2-Overview of Antibacterial Agents

Question 1

Name the four classes of beta-lactam antibiotics

Answer 1

Penicillins, cephalosporins, monobactams, carbapenems

Question 2

How do beta-lactam antibiotics work?

Answer 2

Bind crosslinking (DAP) and transpeptidation enzymes to inhibit cell wall synthesis.

Question 3

How do penicillins work?

Answer 3

beta-lactam activity inhibits cell wall synthesis Bind penicillin-binding proteins on cell wall = lysing enzymes

Question 4

Name two ways bacteria have acquired resistance to penicillins

Answer 4

1. production of beta-lactamase enzymes to destroy beta-lactam ring 2. Mutate PBPs to prevent binding

Question 5

How are penicillins excreted?

Answer 5

Renally - remember they used to have soldiers drink urine of other soldiers on penicillins during shortage

Question 6

What are the important adverse reactions to penicillins?

Answer 6

Hypersensitivity reactions with cross sensitivity between all penicillins

Question 7

What is the treatment for syphilis?

Answer 7

Natural penicillins (G and V)

Question 8

Name the four organisms that still respond to natural penicillin treatment

Answer 8

1. streptococci (pyogenes and pneumoniae) 2. Nisseria meningitidis 3. Clostridium sp 4. Treponema pallidum (syphilis!!***)

Question 9

Do aminopenicillins work via a time-dependent or concentration-dependent manner?

Answer 9

Time dependent- requires repeated administration

Question 10

Name two examples of aminopenicillins

Answer 10

Ampicillin and amoxicillin

Question 11

What organisms are aminopenicillins used for?

Answer 11

Upper respiratory tract pathogens:

• S. pyogenes
• S. pneumoniae
• Hemophilus influenza
• Enterococcus

community gram negative bacteria (E. Coli; proteus sp)

Question 12

Do aminopenicillins have activity against Staphylococcus?

Answer 12

NO

Question 13

Piperacillin (Class, Excretion, Uses, adverse effects)

Answer 13

Class: extended spectrum penicillin

Excretion: biliary tract

Uses: usu in combination with tazobactam (zosyn) **anti-pseudomonal

Adverse effects: Sodium overload Thrombocytopenia

Question 14

Name anti-pseudomonal antibiotics

Answer 14

1. Piperacillin (extended spectrum penicillin)
2. Cetazimide (3rd generation cephalosporin)
3. Cefepime (4th generation cephalosporin)
4. Azetronam (monobactram)
5. Doripenem, imipenem, meropenem (Carbapenems)
6. Aminoglycosides (GNATS)

Question 15

What organisms are treated with extended-spectrum penicillins?

Answer 15

NOT Staphylococcus

• Gram-negative bacteria
• Psudomonas aeruginosa
• Enterococcus

Question 16

Name three Beta-lactamase inhibitors and their penicillin combination

Answer 16

1. Cavulanic acid + amoxicillin = augmentin
2. Sulbactam + ampicillin = Unasyn
3. Tazobactam + piperacillin = Zosyn***​

most widely used IV antibiotic in hospitals & gram +, gram -, & anaerobic activity

Question 17

What is the method of action of beta-lactamase inhibitors? Do they have bactericidal effects?

Answer 17

Inhibit Beta-lactamase enzymes

NO bactericidal effect

Widen spectrum of penicillins to increase activity against Staphylococcus, gram -, and anaerobic bacteria

Question 18

Name 2 penicilinase-resistant penicillins

Answer 18

1. Nafcillin (can cause serum sickness rxn)
2. Dicloxacillin

Question 19

How does the spectrum of activity change for cephalosprin generations?

Answer 19

Start gram + then become more gram -

Question 20

Which category of antibiotics do Cephalexin, Cephradine, and Cefadroxil belong to?

Answer 20

First generation cephalosporins (oral)

Cephalexin= used for community Staphyloccal and stretococcal infections

Question 21

Cefazolin (Class, Administration, Uses)

Answer 21

• Class: 1st generation cephalosporin
• Administration: IV
• Uses: gram positive
  
  • Streptococcus sp & methicillin-sensitive Staphylococcus
  • Used in hospitals for wound infections & surgical prophylaxis
  • E. coli and Klebsiella sp

Question 22

Cefuroxime and Cefoxitin belong to what category of antibiotics?

