Penicillins and Cephalosporins Flashcards
Prontosil Discovery
Sulphonamide
First effective antibiotic drug discovered by Gerhard Domagk in 1939
Penicillin History
True miracle drug that revolutionized modern medicine. Nobel prize for discovery in 1945
Gram+ vs Gram-
Gram - has a three layer envelope and stains red/pink
Gram + has a two layer envelope and stains blue/purple
Types of antimicrobials
Natural antibiotics
Semi-synthetic
Synthetic Compounds
B-Lactams
All are bacteriocidal
Penicillins and pinicillin analogues
Cefalosporins
Bind to pinicillin-binding proteins inhibit transpeptidases
Also stimulate autolysins to promote cell wall expansion.
B-Lactam Resistance
B-lactamases Reduced PBP's affinity for B-lactams Changes in membrane permeability Acquired tolerance Gene transfer
B-Lactam Side Effects
Low toxicity
Hypersensitivity/allergic reactions to penicillinoic acid
Up to 15% of adult population susceptible to anaphylaxis.
Penicillins Pharmacokinetics
Excreted by renal tubular cells.
Short half life
Do no enter CNS except when the meninges is inflamed.
Types of Penicillins
Natural Penicillins
Penicillin G for IV, and IM
Penicillin V for oral
Gram + only
Semisynthetic Compounds
Nafcillin IV and IM
Dicloxacillin oral
Methicillin - no longer used
Semi-synthetic extended spectrum
Amoxicillin/clavulanate - oral
Ampicillin/ sulbactam - IV
Piperacillin/tazobactam - oral, IV, IM
Extended gram + coverage and some gram -
Synthetic Carbapenems
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
Clinical Use of Imipenem
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.
Semi-synthetic Monobactams
Aztreonam (azactam)
Activity spectrum: inhibits PBPs of gram - only, not against gram + strains
Clinical Use of Monobactams
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
Cephazolin (ancef) (IV and IM)
Cephalexin (keflex) (Oral)
First Generation Cephalosporins
Gram + and some Gram -
Used for Surgical Prophylaxis, UTIs, and ENT infections
Cefuroxime (zinacef) - IV Cefuroxime Axitel (ceftin) - Oral
Second Generation Cephalosporins
Intermediate Sepctrum (gram + and extended gram -)
Effective for infections due to influenza, E. coli, klebesilla, and other gram -
Ceftriaxone (Rocephin) - IV, IM
Ceftazidim (Fortaz) - IV
Third Generation Cephalosporins
Broad Spectrum (gram + and extended gram -)
CNS penetration and long half-life
Surgical prophylaxis, meningitis, compilcated UTI’s, sepsis
Cefepime (Maxiprime) - IV,IM
Very Broad Activity (Gram+, gram-, and aerobic)
Very broad activity
Most useful for nosocomial infection resistant to 3rd generation agents.
B-Lactam Adverse Reactions
Immediate (<72 hr)
Late allergic reactions (days-weeks)
Immediate Allergic Reactions (rare but serious)
IgE mediated
Penicillins > Cephalosporins
Anaphylaxis, wheezing, urticaria skin eruptions, hypotension
Rare (1:10,000 - 10% fatal)
Monobactams safe alternative for gram - infections
Accelerated Allergic Reactions
Also IgE mediated (type 1)
Urticaria skin eruptions (most common)
Milder, no anaphylaxis, but rash
Late Allergic Reactions
Type 2: IgG, IgM mediated
Long course of therapy
Hemolytic anemia, neutropenia, thrombocytopenia, nephritis
Late Allergic Reactions
Type 3: Immune Complex Mediated
7-14 days into therapy Drug Fever (B-lactams very common)
