Finals: 3.1 Antibacterial Agents

Cell membrane of a bacteria is a…

Phospholipid bilayer

Major structural polymer in most bacterial cell walls

Peptidoglycan

TRUE OR FALSE: Bacteria have nuclear membrane

False

Gram positive: Layer of peptidoglyan?

Thick layer

Gram negative: Layer of peptidoglycan?

Thin Layer + Outer membrane

Peptidoglycans, hydrophilic or hydrophobic

Hydrophilic

Which is harder to combat, Gram positive or Gram negative

Gram negative

Why is it harder to combat Gram negative bacteria?

Because of its cell wall

Components of Peptidoglycans

N-acetylglucosamine and N-acetylmuramic acid

Tetrapeptides that make peptidoglycans tougher

L-alanine, D-alanine, L-lysine, D-glutamine

Advantages of narrow spectrum

target specific organisms (not used in some countries (i.e. Philippines)

Disadvantages of wide spectrum

affect the other commensal/non-pathogenic

Penicillium mold scientific name

*Penicillium chrysogenum*

Person to discover Penicillin

Alexander Flemming

Basic structures of Penicillin

1. Thiazolidine ring (contains sulfur)
2. Beta-lactam ring (carries secondary amino group)

TRUE OR FALSE: Penicillin can cross the BBB when meninges are inflamed

True

TRUE OR FALSE: Penicillin must be given on an empty stomach

True

Exception for Penicillin to NOT be given on an empty stomach

Amoxicillin

Penicillin, bactericidal or bacteriostatic

Bactericidal

Penicillin mechanism of action

1. Binds to Penicillin-binding Proteins
2. Inhibits transpeptidation
3. Activation of autolytic enzymes (lesions)

Ways in which bacteria can be resistant to Penicillin

1. Hydrolysis of beta-lactam ring by **beta lactamase**
2. Modification of PBP
3. Changes in membrane permeability

Narrow spectrum penicillinase susceptible agents

1. Penicillin G
2. Penicillin V

Penicillin G diseases

* Streptococci
* Meningococci
* Spirochetes (STDs)
* Enterococci
* Pneumococci
* **Anaerobes**

First line drug for Syphilis

Benzathine Penicillin G

Penicillin G intake

Intramuscularly

Penicillin V intake

Orally

Very Narrow spectrum penicillinase resistant agents

1. Methicillin
2. Oxacillin
3. Cloxacillin

Penicillins that are taken orally

1. Penicillin V
2. Dicloxacillin
3. **Amoxicillin**

Drugs for skin infections

1. Methicillin
2. Oxacillin
3. Cloxacillin

Wider spectrum penicillinase susceptible drugs

1. Ampicillin
2. Amoxicillin

\

1. Piperacillin
2. Ticarcillin

Drugs that are acid-stable and relatively well absorbed

* Dicloxacillin
* Ampicillin
* Amoxicillin

How long do oral penicillins have to be administered before a meal?

1–2 hours before or after a meal

Drugs that are ONLY cleared through billary

Nafcillin

Drugs eliminated through BOTH renal and biliary

* Oxacillin
* Dicloxacillin
* Cloxacillin

Drug suitable for treatment of mild to moderate localized staphylococcal infections

Dicloxacillin

The first antistaphylococcal penicillin to be developed,

Methicillin

Drugs of choice for serious staphylococcal infections such as endocarditis.

* Oxacillin
* Nafcillin

Example of an isoxazolyl penicillin 

Dicloxacillin

Drugs used for **Penicillins Resistant to Staphylococcal Beta-Lactamase**

1. Methicillin
2. Oxacillin
3. Nafcillin
4. Dicloxacillin

Extended-Spectrum Penicillins

* Aminopenicillins,
* Ampicillin
* Amoxicillin
* Carboxypenicillins, and
* Ureidopenicillins

Aminopenicillin drugs

1. Ampicillin
2. Amoxicillin

Amoxicillin diseases

* Bacterial sinusitis,
* otitis, and
* lower respiratory tract infections

Drugs that are the most active of the oral β-lactam antibiotics against pneumococci with elevated MICs to penicillin and are the **preferred β-lactam antibiotics for treating infections suspected to be caused by these strains**

1. Ampicillin
2. Amoxicillin

Drug effective against susceptible strains of *Shigella*.

Ampicillin

Ampicillin diseases

* **Anaerobes**
* Enterococci
* L monocytogenes

Diseases Ampicillin is NOT active against

* *Klebsiella* sp, 
* *Enterobacter* sp, 
* *P aeruginosa*, 
* *Citrobacter* sp, 
* *Serratia marcescens*,
* indole-positive *Proteus* species, and
* other gram-negative aerobes that are commonly encountered in hospital-acquired infections.

