Lecture 1: Pharm of Renal Infections Flashcards

1
Q

What type of UTI is most likely in a nonpregnant women without anatomic abnormalities or instrumentation of the urinary tract?

A

Uncomplicated UTI

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2
Q

What are some of the predisposing factors which would make a UTI be considered complicated?

A
  • Urinary obstruction
  • Urinary retention caused by neuro disease
  • Immunosuppression
  • Renal failure or Renal Transplantation
  • Pregnancy
  • Foreign bodies: Calculi or Indwelling Catheters
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3
Q

UPEC relies on what adhesive organelle to form a biofilm?

A

Type 1 pili, antigen 43, curli

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4
Q

How is P. mirabilis able to form a biofilm for inhabiting the urinary tract?

What are the components of this biofilm?

A
  • Produce urease
  • Calcium crystals + magnesium ammonium phosphate precipitates
  • Crystalline biofims
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5
Q

How is P. aeruginosa able to form a biofilm for inhabiting the urinary tract?

What are the components of this biofilm?

A
  • Changes hydrophobicity of its surface
  • Uses lectins, rhamnolipids
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6
Q

What does E. faecalis use to form a biofilm?

A

Fibrinogen

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7
Q

A young, non-pregnant female presents with dysuria, frequency, urgency, nocturia, and some suprapubic discomfort. On PE you notice some gross hematuria.

What type of UTI does this fit the criteria of?

A

Uncomplicated Cystitis

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8
Q

What are the 3 first line agents for Uncomplicated Cystitis?

A
  1. Nitrofurantoin
  2. Trimethoprim-Sulfamethoxazole (TMP-SMX)
  3. Fosfomycin
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9
Q

What class of agents is used as a second line treatment for Uncomplicated Cystitis?

List 4 drugs in this class.

A
  • Oral beta lactams
  • Amoxicillin, Cefpodoxime, Cefdinir, Cefadroxil
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10
Q

Which class is of Abx is uses as the third line for treatment of Uncomplicated Cystitis?

List 3 drugs in this class

A
  • Fluoroquinolones
  • Ciprofloxacin, Levofloxaxin, Ofloxacin
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11
Q

The first line agents for cystitis, Fosfomycin and Nitrofurantoin, target which gram-type of bacteria?

A

Gram positive and gram negative

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12
Q

What is the MOA of Nitrofurantoin?

A
  • Converted into highly reactive intermediate
  • Disrupts synthesis of proteins, RNA, and DNA
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13
Q

Nitrofurantoin antagonizes what other drug?

Contraindicated in which pts?

A
  • Antagonizes nalidixic acid (synthetic quinolone Abx)
  • Contraindicated in pts w/ G6P dehydrogenase deficiency
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14
Q

What is the MOA of Fosfomycin?

A
  • Cell wall synthesis inhibitor
  • Inhibits cytoplasmic enzyme enolpyruvate transferase
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15
Q

By which method may a bacteria become resistant to Fosfomycin?

A

Inadequate transport of drug into cell

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16
Q

Which first line agent for cystitis come in an oral form and is safe to use in pregnancy?

A

Fosfomycin

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17
Q

Nitrofurantoin and Fosfomycin should not be taken in pts when there is suspicion of?

A
  • Early pyelonephritis
  • Does NOT achieve adequate renal tissue levels
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18
Q

What are the two 3rd gen Cephalosporins used as a second line to treat cystitis?

Target which gram-type of bacteria?

A
  • Cefpodoxime
  • Cefdinir

*Target gram negatives

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19
Q

What is the 1st generation cephalosporin used as a second line tx for Cystitis?

Targets which gram-type of bacteria?

A
  • Cefadroxil
  • Targets gram positive and gram negatives
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20
Q

Which adverse effects exist for Fluoroquinolones and is why the FDA states that disabling and potentially irreversible effects of these drugs outweight their benefits in treating uncomplicated cystitis?

A
  • Tendinitis and tendon rupture
  • Peripheral neuropathy
  • CNS effects
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21
Q

Which 2 drugs should not be used to emperically treat uncomplicated cystitis due to possibility of resistance?

A
  1. Ampicillin
  2. Amoxicillin
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22
Q

If resistance is identified in someone with uncomplicated cystitis, which drug/class can be used?

This drug is insufficiently active against what bacteria?

