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Pharm Block 3 > 9 - Antibacterials Part 2 > Flashcards

9 - Antibacterials Part 2 Flashcards

1
Q

What are the uses of ciprofloxacin?

A

UTIs, infectious diarrhea, bone and joint infections, skin infections, and chlamydia.

Not best choice for gram + infections or respiratory infections, other quinolones have better activity for these.

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2
Q

What quinolone is much better than ciprofloxacin at treating gram positives? What else is this drug good at treating? What isn’t it good against?

A

Moxifloxacin

Good for respiratory infections, community-acquired pneumonia, bacterial bronchitis, NOT approved for strep throat.

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3
Q

Some quinolones, such as _______ and ______ can only reach therapeutic concentrations in the urinary tract.

A

Norfloxacin and the non-fluorinated agents.

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4
Q

What are side effects of quinolones? When should pts stop the drug?

A

Nausea, vomiting, abd. pain, enterocolitis, dizziness, headache, restlessness, depression, seizures, rashes.

STOP drug if rash appears because fatality could follow.

EKG irregulrities and arrhythmias (prolonged QT), and peripheral neuropathy.

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5
Q

In what causes should quinolones be used with caution?

A

Those with seizure disorders and pregnancy.

In children due to possible cartilage damage. FDA approved as 2nd line agens for certain SERIOUS infections in children such as pyolonephritis

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6
Q

What musculoskeletal adverse effects can occur with quinolones?

A

Arthropathy (joint inflammation) in 10-15% of patients.

Tendon rupture - black box warning.

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7
Q

What drug is converted to a reactive compound that can damage DNA by a nitroreductase enzyme? What can this drug be used to treat?

A

Nitrofurantoin

UTIs (lower only, not renal) from E. coli, enterococcus, and staphylococcus.

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8
Q

What are side effects of nitrofurantoin?

A

Nausea, vomiting, diarrhea, hypersensitivity, fever, chills.

Peropheral neuropathy, acute and chronic pulmonary reactions with pulmonary fibrosis.

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9
Q

What are the more dangerous side effects of nitrofurantoin?

A

Acute and chronic liver damage.

Granulocytopenia, leukopenia, megaloblastic anemia, and acute hemolytic anemia.

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10
Q

What bactericidal drug binds and inhibits bacterial RNA polymerase B and inhibits RNA synthesis? What can it be used to treat?

A

Rifampin

Treats TB and for meningitis prophylaxis from neisseria meningitidis and haemophilus influenza type B.

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11
Q

What are side effects of rifampin?

A

Serios hepatotoxicity.

Strongly induces many enzymes: CYP3A, 2C9, 2C19, 1A, 22A, 2B that inactivate other drugs

Orange color to urine, saliva, sweat, and tears.

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12
Q

What drug is a 1st line choice for C. diff and works by inhibiting RNA polymerase and thus inhibits RNA synthesis? How is this drug given?

A

Fidaxomicin

Bactericidal, narrow spectrum, mainly for clostridium.

Oral admin, poorly absorbed (which is good for treating C diff)

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13
Q

What are the side effects of fidaxomicin?

A

GI upset and GI bleeding.

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14
Q

What drug has a nitro group that is reduced by anaerobes and the resulting product damages DNA?

A

Metronidazole

Bactericidal

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15
Q

What are uses of metronidazole?

A

Anaerobes, C diff enterocolitis, helicobacter pylori (with a proton pump inhibitor), and gardnerella vaginalis (bacterial vaginosis).

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16
Q

What are side effects of metronidazole?

A

Nausea, vomiting, anorexia, diarrhea.

Transient leukopenia, neutropenia.

Thrombophlebitis after IV infusion.

Bacterial and fungal superinfections (esp candida).

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17
Q

What causes C. difficile enterocolitis?

A

Can be caused by all antibacterials, consider in pts with antibacterial drugs in last 2 mo.

