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Pediatric Pharmacology Exam 2 > Antibiotics > Flashcards

Antibiotics Flashcards

1
Q

Natural Prevention

A
  • Anatomical/Physiological barriers
    • Skin
      • pH
      • Barrier
    • Lungs
      • Ciliary clearance
    • Stomach
      • Lower stomach pH
  • Innate immunity
    • Non-specific
  • Adaptive immunity
    • Takes several days to develop response
    • Long-term memory of a specific pathogen
  • Modulating immune system:
    • GCSF
    • Immuneglobulins
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2
Q

Infection definition

A
  • Infection: An invasion of any host organism by disease-causing organisms
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3
Q

Micro-organisms classification

A
  • Bateria
  • Fungi/Mold
  • Viruses
  • Parasites
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4
Q

Antibiotic Classification

A
  • Antibacterial
  • Antifungal
  • Antiviral
  • Antiparasitic
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5
Q

Increased Risk of Infection

A
  • Age
  • Nutrition
  • Pregnancy
  • Decreased defense barriers (ex. Severe burns)
  • Cancer, HIV, other infections
  • Immunocompromised
  • Immunization history
  • Indwelling catheters
  • Corticosteroids
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6
Q

Considerations of Treatment – General

A
  • General considerations
    • Cost
    • Insurance formulary
    • Administration considerations (IV vs. PO, q24 vs. q8)
    • Patient population (antibiogram)
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7
Q

Considerations of Treatment – medication consideration

A

Medication considerations

  • Combination therapy (synergy)
  • Antibiotic susceptibility
  • Empiric Therapy
  • Targeted “narrower” treatment
  • Diagnostic tests
  • PK/PD parameters
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8
Q

Considerations of Treatment - patient

A

Patient considerations

  • Age
  • Immune function
  • Allergies
  • Response to antibiotics (improving or worsening)
  • Adverse events (ADRs)
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9
Q

Antibacterial Testing

Diagnostic testing

A
  • Gram Stain
    • Gram (+) vs. Gram (-)
  • Cultures
    • Growth of causative infection taken from site of infection
    • Susceptibility
  • Serology
    • Titers or antibodies measured
  • CBC
    • Elevation (or decrease) in WBC
  • PCR testing
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10
Q

Obtaining Cultures

A
  • Ideally should always be done BEFORE starting antibiotic therapy
  • Depending on infection concern, multiple cultures should be drawn simultaneously
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11
Q

Antibiotic Pharmacokinetic and Pharmacodynamic Concepts

A
  • Pharmacokinetics and Pharmacodynamics of Antibacterial Agents
    • Best antibiotic choice may depend on the different PK and PD properties
      • Example: Daptomycin
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12
Q

Medication considerations – antibiotics

A
  • Pharmacodynamics
  • Pharmacokinetics
  • Tissue penetration
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13
Q

Routes of Admin

A
  • Bioavailability
  • Severity of infection
  • Location of infection
  • Organ function
  • Drug levels required
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14
Q

Bactericidal

A
  • Destroy microbes
  • Example: Penicillin
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15
Q

Bacteriostatic

A
  • Inhibit the growth of bacteria but do not kill them
  • Need immunologic response to eliminate organisms
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16
Q

Pharmacodynamic Efficacy – Both

A
  • Some antibiotics exhibit bactericidal and bacteriostatic properties depending on concentration in the blood
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17
Q

Spectrum of Activity

Narrow vs. Broad

A
  • Narrow spectrum
    • Active against limited groups of pathogens
    • Generally, may only work against gram (-) or gram (+) organisms but not both
  • Broad spectrum
    • Active against wide range of pathogens
    • Often used for empiric therapy
    • Generally, has activity against both gram (-) and gram (+) organisms
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18
Q

Time-dependent kinetics

A

Relies on the amount of time the serum concentration remains above the MIC

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19
Q

Concentration-dependent kinetics

A
  • Relies on the highest concentration in the serum reached, must greatly exceed the MIC
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20
Q

Post antibiotic effect (PAE)

A
  • Delayed regrowth of bacteria following antibiotic exposure
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21
Q

