MOA

Question 1

Polymyxins

Answer 1

• Bacteriocidal

• MOA:
Acts as a detergent and damages the bacterial cytoplasmic membrane

• Only active against gram (-) organisms
• Has activity against highly resistant strains:
– Examples: P. aeruginosa, K. pneumonia, Acinetobacter

Question 2

Active TB infection

Answer 2

Typical therapy is:
• RIF,INH, PZA & EMB (RIPE) x 2 mo then
INH & RIF (RI) x 18 weeks (4 months)

• The greater # of doses pt receives in 26 weeks (6 months) the better efficacy of regimen
• Note: If it is known that M. tuberculosis is susceptible to both INH and RIF then EMB is not necessary

Question 3

Echinocandins

Answer 3

• MOA:
– Inhibits glucan synthase blocking fungal production of D-glucan, an essential component of fungal cell walls
– Leads to cell lysis (fungicidal)

• Spectrum:
activity against aspergillus species and most candida species including the species resistant to azoles

Question 4

Monobactams

Answer 4

– Coverage very similar to ceftazidime
– Gram (-) coverage: P. aeruginosa and enterobacteriaceae
– No gram (+) or anaerobic coverage
– Can use in PCN/cephalosporin allergic patients

Question 5

Macrolides

Answer 5

• MOA:
Inhibits bacterial protein synthesis by irreversibly binding to 50S ribosomal complex.
• Bacteriostatic but may become bactericidal at high concentrations

• Spectrum:
– Good: Atypicals, H. influenzae, M. catarrhalis, H. pylori, M. avium
– Moderate: S. pneumoniae (ketolides > macrolides), S. pyogenes
– Poor: Staphylococci, GNR, anaerobes, enterococci

Question 6

Fusion inhibitors

Answer 6

MOA:

binds to gp41, preventing the conformational change of HIV; thereby preventing entry into the host cell

Question 7

HIV

Answer 7

Virus that can lead to AIDS
– HIV attacks the immune system CD4 cells
– Untreated, HIV reduces the number of CD4 cells in the body:
• This damage to the immune system makes it harder and harder for the body to fight off infections and some other diseases
• Opportunistic infections or cancers take advantage of a very weak immune system and signal that the person has AIDS

– Transmission:
• HIV virus is passed through blood, semen, pre-seminal fluid, rectal fluids, vaginal fluids, and breast milk of a person who is infected with HIV

Question 8

NNRTI

Answer 8

Act by inhibiting HIV reverse transcriptase, an enzyme responsible for viral replication early in the viral life cycle

Question 9

Integrate inhibitors

Answer 9

Block the integrase enzyme needed for viral DNA to enter into the host nucleus

Question 10

Lincosamides

Answer 10

MOA:
Binds to 50S ribosomal subunit and prevents protein synthesis
• Can be bacteriostatic or bactericidal depending on drug concentration

• Spectrum:
– Good: many Gm (+) aerobes/anaerobes, plasmodium Spp. (malaria), S. pyogenes, S. aureus (MSSA)
– Moderate: S. aureus (MRSA), Gm (-) anaerobes, C. trachomatis, pneumocystis jirovecii (PCP)
– Poor: Enterococci Spp., C. difficile, Gm (-) aerobes

Question 11

Neuraminidase inhibitors

Answer 11

MOA:
Prevents virus from escaping and spreading to other cells

• Post- and Pre-exposure prophylaxis:
– For patients at a very high risk for influenza complications (e.g. severely immunocompromised, 3rd trimester pregnancy)

– To control of outbreaks in institutional setting

– Recommended for all residents once an outbreak is determined (>2 confirmed cases in 72hrs)

– Administer when influenza vaccine is not available or not used

Question 12

Folate antagonists pyrimethamine/proguanil

Answer 12

MOA pyrimethamine & proguanil:

Selective inhibition of plasmodial dihydrofolate reductase; key enzyme for synthesis of folate

Question 13

Nitroimididazoles

Answer 13

– MOA:
after diffusing into the organism, interacts with DNA to cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis and cell death

– Spectrum:
• Good: Gram (-) and gram (+) anaerobes, including Bacteroides, Fusobacterium, and Clostridium species, protozoa, including Trichomonas, and Giardia
• Moderate: Helicobacter pylori
• Poor: aerobic Gram-negative and Gram positive organisms, anaerobes that reside in the mouth.

