Which one is correct about the def. of Antibotic?

a. Agent, natural or synthetic that has the ability to kill or supress microorganism.

b. A chemical that is produced by one microbe and has the ability to harm other microbe

Answer is A.

Choice B is the definition of Antimicrobial Drug

Infection-- Present of organisms resutling in as immune response and/or destruction of the tissue

Colonization-- Present of organisms Not! resulting in pain or immune response or destruction of tissue.

Which one in the following has a ability to inhibit growth and replication of bacteria?

a. Bacteriostasis

b. Bacteriocidal

Answer A.

Bacteriocidal --> the ability to kill bacteria independent of the immune system.

Synergy !

Any combination of antimicrobials that when used together, increases the killing of an organism beyond that of either used alone 

**** (1+1 = 3)***

Antagonism

Any combination of antimicrobial that decrease the killing of an organism beyond that obtained from either used alone.

*** (1+1 = 0)***

Selective Toxicity

Ability of drug to insure a target cell or target organism w/o injuring other cells

Ex. Drug kills bacteria but not host!

Bacteriostasis--> inhibit bacteria

Bacteriocidal --> Kill bacteria

1. By organism (x2)

2. By mechanism of action (x7)

Describes antimivrobial classification by organism

Dividered into 2 subclasses

1. Narrow-spectrum: active only against few bugs

- Gram-positive cocci & bacilli

  Drugs: PCN, Erythromycin,    Clindamycin.

- Gram-negative aerobes

   Drug: Aminoglycosides, cephalosporins

2. Broad spectum: active against a variety of bugs

- Gram +cocci and Gram- bacilli

Drugs: Ampicilin, tetracycline, 3^rd generation cephalosposin

MOA (x7)

1. Inhibit cell wall synthesis --> activate enzyme that disturb cell wall; weaken cell wall and promote cell lysis [PCN, Cephalosporins]

2. Increase cell membrane permeability; leakage of intracellular material [Amphotericin B, Daptomycin]

3. CAuse lethal inhibition of BacT protein synthesis [Aminoglycosides]

4. Cause non lethal inhibition of protein synthesis; inhibit BacT protein synth ---only slows microbe growth. [Tetracycline]

5. Inhibit BacT synthesis of DNA/RNA ; distrup DNA synthesis---bind to nucleic acids or interacts with enzyme required for nucleic acid synthesis [Rifampin, Metronidazole, floroquinolones]

6. Antimetabolites; disrupt specific biochemical reaction so disrupt essential cell constituent or synthesis of nonfunctional analogs of normal metabolites [Trimethoprim, Sulfonamide]

7. Suppress viral replication ; inhibit specific enzyme-- DNA, reverse transcriptase, protease [Acyclovir, interferon alpha]

1. Gram stain +,-

2. Shape ; rod, cocci

3. Need for o₂ (aerobic or anaerobic)

4. Site of residence in host cells (intra/extracellular)

1. Minimum Inhibitory Concentration --> Lowest concentration of an antimicrobial agent that result in inhibition of visible growth (doesn't kill the BacT, just inhibit it)

2. Minimum Bactericidal Concentration --> Lowest concentration of the antibiotic that kill 99.9% of the original inoculum in a given time.

Beta-lactamases are enzyme produced by some bacteria and responsible for resistant to Beta-Lactam antibiotics

** Lactamase enzymes break the ring (beta-lactam ring) open, deactivating the molecule's antibacterial properties

**That's one of the reason why bacteria become resistant to Beta- lactam antibody (ex. penicillin)

Which drug is an antistaphylococcal?

a. Penicillin G

b. Nafcillin

c. Oxacillin

d. Cloxacillin

e. All of the above except A

Answer E.

Note..

• Antistaphylococcal is in a narrow spectrum penicillins
• Resistant to staph beta-lactamases; active against staph and strep; inactive against Enterococci anaerobes.

Antistaphylococcal = NOCD

N = Nafcillin

O = Oxacillin

C = Cloxacillin

D = Dicloxacilln

What is the weakness of antibiotic drug of broad-spectrum penillin?

Which gram bacteria does Ampicillin work against?

Gram -

1. Inactivation of antibiotic by beta-lactamase (most common)

2. Modification of target PBP's

3. Presence of efflux pump

4. Impair penetration of drug to target PBP's

** In gram(-), drug must get through the outer cell wall via protein channels or porins

What drug classes make up the beta-lactam family?