Aerobic

A

Grow and live in the presence of oxygen

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22
Q

Anaerobic

A

Grow and live in the absence of oxygen

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23
Q

Gram Positive

A
  • Thick peptidoglycan cell wall
  • Cocci
  • Bacilli
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24
Q

Gram Negative

A
  • Thin peptidoglycan cell wall
  • Addition of a thick outer lipid membrane
  • Coccobacilli
  • Cocci
  • Bacilli
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25
Q
  • Minimum Inhibitory Concentration (MIC)
A
  • The lowest concentration of an antibacterial agents to prevent growth
  • Predicts bacteriological response to therapy
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26
Q

Testig for susceptibility is defined by…

A

Clinical laboratory standard institute (CLSI)

Some bacteria are inherently resistant to certain classifications

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27
Q
  • CLSI Breakpoints –
A
  • Sensitive
  • Intermediate
  • Resistant
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28
Q

Beta-Lactams General

A
  • Generally considered ‘broad spectrum’ antibiotics
    • Gram (+)
    • Gram (-)
    • Anaerobes
    • Pseudomonas
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29
Q

Beta-Lactam Classifications

A
  • Penicillins
  • Extended-Spectrum Penicillin (ESPCN)
  • ß-Lactam/ß-Lactamase Inhibitors
  • Cephalosporins
  • Carbapenems
  • Monobactam
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30
Q

Beta-Lactams Mechanism of Action

A
  • Bactericidal
  • Binds to cell wall and inactivates Penicillin Binding Proteins (PBPs)
  • Interferes with the last step of bacterial wall synthesis
  • Time dependent killing
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31
Q

Penicillins

General

A
  • Natural penicillins
  • Aminopenicillins
  • Penicillinase-Resistant Synthetic Penicillins (PRSPs)
  • Extended-Spectrum Penicillins (ESPCN)
  • Beta-Lactam/Beta-Lactamase Inhibitors
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32
Q

Natural Penicillin

Clinical use

A
  • Clinical use
    • Pneumococcal and streptococcal infections
    • Drug of Choice (DOC) for syphilis
    • Prophylaxis of enapsulated organisms
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33
Q

Penicillin

IM

Oral

A

IM=Penicillin G

Oral = Penicillin VK

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34
Q

Aminopenicillin

Clinical Use

A
  • Minimal activity against Gram (-)
  • Clinical Use
    • DOC for enterococcal infections
    • Community-acquired respiratory infections
    • Otitis media
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35
Q

Aminopenicillin

IV/IM

Oral

A

IM/IV = ampicillin (IV/IM), ampicillin (IV/IM)

Oral = ampicillin, amoxicillin

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36
Q

Penicillinase-Resistant Synthetic Penicillins (PRSPs)

Clinical Use

A
  • No enterococcal coverage
  • No coverage of Methicillin Resistant S. Aureus (MRSA)
  • Clinical Use
    • DOC for beta-lactamase (penicillinase) positive
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37
Q

PRSPs

IV/IM agent

Oral agent

A

IV/IM = oxacillin, nafcillin

Oral = dicloxacillin, dicloxacillin

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38
Q

Extended-Spectrum Penicillin

Clinical Use

A
  • Pseudomonasaeruginosa
    • Usually in combination with an aminoglycoside
    • Monotherapy okay for UTI
  • Enterococcalactivity
  • Goodanaerobicactivity
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39
Q

Extended-Spectrum Penicillin

IV formulation

A
  • Only available as IV formulation
    • Piperacillin
    • Ticarcillin
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40
Q

Extended spectrum penicillin is used in combination with

A

B-lactamase inhibitor

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41
Q

B-Lactamase Inhibitor

A
  • The beta-lactamase inhibitor restores the activity of the beta- lactam component in the presence of beta-lactamase
    • Increases spectrum of activity
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42
Q

Selected B-Lactamase Producing Organisms

A

Staph aureus (Not MRSA)

H. influenza

Most anaerobes

Many gram negative bacilli

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43
Q

B-Lactam – Mixed Infections

A

Respiratory infections

Abdominal infections

Skin/soft tissue infections

Bite wound infections

Resistant UTIs

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44
Q

B-Lactams

IV/IM Agents

A

IV/IM

  • Piperacillin/Tazobactam (Zosyn)
  • Ampicillin/Sulbactram (unasyn)
  • Ticarcillin/Clavulanate (Timentin)

