Antibiotics - Drug & Class Details

Question 1

Penicillin G

Answer 1

MOA: Cell wall synthesis inhibition stage 3, bactericidal

PK: IM, IV (poor oral); renally excreted

Use limited to hospitalized patients with severe infections:

Gram positive cocci (Strep, entero)
C. perfringens

Question 2

Penicillin V

Answer 2

MOA: Cell wall synthesis inhibition, stage 3; bactericidal

PK: Oral (acid stable); renally excreted

Gram positive cocci (Strep, Entero)
Anaerobes: C. perfringens

Question 3

Dicloxacillin

Answer 3

Penicillinase-resistant Penicillin

MOA: Cell wall synthesis inhibition; bactericidal

PK: Oral administration; renal excretion

Spectrum/Uses:
Gram positive cocci (Strep, entero) + MSSA

Question 4

Amoxicillin +/- Clavulanate

Ampicillin

Answer 4

Extended spectrum Penicillin

MOA: Cell wall synthesis inhibition; bactericidal; Increased hydrophilicity allows penetration through porins of gram negative OM; coupling to B-lactamase inhibitor allows activity against penicillinase-producing organisms

PK: Good Oral, Renally excreted

Spectrum:
Gram positive cocci (strep, entero) + MSSA
Gram negative rods (E. coli)
Anaerobes (C. perfringens, Bacteroides)

Adverse Reactions: Superinfection more likely, diarrhea (ampicillin > amoxicillin due to poorer oral absorption)

Question 5

Piperacillin +/- Tazobactam

Answer 5

Antipseudomonal Penicillin

MOA: Cell wall synthesis inhibition; bactericidal; coupled to Beta lactamase inhibitor Tazobactam

PK: IV only

Spectrum:
Gram positive cocci (strep, entero) + MSSA
Gram negative rods (E. coli, K. pneumoniae, pseudomonas)
Anaerobes (C. perfringens, Bacteroides)

Question 6

Cefazolin

Answer 6

1st Generation Cephalosporin

MOA: Cell wall synthesis inhibition, stage 3; bactericidal

PK: Oral absorption, renal elimination

Spectrum:
Gram positive cocci (Strep) + MSSA
Gram negative rods (E. coli, K. pneumoniae)

Adverse Reactions: Cross reactivity (1.5%) with penicillin hypersensitivity

Question 7

Ceftriaxone

Answer 7

3rd generation Cephalosporin

MOA: Cell wall synthesis inhibition, stage 3; bactericidal

PK: IV, IM absorption with good CNS penetration

Spectrum:
Gram positive cocci (Strep) + MSSA
Gram negative cocci (N. gonorrhea)
Gram negative rods (E. coli, K. pneumoniae)

Question 8

Vancomycin

Answer 8

MOA: Cell wall synthesis inhibition, stage 2; bactericidal

PK: Poor oral absorption - administered IV (except for GI C. diff); renal elimination

Gram positive cocci (Strep, entero) + MSSA + MRSA
Anaerobes (C. diff)

Adverse reactions: Infusion-related reactions (histamine flushing), nephrotoxicity, ototoxicity; Cp levels must be monitored. Pre-treat with diphenhydramine and acetaminophen.

Question 9

Erythromycin

Answer 9

Macrolide class

MOA: Protein synthesis inhibition (50S); bacteriostatic

PK: Oral absorption; metabolized in liver and excreted in bile

Spectrum:
Gram positive cocci (Strep, Staph)
Gonorrhea
Atypicals (Mycoplasma, Chlamydia)

ARs: GI upset, DDI due to inhibition of P450 metabolism

Question 10

Azithromycin

Answer 10

Macrolide class

MOA: Protein synthesis inhibition (50S); bacteriostatic

PK: Oral (empty stomach); biliary excretion

Spectrum:
Gram positive cocci (Strep, Staph)
Gonorrhea
Atypicals (Chlamydia, Mycoplasma)

ARs: GI disturbance (nausea, vomiting, diarrhea)

Question 11

Clarithromycin

Answer 11

Macrolide class

MOA: Protein synthesis inhibition (50S); bacteriostatic

PK: Absorbed orally, metabolized to active compound that is renally eliminated

Spectrum:
Gram positive cocci (Strep, Staph)
Atypicals (Chlamydia, Mycoplasma)

