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Anti-infectives Exam 1 > Penicillin > Flashcards

Penicillin Flashcards

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1
Q

Natural Penicillins Examples with Routes

A

Penicillin G (IV)

Benzathine Penicillin (IM)

Penicillin V Potassium (PO)

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2
Q

Natural Penicillins MOA

A

Bind to penicillin binding proteins (PBPs)

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

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3
Q

Natural Penicillins Mechanism of Resistance

A

Beta-lactamase enzymes -> destruction of antibiotic (more common for Gram-negative)

Failure to penetrate outer membrane of bacteria and reach binding site (Gram-negative)

Pumped out of the cell via efflux pump (Gram-negative)

Alteration of binding site (Gram-positive)

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4
Q

Natural Penicillins

Gram-positive Aerobes

Good against: ___
Limited activity against___
Treatment of Choice for ___

A

Good against: Enterococcus faecalis

Limited activity against: Staphylococcus aureus

TOC: for susceptible Streptococcus spp.

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5
Q

Group A streptococcus

A

strep pyogenes

skin flora –> cellulitis

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6
Q

Group B Streptococcus

A

Strep agalactiae

Skin and vaginal flora

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7
Q

Group C, F, G Streptococcus

A

Skin flora –> cellulitis

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8
Q

Streptococcus pneumoniae

A

Respiratory flora –> pneumonia

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9
Q

Viridans Streptococcus

A

oral flora –> dental infections, endocarditis

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10
Q

Natural Penicillins

Gram Negative Aerobes

A

Minimal Activity

Some activity against: Neisseria Meningitidis

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11
Q

Natural Penicillins

Atypical

A

No activity

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12
Q

Natural Penicillins

Anaerobes

Good activity against:
TOC:
Limited activity:

A

Good activity: Gram + anaerobes (oral flora)

    • Actinomyces spp.
  • -Peptostreptococci
  • -Propionibacterium acnes (Cutibacterium acnes)

TOC: Clostridium perfringens

Limited activity: Gram - anaerobes

  • -Bacteroides fragilis
  • -Prevotella spp.
  • -Fusobactierium necrophorum
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13
Q

Natural Penicillins

Other organisms

A

TOC against spirochete, Treponema pallidum, which causes syphilis

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14
Q

Natural Penicillins

Metabolism

A

Substrate of organic transporters (OAT) 1/3

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

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15
Q

Natural Penicillins

Elimination: Half life

A

Half-life in normal renal function is only 30-60 minutes -> leading to frequent dosing
–> often seen dosed as 2-3 million units q4hr

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16
Q

Natural Penicillins

Elimination: Excretion

A

Excreted in urine, mostly as unchanged drug -> requires dose adjustment in renal dysfunction

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17
Q

Natural Penicillins

Adverse effects: CNS

A

Seizures at very high doses (40-100 million units/day)

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18
Q

Natural Penicillins

Adverse effects: hematologic

A

Neutropenia

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19
Q

Natural Penicillins

Adverse effects: Hypersensitivity

A

Ranges from rash/hives to anaphylaxis

Serum sickness can occur but is uncommon

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20
Q

Natural Penicillins

Adverse effects: Renal

A

Acute interstitial nephritis

Renal tubular disease

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21
Q

Natural Penicillins

Drug Interactions

A

Drugs that interact with the organic anion transporters 1/3
–Pretomanid, Teriflunomide, Fexinidazole

Probenecid

  • -Increases plasma levels of penicillin by competitively inhibiting renal tubular secretion
  • -Used as alternative dosing strategy to extend half-life and increase drug concentrations
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22
Q

Penicillinase-resistant Penicillins

Examples with Routes

A

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

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23
Q

Penicillinase-resistant Penicillins

MOA

A

Bind to penicillin binding proteins (PBPs)

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

Acyl side chain prevented disruption of the beta-lactam ring

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24
Q

Penicillinase-resistant Penicillins

Gram + Aerobes

No activity:
Good activity:
TOC:

A

No activity: Enterococcus faecalis or MRSA

Good activity: penicillin-susceptible Streptococcus spp.

