Pharmacology: UTI Flashcards
1
Q
How many cases of symptomatic UTI are seen each year?
A
150 million
2
Q
What is the lifetime risk of having at least 1 UTI among women?
A
Higher than 50%
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
4
Q
In older kids, who gets more UTIs?
A
Girls
5
Q
In adults, who gets more UTIs?
A
Women
6
Q
Why do women get more UTIs?
A
They have a short urethra, so bacteria has easier access to the urinary tract
7
Q
What category of women get UTIs most commonly?
A
Sexually active
8
Q
In people over 50, who gets more UTIs?
A
It is equal between elderly men and elderly women
9
Q
What are the 3 types of UTI with associated % of occurrence?
A
- Cystitis (90%)
- Pyelonephritis (10%)
- Asymptomatic
10
Q
Which types of UTI are symptomatic?
A
Cystitis and pyelonephritis
11
Q
What is the description of asymptomatic UTI?
A
Bacteria in urine, no symptoms
12
Q
Where does cystitis affect?
A
Bladder and lower UT
13
Q
Where does pyelonephritis affect?
A
Kidney and upper UT
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%
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%
16
Q
What are the 2 subcategories under recurrent UTI and describe
A
- Relapse: No time between infection and usually with same strain of bacteria
- 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
17
Q
What % of UTI are considered complicated?
A
2%
18
Q
What 4 features are associated with complicated UTI?
A
- Structural abnormalities, like a urinary tract obstruction (calculi, catheters, prostatic hypertrophy)
- Metabolic/hormonal abnormalities (diabetes and pregnancy)
- Impaired host responses (renal transplants) and AIDS
- Unusual pathogens (yeast or hospital-acquired infection)
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)
20
Q
What are symptoms of cystitis?
A
Frequent voiding, burning during and after voiding, suprapubic pain, hematuria and/or cloudy urine
21
Q
What are symptoms of pyelonephritis?
A
FEVER, flank pain, chills, with or without cystitis symptoms
22
Q
What can cystitis symptoms mimic?
A
Urethritis from STDs
23
Q
What can be done to differentiate between cystitis and urethritis?
A
Urinalysis and urine culture
24
Q
What is seen in urinalysis and culture for cystitis?
A
Pyuria, most have bacteriuria, half have hematuria
-See organisms on culture
25
What is is seen in urinalysis and culture for urethritis?
Pyuria, no bacteruria, no hematuria
| -No bacteria on culture
26
What can pyelonephritis be mixed up with?
Renal stones
27
How do you differentiate from pyelonephritis and renal stones?
Similar pain location for both... but pyelonephritis has FEVER
28
What is seen on urine analysis for diagnosis of UTI?
Pyuria with bacteruria
29
What blood tests need to be done with pyelonephritis?
Blood cultures
30
Is CRP a good marker for diagnosis of cystitis and pyelonephritis?
YES
31
Is CRP increased in cystitis?
NO, it's increased in pyelonephritis
32
Is imaging useful in diagnosing UTI?
NO
33
What situation would you use imaging to diagnose UTI?
Suspicion that urine flow is blocked (Obstruction...stone, tumor, or abscess)
34
Do you treat all symptomatic UTI?
YES
35
Why do we treat all symptomatic UTI?
To prevent procression to either pyelonephritis or urosepsis
36
What 3 situations are asymptomatic UTIs treated?
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
37
What are general strategies in treating UTI?
Treat according to drug susceptibility profile to prevent emergence of bacterial resistance
38
What is the main principle in treating acute uncomplicated cystitis?
Active drug excreted into the urine and have good safety profile
39
What is the 1st Line Treatment for acute uncomplicated cystitis?
1. Nitrofurantoin
2. TMP-SMZ
3. Fosfomycin
40
Which drug is avoided in elderly due to risk of reducing renal function?
TMP-SMZ
41
Which drugs should be avoided in patients with early pyelonephritis and why?
Nitrofurantoin and fosfomycin because they don't achieve sufficient levels in renal tissues
42
Is fosfomycin as effective as nitrofurantoin and TMP-SMZ?
NO
43
What is the advantage of fosfomycin?
Single dose and low resistance
44
Which drug has no systemic antibacterial action and is a urinary antiseptic (only indication is for UTI)?
Nitrofurantoin
45
Is nitrofurantoin metabolized and excreted rapidly?
YES
46
What % of nitrofurantoin is recovered in urine unchanged?
20-25% (it is filtered and secreted by the kidney)
47
What is the MOA of nitrofurantoin?
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)
48
Tell me about the resistance of nitrofurantoin?
Lack of acquired bacterial resistance due to multiple mutation of target macromolecules...it is bactericidal (inhibits everything)
49
Can bacteria use exogenous folate?
NO, they have to make their own folate from PABA
50
What's the general MOA of TMP-SMZ?
It is a competitive inhibitor of endoigenous substrates for folate production in bacteria
51
What does sulfamethoxazole inhibit?
Dihydropteroate synthase (which converts PABA to dihydrofolic acid
52
What does trimethoprim inhibit?
