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antimicrobial Flashcards

Mechanism Mechanism of resistance Clinical use

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USMLE® Step 1 flashcards
1
Q

Mechanism of Penicillin sensitive penicillinase (amoxicillin, ampicillin, aminopenicillin)

A
  • Same as Penicillins; block transpeptidase cross-linkingof peptidoglycan wall.
  • Wider spectrum than penicillins
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2
Q

Clinical use of amoxicillen

A

HHELPSS

H.influenza, H.pylori, E.coli, Listeria, proteus, salmonella, shigella

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3
Q

Mechanism of Penicillin resistant penicillinase (dicloxacillin, nafcillin, oxacilllin

A
  • Same as penicillins

- Narrow spectrum

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4
Q

What makes dicloxacillin

nafcillin, oxacilllin resistent to penicillinase?

A

Bulky R group blocks access of B-lactamase to B lactam ring.

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5
Q

Clinical use of dicloxacillin

A

S. Aureus (except MRSA)

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6
Q

Mechanism of resistance of nafcillin

A

MRSA alters penicillin-binding target site

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7
Q

Oxacillin side effects

A

Hypersensitivity

Interstitial nephritis

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8
Q

Mechanism of Antipseudomonal penicillins (piperacillin, ticarcillin)

A
  • Same as penicillin

- Extended spectrum

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9
Q

Clinical use of piperacillin

A

Pseudomonas spp.

Gram - rods

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10
Q

B lactamase inhibitors aka penicillins BFFs

A

Added to penicillin antibiotics to protect from destruction.
Clavulanic acid, avibactam,sulbactam,tazobactam

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11
Q

Carbapenams

A
  • IV only
  • Life threateninig infections
  • Given with cilastatin to decrease metaboism of drug (inhibits renal dehydropeptidase l to decrease inactivation of drug)
  • SE: seizures
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12
Q

Which carbapenam is stable to dehydropeptidase l and has a decreased risk of seizures?

A

Meropenam

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13
Q

Monobactams (Aztreonam)

A
  • Prevents cross linking by binding to penicillin-binding protein 3.
  • Synergistic with aminoglycosides (mycins)
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14
Q

Clinical use of aztreonam

A
  • Gram negative rods ONLY

- Pts with renal insufficiency who cannot tolerate gentamycin/streptomycin

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15
Q

Vancomycin

A
  • Diffuse flushing
  • Prevent side effects by slow infusion rate.
  • Drug reaction with eosinophilia
  • mechanism of resistance via amino acid modification to D-ALA D-LAC
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16
Q

Neomycin

Streptomycin

A
  • Require O2 for uptake
  • inhibit initiation complex by binding to 30s
  • Can cause misreading of mRNA.
  • Blocks transcription and translocation.
  • neomycin for bowel surgery
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17
Q

Streptomycin clinical uses

A
  • Severe gram negative rod infections.
  • Synergistic with aztreonam
  • Ototoxicity esp when given with loop diurectics like furosemide,bumetanide, torsemide
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18
Q

Streptomycin mechanism of resistance

A

Drug is inactivated by acetylation, phosphorylation or adenylation.

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19
Q

30s inhibitors

50s inhibitors

A

30s inhibitos:
aminoglycosides (bacteriocidal)
tetracyclines

50s inhibitors: macrolides (erythomycin) clindamycin, chloramphenicol, lizezolid

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20
Q

Tetracycline;
Doxy
Minocycline
Tertracycline

A
  • Doxy can be used in renal failure and effective agaisnt MRSA
  • prevent attachment of aminoacyl-tRNA
  • Divalent cations inhibit drugs absorption in gut
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21
Q

Doxycycline mechanism of resistance

A

Decrease uptake or increase efflux out of bacterial cells by plasmid encoded transport pumps

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22
Q

Glycycycline (tigecycline)

A

-infections requiring deep tissue penetration.

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23
Q

Chloramphenicol

A
  • Best CNS penetration
  • Rapid absorption
  • blocks peptidyltransferase at 50s
  • Uses meningitis (h.influenza, n. Meningitidis, s. Pneumonia), rickettsial diseases
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24
Q

Chloramphenicol side effects

A

Side effects are mainly dose dependent (anemia, aplastic anemia)

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25
Q

Chloramphenicol resistance mechanism

A

Plasmid encoded acetyltransferase inactivates the drug.

