L78 – Drugs used in urinary tract infection

Question 1

Name the infection of bladder, urethra, prostate and upper urinary tract?

Answer 1

Bladder= cystits
Urethra = Urethritis
Prostate = Prostatitis
Upper urinary tract = Pyelonephritis

Question 2

Most common causative agent of Catheter-associated UTI?

Answer 2

Candida spp

E. coli

Question 3

Most common pathogens for urethritis?

Answer 3

Chlamydia trachomatis

Neisseria Gonorrhea

Question 4

Klebsiella pneumoniae is 100% resistant to ?

Answer 4

ampicillin

Question 5

Proteus mirabilis is 100% resistant to ?

Answer 5

nitrofurantoin

Question 6

Quantitative cultures may be optional before treatment of what UTI?

Answer 6

typical acute uncomplicated cystitis

Question 7

Culture urine in patients with which UTI?

Answer 7

upper UTI / complicated UTI / treatment failure

Question 8

What testing is done in all recurrent or complicated UTI?

Answer 8

Susceptibility testing

Question 9

What is the guideline for FIRST LINE antibiotic use in acute Uncomplicated UTI in female adults?

Answer 9

nitrofurantoin (7 days, oral)

amoxicillin-clavulanate (7 days, oral)

Question 10

Why is nitrodurantoin used for acute Uncomplicated UTI in female adults?

Answer 10

Low local resistance rate

Less likely to select drug-resistant organisms

Question 11

What is the guideline for SECOND LINE antibiotic use in acute Uncomplicated UTI in female adults?

Answer 11

All oral:

Cefuroxime (cephalosporin)

Fluoroquinolones:

• Levofloxacin
• Ciprofloxacin
• Ofloxacin

Question 12

Bacteria that cause Acute cystitis?

Answer 12

Escherichia coli,

Staphylococcus saprophyticus,

Group B streptococcus

Question 13

What is the guideline for FIRST LINE antibiotic use in uncomplicated UTI in children?

Answer 13

1st-line: cefuroxime / co-trimoxazole

Question 14

Which drugs are not recommended for infants under 3 months old with UTI?

Answer 14

co-trimoxazole, nitrofurantoin, nalidixic acid

Question 15

What precaution is taken when treating children younger than 3 with UTI?

Answer 15

Higher chance of recurrent infection

> > consider antibiotics prophylaxis after
curative treatment

Question 16

What is the guideline for Asymptomatic Candiduria UTI due to Candida spp?

Answer 16

Asymptomatic Candiduria:

 Eliminate predisposing factors, e.g. remove bladder catheters

 DO NOT treat with local / systemic antifungal agents unless patient belongs to high-risk group for
dissemination (e.g. Neutropenic patients)

Question 17

What is the guideline for Symptomatic Candiduria UTI due to Candida spp?

Answer 17

For fluconazole-susceptible organisms: oral fluconazole

For fluconazole-resistant species: AmB deoxycholate, Oral flucytosine

Question 18

What is the guideline for Symptomatic ascending Candida pyelonephritis due to Candida spp?

Answer 18

fluconazole-susceptible organisms: oral fluconazole

For fluconazole-resistant:
AmB deoxycholate, oral flucytosine

Question 19

What do Azoles inhibit?

Answer 19

inhibit synthesis of

ergosterol from lanosterol&raquo_space; inhibit formation of cell membrane

Question 20

What do Polyenes (e.g. amphotericin B) inhibit?

Answer 20

bind
to ergosterol = cannot form
membrane (impaired integrity)

Question 21

What does Flucytosine inhibit?

Answer 21

inhibits DNA/RNA synthesis

Question 22

Treatment of Candida UTI associated with Fungus Ball?

Answer 22

 Adults: surgical intervention

 Cystitis / pyelonephritis: anifungal treatment

Question 23

What are the 2 Chlamydial infections?

Answer 23

urethritis, cervicitis

Question 24

What is the empirical treatment for Chlamydial infections?

Answer 24

 Azithromycin (oral daily)
or
 Doxycycline (orally twice daily for 7 days)

Question 25

What is the empirical treatment for Chlamydial infections if the patient is pregnant??

Answer 25

use azithromycin instead of Doxycycline

Question 26

WHat are alternative drugs for Chlamydial infections?

Answer 26

tetracycline / erythromycin / ofloxacin

Question 27

WHat are adverse drug reactions from Chlamydial infection drugs?

Answer 27

mostly gastrointestinal (mild to moderate)

Question 28

What is Gonococcal infections?

Answer 28

urethritis (purulent discharge), cervicitis

Question 29

What bacteria causes Gonocaccal infections?

Answer 29

Neisseria gonorrhoeae Could be penicillin- and tetracycline-resistant strains

Question 30

What is the empirical therapy for penicillin- and tetracycline-resistant strains of Neisseria gonorrhoeae?

Answer 30

dual therapy: 1) Single IM injection of ceftriaxone or cefixime orally 2) Single oral dose of azithromycin

Question 31

Which drugs are no longer the first line for gonococcal infections and why?

Answer 31

Increased resistance to oral cephalosporins / fluoroquinolones = no longer 1st-line

Question 32

Always treat for what infection when treating gonococcal infection?

Answer 32

Always treat also for Chlamydia when treating for gonorrheae (usually infected by both)

Question 33

What is caused by unsuccessful treatment of gonococcal infections?

Answer 33

Unsuccessful treatment can cause pelvic inflammatory disease

Question 34

What is the preferred drug for treating prostatitis? Why?

