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Renal 2 > Pharmacology: UTI > Flashcards

Pharmacology: UTI Flashcards

1
Q

How many cases of symptomatic UTI are seen each year?

A

150 million

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2
Q

What is the lifetime risk of having at least 1 UTI among women?

A

Higher than 50%

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3
Q

In very young children, do boys or girls get more UTIs?

A

Very young boys–> They have a higher frequency of urethral malformations

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4
Q

In older kids, who gets more UTIs?

A

Girls

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5
Q

In adults, who gets more UTIs?

A

Women

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6
Q

Why do women get more UTIs?

A

They have a short urethra, so bacteria has easier access to the urinary tract

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7
Q

What category of women get UTIs most commonly?

A

Sexually active

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8
Q

In people over 50, who gets more UTIs?

A

It is equal between elderly men and elderly women

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9
Q

What are the 3 types of UTI with associated % of occurrence?

A
  1. Cystitis (90%)
  2. Pyelonephritis (10%)
  3. Asymptomatic
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10
Q

Which types of UTI are symptomatic?

A

Cystitis and pyelonephritis

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11
Q

What is the description of asymptomatic UTI?

A

Bacteria in urine, no symptoms

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12
Q

Where does cystitis affect?

A

Bladder and lower UT

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13
Q

Where does pyelonephritis affect?

A

Kidney and upper UT

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14
Q

What categorizes sporadic recurrence and what is the % of affect?

A

Under or equal to 1 UTI in 6 months and under or equal to 2 UTI in a year
75%

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15
Q

What categorizes recurrent UTI and what is the % of affect?

A

Over or equal to 2 UTI in 6 months and over or equal to 3 UTI in a year
25%

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16
Q

What are the 2 subcategories under recurrent UTI and describe

A
  1. Relapse: No time between infection and usually with same strain of bacteria
  2. Reinfection: Patient is cured from bacteria in urine and there is a period of time with no bacteria…if it comes back, it is usually a different strain
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17
Q

What % of UTI are considered complicated?

A

2%

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18
Q

What 4 features are associated with complicated UTI?

A
  1. Structural abnormalities, like a urinary tract obstruction (calculi, catheters, prostatic hypertrophy)
  2. Metabolic/hormonal abnormalities (diabetes and pregnancy)
  3. Impaired host responses (renal transplants) and AIDS
  4. Unusual pathogens (yeast or hospital-acquired infection)
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19
Q

What is the consequence of complicating factors?

A

Longer therapy and a more detailed workup (no guidelines just recommendations…. make sure to treat complication 1st before bacterial infections)

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20
Q

What are symptoms of cystitis?

A

Frequent voiding, burning during and after voiding, suprapubic pain, hematuria and/or cloudy urine

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21
Q

What are symptoms of pyelonephritis?

A

FEVER, flank pain, chills, with or without cystitis symptoms

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22
Q

What can cystitis symptoms mimic?

A

Urethritis from STDs

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23
Q

What can be done to differentiate between cystitis and urethritis?

A

Urinalysis and urine culture

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24
Q

What is seen in urinalysis and culture for cystitis?

A

Pyuria, most have bacteriuria, half have hematuria

-See organisms on culture

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25
Q

What is is seen in urinalysis and culture for urethritis?

A

Pyuria, no bacteruria, no hematuria

-No bacteria on culture

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26
Q

What can pyelonephritis be mixed up with?

A

Renal stones

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27
Q

How do you differentiate from pyelonephritis and renal stones?

A

Similar pain location for both… but pyelonephritis has FEVER

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28
Q

What is seen on urine analysis for diagnosis of UTI?

A

Pyuria with bacteruria

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29
Q

What blood tests need to be done with pyelonephritis?

A

Blood cultures

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30
Q

Is CRP a good marker for diagnosis of cystitis and pyelonephritis?

A

YES

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31
Q

Is CRP increased in cystitis?

A

NO, it’s increased in pyelonephritis

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32
Q

Is imaging useful in diagnosing UTI?

A

NO

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33
Q

What situation would you use imaging to diagnose UTI?

A

Suspicion that urine flow is blocked (Obstruction…stone, tumor, or abscess)

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34
Q

Do you treat all symptomatic UTI?