Oral

  • Amoxicillin/clavulanate (Augmentin) – depending on infection
  • SAME^
  • N/A (change antibiotic class)
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45
Q

PCN ADE

A
  • Rash (usually delayed)
  • Seizures (rare)
  • Abdominal discomfort
  • Neutropenia
  • Fever (drug-induced fever)
  • Acute renal failure (AKI)
  • Elevated LFTs (oxacillin and nafcillin)
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46
Q

PCN CLINICAL PEARLS

A
  • Generally considered broad spectrum
  • Increasing rates of resistance seen
    • Specifically Enterobacteriaceae
    • Common with failure to narrow therapy
    • Common with prolonged duration of use
  • Should not be used for MRSA infections
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47
Q

Cephalosporins Generations

A
  • 1st generation
  • 2nd generation
    • Enteric
    • Respiratory
  • 3rd generation
    • Non-pseudomonal
    • Pseudomonal
  • 4th generation
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48
Q

1st Generation Cephalosporin

Clinical uses

A
  • Primarily for GPC infections
    • EXCEPT: Enterococcus
    • Garden-variety gram (-) bacillary infections (PECK)
      • Proteus
      • E. Coli
      • Klebsiella
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49
Q

Cephalosporins 1st generation

IV/IM – Oral

A

IV/IM

  • Cefazolin (IV)

Oral

  • Cephalexin
  • Cefadroxil
50
Q

2nd Generation Cephalosporins

A
  • Enteric Cephalosporins
  • Only available as IV/IM formulations
    • Cefoxitin
    • Cefotetan
51
Q

2nd generation ceph

Clinical uses

A
  • Anaerobic coverage (Bacteroides fragilis)
  • Enhanced GNR activity, but not GPC activity
  • Surgical prophylaxis (colorectal, abdominal)
52
Q

2nd generation ceph

Enteric cephalosporins

A

Available agents – cefoxitin (IV/IM)

Clinical use

  • Surgical prophylaxis (colorectal, abdominal)

Spectrum of activity

  • Anaerobic coverage (Bacteroides fragilis)
  • Enhanced GNR activity (lacks GPC activity)
53
Q

2nd generations cephalosporins

Respiratory

Available agent, clinical use, Spectrum of activity

A

Available agents – Cefuroxime (IV/IM/PO)

Clinical Use

  • Lower respiratory tract infections

Spectrum of Activity

  • Streptococcus pneumonia
  • H. Influenza
54
Q

3rd Generation Cephalosporins

Spectrum of Activity

A
  • Enhanced Gram (-) activity
  • Activity against PCN-resistant pneumococcus
  • Ceftazidime effective against Pseudomonas
55
Q

3rd Generation Cephalosporins

Clinical use

A
  • Community Acquired Pneumonia (CAP)
  • Meningitis
  • Gonorrhea
56
Q

3rd Generation Cephalosporins

Benefit

A
  • Once daily dosing (ceftriaxone and forms)
57
Q

3rd Generation Cephalosporin

IV/IM

Oral

A

IV/IM agents

  • Cefotaxime
  • Ceftriaxone (Rocephin)
  • Ceftazidime
  • Cefotaxime

Oral

  • Cefpodoxime (Vantin)
  • Cefixime (Suprax)
  • Cefdinir (Omnicef)
58
Q

4th Generation Cephalosporins

Clinical Use

A
  • Best cephalosporin for GNR
  • Any serious infection
59
Q

4th Generation Cephalosporin

Spectrum of Activity

A
  • Exhibits excellent gram (+) and gram (-) activity
  • Covers Staphylococcus, Streptococcus, P. aeruginosa
  • IV/IM Agent
60
Q

4th Generation Cephalosporin

Oral Agent Equivalent

A
  • Can sometimes be used even if isolate is resistant Cefepime (IV/IM)
  • None to 3rd generation cephalosporins
61
Q