Answer 34

quinolones (e.g. ciprofloxacin, levofloxacin) favourable pharmacokinetic properties: - high tissue penetration, mainly excreted into urine

Question 35

Alternative drugs to quinolones for treating prostatitis?

Answer 35

clarithromycin, azithromycin, doxycycline

Question 36

What additional therapeutic effects arise from drugs treating prostatitis?

Answer 36

anti-inflammatory and/or anti-neuropathic effect

Question 37

How do Non-beta-lactams inhibit cell wall synthesis? (e.g. Vancomycin, Bacitracin?

Answer 37

``` inhibit early steps of peptidoglycan synthesis (not cross-linkage) ```

Question 38

Extended spectrum penicillins are effective against which bacteria? Sensitive to what?

Answer 38

Effective vs. many Gram –ve bacilli in UTI, bacteremia, skin infections.. etc Sensitive to Beta-lactamase, acid labile

Question 39

What is the drug combo used to counter act B-lactamase produced by bacteria?

Answer 39

ß-lactam (broad spectrum penicillin) + ß-lactamase inhibitors (prevent hydrolysis of β-lactam ring, irreversible)

Question 40

What are the 4 preparations of B-lactam + B-lactamase inhibitors?

Answer 40

 Augmentin® (amoxicillin + clavulanic acid  Unasyn® (ampicillin + sulbactam  Timentin® (ticarcillin + clavulanic acid)  Tazocin® (piperacillin + tazobactam)

Question 41

Apart from Beta-lactamase, name another mechanism of resistance against Beta-lactams?

Answer 41

Change in structure of transpeptidase to bind less effectively to B-lactam antibiotics

Question 42

MoA of Macrolides and Tetracyclines?

Answer 42

Inhibit 30S:  Tetracyclines: blocks tRNA binding to ribosome (30S) Inhibit 50S:  Macrolides: bind to P site >> inhibit polypeptide chain to be translocated from A to P site

Question 43

What does Aminoglycosides interfere with in bacteria?

Answer 43

binds to 30S ribosome >> disrupt protein synthesis

Question 44

Apart from macrolides, name some other 50s inhibitors?

Answer 44

 Clindamycin  Linezolid  Chloramphenicol:

Question 45

Name 2 antibiotics that inhibit folate synthesis in bacteria?

Answer 45

Sulfonamides, trimethoprim Both structurally similar to folate intermediates of DNA synthesis

Question 46

MoA of sulfamethoxazole?

Answer 46

structural analog of para-aminobenzoic acid (PABA)): competitively inhibits synthesis of dihydrofolic acid from PABA

Question 47

MoA of Trimethoprim?

Answer 47

structural analog of a potion of dihydrofolic acid): ``` competitively inhibits synthesis of tetrahydrofolic acid (precursor of DNA, RNA and proteins) ```

Question 48

Are folate inhibitors bacteriostatic or cidal?

Answer 48

Bacteriostatic

Question 49

What is the synergistic ratio for inhibiton of folate synthesis? Why?

Answer 49

Cotrimoxazole: Trimethoprim/ Sulmethoxazole ratio 1:5 >> sequential blockade in folic acid synthesis

Question 50

Adverse effects of folate synthesis inhibitors?

Answer 50

Skin rash, Megaloblastic anaermia, Haemolytic anaemia (in patients with G6PD deficiency)

Question 51

Name antibiotics that inhibit DNA and RNA synthesis?

Answer 51

RNA = Rifampin/ Riframpicin DNA = Metronidazole, Quinolones

Question 52

Metronidazole MoA?

Answer 52

Metabolized to unstable molecule with DNA >> DNA breaks > inhibit DNA synthesis

Question 53

MoA of quinolones?

Answer 53

bind to gyrase- / topoisomerase IV-DNA complex >> inhibit DNA unwinding during replication >> block DNA synthesis

Question 54

Name some 1st and 2nd gen quinolones?

Answer 54

1st = nalidixic acid 2nd = ciprofloxacin, ofloxacin

Question 55

Name some 3rd and 4th gen quinolones?

Answer 55

3 = Levofloxacin 4 = Gemifloxacin

Question 56

When is Nitrofurantoin taken and not taken?

Answer 56

Taken: For uncomplicated UTI, prophylaxis for recurrent UTI Not taken: for pyelonephritis due to low tissue penetration

Question 57

Resistance, serum and urine levels of Nitrofurantoin?

Answer 57

Low rate of resistance (due to many mechanisms of action) Serum level low Concentrated in urine

Question 58

Harmless side effect of Nitrofurantoin?

Answer 58

Brown urine, but harmless

Question 59

MoA of Nitrofurantoin?

Answer 59

Nitrofuran reductase activates nitrofurantoin produce reactive intermediates (free radicals) to attack: - DNA, - ribosomal proteins, - respiration, - macromolecules

Question 60

What is Fosfomycin? MoA?

Answer 60

Phosphenolpyruvate analogue >> irreversibly inhibits enolpyruvate transferase (MurA) to prevent formation of NAM for cell wall

Question 61

WHat is the gold standard for bacteria?

Answer 61

antibiotic susceptibility testing: agar diffusion test >> zone of inhibition

Question 62

What is the new method of identifying bacteria?

Answer 62

barcoding approach: sequence bacterial DNA >> identify a few fingerprint region of bacteria >> compare with database to assess susceptibility

Question 63

How is drug dose determined whilst considering genetics and adverse reaction?

Answer 63

Screen biomarkers / genome to assess adverse reaction >> determine dose