2-Overview of Antibacterial Agents Flashcards

1
Q

Name the four classes of beta-lactam antibiotics

A

Penicillins, cephalosporins, monobactams, carbapenems

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2
Q

How do beta-lactam antibiotics work?

A

Bind crosslinking (DAP) and transpeptidation enzymes to inhibit cell wall synthesis.

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3
Q

How do penicillins work?

A

beta-lactam activity inhibits cell wall synthesis Bind penicillin-binding proteins on cell wall = lysing enzymes

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4
Q

Name two ways bacteria have acquired resistance to penicillins

A
  1. production of beta-lactamase enzymes to destroy beta-lactam ring 2. Mutate PBPs to prevent binding
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5
Q

How are penicillins excreted?

A

Renally - remember they used to have soldiers drink urine of other soldiers on penicillins during shortage

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6
Q

What are the important adverse reactions to penicillins?

A

Hypersensitivity reactions with cross sensitivity between all penicillins

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7
Q

What is the treatment for syphilis?

A

Natural penicillins (G and V)

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8
Q

Name the four organisms that still respond to natural penicillin treatment

A
  1. streptococci (pyogenes and pneumoniae) 2. Nisseria meningitidis 3. Clostridium sp 4. Treponema pallidum (syphilis!!***)
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9
Q

Do aminopenicillins work via a time-dependent or concentration-dependent manner?

A

Time dependent- requires repeated administration

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10
Q

Name two examples of aminopenicillins

A

Ampicillin and amoxicillin

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11
Q

What organisms are aminopenicillins used for?

A

Upper respiratory tract pathogens:

  • S. pyogenes
  • S. pneumoniae
  • Hemophilus influenza
  • Enterococcus

community gram negative bacteria (E. Coli; proteus sp)

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12
Q

Do aminopenicillins have activity against Staphylococcus?

A

NO

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13
Q

Piperacillin (Class, Excretion, Uses, adverse effects)

A

Class: extended spectrum penicillin

Excretion: biliary tract

Uses: usu in combination with tazobactam (zosyn) **anti-pseudomonal

Adverse effects: Sodium overload Thrombocytopenia

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14
Q

Name anti-pseudomonal antibiotics

A
  1. Piperacillin (extended spectrum penicillin)
  2. Cetazimide (3rd generation cephalosporin)
  3. Cefepime (4th generation cephalosporin)
  4. Azetronam (monobactram)
  5. Doripenem, imipenem, meropenem (Carbapenems)
  6. Aminoglycosides (GNATS)
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15
Q

What organisms are treated with extended-spectrum penicillins?

A

NOT Staphylococcus

  • Gram-negative bacteria
  • Psudomonas aeruginosa
  • Enterococcus
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16
Q

Name three Beta-lactamase inhibitors and their penicillin combination

A
  1. Cavulanic acid + amoxicillin = augmentin
  2. Sulbactam + ampicillin = Unasyn
  3. Tazobactam + piperacillin = Zosyn***

most widely used IV antibiotic in hospitals & gram +, gram -, & anaerobic activity

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17
Q

What is the method of action of beta-lactamase inhibitors? Do they have bactericidal effects?

A

Inhibit Beta-lactamase enzymes

NO bactericidal effect

Widen spectrum of penicillins to increase activity against Staphylococcus, gram -, and anaerobic bacteria

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18
Q

Name 2 penicilinase-resistant penicillins

A
  1. Nafcillin (can cause serum sickness rxn)
  2. Dicloxacillin
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19
Q

How does the spectrum of activity change for cephalosprin generations?

A

Start gram + then become more gram -

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20
Q

Which category of antibiotics do Cephalexin, Cephradine, and Cefadroxil belong to?

A

First generation cephalosporins (oral)

Cephalexin= used for community Staphyloccal and stretococcal infections

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21
Q

Cefazolin (Class, Administration, Uses)

A
  • Class: 1st generation cephalosporin
  • Administration: IV
  • Uses: gram positive
    • Streptococcus sp & methicillin-sensitive Staphylococcus
    • Used in hospitals for wound infections & surgical prophylaxis
    • E. coli and Klebsiella sp
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22
Q

Cefuroxime and Cefoxitin belong to what category of antibiotics?