ARs: GI disturbance, DDI due to inhibition of CYP450

Question 12

Tetracycline

Answer 12

Tetracycline class

MOA: Protein synthesis inhibition; bacteriostatic

PK: oral administration, renal excretion

Spectrum - Broad (but high resistance)
Gram positive cocci (Strep, Staph + MSSA + MRSA)
Gram negative rods (E. coli, K. pneumoniae,)
Other Gram negatives (V. cholera, H. pylori)
Spirochetes (Borrelia burgdorferi)
Atypical (Mycoplasma, Chlamydia)

Question 13

Doxycycline

Answer 13

Tetracycline class

MOA: Protein synthesis inhibition; bacteriostatic

PK: Oral administration, biliary excretion; choice for patients with renal disease

Spectrum - Broad (but high resistance)
Gram positive cocci (Strep, Staph + MSSA + MRSA)
Gram negative rods (E. coli, K. pneumoniae)
Atypicals (Mycoplasma, Chlamydia)

Question 14

Clindamycin

Answer 14

Lincomycin class

MOA: Binds to ribosome preventing translocation of peptidyl tRNA; bacteriostatic

PK: Oral absorption, penetrates most tissues well (especially bone) but not CSF; metabolized by the liver and excreted through the bile

Spectrum:
Gram positive cocci (Strep, Staph + MSSA + MRSA)
Anaerobes (C. perfringens, Bacteroides)
Choice in CA-MRSA

ARs: Selection of C. diff overgrowth leading to pseudomembranous colitis; nausea, diarrhea

Question 15

Ciprofloxacin

Answer 15

Fluoroquinolone Class, 2nd generation

MOA: Preferential inhibition of DNA gyrase; bactericidal

PK: Oral absorption, primarily renal excretion

Spectrum:
Gram negative rods (E. coli, K. pneumoniae, Pseudomonas)
Atypical (Chlamydia, Mycoplasma)

Question 16

Levofloxacin

Answer 16

Fluoroquinolone Class, 3rd generation; “respiratory quinolone”

MOA: Inhibition of both DNA gyrase and Topoisomerase IV; bactericidal

PK: Oral absorption, primarily renal excretion

Spectrum
Gram positive cocci (Strep)
Gram negative rods (E. coli, K. pneumoniae, pseudomonas)
Atypical (Chlamydia, Mycoplasma)

Question 17

Moxifloxacin

Answer 17

Fluoroquinolone Class, 4th generation, “respiratory quinolone)

MOA: Preferential inhibition of Topoisomerase IV; bactericidal

PK: Primarily hepatic excretion (20% renal)

Spectrum
Gram positive cocci (Strep)
Gram negative rods (E. coli, K. pneumoniae)
Atypicals (Chlamydia, Gonorrhea)

Question 18

Nitrofurantoin

Answer 18

MOA: Reduced in cell to intermediates that damage bacterial DNA; bactericidal

PK: Rapid, complete GI absorption followed by rapid excretion via kidneys (contraindicated in renal impairment); not used for systemic infections because effective Cp cannot be obtained with safe doses

Spectrum:
Gram negative rods (E. coli, K. pneumoniae)

ARs: GI upset, occasional hypersensitivity, neuropathies

Question 19

Metronidazole

Answer 19

MOA: Reduced intracellularly to active form, a highly reactive radical anion that interferes with DNA function; bactericidal

PK: Oral absorption, distribution includes CSF and bone; hepatic metabolism

Spectrum:
Anaerobes (C. diff, Bacteroides, H. pylori)
Protozoa (trichomoniasis, amebiasis, giardiasis)

ARs: Antabuse-like reaction (via inhibition of aldehyde dehydrogenase), GI upset, candidal superinfections

Question 20

Penicillins - Adverse Reactions & Toxicity

Answer 20

Type I: Immediate hypersensitivity mediated by IgE & Mast cells (0.05%)

Maculopapular rash most common (1-4%), Diarrhea,

Question 21

Penicillins - Mechanisms of Resistance

Answer 21

Production of penicillinase enzyme via plasmid transfer

Alterations of penicillin-binding proteins (responsible for MRSA)

Inability to penetrate into bacterial cell

Escape or Persisters - metabolically inactive organisms (“L forms”) that can survive in a hypertonic environment

