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Antibiotics Flashcards

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1
Q

Beta-lactam antibiotics (mechanism of action)

A

Mechanism of action:

  • Bind PBPs and thus inhibit peptidoglycan crosslinking
  • bactericidal except against Enterococcus spp)

Includes: penicillins, cephalosporins, carbapenems, monobactams

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2
Q

Vancomycin (Mechanism of action)

A
  • Binds to D-Ala and interrupts chain for peptidoglycan synthesis
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3
Q

Vancomycin (Mechanism of resistance)

A

Altered binding site, D-alanyl-D-alanine

Thickened cell wall

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4
Q

Vancomycin (Pharmacokinetics)

A
  • Poor oral bioavailability
  • Give IV
  • Well distributed
  • Not extensively metabolized
  • Renal elimination
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5
Q

Vancomycin (Adverse effects)

A

Red Man’s syndrome

Nephrotoxicity

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6
Q

Beta-lactam antibiotics (mechanism of resistance)

A

Mechanisms of resistance:

  • Altered PBPs with decreased affinity for beta-lactam drug
  • Mechanism in gram+ (Staphylococcus, Enterococcus, Streptococcus)
    • Overexpression of efflux pumps, loss of porins, B-lactamases (catalyze hydrolysis of B-lactam ring; periplasmic space of gram-, outside cell wall in gram+)
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7
Q

Beta-lactams (Pharmacokinetics)

A

Pharmacokinetics:

  • Moderate absorption
  • Moderate distribution (some carbapenems good for CNS)
  • Not extensively metabolized
  • 80-100% excreted renally unchanged (except nafcillin, oxacillin, ceftriaxone)
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8
Q

Beta-lactams (Adverse effects)

A

Adverse effects:

  • Hypersensitivity (rash)
  • Seizures (at high doses; esp carbapenems)
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9
Q

Fosfomycin (mechanisms)

A

Mechanism of action:
- inhibits first step in peptidoglycan synthesis by binding to enzyme that catalyzes formation of N-acetylmuramic acid (precursor of peptidoglycan)

Mechanism of resistance:
- decreased drug uptake, target site modification, enzymatic inactivation

Pharmacokinetics:

  • Orally
  • Excellent distribution
  • Excreted unchanged

Notes:

  • well tolerated
  • use for uncomplicated UTIs
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10
Q

Inhibitors of protein synthesis

A

Mechanism of action:
- inhibition of ribosomal function results in impaired protein synthesis

Mechanism of resistance:
- Efflux pump overepxression, ribosomal mutation or modification

Includes: aminoglycosides, macrolides, tetrcyclines, linezolid, clindamycin, tigecycline

Can be 50S or 30S inhibitors

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11
Q

Linezolid (mechanism)

A

Mechanism of action:
50S inhibitor that blocks initiation of protein translation

Pharmacokinetics:

  • Excellent absorption
  • Extensive, including CSF, distribution
  • Metabolized by oxidation
  • 30-40% excreted unchanged in urine

Toxicity:

  • MYELOSUPPRESSION
  • Serotonin syndrome (with other serotonergic agents)
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12
Q

Macrolides, clindamycin (mechanism)

A

Mechanism of action:
50S inhibitor that blocks translocation of peptidyl-rRNAs which elongate peptide chain

(MACROLIDES)
Pharmacokinetics:
- Moderate absorption
- Extensive distribution (minimal CSF)
- Extensively metabolized hepatically (clarithromycin)
- Unchanged drug eliminated via feces (azithromycin). Unchanged drug and metabolites via urine (clarithromycin)

Toxicity:

  • Erythromycin used for pro-kinetic GI effects
  • Clarithro/Azithro have fewer GI side effects
  • Torsades de pointes (ventricular tachycardia with clarithromycin + CYP3A4 hepatic enzymes)
----------------------------------------------------------
(CLINDAMYCIN)
Pharmacokinetics:
- Very good absorption
- Extensive (minimal CSF) distibution
- Extensively metabolized hepatically
- Elimination mostly via bile/feces

Toxicity:
- C. dificile colitis

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13
Q

Tetracyclines, tigecycline (mechanism)

A

30S inhibitors that block access of tRNAs to ribosomes

(TETRACYCLINES)
Pharmacokinetics:
- Good oral absorption (90-100% bioavailable); chelation decreases
- Extensive distribution, poor CSF
- Minocycline extensively metabolized hepatically, > doxycycline > tigecycline
- Mino eliminated biliary; doxy by feces/20% unchanged in urine; tige: via bile

Toxicity:

  • GI, esophageal ulceration (take with fluid and remain upright)
  • Gray to brown discoloration of teeth in children
  • Photosensitivity
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14
Q

