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Renal II Quiz II > Pharmacology Of Renal Infections > Flashcards

Pharmacology Of Renal Infections Flashcards

1
Q

Urinary tract infection does not automatically equal cystitis. UTI is really the top of the pyramid, an over-arching term. What falls under the category of UTI?

A
  • Cystitis
  • Prostatitis
  • Pyelonephritis
  • Asymptomatic bacteruria (ASB) (Low yield)
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2
Q

What are the common causes of UTI in infant boys and older men?

A

Infant boys - congenital defects

older men - BPH (benign prostatic hypertrophy)

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3
Q

A non pregnant outpatient woman without anatomic abnormalities or instrumentation of the urinary tract

A

a typical presentation of uncomplicated UTI

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4
Q

What term do we associate with infection of the bladder?

A

cystitis

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5
Q

What term do we associate with infection of the kidney?

A

pyelonephritis

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6
Q

What is the most common cause of complicated UTI?

A

In-dwelling catheter

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7
Q

What are the causes of complicated UTI?

A
  1. urinary obstruction
  2. urinary retention caused by neurological disease
  3. immunosuppression
  4. renal failure
  5. renal transplantation
  6. pregnancy
  7. foreign bodies: calculi, indwelling catheters
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8
Q

What is the most common pathogen in both complicated and uncomplicated UTI?

A

UPEC (uropathogenic E. Coli)

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9
Q

What pathogen doubles in prevalence when moving from uncomplicated to complicated cases?

A

P. Aeruginosa

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10
Q

What type of UTI do you see E. Faeclais?

A

Complicated cases only

The microbe depends on the catheter and fibrinogen (clotting) to grow

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11
Q

How do we treat a patient with asymptomatic bacteriuria (ASB)?

A

usually no treatment is warranted

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12
Q

What is the first-line treatment for cystitis?

A
  1. Nitrofurantoin
  2. trimethoprim-sulfamethoxazole (TMP-SMX)
  3. Fosfomycin
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13
Q

What is the second-line treatment for Cystitis?

A

Oral beta lactams:

  • amoxicillin (aminopenicillin)
  • cefpodoxime (3rd gen cephalosporin)
  • cefdinir (3rd gen cephalosporin)
  • cefadroxil (1st gen cephalosporin) - attacks gram (-) breaks the normal rule
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14
Q

What is the third-line treatment for Cystits?

A

Fluoroquinolones:

  • ciprofloxacin
  • levofloxacin
  • ofloxacin
  • Moxifloxacin is NOT recommended
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15
Q

What two microbes are resistant to Nitrofurantoin, a first-line treatment drug for cystitis? In a more broad sense what is Nitrofurantoin bactericidal against?

A
  • P. Aeruginosa
  • Proteus

bactericidal for gram positive and gram negative bacteria

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16
Q

Why is nitrofurantoin such an excellent first-line Drug used in the treatment of Cystitis?

A

The drug is metabolized and excreted so quickly that no systemic antibacterial action is achieved

only works in the bladder, never makes it to the system

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17
Q

What are the AE of nitrofurantoin?

A
  • Anorexia
  • nausea
  • vomiting
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18
Q

What are the contraindications of Nitrofurantoin use?

A

antagonizes nalidixic acid (a quinolone) - old drug, prior to introduction of fluoroquinolones

contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency (toxic metabolites of the drug can build up)

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19
Q

What is the MOA of Fosfomycin?

A

Bacterial cell wall synthesis inhibitor

inhibits the bacterial cytoplasmic enzyme enolpyruvate transferase by blocking additions to UDP-N-acetylglucosamine

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20
Q

What is the only route of administration of Fosfomycin?

A

oral only

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21
Q

Why are nitrofurantoin and Fosfomycin inappropriate treatments for pyelonephritis?

A

because of the fast rate of metabolism neither one of these medications make it past the bladder

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22
Q

Why might trimethoprim-sulfmethoxazole (TMP-SMX) be an inappropriate treatment for Cystitis?

A

if the prevelance of resistance within the community exceeds 20%

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23
Q

Beta lactams are less effective than fluoroquinolones yet fluoroquinolones are a third-line treatment for cystitis while beta lactams are a second-line treatment? Explain this.