A
  • Ertapenem (a carbapenem)
  • Insufficient against P. aeruginosa
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23
Q

To determine what drugs to use, what are the major signs/sx’s of someone with Pyelonephritis?

A
  • Unilateral back or flank pain
  • Fever (can be high or low grade) w/ N?V
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24
Q

Which antibiotic class is the first line for Pyelonephritis?

List the 2 drugs that are used?

A
  • Fluoroquinolones
  • Ciprofloxacin or Levofloxacin
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25
Q

If severe pyelonephritis or risk factors for resistance, fluoroquinolones should be adminstered with what parenteral broad spectrum antibiotics until susceptibility data is available?

A
  • Ceftriaxone (3rd gen.)

OR

  • Aminoglycosides: Gentamicin or Tobramycin
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26
Q

Aminoglycosides (i.e., Tobramycin or Gentamicin) are active against which gram-type and specific bacteria?

A

Aerobic gram negatives + P. aeruginosa

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27
Q

What is the MOA of aminoglycosides?

A

Irreversible protein synthesis inhibitor, binds 30S ribosomal subunit

28
Q

What are 3 AE’s associated w/ Aminoglycosides?

*Hint: Sheehy gave us a way to remember using the name.

A
  • CN VIII toxicity: vertigo and hearing loss
  • Renal toxicity
  • Neuromusclar blockade

*“A-Mean-Guy will punch you in the ear, then the kidney, and finally knock you out”

29
Q

What are the 3 second-line agents which can be used for pyelonephritis in a pt who is hypersensitive to fluoroquinolones or there is resistance?

A
  • TMP-SMX
  • Oral beta lactams –> Amoxicillin, Cefpodoxime, Cefdinir, Cefadroxil
  • Aztreonam
30
Q

If a pt w/ pyelonephritis cannot tolerate TMP-SMX or oral beta lactams, what do you give them?

A

Aztreonam

31
Q

What is the structure of Aztreoname that allows it be used in penicillin hypersensitive patients?

A

Monobactam, monocyclic beta-lactam ring

32
Q

Aztreonam has activity against which type of bacteria?

*Way to remember from CMMRS*

A

Aerobic gram-negatives (P. aeruginosa)

*“Tree falls on house = negative experience and will probably let air in (aerobes)

33
Q

What is the MOA of Aztreonam?

A
  • Cell wall synthesis inhibitor
  • Transpeptidase inhibitor
34
Q

Which 2nd line agent for Pyelonephritis comes in IV form?

A

Aztreonam

35
Q

What are the AE’s seen in children associated with Aztreonam?

A
  • Neutropenia (3-11%)
  • Pain at injection site (12%)
36
Q

What is the clinical presentation of Complicated UTI and is often due to what?

A
  • Severe dysuria (painful urination)
  • Often due to an indwelling catheter
37
Q

What are the 2 first line agents for complicated cystitis?

A

Ciprofloxacin or Levofloxacin = Fluoroquinolones

38
Q

Fluoroquinolones are used for complicated cystitis due to their coverage of which bacteria?

A

P. aeruginosa

*Ciprofloxacin or Levofloxacin

39
Q

In complicated cystitis, the presence of gram-positive cocci on gram stains suggests what type of organism causing the UTI?

Can use what 2 antibiotics?

A
  • Enterococcal UTI (i.e., E. faecalis or E. faecium)
  • Ampicillin or Amoxicillin
40
Q

Which urinary analgesic can be used for pain relief in complicated cystitis?

Common finding/AE of this drug?

A
  • Phenazopyridine
  • Colors urine orange/red
41
Q

What are the 3 first line agents used in mild complicated pyelonephritis?

When is each used (i.e., bacteria and hypersensitivities)?

A

1) Ceftriaxone
2. Ciprofloxacin or Levofloxacin –> covers P. aeruginosa
3) Aztreoname –> alt. in setting of beta lactam allergy

42
Q

The beta-lactamase inhibitors: tazobactam and avibactam are available in combinations with beta lactam drugs and can be used for severe complicated pyelonephritis, what 3 combos exist?

A
  1. Piperacillin + Tazobactam
  2. Ceftolozane (5th gen.) +Tazobactam
  3. Ceftazidime (3rd gen.) + Avibactam
43
Q

The beta-lactamase inhibitors used in combo for severe complicated pyelonephritis are good inhibitors of which type of beta-lactamases?

