Drugs Treatment of LUT Infections and STI's (Kinder)

Question 1

what is the MOA of trimethoprim/sulfamethoxazole (TMP/SMX)

Answer 1

sulfonamides are bacteriostatic, competitive inhibitors of dihydropteroate synthase; while synergistic trimethoprim inhibits dihydrofolate reductase.

i) Administering both sulfamethoxazole and trimethoprim inhibits sequential steps in the folic acid pathway. Prevents bacterial use of para-aminobenzoic acid (PABA) for synthesis of folic acid and inhibits final reduction step.

Question 2

do you need to adjust TMP/SMX in renal impairement

Answer 2

yes

Question 3

ADR’s of TMP/SMX

Answer 3

allergic skin rashes, nausea, vomiting,

CNS (headache, depression),

photosensitivity,

renal dysfunction, Stevens-Johnson syndrome.

Question 4

What are the drug-drug interactions of TMP/SMX

Answer 4

inhibits CYP metabolism of drugs → potentiates the effects of warfarin!!

May also increase serum concentrations of digoxin, phenytoin, and others.

May enhance hyperkalemic effect of ACEIs, ARBs, and spironolactone.

Question 5

MOA of Nitrofurantoin

Answer 5

this is a urinary tract antiseptic

taken PO

drug reduced forming highly reactive intermediates which damage DNA, bacteria reduce drug more rapidly than mammalian cells, thought to account for selective activity.

Question 6

what are the ADR’s of Nitrofurantoin

Answer 6

nausea, vomiting, diarrhea, macro-crystalline prep better tolerated.

Course of therapy should not exceed 14 days and repeated course should be separated by rest periods.

Question 7

in what pt’s is nitrofurantoin contraindicated

Answer 7

pregnant women,

impaired renal function (40 mL/min),

children < 1 month.

Question 8

Methenamine MOA

Answer 8

MOA
decomposes in water to formaldehyde, acidification of urine promotes formaldehyde formation, slow process (requires 3 hours to complete).

not primary drug in UTI but has value in chronic suppressive therapy.

Question 9

when is methenamine contraindicated

Answer 9

i) Ammonia produced so CI in hepatic insufficiency.

Question 10

what are the ADR’s of methenamine

Answer 10

GI distress,

painful/frequent micturition,

hematuria,

rash,

low systemic toxicity at usual doses.

Question 11

Fosfomycin MOA

Answer 11

bactericidal, inhibits very early stage of bacterial cell wall synthesis. Inactivates pyruvyl transferase which leads to reduced formation of N-acetylmuramic acid, which is only found in bacterial cell walls.

Question 12

what is the t1/2 life of fosfomycin if creatinine clearance is <54 mL/min

Answer 12

50 hours LONG

Question 13

ADR’s of fosfomycin

Answer 13

c) ADRs: diarrhea, nausea, abdominal pain, headache.

Question 14

MOA of fluoroquinolones (Ciprofloxacin)

Answer 14

a) MOA: concentration-dependent killing, targets bacterial DNA gyrase and topoisomerase IV.

Question 15

do you need to adjust fluoroquinolones in renal impairment?

Answer 15

yes

Question 16

what are the ADRs of fluoroquinolones

Answer 16

GI 3-17% most common (mild nausea, vomiting, abdominal discomfort)

CNS 0.9-11% (mild headache, dizziness, delirium, rare hallucinations)

rash

photosensitivity

Achilles tendon rupture.

Question 17

MOA of B-lactams

Answer 17

inhibits the transpeptidation reaction, the last step in peptidoglycan synthesis.

Peptidoglycan composed of two alternating sugars (N-acetylglucosamine and N-acetylmuramic acid).

Five-amino-acid peptide linked to final N-acetylmuramic acid which terminates in D-alanyl-D-alanine.

Penicillin binding proteins (PBPs) remove the terminal D-alanine in the process of forming the cross-link.

B-lactams are structural analogs of D-Ala-D-Ala.

B-lactams covalently bind PBPs preventing cross-linking ultimately leading to cell autolysis.