4th generation

IV/IM

Oral

A

IV/IM – cefepime

Oral – none

62
Q

Cephalosporin ADE

A
  • Rash (usually delayed)
  • Seizures (rare)
  • Abdominal discomfort
  • Neutropenia
  • Fever (drug induced fever)
  • Biliary sludging (ceftriaxone)
63
Q

Cephalosporin Clinical Pearls

A
  • Use in caution in patients with PCN allergies
    • ~10% cross sensitivity
  • Coverage changes with change in generation
    • GPC
    • GNR
    • Pseudomonas
64
Q

Carbapenems

General

A
  • Broadest spectrum of all antibiotics
  • Potential cross sensitivity for PCN allergies
    • ~15%
65
Q

Carbapenems

Spectrum of Activity

A
  • Pseudomonas infections
66
Q

Carbapenems

Clinical Use

A
  • Serious infections with multiple resistant bacteria
  • Febrile neutropenia
  • Monotherapy for polymicrobial infections
67
Q

Organisms intrinsically resistant to carbapenems (7)

A
  • MRSA
  • E. faecium
  • Stenotrophomonas
  • Burkholderia
  • Chlamydia
  • Mycoplasma
  • Corynebacterium
68
Q

Carbapenems

IV/IM

A

Imipenem

Meropenem

Doripenem

Ertapenem (IV/IM)

69
Q

Monobactam (Aztreonam)

Spectrum of Activity

A
  • NO activity against GPC or anaerobes
  • ONLY active against GNR
  • No apparent cross-reactivity in ß-lactam allergic patients
70
Q

Aminoglycosides

Mechanism of Action

A
  • Bactericidal
    • Concentration dependent killing
    • Inhibits protein synthesis at 30s ribosome
71
Q

Aminoglycosides

Spectrum of Activity

A
  • Gram Negative Rod infections
  • Used in combination for gram (+) organisms (i.e. endocarditis)
  • GI bacterial overgrowth
72
Q

Aminoglycosides

Clinical Use

A
  • Gram (-) infections
  • Poor penetration in to abscesses
73
Q

Aminoglycosides

Specific Agents

A
  • Amikacin
    • Greatest risk of toxicity
    • Tends to defer resistance compared to gentamicin and tobramycin
  • Gentamicin
  • Tobramycin
    • Pseudomonal coverage than gentamicin
  • (Streptomycin)
74
Q

Aminoglycosides

Dosing

A
  • Requires narrow therapeutic monitoring
  • Interval dosing can be traditional or extended
75
Q

Aminoglycosides

Toxicity (associated with long-term use and acute toxicity)

A
  • Nephrotoxicity (renal tubular damage)
  • Ototoxicity (Irreversible hearing loss)
76
Q

Sulfonamides (Sulfamethoxazole)

AKA…

A

Folic acid metabolism inhibitors

77
Q

Sulfonamides (Sulfamethoxazole)

Mechanism of Action

Bacteriocidal vs. static?

A
  • Bacteriostatic
  • Inhibits cell growth via interfering with folic acid synthesis
  • Generally abbreviated as ‘sulfa’ medications
78
Q

Sulfonamides (Sulfamethoxazole)

Spectrum of Activity

Drug of choice for (3)

A
  • Gram (-) & gram (+)
  • MSSA & MRSA
  • Drug of choice for: Stenotrophomonas, Nocardia, & Pneumocystis jiroveci pneumonia (PCP)
79
Q

Sulfonamides (Sulfamethoxazole)

Clinical Use

A
  • UTI (treatment and prophylaxis)
  • Respiratory tract infections
  • PCP prophylaxis
  • Abdominal infections
  • Cellulitis
80
Q

Sulfonamide ADE (7)

A
  • Rash
  • Photosensitivity
  • Nephrotoxicity
  • Obstructive uropathy
  • Neutropenia
  • Thrombocytopenia
  • Hyperkalemia
81
Q

Sulfamethoxazole/Trimethoprim (Bactrim®, Co-trimoxale®,SMX/TMP)

IV/PO information

Clinical Pearls (2); PCP dosing, allergies

A
  • Only available in combination with trimethoprim
  • Available as IV and PO
    • IV has short stability and requires more frequent dosing
    • PO dosing is typically q12
  • Clinical Pearls
    • PCP ppx dosing is TIW (FSS, MWF, etc)
    • Watch for sulfa allergies
82
Q