A

While more effective, fluoroquinolones tend to have more adverse effects than beta lactams

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24
Q

Ciprofloxacin, levofloxacin, and ofloxacin are all fluoroquinolones used to treat Cystitis. Moxifloxacin is also a fluoroquinolone, why is it not recommended for Cystitis treatment?

A

Moxifloxacin is not recommended due to the lower urinary levels it obtains. Not concentrated enough to treat cystitis.

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25
Q

What are the AE of third-line treatment of cystitis, Fluoroquinolones?

A
  • Tendinitis and tendon rupture
  • Peripheral neuropathy
  • CNS effects
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26
Q

If you have a patient who is resistant to normal treatment of Cystits which drugs should you not empirically treat uncomplicated cystitis?

A
  • Ampicillin
  • Amoxicillin

The above drugs are beta lactams. Cystitis resistant treatment is often due to bacteria acquiring beta lactamase enyzme allowing them to breakdown and inactivate beta lactams such as those above.

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27
Q

In addition to ceftriaxone, aminoglycosides can be used in addition to Fluoroquinolones to treat resistant pyelonephritis. What are the aminoglycosides?

A
  • Gentamicin
  • Tobramycin
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28
Q

What is the last back-up drug that can be used to treat treatment resistant cystitis?

A

Ertapenem (a carbapenem)

effective against gram negatives, gram positives, and anaerobes

Not effective against P aeruginosa

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29
Q

What is the main clinical differentiator between Pyelonephritis and cystitis?

A

Pyelonephritis will show unilateral back or flank pain with fever

Mild Pyelonephritis - low grade fever +/- lower back pain

Severe Pyelonephritis:

  • high fever
  • rigors
  • nausea, vomiting
  • flank or loin pain
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30
Q

What is the first-line treatment for Pyelonephritis? Why is this the first line treatment?

A

Flouroquinolons:

  • ciprofloxacin
  • levofloxacin

Used because of their high efficacy (even though they have significant AE), with a seriously infection they need to be utilized

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31
Q

What is the second line treatment for pyelonephritis?

A
  1. Trimethoprim-sulfamethoxazole (TMP-SMX)
  2. oral beta lactam (amoxicillin and the “cefs”)
  3. Aztreonam (last of the second line tx options)
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32
Q

Flouroquinolones (ciprofloxacin, levofloxacin) are first line drugs used in the treatment of pyelonephritis. For resistant cases of pyelonephritis what parenteral broad spectrum antibiotics can be used to enhance the efficacy of treatment and overcome resistance?

A
  • Ceftriaxone
  • Aminoglycosides (gentamicin, tobramycin)
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33
Q

What is the MOA of aminoglycosides?

A

Irreversible protein synthesis inhibitors

binds to 30s ribosomal subunit of bacteria interfering w/ initiation complex peptide formation

active against aerobic gram-negative bacteria and P aeruginosa

34
Q

What AE are associated with aminoglycosides (gentamicin, tobramycin)

A

”A Mean Guy”

punched in the ear, kidney, and knock you out

punched in the ear - 8th CN toxicity: vertigo, hearing loss

punched in the kidney - renal toxicity

knocked out - neuromuscular blockade

35
Q

What bacteria subtype are aminoglycosides most active against?

A
  • aerobic gram-negatives (only active in aerobes!)
  • P aeruginosa
36
Q

What are the oral beta lactams (2nd line treatemt) used to treat pyelonephritis?

A

Amoxicillin and the “Cefs”

  • Amoxicillin
  • cefpodoxime
  • cefdinir
  • cefadroxil

2nd Line tx for Pyelonephritis: TMP-SMX + Oral Beta Lactams + Aztreonam

37
Q

What is the advantage of Aztreonam in the second line treatment of pyelonephritis?

A

it’s a monobactam (monocyclic beta-lactam ring) and can be used in individuals who are hypersensitive to beta lactams will not be hypersensitive to aztreonam

can be used in penicillin hypersensitive patients

38
Q

Aztreonam is given by IV and is a second line “2.5” treatment for pyelonephritis. Broadly, what kind of bacteria is it effective against?

A

effective against aerobic gram-negatives (p aeruginosa)

39
Q

70-80% of all complicated UTIs are due to?

A

An indwelling catheter

compicated UTI can be cystitis or pyelonephritis or both

40
Q

What is the MOA of Aztreonam? An IV, monobactam, second line treatment, used in the treatment of pyelonephritis.