(Class and administration)

A

2nd generation Cephalosporins (Beta-lactam Abx)

Administration: IV

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23
Q

Cefoxitin (Class, Administration, Microbe)

A
  • Class: 2nd generation Cephalosporin
  • Administration: IV
  • *Microbe**: anaerobic activity- abdominal and gynecologic infx
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24
Q

Cefuroxime, Cefaclor, and Cefprozil

(Class, administration, microbe)

A
  • Class: 2nd generation Cephalosporins
  • Administration: Oral
  • Microbes:
    • gram negative bacteria: Klebsiella pneumoniae, Hemophilus influenzae, Moraxella catarrhalis
    • Community acquired pnemonia, URI, otitis media
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25
Q

Cefotaxime and Ceftriaxone (Rocephin)

(Class, Administration, Microbe, Adverse rxn)

A
  • Class: 3rd generation Cephalosporin
  • Administration: IV
  • Uses: cross BBB = useful for meningitis (“Ax to the head”)
  • Adverse rxn: Disulfram-like reaction
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26
Q

Ceftazidime (Fortaz)

(Class, Administration, Use, Adverse reaction)

A
  • Class: 3rd generation Cephalosporin
  • Administration: IV
  • Microbe: only 3rd generation with anti-pseudomonas
    • alternative to piperacillin
  • Adverse rxn: Disulfram-like reaction
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27
Q

What are the general uses for 3rd generation Cephalosporins?

A
  • gram (-) and gram (+) bacteria
  • nosocomial infx, pneumonia, meningitis, advanced Lymes disease
  • Ceftazidime = anti-pseudomonal
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28
Q

What is a common adverse rxn to 3rd generation Cephalosporins (Cefotaxime, Ceftriaxone, Ceftazidime, Cefixime, Cefpodoxime)?

A

Disulfram-like rxn: nausea, vomiting, palpitations if abx consumed with alcohol

29
Q

Cefixime and Cefpodoxime (Class, Administration, Uses, Adverse rxn)

A
  • Class: 3rd generation Cephalosporins
  • Administration: Oral
  • Uses: gram (+) and gram (-) bacteria
    • nosocomial infx, pneumonia, meningitis, advanced Lymes
  • Adverse rxn: disulfram-like reaction
30
Q

Cefepime (Class, Admin, Microbe)

A
  • Class: 4th generation Cephalosporin
  • Admin: IV
  • Microbes: resistant to chromosomal beta-lactamase enzymes
    • Enterobacteriaceae
    • Pseudomonas aeruginosa
    • Penicillin-resistant Streptococcus pneumoniae
31
Q

Ceftaroline (Class, Microbe)

A
  • Class: 5th generation Cephalosporin
  • Admin: IV
  • Microbe: MRSA infection (high affinit for PBP2a encoded by mecA gene in MRSA)
    • similar to 3rd generation (gram+/-)
    • NO pseudomonas or enterococcus
32
Q

Azetronam (Class, Structure, Action, Other)

A
  • Class: Monobactam
  • Structure: monocyclic beta-lactam ring
  • Action: anti-psudomonal
    • NO gram (+) activity
  • Other: no cross-sensitivity with penicillin or cephalosporin
    • =useful for beta-lactam allergies
33
Q

What is the first line choice for a patient with a gram (-) infection that is allergic to penicillins and cephalosporins?

A

Azetronam (monobactam with monocyclic beta-lactam ring)

34
Q

Imipenem-cilistatin, Meropenem, Ertapenem, and Dripenem (class, administration, general uses, adverse effects)

A
  • Class: Carbapenems
  • Admin: IV
  • Uses: broad spectrum antibiotic for multi-resistant infections
    • Polymicrobial and nosocomial infections
    • Anti-pseudomonas except for Ertapenem
  • Adverse rxn
    • Neurotoxic - seizures
    • Superinfections (C. diff)
    • High cost
    • Cross-sensitivity with pencillin-allergic patiets
35
Q

Why is cilistatin used with imipenem?

A

Cilistatin inhibits renal dihydropeptidase enzyme that would normally hydrolyze imipenem in the kidney

36
Q

Which Carbapenem does NOT have activity against pseudomonas?

