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USMLE Step I > Antibiotics > Flashcards

Antibiotics Flashcards

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USMLE® Step 1 flashcards
1
Q

Sulfonamides

  1. Mechanism
  2. Resistance
A

Bacteriostatic (Bactericidal when administered with Trimethoprim)

PABA analog that acts as a competitive antagonist against dihydrojpterate synthase. Inhibitor of folic acid biosynthesis which inhibits nucleic acid biosynthesis.

Resistance: mutations that result in alterations of target enzyme, decreased uptake, or increased PABA synthesis

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2
Q

Trimethoprim (Benzylpyrimidine)

  1. Mechanism
  2. Resistance
A

Bacteriostatic (Bactericidal when administered with Sulfonamides)

Inhibits dihydrofolate reductase. Inhibitor of folic acid biosynthesis which inhibits nucleic acid biosynthesis

Resistance: decreased influx, increased production of dihydrofolate reductase, decreased antibiotic binding affinity to dihydrofolate reductase

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3
Q

Fluoroquinolones

  1. Mechanism
  2. Resistance
A

Bactericidal

Inhibits DNA Gyrase (DNA Topoisomerase II) in gram negative bacteria → Prevents relaxation of the DNA strand as it is unwound by helicase

Inhibits DNA Topoisomerase IV in gram positive bacteria → Prevents separation of the replicated chromosomal DNA into daughter cells during cell division

Resistance: chromosome-encoded mutation in DNA gyrate which decreases the binding affinity of the antibiotic, plasmid mediated resistance, efflux pumps, decreased influx

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4
Q

Metronidazole

  1. Mechanism
  2. Resistance
A

Bactericidal

Pro-drug → the nitro group is chemically reduced by bacterial oxidoreductases to become active (mammalian cells lack the enzymes that reduce the pro-drug)

The reduced form of the drug causes damage to DNA strands

Resistance: observed but unknown

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5
Q

Rifamycins

  1. Mechanism
  2. Resistance
A

Bactericidal

Binds non-covalently to the β-subunit of DNA dependent RNA polymerase. Inhibits the initiation of transcription but does not inhibit transcription already in progress

Resistance: mutations that reduce drug binding to RNA polymerase.
Monotherapy rapidly leads to resistance

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6
Q

Chloramphenicol

  1. Mechanism
  2. Resistance
A

Bacteriostatic for most organisms
Bactericidal for H. influenzae, S. Pneumoniae, N. meningitidis

Inhibits elongation of the peptide chain during translation by inhibiting peptidyltransferase (forms peptide bonds between adjacent amino acids) in the 23S component of the 50S subunit

Resistance: decreased influx, plasmid-encoded acetyl transferase inactivates the drug

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7
Q

Clindamycin (Lincosamides)

  1. Mechanism
  2. Resistance
A

Bacteriostatic

Inhibits translocation (peptide transfer) during translation by binding to the P and A sites in the 50S subunit

Resistance: production of a methylase that modifies the ribosomal target and leads to decreased drug binding (ribosomal methylation)

Expression of MLS-B resistance can be constitutive or inducible. In inducible resistance, the bacteria produce inactive mRNA that is unable to encode methylase. The mRNA becomes active only in the presence of a macrolide inducer. By contrast, in constitutive expression, active methylase mRNA is produced in the absence of an inducer.

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8
Q

Linezoid (Oxazolidinones)

  1. Mechanism
  2. Resistance
A

Bacteriostatic (sometimes bactericidal)

Prevents initiation of translation by binding to the 50S ribosomal subunit and inhibiting the formation of the 70S ribosomal initiation complex

Resistance: point mutations of the 23 S rRNA component prevent binding of the drug

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9
Q

Macrolides

  1. Mechanism
  2. Resistance
A

Bacteriostatic

Inhibits translocation during translation by binding to the 23S rRNA component of the 50S subunit

Resistance: efflux via an ATP-dependent pump, production of a methylase that modifies the ribosomal target and leads to decreased drug binding (ribosomal methylation), hydrolysis by esterases, mutation of the 23S rRNA component of the 50S ribosomal subunit

Expression of MLS-B resistance can be constitutive or inducible. In inducible resistance, the bacteria produce inactive mRNA that is unable to encode methylase. The mRNA becomes active only in the presence of a macrolide inducer. By contrast, in constitutive expression, active methylase mRNA is produced in the absence of an inducer.