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18
Q

What therapies can be used to treat C. diff enterocolitis?

A

1st line (as of march)

  • Vancomycin (mod - severe)
  • Fidaxomicin (mod-severe)

Alternates: metronidazole (mild to moderate)
Vanco + metronidazole (very severe)

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19
Q

What are the general properties of aminoglycosides (how are they given, what is their MOA)?

A

Bactericidal, IV, IM, topical.

Transported into bacteria by energy-requiring aerobic process and binds to several ribosome sites (30S/50S interface) and stops initiation and causes premature release of ribosome from mRNA and causes misreading.

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20
Q

What are the uses of aminoglycosides? What are they not used for?

A

Primarily gram ngeative aerobic bacilli:

  • enterobacteriaceae (E. coli, klebsiella, enterobacter, serratia)
  • pseudomonas aeruginosa
  • often used in combo with cell wall inhibitors or quinolones

Poor activity against anaerobes and facultatives in anaerobic environment

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21
Q

What does the gram positive activity of aminoglycosides require?

A

Drug combos such as cell wall inhibitors (B-lactams, vanco) to enhance the permeability of the aminoglycosides.

DO NOT MIX aminoglycosides with B lactams in vitro; chemical rxns will inactivate the aminoglycosides

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22
Q

What is the post-antibiotic effect that occurs with aminoglycosides?

A

Sustained activity for hours after concentration below “effective” levels because they are concentration-dependent killers.

Narrow therapeutic window, use restricted to serious infections.

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23
Q

Describe the killing of aminoglycosides, what is it dependent on?

A

Concentration-dependent.

Problem is that toxicity is dose-related.

Cmax killing and post-antibiotic effect allows for less frequent dosing.

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24
Q

What are the three aminoglycosides? How do you treat resistant strains?

A

Gentamicin, tobramycin, and amikacin.

Amikacin is the choice agent for gentamicin and tobramycin resistant strains.

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25
Q

What are the side effects of aminoglycosides?

A

Narrow window.

Nephrotoxicity, ototoxicity (mostly irreversible, deafness delayed), neuromuscular blockage.

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26
Q

What drugs are transported into cells and prevent the attachment of aminoacyl-tRNA binding to 30S ribosomal subunits? What type of drug are they? What resistance is seen?

A

Tetracyclines: bacteriostatic.

Resistance: most commonly drug efflux pumps. Resistance to one often implies resistance to all.

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27
Q

What are tetracyclines the preferred agents for?

A

Unusual bugs:

  • Rickettsial diseases
  • Lyme disease
  • Chlamydia, mycoplasma, ureaplasma
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28
Q

What can doxycycline and minocycline be used to treat? How do they differ?

A

They are tetracyclines.

Used for Pen-G sensitive syphilis and uncomplicated N. gonorrhoeae

Doxycycline has least affinity for calcium, minocycline has less calcium binding than tetracycline but more than doxycycline.

29
Q

What prevents tetracyclines from being absorbed?

A

Binding calcium inhibits their absorption (bad)

Tetracycline (most Ca binding), minocycline, doxycycline.

30
Q

What are the side effects of tetracyclines? Who shouldn’t they be given to?

A

GI disturbances like enterocolitis.

Candida superinfection in colon, photosensitization with rash, teeth discoloration (avoid in children less than 8 and avoid in pregnant).

31
Q

What is the function of tigecycline?

A

Like tetracyclines, also bind to additional unique sites in the ribosomes.

No cross-resistance with other antibacterials including tetracyclines.

32
Q

What types of infections can tigecycline be used for?

A

Skin/skin infections, complicated intra-abd infections, and community acquired pneumonia (CAP)

33
Q

What type of bacteria can tigecycline be used against?

A

Gram neg:
-E coli, citrobacter, klebsiellam enterobacter (NOT pseudomonas)

Gram pos:

  • staph (MSSA and MRSA)
  • strep

Anaerobes: bacteroides, clostridium perfringens

34
Q

What adverse rxns are associated with Tigecycline?