A

Ertapenem

Imipenem-cilistatin, Meropenem, and Doripenem DO

Doripenem has the most activity

37
Q

Bacitracin (MOA, Microbe, Adverse Rxn)

A
  • MOA: inhibitor of bacteria cell wall synthesis
  • Use: topical preparation for Streptococcus and Staphylococcus
    • gram (+) bacteria only
  • Adverse rxn: nephrotoxic if given systemically
38
Q

Fosfomycin (Class, Microbe)

A
  • Class: phosphonic antibiotic inhibiting peptidoglycan synthesis in urine
  • Use: gram (-) UTI if resistant to sufla and fluoroquinolone abx
39
Q

Nitrofurantoin (Use, adverse rxn, contraindications)

A
  • Uses: lower UTI
    • bactericidal against E. coli, Enterococcus
  • Adverse rxn: GI irritation, nausea, vomiting
  • Contraindications
    • Elderly due to increased risk of pneumonitis and neuropathy
    • renal failure
40
Q

Vancomycin (Class, MOA, Admin, Use, Pharmacokinetics, Adverse Rxn)

A
  • Class: glycopeptide w/ high molecular weight
  • MOA: blocks transglycosylation to inhibit peptidoglycan elongation
  • Admin: mostly IV
    • Oral for pseudomembranous colitis /C. diff colitis
  • Use: MRSA *first line
  • Pharmacokinetics: renal excretion (proportional to creatinine clearance)
    • Narrow therapeutic index
  • Adverse Rxn: Red man syndrome- massive histamine release if given too fast
    • Ototoxicity
41
Q

What is the first line choice for MRSA infection and how does that drug work?

A

Vancomycin - blocks elongation of peptidoglycan (transglycosylation)

42
Q

What is Red Man Syndrome and what antibiotic is it associated with?

A

Massive histamine release caused by infusion of vacomycin that is too fast or too high of a dose

43
Q

Daptomycin (Class, Admin, MOA, Microbe, Other)

A
  • Class: cyclic lipopeptide
  • Admin: IV
  • MOA: inhibits cell membrane synthesis
  • Microbe: gram (+) and vancomycin-resistant bacteria
  • Other: Concentration-dependent activity
44
Q

Colistin (Admin, Microbe, Adverse Rxn)

A
  • Admin: IV
  • Microbe: MDR resistant bacteria- CRE
  • Adverse Rxn: Nephrotoxic
45
Q

What are the 3 categories of bacterial protein synthesis inhibitors?

A
  1. Macrolides
  2. Tetracyclines
  3. Aminoglycosides
    (4. Miscellaneous: Clindamycin, Linezolid & Mupirocin)
46
Q

Macrolide antibiotics MOA

A

Reversibly bind to 50S ribosomal subunit

47
Q

Macrolide antibiotics:

Uses & Bacterial susceptibility

A
  1. Bacteriostatic effect
  2. Upper & lower respiratory infections: activity against atypical bacteria causing pneumonia (Mycoplasma, Legionella & Chlamydophyla)

3. Chlamydia trachomatis STD infections

  1. Streptococcus & Staphylococcus
  2. Hemophilus Influenzae & Bordetella
  3. Penicillin-allergic patients
48
Q

Name 3 Macrolide antibiotics.

A

mACErolides

  1. Azithromycin (Zithromax)
  2. Clarithromycin
  3. Erythromycin
49
Q

Erythromycin

(class, MOA, adverse rxns, drug interactions)

A
  1. Class: Macrolide
  2. MOA: 50S ribosome inhibitor
  3. Adverse:
    - Oral: abdominal pain & diarrhea (macrolides = motillin receptor agonists)
    - IV: High doses can cause ototoxicity (Vancomycin also ototoxic)
  4. Drug interactions: inhibits CYP450-3A4 (which metabolizes 50% of drugs), thus increases serum levels of statins, benzos, ca ch blockers, cyclosporines, etc.
50
Q

Which antibacterial drug class acts as Motillin receptor agonists, thus causes diarrhea as an adverse effect?