TOC: methicillin-susceptible Staphylococcus aureus (MSSA)

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25
Penicillinase-resistant Penicillins Gram - Aerobes
No activity
26
Penicillinase-resistant Penicillins Anaerobes
No activity
27
Penicillinase-resistant Penicillins Atypical
No activity
28
Penicillinase-resistant Penicillins Metabolism: Nafcillin/Oxacillin
Nafcillin is moderate CYP3A4 inducer Widely distributed with increased CSF penetration with meningeal inflammation 90-95% protein bound
29
Penicillinase-resistant Penicillins Elimination: Nafcillin/Oxacillin
Half-life only 20-60 min -> dosed every 4 hours Excreted primarily through feces (nafcillin) and bile/urine (oxacillin) -> no renal dose adjustments
30
Penicillinase-resistant Penicillins Metabolism: 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
31
Penicillinase-resistant Penicillins Elimination: Dicloxacillin
45 min half-life - > dosed every 6 hours Excreted in feces and urine as unchanged drug -> no renal dose adjustments
32
Penicillinase-resistant Penicillins Adverse Effects: GI
Dicloxacillin Abdominal pain, diarrhea, nausea
33
Penicillinase-resistant Penicillins Adverse Effects: Hepatic
nafcillin/oxacillin Increased serum transaminases Hepatotoxicity
34
Penicillinase-resistant Penicillins Adverse Effects: Hematologic
nafcillin/oxacillin Neutropenia
35
Penicillinase-resistant Penicillins Adverse Effects: Renal
nafcillin/oxacillin Acute interstitial nephritis Renal tubular disease
36
Penicillinase-resistant Penicillins Adverse Effects: Local
nafcillin/oxacillin injection site reactions phlebitis
37
Penicillinase-resistant Penicillins Drug interactions
CYP3A4 substrates will be affected by Nafcillin and should be monitored Antifungal azoles, anti-epileptics, statins, transplant medications, etc. ``` Dicloxacillin Transplant medications (sirolimus, tacrolimus, mycophenolate) CYP3A4 Carbamazepine CYP3A4 Fosphenytoin/Phenytoin CYP2C19 Omeprazole CYP2C19 ```
38
Aminopenicllins | Examples and Routes
Ampicillin (IV) Amoxicillin (PO)
39
Aminopenicllins MOA
Bind to penicillin binding proteins (PBPs) Inhibit cross-linking of peptidoglycan in the cell wall -> autolysis -> cell death
40
Aminopenicllins Gram + aerobes TOC: Limited activity: Same as penicillin against:
TOC: Enterococcus Faecalis and Listeria Monocytogenes Limited Activity: Staphylococcus aureus Same as penicillin against: Streptococcus spp. but broader
41
Aminopenicillins Gram - Aerobes Limited activity:
Limited activity overall - > expanded activity compared to natural penicillins Not active if beta-lactamase producing E. coli and P. mirabilis can be susceptible, especially in younger patients without prior antibiotic exposure H. influenzae is covered if beta-lactamase negative (otitis media or sinusitis)
42
Aminopenicillins Atypical
no activity
43
Aminopenicillins Gram + Anaerobes
Good activity against Gram-positive anaerobes (oral flora) Actinomyces spp. Peptostreptococci Propionibacterium acnes (Cutibacterium acnes)
44
Aminopenicillins Gram - 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
45
Aminopenicillins Gram - 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
46
Aminopenicllins Metabolism and Elimination Ampicillin
Distributes well into bile, penetration into CSF with inflamed meninges 10-18% Protein bound Half-life 1 to 2 hours, extended up to 20 hours in anuric patients Primarily excreted in urine as unchanged drug (∼90%) -> requires renal dose adjustment
47
Aminopenicllins Metabolism and Elimination Amoxicillin