1. Penicillin

2. Cephalosporins

3. Carbapenems

4. Monobactams

Broad spectum penicillin.

- Ampicillin

- Amoxicillin

Penicillin G = 30 mins

Ampicillin (and extended spectum) = 1 hr

1. Narrow spectrum

  - Penicillin G and and V

  - Antistaphylococcal--> NOCD

2. Broad spectrum

   - Ampicillin, Amoxicillin---> treat gram (-)

3. Extended spectrum--> treat pseudomonal infection

   - Piperacillin, Ticarcillin

Which drug class is also known as " Aminopenicillin" ?

a. Broad spectrum (Amipicillin &Amoxcilin)

B. Extended spectrum (Piperacillin, Ticarcillin)

C. Narrow spectrum (Penicillin G, Nafcillin)

Penicillin G

"Drug of choice"

• Treat infection caused by strep., meningococci, some pneumococci
• IV form

DOC for Staph

• Antistaphylococcal !
• " NOCD"
• Narrow spectrum penicillinase resistant
• Limited by MRSA (Methicillin-resistant Staphylococcus aureus)

Doc for strep

• Penicillin G (IV)
• Penicillin V (Oral)

Aminopenicillins class

: Ampicillin, Amoxcillin

Due to hepersensitivity!

• Rashes- Most common reaction
• Ampicillin- rash in 50-100% pt w/EBV

Anaphylaxis reaction d/t Penicillin

1. Immediate (30-60 mins)--> uticaria (skin rash), anaphylaxis (<0.05%), laryngeal edema
2. Accelerated (1-72 h)---> urticaria: less severe
3. Late (>72 h)maculopopular rash, drug fever, hemolytic anemia, thrombocytopenia, interstitial nephrittis
4. Avoid all beta-lactam

Ampicillin

Cephalosporins

(Bactericidal)

• Share beta-lactam ring with penicillin
• Similar MOA and toxicity
• More stable than penicillin to many beta- lactamases--> Broader spectrum activity (but maybe susceptable to new beta-lactamase)

Which class of antimicorbial is more resistant to beta-lactamases and effective against Samonella typhi?

a. Cephalosporins

b. Beta-lactam family

c. Carbapenems

Recap.. Cephalosporins....!

1. More resistant to beta-lactamase enzume

2. Effective against Samonella typhi

3. Similar MOA and toxicity to Penicillin.

Cephalosorin Generation

(General perspective)

• Contains 5 generations
• Increase its effectiveness as its generation go higher
• Ex. 1st generation works against gram +; Strep, staph, pneumococci

1^st generation of

Cephalosporins

• Works against GRAM +
• Strep, Staph, Pneumococci
• Clinical use: UTI, minor staph injury, celluitis

Which drug class is best to treat only Klebsiellae but not pseudonomas?

a. Extended spectrum penicillin

b. 1^st of Cephalosporin

c. 2^nd of Cephalosporin

d. Broad spectrum penicillin

Answer C

It can't be choice A bcoz Extended spectrum penicillin treat both Klebsiellae and pseudomonas.

Which generation of Cephalosporins has activity aganist "Anaerobes"

a. 2

b.3

c.4

d.5

Answer A

Generation 2--> Bacteroides fragilis, bacteroides fragilis froup

Gram - & anaerobes

coverage

Describe when penicillin and cephalosporins should be avoid?

• Pt with anaphylaxis to penicillin should not get cephalosporins
• Pt with mild PCN allergy, cephalosporin can be used but at minimal concern
• Broader spectrum leads to opportunistic infection (C.diff)
• A few 2nd/ 3 rd, may cause hypothrombinemia

• Good for gram- rod, gram +, anaerobes!
• Imipenem--> used for highly penicilin resistant pneusodococci.
• New Drugs (DOMERER; doripenem, meropenem, ertapenem)---> used for nosocomial infection***
• Susceptable to metallo-beta-lactamase

What is an Aztreonam?

• Monobactams
• Monocyclic beta-lacyam ring
• GRAM- rod, no activity against gram + or anaerobes.
• Less toxic alternative to aminoglycoside

• Monocyclic bata-lactam ring
• Gram- rods, less toxic alternative to aminoglycosides.
• severe urinary or lower respiratory tract infections, skin, stomach, etc. (not elaborated on in slides, only that it is a Monobactam)
  

Which group is considered broadest spectrum of beta- lactases?

a. Carbapenems

b. Cephalosporins

c. Penicillin

d.Monobactams

Which one in the following is not bactericidal?

a. Penicillin

b. Macrolides

c. Carbapenems

d. Cephalosporins

e. Glycopeptides

Answer B.