Question 18

Penicillin G benzathine (B-lactam) ADR’s

Answer 18

allergic reactions (0.7-10%),

anaphylaxis (0.004-0.04%),

interstitial nephritis (rare),

pseudomembranous colitis,

Jarisch-Herxheimer reaction.

Question 19

what is the drug of choice for susceptible enterococci

Answer 19

Ampicillin (B-lactam)

Question 20

Ceftriaxone- a cephalosporin (B-lactam)

ADR’s

Answer 20

1% risk of cross-reactivity to penicillins,

injection site reaction,

diarrhea.

***usually reserved for serious infections

Question 21

MOA of Azithromycin

Answer 21

This is a macrolide

works at 50S

bacteriostatic, binds reversibly to 50S ribosomal subunit, inhibits translocation of newly synthesized peptidyl tRNA molecule from acceptor site on ribosome to peptidyl donor site.

Question 22

what can reduce the absorption of azithromycin

Answer 22

administration of aluminum and magnesium hydroxide antacids

Question 23

what are the ADR’s of azithromycin

Answer 23

GI (epigastric distress)

hepatotoxicity

arrhythmia

QT prolongation

Question 24

in general what are the DDI’s of macrolides

Answer 24

CYP3A4 inhibition – prolongs effects of digoxin, valproate, warfarin, others.
i) Azithromycin structure differs making it less likely to produce DDIs but should use caution.

Question 25

Metronidazole MOA

Answer 25

: prodrug, requires reductive activation of nitro groups. Single electron transfer in anaerobic bacteria forms highly reactive nitro radical anions, kills organisms by radically mediated mechanisms that target DNA. Increasing 02 inhibits metronidazole as 02 competes for electrons.

Question 26

what are the ADR's of metronidazole

Answer 26

: headache, nausea, dry mouth, metallic taste. Vomiting, diarrhea, abdominal distress occasionally . Neurotoxic: dizziness, vertigo, very rarely encephalopathy. Well-reported disulfiram effect → abdominal distress, vomiting, flushing, headache, if alcohol consumed during/within 3 days of drug.

Question 27

what are the DDI's of metronidazole

Answer 27

induced metabolism of phenobarbital, prednisone, and rifampin. Prolongs prothrombin time in those receiving warfarin.

Question 28

what is a UTI

Answer 28

a) Urinary Tract Infection (UTI): presence of microorganisms within the urinary tract; not due to contamination. Organisms have potential to invade tissues of urinary tract and adjacent structures.

Question 29

what is an uncomplicated UTI

Answer 29

infection in individuals who lack structural or functional abnormalities of the urinary tract. Occurs in pre-menopausal females of childbearing age (15-45 years) who are otherwise healthy.

Question 30

why are male UTI's never uncomplicated?

Answer 30

not considered uncomplicated because these infections are rare and most often a result of a structural or neurological abnormality.

Question 31

what is a complicated UTI

Answer 31

likely the result of a predisposing lesion (congenital abnormality or distortion), a stone, indwelling catheter, prostatic hypertrophy, obstruction, or neurologic deficit that interferes with the normal flow of urine and urinary tract defenses. i) Occurs in both genders. Frequently involves upper and lower urinary tracts.

Question 32

what constitutes a Recurrent UTI? what accounts for majority of recurrent UTI's

Answer 32

: in healthy, non-pregnant women; two or more UTIs within 6 months or three or more within one year. Reinfection– different microorganism than what was originally isolated (accounts for the majority of recurrent UTIs).

Question 33

what is a relapse of a recurrent UTI

Answer 33

ii) Relapse – same initial organism; usually indicates a persistent infectious source.

Question 34

UTI organisms usually originate from where

Answer 34

bowel flora however, virtually every organism can be associated with UTI

Question 35

what are the organisms involved in uncomplicated infections most often?

Answer 35

E coli- 80-90% of CAI's staphylococcus saprophyticus iii) Klebsiella pneumoniae iv) Proteus spp. v) Pseudomonas aeruginosa vi) Enterococcus spp.

Question 36

what organisms are involved in complicated infections ?