(Class and administration)

Answer 22

2nd generation Cephalosporins (Beta-lactam Abx)

Administration: IV

Question 23

Cefoxitin (Class, Administration, Microbe)

Answer 23

• Class: 2nd generation Cephalosporin
• Administration: IV
• *Microbe**: anaerobic activity- abdominal and gynecologic infx

Question 24

Cefuroxime, Cefaclor, and Cefprozil

(Class, administration, microbe)

Answer 24

• Class: 2nd generation Cephalosporins
• Administration: Oral
• Microbes:
  
  • gram negative bacteria: Klebsiella pneumoniae, Hemophilus influenzae, Moraxella catarrhalis
  • Community acquired pnemonia, URI, otitis media

Question 25

Cefotaxime and Ceftriaxone (Rocephin) (Class, Administration, Microbe, Adverse rxn)

Answer 25

* **Class:** 3rd generation Cephalosporin * **Administration:** IV * **Uses:** _cross BBB_ = useful for meningitis ("Ax to the head") * **Adverse rxn**: Disulfram-like reaction

Question 26

Ceftazidime (Fortaz) (Class, Administration, Use, Adverse reaction)

Answer 26

* **Class:** 3rd generation Cephalosporin * **Administration:** IV * **Microbe:** **only** 3rd generation with **anti-pseudomonas** * alternative to piperacillin * **Adverse rxn**: Disulfram-like reaction

Question 27

What are the general uses for 3rd generation Cephalosporins?

Answer 27

* gram (-) and gram (+) bacteria * nosocomial infx, pneumonia, meningitis, advanced Lymes disease * Ceftazidime = anti-pseudomonal

Question 28

What is a common adverse rxn to 3rd generation Cephalosporins (Cefotaxime, Ceftriaxone, Ceftazidime, Cefixime, Cefpodoxime)?

Answer 28

**Disulfram-like rxn**: nausea, vomiting, palpitations if abx consumed with alcohol

Question 29

Cefixime and Cefpodoxime (Class, Administration, Uses, Adverse rxn)

Answer 29

* **Class**: 3rd generation Cephalosporins * **Administration**: Oral * **Uses:** gram (+) and gram (-) bacteria * nosocomial infx, pneumonia, meningitis, advanced Lymes * **Adverse rxn:** disulfram-like reaction

Question 30

Cefepime (Class, Admin, Microbe)

Answer 30

* **Class:** 4th generation Cephalosporin * **Admin**: IV * **Microbes:** resistant to chromosomal beta-lactamase enzymes * *Enterobacteriaceae* * ***Pseudomonas aeruginosa*** * Penicillin-resistant *Streptococcus pneumoniae*

Question 31

Ceftaroline (Class, Microbe)

Answer 31

* **Class:** 5th generation Cephalosporin * **Admin:** IV * **Microbe: MRSA infection** (high affinit for PBP2a encoded by mecA gene in MRSA) * similar to 3rd generation (gram+/-) * NO pseudomonas or enterococcus

Question 32

Azetronam (Class, Structure, Action, Other)

Answer 32

* **Class:** Monobactam * **Structure:** monocyclic beta-lactam ring * **Action**: **anti-psudomonal** * NO gram (+) activity * **Other**: no cross-sensitivity with penicillin or cephalosporin * =useful for **beta-lactam allergies**

Question 33

What is the first line choice for a patient with a gram (-) infection that is allergic to penicillins and cephalosporins?

Answer 33

Azetronam (monobactam with monocyclic beta-lactam ring)

Question 34

Imipenem-cilistatin, Meropenem, Ertapenem, and Dripenem (class, administration, general uses, adverse effects)

Answer 34

* **Class:** Carbapenems * **Admin**: IV * **Uses**: broad spectrum antibiotic for multi-resistant infections * Polymicrobial and nosocomial infections * Anti-pseudomonas **except** for Ertapenem * **Adverse rxn** * **Neurotoxic** - seizures * Superinfections (*C. diff*) * High cost * Cross-sensitivity with pencillin-allergic patiets

Question 35

Why is cilistatin used with imipenem?

Answer 35

Cilistatin inhibits renal dihydropeptidase enzyme that would normally hydrolyze imipenem in the kidney

Question 36

Which Carbapenem does NOT have activity against pseudomonas?