Question 14

Fluroquinolones

Answer 14

• Bactericidal
• Exhibit concentration dependent killing

• MOA:
Inhibits the replication of bacterial DNA by interfering with DNA gyrase leading to breaks in the DNA and death of the cell

Oral absorption – reduced by antacids (Ca++, iron, Al++)
Ciprofloxacin – 80%
Moxifloxacin – 90%
Levofloxacin – 100%

Penetrates well into skin, soft tissues, and most organs
CNS, bone concentrations are lower but can reach therapeutic levels

Question 15

Protease inhibitor

Answer 15

Block the activity of the HIV enzyme protease that is essential for viral replication late in the virus life cycle

PI’s should be administered with a boosting agent: Ritonavir or Cobicistat

Question 16

Sulfonamides

Answer 16

Bacteriostatic

MOA:
– Inhibits normal bacterial utilization of PABA for the synthesis of folic acid

• Spectrum:
– Good: S. aureus (includes MRSA), H. influenzae, Stenotrophomonas maltophilia, Listeria, Pneumocystis jirovecii, Toxoplasma Spp.
– Moderate: enteric GNRs, S. pneumoniae, Salmonella, Shigella, Nocardia
– Poor: Pseudomonas Spp., enterococci, S. pyogenes, anaerobes

• Time dependent killing: needs to have steady concentrations throughout therapy

• Oral bioavailability varies widely:
– Well absorbed (90-100%): Sulfamethoxazole, sulfadiazine, sulfadoxine
– Poorly absorbed (<15%): Sulfasalazine
– Topical or ophthalmic only: Sulfacetamide, Silver Sulfadiazine, Mafenide

• Distributes widely to many tissues including CNS
• Concentrates in urine –> so use in UTI
• Must adjust for renal function

Question 17

Cyclic lipopeptide

Answer 17

• Bacteriocidal
• Concentration-dependent killing

• MOA:
Binds to bacterial cell membrane causing rapid depolarization and death

Question 18

NRTI

Answer 18

Act by inhibiting HIV reverse transcriptase, an enzyme responsible for viral replication early in the viral life cycle

Question 19

Pyrazinamide

Answer 19

MOA:
- Inhibits cell membrane synthesis
– Prodrug with an unknown mechanism
– Converted to pyrazinoic acid which lowers pH of the environment in susceptible bacteria

• Spectrum:
Bactericidal activity against even slow-growing M. tuberculosis

No longer used in combination with rifampin for LTBI due to the high rates of hepatitis

Question 20

Quinolone

Answer 20

Originates from bark of Cinchona tree
– 1st antimalarial agent used: Quinine

• MOA:
– Unknown; appears to interfere with the ability of the malaria parasite to detoxify hemoglobin metabolites
– Primaquine appears to affect parasitic mitochondrial function

• Spectrum:
– Protozoa (activity variable by regions):
P. falciparum, P. malariae, P. ovale. P. vivax
– Like a parasite but technically a fungus: Pneumocystis jirovecii (PCP) (primaquine)

Question 21

Polyenes

Answer 21

Fungicidal

• MOA:
– Bind to Ergosterol in fungal cell membrane and disturbs its function

• Spectrum:
– Good: most species of Candida and Aspergillus, Cryptococcus neoformans, dimorphic fungi, many molds
– Moderate: Zygomycetes

Question 22

B-Lactams

Answer 22

• Bactericidal

– MOA: Interfere with the last step of bacterial cell wall synthesis (transpeptidation or cross-linkage), resulting in unstable cell membrane and cell lysis

• Time-Dependent killing:
– Optimal response occurs when the time that the drug remains above the MIC is >50% of the dosing interval

Question 23

Streptogramins

Answer 23

• Bactericidal

• MOA:
Quinupristin binds to same site as the macrolides on 50S ribosomal complex.
Dalfopristin binds near it causing a conformational change

• Spectrum: Mostly Gm (+) organisms
– Good: MSSA, MRSA, Streptococci Spp., Enterococcus faecium (includes VRE)
– Poor: Enterococcus faecalis, most Gm (-)

Question 24

Chloramphenicol

Answer 24

• MOA:
– Binds to 50S ribosomal subunit and inhibits peptide bond formation
• Bacteriostatic in most cases

• Spectrum:
– Broad-spectrum Gm (+) and Gm (-), aerobes, anaerobes, rickettsia, spirochetes, and chlamydia.
– Weak/No activity against: P. aeruginosa, S. aureus