A

Nausea, vomiting, enterocolitis.

Other side effects similar to tetracyclines including calcium binding.

FDA alert for increased risk of death in those with serious infections (considered last line agent)

35
Q

What drug interferes with binding of aminoacyl-tRNA to 50S ribosomal subunit and inhibits peptide bond formation?What is the spectrum?

A

Chloramphenicol.

Originally broad spectrum but very serious side effects restrict use; only used when no other agent is suitable.

36
Q

What type of infections is chloramphenicol used to treat? What type of drug is it, cidal or static?

A

Used for meningitis as an alternative for those with a cephalosporin allergy and for brain abscesses.

Generally bacteriostatic

37
Q

What are side effects of chloramphenicol?

A

BM depression: fatal aplastic anemia (1 in 30,000), not dose related, can be delayed.

Grey baby syndrome: accum of unmetabolized drug

Optic neuritis and blindness

GI effects including enterocolitis.

38
Q

What drugs are macrolides and what is their mechanism of action?

A

Erythromycin
Clarithromycin
Azithromycin

Bind 50S subunit to block translocation along ribosome.

Bacteriostatic.

39
Q

What are the uses of erythromycin?

A

Primarily gram + (alternate for strep throat in penicillin allergic pts)

Usual bugs: chlamydia, mycoplasma, legionella, campylobacter, bordetella.

40
Q

What are side effects of erythromycin?

A

Nausea and vomiting in 20-40%, directly causes GI motility.

Inhibits CYP3A metabolism and excretion of other drugs.

Increase risk of arrhythmias and card arrest, increased QT intervals

41
Q

How does clarithromycin differ from erythromycin?

A

Better kinetics: less frequent dosing needed

Less GI motility effects (50% less), somewhat wider antibacterial spectrum.

Also has some CV risks though such as prolonged QT intervals.

42
Q

What bugs can be treated with clarithromycin?

A

Same as erythromycin, plus:

  • haemophilus influenzae, moraxella
  • penicillin-resistant strep pneumoniae
  • atypical mycobacteria
  • liscensed for helicobacter pylori (with amox and an acid blocker)
43
Q

What is needed to treat helicobacter pylori? Give three examples of drug combos that would work?

A

At least 2 antibacterials + PPI

Clarithromycin + amox + omeprazole

Clarithromycin + metronidazole + omeprazole

Metronidazole + tetracycline + bismuth subsalicylate + PPI

44
Q

What is Azithromycin commonly used to treat?

A

Outpatient respiratory tract infections.

Genital infections: chlamydia; with ceftriaxone and doxy for gonorrhea.

Off-label for GI infections such as campy, shigella, and salmonella

45
Q

How do GI effects and drug metabolism compare in the macrolides?

A

Erythromycin > clarithromycin > azithromycin

Azithromycin has few effects on CYP3A4

Erythromycin has lower incidence of cardiac side effects compared to erythromycin but still need to be considered because they can cause arrhythmia and death.

46
Q

What drug bind the 50S ribosomal subunit to block translocation and is a significant cause of enterocolitis?

A

Clindamycin.

47
Q

What are the uses of clindamycin?

A

Gram + cocci (strep and MSSA)

Suppresses bacterial toxin production in Strep and Staph.

Many anaerobes including bacteroides fragilis (NOT for C. diff).

48
Q

What are side effects of Clindamycin?

A

GI irritation, diarrhea (~20%)

Antibiotic associated enterocolitis (3-5%)

Hepatotoxicity

49
Q

What drug inhibits protein synthesis by binding to the 50S ribosomal subunit to interfere with the formation of the 70S initiation complex? What type of drug is this?

A

Linezolid.

Bacteriostatic.

50
Q

What bacteria does linezolid work on?