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10
Q

Streptogramins

  1. Mechanism
  2. Resistance
A

Bactericidal

Streptogramin A (Dalfopristin): binds to the 50S subunit and induces a conformational change in the subunit which enhances the binding of streptogramin B (quinupristin)

Streptogramin B (Quinupristin): inhibits translocation during translation by binding to 23S rRNA of the 50S subunit (occupies the same location as macrolides)

Resistance: production of a methylase that modifies the ribosomal target and leads to decreased drug binding (ribosomal methylation)
Active transport efflux and acetyltransferases are the mechanisms for resistance against Streptogramin A

Expression of MLS-B resistance can be constitutive or inducible. In inducible resistance, the bacteria produce inactive mRNA that is unable to encode methylase. The mRNA becomes active only in the presence of a macrolide inducer. By contrast, in constitutive expression, active methylase mRNA is produced in the absence of an inducer.

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11
Q

Aminoglycosides

  1. Mechanism
  2. Resistance
A

Bactericidal

Inhibits the initiation and translocation steps of translation and causes misreading of the mRNA.
Covalently binds to the 30S subunit to prevent formation of the initiation complex.

Resistance: acquisition of plasmid encoded inactivating enzymes - acetylases, adenylases, phosphorylases
decreased drug permeability / influx

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12
Q

Tetracyclines and Tigecycline

  1. Mechanism
  2. Resistance
A

Bacteriostatic

Inhibits elongation of the peptide chain during translation by preventing aminoacyl-tRNA from binding the A site of the ribosome.
Binds to the 30S subunit

Resistance: decreased intracellular accumulation due to decreased influx or acquisition of an energy dependent efflux mechanism, decreased access to the ribosome due to ribosome protecting proteins encoded by the TetO genes, enzymatic inactivation of the drug (TetX modification)

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13
Q

β-lactam antibiotics
(Penicillins, Cephalosporins, Carbapenems, Monobactams)
1. Mechanism
2. Resistance

A

Bactericidal

Structural analogs of D-alanyl-D-alanine that covalently (irreversibly) bind to transpeptidases (penicillin binding proteins) and prevent transpeptidase cross-linking of the peptidoglycan in the cell wall

Resistance: β-lactamase (penicillinase) inactivates the antibiotic, decreased drug permeability / influx, ATP-dependent efflux pumps, decreased binding affinity of the antibiotic to penicillin binding proteins (transpeptidases) through mutation or recombination

**Carbapenems are resistant to β-lactamases

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14
Q

β-lactamase-resistant antibiotics
(Nafcillin, Oxacillin, Methicillin, Flucloxacillin, Cloxacillin, Dicloxacillin)
1. Mechanism
2. Resistance

A

Bactericidal

Same mechanism of action as other β-lactam antibiotics, but they are resistant to β-lactamase because they have a bulky R group that blocks access of β-lactamase to the β-lactam ring

Resistance: decreased binding affinity of the antibiotic to penicillin binding proteins (transpeptidases) through mutation or recombination

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15
Q

Mechanism: β-lactamase inhibitors

A

Protect β-lactam antibiotics from destruction by β-lactamase (penicillinase)

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16
Q

Vancomycin

  1. Mechanism
  2. Resistance
A

Bactericidal for gram positive rods
Bacteriostatic for gram positive cocci

Binds the D-ala-D-ala terminus of the muerin monomer of cell wall precursors which inhibits the attachment of disaccharide subunits to the pre-existing cell wall

Resistance: acquisition of the vancomycin HAX genes - replace the terminal D-ala-D-ala normally found at the end of the pentapeptide chain (where vancomycin binds) with D-lactate

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17
Q

Mechanism: Polymyxins

A

Bactericidal

Cationic detergents that disrupt the membranes of gram negative bacteria

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18
Q

Mechanism: Daptomycin

A

Bactericidal: VRE
Bacteriostatic: S. pneumoniae, S. aureus

Lipopeptide that disrupts the cell membrane of gram positive cocci. It inserts into the cell membrane and aggregates which creates holes in the membrane that leak ions. This causes rapid depolarization resulting in a loss of membrane potential which inhibits protein, DNA, and RNA synthesis and leads to cell death.