Question 22

Penicillins - Pharmacokinetics

Answer 22

Absorption: varies depending on acid stability
Pen G: IV or IM (poor oral)
Pen V, Amoxicillin, and Dicloxacillin: Good oral
Piperacillin: IV only

Distribution: strong acid, largely ionized at physiological pH; penetrates tissues poorly but enters inflamed tissues more easily

Metabolism/Excretion: Excreted as active drug via the kidney; also excreted into breast milk

Question 23

Cephalosporins - Pharmacokinetics

Answer 23

Absorption: Oral, IV / IM

Distribution: Penetrate well into most tissues and fluids, including placenta; only 3rd gen penetrates into CSF

Metabolism-Excretion: Kidneys, requires renal dosing

Question 24

Cephalosporins - Adverse Reactions

Answer 24

Hypersensitivity

Cross-hypersensitivity with Penicillins <1% - increased risk with 1st gen

Superinfection - increased risk with 2nd and 3rd gen

Alterations of normal gut flora may decrease synthesis of Vitamin K and intensify the anticoagulant effect of Warfarin

Question 25

Vancomycin - Pharmacokinetics

Answer 25

Administered IV (poor oral absorption) Excreted by kidneys; half life is extended in renal failure

Question 26

Vancomyosin - Adverse Reactions

Answer 26

Ototoxicity, chills, fever, rash, renal toxicity Routine monitoring of Cp levels required with infusion

Question 27

B-lactamase Inhibitors

Answer 27

i.e. Clavulanic acid and Tazobactam Resemble B-lactam molecules; they are potent, irreversible inhibitors of B-lactamase; they are coupled to a penicillins to extend the antibacterial spectrum against resistant organisms that exhibit B-lactamase activity Clavulanic acid + Amoxicillin Tazobactam + Piperacillin

Question 28

Cefazolin

Answer 28

1st Generation Cephalosporin MOA: Cell wall synthesis inhibition; bactericidal PK: IV / IM Spectrum: Cocci: gram + (Strep, Staph, non MRSA) Bacilli: gram - (Proteus, diarrhea E. coli, Klebsiella)

Question 29

Aminoglycosides

Answer 29

MOA: Actively transported into cells (O2-dependent), binds irreversibly to bacterial ribosome, blocking initiation of translation; bacteriocidal PK: IV/IM (poor oral) absorption; distribution is limited to extracellular fluid (excluded from CNS) but accumulates in renal cortex and inner ear; renal elimination - 1x/daily dosing possible due to concentration-dependent killing and post-antibiotic effect Spectrum: Gram negative rods (E. coli, K. pneumoniae, Pseudomonas) ARs: Very toxic! 8th nerve damage, renal toxicity

Question 30

Macrolides - Adverse Reactions & Toxicity

Answer 30

GI upset (worse with erythromycin due to direct sitmulation of gut motility) Hepatotoxicity Prolonged QT interval DDIs due to inhibition of CYP450 (erythromycin and clarithromycin only)

Question 31

Macrolides - Mechanism of Action

Answer 31

Macrolides bind to the 23S ribosomal RNA of the 50S subunit, preventing chain elongation and inhibiting protein synthesis

Question 32

Tetracyclines - MOA and Resistance

Answer 32

MOA: Binds to ribosomal A site, preventing access of aminoacyl-tRNAs to the ribosomal active site; bacteriostatic Resistance: Decreased influx, increased efflux, alterations to the ribosome that prevent tetracycline binding

Question 33

Tetracyclines - Adverse Reactions & Toxicity

Answer 33

Inhibition of bone growth & discoloration of teeth (avoid use < 8 years old) GI disturbance DDIs with metal ions (antacids, iron) in stomach Photosensitivity

Question 34

Fluoroquinolones - MOA in Gram negative vs. Gram positive

Answer 34

Fluoroquinolones target DNA Gyrase and DNA Topoisomerase IV causing release of lethal, double-stranded DNA breaks DNA gyrase is more susceptible to inhibition in Gram negative bacteria; Ciprofloxacin preferentially targets DNA gyrase and is more active against gram negative bacteria DNA topoisomerase is more susceptible to inhibition in Gram positive bacteria; Levofloxacin and Moxifloxacin target Topoisomerase and so are effective against gram positive bacteria