A

Macrolides (Azitromycin, Clarithromycin & Erythromycin)

mACErolides

51
Q

Clarithromycin (class, MOA, adverse, drug interactions)

A

Very similar to Erythromycin

  1. Class: Macrolides
  2. 50S ribosome inhibitor
  3. Adverse: Less GI effects than Erythro
  4. Drug interactions: stronger CYP450-3A4 inhibition than Erythro
52
Q

Azithromycin

(class, MOA, adverse, drug interactions, benefits)

A
  1. Class: Macrolides
  2. MOA: 50S ribosome inhibitor
  3. Minimal adverse effects
  4. No drug interactions
  5. Other:
    - Post-antibiotic effect (thus given 1/day for 3-5 days)
    - Most popular, safest macrolide antibiotic
53
Q

Tetracyclines

(MOA, bacterial susceptibility/uses, adverse & drug interactions)

A
  1. MOA: Reversibly bind 30S ribosomal subunit
  2. Bacterial susceptibility/Uses:
    - Bacteriostatic
    - Gram +/- bacteria,
    - Lyme disease, Erlichiosis, Rocky Mountain Spotted Fever, Atypical pneumonia, Acne (w/ Minocycline)
  3. Adverse:
    - Discoloration of tooth enamel (children/fetus)
    - Super infection: C. difficle = antibiotic-associated pseudomembranous collitis (also caused by Clindamycin)
    - GI irritation, photosensitivity, hepatotoxicity w/ extended use
  4. Drug interactions: Cheleating agent = binds cations (calcium) and prevents absorption (avoid w/ dairy/antacids)
54
Q

Name 4 Tetracyclines

(& a fun fact about each!)

A

Tetra = 4; DMT (psychedelic) is fun!

  1. Doxycycline: Most popular tetracycline
    - Fecal elimination = can use w/ renally impaired pts
  2. Minocycline: Acne
  3. Tetracycline: Rarely used b/c low bioavailability/short half life
  4. Tigecycline: active against gram +/- & anaerobic bacteria

- Reserve for antibiotic-resistant infections (like MRSA)

55
Q

Aminoglycosides

(MOA, bacterial susceptibility/uses, pharmacokinetics & adverse)

A
  1. MOA: irreversibly binds 30S ribosomal subunit
  2. Bacterial Susceptibility/Uses:
    - Bactericidal
    - Gram - (including Pseudomonas)
  3. PK:
    - Give high dose once b/c conc-dep effect
    - Eliminated renally; accumulate in renal failure
    - Narrow therapeutic index
  4. Adverse:

- Nephrotoxic

- Ototoxic

- NMJ blocking

56
Q

Name 5 Aminoglycosides

A

G-ANTS (gangsta ants, bruh)

  1. Gentamicin
  2. Amikacin
  3. Neomycin
  4. Tobramycin
  5. Streptomycin
57
Q

Tobramycin (class, MOA, uses)

A
  1. Class: Aminoglycoside
  2. MOA: irreversibly bind 30S ribosomal subunit
  3. Uses: Inhaled form for Cystic Fibrosis Patients w/ Pseudomonas pneumoniae
58
Q

Neomycin (class, MOA, uses & adverse)

A
  1. Class: Aminoglycoside
  2. MOA: irreversibly bind 30S ribosomal subunit
  3. Adverse: most toxic/never used as IV
  4. Uses:
    - Topical formulas
    - Oral form for prophylaxis before elective bowel surgery
    - Recurrent GI infections
    - Hepatic encephalopathy management (kills NH3 producing bacteria that worsen encephalopathy)
59
Q

Streptomycin

(class, MOA, uses)

A
  1. Class: aminoglycoside
  2. MOA: irreversibly bind 30S subunit
  3. Uses: second line therapy for active tuberculosis
60
Q

Clindamycin

(Class, MOA, Bacterial susceptibility/Uses, Adverse)

A
  1. Class: class of its own, baby
  2. MOA: binds 50S ribosomal subunit (like macrolides)
  3. Bacterial susceptibility/Uses:
    - Bacteriostatic
    - Anaerobic infections (Bacteroides fragilis & Clostridium perfringies)

- Streptococci, Staphylococci & Pneumocci

  • Gram + infections in penicillin-alergic patients
  • Newly discovered CA-MRSA
    4. Adverse:
  • Primary cause of antibiotic-associated Pseudomembranous colitis (other is Tetracycline)
  • Treatment: Vancomycin & Metrometazole
61
Q