A

YES

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35
Q

Why do we treat all symptomatic UTI?

A

To prevent procression to either pyelonephritis or urosepsis

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36
Q

What 3 situations are asymptomatic UTIs treated?

A
  1. Pregnant women
  2. Patients undergoing traumatic genitourinary procedures associated with mucosal bleeding (increased risk of urosepsis)
  3. Patients with catheter-acquired bacteriuria 48 hours after catheter removal
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37
Q

What are general strategies in treating UTI?

A

Treat according to drug susceptibility profile to prevent emergence of bacterial resistance

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38
Q

What is the main principle in treating acute uncomplicated cystitis?

A

Active drug excreted into the urine and have good safety profile

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39
Q

What is the 1st Line Treatment for acute uncomplicated cystitis?

A
  1. Nitrofurantoin
  2. TMP-SMZ
  3. Fosfomycin
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40
Q

Which drug is avoided in elderly due to risk of reducing renal function?

A

TMP-SMZ

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41
Q

Which drugs should be avoided in patients with early pyelonephritis and why?

A

Nitrofurantoin and fosfomycin because they don’t achieve sufficient levels in renal tissues

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42
Q

Is fosfomycin as effective as nitrofurantoin and TMP-SMZ?

A

NO

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43
Q

What is the advantage of fosfomycin?

A

Single dose and low resistance

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44
Q

Which drug has no systemic antibacterial action and is a urinary antiseptic (only indication is for UTI)?

A

Nitrofurantoin

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45
Q

Is nitrofurantoin metabolized and excreted rapidly?

A

YES

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46
Q

What % of nitrofurantoin is recovered in urine unchanged?

A

20-25% (it is filtered and secreted by the kidney)

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47
Q

What is the MOA of nitrofurantoin?

A

It is reduced by bacterial flavoproteins to reactive intermediates, which inactivate or alter bacterial ribosomal proteins and other macromolcules…the vital biochemical processes of protein synthesis, aerobic energy metabolism, DNA synthesis, RNA synthesis, and cell wall synthesis are inhibited (it’s not quite clear, but it basically inhibits everything and it bactericidal)

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48
Q

Tell me about the resistance of nitrofurantoin?

A

Lack of acquired bacterial resistance due to multiple mutation of target macromolecules…it is bactericidal (inhibits everything)

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49
Q

Can bacteria use exogenous folate?

A

NO, they have to make their own folate from PABA

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50
Q

What’s the general MOA of TMP-SMZ?

A

It is a competitive inhibitor of endoigenous substrates for folate production in bacteria

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51
Q

What does sulfamethoxazole inhibit?

A

Dihydropteroate synthase (which converts PABA to dihydrofolic acid

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52
Q

What does trimethoprim inhibit?

A

Dihydrofolate reductase (which converts dihydrofolic acid to tetrahydrofolic acid)

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53
Q

What is the synthesis of folate essential for in bacterial?

A

Purine and nucleic acid synthesis

54
Q

What % of trimethoprim is excreted in urine?

A

50-60%

55
Q

Where can trimethoprim concentrate and what is the effect of this?

A

Prostatic and vaginal fluid… since it can concentrate in tissue it can be used for things other than cystitis

56
Q

What % of sulfamethaxazole is excreted in the urine?

A

30-50%

57
Q

What is the MOA of sulfamethoxazole?

A

It is a structural analog of PABA and inhibits dihydropteroate synthase

58
Q

What is the MOA of trimethoprim?

A

It is a stuctural analog of a portion of dihydrofolic acid, which inhibits dihydrofolate reductase

59
Q

What is the overall effect of the combination of TMP-SMZ?

A

It blocks the sequential steps of folate synthesis and is bactericidal

60
Q

What are the 3 mechanisms of resistnace against TMP-SMZ?

A
  1. Reduced permeability to sulfonamides
  2. Increased PABA
  3. Produce enzymes that has less selectivity for sulfonamides
61
Q

What are the 3 main AE for TMP-SMZ?

A
  1. Megaloblastic anemia
  2. Leukopenia
  3. Granulocytopenia
62
Q

With regards to pregnancy, what are important AE associated with TMP-SMZ?