Fluoroquinolones

General and MOA

A
  • Broad spectrum of activity against GNR
  • Poor anti-anaerobic activity
  • Mechanism of Action
    • Bactericidal
    • Inhibits topoisomerase IV and DNA gyrase
83
Q

Fluoroquinolones

Spectrum of Activity (4)

A
  • Broad spectrum of activity against GNR
  • Variable Pseudomonal & Streptococcal activity
  • Covers MSSA but not MRSA reliably
  • E coli
84
Q

Fluoroquinolones

Clinical Use

A
  • Poor anti-anaerobic activity
  • UTI
  • STD
85
Q

Fluoroquinolones

Available Agents

A
  • Ciprofloxacin (CIPRO)
    • IV/PO otic and optic suspension
    • Best for pseduomonal activity
  • Levofloxacin (Levaquin)
    • IV/PO
  • Moxifloxacin (Avelox)
    • IV, PO
  • Ofloxacin (ocular suspension)

Decision which FQ may be dictated by patient’s insurance

86
Q

Fluoroquinolones ADE

A
  • Photosensitivity
  • Seizures(rare)
  • Abdominal discomfort
  • QTc interval prolongation
  • CNS stimulation
  • BBB for:
    • Tendon ruptures
    • Peripheral neuropathy
    • CNS effects
87
Q

FQs Clinical Pearls

A
  • Ideal oral antibiotic if broad spectrum is needed
  • Caution with BBB
  • Watch for increasing rates of resistance
  • Avoid in pregnancy and lactation
  • Requires renal dose adjustment
  • Polyvalent metallic cationic adsorptive interactions
    • Avoid taking with foods and/or medications with metallic cautions
88
Q

Tetracyclines

Mechanism of Action

A
  • Bacteriostatic
  • Inhibits 30s and 50s ribosomal subunits in susceptible bacteria
89
Q

Tetracyclines

Spectrum of Activity

A
  • Stenotrophamonas (minocycline)
  • MSSA, MRSA
  • Mycoplasma pneumonia
  • Lots more…
90
Q

Tetracyclines

CLinical Use

A
  • Community-acquired respiratory tract infections
  • STDs (chlamydia)
  • Lime disease and Rickettsial diseases
  • Malaria prophylaxis
  • Acne
91
Q

Tetracyclines

Available Agents

A
  • (all have IV & PO formulations)
    • Minocycline*
    • Tetracycline
    • Doxycycline *

* Used more orally than tetracycline

92
Q

Tetracycline ADE

A
  • Photosensitivity
  • Abdominal discomfort
  • Stained teeth (cosmetic)
  • Absorption may be decreased with foods and metallic cations
93
Q

Macrolides

Mechanism of Action

A
  • Bacteriostatic
  • Binds to 50s ribosomal subunit to inhibit RNA synthesis
94
Q

Macrolides

Spectrum of Activity

A
  • H. pylori
  • Atypical pathogens
    • Legionella
    • Mycoplasma
    • Chlamydia pneumoniae
95
Q

Macrolides

Clinical Use

A
  • Respiratory infections & community-acquired pneumonia
  • Skin and soft tissue infections
  • STDs
96
Q

Macrolides

Available Agents

A
  • Erythromycin (EES)
    • Used largely in pediatric for pro-motility & enhance gastric emptying
    • Causes QT prolongation
  • Azithromycin
  • Clarithromycin
97
Q

Macrolides

ADE

A
  • Abdominal discomfort
  • Ototoxicity (rare)
  • Taste disturbances
98
Q

Macrolides

Clinical Pearls

A
  • Erythromycin is used more for its intestinal pro-motility agent
  • Decreased clearance of many drugs via CYP 450 inhibition
    • Not seen with azithromycin
  • Do not use clarithromycin during pregnancy
    • Pregnancy category C
99
Q

Clindamycin

Mechanism of Action

A
  • Mechanism of Action
    • Bacteriostatic
    • Bacteriocidal
  • Inhibits protein synthesis by binding to 50s ribosomal subunit
100
Q