Answer 36

Ertapenem Imipenem-cilistatin, Meropenem, and Doripenem DO Doripenem has the **most activity**

Question 37

Bacitracin (MOA, Microbe, Adverse Rxn)

Answer 37

* **MOA**: inhibitor of bacteria cell wall synthesis * **Use**: topical preparation for *Streptococcus* and *Staphylococcus* * *​*gram (+) bacteria _only_ * **Adverse rxn**: nephrotoxic if given systemically

Question 38

Fosfomycin (Class, Microbe)

Answer 38

* **Class**: phosphonic antibiotic inhibiting peptidoglycan synthesis in urine * **Use**: gram (-) UTI if resistant to sufla and fluoroquinolone abx

Question 39

Nitrofurantoin (Use, adverse rxn, contraindications)

Answer 39

* **Uses**: lower UTI * bactericidal against *E. coli, Enterococcus* * **Adverse rxn:** GI irritation, nausea, vomiting * **Contraindications** * Elderly due to increased risk of pneumonitis and neuropathy * renal failure

Question 40

Vancomycin (Class, MOA, Admin, Use, Pharmacokinetics, Adverse Rxn)

Answer 40

* **Class:** glycopeptide w/ high molecular weight * **MOA:** blocks transglycosylation to inhibit peptidoglycan elongation * **Admin:** mostly IV * **Oral for pseudomembranous colitis /*C. diff* colitis** * **Use: MRSA \*first line** * **Pharmacokinetics**: renal excretion (proportional to creatinine clearance) * Narrow therapeutic index * **Adverse Rxn: Red man syndrome-** massive histamine release if given too fast * **Ototoxicity**

Question 41

What is the first line choice for MRSA infection and how does that drug work?

Answer 41

**Vancomycin** - blocks elongation of peptidoglycan (transglycosylation)

Question 42

What is Red Man Syndrome and what antibiotic is it associated with?

Answer 42

Massive histamine release caused by infusion of **vacomycin** that is too fast or too high of a dose

Question 43

Daptomycin (Class, Admin, MOA, Microbe, Other)

Answer 43

* **Class:** cyclic lipopeptide * **Admin:** IV * **MOA**: inhibits cell membrane synthesis * **Microbe:** gram (+) and vancomycin-resistant bacteria * **Other:** Concentration-dependent activity

Question 44

Colistin (Admin, Microbe, Adverse Rxn)

Answer 44

* **Admin:** IV * **Microbe**: MDR resistant bacteria- CRE * **Adverse Rxn**: Nephrotoxic

Question 45

What are the 3 categories of bacterial protein synthesis inhibitors?

Answer 45

1. Macrolides 2. Tetracyclines 3. Aminoglycosides (4. Miscellaneous: Clindamycin, Linezolid & Mupirocin)

Question 46

Macrolide antibiotics MOA

Answer 46

Reversibly bind to 50S ribosomal subunit

Question 47

Macrolide antibiotics: Uses & Bacterial susceptibility

Answer 47

1. Bacteriostatic effect 2. Upper & lower respiratory infections: **a****ctivity against _atypical bacteria_ causing pneumonia (*Mycoplasma, Legionella & Chlamydophyla)*** ***3. Chlamydia trachomatis STD infections*** 4. *Streptococcus & Staphylococcus* 5. *Hemophilus Influenzae & Bordetella* 6. Penicillin-allergic patients

Question 48

Name 3 Macrolide antibiotics.

Answer 48

mACErolides 1. Azithromycin (Zithromax) 2. Clarithromycin 3. Erythromycin

Question 49

Erythromycin (class, MOA, adverse rxns, drug interactions)

Answer 49

1. Class: Macrolide 2. MOA: 50S ribosome inhibitor 3. Adverse: - Oral: abdominal pain & diarrhea (macrolides = motillin receptor agonists) - IV: High doses can cause ototoxicity (Vancomycin also ototoxic) 4. Drug interactions: inhibits CYP450-3A4 (which metabolizes 50% of drugs), thus increases serum levels of statins, benzos, ca ch blockers, cyclosporines, etc.

Question 50

Which antibacterial drug class acts as Motillin receptor agonists, thus causes diarrhea as an adverse effect?