A
  1. Sulfonamides taken near end of pregnancy increase risk of kernicterus in newborns (bilirubin induced brain dysfunction)
  2. Trimethoprim may interfere with folic acid metabolism of fetus
63
Q

What class of drugs blocks cell wall synthesis?

A

B-lactams

64
Q

What is the general MOA of fosfomycin?

A

It inhibits synthesis of murein monomers.. the 1st step of cell wall synthesis

65
Q

Is fosfomycin excreted unchanged in the urine?

A

Yes

66
Q

What is fosfomycin an analog of?

A

Phosphoenolpyruvate

67
Q

How does fosfomycin get into the bacterial cell?

A

Transported in by glycerophosphate or glucose 6 phosphate tansport system

68
Q

What does fosfomycin bind to and what is the effect of this?

A

Binds covalently to the active site of cytoplasmic enzyme enolpyruvate transferase (MurA)…this blocks the addition of phosphoenolpyruvate to UDP-NAG, which is the first step in the formation of UDP-NAM (Precursor of NAM)

69
Q

What are the 3 mechanisms of resistance to fosfomycin?

A
  1. Mutations relating to the transporters
  2. Mutation to MurA (enol pyruvate transferase)
  3. Enzymes that inactivate fosfomycin
70
Q

What drug causes D-ala-D-ala blockage to tripeptide?

A

Cycloserine

71
Q

What blocks the lipid carrier that injects Nam+pentapeptide into cytoplasm?

A

Bacitracin

72
Q

What drug blocks the polymerization of murein momomers via D-ala, D-ala?

A

Vancomycin

73
Q

What drugs block the transpeptidation involved in cell wall synthesis?

A

Beta-lactams

74
Q

What are the AE of fosfomycin?

A

Really none… it’s non-toxic and safe in pregnancy

75
Q

If you can’t use 1st line drugs for acute uncomplicated cystitis, what can you give?

A
  1. Fluoroquinolones (ofloxacin, ciprofloxacin, levofloxacin)

2. Beta-lactam/cephalosproins (amoxicillin-claculanate, cefaclor, cefpodoxime-proxetil)

76
Q

What’s the problem with fluoroquinolones for acute uncomplicated cystitis?

A

They have a propensity for collateral damage (increased bacterial resistance) and are usually reserved for complicated cystitis or acute pyelonephritis

77
Q

Whats the issue with Beta-lactams and cephalosporins for acute uncomplicated cysitis?

A

Inferior efficacy and adverse effects

78
Q

What is the main principle in treating acute pyelonephritis?

A

The primary decision should be if the patient needs initial treatment with parenteral (IV) or if oral treatment alone with suffice

79
Q

Which type of treatment should we try to give first for acute pyelonephritis?

A

Oral to save $$

80
Q

What tests should be performed before treating acute pyelonephritis and how does this affect initial therapy?

A

Urine culture and susceptibility should always be performed and initial therapy should be tailored on basis of infecting uropathogen

81
Q

What is the 1st line treatment for acute pyelonephritis?

A
  1. Oral ciprofloxacin or levofloxacin with or without IV fluoroquinolone (if resistance is under 10%)
  2. Oral TMP-SMZ
82
Q

In acute pyelonephritis, if resistance is greater than 10% what is the initial treatment?

A

IV Ceftriaxone or consolidated 24hr dose of aminoglycoside

83
Q

Before giving TMP-SMZ for acute pyelonephritis, what do you need to do?

A

Make sure the pathogen is susceptible… if it isn’t then give a fluoroquinolone

84
Q

What is an alternative for acute pyelonephritis and how should it be given?

A

Beta-lactams…because they are less effective for pyelonephritis, an initial IV ceftriaxone or consolidated 24 hour dose of aminoglycoside is used followed by10-14 days of treatment with beta-lactams

85
Q

If a patient with acute pyelonephritis requires hospitalization, what drugs will you give? (5)

A
  1. Fluoroquinolone
  2. Amingoglycoside with or without ampicillin
  3. Cephalosporin
  4. Penicillin with or without amingoglycoside
  5. Carbapenem
86
Q

In acute uncomplicated cystitis, what are 3 options for 1st line treatment?