Macrolides is bacteriostasic, MOA---> inhibit protein synthesis of bacteria.

What new drug is availible to treat vancomycin resistant enterococci (VRE)?

a. Metronidazole

b. Linezolid

c. Ertapenems

d. Ampicillin

If the pt come in with Salmonella, what antimicrobial would you give the pt.?

a. Ampicillin

b. Amoxicillin

c. Linezolid

d. Telavancin

e. a,b are correct

What is a MOA of Tetracycline?

Is Tetracycline a bacterostatic or bactericidal or both?

What is a MOA of Macrolides? and Is it bacteriostatic or -cidal?

Which class of drugs inhibit protein sunthesis in three ways and is bactericidal? 

a. Tetracycline

b. Streptogramins

c. Aminoglycosides

d. Macrolides

Answer Tetracycline - for sure!

It could also be Macrolides bcoz it can be either one.

Which one in following is bacteriostatic?

a. Streptogramins

b. Chloramphenicol

c. Tetracycline

d. Ampicillin

Answer is C.

Note...

Streptogramins---> bind to 50s subunit of ribosomal  and it's bactericidal!

Which Tetracycline has a long-acting?

a. Doxycycline

b. Tetracycline

c. Demeclocycline

d. Minocycline

e. Choice a,d are correct

Answer E

Doxycycline and Minocycline have a long-active, t_1/2 16/18 h

Intermediate acting of Tetracycline?

1. Efflux of by active transport protien pump encoded on plasmid***

2. Ribosomal protection by protein-> Tetracycline can no longer bind with ribosomal subunits.

3. Enzymatic inactivity.

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If your pt has staph infection and also allergic to penicillin, what drug will u give the pt. in substitute to penicillin?

a. Macrolide

b. Tetracycline

c. Aminoglycoside

d. Cephalosporins

Answer A

Macrolide contains 3 drugs: Erythronmycin (prototype), Clarithromycin, Azithromycin

Treat: Gram +, esp. pneumococci, streptococci, staphlococci, coryne bacteria

DOC: Diphtheria, all Chlamydial infection, CAP

What drug has an unique pharmacokinetic?

a. Azithromycin

b. Doxycycline

c. Erythromycin

c. Clarithromycin

Name 3 major drugs includeed in the macrolide classification

Which drug has fewer drug interaction and unique pharmacokenetic?

a. Erythromycin

b. Clarithromycin

c. Azithromycin

1. Fewer drug interaction

2. Penetrate tissues

3. t_1/2 3days, permits daily dosing, short treatment.

List 2 main toxocities associated with aminoglycosides antibiotics.

1. Ototoxicity---> (1-5%, irreversible)

2. Nephrotoxicity---> (5-25%, reversible)

What drug has dual MOA?

Describe the main clinical use of Aminoglycosides

Which one the following is not in aminoplycosides group?

a. Streptomycin

b. Neomycin

c. Gentamicin

d. Azithromycin

Answer is D

Azithromycin is in Macrolides class (has unique pharmacokinetic)

Aminoglycoside***

Azithromycin

Think of beta- lactam family & Macrolides.

• Penicillin
• Cephylosporins
• Erythromycin
• Azithromycin
• Clarithromycin

• Fluoroquinolones
• Tetracyclines

TB drug called " Izoniazid" can cause pyridoxine deficiency which leads to peripheral neuropathy. Thus, pt who are disposed to neuropathy should receive pyridoxine

***Prevent development of peripheral neuropathy.

Induction phase of TB therapy

Think...... R.I.P.E (for 2 months)

R= Rifampin

I= Isoniazid

P= Pyrazinaminde

E= Ethambutol

Continuation phase of TB therapy

Think....... IR   (4 months)

I= Isoniazid

R= Rifampin

What pathogen are responsible for CAP?

S. pneumonia (Strep)= gram +

M. pneumonia = Atyp

What pathogens are responsible for AECB?

H. influenza = gram -

S. pneumoniae = gram +

What pathogens are responsible for Rhinosinustitis?