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26
Q

Clindamycin

A
  • Blocks peptide transfer at 50s

- Treats anaerobic infections ABOVE the diaphragm (vs metronidazole)

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27
Q

Clindamycin clinical use

A

Anaerobic infections; (bacteroides, clostridium perfringes) in aspiration pneumonia, lung abscesses and oral infections
-group A srep infection

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28
Q

Oxazolidinones (Linezolid)

A
  • MRSA, VRE
  • Inhibit protein synthesis by inhibiting initation complex.
  • Resistance: point mutation of ribosomal RNA.
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29
Q

Linezolid side effects

A

-Bone marrow suppression;
Decreases platelet count
-Serotonin syndrome
-peripheral neuropathy.

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30
Q

Mechanism of action and mechanism of resistance of Erythromycin,
Clarithromycin
Azithromycin

A
  • Block translocation; bind to 23s of 50s

- mechanism of resistance: methylation of 23s rRNA binding site prevents drug binding.

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31
Q

Azithromycin clinical uses

A 
-Atypical pneumonias;
Mycoplasma
Chlamydia
Legionella
-STIs; chlamydia
-B.pertussis (whooping cough)
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32
Q

Clarithromycin side effects

A

MACRO: motility issues, arrhythmia caused by prolonged QT interval, acute cholestatic hepatitis, RASH, eosinophilia
-Clarithromycin and erythromycin inhibit cytochrome p-450; increase serum conc of theophylline and anticoags

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33
Q

Polymyxins (colistin)

A
  • Disrupt membrane integrity of bacterial cell

- leakage of cellular contents =death

34
Q

Clinical use and adverse effects of colistin

A

Use: salvage therapy for MDR gram neg bacteria (p.saeruginosa, e.coli, k.pneumoniae.

  • polymyxin B is used for superficial skin infections as triple therapy.
  • Side effects: neurotoxicity; slurred speech, paresthesias, respiratory failure.
35
Q

Sulfonamides

A

-mechanism of resistance: altered enzyme (bacterial dihydropteroate synthase) decrease uptakee of increase PABA synthesis

36
Q

Dapsone

A

Uses:
-leprosy
-pneumocystis jirovecci prophylaxis
SE: methemoglobinemia

37
Q

Trimethoprim

A

-Prophylaxis for toxoplasmosis
-Prophymaxis and tx for pneumocystis jirovecii
SE: bone marrow suppresion; leukopenia, megaloblastic anemia etc

38
Q

Fluoroquinolones (ciprofloxacin)

A
  • inhibit top ll (dna gyrase)
  • must not be taken with antacids
  • cipro is a p-450 inhibitors
39
Q

Cipro contraindications

A
  • Pregnant/nursing mothers
  • children <18 due to possible cartilage damge
  • patients taking prednisone
  • pts >60 yrs due to tendon rupture.
  • leg cramps and myalgias
  • superinfections
40
Q

Ciprofloxacin uses:

A
  • Gram - rods in urinary and GI

- otitis externa

41
Q

Ciprofloxacin mechanism of resistance:

A
  • Chromosone encoded mutation in DNA gyrase.
  • plasmid mediated resistance
  • eflux pumps
42
Q

Daptomycin

A
  • disrupts cell membrane of gram positive cocci
  • creates transmembrane channels
  • SE: rhabdomyolysis, myopathy
43
Q

Daptomycin contraindications

A

Pneumonia (avidly binds to and is inactivated by surfactant,)

44
Q

Metronidazole

A
  • Damages DNA by creating free radicals
  • SE: metallic taste
  • Uses: GET GAP giardia, entamoeba, trichomonas, gardenella, anaerobes, h.pylori
45
Q

Rifampin, rifabutin

A
  • Inihibit DNA dependent RNA plymerase
  • increases p-450
  • Delay resistance to dapsone when used for leprosy
  • Rifabutin preferred iver rifampin in HIV due to less p-450 stimulation.
46
Q

Rifampin prophylaxis

A
  • Contacts of children with H.influenza type B

- Meningococcal prophylaxis

47
Q

Rifampin resistance

A

Mutations reduce drug binding to RNA polymerase. Avoid monotherapy=resistance.

48
Q

Isoniazid mechanism and resitance

A
  • actually a prodrug
  • Needs catalase-peroxidase from the bacteria to activate it.
  • encoded by KatG
  • decreases mycolic acid synthesis
  • Mutations=underexpression of KatG
49
Q

Isoniazid uses and side effects

A
  • Monotherapy in prophylaxis of TB
  • Monotherapy in latent TB
  • Inhibits p-450
  • anion gap metabolic acidosis
  • drug induced SLE
50
Q

Pyrazinamide

A
  • used in m. TB
  • works best in acidic pH in host phagolysosomes.
  • SE; hyperuricemia
51
Q

Ethambutol

A
  • Decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase.
  • SE: optic neuropthy
52
Q

Which aminoglycoside can be given as second line tx of m. TB?