Answer 36

more varied and often more resistant E. coli (<50%) Enterococci - second most common isolated organism in hospitalized patients - may be due to widespread use of cephalosporins which are NOT active against enterococci - VRE faecalis and enterococcus faecium have become resistant- ``` Proteus K. pneumoniae Enterobacter spp. P aeruginosa Staphylococci Candida - critically ill and chronically catheterized ```

Question 37

what organism is commonly a result of bacteremia producing metastatic abscesses in the kidney

Answer 37

staph aureus

Question 38

what organism is a common cause of UTI in critically ill and chronically catheterized

Answer 38

candida

Question 39

what is the clinical presentation of lower UTI

Answer 39

``` dysuria urgency frequency nocturia suprapubic heaviness ```

Question 40

symptoms of upper UTI

Answer 40

flank pain, fever, nausea, vomiting, malaise

Question 41

what is the clinical presentation of a UTI in the elderly

Answer 41

a) do not usually experience specific urinary symptoms but will present with altered mental status, change in eating habits, or gastrointestinal symptoms.

Question 42

what are the laboratory findings specific for UTI

Answer 42

bacteriuria pyuria (WBC >10/mm^3) nitrite-positive leukocyte esterase positive

Question 43

what are the treatment goals when treating a UTI

Answer 43

a) Eradicate organism b) Prevent or treat systemic consequences c) Prevent recurrence d) Decrease potential collateral damage (emergence of bacterial resistance due to broad antimicrobial coverage)

Question 44

how do you treat uncomplicated cystitis

Answer 44

urinanalysis and empiric antibiotics without culture 3 day treatment course- increased adherence, fewer side effects, decreased cost, less potential for the development of resistance

Question 45

in what patients with uncomplicated cystitis is the 3 day course treatment inappropriate ?

Answer 45

those with previous infection caused by resistant microorganisms, male patients, and complicated UTI's

Question 46

what are the drugs of choice for uncomplicated cystitis

Answer 46

TMP/SMX x3 days Nitrofurantoin x5 days Fosfomycin Fluoroquinolones (ciprofloxacin or levofloxacin) (reserved for suspected or possible pyelonephritis due to risk of collateral damage)

Question 47

what is the treatment course for acute pyelonephritis - mild to moderately symptomatic (oral therapy considered)

Answer 47

obtain urine gram stain urinalysis and culture&sensitivity initiate empiric antimicrobials: Ciprofloxacin or levofloxacin preferred 1st line for 7-10 days TMP/SMX x14 days If amoxicillin/clavulante or oral cephalosporin used, give ceftriaxone first then continue with oral agent to complete 10-14 day course

Question 48

what if gram positive cocci are identified on gram stain in the acute pyelonephritis? what is the treatment

Answer 48

consider E. faecalis, and direct treatment towards this potential pathogen with ampicillin

Question 49

what is the treatment of the seriously ill patient's who have acute pyelonephritis

Answer 49

initiate IV antimicrobials initially – broad spectrum, directed towards bacteremia or sepsis. (a) Fluoroquinolone IV (b) Extended spectrum cephalosporin (ceftriaxone) +/- aminoglycoside (c) Aminoglycoside +/- ampicillin

Question 50

what are the risk factors for multidrug resistant bacteria (Pseudomonas aeruginosa and enterococci) acute pyelonephritis

Answer 50

hospitalization in the last 6 months, urinary catheter, or nursing home resident

Question 51

if a pt is at risk for multidrug resistant bacterial acute pyelonephritis, what is the treatment?

Answer 51

(1) Empiric coverage: (a) Ampicillin + gentamicin (b) B-lactam/B-lactamase combination (c) Carbapenem (d) Fluoroquinolone (e) Ceftazidime or cefepime

Question 52

effective therapy in treatment of MDR acute pyelonephritis should stabilize the pt within what time and the patient will be afebrile by what day of treatment ?

Answer 52