Linezolid

(Class, MOA, Bacterial susceptibility/Uses, Adverse)

A
  1. Class: class of its own
  2. MOA: unique activity against 50S ribosomal subunit
  3. Bacterial susceptibility/Uses:
    - Bacteriostatic
    - Reserved for multi-drug resistant bacteria (VRE/MRSA)
  4. Adverse: Hematologic toxicity (thrombocytopenia/neutropenia)
62
Q

Mupirocin

(class, MOA, uses)

A
  1. Class: of its own
  2. MOA: unrelated to other antibiotics (?)
  3. Uses:
    - Topical preparations for Staphylococcal infections
    - Nasal formulation reserved for MRSA
    - Impetigo (streptococci/staphylococci)
63
Q

Fluoroquinolones

(MOA, Bacterial susceptibility/Uses, Adverse, Drug interactions)

A
  1. MOA: DNA gyrase/topoisomerase inhibitors
  2. Bacterial susceptibility/Uses:
    - Bactericidal against
    - Most gram (-), gram (+) (3rd gen) & Atypical bacteria

- Complicated UTI & prostatitis

  1. Adverse:
    - Arthropathy (avoid in children/pregnancy) = Achilles tendon rupture
    - Neurotoxic @ high doses
  2. Drug interactions:
    - Oral dose inhibited by cations (Ca2+, Mg2+, Fe, Zn)
    - Inhibits caffeine/theophylline metabolism
64
Q

Name two 2nd generation Fluoroquinolones

(& their uses)

A
  1. Ciprofloxacin: only quinolone w/ anti-Pseudomonas aeruginosa
  2. Norfloxacin: UTI infections
65
Q

Name three 3rd generation Fluoroquinolones

(Bacterial susceptibility/use, metabolization)

A

“Respiratory fluoroquinolones” + (LGM)

Bacterial Susceptibility/Uses:

  • Gram (-)

- Atypical bacteria (respiratory infections)

  • Multidrug-resistant Streptococci pneumoniae
    1. Levofloxacin (renal elimination)
    2. Gemifloxacin (hepatic metabolism: don’t use for UTI)
    2. Moxifloxacin (hepatic metabolism: don’t use for UTI)
  • Better anaerobic activity than Levofloxacin
66
Q

Trimethoprim-Sulfamethoxazole

(MOA, Bacterial susceptibility/Uses)

A

aka Bactrim, TMP-SMX or Cotrimoxazol

  1. MOA: “Sequential inhibition”
    - Sulfonamides: inhibit DHF synthesis (via substituting as PABA)
    - Trimethoprim: inhibit Folate reductase (DHF -> THF rxn)
  2. Bacterial Susceptibility/Uses:
    - Most gram (+)/(-) including CA-MRSA
    - Nocardia, Pneumocytis jiroveci = AIDS pts
    - Primary drug for UTI
    - Secondary drug for upper/lower respiratory tract infections, sepsis, meningitis, travelers diarrhea, typhoid, cholera
67
Q

Trimethoprim-Sulfamethoxazole (Bactrium)

(Adverse, Drug interactions)

A
  1. Adverse:
    - Hypersensitivity rxn to SMX (Stevens-Johnson syndrome & Exfoliative dermatitis)
    - High doses (P. jiroveci in AIDS) = thrombocytopenia, neutropenia, allergic rxns & hyperkalemia
  2. Drug interactions:
    - Sulfa drugs = CYP inhibitors: increase serum levels/toxicity of warfarin, phenytoin & oral sulfonylureas (for DM)
68
Q

Metronidazole (Flagyl)

(MOA, uses, adverse)

A
  1. MOA: Disrupts DNA helical structure
  2. Uses:
    - Antibacterial + Antiprotozoal
    - THE best drug for anaerobic bacteria (including C. difficile colitis)
  3. Adverse:
    - Disulfiram-like effect (avoid alcohol)
69
Q

FDA Categories for Drug Use in Prenancy

A

A, B, C, D, X

A = research shows no risk to human fetus

B = animal studies no risk; animals studies show risk, but preg women no risk

C = no available studies; animal studies show risk, but no women trials (most common category)

D = fetal risk, but benefits outweigh risks

X = definite fetal risk; outweighs benefits