Penicillins and Cephalosporins

Question 1

Prontosil Discovery

Answer 1

Sulphonamide

First effective antibiotic drug discovered by Gerhard Domagk in 1939

Question 2

Penicillin History

Answer 2

True miracle drug that revolutionized modern medicine. Nobel prize for discovery in 1945

Question 3

Gram+ vs Gram-

Answer 3

Gram - has a three layer envelope and stains red/pink

Gram + has a two layer envelope and stains blue/purple

Question 4

Types of antimicrobials

Answer 4

Natural antibiotics
Semi-synthetic
Synthetic Compounds

Question 5

B-Lactams

Answer 5

All are bacteriocidal
Penicillins and pinicillin analogues
Cefalosporins
Bind to pinicillin-binding proteins inhibit transpeptidases
Also stimulate autolysins to promote cell wall expansion.

Question 6

B-Lactam Resistance

Answer 6

B-lactamases
Reduced PBP's affinity for B-lactams
Changes in membrane permeability
Acquired tolerance
Gene transfer

Question 7

B-Lactam Side Effects

Answer 7

Low toxicity
Hypersensitivity/allergic reactions to penicillinoic acid
Up to 15% of adult population susceptible to anaphylaxis.

Question 8

Penicillins Pharmacokinetics

Answer 8

Excreted by renal tubular cells.
Short half life
Do no enter CNS except when the meninges is inflamed.

Question 9

Types of Penicillins

Answer 9

Natural Penicillins
Penicillin G for IV, and IM
Penicillin V for oral
Gram + only

Question 10

Semisynthetic Compounds

Answer 10

Nafcillin IV and IM
Dicloxacillin oral
Methicillin - no longer used

Question 11

Semi-synthetic extended spectrum

Answer 11

Amoxicillin/clavulanate - oral
Ampicillin/ sulbactam - IV
Piperacillin/tazobactam - oral, IV, IM
Extended gram + coverage and some gram -

Question 12

Synthetic Carbapenems

Answer 12

Imipenem/cilastatin
Broadest spectrum (90% of all strains)
Most gram+ and gram -
Rapidly degraded by renal dehydropeptidase, always co-administered with the inhibitor of this enzyme, cilastatin

Question 13

Clinical Use of Imipenem

Answer 13

Last line drug to minimize emerging resistance
Useful for life threatening infections previously treated with broad spectrum agents.
Some mixed infections to avoid multi-drug therapy.

Question 14

Semi-synthetic Monobactams

Answer 14

Aztreonam (azactam)

Activity spectrum: inhibits PBPs of gram - only, not against gram + strains

Question 15

Clinical Use of Monobactams

Answer 15

Broad gram - activity including pseudomanas
NOT affected by B-lactamases
No B-lactam-like allergic reaction
Used as safe alternative to B-lactam allergic patients w/ gram - infections

Question 16

Cephazolin (ancef) (IV and IM)

Cephalexin (keflex) (Oral)

Answer 16

First Generation Cephalosporins
Gram + and some Gram -
Used for Surgical Prophylaxis, UTIs, and ENT infections

Question 17

Cefuroxime (zinacef) - IV
Cefuroxime Axitel (ceftin) - Oral

Answer 17

Second Generation Cephalosporins
Intermediate Sepctrum (gram + and extended gram -)
Effective for infections due to influenza, E. coli, klebesilla, and other gram -

Question 18

Ceftriaxone (Rocephin) - IV, IM

Ceftazidim (Fortaz) - IV

Answer 18

Third Generation Cephalosporins
Broad Spectrum (gram + and extended gram -)
CNS penetration and long half-life
Surgical prophylaxis, meningitis, compilcated UTI’s, sepsis

Question 19

Cefepime (Maxiprime) - IV,IM

Answer 19

Very Broad Activity (Gram+, gram-, and aerobic)
Very broad activity
Most useful for nosocomial infection resistant to 3rd generation agents.

Question 20

B-Lactam Adverse Reactions

Answer 20

Immediate (<72 hr)

Late allergic reactions (days-weeks)

Question 21

Immediate Allergic Reactions (rare but serious)

Answer 21

IgE mediated
Penicillins > Cephalosporins
Anaphylaxis, wheezing, urticaria skin eruptions, hypotension
Rare (1:10,000 - 10% fatal)
Monobactams safe alternative for gram - infections

Question 22

Accelerated Allergic Reactions

Answer 22

Also IgE mediated (type 1)
Urticaria skin eruptions (most common)
Milder, no anaphylaxis, but rash

Question 23

Late Allergic Reactions

Type 2: IgG, IgM mediated

Answer 23

Long course of therapy

Hemolytic anemia, neutropenia, thrombocytopenia, nephritis

Question 24

Late Allergic Reactions

Type 3: Immune Complex Mediated

Answer 24

7-14 days into therapy
Drug Fever (B-lactams very common)