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Antibiotics 1 Flashcards

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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

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A

Good activity against enterococcus faecalis

Limited to no activity against S. aureus

18
Q

Natural penicillin is a tx of choice in?

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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?

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A

Neisseria meningitidis

20
Q

Natural penicillin: spectrum of activity in gram positive anaerobes

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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?

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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?

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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

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A

Spirochete - treponema pallidum - causes STI –> syphilis

24
Q

Natural penicillin - metabolism and elimination (humans)

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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
Natural penicillins adverse effects
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
Natural penicillins drug interactions
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
Name penicillinase resistant penicillins (PRP)
Nafcillin (IV) Oxacillin (IV) Dicloxacillin (PO)
28
PRP MOA
- bind to PBPs | - inhibit cross-linking of peptidoglycan in the cell wall --> autolysis --> cell death
29
PRP has no activity against which gram positive organism?
Enterococcus faecalis
30
PRP is a tx of choice for?
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
PRP activity in other organisms
Gram negative, anaerobes, atypical --> no activity
32
PRP - Metabolism and elimination
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
PRP adverse effects
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
PRP drug interactions
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
Aminopenicillins
Ampicillin (IV) | Amoxicillin (PO)
36
Aminopenicillins - MOA
Bind to PBPs | Inhibit cross linking of peptidoglycan in the cell wall --> autolysis --> cell death
37
Aminopenicillins - spectrum of activity
Gram positive: tx of choice for enterococcus faecalis - Intra abdominal infxn - Polymicrobial diabetic foot infections - Bacteremia and infective endocarditis (ampicillin + gentamicin)
38
Does Aminopenicillin work against S. aureus?
No
39
Aminopenicillin is a tx of choice for?
Listeria monocytogenes - neonatal sepsis - Bacteremia and meningitis (ampicillin + gentamicin)
40
Ampicillin activity in gram negatives
- 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
Aminopenicillin activity in gram + anaerobes
- good activity in gram positive anaerobes - oral flora --> actinomyces spp., peptostreptococci, propionibacterium acnes (Cutibacterium acnes)
42
Aminopenicllin act in gram negative anaerobes
- 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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