A

Cell wall synthesis inhibitor (transpeptidase inhibitor)

41
Q

What are the AE of Aztreonam?

A

AE in children (limited AE):

  • neutropenia 3-11%
  • pain at injection site 12%
42
Q

For a complicated UTI showing cystitis what is your first line treatment?

A

Because this is a complicated UTI and more likely to be resistant you should jump straight to using Fluorquinolones:

Ciprofloxacin or Levfloxacin

43
Q

For a complicated UTI caused by mild Pyelonephritis what is your first line treatment?

A

Ceftriaxone

or

Flouroquinoline (ciprofloxacin, levofloxacin)

  • covers P aeruginosa

or

Aztreonam - monobactam (used for beta lactam allergy)

  • Resolves gram negative aerobes (negative experience of tree falling on your house)
44
Q

For a complicated UTI as a result of severe pyelonephritis what is your first line treatment?

A

Beta Lactam + beta lactamase inhibitor

or

carbapenem

45
Q

Among the flouroquinolones used for treatment which flouroquinolone is advised against use?

A

Moxifloxacin

attains lower urinary levels than other flouroquinolones

46
Q

A patient with a complicated UTI give a UA sample which shows the prescence of gram-positive cocci on gram stain suggesting what organism is present? What drug should be used against this organism once this type of organsim is identified?

A

Enterococcus species (E faecalis, E faecium)

use: ampicillin or amoxicillin

Only use these drugs once the organism has been identified and not empiricallly

47
Q

What drugs should not be used empirically due to high resistance?

A
  • Nitrofurantoin
  • Trimethoprim-sulfamethoxazole (TMP-SMX)
  • Fosfomycin
  • Oral beta-lactams (amoxicillin, cefpodoxime, cefdinir, cefadroxil)
48
Q

An urinary analgesic with unknown mechanism than can be used with antibiotics to relieve pain while antibiotics are destroying bacteria. Changes urine to an orange/red color, but can cause nausea.

A

Phenazopyridine

49
Q

What are the beta lactamase inhibitors?

A

Tazobactam

Avibactam

these inhibitors come co-formulated w/ a beta lactam so it’s still one pill

50
Q

For cases of complicated UTI due to severe pyelonephritis what are the first line beta lactam/beta lactamase inhibitor formulations?

A

Ceftolozane (5th gen cephalosporin) + tazobactam

ceftazidime (3rd gen cephalosporin) + avibactam

51
Q

For complicated cases of UTI due to severe pyelonephritis what are the beta lactams that can be given that do not need to be paired with a beta lactamase inhitor?

A
  • Cefepime
  • Meropenem (up the dose when P aeruginosa suspected)
  • Imipenem
  • Doripenem
52
Q

What is the MOA of beta lactamase inhibtors, how are they able to be so effective?

A

Beta lactamase inhibitors are actually weak antibiotics that are bound by bacterial beta lactamase

with binding of bacterial beta lacatamase the beta lactam given in conjunction with the beta lactamase inhibitors are free to do there job w/o interruption

53
Q

β lactamase inhibitors (tazobactam, avibactam) are good inhibitors of ______ ____ ______ β-lactamases, but poor inhibitors of ______ ______ β-lactamases.

A

Ambler Class A; Class C

54
Q

Beta lactamases (tazobactam, avibactam) are poor inhibitors of Class C β-lactamases. Which bacteria produce this isoform of beta lactamase?

A
  • Enterobacter species
  • Citrobacter species
  • S marcescens
  • P aeruginosa
55
Q

In the treatment of complicated UTI as a result of severe pyelonephritis, carbapenems are a first line treatment. What are the carbapenems?

A
  • Imipenem
  • doripenem
  • meropenem
  • ertapenem (used for resistant cystitis)
56
Q

Of the carbapenems which drug of the four is insufficiently active against P aeruginosa?

A

Ertapenem

57
Q

Why are carbapenems good for complicated UTI as a result of severe pyelonephritis?

A

Wide spectrum good against:

  • gram negatives (including P aeruginosa)
  • Gram positives
  • anaerobes
  • Resistant to β-lactamases
58
Q

What is the MOA of carabapenems?