Clindamycin

Spectrum of Activity

Clinical Use

A
  • Spectrum of Activity
    • Aerobic GPCs
    • MRSA & MSSA
    • Anaerobic organisms
  • Clinical Use
    • Inhibits toxin release
    • Cellulitis
101
Q

Lincodamide ADE

A
  • Abdominal discomfort
    • Pseudomembranous colitis
  • Taste!
    • Capsules can be opened and dissolved
102
Q

Metronidazole

Mechanism of Action

Spectrum of Activity

A
  • Mechanism of Action
    • Bactericidal
    • Interacts with DNA to cause a loss of helical DNA structure and strand breakage
  • Spectrum of Activity
    • Clostridium difficile colitis
    • Anaerobic infections
    • Protozoal infections
103
Q

Metronidazole

Clinical Use

A
  • STDs
  • Bacterial overgrowth
104
Q

Metronidazole

ADE

A
  • Peripheral neuropathy
  • Taste disturbances
  • Disulfiram reaction
  • Seizures (rare)
  • Abdominal discomfort
105
Q

Vancomycin

Mechanism of Action

Spectrum of Activity

A
  • Mechanism of Action
    • Slowly bactericidal
    • Glycopeptide that Inhibits cell wall synthesis
  • Spectrum of Activity
    • Gram (+) organisms
    • C. difficile
106
Q

Vancomycin

Clinical Use

A
  • Treatment of choice for MRSA
  • Empiric therapy for pneumococcal meningitis
  • Oral therapy for C. difficile colitis
  • In place of penicillin in patients with a PCN allergy
107
Q

Vancomycin

ADE

A
  • Ototoxicity (rare)
  • Nephrotoxicity
  • (Red-man syndrome)
  • Neutropenia
108
Q

VANCO ADME

A
  • Requires serum level monitoring for efficacy and safety
  • Not orally absorbed
109
Q

Linezolid

Mechanism of Action

A
  • Bacteriostatic in vitro
  • Bactericidal in vivo
  • Inhibits cell wall synthesis
110
Q

Linezolid

Clinical Use

A
  • Vancomycin Resistant Enterococcus (VRE)
  • Systemic oral GPC-specific product is needed
  • Does not need renal adjustment
111
Q

Linezolid

ADE

A
  • Thrombocytopenia
  • Peripheral neuropathy
  • Optic neuropathy
  • Lactic acidosis
112
Q

Daptomycin

Mechanism of action

Spectrum of Activity

A
  • Mechanism of Action
    • Bactericidal
    • Depolarizes cell wall
  • Spectrum of Activity
    • VRE
    • MRSA
    • VRSA
113
Q

Daptomycin

Clinical USe

A
  • Skin & soft tissue infections
  • Endocarditis
  • AVOID in pneumonia
114
Q

Daptomycin

ADE

A
  • CPK elevations
  • Myopathies
    • Avoid in combination with statins
115
Q
  • Azole Antifungal
    • Mechanism of Action
A
  • Inhibits ergosterol synthesis (main sterol in fungal cell wall) therefore prevents cell wall growth
116
Q

Azole Antifungal

Available Agents

A
  • Fluconazole
  • Ketoconazole (used topically)
  • Voriconazole
117
Q

Azole Antifungal

Spectrum of Activity

  • Fluconazole
  • Voriconazole
A
  • Fluconazole
    • Candida
    • Cyptococcus, blastomyces, etc.
  • Voriconazole
    • Candida species
    • Aspergillus
    • Mold
118
Q

Azole Antifungal

Side effects

A
  • Increase in LFTs
  • Abdominal pain, N/V (general well tolerated)
  • QT prolongation
  • Specific to voriconazole:
    • CNS hallucinations or visual disturbances
    • Increased SCr
119
Q

Azole Antifungal

Clinical Pearls

A
  • Voriconazole requires therapeutic drug monitoring
  • Major interaction with CYP enzymes
    • CYP3A4 (strong inhibitor)
    • CYP2C9 & CYP2C19 (moderate inhibitor)
120
Q
A

Pediatric Pharmacology Exam 2 (9 decks)

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