Question 35

Tetracyclines - Pharmacokinetics

Answer 35

Oral absorption BUT impaired by milk products, metal cations, and iron salts Distribution - good penetration into tissues, including placenta Elimination - concentrated in liver, secreted into bile; tetracycline is excreted into urine (doxy and mino are not)

Question 36

Fluoroquinolones - Pharmacokinetics

Answer 36

Oral absorption Good penetration into most tissues including high urinary levels Primarily renal excretion

Question 37

Fluoroquinolones - Adverse Reactions

Answer 37

Overall very well tolerated but rarely GI upset, dizziness, headache Black Box Warning: increased risk of tendon rupture and potential for arthropathies DDIs with Theophylline and caffeine due to FQ inhibition of metabolism DDIs with antacids containing metal cations; reduced oral absorption of FQ

Question 38

Community- vs. Hospital-acquired pneumonia

Answer 38

CAP: Strep pneumo is a normal flora in the oropharynx that can become micro-aspirated into the lungs, causing infection; treated with B-lactam + macrolide or respiratory fluoroquinolone (i.e. Ceftriaxone + Azithromycin) HAP: Occurs as a result of colonization with gram negative rods that occurs in over 40% of patients by day 5 of a hospital stay; treated with Vancomycin + Pip-Tazo

Question 39

B - Lactams Mechanism of Action (Penicillins) & Cephalosporins

Answer 39

B-lactams irreversibly bind to and inactivate Penicillin Binding Proteins (PBPs) in the susceptible organism which carry out the transpeptidase (cross-linking) reaction necessary for peptidoglycan synthesis in the cell wall

Question 40

B-lactamase

Answer 40

B-lactamases are enzymes that inhibit B-lactam antibiotics by hydrolyzing the B-lactam ring; they can be encoded by chromosomal or plasmid genes and are found in both gram positive and gram negative bacteria; generally associated with gram negative enterics (E. coli, Enterobacter, Klebsiella)

Question 41

Methicillin Resistant Staph Aureus

Answer 41

MRSA contains an exogenous piece of DNA called staphylococcal chromosome cassette (SCCmec) containing the gene MecA which codes for PBP2a; PBP2a has low affinity for methicillin-type antibiotics (Remember, MRSA also contains the plasma-encoded narrow spectrum B-lactamase that confers resistance to Penicillin & Ampicillin)

Question 42

Vancomycin - Mechanism of Action

Answer 42

Vancomycin binds to the terminal D-ala-D-ala portion of the five member peptide chain of the peptidoglycan precursor molecule which hangs off of MurNAc; it physically blocks the ability of the PBPs to put the precursor molecule into the growing peptidoglycan, thereby blocking both transglycosylase AND transpeptidase activity (stage 2 synthesis inhibitor)

Question 43

Mechanism of Vancomycin-Resistant Enterococci (VRE)

Answer 43

VRE expresses a plasmid-encoded VanA gene, which codes for an enzyme that results in synthesis of precursor peptidoglycan molecules with peptide chains terminating as D-ala-D-lactate; this modified peptidoglycan precursor binds Vancomycin with reduced affinity Most VRE isolates are E. faecium; VRE is rarer in E. faecalis *Also VERY RARELY seen in staph (VRSA)

Question 44

Mechanism of Vancomycin-intermediate S. aureus (VISA)

Answer 44

VISA expresses an unusually thick peptidoglycan cell wall that is less completely cross-linked and therefore contains free D-ala-D-ala tails which can bind Vancomycin, "absorbing" it into the wall and preventing its binding to peptidoglycan precursor molecules and inhibition of peptidoglycan synthesis

Question 45

Respiratory Fluoroquinolones

Answer 45

Levofloxacin and Moxifloxacin are respiratory fluoroquinolones because they preferentially target Topoisomerase IV in Gram positive organisms common in respiratory infections Ciprofloxacin is NOT a respiratory fluoroquinolone because it preferentially targets DNA gyrase in gram negative organisms that are less frequently found in respiratory infections

Question 46

Mechanism of Fluoroquinolone resistance

Answer 46

Fluoroquinolone resistance occurs as a result of the accumulation of point mutations in the region GyrA of DNA gyrase or ParC of topoisomerase IV; these regions are called the quinolone-resistance-determining region (QRDR); these mutations reduce the affinity of the enzyme-DNA complex for the quinolone

