluconazole tablets Itraconazole tablets
33
True or false... azoles inhibit CYP-450 function
True
34
What is bacteriuria?
Bacteria in urine Often colonization, not infection
35
What is acute cystitis?
Bacterial infection of the bladder Infection (and symptoms) confined to lower urinary tract
36
What is acute pyelonephritis?
Bacterial infection of the upper urinary tract (ureters, renal pelvis, kidney parenchyma)
37
In order for a patient to have an uncomplicated UTI, what criteria should be met?
Not pregnant Normal urinary anatomy No co-morbidities (healthy, outpatient)
38
If a patient has any of these criteria, they are considered to have a complicated UTI. What are the criteria? (6 things)
Pregnant Male gender Abnormal urinary anatomy Diabetes mellitus Immune compromise Indwelling bladder catheter
39
True or false.. UTI is one of the most common bacterial infection seen in outpatient setting
True
40
True or false... by age 18, half of women have had at least one UTI. (Cystitis more common than pyelonephritis)
False. By age 32
41
UTIs develop in ___% of patients with indwelling urinary catheters
10
42
In healthy individuals, in the absence of infection, which bacteria typically colonize the lower urinary tract?
None. The urinary tract is normally sterile in young, healthy patients
43
85% of bacteria that cause UTIs are _____
Gram negative colonizers of GI tract E. Coli (predominant pathogen of UTIs) May also be proteus mirabilis, klebsiella pneumoniae, staphylococcus saprophyticus
44
Describe the pathogenesis of UTIs
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
True or false.. most untreated lower UTIs will progress to pyelonephritis
False
46
What are some virulence factors of uropathogenic E.coli?
``` Pili Flagella Adhesins Siderophores Toxins Polysaccharide coating ```
47
What are the symptoms of cystitis?
Increased frequency of urination Increased urgency of urination Pain or burning with urination Suprapubic pain
48
What are some symptoms pyelonephritis?
*fever or chills Flank or Costco-vertebral angle pain Nausea/vomiting May also have symptoms of cystitis
49
What is the gold standard for diagnosis of a UTI?
SYMPTOMS + urine culture demonstrating >10^5 colony-forming units of uropathogenic bacteria per ml
50
True or false... a positive urine culture alone is indicative of a UTI
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
What are some indications of a normal urinalysis?
Specific gravity (urine density/water density) = ~1.01 Negative urine nitrite (metabolic product of bacteria) RBC/WBC count should be less than 5
52
What are some indications of an abnormal urinalysis?
Cloudy urine with an increased specific gravity Positive nitrite (indicates nitrogen-metabolising bacteria) Hematuria and pyuria present (increased WBCs and RBCs
53
What are the four roles of urinalysis?
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
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
True
55
True or false... antibiotics are generally needed in order to resolve uncomplicated cystitis, otherwise they will continue to persist.
False. Cystitis generally resolved without antibiotics; they are used to provide symptom relief
56
Name three drugs that can be used to treat uncomplicated cystitis.
Nitrofurantoin Trimethoprim-sulfa methoxazole Fosfomycin -note that all of these drugs can be taken orally
57
Name three drugs that are used to treat uncomplicated pyelonephritis
Fluoroquinolones Trimethoprim-sulfa methoxazole B-lactams - note that if the patient is unstable, they should be admitted to the hospital for IV antibiotics
58
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
E.coli resistance to amoxicillin Most UTI bacteira resistant to fluoroquinolone
59
Asymptomatic bacteriuria is a positive urine culture without symptoms. Usually you do not prescribe antibiotics, unless.... (4 things)
Pregnant Pre-urology procedure Renal transplant Neutropenia
60
True or false... antibiotics do not decrease ASB or prevent subsequent development of UTI
True
61
What are the main consequences of over-testing and treatment of UTIs?
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
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?
Remove catheter if possible, no further treatment
63
What are some symptoms of a catheter-associated UTI?
Usually lack typical UTI symptoms New fever with no other source CVA tenderness, flank pain, pelvic discomfort
64
Explain the diagnosis of a catheter associated UTI
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
What is the treatment for a catheter-associated UTI?
