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Antibiotics 1 Flashcards

1
Q

Describe gram positive bacterial structure

A

Cytoplasmic membrane –> Thick peptidoglycan layer - has penicillin binding proteins (PBPs)

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2
Q

Describe gram negative bacterial structure

A

Cytoplasmic membrane –> thin peptidoglycan layer - has PBPs –> periplasmic space - location of beta lactamases (only in gram -ve) –> outer membrane - has porins and LPS

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3
Q

Clinically important gram positive aerobic organisms - coccus and occuring in clusters

A

Coagulase positive - Staphylococcus aureus

Coagulase negative - Staphylococcus spp. –> epidermidis, hominis, haemolyticus capitus, saprophyticus

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4
Q

Clinically important gram positive aerobic organisms - coccus and occuring in pairs/chains

A

Streptococcus spp. and enterococcus spp.

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5
Q

Clinically important gram positive aerobic organisms - Rods

A

Listeria and Nocardia

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6
Q

Clinically important gram positive anaerobic organisms - coccus

A

Peptostreptococcus

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7
Q

Clinically important gram positive anaerobic organisms - Rods

A

Clostridium spp.
Propionibacterium
Actinomyces

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8
Q

Clinically important gram negative aerobic organisms - rods and Lactose fermenting

A

Enterobacteriaceae family

E.coli, Klebsiella pneumoniae, enterobacter spp., proteus mirabilis, salmonella spp.

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9
Q

Clinically important gram negative aerobic organisms - Rods and non - Lactose fermenting

A

Non-enterobacteriaceae - usually nasocomial pathogens

Pseudomonas aeruginosa, Actinobacter baumannii, Stenotrophomonas maltophilia

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10
Q

Clinically important gram negative aerobic organisms - coccus

A

Neisseria meningitidis, Neisseria gonorrhea, Moraxella catarrhalis

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11
Q

Clinically important gram negative anaerobic organisms - rods

A

Bacteroides, Prevotella, Fusobacterium

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12
Q

Clinically important Atypical organisms

A

Chlamydia spp. – C. pneumoniae, C. trachomatis
Mycoplasma spp. – M. pneumoniae, M. genitalium
Legionella spp. - L. pneumophilia

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13
Q

Name 3 drugs that are natural penicillins

A 
Pen VK (PO)
Penicillin G (IV)
Benzathine Penicillin (IM)
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14
Q

Natural penicillin MOA

A

Binds to PBPs

Inhibits cross-linking of peptidoglycan layer in the cell wall which causes autolysis and cell death

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15
Q

Natural penicillin mechanism or resistance - gram negative

A
  • efflux pump
  • beta lactamase enzyme –> destruction of antibiotic
  • failure to penetrate outer membrane of bacteria (porins) and reach binding site
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16
Q

Natural penicillin mechanism or resistance - gram positive

A

Alteration of binding site

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17
Q

Natural penicillin spectrum of activity in gram positive bacteria

A

Good activity against enterococcus faecalis

Limited to no activity against S. aureus

18
Q

Natural penicillin is a tx of choice in?

A

Gram positive bacteria
Streptococcus spp.
Group A - S. pyogenes –> skin flora - cellulitis
Group B - S. agalactiae –> skin and vaginal flora
Group C,F,G - Streptococcus –> skin flora - cellulitis
S. pneumoniae –> respiratory flora - pneumonia
Viridans streptococcus –> oral flora - dental infxn, endocarditis

19
Q

Natural penicillin has activity against which gram negative bacteria?

A

Neisseria meningitidis

20
Q

Natural penicillin: spectrum of activity in gram positive anaerobes

A

Good activity against gram positive anaerobes in oral flora

  • Actinomyces spp.
  • Peptostreptococci
  • Propionibacterium
21
Q

Natural penicillin

Tx of choice against which anaerobic bacteria?

A

Clostridium perfringens - anaerobe that causes gas gangrene necrotizing fascitis and clostridial toxic shock

22
Q

Does natural penicillin have activity against gram negative anaerobes?

A

Limited activity due to resistance

  • Bacteroides considered resistant
  • Prevotella and fusobacterium have high likelihood of producing beta-lactamases and being resistant
23
Q

Natural penicillin - activity against other organisms

A

Spirochete - treponema pallidum - causes STI –> syphilis

24
Q

Natural penicillin - metabolism and elimination (humans)

A

Substrate of organic anion transporter (OAT) 1/3
- drugs that effect OAT 1/3 transporters effect concentrations

Poor penetration against BBB but with inflamed meningitis, does exceed MIC of susceptible organisms with new breakpoints (streptococcus)

T 1/2: 30-60 mins –> needs frequent dosing

  • dose: 2 - 3 million units every 4 hrs –> max dose = 24mill U/day divided in q4 dosing
  • continuous infusion to optimize Pk-Pd parameters given its short T1/2