Aminoglycosides (mechanism)

A

30S inhibitors that bind 16S rRNA component of ribosome leading to mistranslation

Pharmacokinetics:

  • Minimal absorption
  • Poor distribution (not CNS)
  • No hepatic metabolism
  • Exclusively filtered as unchanged drug
    • Need pharmacokinetic monitoring to maximize peaks and minimize toxicity

Adverse effects:

  • Nephrotoxicity (proximal tubular cell accumulation, reversible)
  • also ototoxicity

Includes:

  • Gentamycin
  • Tobramycin
  • Amikacin
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15
Q

Trimethoprim/Sulfamethoxazole (mechanism)

A

Inhibitor of DNA/RNA synthesis
Inhibit nuclear acid synthesis

Mechanism of resistance:
- Bypass targets; structural changes in target enzymes

Pharmacokinetics:

  • Excellent absorption
  • Extensive distribution, including CSF
  • SMX extensively metabolized hepatically; minimal hepatic metabolism for TMP
  • SMX 30% excreted unchanged in urine; 70-90% for TMP

Toxicity:

  • Skin reactions in 3-4% patients (mild, Stevens-Johnson, toxic epidermal necrolysis)
  • Renal - mild elevations of serum creatinine; acute interstitital nephritis
  • Hematological - neutropniea, thrombocytopenia (rare)
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16
Q

Rifamycins (mechanism)

A

Mechanism of action:
Inhibits DNA-dependent RNA polymerase (inhibits RNA synthesis)

Mechanism of resistance:
- target site mutation

Pharmacokinetics:

  • Very well absorbed orally
  • Extensively distributed including CSF
  • Extensively metabolized hepatically
  • Biliary elimination

Toxicity:

  • Orange-red discoloration of tears, sweat, urine
  • Gastrointestinal
  • Hepatotoxicity (elevation in bilirubin to fulminant hepatitis)
  • Many drug-drug interactions
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17
Q

Fluoroquinolones ( mechanism)

A

Mechanism of action:
- inhibit topoisomerases which catalyze reactions vital for DNA replication, transcription, recombination and repair

Pharmacokinetics:

  • Excellent absorption
  • Extensive distribution, moderate CNS penetration
  • Metabolism differs among agents:
    • Levo: no hepatic metabolism
    • Cipro: 10-20% total elimination
    • Moxi: >60% dose hepatically metabolized
  • Renal clearance depends on degree of hepatic metabolism

Toxicity:

  • CNS
  • Tendinitis with rupture
  • C dificile
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18
Q

Fidaxomicin (mechanism)

A

Mechanism of action:
- inhibiting transcription of bacterial RNA polymerase

Macrocyclic antibiotic, only used for C. dif infections

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19
Q

Nitrofurantoin (mechanism)

A

Mechanism:
- appears that parent compound is reduced to form DNA-damaging oxygen radicals

Mechanisms of resistance:
- Mutations resulting in inhibition of reductase activity

Pharmacokinetics:

  • only PO availability
  • Very low drug levels in tissues and serum
  • Minimal metabolism
  • Extensively eliminated via urine (high urine concentrations), short half-life
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20
Q

Metronidazole (mechanism)

A

Mechanism:
- Pro-drug; anaerobic nitro-reduction to radical metabolites that bind to and perturb DNA function

Mechanism of resistance:
- Rare outside of intrinsically-resistant organisms

Pharmacokinetics:

  • Excellent absorption (100% BA)
  • Extensive distribution (including CSF)
  • Extensive metabolism
  • Minimal renal elimination of unchanged drug but metabolites eliminated renally

Toxicity:

  • GI: metallic taste
  • Peripheral neuropathy
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21
Q

Daptomycin (mechanism)

A

Mechanism of action:
- Inserts into CM in Ca++ dependent manner, resulting in membrane depolarization via efflux of potassium that is associated with disruption of DNA, RNA, protein synthesis and possibly death

Mechanism of resistance:
- Multiple; thickened cell wall and altered binding site

Pharmacokinetics:

  • only IV absorption
  • LImited distribution, minimal CSF penetration
  • LImited metabolism
  • 90% excreted via kidney

Toxicity:

  • Muscle pain/weakness (CPK elevations)
  • Rash
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22
Q

Polymyxins (mechanism)

Colistin or Polymyxin B)

A

Mechanism of action:
- Inserts into membranes and interacts with phospholipids, acts as cationic detergent

Mechanism of resistance:
- possible altered binding site (modification of phospholipids)

Pharmacokinetics:

  • IV only
  • Limited with minimal CSF penetration
  • Unclear metabolism
  • Minimal renal elimination of unchanged drug