A
  1. Fosfomycin: Single dose
  2. Nitofurantoin: 2x daily for 5 days
  3. TMP-SMX: 2x daily for 3 days
87
Q

In acute pyelonephritis what are the 2 options for 1st line treatment?

A
  1. Oral ciprofloxacin 7 days or levofloxacin 5 days with or without IV fluoroquinolone if comminty resistance is under 10% (if community resistance is greater than 10%, an initial 1-time IV ceftriaxone or a consolidated 24 hour dose of aminoglycoside)
  2. If pathogen is susceptible to TMP-SMZ, oral 2 times a day for 14 days
88
Q

What are 3 main things contributing to UTI in pregnancy?

A
  1. Short urethra (3-4cm in females)
  2. Difficulty with hygeine because of a giant belly
  3. Smooth muscle relaxation and subsequent ureteral dilation facilitate ascent of bacteria from bladder to kidney
89
Q

What is increase in risk of developing pyelonephritis during pregnancy in women with asymptomatic bacteriuria compared with women without bacteriuria?

A

20-30 fold risk increase…. Always treat UTI in pregnant women aggressively

90
Q

What birth complications do women with untreated UTI have?

A
  1. Increased risk of preterm delivery

2. Low birth weight babies

91
Q

What 5 drugs are given for asymptomatic bacteriuria in pregnant women to prevent cystitis?

A
  1. Amoxicillin, 2x daily for 3-7 days
  2. Amoxicillin-clavulanate, 2x daily for 3-7 days
  3. Cephalexin, 2x daily for 3-7 days
  4. Fosfomycin, single dose
  5. Nitrofurantoin, 2x daily for 5 days
92
Q

What problems are associated with nitrofurantoin in pregnant women?

A
  1. Associated with birth cardiac defects…don’t use in first trimester
  2. Can cause hemolytic anemia in G-6PD deficienct mothers and fetus…avoid near termn
    * These are rare, and nitrofuantoin is generally safe
93
Q

Which drugs are contraindicated in pregnancy and why?

A
  1. Fluoroqinolones: Damage articular cartilage

2. Tetracycline: Affect bone formation

94
Q

What drugs are given for complicated acute cystitis in pregnancy women to prevent pyelonephritis?

A
  1. Amoxicillin-clavulanate, 2x daily for 3-7 days
  2. Cefpodoxime, 2x daily for 3-7 days
  3. Fosfomycin, single dose
  4. Nitrofurantoin, 2x daily for 5 days
95
Q

What other drugs can be given in pregnant women with complicated acute cystitis to prevent pyelonephritis?

A
  1. TMP-SMZ, 2x daily for 3 days

2. Amoxillin, 2x daily for 7 days

96
Q

What is amoxicillin used for specifically in pregnant women with complicated acute cystitis to prevent pyelonephritis?

A

Enterococcus

97
Q

What’s the problem with TMP-SMZ in pregnant women?

A

Trimethoprim inhibits folate synthesis which can cause neural tube defects
Sulfonamides compete with biliorubin binding to serum albumin and increase free filirubin leves–> Neonates are at risk of hyperbilirubinemia, jaindice, and kernicterus near term

98
Q

When is is safe to use TMP-SMZ in pregnancy?

A

2nd trimester (avoid in 1/3)

99
Q

What is the general principle in treating acute pyelonephritis in a pregnant patient?

A

Hospitaliozation and IV antibacterials until afebrile for 48 hours, then switch to oral therapy

100
Q

What 2 drug classes are used in treating acute pyelonephritis in a pregnant patient?

A
  1. Parenteral B-lactams (preferred antibacerials

2. Carbapnems (ertapenem, doripenem)

101
Q

Which specific B-lactams are used in treating acute pyelonephritis in a pregnant patient and why?

A

3rd generation beta-lactams (ceftriazone)… 1 and 2 generation beta-lactams are less effective and have narrower spectrum

102
Q

Why are carbapenems more effective than cefalosporins?

A

They aren’t susceptible to Beta-lactamase

103
Q

When would be use a carbapenem over a beta-lactam in treating acute pyelonephritis in a pregnant patient?