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19
Q

Isoniazid (INH)

  1. Mechanism:
  2. Resistance:
  3. Toxicity:
  4. Pharmacokinetics
A

Bacteriostatic

Inhibits the synthesis of mycolic acids which are essential components of the mycobacterial cell wall and are unique to mycobacteria

Resistance: mutations leading to the under expression of KatG

Toxicity: neurotoxicity and hepatotoxicity
Pyridoxine (vitamin B6) can prevent neurotoxicity

Pharmacokinetics: inactivated by acetylation
The rate of acetylation (different for each patient) determines the drug’s effectiveness

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20
Q

Ethambutol (EMB)

  1. Mechanism:
  2. Toxicity:
A

Bacteriostatic
Only effective aganist mycobacteria

Inhibits the polymerization of arabinogalactan in the cell wall by inhibiting arabinosyltransferase

Toxicity: optic neuropathy (red-green color blindness)

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21
Q

Pyrazinamide (PZA)

  1. Mechanism:
  2. Toxicity:
A

Bacteriostatic

Prodrug → converted into the active compound pyrazinoic acid by pyrazinamidase in tuberculosis.
Unknown mechanism - maybe inhibits mycobacterial fatty acid synthase I (FAS-I) gene involved in mycolic acid biosynthesis

Toxicity: hyperuricemia, hepatotoxicity

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22
Q

Dapsone

  1. Mechanism
  2. Toxicity:
  3. Pharmacokinetics
A

Bacteriostatic

Inhibits folate synthesis (same mechanism as sulfonamides)

Toxicity: hemolysis at doses >200mg/day, GI intolerance, fever, pruritus, erythema nodosum leprosum may develop during therapy

Pharmacokinetics: acetylated in the liver by the same enzymes as INH, 70-80% is excreted in the urine

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23
Q

Clinical Use: Sulfonamides

A

Broad spectrum

Nocarida, Chlamydia

Combination therapy with TMP (TMP-SMX):
Urinary tract infections
Cellulitis
Pneumocystis jirovecii pneumonia or toxoplasmosis prophylaxis in HIV patients
Shigella, Salmonella
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24
Q

Clinical Use: Trimethoprim

A

Broad spectrum

Combination therapy with TMP (TMP-SMX):
Urinary tract infections
Cellulitis
Pneumocystis jirovecii pneumonia or toxoplasmosis prophylaxis in HIV patients
Shigella, Salmonella
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25
Q

Clinical Use: Fluoroquinolones

A

Gram-negative rods of the urinary and GI tracts including Pseudomonas and Neisseria

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26
Q

Clinical Use: Metronidazole

A

Treats anaerobic infections below the diaphragm (ex: C. difficile)

Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis

Used with a proton pump inhibit and clarithromycin for “triple therapy” against H. pylori

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27
Q

Clinical Use: Rifamycins

A

Mycobacterium tuberculosis, Neisseria
Used in combination with Dapsone for Leprosy

Prophylaxis for meningitis from meningococci and H. influenzae

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28
Q

Clinical Use: Chloramphenicol

A

Meningitis: H. influenzae, Neisseria meningitidis, S. pneumoniae
Rocky Mountain Spotted Fever (Rickettsia rickettsii)

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29
Q

Clinical Use: Clindamycin

A

Treats anaerobic infections above the diaphragm (aspiration pneumonia, lung abscess, oral infections)

30
Q

Clinical Use: Linezoid

A

Treats MRSA, VRE

Gram positive organisms

31
Q

Clinical Use: Macrolides

A

Atypical pneumonias (Mycoplasma, Chlamydia, Legionella)
STI (Chlamydia)
B. pertussis
Gram positive cocci

32
Q

Clinical Use: Streptogramins

A

VRE

33
Q

Clinical Use: Aminoglycosides

A

Severe gram negative rod infections
Synergistic with β-lactam antibiotics
Pseudomonas aeruginosa

34
Q

Clinical Use: Tetracyclines

A

Drug is able to accumulate intracellularly - effective against Rickettsia and Chlamydia

Borrelia burgdorferi, M. pneumoniae

Treats acne

Tigecycline: MRSA

35
Q

Clinical Use: Penicillin G, V

A

Gram positive cocci, gram positive rods, gram negative cocci, and spirochetes (T. pallidum)

36
Q

Clinical Use: Amoxicillin, ampicillin

A

Wider spectrum than penicillin

H. pylori, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, and enterococci

37
Q

Clinical Use: β-lactamase-resistant antibiotics

Nafcillin, Oxacillin, Methicillin, Flucloxacillin, Cloxacillin, Dicloxacillin

A

Narrow spectrum

S. aureus

38
Q

Clinical Use: Anti-pseudomonals

Piperacillin, Ticarcillin

A

Pseudomonas aeruginosa

Gram negative rods

39
Q

Clinical Use: Cephalosporins (I)