• Metabolized hepatically, excreted renally – must monitor levels
• Readily enters CSF; secreted into breast milk

Question 25

Cephalosporins

Answer 25

• Bactericidal
• β-lactam that inhibit cross-linking of peptidoglycan in the cell wall, leading to autolysis and cell death
• Time-Dependent killing

Question 26

Antiretroviral booster

Answer 26

Boosting agents ↓ metabolism reduces pill burden and allows for steadier levels

Question 27

Triazoles

Answer 27

MOA:
– Inhibits P450 fungal enzyme, lanosterol 14α-demethylase involved in biosynthesis of ergosterol
– Mostly fungistatic
– Fungicidal at certain doses/certain organisms

more selectivity for ergosterol and fungal CYP450 enzymes than human

Question 28

Topical polymixin

Answer 28

Topical polymyxins B
Only effective against: Gram (-) organism

Neomycin
Only effective against: Gram (-) organism

Bacitracin
Gram (+) organisms
MOA:
inhibits cell wall synthesis

– Topical
– Ophthalmic
– IM

• May cause renal failure due tubular and glomerular necrosis
– Do not administer IV

Question 29

Allyamines

Answer 29

Fungicidal
• MOA:
– Inhibiting squalene epoxidase resulting in a deficiency of ergosterol and an accumulation of squalene causing cell wall damage and cell death
– Does not inhibit the fungal or human CYP450 system
– Has very few drug interactions compared to itraconazole, fluconazole and ketoconazole

Question 30

Carbapenems

Answer 30

– Very broad spectrum antibiotics : should not to be used liberally
– Gram (+) coverage: MSSA, Streptococci
• Moderate effect against Enterococci Spp. (not ertapenem)
– Gram (-) coverage: P. aeruginosa (not ertapenem), Acinetobacter (not ertapenem),

– Good anaerobic coverage

– No activity against MRSA!!

Question 31

Hep B

Answer 31

• HBeAg-positive (immune active phase)
– Treatment should be avoided due to high risk of failure
– Treat if ALT > 2 x UNL or other significant risks
– End-point: conversion from HBeAg to anti-HBe or HBsAg-loss

• HBeAg-negative (chronic hepatitis)
– Treat if ALT > 1-2 x UNL
– End-point: HBsAg loss

Question 32

Oxazolindinones

Answer 32

MOA:
Inhibits protein synthesis by binding to the P site of 50S ribosomal subunit and preventing the formation of 70S initiation complex
• Bacteriostatic mostly

• Spectrum:
– Good: MSSA, MRSA, streptococci, Enterococcus Spp. (Includes VRE)
– Moderate: some atypicals, M. tuberculosis (used in MDR strains)
- Poor: No effect on Gram (-)

– Oral bioavailability
• Linezolid 100%
• Tedizolid 91%
– Only advantage of tedizolid is QD Vs. BID dose for linezolid
– Widely distributed – blood levels are low
– No dosage adjustments for renal or hepatic dysfunction

Question 33

Ethambutol

Answer 33

MOA:
Inhibits cell wall synthesis

May D/C if known to be susceptible to INH & RIF

Spectrum:
M.tuberculosis, MAC , M. kansasii

Question 34

CCR5 receptor antagonists

Answer 34

MOA:
blocks CCR5 co-receptor that works with gp41 to facilitate HIV entry through the membrane into the cell (prevents entry)

Question 35

Atovaquone &
Proguanil
(Malrone®)

Answer 35

Atovaquoneb MOA:
Interfere with electron transport in the parasitic mitochondria

Atovaquone & Proguanil spectrum:
Pneumocystis jirovecii (PCP)
Plasmodium species, Toxoplasma Gondi, & others

Fixed combination dose of atovaquone and proguanil

Advantages over mefloquine and doxycycline:

• Requires shorter periods of treatment before and after travel
• Atovoquone & proguanil are better tolerated than other agents

Disadvantages:

• Lack of IV formulation
• High cost
• Lower efficacy for pneumocystis pneumonia

Question 36

RSV

Answer 36

Palivizumab
RSV Prophylaxis
MOA:
binds to a protein on virus and prevents it from entering cells

Ribavirin
RSV Treatment
MOA:
Inhibits RSV replication and also improves arterial blood oxygenation, decreases illness severity and viral spread

Question 37

Uti antiseptics

Answer 37

Concentrate in the urine therefore only effective for lower urinary tract infections