Dihydrofolate reductase (which converts dihydrofolic acid to tetrahydrofolic acid)
53
What is the synthesis of folate essential for in bacterial?
Purine and nucleic acid synthesis
54
What % of trimethoprim is excreted in urine?
50-60%
55
Where can trimethoprim concentrate and what is the effect of this?
Prostatic and vaginal fluid... since it can concentrate in tissue it can be used for things other than cystitis
56
What % of sulfamethaxazole is excreted in the urine?
30-50%
57
What is the MOA of sulfamethoxazole?
It is a structural analog of PABA and inhibits dihydropteroate synthase
58
What is the MOA of trimethoprim?
It is a stuctural analog of a portion of dihydrofolic acid, which inhibits dihydrofolate reductase
59
What is the overall effect of the combination of TMP-SMZ?
It blocks the sequential steps of folate synthesis and is bactericidal
60
What are the 3 mechanisms of resistnace against TMP-SMZ?
1. Reduced permeability to sulfonamides
2. Increased PABA
3. Produce enzymes that has less selectivity for sulfonamides
61
What are the 3 main AE for TMP-SMZ?
1. Megaloblastic anemia
2. Leukopenia
3. Granulocytopenia
62
With regards to pregnancy, what are important AE associated with TMP-SMZ?
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
What class of drugs blocks cell wall synthesis?
B-lactams
64
What is the general MOA of fosfomycin?
It inhibits synthesis of murein monomers.. the 1st step of cell wall synthesis
65
Is fosfomycin excreted unchanged in the urine?
Yes
66
What is fosfomycin an analog of?
Phosphoenolpyruvate
67
How does fosfomycin get into the bacterial cell?
Transported in by glycerophosphate or glucose 6 phosphate tansport system
68
What does fosfomycin bind to and what is the effect of this?
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
What are the 3 mechanisms of resistance to fosfomycin?
1. Mutations relating to the transporters
2. Mutation to MurA (enol pyruvate transferase)
3. Enzymes that inactivate fosfomycin
70
What drug causes D-ala-D-ala blockage to tripeptide?
Cycloserine
71
What blocks the lipid carrier that injects Nam+pentapeptide into cytoplasm?
Bacitracin
72
What drug blocks the polymerization of murein momomers via D-ala, D-ala?
Vancomycin
73
What drugs block the transpeptidation involved in cell wall synthesis?
Beta-lactams
74
What are the AE of fosfomycin?
Really none... it's non-toxic and safe in pregnancy
75
If you can't use 1st line drugs for acute uncomplicated cystitis, what can you give?
1. Fluoroquinolones (ofloxacin, ciprofloxacin, levofloxacin)
| 2. Beta-lactam/cephalosproins (amoxicillin-claculanate, cefaclor, cefpodoxime-proxetil)
76
What's the problem with fluoroquinolones for acute uncomplicated cystitis?
They have a propensity for collateral damage (increased bacterial resistance) and are usually reserved for complicated cystitis or acute pyelonephritis
77
Whats the issue with Beta-lactams and cephalosporins for acute uncomplicated cysitis?
Inferior efficacy and adverse effects
78
What is the main principle in treating acute pyelonephritis?
The primary decision should be if the patient needs initial treatment with parenteral (IV) or if oral treatment alone with suffice
79
Which type of treatment should we try to give first for acute pyelonephritis?
Oral to save $$
80
What tests should be performed before treating acute pyelonephritis and how does this affect initial therapy?
Urine culture and susceptibility should always be performed and initial therapy should be tailored on basis of infecting uropathogen
81
What is the 1st line treatment for acute pyelonephritis?
1. Oral ciprofloxacin or levofloxacin with or without IV fluoroquinolone (if resistance is under 10%)
2. Oral TMP-SMZ
82
In acute pyelonephritis, if resistance is greater than 10% what is the initial treatment?
IV Ceftriaxone or consolidated 24hr dose of aminoglycoside
83
Before giving TMP-SMZ for acute pyelonephritis, what do you need to do?
Make sure the pathogen is susceptible... if it isn't then give a fluoroquinolone
84
What is an alternative for acute pyelonephritis and how should it be given?
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
If a patient with acute pyelonephritis requires hospitalization, what drugs will you give? (5)
1. Fluoroquinolone
2. Amingoglycoside with or without ampicillin
3. Cephalosporin
4. Penicillin with or without amingoglycoside
5. Carbapenem
86
In acute uncomplicated cystitis, what are 3 options for 1st line treatment?
1. Fosfomycin: Single dose
2. Nitofurantoin: 2x daily for 5 days
3. TMP-SMX: 2x daily for 3 days
87
In acute pyelonephritis what are the 2 options for 1st line treatment?
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
What are 3 main things contributing to UTI in pregnancy?
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
What is increase in risk of developing pyelonephritis during pregnancy in women with asymptomatic bacteriuria compared with women without bacteriuria?
20-30 fold risk increase.... Always treat UTI in pregnant women aggressively
90
What birth complications do women with untreated UTI have?
1. Increased risk of preterm delivery
| 2. Low birth weight babies
91
What 5 drugs are given for asymptomatic bacteriuria in pregnant women to prevent cystitis?