A

Inhibits transpeptidase

(similar to penicillins and cephalosporins)

Resistant to β-lactamases

59
Q

Of the carbapenems which has the worse AE and is metabolized by dihydropeptidase in the kidney?

A

Imipenem

60
Q

What is the major AE of Carabapenems?

A

Seizures (especially with imipenem)

If patient has a hx of seizures use: doripenem, meropenem, or ertapenem (longest half-life)

61
Q

What are the common pathogens causing prostatits?

A
  1. E. coli (58-88%)
  2. Proteus species
  3. P aeruginosa
62
Q

What is the first line treatment for prostatitis?

A
  • Trimethoprim-sulfamethoxazole (TMP-SMX)
  • Flouroquinolone (ciprofloxacin, levofloxacin)
63
Q

What is the most common cause of acute nephritis in children with 97% of cases occurring in regions of the world with poor socioeconomic status?

A

Post-streptococcal Glomerulonephritis (PSGN)

64
Q

What causes the majority of cases of PSGN?

A

Prior infection with group A beta-hemolytic streptococcus (gram positive)

65
Q

What is key to treating patients with recurrent group A beta-hemolytic streptococcus infection?

A

Repeat treatment should be with an agent that has increased resistance to bacterial beta lactamase

66
Q

List the drugs by increasing strength to bacterial beta lactamase (more resistant to bacterial breakdown) for post streptococcal glomerulonephritis (PSGN)

A
  1. Penicillin G (given IM)
  2. Cephalexin or Cefadroxil (1st gen cephalosporin)
  3. Cefpodoxime or Cefdinir (3rd gen cephalosporin)
  4. Amoxicillin (aminopenicillin) or clindamycin - heavy hitters
67
Q

What is the MOA of clindamycin?

A

Protein synthesis inhibitor, binds to 50s ribosomal subunit

68
Q

What are the AE of clindamycin?

A
  • Diarrhea, nausea, skin rashes
  • Risk factor for C. difficile induced diarrhea and colitis
69
Q

A 22-year-old female presents to the emergency department with three days of increased urinary frequency and suprapubic pain after micturition. she has no fevers, chills, or flank pain, nausea or vomiting, and urethral discharge. There have been no similar complaints in the past. She has recently become sexually active and uses a barrier mode of contraception. She has no history of sexuallly transmitted disease. She has no allergies to medications or food. Physical examination is unremarkable. Spot urinary pregnancy test is negative. Urinalysis reveals gram positive cocci.

A. Cystitis

B. Pyelonephritis

C. Complicated cystitis

D. Complicated pyelonephritis

E. Cystitis and pyelonephritis

A

Cystitis

70
Q

A 22-year-old female presents to the emergency department with three days of increased urinary frequency and suprapubic pain after micturition. she has no fevers, chills, or flank pain, nausea or vomiting, and urethral discharge. There have been no similar complaints in the past. She has recently become sexually active and uses a barrier mode of contraception. She has no history of sexuallly transmitted disease. She has no allergies to medications or food. Physical examination is unremarkable. Spot urinary pregnancy test is negative. Urinalysis reveals gram positive cocci. What is the likely pathogen?

A. Uropathogenic E. coli (UPEC)

B. Enterococcus species

C. K pneumoniae

D. P mirabilis

E. P aeruginosa

A

B. Enterococcus species

(honey moon bug)

71
Q

A 22-year-old female presents to the emergency department with three days of increased urinary frequency and suprapubic pain after micturition. she has no fevers, chills, or flank pain, nausea or vomiting, and urethral discharge. There have been no similar complaints in the past. She has recently become sexually active and uses a barrier mode of contraception. She has no history of sexuallly transmitted disease. She has no allergies to medications or food. Physical examination is unremarkable. Spot urinary pregnancy test is negative. Urinalysis reveals gram positive cocci. Patient is prescribed moxifloxacin, what is the likely result?

A. Anaphylaxis

B. Eighth cranial nerve toxicity

C. Seizure

D. C. difficile induced diarrhea

E. Infection persists

A

E. Infection persists

72
Q

What prescribed medication would be associated with the below signs/symptoms?