• Do not cause a systemic antibacterial effect

Question 38

Isoniazid

Answer 38

Bactericidal against growing mycobacteria, but Bacteriostatic against dormant mycobacteria

• Synthetic analog of pyridoxine(Vitamin B6)

MOA : Inhibits cell-wall synthesis
– Interferes with enzymes responsible for assembly of mycolic acids, which are the essential components of mycobacterial cell walls

• Antibacterial Spectrum:
– Active only against M. tuberculosis and M. kansasii
– Absorbed well orally; absorption impaired by food

• Carbohydrates and aluminum impair absorption:
– Crossed CSF rapidly
– No adjustment in renal failure (can accumulate if severe)
– Needs adjustment in hepatic impairment

Question 39

Folate antagonist

Answer 39

Sulfonamides

Bacteriostatic

MOA:
– Inhibits normal bacterial utilization of PABA for the synthesis of folic acid

• Spectrum:
– Good: S. aureus (includes MRSA), H. influenzae, Stenotrophomonas maltophilia, Listeria, Pneumocystis jirovecii, Toxoplasma Spp.
– Moderate: enteric GNRs, S. pneumoniae, Salmonella, Shigella, Nocardia
– Poor: Pseudomonas Spp., enterococci, S. pyogenes, anaerobes

• Time dependent killing: needs to have steady concentrations throughout therapy

• Oral bioavailability varies widely:
– Well absorbed (90-100%): Sulfamethoxazole, sulfadiazine, sulfadoxine
– Poorly absorbed (<15%): Sulfasalazine
– Topical or ophthalmic only: Sulfacetamide, Silver Sulfadiazine, Mafenide

• Distributes widely to many tissues including CNS
• Concentrates in urine –> so use in UTI
• Must adjust for renal function

Question 40

Imidazoles

Answer 40

MOA:
- Inhibits fungal membrane (ergosterol synthesis) function and ↑ permeability

• ↑ affinity to inhibit fungus CYP450 enzymes rather than mammalian CYP450

Imidazoles: less selectivity for ergosterol and fungal CYP450; results in more drug-drug interactions

Question 41

Tetracyclines

Answer 41

Bacteriostatic
MOA:
inhibit bacterial protein synthesis at the 30S ribosomal subunit
– Prevents addition of amino acids to the growing peptide
– Enter the microorganism by passive diffusion and in part by energy-dependent process of active transport

• Tetracyclines spectrum:
– Good: Atypicals, rickettsia, spirochetes(e.g. B. burgdorferi, Helicobacter pylori), Plasmodium species (malaria)
– Moderate: MRSA, S. pneumoniae
– Poor: most GNRs, anaerobes, enterococci

• Glycylcyclines spectrum:
– Mostly the same as Tetracyclines
– Has Good coverage of MRSA, enterococci including VRE, and S. pneumoniae

Question 42

Aminoglycosides

Answer 42

Bacteriocidal
MOA:
Blocks initiation, translation or incorporation of the protein synthesis process by binding at the 30S ribosomal subunit

• Concentration-Dependent Killing:
– Best responses occur when the concentrations are > 10 times above MIC at site of infection

• Post-antibiotic effect: (6 months after)
– Antibacterial activity persists beyond the time where medication can be measured

• Very effective against Gram (-) organisms:
– E.coli, Klebsiella, P. Aeruginosa, Acinetobacter

• Has synergistic effect with cell-wall modulating agents (e.g. β-Lactams, vancomycin, daptomycin)
– In combination is effective for broad spectrum Gm (+) and Gm (-) bacteria (MRSA, Enterococci Spp.)
– Cell-wall agent destroys/weakens the cell wall allowing for aminoglycosides to enter

Need something to break cell wall for it to enter

Question 43

Rifampin

Answer 43

Bactericidal for both intracellular and extracellular mycobacteria and many
Gram (+) & Gram (-) organisms

MOA:
Protein synthesis inhibitors that work by inhibiting RNA polymerase, preventing transcription by blocking the production of messenger RNA

• Spectrum:
– Good: most Mycobacteria Spp.
– Moderate: Staphylococcus, Acinetobacter, Enterobacteriaceae, E. coli
– Poor: “typical” bacteria as monotherapy, some very rare mycobacteria

Question 44

Glcopeptides

Answer 44

• Bacteriocidal – much slower than β-lactams
• Time-dependent killing

• MOA:
Inhibits bacterial cell wall synthesis