(2) Effective therapy should stabilize patient within 12-24 hours. Patient will usually become afebrile by day 3. (3) If patient fails to respond clinically within 3-4 days or has persistently positive blood or urine cultures, further investigation is needed to exclude resistance, possible obstruction, intra-renal or perinephric abscess or some other disease process. (4) After patient is afebrile x24 hours, parenteral therapy may be discontinued and oral therapy initiated to complete a two week course.

Question 53

what are the limitations/considerations pharmokinetically in the treatment of bacterial prostatitis barriers? ph?

Answer 53

i) The barrier between the microcirculation and the prostate gland stroma limits drug entry to passive diffusion, which only permits non-protein-bound, lipophilic antimicrobial agents to reach therapeutic levels within the gland. ii) The low pH of prostatic fluid permits antibiotics with alkaline pKas (such as quinolones and sulfonamides) to achieve high concentrations in prostatic tissue more readily than antibiotics with acidic pKas (antibiotic prostatic penetration in the setting of inflammation occurs more readily).

Question 54

what is the treatment for bacterial prostatitis

Answer 54

total cours of therapy is 4 weeks OR 6-12 weeks if chronic (if chronic there is low likelihood of curing) (1) Most can be managed with oral antimicrobials – TMP/SMX or fluoroquinolones. (2) Hospitalized patients may require IV therapy – intravenous fluoroquinolones or aminoglycosides. (3) Alternatives – cephalosporins, B-lactam/B-lactamase combination, carbapenems.

Question 55

what is gram positive cocci are identified ?

Answer 55

enterococci chains? -amoxicilin or ampicillin staphylococci clusters? - cephalexin - cefazolin - nafcillin - vancomycin

Question 56

which drug cannot be used in the treatment of bacterial prostatitis because of poor tissue penetration

Answer 56

nitrofurantoin

Question 57

how do you treat gonorrhea

Answer 57

ceftriaxone (IM injection) Co-existing chlamydial infection documented in up to 50% of women and 20% of men with gonorrhea. Thus, all patients treated for gonorrhea should be treated with concomitant azithromycin or doxycycline for chlamydia. In penicillin-allergic: azithromycin

Question 58

what is the treatment of chlamydia

Answer 58

azithromycin as a single, one-time dose doxycycline twice daily for 7 days abstinence for 7 days after start of therapy

Question 59

what is the treatment of chlamydia in pregnancy

Answer 59

azithromycin and amoxicillin

Question 60

what is the treatment of choice for syphilis

Answer 60

Parenteral penicillin G

Question 61

if a patient has an allergy to penicillin what should be the next line of treatment for syphillis

Answer 61

doxycycline

Question 62

what is the treatment for neurosyphilis

Answer 62

penicillin G given IV every 4 hours x 10-14 days

Question 63

what if a patient is pregnant and has an allergy to penicillin and has syphilis

Answer 63

Pregnancy and penicillin allergy: perform skin testing, if positive must undergo desensitization.

Question 64

what is the treatment for trichomonas

Answer 64

metronidazole or tinidazole

Question 65

what is the Jarisch - Herxheimer reaction

Answer 65

Jarisch-Herxheimer reaction: benign, self-limiting reaction, characterized by flu-like illness (transient headache, fever, chills, malaise, myalgia, tachypnea), peripheral vasodilation, and aggravation of syphilitic lesions. Occurs independent of drug or dose used. Begins within 2-4 hours of initiating therapy, peaks at 8 hours, and is complete in 12-24 hours.

Question 66

when is metronidazole contraindicated (treatment of trichomonas)

Answer 66

in the first trimester it is excreted in breast milk interrupt breast feeding for 12-24 hours after maternal ingestion

Question 67

in trichomonas, what can happen with males in terms of their prognosis

Answer 67

Males have high spontaneous cure rate even in the absence of treatment.

Question 68

high, onte time doses of metronidazole or tinidazole can cause what ADR's (treatment of trichomonas) and what if the patient cannot tolerate these ADR's?

Answer 68