Excreted in urine, mostly unchanged –> requires dose adjustment in renal dysfunction

25
Q

Natural penicillins adverse effects

A

CNS - seizures at high doses (40-100 million u/day)
Hematologic - neutropenia
Hypersensitivity - ranges from rash/hives to anaphylaxis, serum sickness can occur but is uncommon
Renal - AIN, renal tubular disease

26
Q

Natural penicillins drug interactions

A

Drugs that interact with OAT 1/3 - pretomanid, teriflunomide, fexinidazole
Probenecid - increase plasma levels of penicillin by competitively inhibiting renal tubular secretion
- used as alternative dosing strategy to extend T1/2 and increase drug concentrations

27
Q

Name penicillinase resistant penicillins (PRP)

A

Nafcillin (IV)
Oxacillin (IV)
Dicloxacillin (PO)

28
Q

PRP MOA

A
  • bind to PBPs

- inhibit cross-linking of peptidoglycan in the cell wall –> autolysis –> cell death

29
Q

PRP has no activity against which gram positive organism?

A

Enterococcus faecalis

30
Q

PRP is a tx of choice for?

A

Staph. aureus (MSSA)
- Skin and soft tissue infxn due to MSSA (abscess or cellulitis)
- Osteomyelitis, septic arthritis, or prosthetic joint infxn
- Bacteremia or infective endocarditis
NO activity against MRSA
Good activity against penicillin susceptible streptococcus spp.

31
Q

PRP activity in other organisms

A

Gram negative, anaerobes, atypical –> no activity

32
Q

PRP - Metabolism and elimination

A

Nafcillin/Oxacillin (IV)

  • moderate CYP3A4 inducer
  • widely distributed with increased CSF penetration with meningeal information
  • 90-95% protein bound
  • T1/2 - 20 to 60 mins –> dosed q4h
  • excreted in feces (nafcillin) and bile/urine (oxacillin) –> no renal dose adj needed

Dicloxacillin

  • moderate CYP2C19, weak CYP2C9 and weak CYP3A4 inducer
  • rapid and incomplete absorption that is affected by food
  • low CSF-penetration
  • 95-99% protein bound
  • 45 min half life –> dosed q6h
  • excreted in feces and urine as unchanged drug –> no renal dose adj needed.
33
Q

PRP adverse effects

A

GI (dicloxacillin) - abdominal pain, diarrhea, nausea
Hepatic (nafcillin/oxacillin) - increased serum transaminases, hepatotoxicity
Hematologic (n/o) - neutropenia
Renal (n/o) - AIN, renal tubular disease
local (n/o) - injection site rxn, phlebitis

34
Q

PRP drug interactions

A

CYP3A4 substrates will be affacted by Nafcillin and should be monitored
- antifungal azoles, anti-epileptics, statins, transplant meds etc.

Dicloxacillin:

  • transplant meds (sirolimus, tacrolimus, mycophenolate) CYP3A4
  • carbamazepine 3A4
  • Fosphenytoin/phenytoin CYP2C19
  • Omeprazole CYP2C19
35
Q

Aminopenicillins

A

Ampicillin (IV)

Amoxicillin (PO)

36
Q

Aminopenicillins - MOA

A

Bind to PBPs

Inhibit cross linking of peptidoglycan in the cell wall –> autolysis –> cell death

37
Q

Aminopenicillins - spectrum of activity

A

Gram positive: tx of choice for enterococcus faecalis

  • Intra abdominal infxn
  • Polymicrobial diabetic foot infections
  • Bacteremia and infective endocarditis (ampicillin + gentamicin)
38
Q

Does Aminopenicillin work against S. aureus?

A

No

39
Q

Aminopenicillin is a tx of choice for?

A

Listeria monocytogenes

  • neonatal sepsis
  • Bacteremia and meningitis (ampicillin + gentamicin)
40
Q

Ampicillin activity in gram negatives

A
  • limited activity overall –> expanded activity compared to natural penicillins
  • E.coli and P. mirabilis can be susceptible, especially in younger patients w/o prior abx exposure
  • H. influenzae is covered if beta-lactamases negative (otitis media or sinusitis)

Atypical - no activity

41
Q

Aminopenicillin activity in gram + anaerobes

A
  • good activity in gram positive anaerobes - oral flora –> actinomyces spp., peptostreptococci, propionibacterium acnes (Cutibacterium acnes)
42
Q

Aminopenicllin act in gram negative anaerobes

A
  • limited activity against gram negative anaerobes due to resistance
  • Bacteroides fragilis is considered resistant
  • Prevotella spp. and Fusobacterium necrophorum have high likelihood of producing beta-lactamases and being resistant

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