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
What problems are associated with nitrofurantoin in pregnant women?
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
Which drugs are contraindicated in pregnancy and why?
1. Fluoroqinolones: Damage articular cartilage
| 2. Tetracycline: Affect bone formation
94
What drugs are given for complicated acute cystitis in pregnancy women to prevent pyelonephritis?
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
What other drugs can be given in pregnant women with complicated acute cystitis to prevent pyelonephritis?
1. TMP-SMZ, 2x daily for 3 days
| 2. Amoxillin, 2x daily for 7 days
96
What is amoxicillin used for specifically in pregnant women with complicated acute cystitis to prevent pyelonephritis?
Enterococcus
97
What's the problem with TMP-SMZ in pregnant women?
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
When is is safe to use TMP-SMZ in pregnancy?
2nd trimester (avoid in 1/3)
99
What is the general principle in treating acute pyelonephritis in a pregnant patient?
Hospitaliozation and IV antibacterials until afebrile for 48 hours, then switch to oral therapy
100
What 2 drug classes are used in treating acute pyelonephritis in a pregnant patient?
1. Parenteral B-lactams (preferred antibacerials
| 2. Carbapnems (ertapenem, doripenem)
101
Which specific B-lactams are used in treating acute pyelonephritis in a pregnant patient and why?
3rd generation beta-lactams (ceftriazone)... 1 and 2 generation beta-lactams are less effective and have narrower spectrum
102
Why are carbapenems more effective than cefalosporins?
They aren't susceptible to Beta-lactamase
103
When would be use a carbapenem over a beta-lactam in treating acute pyelonephritis in a pregnant patient?
When you have a beta-lactamase producing strain... Carbapenems are effective for extended-spectrum b-lactamase-producing strains
104
Why are aminoglycosides avoided in treating pregnant patients with pyelonephritis?
They have an association with ototoxicity following prolonged fetal exposure
105
When is prophylaxis indicated for UTI?
Only in recurrent uncomplicated UTIs
106
What do you have to do before any prophylaxis regimen is initiated?
Assure eradication of a previous UTI by obtaining a negative urine culture 1-2 weeks after treatment (avoid bacterial resistnace)
107
What case is the exception for prophylaxis against a complicated UTI?
Pregnant women (even if the UTI is complicated, prophylatic treatment is justified)
108
What drugs are given as prophylaxis for recurrent cystitis and pyelonephritis?
1. Cephalexin
| 2. Nitrofurantoin
109
What drugs are given as prophylaxis for a sexually related even in a single postcoital dose?
1. Cephalexin
2. Nitrofurantoin
3. TMP-SMZ
110
What do you do for prophylaxis is the single postcoital dose fails?
Treat 3 times weekly continuously 6mo-1yr with
1. Nitrofurantoin
2. TMP-SMZ
3. Norfloxacin
111
What is given as prophylaxis for post-menopausal women?
1. Estrogen replacement reduces pH and normalizes vaginal flora
112
What can be given OTC to prevent UTI?
CRANBERRY JUICE (10oz/day) or tablets may offer some benefit in reducing recurrent UTI
113
What is in cranberries and how does this work to prevent UTI?
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
Do cranberries induce bacterial resistnace?
No
115
Are cranberries as effective as antibacterials?
No
116
Why is it difficult to design a valid study to compare cranberries to antibacterials?
There is variable intestinal absorption and metabolism
117
Which drugs pose risks in patients with renal insufficiency?
Nitrofurantoin and TMP-SMZ because they are secreted into the urine
118
What can funguria be treated with?
Fluconazole
119
When do you treat funguria?
Only when it's symptomatic (in catheterized patients)
120
Should asymptomatic bacteruria in pregnancy be treated as prophylaxis to prevent cystitis?
YES
121
What are 2 drugs that would be used to treat recuurent asymptomatic bacteruia in pregnancy?
Cephalexin and nitrofurantoin
122
What drugs for acute uncomplicated cystitis in non-pregnant women?
1. Nitrofurantoin
2. TMP-SMZ
3. Fosfomycin
123
What drugs for acute pyelonephritis in non-pregnant women?
1. TMP-SMZ
| 2. Fluoroquinolones
124
What drugs for asymptomatic bacteriuria in pregnant women?
1. Amoxicillin
2. Amoxicillin-clavulanate
3. Cephalexin
4. Fosfomycin
5. Nitrofurantoin
125
What drugs for acute complicated cystitis in pregnant women?
1. Amoxicillin-clavulanate
2. Cefpodoxime
3. Fosfomycin
4. Nitrofurantoin
126
What drugs for acute pyelonephritis in pregnant women?
1. Ceftriaxone
| 2. Carbapenems
127
What drugs for recurrent infections in pregnant women?
1. Cefalexin
| 2. Nitrofurantoin
128
What drugs for recurrent sexually-related UTI?
1. Cefalexin
2. Nitrofurantoin
3. TMP-SMZ
129
What drugs for recurrent UTI in single post-coital fails?
1. Nitrofurantoin
2. TMP-SMZ
3. Norfloxacin
130
What drugs for recurrent UTI in post-menopausal women?
Estrogen replacement