Question 47

Macrolides - Resistance

Answer 47

1. The erm gene, usually found on plasmids, encodes an enzyme that dimethylates the 23S ribosomal RNA, preventing macrolide (and clindamycin) binding erm can be inducible or constitutive; microbes are resistant to Macrolides under inducible or constitutive conditions but resistant to clindamycin only under inducible conditions 2. Macrolide-specific efflux pump

Question 48

D test

Answer 48

When an isolate is found to be macrolide resistant, the D test distinguishes between efflux- and erm-mediated resistance Disks of erythromycin and clindamycin are placed on a plate spread with the test pathogen; if the pathogen expresses inducible erm then erythromycin will induce resistance to clindamycin and the zone of inhibition for clindamycin will be blunted, forming a "D" shape of colony growth; if the efflux system is present no blunting will occur

Question 49

Which antimicrobials are effective vs. MRSA?

Answer 49

Vancomycin Clindamycin Macrolides

Question 50

Which antimicrobials are effective vs. Pseudomonas?

Answer 50

``` Pip/Tazo Aminoglycosides Aztreonam Ciprofloxacin Levofloxacin ```

Question 51

Which antimicrobials are effective vs. Atypical organisms (Mycoplasma, Chlamydia)?

Answer 51

Macrolides Tetracyclines Fluoroquinolones (all) SMX / TMP

Question 52

Which antimicrobials are effective vs. C. diff?

Answer 52

Vancomycin | Metronidazole

Question 53

1st generation Cephalosporins (2)

Answer 53

Cephalexin | Cephazolin

Question 54

Second generation Cephalosporins (2)

Answer 54

Ceflacor | Cefuroxime

Question 55

Third generation Cephalosporins (4)

Answer 55

Ceftriaxone Ceftazidime Cefdinir Cefepime

Question 56

Carbapenem Agents (2)

Answer 56

Imipenem / Cilastatin Ertapenem

Question 57

Carbapenem - Mechanism & Pharmacokinetics

Answer 57

Structurally related to B-lactams but are B-lactamase resistant; cell wall synthesis inhibitor (Stage 3) IV/IM administration only Penetrates CSF Renal excretion

Question 58

Carbapenems - Spectrum

Answer 58

Gram positive cocci (except MRSA) Gram negative rods (including Pseudomonas) Anaerobic (including Bacteroides; not C.diff)

Question 59

Carbapenems - Adverse Reactions

Answer 59

Nausea, vomiting, diarrhea Skin rash Rarely seizures - usually in patients with a history of CNS and renal disease

Question 60

Cilastatin

Answer 60

Inhibits dihydroreductase in the kidney, which prevents Imipenem from being prematurely inactivated

Question 61

Aztreonam - Mechanism & Pharmacokinetics

Answer 61

Monobactam class; synthetic B-lactam ring that is resistant to B-lactamases Administered IV/IM only Penetrates CSF Renal elimination

Question 62

Aztreonam - Spectrum

Answer 62

Gram negative, aerobic bacteria ONLY Synergistic use with aminoglycosides vs. Pseudomonas

Question 63

Chloramphenicol - Mechanism, Pharmacokinetics

Answer 63

Protein synthesis inhibitor; binds 50S bacterial ribosome; bacteriostatic Oral absorption with good distribution to the CNS Hepatic elimination

Question 64

Gray baby syndrome

Answer 64

Toxic complication of chloramphenicol Occurs in infants 2-9 days after therapy initiated with vomiting, abnormal respiration, cyanosis, and vasomotor collapse 40% mortality rate

Question 65

Chloramphenicol - Spectrum and Toxicity

Answer 65

Wide spectrum BUT not used in the US due to toxicity ``` Gram positive cocci (except MRSA) Gram negative cocci (Gonorrhea) Gram negative rods (except Pseudomonas) Anaerobes (except C. diff) Atypicals ``` Poor selectivity for bacterial ribosome; also inhibits ribosomes in mammalian bone marrow. Causes aplastic anemia / myelosuppression, requiring CBC monitoring every 2-3 days; also causes Gray Baby syndrome

Question 66

Streptogramins - Combo agent mechanisms & pharmacokinetics

Answer 66

