Beta Lactam Antibiotics

Question 1

Beta Lactam Antibiotics

Answer 1

most commonly prescribed antibiotics.
structure consist of the beta-lactam ring, essential for the activity of the antibiotic against a pathogen.
work by inhibiting cell wall biosynthesis in the bacterial organism.

Question 2

Mechanism of Action

Answer 2

Bactericidal to growing bacteria
Interferes with transpeptidation of cell wall synthesis
bind to a family of related enzymes that are called—penicillin binding proteins (PBPs)‏
and inhibit transpeptidation which stops the cross-linking of polysaccharides, the cell wall is destroyed and the bacterial cell dies.

Question 3

Beta-Lactam Compounds Classes

Answer 3

Penicillins
Cephalosporins
Beta-Lactamase Inhibitors- combined w/ PCN’s

Question 4

Combinations w/ beta-lactamase inhibitors

Answer 4

amoxacillin/potassium clavulanate (Augmentin)
ampicillin/sulbactam (unasyn)
Ticarcillin/potassium clavulanate (Timentin)
Piperacillin & tazobactam sodium (Zosyn)

Question 5

PCNs General Points

Answer 5

ALL antibiotics cause interference with protective effects of normal host microflora

Except for oral amoxacillin PCNs should be given on an empty stomach

PCNs can cause encephalopathy: somnolence, stupor, coma, seizures; rare, mainly seen with high doses

GI reactions especially diarrhea most frequent complaint; remember ALL antibiotics can cause Clostridium difficile colitis

Question 6

Penicillin G

Answer 6

Use: Treatment of infections (including sepsis, pneumonia, pericarditis, endocarditis, meningitis, anthrax)

Active against:
Gram-positive cocci (streptococci, staphylococci)
Gram-positive rods (Listeria, actinomyces)
Gram-negative cocci (Neisseria)
Most anaerobes (clostridium)
NOT for Gonorrhea!!

Question 7

Penicillin G Adverse Reactions

Answer 7

Central nervous system (high doses): Coma, hyperreflexia, myoclonus, seizure

Hematologic & oncologic: Neutropenia, positive direct Coombs test (rare, high doses)

Hypersensitivity: Anaphylaxis, hypersensitivity reaction (immediate and delayed), serum sickness

Renal (high doses): Acute interstitial nephritis, renal tubular disease

Contraindications: Hypersensitivity to penicillin or any component of the formulation

Question 8

Antistaphylococcal PCNs

Answer 8

Dicloxacillin
Oxacillin
Nafcillin

Question 9

Second Generation PCNs (AMOXICILLIN)

Answer 9

Use: treat otitis, sinusitis, lower RTI
Amoxicillin can be combined with clavulanic acid (Augmentin) which is a beta-lactamase inh so expands coverage to cover gram-pos, gram-neg and anaerobic organisms

Question 10

Second Generation PCNs adverse reactions

Answer 10

Anaphylaxis
Central nervous system
Hematologic: Agranulocytosis, anemia, eosinophilia, hemolytic anemia, leukopenia,thrombocytopenia, thrombocytopenia purpura
Renal: Crystalluria

Question 11

Third Generation PCNs

Answer 11

carbenicillin and Ticarcillin

IV only

Question 12

Fourth Generation PCN

Answer 12

piperacillin

IV

Question 13

PCN Pearls

Answer 13

PCNs can cause bleeding problems
Can cause interstitial nephritis—autoim-mune reaction to a penicillin-protein complex
PCN high doses can cause neurological complications and seizures
Common to see secondary infections such as vaginal candidiasis

Question 14

Beta-Lactamase Inhibitors

Answer 14

Drugs: clavulanic acid, sulbactam, tazobactam
Activity: inhibitors of many bacterial beta-lactamases
Inactivate aminoglycosides
Use: only in combination with a PCN, activity spectrum determined by that PCN
Intra-abdominal/gynecological infections
Skin and soft tissue infections
RTI, sinusitis and lung abscesses

Question 15

Beta-Lactamase Inhibitors Dosage

Answer 15

Amoxacillin-clavulanic acid (Augmentin)
500-875mg q 12h
20-40 mg/kg/d q8-12h

Piperacillin-tazobactam (Zosyn) Dosage
Ampicillin-sulbactam (Unasyn) Dosage Ticarcillin + clavulanate (Timectin)

Question 16

Cephalosporins

Answer 16

Progression from 1st to 3rd “generation”:
An increase in gram-negative coverage
A loss in gram-positive coverage

Well absorbed from the GI tract—food enhances absorption

Question 17

1st Generation Cephalosporins

Answer 17

Drugs: cefadroxil oldest,* cephalexin (Keflex) and *cefazolin (Ancef)– still used a lot

Activity: good activity vs. gram positive organisms such as streptococcus and staphylococcus (not MRSA), some gram negative activity; good against anaerobic cocci (eg, peptococcus, peptostreptococcus)

Cephalexin: uncomplicated cellulitis
Cefazolin: IV prophylaxis prior to surgery

Question 18

2nd Generation Cephalosporins

Answer 18

*cefuroxime (ceftin
Activity: active against gram-pos cocci, but also Better gram negative coverage Klebsiellae, H. influenzae, none against Pseudomonas

Question 19

3rd Generation Cephalosporins

Answer 19

ceftriaxone (Rocephin)… used to treat gonorrhea

IV only

Question 20

4th Generation Cephalosporin

Answer 20

Drug:*cefepime
Activity: Gram positive and negative, including pseudomonas

Question 21

General Points Cephalosporins

Answer 21

1st generation cephalosporins , cephalexin (Keflex) and cefazolin (Ancef) still used a lot

2nd generation cephalosporins are used to treat otitis, sinusitis and RTI (ceftin)

3rd & 4th generation cephalosporins:
drugs of choice for gram-neg meningitis
good alternative to aminoglycosides
need to watch for resistance strains so sometimes combination therapy best especially w/ pseudomonas
Ceftriaxone DOC for gonorrhea
Ceftazidime is effective in pseudomonas meningitis