H. influenza = gram -

S. pneumonia = gram +

Which gram usually involves with UTIs?

Gram -

Levofloxacin    

Sparfloxacin

What is the first-choice drug for uncomplicated UTIs in women?

a. Levofloxacin

b. Ciprofloxacin

c. Trimethoprim-sulfamethoxazole

d. Macrolide

e. Choice a,b are correct

How long should the treatment for uncomplicated UTIs be given?

Which antibacterial agent is used to treat bacteriemia, sepsis?

a. Macrolides

b. Glycopeptides

c. Aminoglycoside

d. Fluroquinolones

Drugs the provide good coverage for anaerobes?

Think----> TIM-C

T= tetracyclines (whole class; broad spectrum)

I = Imipenem (Carbapenem class)

M= Metronidazole

** C=  Cephamycin (Cephalosporins;2 nd generation)

*** Likely occur with any Broad spectrum 

• 2nd-3rd gen of cephalosporins-> bcoz these 2 gen. are more effective against gram - than gram +. Thus, superinfection may occur!

*C. difficile and Pseudomembranous colitis**

Strongly prefered: Metronidazole

Alternative drug: Oral Vancomycin

Fidaxomycin (macroglide)** New drug

What is the first line therapy for otitis media?

a. Amoxicillin

b. Cefpodoxine proxetil

c. Cefuromine axetil

d. Cefzil

Answer A.

***Amoxicillin, Amoxicillin clavulanate

• 2nd gen. Cephalosporins: Cefuroxine axetil
• 3rd gen. Cephalosporins: Cefpodoxine proxetil, Cefdinir

• High dose amoxicillin
• Amoxicillin-clavulanate
• Cefuroxime (2nd)
• Cefprozil

• E.coli= enteric gram negative bacillus
• Fluoroquinoles: Ciprofloxacin (children and pregnant)
• Macrolide: Azithromycin

   PCN: Extended Specrum Antipseudomonials – Piperacillin, Ticarcillin;4^th Generation Cephalosporins.

• (gram positive cocci)
• PCN: Narrow Spectrum Antistaphylococcus – Nafcillin.

    Amantidine and Aminopenicillins

*Amantidine is also used in Parkinson’s disease and antiviral therapy

·       Microbes may elaborate drug-metabolizing enzymes

o   E.g., increased production of pencillinase so able to inactivate several different kinds of antibiotics.

·       Microbe may cease active uptake of certain drugs.

·       Microbial drug receptors may undergo change, resulting in decreased antibiotic binding and action.

o   Undergo structural changes in bacterial ribosome.

·       Microbe may synthesize compounds that antagonize drug actions.

o   E.g., acquiring ability to synthesize increased quantities of PABA, bacteria have developed resistance to sulfonamides.

o   The microorganism increases production of PABA to outweight sulfonamides activity, allowing it to continue folic acid synthesis, which is necessary for bacterial DNA synthesis.

12 steps to dely resistance 

Key features that distinguish atypical organism (i.e. Mycoplama, chlamydia).

Which one in the following is not an atypical organism?

a. Mycoplamas

b. E.coli

c. Chlamydia

• AE of Trimethoprim-sulfamethoxazole and Telaprevir
• ~ 1%
• Fatal skin reaction & mucus membranes that result in erythema (redness), and may appear as papules, nodule, or macule, may ahve vesicle formation and target or iris shaped lesion.

Antimetabolites ---> Trimethoprim-sulfamethoxazole,

Hep C drug -->Telaprevir 

1. Metronidazole
2. Vancomycin (oral)

What is empiric therapy?

" Match the drug with the bug " 

• Treat by knowledge of where the microbe are likely to be found, but need culture and sensitivity result to be sure
• Medical term referrring to the initiation of treatment prior to determination of a firm diagnosis.

1. Allergic to DOC
2. Inability of DOC to penetrate the site of infection.
3. Unusual pt susceptibility to toxicity of DOC

Amphotericin B is used to treat systemic fungal infections

These are lipid based formulations that improve toxicity profile somewhat but are very expensive.­

DOC for Cellulitis & Impetigo

·       1^st and 2^nd generation Cephalosporins, PCN, Dicloxcillian PCN are also used for cellulitis and impetigo.

·       Fluconazole (Diflucan) and others include Miconazole (Monistat) and Clotrimazole (Lotrimin)