A

Gram + spectrum

Approved for VRE, staph aureas (MSSA and MRSA), strep groups A and B, strep pneumonia, and staphylococcus.

51
Q

What are side effects of linezolid?

A

Non-selective inhibitor of MAO - avoid foods with tyramine, possible serotonin syndrome if given with SSRIs, TCAs, or buspirone.

Diarrhea, superinfection, enterocolitis, headache, nausea/vomiting, and BM suppression.

52
Q

What is the function of antifolates? Which drugs do this?

A

Inhibit folate synthesis.

Sulfonamides: sulfamethoxazole and sulfadiazine
Trimethoprim

53
Q

What is the mechanism of action of sulfonamides such as sulfamethoxazole and sulfadiazine? How are these usually used?

A

Bacteriostatic.

Competitive analogs of p-aminobenzoic acid, a precursor in folate synthesis.

Commonly used in combo with other antibacterials.

54
Q

What is sulfamethoxazole usually used with?

A

Trimethoprim as part of a synergistic combination.

55
Q

What is silver sulfadiazine used for?

A

Topically for infection prevention in burn pts.

56
Q

What are side effects of sulfonamides?

A

Hypersensitivity (2-10%): rashes, serum sickness, sunlight makes rash worse

GI disturbances, renal damage (crystalluria-drug metabolites precipitate in renal tubules)

Potentiate action of other drugs - inhibits CYP2C9 )warfarin)

57
Q

What drug inhibits folate synthesys by competitively inhibiting dihydrofolate reductase?

A

Trimethoprim

A dihydrofolate analog.

58
Q

What is trimethoprim often used in conjunction with?

A

Sulfamethoxazole: synergistic effects - two static drugs together having a cidal effect.

This combo also called TMP/SMX and is first choice for empiric treatment of uncomplicated UTIs.

59
Q

Other than UTIs, what are uses for trimethoprim in conjunction with sulfamethoxazole?

A

Also used to URIs from H. influenza, Moraxella, and strep pneumonia.

Pneumocystitis jiroveci - 1st choice to treat and for prophylaxis

60
Q

What are the side effects of TMP/SMX?

A

All of the sulfanomide effects + nausea, vomiting, diarrhea, rashes, and BM suppression.

Trimethoprim effects esp pronounced with long term use (AIDs pts)

61
Q

What are the four categories of antibacterial use? What does each mean and how do you select a drug for each?

A
  1. Prophylactic: select drug based on predominant flora at site of interest.
  2. Empiric : organism known but syndrome known. Use drug based on good activity against most common pathogens.
  3. Pathogen-directed: pathogen known but susceptibility not. Use drug that likely targets this pathogen.
  4. Susceptibility-guided: pathogen and susceptibility known. Select drug based on susceptibility.
62
Q

What are the diagnostic steps taken to determine drug choice?

A

Obtain culture/diagnostic tests.

Empiric therapy

Diagnostic results, sensitivity profile

Modify therapy as needed

63
Q

To discourage guessing of pathogen/susceptibility, what does Froedtert pharmacy do?

A

Stops empiric therapy after 72 hours, unless the order is rewritten.

64
Q

What is one common use of empiric therapy? What are the 1st line drugs recommended?

A

Uncomplicated cystitis in nonpregnant women.

1st line drugs:

  • TMP/SMX
  • Nitrofurantoin
  • fosfomycin
65
Q

What are reasons for antibacterial failures?

A

Drug choice and host factors.

66
Q

Quinolone resistance in ____ ________ has increased concurrently with quinolone use.

A

gram negatives

67
Q

What drugs should be used to treat hospital-acquired MRSA (HA-MRSA)?

A

Vancomycin
Linezolid
Daptomycin
Tigecycline

68
Q

What drugs should be used to treat community-acquired MRSA (CA-MRSA)?

A

Linezolid
Doxycycline, minocycline
Clindamycin
TMP/SMX

Pharm Block 3 (15 decks)

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