Drugs Treatment of LUT Infections and STI's (Kinder) Flashcards
what is the MOA of trimethoprim/sulfamethoxazole (TMP/SMX)
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.
do you need to adjust TMP/SMX in renal impairement
yes
ADR’s of TMP/SMX
allergic skin rashes, nausea, vomiting,
CNS (headache, depression),
photosensitivity,
renal dysfunction, Stevens-Johnson syndrome.
What are the drug-drug interactions of TMP/SMX
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.
MOA of Nitrofurantoin
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.
what are the ADR’s of Nitrofurantoin
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.
in what pt’s is nitrofurantoin contraindicated
pregnant women,
impaired renal function (40 mL/min),
children < 1 month.
Methenamine MOA
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.
when is methenamine contraindicated
i) Ammonia produced so CI in hepatic insufficiency.
what are the ADR’s of methenamine
GI distress,
painful/frequent micturition,
hematuria,
rash,
low systemic toxicity at usual doses.
Fosfomycin MOA
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.
what is the t1/2 life of fosfomycin if creatinine clearance is <54 mL/min
50 hours LONG
ADR’s of fosfomycin
c) ADRs: diarrhea, nausea, abdominal pain, headache.
MOA of fluoroquinolones (Ciprofloxacin)
a) MOA: concentration-dependent killing, targets bacterial DNA gyrase and topoisomerase IV.
do you need to adjust fluoroquinolones in renal impairment?
yes
what are the ADRs of fluoroquinolones
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.
MOA of B-lactams
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.
Penicillin G benzathine (B-lactam) ADR’s
allergic reactions (0.7-10%),
anaphylaxis (0.004-0.04%),
interstitial nephritis (rare),
pseudomembranous colitis,
Jarisch-Herxheimer reaction.
what is the drug of choice for susceptible enterococci
Ampicillin (B-lactam)
Ceftriaxone- a cephalosporin (B-lactam)
ADR’s
1% risk of cross-reactivity to penicillins,
injection site reaction,
diarrhea.
***usually reserved for serious infections
MOA of Azithromycin
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.
what can reduce the absorption of azithromycin
administration of aluminum and magnesium hydroxide antacids
what are the ADR’s of azithromycin
GI (epigastric distress)
hepatotoxicity
arrhythmia
QT prolongation
in general what are the DDI’s of macrolides
CYP3A4 inhibition – prolongs effects of digoxin, valproate, warfarin, others.
i) Azithromycin structure differs making it less likely to produce DDIs but should use caution.
Metronidazole MOA
: 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.
what are the ADR’s of metronidazole
: 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.
what are the DDI’s of metronidazole
induced metabolism of phenobarbital, prednisone, and rifampin.
Prolongs prothrombin time in those receiving warfarin.
what is a UTI
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.
what is an uncomplicated UTI
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.
why are male UTI’s never uncomplicated?
not considered uncomplicated because these infections are rare and most often a result of a structural or neurological abnormality.
what is a complicated UTI
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.
what constitutes a Recurrent UTI?
what accounts for majority of recurrent UTI’s
: 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).
what is a relapse of a recurrent UTI
ii) Relapse – same initial organism; usually indicates a persistent infectious source.
UTI organisms usually originate from where
bowel flora
however, virtually every organism can be associated with UTI
what are the organisms involved in uncomplicated infections most often?
E coli- 80-90% of CAI’s
staphylococcus saprophyticus
iii) Klebsiella pneumoniae
iv) Proteus spp.
v) Pseudomonas aeruginosa
vi) Enterococcus spp.
what organisms are involved in complicated infections ?
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
what organism is commonly a result of bacteremia producing metastatic abscesses in the kidney
staph aureus
what organism is a common cause of UTI in critically ill and chronically catheterized
candida
what is the clinical presentation of lower UTI
dysuria urgency frequency nocturia suprapubic heaviness
symptoms of upper UTI
flank pain, fever, nausea, vomiting, malaise
what is the clinical presentation of a UTI in the elderly
a) do not usually experience specific urinary symptoms but will present with altered mental status, change in eating habits, or gastrointestinal symptoms.
what are the laboratory findings specific for UTI
bacteriuria
pyuria (WBC >10/mm^3)
nitrite-positive leukocyte esterase positive
what are the treatment goals when treating a UTI
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)
how do you treat uncomplicated cystitis
urinanalysis and empiric antibiotics without culture
3 day treatment course- increased adherence, fewer side effects, decreased cost, less potential for the development of resistance
in what patients with uncomplicated cystitis is the 3 day course treatment inappropriate ?
those with previous infection caused by resistant microorganisms, male patients, and complicated UTI’s
what are the drugs of choice for uncomplicated cystitis
TMP/SMX x3 days
Nitrofurantoin x5 days
Fosfomycin
Fluoroquinolones (ciprofloxacin or levofloxacin) (reserved for suspected or possible pyelonephritis due to risk of collateral damage)
what is the treatment course for acute pyelonephritis - mild to moderately symptomatic (oral therapy considered)
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
what if gram positive cocci are identified on gram stain in the acute pyelonephritis? what is the treatment
consider E. faecalis, and direct treatment towards this potential pathogen with ampicillin
what is the treatment of the seriously ill patient’s who have acute pyelonephritis
initiate IV antimicrobials initially – broad spectrum, directed towards bacteremia or sepsis.