Produced by which 2 bacteria which can cause UTI’s?

A
  • Ambler class A β-lactamase
  • E. coli and K. pneumoniae
44
Q

The beta-lactamase inhibitors used in combo for severe complicated pyelonephritis are poor inhibitors of which type of beta-lactamases?

Produced by which 2 bacteria which can cause UTI’s?

A
  • Class C β-lactamases
  • Produced by Enterobacter spp. and P. aeruginosa
45
Q

Which 3 Carbapenems can be used as first line therapy for severe complicated pyelonephritis?

Effective against which types of bacteria?

A
  • Imipenem, Doripenem, and Meropenem
  • Wide spectrum = good activity against gram negatives (including P. aeruginosa) + gram positives and anaerobes
46
Q

Carbapenems are resistant to?

A

Beta-lactamases

47
Q

What is the MOA of carbapenems?

A

Inhibit transpeptidase

48
Q

What is significant about the pharmacokinetics of Doripenem, Meropenem, and Ertapenem?

A

NOT metabolized by dihydropeptidase

49
Q

Which carbapenem is most commonly used, but is associated w/ seizures so should be avoided in pts with a history or risk of seizure?

A

Imipenem

50
Q

Which β-lactam can be used as a first line monotherapy for treating severe complicated pyelonephritis?

A

Cefepime (4th gen Ceph)

51
Q

Which β-lactamase inhibitor + β-lactam combo can be given at a higher dose as a first line treatment for severe complicated pyelonephritis if P. aeruginosa is suspected?

A
  • Piperacillin + tazobactam
52
Q

Which carbapenem can be given at a higher dose as a first line treatment for severe complicated pyelonephritis if P. aeruginosa is suspected?

A

Meropenem

53
Q

Which 2 carbapenems have slightly greater activity against gram negatives and slightly less against gram positives?

A

Doripenem and Meropenem

54
Q

What is the MOA of the β-lactams?

A

Cell wall synthesis inhibitors, bind/inhibit transpeptidase

55
Q

Prostatitis is most often caused by what bacteria?

A

E. coli

56
Q

What are the 3 agents which can be used to treat Prostatitis?

A
  1. TMP-SMX
  2. Ciprofloxacin
  3. Levofloxacin
57
Q

What is the MOA of fluoroquinolones?

A
  • Inhibit transcription and replication of bacterial DNA
  • Through inhibition of topoisomerase II (DNA gyrase) and topoisomerase IV
58
Q

Describe the 3 different mechanisms by which bacteria can develop resistance to fluoroquinolones

A
  • Mutation to quinolone binding region on either DNA gyrase or topoisomerase IV
  • Active drug efflux
  • Upregulation of proteins that protect and shield both DNA gyase and topoisomerase IV
59
Q

Prolonged treatment with trimethoprim part of TMP/SMX can cause what AE’s?

A
  • Anemia
  • Leukopenia
  • Granulocytopenia
60
Q

PSGN is caused by prior infection with what bacteria and what is it’s gram stain?

A
  • Group A β-hemolytic streptococcus
  • Gram positive
61
Q

Which drug can be given IM for patient with recurrent group A β-hemolytic streptococcus infection especially if adherence to previous antibiotic uncertain?

A

Penicillin G

62
Q

When giving β-lactams such as piperacillin and cephalosporins, what AE/contraindication must you be aware of?

A

β-lactam hypersensitivity –> Anaphylaxis

63
Q

Repeat treatment for group A beta-hemolytic streptococcus infection should be given with an agent with greater what?

A

β-lactamase stability

64
Q

For tx of recurrent group A β-hemolytic strep infection focused on using agents with greater β-lactamase stability describe which drugs/class can be used in order of greater β-lactamase stability?

A
  • Penicillin G (given IM)
  • 1st gen. cephalosporins –> Cephalexin or Cefadroxil
  • 3rd gen. cephalosporins –> Cefpodoxime or Cefdinir
  • Amoxicillin (aminopenicillin) or Clindamycin = greatest β-lactamase stability
65
Q

Clindamycin, used for recurrent PSGN, is very effective against bacteria which grow under what kind of conditions?

A

Anaerobes

66
Q

What is the MOA of clindamycin?

A

Protein synthesis inhibitor, binds to the 50S ribosomal subunit

67
Q

What is a major AE associated w/ Clindamycin use?

A

C. difficile induced diarrhea and colitis