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
What are anaerobes?
Do not require oxygen for life and reproduction and oxygen direct toxic effect may prohibit their growth
67
Name three toxic byproducts of oxygen
Superoxide Hydrogen peroxide Hydroxyl radical
68
Explain why anaerobes are party animals
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
What genus of anaerobes are typically exogenous?
Clostridium
70
True or false.... most anaerobic infections are seeded from normal endogenous flora.
True
71
What parts of the body have anaerobes as part of the normal flora?
Mouth Vagina Bowels Skin (deep in pores)
72
Some anaerobic species are characteristic of the site they are from, without much crossover. Name the anaerobes of the mouth, skin, vagina, and colon
``` Mouth Fusobacterium Veilonella Actinomyces Porphyromonas Prevotella ``` Skin Proprionibacterium Vagina Lactobacillus Prevotella bivia Colon Bacteriodes fragilis
73
What are predisposing factors for an anaerobic infection?
Trauma to mucous membranes or skin Vascular stasis Tissue necrosis Decrease of redox potential (cutting off blood supply)
74
True or false... anaerobes typically require longer incubation periods in the laboratory
True
75
Name three anaerobic non-spore forming gram positive rods
Actinomyces Proprionibacterium Mobiluncus
76
Describe actinomyces species
Chronic, granulomatous, infectious disease with sinus tracts and fistulae, which erupt to the surface and drain pus containing sulfur granules.
77
Describe proionibacterium species
Normal skin and and respiratory flora. Scope of infection similar to coagulase negative staphylococcus species P. Acnes is often found in acne pustules
78
Describe mobiluncus species
Act synergistically with organisms including gardenella vaginosis to cause bacterial vaginosis
79
Name two gram positive cocci anaerobic groups. Describe them
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
Name one anaerobic gram negative cocci group and describe it
Veillonella - th only anaerobic genus of gram negative cocci usually implicated as pathogenic. Found in mixed infections of oral origin
81
Name three gram negative anaerobic rods and describe them.
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
What is the treatment for anaerobes?
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
What are the five stages of biofilm formation?
Attachment Irreversible binding Layering/maturation Ultimate thickness/maturation Dispersion
84
Describe the attachment phase of biofilm formation
Occurs in seconds Reversible binding Logarithmic growth Pili and bacterial adhesion molecules Changes in gene expression (decrease flagella, increase adhesion molecules)
85
Describe the irreversible binding phase of biofilm formation
Occurs in minutes Exopolysaccharides trap nutrients and planktonic bacteria Cells are sessile
86
Describe the difference between the layering and ultimate thickness phases in biofilm formation
Layering - greater than 10 um thickness Ultimate thickness - greater than 100 um thickness. Some cells released from substrate, but trapped in the EPS
87
Describe the dispersion phase of biofilm formation
Occurs in several days Cells leaving As nutrition become scarce, there are changes in gene expression Cells again become planktonic
88
What are three purposes of fluid-filled channels in biofilms?
Exchange nutrients Dispose of wastes Some motile organisms
89
What are the three layers of mature biofilm? Describe them.
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
What are planktonic cells?
Free living. The can begin biofilm formation and leave the biofilm at any time
91
What are sessile cells?
Attached/ participating in the biofilm community
92
What are persister cells?
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
What are some advantages to living in a biofilm?
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
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
True
95
What are the primary colonizers of dental plaque?
Streptococcus mutans and actinomyces Pili and adhesion molecules Glucan polymer glycocalyx (EPS)
96
What are the bridge bacteria in dental plaque?
Glucan-binding proteins Fusobacterium Cant bind to pellicle, but can bind to primary colonizers
97
What are the late colonizers of dental plaque?
Streptococcus salivarius, proprionibacterium, prevotella, veillonella, selenomonas Generally considered non-pathogenic
98
True or false... dental plaque is mostly comprised of gram-negative organisms
False.. mostly gram positive
99
Name four dental pathogens associated with plaque
Porphyromonas gingivalis Bacteroides forsythia Aggregatibacter actinomycetemcomitans Treponema denticola (spirochete)

Host and Defense (17 decks)

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