Cefazolin, Cephalexin

A

Narrow spectrum
Gram positive cocci (staphylococci and streptococci)
Proteus mirabilis, E. coli, Klebsiella pneumoniae

Cefazolin: Antibiotic prophylaxis against S. aureus for surgical procedures

Cephalexin: recommended for mild foot infections in diabetics

40
Q

Clinical Use: Cephalosporins (II)

Cefoxitin, Cefaclor, Cefuroxime

A

Gram positive cocci

H. influenzae, Enterobacter aerogenes, Neisseria, Proteus mirabilis, E. coli, Klebsiella pneumoniae, Sebratia marcescens

41
Q

Clinical Use: Cephalosporins (III)

Ceftriaxone, Cefotaxime, Ceftazidime

A

Serious gram negative organisms resistant to other β-lactams

Ceftriaxone: meningitis, gonorrhea, disseminated lyme disease. Primary choice for Neisseria gonorrhea and Neisseria meningitis

Ceftazidime: Pseudomonas aeruginosa

42
Q

Clinical Use: Cephalosporins (IV)

Cefepime

A

Broad spectrum

Increased activity against Pseudomonas aeruginosa

43
Q

Clinical Use: Cephalosporins (V)

Ceftaroline

A

Broad spectrum
MRSA
Does not cover Pseudomonas aeruginosa

44
Q

Clinical Use: Carbapenems

Imipenem, Meropenem, ertapenem, Doripenem

A

Wide spectrum

Gram positive cocci, gram negative rods, anaerobes

45
Q

Clinical Use: Monobactams

Aztreonam

A

Gram negative rods only
No activity against gram positive organisms or anaerobes

Used for patients allergic to PCN (no cross-allergenicity with PCN) or for patients with severe renal insufficiency who cannot tolerate aminoglycosides

46
Q

Clinical Use: Vancomycin

A

Gram positive organisms only

C. difficile, MRSA, S. epidermis, sensitive enterococcus species

47
Q

Clinical Use: Daptomycin

A

MRSA
VRE (not first choice)

Cases of bacteremia or endocarditis

48
Q

Treatment of MRSA

A 
Ceftaroline (5th Gen Cephalosporin)
Clindamycin
Daptomycin
Linezolid
Tigecycline
Vancomycin
49
Q

Treatment of VRE

A

Linezolid

Streptogramins

50
Q

Treatment of Pseudomonas aeruginosa

A 
Aminoglycosides
Carbapenems (ertapenem)
Piperacillin
Ticarcillin
Fluoroquinolones
Ceftazidime (3rd Gen)
Cefepime (4th Gen)

For multi-drug resistant strains: polymyxins B and E (colistin)

51
Q

Treatment of Mycoplasma tuberculosis

A

Prophylaxis: Isoniazid
Treatment: Rifampin, Isoniazid, Pyrazinamide, Ethambutol

52
Q

Treatment of Mycoplasma avium

A

Prophylaxis: Azithromycin, Rifabutin
Treatment: Azithromycin or clarithromycin with ethambutol. Can add rifabutin or ciprofloxacin

53
Q

Treatment of Mycoplasma leprae

A

Tuberculoid form: dapsone and rifampin

Lepromatous form: dapsone, rifampin, and clofazimine

54
Q

β-lactam antibiotics: Penicillin

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: hypersensitivity reactions, hemolytic anemia, diarrhea (infants)

Pharmacokinetics: renal secretion
Route: G = IV, IM; V = PO
Amoxicillin is more completely absorbed after oral administration than ampicillin

55
Q

β-lactam antibiotics: Cephalosporins

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: hypersensitivity reactions (do not use in patients allergic to penicillin), autoimmune hemolytic anemia, vitamin K deficiency (bleeding)
Bleeding: Hypoprothrombinemia, thrombocytopenia, and/or platelet dysfunction
Nephrotoxicity: especially when used in combination with aminoglycosides
Disulfiram-like alcohol reaction: flushing, hypotension, tachycardia, dyspnea, nausea, vomiting