Quinupristin / Dalfopristin (30:70) Quinupristin binds to 50S ribosome (same sate as Macrolides) to inhibit peptide elongation Dalfopristin binds at a nearby site on the 50S ribosome, inducing a conformational change that enhances Quinupristin binding IV Administration only

Question 67

Streptogramins - Spectrum

Answer 67

Gram positive cocci (including MRSA and VRE) Use held in reserve for life-threatening infections only

Question 68

Streptogramins - Adverse Effects

Answer 68

Irritation at infusion site Arthralgias / myalgias Nausea, diarrhea Rash

Question 69

Linezolid - Mechanism & Pharmacokinetics

Answer 69

Oxazolidinone class; binds to 50S ribosome at a different site than other agents, so no cross-resistance with other protein synthesis inhibitors Inhibits early formation of 70S ribosome complex; bacteriostatic Administered oral or IV Renally excreted but no dosage adjustment necessary in mild renal impairment

Question 70

Linezolid - Spectrum & Uses

Answer 70

Gram positive cocci (including MRSA and VRE)

Question 71

Linezolid - Adverse Effects / Toxicity

Answer 71

Well tolerated with minor side effects - diarrhea, headache, nausea Rarely, thrombocytopenia Inhibits MAO - risk of hypertensive response with co-administration of sympathomimetics or foods high in tyramine; serotonin syndrome if given with SSRIs

Question 72

Sulfamethoxazole / Trimethoprim - Mechanism

Answer 72

Sulfamethoxazole inhibits dihydropteroate synthetase Trimethoprim inhibits dihydrofolate reductase In combination, these two agents inhibit two sequential steps in the enzymatic conversion of PABA to tetrahydrofolic acid, necessary for synthesis of DNA and certain AAs Bacteriostatic with delayed onset of action

Question 73

SMX / TMP - Pharmacokinetics & Adverse Effects

Answer 73

Good oral absorption with distribution into CSF Hepatic acetylation to an inactive compound which can be toxic due to low solubility, causing renal crystalluria; Na-HCO3 alkalinizes the urine and decreases crystal formation

Question 74

SMX / TMP - Spectrum and Uses

Answer 74

Gram positive cocci including MRSA Gram negative cocci (Gonorrhea) Gram negative rods (including pseudomonas) Atypical

Question 75

SMX / TMP - Adverse Effects

Answer 75

Sensitization - fever, rashes Rarely - agranulocytosis, aplastic anemia, Stevens-Johnson Syndrome Renal damage via crystalluria Hemolytic anemia in patients with G6PD deficiency Displaces bilirubin from albumin binding sites in infants, causing kernicterus

Question 76

Polymixins

Answer 76

Cell membrane disrupter; interacts with membrane phospholipids to lyse cells with detergent-like action; bactericidal Active against gram negative only; used for pseudmonas meningitis after other agents have failed Highly nephrotoxic

Question 77

Daptomycin

Answer 77

Binds to bacterial cell membrane causing rapid depolarization which inhibits protein, DNA, and RNA synthesis resulting in cell death (bactericidal) Spectrum similar to Vancomycin; active against MRSA, including Vancomycin-resistant MRSA IV administration Renal elimination

Question 78

Treatment of uncomplicated Gonorrhea

Answer 78

Ceftriaxone - 250mg IM Azithromycin (1g oral) OR Doxycycline (100mg 2x/day for 7 days) - empirical coverage of Chlamydia

Question 79

Treatment of ocular Chlamydia in infants

Answer 79

1% silver nitrate OR 1% tetracycline OR 0.5% Erythromycin topical to eyes at time of birth

Question 80

Treatment of pregnant women with Gonorrhea

Answer 80

3rd Generation Cephalosporins

Question 81

Treatment of uncomplicated Chlamydia

Answer 81

Azithromycin - 1g oral OR Tetracycline - 100mg BID x 7 days

Question 82

Prevention of neonatal transmission of Chlamydia

Answer 82

Erythromycin or amoxicillin to treat the mother

Question 83

Treatment of neonatal inclusion conjunctivitis (chlamydial)

Answer 83

Erythromycin (oral)

Question 84

Treatment of syphilis

Answer 84

Penicillin is first line Azithromycin for patients who are penicillin allergic