Drug Classes

Question 1

B-lactams: MOA

Answer 1

Structural analogs of D-Ala-D-Ala
Covalently bind to PBPs to prevent cross linking, inhibit transpeptidation reaction (last step in peptidoglycan synthesis)

Bacterial resistance:
gram negative (can’t reach site of action)
Inactivation by B-lactamases
Structural differences in PBP

Question 2

Penicillins: class, MOA

Answer 2

B-lactam

Inhibit cell wall synthesis

Question 3

Natural Penicillins: spectrum, ADRs

Answer 3

Gram positive cocci (however, easily hydrolyzed by penicillinase)

Hypersensitivities: anaphylaxis, interstitial nephritis
Large dose: N/V/D, pseudomembranous colitis

Question 4

Anti-Staphylococcal Penicillins: Spectrum, MOA

Answer 4

DOC for S. aureus, S. epidermis (not MRSA)
Penicillinase resistant

Hypersensitivities: anaphylaxis, interstitial nephritis
Large doses: N/V/D, pseudomembranous colitis

Question 5

B-lactams: sub classes

Answer 5

Penicillins
Cephalosporins
Monobactams
Carbapenems

Question 6

Aminopenicillins: Spectrum, ADRs, important drugs

Answer 6

Extended spectrum, frequently used with a B-lactamase inhibitor to reach gram negative, in addition to gram positive.

Hypersensitivities: anaphylaxis, interstitial nephritis
Large dose: N/V/D, pseudomembranous colitis

Ampicillin (+/- sulbactam)
Amoxicillin (+/- clavulanic acid)

Question 7

Anti-Pseudomonal Penicillins: Spectrum, ADRs, important drugs

Answer 7

extends to P. aeruginosa, Enterobacter, anaerobes; can be used for serious gram negative infections (ie HAP, immunocompromised, etc.)

Hypersensitivities: anaphylaxis, interstitial nephritis
Large dose: N/V/D, pseudomembranous colitis

Piperacillin

Question 8

Cephalosporins: MOA, resistance, ADRs

Answer 8

B-lactam, so same general MOA/ resistance as Penicillins
None have coverage with MRSA/MR- Listeria/Enterococci

1% risk of cross-reactivity with penicillins (esp when pt has true hypersensitivity) diarrhea, intolerance to alcohol

Question 9

First Generation Cephalosporins: Spectrum, uses

Answer 9

Good gram positive coverage, modest gram negative coverage, oral anaerobes

Skin and soft tissue infections (SSTIs), surgical prophylaxis

Question 10

Second Generation Cephalosporins: Spectrum

Answer 10

still good gram positive coverage, somewhat increased gram negative coverage

Question 11

Third Generation Cephalosporins: Spectrum, uses, important drugs, ADRs

Answer 11

Less active against gram positive, better with gram negative, good coverage with Enterobacteriacea

DOC for serious gram negative infections (Klebsiella, Proteus, Serratia, Haemophilus)

Ceftriaxone
Ceftazidime

1% cross reactivity with penicillins; diarrhea; intolerance to alcohol

Question 12

Fourth Generation Cephalosporins: Spectrum, uses, important drugs, ADRs

Answer 12

similar spectrum to third generation cephalosporins (prototype is resistant to many B-lactamases, excellent penetration to CSF)

EMPIRICAL TREATMENT OF NOSOCOMIAL INFECTIONS; serious infections in hospitalized patients (P. aeruginosa, Enterobacteriacae, S. aureus, S. pneumoniae)

Cefepime

1% cross reactivity with penicillins; diarrhea, intolerance to alcohol

Question 13

Carbapenems: MOA, resistance, important drugs, spectrum, ADRs

Answer 13

B-lactam, so similar MOA and resistance to penicillins

Meropenem
Ertapenem

aerobic and anaerobic gram positive; excellent activity against Enterobacteriacae, Pseudomonas, Acinetobacter;
lower respiratory infections, abdominal/gynecological/ bone and joint

N/V; seizures; hypersensitivity

Question 14

Monobactams: MOA, resistance, spectrum, use

Answer 14

B-lactam, so same MOA and resistance as penicillins

aerobic gram negative coverage only (Enterobacteriacae, Pseudomonas, H. influenzae, gonococci)

Use in pts who are allergic to penicillins/cephalosporins

Question 15

Glycopeptides: MOA, resistance, important drugs, spectrum, uses, ADRs

Answer 15

Inhibits cell wall synthesis: binds with D-Ala-D-Ala terminal

Alteration to terminal (no longer D-Ala-D-Ala), or abnormally thick cell wall (NOT active with gram negative)

Vancomycin

Broad gram positive coverage: S.aureus (including MRSA); S. epidermis (including MRSE); Streptococci; Bacillus; Corynebacterium, Actinomyces; CLostridium

ORALLY FOR C. DIFF; osteomyelitis, endocarditis, CNS infections, bacteremia

macular skin rash, chills, fever, “Red Man Syndrome” (extreme flushing) due to rapid infusion; tachycardia, HTN

*Vancomycin has a direct effect on mast cells, causes them to release histamine

Question 16

Fluoroquinolones: MOA, resistance, important drugs, spectrum, uses, ADRs

Answer 16

Concentration-dependent killing, targets bacterial DNA gyrase and topoisomerase (allows positive coiling of bacterial DNA)

Mutations in gyrase/topoisomerase

Levofloxacin (“respiratory fluoroquinolone”)

H. influenzae, Moraxella, S. aureus, E.coli, Salmonella, Shigella, Enterobacter, Campylobacter, Neisseria, P. aeruginosa, S. aureus, atypicals, intracellular pathogens (Legionella, mycobacterium)

Levofloxacin, in particular, as a respiratory fluoroquinolone: Streptococcus pneumoniae

mild GI sx’s, mild CNS sx’s, rash, photosensitivity,
Achilles tendon rupture (contraindicated in children)

Question 17

Aminoglycosides: MOA, resistance, important drugs, spectrum, uses, ADRs

Answer 17

concentration-dependent killing; binds 30s ribosomal subunit, disrupts protein synthesis
entry is electron/oxygen transport-dependent
AGs have a residual bacteriocidal effect (after MIC)

AG-metabolizing enzymes, impaired transport of drug into cell

Gentamicin

aerobic gram negative; limited against gram positive (but has synergistic bacteriocidal effects on gram positive when combined with a cell wall-active agent (B-lactam, Vancomycin)

When there is resistance to other agents, or pt is very ill; Gentamicin is active against Serratia; used in HAP, peritonitis in peritoneal dialysis, synergistic in bacterial endocarditis

Ototoxicity (up to 25%), nephrotoxicity, neuromuscular block, apnea

Question 18

Tetracyclines/Glycylcyclines: MOA, resistance, important drugs, spectrum, uses, ADRs

Answer 18

Bacteriostatic; binds to 30 s ribosomal subunit, blocks acceptor (A) site on mRNA (prevents addition of aa’s to growing peptide)

Decreased drug influx, energy-dependent efflux, ribosomal protection proteins, enzymatic inactivation