A

Streptomycin

53
Q

Antimicrobials that disrupt membrane by forming pores or channels allowing for leakage of cellular contents.

A

Amphotericin B
Daptomycin
Polymyxin (colistin)

54
Q

Amphotericin B protocol

A
  • Supplement K+ and Mg+ because of altered renal tubule permeability
  • Hydrate to decrease nephrotoxicity,
  • Liposomal amphotericin decreases toxicity.
55
Q

Azoles

A
  • Voriconazole for mild aspergillus
  • Itraconazole for blastomyces, coccidioides, histoplasma
  • Isavuconazole for serious aspergillus and Mucor infections.
  • Clotrimazole and miconazole for topical infections.
56
Q

Fluconazole

A

-INHIBIT ERGOSTEROL BY INHIBITING P-450 THAT CONVERTS LANOSTEROL TO ERGOSTEROL.

57
Q

Terbinafine

A

Inhibits squalene epoxidase

  • used in dermatophytes esp onychomycosis; fungal infection of finger or toe nail.
  • SE: taste disTERBance,
58
Q

Fungins

A

Inhibit synth of B-glucan
-uses: invasive aspergillosis/candida

-SE: flushing by histamine release

59
Q

Griseofulvin

A
  • Interferes with microtubule function
  • disrupts mitosis
  • Deposits in keratin containing tissues like nails.
  • inhibits growth of dermatophytes (tinea, ringworm)
60
Q

Antiprotozoa

A

-Pyrimthamine for toxoplasmosis
-Suramin and melarsoprol for trypanosoma brucei
Nifurtimox for T. Cruzi
-Sodium stiboglucnate for leishmenia

61
Q

Chloroquine

A

—blocks detox of heme into hemozoin
-heme accumulates and is toxic to plasmodia
-

62
Q

Antihelminthic therapy

A 
Pyrantel pamoate
Ivermectin
Mebendazole
Praziquantel
Diethylcarbamazine
“Helminths get PIMP’D”
63
Q

Antiviral drugs that require kinase activation

A

Ganciclovir, acyclovir,famciclovir, valacyclovir

64
Q

Antiviral drug activated by intracellular kinases (rather than viral kinases)

A

Cidofovir

65
Q

Acyclovir vs acyclovir in mechanism

A

Acyclovir does not affect normal host cells whereas ganciclovir does which can lead to bone marrow suppresion.

66
Q

Cidofovir

A
  • Long half life
  • high intracellular drug conc = tubular necrosis
  • Activated by intracellular kinases
67
Q

Foscarnet

A
  • Does not require kinase activation.
  • Directly inhibits DNA polymerase
  • used in CMV retinitis and acyclovir resistant HSV.
68
Q

Oseltamivir, zanamivir

A

Decrease release of progeny virus

-inhibit neurominidase

69
Q

Tenofovir

A
  • NRTIs
  • NucleoTide
  • Bone marrow suppression can be reversed by G-CSF and EPO
  • lactic acidosis
70
Q

Zidovudine

A
  • General prophylaxis
  • used in pregnancy to decrease fetal transmission
  • chain termination
  • SE: anemia
71
Q

Abacavir

A

-Contraindicated in patients with HLA-B*5701 mutation due to increased risk of hypersensitivity.

72
Q

Efavirenz

A
  • NNRTI
  • Bind to reverse transcriptase at site diff than NRTIs.
  • Does not require phosphorylation to be active.
73
Q

Efavirenz side effects and contraindications

A
  • Contraindicated in pregnancy (along with delavirdine)
  • Vivid Dreamse
  • CNS symptoms
  • Rash/hepatotoxicity
74
Q

Didanosine

A
  • NRTI
  • Terminate DNA chain
  • SE: pancreatitis
75
Q

Atazanavir

A
  • Protease inhibitor
  • prevent maturation of new viruses
  • interferes with pol gene
76
Q

Ritonavir

A
  • prevents maturation of new virus

- boosts other drug conc by inhibiting p-450 (vs rifampin which reduces proteus inhibitor conc)

77
Q

Indinavir

A

-SE; decrease in platelets

78
Q

Elvitegravir

A
  • prevent integration of HIV into host DNA (strand transfer of viral DNA is blocked from entering host chromosome)
  • SE: increases creatine kinase
79
Q

Maraviroc

A
  • Binds CCR-5 on T cells/monocytes

- Inhibit gp120 interactions

80
Q

Enfuvirtide

A
  • Binds gp41

- inhibits viral entry

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