Antimicrobials

Question 1

Define MIC (Minimal Inhibitory Concentration):

Answer 1

the lowest antimicrobial concentration that prevents visible bacterial growth after overnight incubation. A standard inoculum is introduced to serial dilutions of antibiotics.

Question 2

Define MBC (minimum bactericidal concentration)

Answer 2

the lowest concentration of antimicrobial that will prevent the growth of an organism after subculture on to antibiotic free media. Clear tubes from MIC are subcultured.

Question 3

Vancomycin spectrum and MOA

Answer 3

Spectrum: Gram (+) bacteria incl. MRSA and C. difficile (PO)
Mechanism: inhibit cell wall synthesis by binding to terminal D-Ala-D-Ala of peptidoglycan precursors

Question 4

Vancomycin resistance mechanisms

Answer 4

Resistance mechanisms:
1) Altered target site (terminal D-Ala-D-Ala)
S. aureus (vanA gene, VRSA), E. faecium (vanA gene), E. faecalis (vanB gene)
2) Cell wall thickening
Vancomycin intermediate S. aureus (VISA)

Question 5

Fosfomycin

Answer 5

Spectrum: Gram (+) and Gram (-) bacteria
Mechanism: inhibits peptidoglycan synthesis (formation of N-acetylmuramic acid)

Question 6

Which classes of drugs are considered beta-lactams

Answer 6

penicillins, cephalosporins, carbapenems, monobactams (aztreonam)

Question 7

Beta-lactams spectrum and MOA

Answer 7

Spectrum: Gram (+) and Gram (-) bacteria; monobactams only cover Gram (-) bacteria
Mechanism: inhibit cell wall synthesis by preventing the final cross-linking of the cell wall by PBPs

Question 8

What are the resistance mechanisms to beta-lactams

Answer 8

1) Altered penicillin binding proteins
Gram (+) bacteria incl. MRSA (mecA), S. pneumoniae, and E. faecium
2) B-lactamase enzymes
Gram (-) bacteria, S. aureus, B. cereus
3) Efflux pumps (actively pump the drug out)
Gram (-) bacteria
4) Porin mutations (prevent the drug from entering)
Gram (-) bacteria

Question 9

Define narrow spectrum beta-lactamase

Answer 9

resistance to penicillins and narrow spectrum cephalosporins

Question 10

Define ESBL

Answer 10

resistance to penicillins, narrow and extended spectrum cephalosporins and monobactams, but not cephamycins or carbapenems

Question 11

Define KPC

Answer 11

Klebsiella pneumoniae carbapenemases (KPC): resistance to penicillins, narrow and extended spectrum cephalosporins, and carbapenems

Question 12

Define ampC

Answer 12

resistance to penicillins, cephalosporins (excluding 4th generation) and cephamycins; inhibited by boronic acid and cloxacillin

Question 13

Which organisms have inducible ampC

Answer 13

Enterobacter, Serratia, Citrobacter, Providencia, Morganella, Pseudomonas, Aeromonas (ESCPM+); E. coli does not have inducible AmpC, but mutations can cause increased expression, leading to resistance

Question 14

Name the beta-lactamase inhibitors

Answer 14

Clavulanate
Sulbactam
Tazobactam

Question 15

Beta-lactamase inhibitors spectrum and mechanism

Answer 15

Spectrum: when used in combination with B-lactams, inhibits bacteria with narrow spectrum B-lactamases and ESBLs; clavulanate and tazobactam may inhibit bacteria with KPCs
Mechanism: structural analogues to B-lactams that irreversibly bind to B-lactamase enzymes, inhibiting their activity

Question 16

name the aminoglycosides

Answer 16

Gentamicin
Tobramycin
Amikacin
Streptomycin

Question 17

aminoglycosides spectrum and MOA

Answer 17

Spectrum: Gram (+) and Gram (-) bacteria; need aerobic energy to enter the cell
Mechanism: inhibit protein synthesis by binding to 16S rRNA within the 30S ribosomal subunit

Question 18

Aminoglycoside resistance mechanisms

Answer 18

1) Decreased cell wall permeability
Intrinsic in most Gram (-) bacilli
2) Efflux pumps
3) Target site alteration
Erm gene: methylates ribosome and prevents drug binding; inducible clindamycin resistance with erythromycin (S. aureus)

Question 19

Tetracycline spectrum and MOA

Answer 19

Spectrum: Gram (+) and Gram (-) bacteria incl. Chlamydia, Mycoplasma, Rickettsia
Mechanism: inhibit protein synthesis by binding to 30S ribosomal subunit

Question 20

Tetracyclines resistance mechanisms

Answer 20

1) Efflux pumps
2) Target site alteration
3) Enzymatic inactivation
Bacteroides spp.

Question 21

Tigecycline spectrum and MOA

Answer 21

Spectrum: Gram (+) and Gram (-) bacteria, anaerobes
Mechanism: ribosome inhibition

Question 22

Linezolid spectrum and MOA

Answer 22

Spectrum: Gram (+) bacteria including MRSA and VRE
Mechanism: ribosome inhibition

Question 23

Quinolones (–floxacin) spectrum and MOA

Answer 23

Spectrum: Strep, Gram (-) bacteria, atypical bacteria, anaerobes (moxifloxacin), M. tuberculosis (moxifloxacin)
Mechanism: inhibits DNA replication by binding topoisomerase IV and DNA gyrase

Question 24

Quinolones resistance mechanisms

Answer 24

1) Target site mutations
Pseudomonas: topoisomerase mutations
2) Reduced permeability of outer membrane proteins

Question 25

Trimethoprim/sulfamethoxazole

(TMP/SMX) spectrum and MOA

Answer 25

Spectrum: Gram (+) bacteria including MRSA, Gram (-) bacteria, Pneumocystis jirovecii, Toxoplasma gondii
Mechanism: TMP and SMX act synergistically to inhibit purine synthesis

Question 26

Isoniazied spectrum and MOA

Answer 26

Spectrum: M. tuberculosis
Mechanism: inhibits synthetic pathways of mycolic acids

Question 27

Rifampin spectrum and MOA

Answer 27

Spectrum: M. tuberculosis
Mechanism: inhibits synthetic pathways of mycolic acids