(a) Fluoroquinolone IV
(b) Extended spectrum cephalosporin (ceftriaxone) +/- aminoglycoside
(c) Aminoglycoside +/- ampicillin
what are the risk factors for multidrug resistant bacteria (Pseudomonas aeruginosa and enterococci) acute pyelonephritis
hospitalization in the last 6 months, urinary catheter, or nursing home resident
if a pt is at risk for multidrug resistant bacterial acute pyelonephritis, what is the treatment?
(1) Empiric coverage:
(a) Ampicillin + gentamicin
(b) B-lactam/B-lactamase combination
(c) Carbapenem
(d) Fluoroquinolone
(e) Ceftazidime or cefepime
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 ?
(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.
what are the limitations/considerations pharmokinetically in the treatment of bacterial prostatitis
barriers?
ph?
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).
what is the treatment for bacterial prostatitis
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.
what is gram positive cocci are identified ?
enterococci chains?
-amoxicilin or ampicillin
staphylococci clusters?
- cephalexin
- cefazolin
- nafcillin
- vancomycin
which drug cannot be used in the treatment of bacterial prostatitis because of poor tissue penetration
nitrofurantoin
how do you treat gonorrhea
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
what is the treatment of chlamydia
azithromycin as a single, one-time dose
doxycycline twice daily for 7 days
abstinence for 7 days after start of therapy
what is the treatment of chlamydia in pregnancy
azithromycin and amoxicillin
what is the treatment of choice for syphilis
Parenteral penicillin G
if a patient has an allergy to penicillin what should be the next line of treatment for syphillis
doxycycline
what is the treatment for neurosyphilis
penicillin G given IV every 4 hours x 10-14 days
what if a patient is pregnant and has an allergy to penicillin and has syphilis
Pregnancy and penicillin allergy: perform skin testing, if positive must undergo desensitization.
what is the treatment for trichomonas
metronidazole or tinidazole
what is the Jarisch - Herxheimer reaction
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.
when is metronidazole contraindicated (treatment of trichomonas)
in the first trimester
it is excreted in breast milk
interrupt breast feeding for 12-24 hours after maternal ingestion
in trichomonas, what can happen with males in terms of their prognosis
Males have high spontaneous cure rate even in the absence of treatment.
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?
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.
treatment for Epididymitis
(Chlamydia. trachomatis or
N. gonorrhoeae)
Sexually acquired: ceftriaxone plus doxycycline.
Enteric gram-negative bacteria: ceftriaxone plus levofloxacin.
who is at risk for enteric gram negative bacilli (epididymitis)
older men, those with urinary tract instrumentation, surgery or obstruction, or are immunosuppressed.
what is the treatment for Pelvic Inflammatory Disease
(C. trachomatis or
N. gonorrhoeae)
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.
how long is IV therapy continued in the treatment of PID and when do you start oral meds and which oral meds ?
IV therapy continued until 24 hours after clinical improvement, then oral doxycycline continued to complete 14 day course.
what organisms are involved in bacterial vaginosis
Bacterial Vaginosis
(anaerobic bacteria,
Gardnerella vaginalis,
Ureaplasma spp.,
Mobiluncus curtisii,
Mycoplasma spp.)
what is the treatment of bacterial vaginosis
Oral metronidazole or vaginal metronidazole or clindamycin.
Suppressive therapy: twice-weekly metronidazole gel.
Pregnancy: metronidazole or clindamycin.
what are the concerns in the treatment of bacterial vaginosis
With any treatment regimen, recurrence is common. Retreatment with the same agent or an alternative is usually effective in the short-term.
vulvovaginal candidiasis uncomplicated is treated how;?
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.
how is recurrent vulvovaginal candidiasis treated
weekly oral fluconazole for 6 months may reduce number of recurrences.
in what patients will you see complicated vulvovaginal candidiasis
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.
is vulvovaginal candidiasis an STD?
no its not sexually transmitted but common in women being evaluated for STI’s
what is the treatment for chancroid (haemophilus ducreyi)
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.
S-warfarin uses what CYP system
CYP2C9
S- warfarin is more potent
R warfarin uses what CYP system
CYP3A4
how does TMP/SMX cause increased INR
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)
of the following, which medication could result in pyelonephritis treatment failure if taken concurrently with ciprofloxacin?
Acetaminophen
calcium carbonate
enalapril
hydrochlorothiazide
calcium carbonate (antacid)
why doesn’t chlamydia stain on gram stain
b/c it is intracellular
gram negative diplococci
dysuria and profuse yellow urethral discharge
neisseria gonorrhea
can treponema pallidum be cultured ?
no must directly visualize or more commonly identify by serology testing
drug of choice for the treatment of syphilis
Penicillin G
why are the other penicillins not used?
b/c penicillin G is the longest lasting