  1. Anaphylaxis
  2. Eighth cranial nerve toxicity
  3. Seizure
  4. C difficile induced diarrhea
  5. infection persists
A
  1. Anaphylaxis —> beta lactams allergy (give aztreonam)
  2. 8th CN toxicity —> aminoglycosides
  3. seizure —> imipenem
  4. C difficile induced diarrhea —> clindamycin
  5. infection persists —> moxifloxacin (not effective enough)
73
Q

A 55-year-old female presents with suprapubic pain, dysuria, fever, and costovertebral angle tenderness. Medical history reveals sensitivity to penicillin. She has no history of sexually transmitted diseases. Spot urinary pregnancy test is negative. What is the diagnosis?

A. Cystitis

B. Pyelonephritis

C. Complicated cystitis

D. Complicated pyelonephritis

E. Cystitis and pyelonephritis

A

E. Cystitis and pyelonephritis (costovertebral angle tenderness)

74
Q

A 55-year-old female presents with suprapubic pain, dysuria, fever, and costovertebral angle tenderness. Medical history reveals sensitivity to penicillin. She has no history of sexually transmitted diseases. Spot urinary pregnancy test is negative. Which antibiotic would be contraindicated for this patient?

A. Ciprofloxacin

B. Cefpodoxime

C. Aztreonam

D. Gentamicin

E. TMP-SMX

A

B. Cefpodoxime (cephalosporin has a beta lactam ring)

75
Q

A 55-year-old female presents with suprapubic pain, dysuria, fever, and costovertebral angle tenderness. Medical history reveals sensitivity to penicillin. She has no history of sexually transmitted diseases. Spot urinary pregnancy test is negative. The antibiotic of choice for this patient works by inhibiting which of the following bacterial proteins?

A. Dihydrofolate reductase

B. Dihydropteroate synthase

C. DNA gyrase

A

C. DNA gyrase (inhibited by flouroquinolones)

76
Q

A 53-year-old woman suffering from uncomplicated cystitis started a treatment with trimethoprim-sulfamethoxazole. One week later, burning upon urination was still pronounced, and the physician suspected that resistance to sulfamethoxazole had occurred. This resistance was most likely due to which of the following mechanisms?

A. Increased permeability of bacterial cell membrane

B. Decreased sulfonamide binding to bacterial ribosomes

C. Increased production of para-aminobenzoic acid (PABA)

D. Decreased sulfonamides binding dihydrofolate reductase

E. Decreased activity of the multidrug efflux pump

A

C. Increased production of para-aminobenzoic acid (PABA)

PABA is competitive with TMP. Bacteria have to make their own TH4 and use TMP-SMX instead of PABA stopping bacterial growth. Bacteria overcome this by making more bacteria to outcompete the TMP-SMX

77
Q

A 53-year-old woman suffering from uncomplicated cystitis started a treatment with trimethoprim-sulfamethoxazole. One week later, burning upon urination was still pronounced, and the physician suspected that resistance to sulfamethoxazole had occurred. Which of the following follow-up treatments would best to empirically treat this patient’s cystitis?

A. Phenazopytidine

B. Ampicillin

C. Amoxicillin

D. Nitrofurantoin

E. Moxifloxacin

A

A. Phenazopytidine - analgesic of unknown MOA

B. Ampicillin - shouldn’t be used w/o knowing cause

C. Amoxicillin - shouldn’t be used w/o knowing cause

D. Nitrofurantoin

E. Moxifloxacin - never use, not strong enough

78
Q

Describe biofilm formation by UPEC

A

Most common cause of cystits (complicated and non complicated)

invades epithelial cells and hides there

biofilm:

  • Antigen 43
  • Curli - adhesive surface fibers pulls UPEC together
  • Type 1 pilli needed for structure stabilization
79
Q

Describe biofilm formation by P Mirabilis

A

Produces urease increases urine pH

produces magnesium and ammonium phosphate precipatates forming crystals

80
Q

Describe biofilm formation by P aeruginosa

A

Complicated UTI

Forms rhamnolipids coating itself allowing the bacteria to change lipophilicy from more hydrophobic to more hydrophilic allowing initial colonies to form

Matured by promotion of lectin adhesions allowing cells to stick to eachother

81
Q

Describe biofilm formation by E faecalis

A

Can’t bind a catheter in-vitro or in urine by itself

able to atttach to fibrinogen released as a result of an inflammatory response to catheters

uses fibrinogen as a scaffold to start forming its biofilm facilitating a persistent infection

Renal II Quiz II (12 decks)

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