Carboxypenicillin drugs

1. Carbenicillin
2. Ticarcillin

Ureidopenicillin

1. Pipercillin

Pipercillin diseases

* *Klebsiella pneumoniae* and 
* *P aeruginosa*.

Ampicillin, amoxicillin, and piperacillin are available in combination with one of several β-lactamase inhibitors…

* **sulbactam,** 
* **clavulanic acid,** or 
* **tazobactam**

Drugs associated with **interstitial nephritis**

1. Methicillin
2. Nafcillin

Drug associated with **Hepatitis**

1. Oxacillin

Drugs associated with skin rashes when prescribed in the setting of viral illnesses, particularly noted during acute Epstein-Barr virus infection

1. Ampicillin
2. Amoxicillin

First generation Cephalosporins

1. **cefazolin,** 
2. **cefadroxil,** 
3. **cephalexin,** 
4. **cephalothin,** 
5. **cephapirin, and** 
6. **cephradine**

**Cefazolin** generation

First Gen

**Cephalexin generation**

First Gen

Cefadroxil generation

First Gen

Cephalothin generation

First Gen

Cephapirin generation

First Gen

Cephradine generation

First Gen

1st Gen Cephalosporins Diseases

* gram-positive cocci, such as streptococci and staphylococci.

1st Gen Cephalosporin taken Orally

* Cephalexin

The only first Gen Cephalosporin generally used

* Cefazolin

Cephalexin excretion

Urine

Cefazolin excretion

Urine

R group at 7-position function for Cephalosporins

alters antibacterial activity

R group at 3-position function for Cephalosporins

modifies pharmacokinetic profile

**Drug of choice for surgical prophylaxis** and for many streptococcal and staphylococcal infections requiring intravenous therapy.

* Cefazolin

Cefazolin diseases

* E. coli
* K. pneumoniae

Cefazolin intake

Intravenous and Intramuscularly

Cephalexin intake

Oral

TRUE OR FALSE: Cefazolin cannot penetrate the CNS to treat meningitis

True

Second Generation Cephalosporins

1. cefaclor, 
2. cefamandole, 
3. cefonicid, 
4. **cefuroxime,** 
5. cefprozil, 
6. Cefoxitin
7. Cefotetan
8. loracarbef, and 
9. ceforanide

Cefaclor generation

Second gen

Cefamandole generation

Second gen

Cefonicid generation

Second gen

**Cefuroxime** generation

Second gen

Cefprozil generation

Second gen

Loracarbef generation

Second gen

Ceforanide generation

Second gen

Cefoxitin generation

Second gen

Cefotetan generation

Second gen

Cefoxitin and Cefotetan have activity against… but less active against…

Anaerobes, Serratia, and B. fragilis…

\
H. influenzae

Cefuroxime and Cefaclor are active against… but not against…

H. influenzae…

\
Serratia and B. fragilis

TRUE OR FALSE: First and second generation Cephalosporins are active against Enterococci and P. aeruginosa

False

Oral 2nd Gen Cephalosporin

Cefuroxime

All 2nd Gen Cephalosporins excretion

Urine

2nd Gen Cephalosporin diseases that can produce Beta-lactamase

H influenzae and Moraxella catarrhalis

Cefuroxime diseases

* H influenzae
* Moraxella catarrhalis
* Sinusitis
* Otitis
* Lower respiratory tract infections

Cefoxitin and Cefotetan diseases

* Anaerobes
* peritonitis,
* diverticulitis, and
* pelvic inflammatory disease.

1st Gen Cephalosporins coverage

* Gr(+) cocci,
* E. coli,
* K pneumoniae, and
* Proteus mirabilis

2nd Gen Cephalosporins coverage

* same as 1st gen but with extended Gr(-) activity -
* Klebsiella,
* H. influenzae,
* Bacteroides fragilis,
* Serratia

3rd Gen Cephalosporins coverage

* Expanded Gram-negative coverage:
* Citrobacter,
* serratia,
* providencia,
* Pseudomonas (Ceftazidime)

*Less activity na sila for these*

4th Gen Cephalosporins coverage

* Pseudomonas,
* Enterobacteriaceae,
* methicillin-susceptible S. aureus, S. pneumoniae,
* Haemophilus and
* Neisseria sp

3rd Gen Cephalosporin Drugs

1. cefoperazone, 
2. cefotaxime, 
3. ceftazidime, 
4. ceftizoxime, 
5. **ceftriaxone,** 
6. cefixime, 
7. cefpodoxime proxetil, 
8. cefdinir, 
9. cefditoren pivoxil, 
10. ceftibuten, and 
11. moxalactam

1st Gen Prototype drug

* Cephalexin

2nd Gen Prototype drug

* Cefuroxime

3rd Gen Prototype drug

* Ceftriaxone

Only Cephalosporin that is active against P aeruginosa

* Ceftazidime

3rd Gen Cephalosporin drug to treat UTI

* Cefixime