A

When you have a beta-lactamase producing strain… Carbapenems are effective for extended-spectrum b-lactamase-producing strains

104
Q

Why are aminoglycosides avoided in treating pregnant patients with pyelonephritis?

A

They have an association with ototoxicity following prolonged fetal exposure

105
Q

When is prophylaxis indicated for UTI?

A

Only in recurrent uncomplicated UTIs

106
Q

What do you have to do before any prophylaxis regimen is initiated?

A

Assure eradication of a previous UTI by obtaining a negative urine culture 1-2 weeks after treatment (avoid bacterial resistnace)

107
Q

What case is the exception for prophylaxis against a complicated UTI?

A

Pregnant women (even if the UTI is complicated, prophylatic treatment is justified)

108
Q

What drugs are given as prophylaxis for recurrent cystitis and pyelonephritis?

A
  1. Cephalexin

2. Nitrofurantoin

109
Q

What drugs are given as prophylaxis for a sexually related even in a single postcoital dose?

A
  1. Cephalexin
  2. Nitrofurantoin
  3. TMP-SMZ
110
Q

What do you do for prophylaxis is the single postcoital dose fails?

A

Treat 3 times weekly continuously 6mo-1yr with

  1. Nitrofurantoin
  2. TMP-SMZ
  3. Norfloxacin
111
Q

What is given as prophylaxis for post-menopausal women?

A
  1. Estrogen replacement reduces pH and normalizes vaginal flora
112
Q

What can be given OTC to prevent UTI?

A

CRANBERRY JUICE (10oz/day) or tablets may offer some benefit in reducing recurrent UTI

113
Q

What is in cranberries and how does this work to prevent UTI?

A

Type A proanthocyanidins… this compound and its urinary metabolites attach to bacterial fimbriae and prevent bacteria from attaching to the wall of the urinary tract

114
Q

Do cranberries induce bacterial resistnace?

A

No

115
Q

Are cranberries as effective as antibacterials?

A

No

116
Q

Why is it difficult to design a valid study to compare cranberries to antibacterials?

A

There is variable intestinal absorption and metabolism

117
Q

Which drugs pose risks in patients with renal insufficiency?

A

Nitrofurantoin and TMP-SMZ because they are secreted into the urine

118
Q

What can funguria be treated with?

A

Fluconazole

119
Q

When do you treat funguria?

A

Only when it’s symptomatic (in catheterized patients)

120
Q

Should asymptomatic bacteruria in pregnancy be treated as prophylaxis to prevent cystitis?

A

YES

121
Q

What are 2 drugs that would be used to treat recuurent asymptomatic bacteruia in pregnancy?

A

Cephalexin and nitrofurantoin

122
Q

What drugs for acute uncomplicated cystitis in non-pregnant women?

A
  1. Nitrofurantoin
  2. TMP-SMZ
  3. Fosfomycin
123
Q

What drugs for acute pyelonephritis in non-pregnant women?

A
  1. TMP-SMZ

2. Fluoroquinolones

124
Q

What drugs for asymptomatic bacteriuria in pregnant women?

A
  1. Amoxicillin
  2. Amoxicillin-clavulanate
  3. Cephalexin
  4. Fosfomycin
  5. Nitrofurantoin
125
Q

What drugs for acute complicated cystitis in pregnant women?

A
  1. Amoxicillin-clavulanate
  2. Cefpodoxime
  3. Fosfomycin
  4. Nitrofurantoin
126
Q

What drugs for acute pyelonephritis in pregnant women?

A
  1. Ceftriaxone

2. Carbapenems

127
Q

What drugs for recurrent infections in pregnant women?

A
  1. Cefalexin

2. Nitrofurantoin

128
Q

What drugs for recurrent sexually-related UTI?

A
  1. Cefalexin
  2. Nitrofurantoin
  3. TMP-SMZ
129
Q

What drugs for recurrent UTI in single post-coital fails?

A
  1. Nitrofurantoin
  2. TMP-SMZ
  3. Norfloxacin
130
Q

What drugs for recurrent UTI in post-menopausal women?

A

Estrogen replacement

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