Toxicity:

  • dose-related, reversible nephrotoxicity
  • Neurotoxicity and paresthesias
23
Q

Natural Penicillins

  • Penicillin V (PO)
  • Penicillin G, benzathine (IM)
  • Pencillin G, procaine (IM)
  • Penicillin G, Na/K (IV)
A

Good for:
Streptoccocus, Enterococcus (E. faecalis)
Treponema pallidum
Mouth anaerobes

Not good for:
Staphylococci
S. pneumoniae
Gram -

Notes:

  • only cidal against Enterococcus with aminoglycoside
  • Hypersensitivity, seizures at high dosese
24
Q

Aminopenicillins

A

Amoxicillin and Ampicillin (IV/PO)

Good for:

  • Streptococcus, Enterococcus, PLUS Listeria monocytogenes
  • Treponema pallidum
  • Mouth anaerobes
  • PLUS E coli, Proteus mirabilis, H influenzae (resistance)
  • PLUS Lyme

Notes:
- Hypersensitivity, seizures at high dosese

25
Q

Aminopenicillins PLUS B-lactamase inhibitors

A

Ampicillin + Sulbactam (IV)
Amoxicillin + Clavulanate (PO)

Good for:

  • Streptococcus, Enterococcus, Listeria monocytogenes
  • PLUS MSSA*
  • Treponema pallidum
  • Mouth anaerobes
  • PLUS E coli, Proteus mirabilis, H influenzae, Klebsiella
  • PLUS Lyme
  • PLUS Bacteroides fragilis*

Notes:

  • Hypersensitivity, seizures at high dosese
  • Diarrhea
26
Q

Penicillinase Resistant Penicillins

A

Nafcillin/Oxacillin (IV)
Dicloxacillin (PO)

Good for:

  • EXCELLENT MSSA
  • Streptococcus

Bad for:

  • Enterococcus
  • gram -

Notes:

  • hepatotoxicity (oxacillin)
  • Interstititial nephritis (nafcillin)
  • Unique due to HEPATIC ELIMINATION
27
Q

Extended Spectrum Penicillin PLUS B-lactamase inhibitor

A

Ticarcillin + Clavulanate (IV)
Piperacillin + Tazobactam (IV)

Good for:

  • EXCELLENT MSSA
  • PLUS Enterococcus spp
  • Gram - broad spectrum: including PSEUDOMONAS
  • Excellent anaerobic activity (including Bacteroides f.)

Notes:

  • used commonly in hospitals for empiric coverage
  • diarrhea common
  • P/T is more potent gram- agent
28
Q

1st Generation Cephalosporins
Cefazolin (IV)
Cephalexin (PO)
Cefadroxil (PO)

A

Good for:

  • EXCELLENT for MSSA, Streptococcus
  • Limited gram-; some against E. coli, Klebsiella
  • Oral anaerobes

Not for:
- Enterococcus

Notes:

  • hypersensitivity
  • seizures at high doses
  • Cefadroxil has longer half-life than cephalexin
  • Not for sinusitis, otitis media and lower respiratory infections
29
Q

2nd Generation Cephalosporins 2A

  • Cefuroxime (IV/PO)
  • Cefaclor (PO)
  • Cefprozil (PO)
A

Good for:

  • MSSA, Streptococci
  • Limited gram-; E coli, Klebsiella PLUS H. influenzae
  • Oral anaerobes

Not for:
- Enterococcus

Notes:
- Use for sinusitis, otitis media (but many hospital gram- are resistant)

30
Q

2nd Generation Cephalosporins 2B

- Cefoxitin

A

Good for:

  • Streptoccocus
  • PLUS B. fragilis (moderate)

Not for:

  • MSSA
  • Enterococcus

Notes:
- Intraabdominal and pelvic infections

31
Q

3rd Generation Cephalosporins

  • Ceftriaxone (IV)
  • Ceftibuten (PO)
  • Cefdinir (PO)
  • Cefpodoxime (PO)
  • Cefotaxime (IV)
  • Cefixime (PO)
A

Good for:

  • MSSA (moderate)
  • EXCELLENT Streptococcus
  • Broad gram- activity (no pseudomonas)

Not for:
- Enterococcus

Notes:

  • Ceftriaxone has biliary elimination - extended half-life and Q12-24hr dosing
  • Ceftriaxone/Cefotaxine: gold-standard for community-acquired meningitis, N. gonorrhea, neuro Lyme
32
Q

3rd Generation Cephalosporin

- Ceftazidime (IV)

A

Good for:

  • Gram- PLUS PSEUDOMONAS
  • oral anaerobes

Not for:
- Poor MSSA, Streptococcus, Enterococcus (none)

33
Q

3rd Generation Cephalosporins

- Ceftaroline (IV)

A

Good for:

  • MRSA* (only B-lactam)
  • EXCELLENT Streptococcus
  • Broad gram- (not pseudomonas)
  • oral anaerobes

Not for:

  • Enterococcus
  • Pseudomonas

Notes:
- Ceftaroline = ceftriaxone + MRSA

34
Q

4th Generation Cephalosporin

- Cefepime (IV)

A

Good for:

  • MSSA, Streptococcus
  • Broad gram-, PLUS Pseudomonas
  • Oral anaerobes

Not for:
- Enterococcus

35
Q

Aztreonam (monobactam)

A

Good for:
- gram- including Pseudomonas

Not for:

  • Gram+
  • Anaerobes

Notes:
- Safe for patients with severe allergic reactions to other beta-lactams

36
Q

Carbapenems

  • Imipenem/Cilastatin (IV)
  • Meropenem
  • Doripenem
A

Good for:

  • Streptococcus, MSSA
  • Decent: E. faecalis
  • EXCELLENT gram- including Pseudomonas and other MDRs
  • Broad anaerobes including excellent B. fragilis

Notes:

  • imipenem has higher incidence of seizures in patients with decreased renal function or history
  • Cilastatin inhibits renal tubule brush border enzyme that hydrolyzes imipenem (not B-lactamase inhibitor)
37
Q

Carbapenems

- Ertapenem

A

Good for:

  • EXCELLENT gram- (NOT PSEUDOMONAS)
  • Anaerobes (excellent B. fragilis)

Not for:

  • less active for Gram+
  • no Enterococcus
  • Pseudomonas

Notes:
- Q24 hr dosing

38
Q

Vancomycin (IV and PO)

A

Good for:

  • Very good strep and MRSA/MRSE, Enterococcus( static) - (first line empirical)
  • C. DIFICILE (PO)

Not for:

  • no Gram- (including gram- anaerobes)
  • no VRE

Notes:

  • Causes Red Man’s syndrome at infusion site
  • Nephrotoxicity
  • Used exclusively for GRAM+ and C.dif diarrhea
39
Q

Fosfomycin (PO)

A

Good for:

  • EXCELLENT against E. COLI and other gram- (not pseudomonas)
  • Staphylococcus, Enterococcus, Streptococcus

Not for:
- Pseudomonas

Notes:

  • well-tolerated
  • used as single dose oral regimen for acute cystitis in female (good due to increasing E. coli resistance
40
Q

Trimethoprim/Sulfamethoxazole (IV/PO)

A

Good for:

  • Staph. aureus, Staph. epi, most MRSA/MRSE (STAPHYLOCOCCUS)
  • Most gram- (stenotrophomonas maltophilia)
  • PCP
  • Nocardia, Toxoplasma gondii

Not for:

  • Strep, entero
  • B. fragilis, other anaerobes
  • Pseudomonas

Notes:

  • Skin rash, elevations of serum creatinine (inhibits secretion), acute interstitial nephritis
  • Myelosuppression
  • Many uses: GI, urinary, skin, pneumocystis, toxoplasmosis, nocardiosis
  • monitor for increase in INR
  • dosing based on Trimethoprim
41
Q

Rifampin (IV/PO)

A

Good for:

  • M. TUBERCULOSIS
  • prophylaxis N. meningitidis
  • Staph/Strep

Not for:

  • monotherapy for Staph/Strep
  • no Enterococcus

Notes:

  • Orange-red discoloration of tears, sweat, urine
  • Hepatotoxicity
  • has MANY drug-drug interactions; used in combination (energing resistance)
  • Used for: tuberculosis, staphylococcal endocarditis, infections of prosthetic materials
42
Q

Fidaxomicin (PO)

A

Good for:

  • variable for Entero, Staph, Strep
  • Gram+ anaerobes (C. dificile)

Not for
- Gram-

Notes:
- Only use for C. dif infection

43
Q

Quinolones

  • Ciprofloxacin (IV/PO)
  • Levofloxacin
  • Moxifloxacin
A

Good for:

  • Levo/moxi - EXCELLENT for S. pneumo
  • Strep (moderate)
  • Cipro/Levo - EXCELLENT gram- (PLUS Pseudomonas)
  • Moxi - moderate gram- (poor pseudomonas)
  • Moxi - increased anaerobe (including B. fragilis)
  • Atypicals: Chlamydia, Mycoplasma, Legionella

Not for:

  • Staph (resistance)
  • Enterococcus
  • anarobes

Notes:

  • CNS, tendinitis with rupture, C. dif diarrhea/colitis
  • Used for: UTI, prostatitis, respiratory tract, GI bone and joint infections, STDs
44
Q

Aminoglycosides

  • Gentamycin (IV)
  • Tobramycin
  • Amikacin
A

Good for:

  • synergistic with cell-wall active against against Enterococcus (cidal)
  • Broad spectrum gram- (including Pseudomonas) - amikacin is best
  • Strep and Staph (moderate)

Notes:

  • Nephrotoxicity (via proximal tubular cell accumulation)
  • Always with cell-wall active agents for staph/strep/entero endocarditis
  • Double coverage for severe gram- infections
  • Need pharmacokinetic monitoring
45
Q

Macrolines

  • Azithromycin (IV/PO)
  • Clarithromycin (PO)
A

Good for:

  • ATYPICALS: Legionella, Chlamydia, Mycoplasma
  • Strep penumoniae, other strep, MSSA (not first line)
  • H influenzae, N. gonorrhea, M. catarrhalis
  • H. pylori
  • Anaerobes, not B. fragilis
  • Mycobacterium avium complex (MAC)

Not for:
- not first line for gram+

Notes:

  • Erythromycin: pro-kinetic GI effects
  • Torsades de pointes - clarithromycin (with CYP34A)
  • USE for: atypicals in community-acquired pneumonia
  • Otitis, Sinusitis, Pneumonia
  • Clarithromycin: more prone to drug-drug interactions
46
Q

Tetracyclines

  • Tetracycline (PO)
  • Doxycycline (IV/PO)
  • Minocycline (PO)
A

Good for:

  • Strep penumoniae, STAPH (MRSA), Enterococcus
  • Minimal for Strep pyogenes
  • H influenzae, N gonorrhea, M. catarrhalis
  • Campylobacter
  • EXTENSIVE against anaerobes, atypicals, Rickettsia, Lyme

Notes:

  • GI/esophageal ulceration
  • Gray/brown discoloration of teeth in children
  • Photosensitivity
  • LImited gram- activity; limited use; good for COPD exacerbations, upper respiratory tract infections
47
Q

Tigecycline (IV)

A

Good for:

  • EXTENSIVE gram+ (MRSA, VRE)
  • EXTENSIVE gram- (but no pseudomonas)
  • EXTENSIVE anaerobes (including b. fragilis)

Not for:
- pseudomonas

Notes:
- Not for bacteria

48
Q

Clindamycin (IV/PO)

A

Good for:

  • Staph aureus (MRSA), S. epi, Strep spp (but not first line)
  • Good anaerobes

Not for:

  • Enterococcus
  • Gram -

Notes:

  • Nausea/vomiting/diarrhea
  • C. DIF COLITIS (so rarely used in oral infections, skin and soft tissue infection for those with penicillin allergy)
  • combination therapy in ncrotizing frasciitis
49
Q

Linezolid (IV/PO)

A

Good for:
- EXTENSIVE Gram+ (MRSA, most VRE)

Not for:
- Gram -

Notes:

  • Myelosuppression
  • Serotonin syndrome
  • Use for resistant gram+ infections with few options
50
Q

Nitrofurantoin (PO)

A

Good for:

  • most gram+ (including VRE)
  • E. coli, Klebsiella, Enterobacter

Not for:
- Proteus, Pseudomonas (always resistant)

Notes:

  • GI symptoms
  • Pulmonary - can cause cough and dyspnea to fibrosis
  • Only used for UTIs (NOT pyelonephritis)
51
Q

Metronidazole (IV/PO)

A

Good for:

  • EXTENSIVE anaerobes (B. fragilis)
  • Trichomonas
  • Giardia
  • H. pylori
  • C. DIF

Not for:
- gram+ or gram-

Notes:

  • GI, metallic taste, peripheral neuropathy
  • Drug of choice for initial C. dificile disease
52
Q

Daptomycin (IV)

A

Good for:
- EXTENSIVE gram+ (MSSA, MRSA, VRE)

Not for:

  • gram-
  • anaerobes/other

Notes:

  • muscle pain/weakness (CPK elevation)
  • NOT for pneumonia
  • Used for: gram+ bloodstream infections resistant to first line
53
Q

Polymyxins:

  • Polymyxin B (IV)
  • Colistin (IV)
A

good for:
- EXTENSIVE gram- (inc Pseudomonas)

Not for:
- Gram+, anaerobes, other

Notes:

  • dose-related, reversible nephrotoxicity
  • neurotoxicity and paresthesias
  • Last resort for MDR gram- infections (used in combination)

Medical Microbiology (1 decks)

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