Pharmacokinetics: first generation drugs do not cross the BBB

56
Q

β-lactam antibiotics: Carbapenems

  1. Toxicity
  2. Pharmacokinetics
  3. Unique feature of Meropenem
A

Toxicity: GI distress, skin rash, and seizures

Pharmacokinetics: rapidly hydrolyzed (inactivated) by renal tubule dipeptidase
*Given in combination with cilastatian (a renal dehydropeptidase inhibitor) as Primaxin
Route: IV only

  1. Meropenem is structurally related to imipenem, but is less susceptible to hydrolysis by renal tubule dipeptidase. Does not require cilastatian to achieve therapeutic concentrations and is less nephrotoxic than imipenem
57
Q

Vancomycin

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: nephrotoxicity, ototoxicity, thrombophlebitis, diffuse flushing (redman syndrome), tissue necrosis if given IM, and neutropenia

Pharmacokinetics: Renal elimination
Route: administer IV; poorly absorbed from the GI tract

58
Q

Daptomycin

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: rhabdomyolysis (increase in CPK), myopathy, nephrotoxicity

Pharmacokinetics: primarily renal elimination
Does not cross the BBB

Route: IV injection only
Do not administer IM because there is a toxic effect on muscles

59
Q

Polymyxins

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: associated with severe nephrotoxicity

Pharmacokinetics: often used topically or in ophthalmic and otic drops

60
Q

Aminoglycosides

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: nephrotoxicity, neuromuscular blockade, ototoxicity (especially when used with loop diuretics), teratogen

Pharmacokinetics: rapid renal excretion

61
Q

Tetracyclines

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: GI distress, IV administration can lead to venous thrombosis, IM administration causes painful local irritation, Renal and hepatic toxicity, photosensitivity

Teratogen: treatment of pregnant women or children less than 8 can result in permanent tooth discoloration, bone deformation, and growth retardation in the child

Pharmacokinetics:
Tetracycline: absorption is impaired by food, diary products, antacids, and supplements containing divalent and multivalent cations, and by alkaline pH.
This is not a problem for doxycycline or minocycline

All penetrates the CNS

Doxycycline is primarily eliminated through the feces
Tetracycline and minocycline is primarily eliminated by the kidneys

62
Q

Chloramphenicol

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: Normocytic Anemia due to erythroid suppression of the bone marrow (dose dependent), aplastic anemia (dose independent)

Gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase - inadequate metabolism): presents as vomiting, flaccidity, hypothermia, respiratory distress, gray pallor, and shock.

Drug interactions:
Inhibits CYP3A4
May prolong the T-1/2 of drugs normally metabolized by these enzymes
Competitively antagonizes the effects of macrolides and clindamycin because chloramphenicol binds to a similar position in the ribosome

Pharmacokinetics: penetrates the CNS

63
Q

Clindamycin

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: pseudomembranous colitis, fever, diarrhea

Pharmacokinetics: does not penetrate the BBB

64
Q

Oxazolidinones (Linezolid)

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: Serotonin syndrome - inhibits monamine oxidase (MAO)
GI: nausea, vomiting, diarrhea
Thrombocytopenia, anemia, myelosuppression

65
Q

Macrolides

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: Gastrointestinal Motility issues, Arrhythmia caused by prolonged QT interval, acute cholestatic hepatitis, Rash, eosinophilia. Increases serum concentration of theophyllines, oral anticoagulants. Clarithromycin and erythromycin inhibit cytochrome P-450

Pharmacokinetics:
Elimination: erythromycin and azithromycin primarily liver; clarithromycin renal and non-renal

Erythromycin is inactivated by gastric acid, but is absorbed in upper small intestine

66
Q

Trimethoprim

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: Megaloblastic anemia, leukopenia, granulocytopenia. (May alleviate with supplemental folinic acid)

67
Q

Sulfonamides

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g., warfarin)

68
Q

Fluoroquinolones

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: GI upset, superinfections, skin rashes, headache, dizziness. Less commonly, can cause leg cramps and myalgias.

Contraindicated in pregnant women, nursing mothers, and children

Contraindicated in patients >60 taking prednisone

69
Q

Metronidazole

1. Toxicity

A

Toxicity: headache, metallic taste

Disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol

70
Q

Rifamycins

  1. Toxicity
  2. Pharmacokinetics
A

Toxicity: Minor hepatotoxicity and drug interactions (􏰊cytochrome P-450); orange body fluids (nonhazardous side effect). Rifabutin favored over rifampin in patients with HIV infection due to less cytochrome P-450 stimulation

Rifampin ramps up cytochrome P-450, but rifabutin does not

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