Widely distributed 20% Protein bound Half-life 2 hours Primarily excreted in urine as unchanged drug (∼60%) -> requires renal dose adjustment
48
Aminopenicllins Adverse Effects: GI
Amoxicillin Abdominal pain, diarrhea, nausea
49
Aminopenicllins Adverse Effects: Dermatologic
ampicillin Erythema multiforme Exfoliative dermatitis Skin rash Urticaria
50
Aminopenicllins Adverse Effects: Hematologic
ampicillin Neutropenia Leukopenia Anemia Eosinophilia
51
Aminopenicllins Adverse Effects: Renal
Ampicillin Acute interstitial nephritis (rare)
52
Aminopenicllins Drug Interactions
No significant drug interactions
53
Penicillin + Beta-Lactamase Inhibitor Examples and Routes
Ampicillin/sulbactam (IV) Amoxicillin/clavulanate (PO) Piperacillin/tazobactam (IV)
54
Penicillin + Beta-Lactamase Inhibitor MOA
Bind to penicillin binding proteins (PBPs) Inhibit cross-linking of peptidoglycan in the cell wall -> autolysis -> cell death
55
___ was the first beta-lactamase inhibitor
Clavulanic acid
56
Penicillin + Beta-Lactamase Inhibitor Gram + Aerobes No added activity: Added activity: No activity:
No added activity: Enterococcus or Streptococcus spp. Added Activity: S.aureus (methicillin susceptible) No activity: MRSA
57
Penicillin + Beta-Lactamase Inhibitor Gram - Aerobes TOC: Activity against:
TOC: Amox/clav and Amp/sulb are TOC for Haemophilus influenza, Moraxella catarrhalis, Pasteurella multocida & Capnocytophaga species Activity against: Acinetobacter baumannii, E.coli, Klebsiella, Proteus spp., psedomonas aeruginosa
58
Penicillin + Beta-Lactamase Inhibitor Gram + anaerobes
TOC: anaerobes that cause oral infections Actinomyces spp. Peptostreptococci Propionibacterium acnes (Cutibacterium acnes)
59
Penicillin + Beta-Lactamase Inhibitor Gram - anaerobes
TOC: Bacteroides fragilis, Prevotella spp. Fusobacterium necrophorum Intra-abdominal infections Diabetic foot infections
60
Penicillin + Beta-Lactamase Inhibitor Metabolism and Elimination Sulbactam
Widely distributed Protein binding: 38% Half-life elimination: 1 to 1.3 hours Excretion: Urine (~75% to 85% as unchanged drug) within 8 hours
61
Penicillin + Beta-Lactamase Inhibitor Metabolism and Elimination Clavulanic Acid
Protein binding: ~25% Half-life elimination: 1 hour Excretion: Urine (25% to 40% as unchanged drug)
62
Penicillin + Beta-Lactamase Inhibitor Metabolism and Elimination Piperacillin/tazobactam
Widely distributed Protein binding: Piperacillin: ~26% to 33%; Tazobactam: 31% to 32% 6 – 9% of Piperacillin is metabolized to desethyl metabolite (weak activity) 22% of tazobactam is metabolized to an inactive metabolite Half-life elimination: Piperacillin and tazobactam’s half-lives are 45 minutes to 1.5 hours Piperacillin and tazobactam are primarily excreted into the urine (68% for piperacillin and 80% for tazoactam as unchanged drug)
63
Penicillin + Beta-Lactamase Inhibitor Adverse Effects: GI
amox/clav Abdominal pain, diarrhea, nausea
64
Penicillin + Beta-Lactamase Inhibitor Adverse Effects: Dermatologic
Skin Rash Urticaria Pruritis
65
Penicillin + Beta-Lactamase Inhibitor Adverse Effects: Hematologic
Pancytopenia Thrombocytopenia
66
Penicillin + Beta-Lactamase Inhibitor Adverse Effects: Hepatic
Increased LFTs Hepatitis
67
Penicillin + Beta-Lactamase Inhibitor Adverse Effects: Renal
Interstitial nephritis
68
Penicillin + Beta-Lactamase Inhibitor Drug Interactions
Piperacillin-tazobactam + Vancomycin increases risk of nephrotoxicity

Anti-infectives Exam 1 (11 decks)

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