Answer 50

Macrolides (Azitromycin, Clarithromycin & Erythromycin) mACErolides

Question 51

Clarithromycin (class, MOA, adverse, drug interactions)

Answer 51

Very similar to Erythromycin 1. Class: Macrolides 2. 50S ribosome inhibitor 3. Adverse: Less GI effects than Erythro 4. Drug interactions: stronger CYP450-3A4 inhibition than Erythro

Question 52

Azithromycin (class, MOA, adverse, drug interactions, benefits)

Answer 52

1. Class: Macrolides 2. MOA: 50S ribosome inhibitor 3. **M****inimal adverse effects** 4. **No drug interactions** 5. Other: - Post-antibiotic effect (thus given 1/day for 3-5 days) - Most popular, safest macrolide antibiotic

Question 53

Tetracyclines (MOA, bacterial susceptibility/uses, adverse & drug interactions)

Answer 53

1. MOA: Reversibly bind 30S ribosomal subunit 2. Bacterial susceptibility/Uses: - Bacteriostatic - Gram +/- bacteria, - Lyme disease, Erlichiosis, Rocky Mountain Spotted Fever, Atypical pneumonia, Acne (w/ Minocycline) 3. Adverse: - **Discoloration of tooth enamel (children/fetus)** - **Super infection: *C. difficle* = antibiotic-associated pseudomembranous collitis** (also caused by Clindamycin) - GI irritation, photosensitivity, hepatotoxicity w/ extended use 4. Drug interactions: Cheleating agent = binds cations (calcium) and prevents absorption (avoid w/ dairy/antacids)

Question 54

Name 4 Tetracyclines | (& a fun fact about each!)

Answer 54

Tetra = 4; DMT (psychedelic) is fun! 1. Doxycycline: Most popular tetracycline - **Fecal elimination** = can use w/ renally impaired pts 2. Minocycline: Acne 3. Tetracycline: Rarely used b/c low bioavailability/short half life 4. Tigecycline: **active against gram +/- & anaerobic bacteria** **- Reserve for antibiotic-resistant infections (like MRSA)**

Question 55

Aminoglycosides (MOA, bacterial susceptibility/uses, pharmacokinetics & adverse)

Answer 55

1. MOA: **irreversibly** binds 30S ribosomal subunit 2. Bacterial Susceptibility/Uses: - Bactericidal - Gram - (including **Pseudomonas**) 3. PK: - Give high dose once b/c **conc-dep effect** - Eliminated renally; accumulate in renal failure - Narrow therapeutic index 4. Adverse: **- Nephrotoxic** **- Ototoxic** **- NMJ blocking**

Question 56

Name 5 Aminoglycosides

Answer 56

G-ANTS (gangsta ants, bruh) 1. Gentamicin 2. Amikacin 3. Neomycin 4. Tobramycin 5. Streptomycin

Question 57

Tobramycin (class, MOA, uses)

Answer 57

1. Class: Aminoglycoside 2. MOA: irreversibly bind 30S ribosomal subunit 3. Uses: Inhaled form for Cystic Fibrosis Patients w/ **Pseudomonas pneumoniae**

Question 58

Neomycin (class, MOA, uses & adverse)

Answer 58

1. Class: Aminoglycoside 2. MOA: irreversibly bind 30S ribosomal subunit 3. Adverse: most toxic/never used as IV 3. Uses: - Topical formulas - Oral form for prophylaxis before elective bowel surgery - Recurrent GI infections - Hepatic encephalopathy management (kills NH3 producing bacteria that worsen encephalopathy)

Question 59

Streptomycin | (class, MOA, uses)

Answer 59

1. Class: aminoglycoside 2. MOA: irreversibly bind 30S subunit 3. Uses: second line therapy for active tuberculosis

Question 60

Clindamycin (Class, MOA, Bacterial susceptibility/Uses, Adverse)

Answer 60

1. Class: class of its own, baby 2. MOA: binds 50S ribosomal subunit (like macrolides) 3. Bacterial susceptibility/Uses: - Bacteriostatic - **Anaerobic infections** (*Bacteroides fragilis & Clostridium perfringies)* **-** *Streptococci, Staphylococci & Pneumocci* - Gram + infections in penicillin-alergic patients - Newly discovered CA-MRSA 4. Adverse: - **Primary cause of antibiotic-associated Pseudomembranous colitis** (other is Tetracycline) - Treatment: Vancomycin & Metrometazole