High, one-time doses may cause GI complaints (anorexia, nausea, vomiting, diarrhea) and some patients may be unable to tolerate → use multi-dose regimen x5-7 days.

Question 69

treatment for Epididymitis (Chlamydia. trachomatis or N. gonorrhoeae)

Answer 69

Sexually acquired: ceftriaxone plus doxycycline. | Enteric gram-negative bacteria: ceftriaxone plus levofloxacin.

Question 70

who is at risk for enteric gram negative bacilli (epididymitis)

Answer 70

older men, those with urinary tract instrumentation, surgery or obstruction, or are immunosuppressed.

Question 71

what is the treatment for Pelvic Inflammatory Disease (C. trachomatis or N. gonorrhoeae)

Answer 71

Cefotetan or cefoxitin PLUS doxycycline; clindamycin PLUS aminoglycoside; single IM dose of ceftriaxone PLUS doxycycline +/- metronidazole. NOTE: Mycoplasma genitalium, M. hominis, and various facultative and anaerobic bacteria may also be involved. Must cover all potential pathogens.

Question 72

how long is IV therapy continued in the treatment of PID and when do you start oral meds and which oral meds ?

Answer 72

IV therapy continued until 24 hours after clinical improvement, then oral doxycycline continued to complete 14 day course.

Question 73

what organisms are involved in bacterial vaginosis

Answer 73

Bacterial Vaginosis (anaerobic bacteria, Gardnerella vaginalis, Ureaplasma spp., Mobiluncus curtisii, Mycoplasma spp.)

Question 74

what is the treatment of bacterial vaginosis

Answer 74

Oral metronidazole or vaginal metronidazole or clindamycin. Suppressive therapy: twice-weekly metronidazole gel. Pregnancy: metronidazole or clindamycin.

Question 75

what are the concerns in the treatment of bacterial vaginosis

Answer 75

With any treatment regimen, recurrence is common. Retreatment with the same agent or an alternative is usually effective in the short-term.

Question 76

vulvovaginal candidiasis uncomplicated is treated how;?

Answer 76

intravaginal butoconazole, clotrimazole, miconazole, terconazole, or tioconazole. OR single dose of oral fluconazole*. *Single, oral dose of fluconazole is as effective as 7 days of intravaginal clotrimazole or miconazole and is preferred by many patients.

Question 77

how is recurrent vulvovaginal candidiasis treated

Answer 77

weekly oral fluconazole for 6 months may reduce number of recurrences.

Question 78

in what patients will you see complicated vulvovaginal candidiasis

Answer 78

Complicated vulvovaginal candidiasis due to azole resistant C. glabrata or other non-albicans species, immunosuppressed patients, poorly controlled diabetes, or pregnancy often require more aggressive treatment.

Question 79

is vulvovaginal candidiasis an STD?

Answer 79

no its not sexually transmitted but common in women being evaluated for STI's

Question 80

what is the treatment for chancroid (haemophilus ducreyi)

Answer 80

Single oral dose of azithromycin or IM dose of ceftriaxone. Treat sex partners if there was sexual contact with infected individual within 10 days of symptom onset.

Question 81

S-warfarin uses what CYP system

Answer 81

CYP2C9 S- warfarin is more potent

Question 82

R warfarin uses what CYP system

Answer 82

CYP3A4

Question 83

how does TMP/SMX cause increased INR

Answer 83

inhibitor of CYP2C9 (S-warfarin) which leads to increased Warfarin levels, which depletes vitamin K and leading to decrease in vitamin K dependent factors (2, 7, 9, 10 Protein C, S)

Question 84

of the following, which medication could result in pyelonephritis treatment failure if taken concurrently with ciprofloxacin? Acetaminophen calcium carbonate enalapril hydrochlorothiazide

Answer 84

calcium carbonate (antacid)

Question 85

why doesn't chlamydia stain on gram stain

Answer 85

b/c it is intracellular

Question 86

gram negative diplococci | dysuria and profuse yellow urethral discharge

Answer 86

neisseria gonorrhea

Question 87

can treponema pallidum be cultured ?

Answer 87

no must directly visualize or more commonly identify by serology testing

Question 88

drug of choice for the treatment of syphilis

Answer 88

Penicillin G why are the other penicillins not used? b/c penicillin G is the longest lasting