Question 61

Linezolid (Class, MOA, Bacterial susceptibility/Uses, Adverse)

Answer 61

1. Class: class of its own 2. MOA: unique activity against 50S ribosomal subunit 3. Bacterial susceptibility/Uses: - Bacteriostatic - Reserved for multi-drug resistant bacteria (VRE/MRSA) 4. Adverse: Hematologic toxicity (thrombocytopenia/neutropenia)

Question 62

Mupirocin | (class, MOA, uses)

Answer 62

1. Class: of its own 2. MOA: unrelated to other antibiotics (?) 3. Uses: - _Topical_ preparations for _Staphylococcal_ infections - **Nasal formulation** reserved for MRSA - Impetigo (streptococci/staphylococci)

Question 63

Fluoroquinolones (MOA, Bacterial susceptibility/Uses, Adverse, Drug interactions)

Answer 63

1. MOA: DNA gyrase/topoisomerase inhibitors 2. Bacterial susceptibility/Uses: - Bactericidal against - Most gram (-), gram (+) (3rd gen) & **Atypical bacteria** **-** Complicated _UTI_ & _prostatitis_ 3. Adverse: - **Arthropathy (avoid in children/pregnancy)** = Achilles tendon rupture - Neurotoxic @ high doses 4. Drug interactions: - Oral dose inhibited by cations (Ca2+, Mg2+, Fe, Zn) - Inhibits caffeine/theophylline metabolism

Question 64

Name two 2nd generation Fluoroquinolones (& their uses)

Answer 64

1. Ciprofloxacin: **only quinolone w/ anti-Pseudomonas aeruginosa** 2. Norfloxacin: UTI infections

Question 65

Name three 3rd generation Fluoroquinolones (Bacterial susceptibility/use, metabolization)

Answer 65

"Respiratory fluoroquinolones" + (LGM) Bacterial Susceptibility/Uses: - Gram (-) **- Atypical bacteria** (respiratory infections) - Multidrug-resistant *Streptococci pneumoniae* 1. Levofloxacin (renal elimination) 2. Gemifloxacin (hepatic metabolism: don't use for UTI) 2. Moxifloxacin (hepatic metabolism: don't use for UTI) - Better anaerobic activity than Levofloxacin

Question 66

Trimethoprim-Sulfamethoxazole | (MOA, Bacterial susceptibility/Uses)

Answer 66

aka Bactrim, TMP-SMX or Cotrimoxazol 1. MOA: "Sequential inhibition" - Sulfonamides: inhibit DHF synthesis (via substituting as PABA) - Trimethoprim: inhibit Folate reductase (DHF -\> THF rxn) 2. Bacterial Susceptibility/Uses: - Most gram (+)/(-) including CA-MRSA - *Nocardia, Pneumocytis jiroveci* = _AIDS pts_ - Primary drug for UTI - Secondary drug for upper/lower respiratory tract infections, sepsis, meningitis, travelers diarrhea, typhoid, cholera

Question 67

Trimethoprim-Sulfamethoxazole (Bactrium) (Adverse, Drug interactions)

Answer 67

1. Adverse: - Hypersensitivity rxn to SMX (Stevens-Johnson syndrome & Exfoliative dermatitis) - High doses (P. jiroveci in AIDS) = thrombocytopenia, neutropenia, allergic rxns & hyperkalemia 2. Drug interactions: - Sulfa drugs = CYP inhibitors: increase serum levels/toxicity of warfarin, phenytoin & oral sulfonylureas (for DM)

Question 68

Metronidazole (Flagyl) | (MOA, uses, adverse)

Answer 68

1. MOA: Disrupts DNA helical structure 2. Uses: - Antibacterial + Antiprotozoal - THE best drug for **anaerobic bacteria (including C. difficile colitis)** 3. Adverse: - Disulfiram-like effect (avoid alcohol)

Question 69

FDA Categories for Drug Use in Prenancy

Answer 69

A, B, C, D, X ## Footnote A = research shows no risk to human fetus B = animal studies no risk; animals studies show risk, but preg women no risk C = no available studies; animal studies show risk, but no women trials (most common category) D = fetal risk, but benefits outweigh risks X = definite fetal risk; outweighs benefits