Antibiotics Flashcards
What are the major antibiotic catagories?
Beta-lactams (penicillins, cephalosporins, carbapenens)
Macrolides and clindamycin
Tetracyclines/glycylcyclines
Glycopeptides
Aminoglycosides
Quinolones
Sulfonamides and trimethoprim
Metronidazole
Linezolid
How is the mechanism of action of penicillins?
Penicillins bind to peniciilin-binding protein (PBP), resulting in inhibition of peptidoglycon synthesis and activation of autolytic enzymes in cell wall
How does resistance to penicillins develop?
Production of beta-lactamase (increased drug break down)
Lack of penicillin binding proteins
Efflux of drug out of the cell
What is the basic component of all penicillins?
The all share the same basic structure, 6-aminopeniciilanic acid (thiozolidine ring attached to a beta-lactam ring)
What are some natural penicillins?
Penicillin G:
Destroyed by stomach acid, so it is only given IV or IM
Destroyed by beta-lactamases
Procaine and benzathine can prolong the effect of penicillin
Penicillin V:
More acid stable, but still needs to be taken on an empty stomach
What infections are treated with penicillin as the drug of choice?
Streptococci, pneumonococci, meningococci, spirochetes, clostridia, anaerobic gram+ rods and actinomyces
enterococci (hard to treat, but penicillin id best agent)
What are isoxazolyl penicillins (“anti-staphylococcus penicillins”)?
These penicillins have relative resistance to beta-lactamases and are designed to treat Staph aureus.
Not intended to be used for other gram + microorganisms like strep or pneumo. Ineffective against MRSA
ex. Methicillin, Cloxicillin, (Flucloxicillin, Dicloxicillin: not covered in sask)
What are aminopenicillins?
They are active against both gram + and - organism
Ampicillin: used IV, more acid stabile than natural penicillins, but cannot be used orally due to low bioavailability
Amoxicillin: used orally (better absorption vs. ampicillin). Often combined with clavulanic acid (b-lactamase inhibitor)
Use (gram positive): Strep, enterococci, Neisseria sp.
Use (gram negative):
non-b-lactamase producing H. influenzae, E. coli, P. mirabilis, Salmonella, etc
What are b-lactamases?
Beta-lactamases open the beta-lactam ring found in penicillins and cephalosporins and become inactive
What are some b-lactamases that are of particular interest?
b-lactamases of interest:
ESBLs (extended-spectrum b-lactamases): They are found in E. coli and K. pneumonia infections of the urinary tract. ESBLs show resistance against b-lactamase inhibitors
NDM-like (New Delhi metallo-beta-lactamase)
ex. acinetobacter baumannii. NDM-like b-lactamases have a grearer ability to destroy b-lactamase inhibitors vs. ESBLs
What are ureidopenicillins?
They are broad spectrum, but have increased activity against gram - rods
Piperacillin is used parenterally against P. aeruginosa
Sometimes combined with b-lactamase inhibitor (tazobactam)
What are some general pharmacokinetics among penicillins?
Oral bioavailability varies between different types of penicillins (some penicillins are IV only like Pen G)
Wide distribution of drugs across body including CNS
Most are excreted by the kidney (need multiple doses/day)
Most oral penicillins should be taken on empty stomach (except amoxicillin)
Safe for pregnant and lactating women
What is a drug interaction with penicillins?
Penicillins can reduce the efficacy of oral contraception. Unplanned pregnancies are rare, but possible
What administration route for penicillins is the most effective?
If disregarding patient comfort and convienence, we can give penicillins via IV for best pharmacodynamic effect. The IV is supplying drug continuously (used in severe conditions)
What are some adverse effects following the use of penicillins?
Allergic reactions (most reported are not real allergies)
Anaphylactic shock, serum sickness, and fever should be taken seriously and get MD to take a look
Seizurem encephalopathy delirium
Neutropenia, thrombocytopenia )seen in longer duration use of penicillins)
What are cephalosporins?
They are a class of drugs that are structurally characterized by the core molecule (7-aminocephalosporanic acid)
They have similar mechanism of action compared to penicillins
Resistance:
Organisms that lack penicillin binding protein (PBP)
b-lactamases produced by Staph aureus and gram negative bacilli
Drug Efflux
Inability of drug to penetrate
What are first-generation cephalosporins?
Oral: cephalexin, cefadroxil
IV/IM: cefazolin
Active against gram positive cocci and some gram negative bacilli (E.coli, Proteus, and Klebisella)
These drugs do not penetrate CNS, therefore do not use in meningitis
They are not the DOC for any condition except for cefazolin for surgical prophylaxis
What are second-generation cephalosporins?
Oral: Cefuroxime axetil, cefprozil
IV/IM: cefuroxime
Active against organisms covered by first generation cephalosporins + greater coverage of gnb (H. influenzae), but not P. aeruginosa
What are cephamycins?
Cefoxitin is a cephamycin and it is associated with second generation cephalosporins.
Cephamycins are used in mixed aerobic/anaerobic infections (found in diabetic foot infections or punctured pancreas)
What are third generation cephalosporins?
These drugs are the most commonly used cephalosporins. Most are IV drugs except cefixime
ex. Cefotaxime, cefttriaxone
Ceftazidime (reserved for P. aeruginosa)
Decreased activity activity against gram positive cocci except Strep pneumoniae
Enhanced activity against hram negative bacilli
Ability to penetrate the CNS (unlike first and second generation cephalosporins)
What are fourth generation cephalosporins?
Cefapime (enhanced activity against Enterobacter and Citrobacter); active against P. aeruginosa (Cefapime is almost reserved for P. aeruginosa)
What are fifth generation cephalosporins?
Ceftaroline and ceftobiprole have actvity against MRSA, ampicillin sensitive E. faecalis and penicillin resistance S. pneumonia
Due to their usefullness and broad-spectrum, they are rarely prescribed
What are some adverse effects associated with cephalosporins?
Cephalosporins in general are considered to be safe
Hypersensitivity
Diarrhea
Skin rash
Fever, granulocytopenia, hemolytic anemia
Gallstones after ceftriazone use
What are carbapenems?
These drusg are very broad spectrum, useful but are extremely susceptioble to resistance
Structurally related to beta-lactams
Imipenem-cilastatin and meropenem:
Activity against gram positive and gram negtive, including Pseudomonas and anaerobic organisms
Ertapenem (long half-life):
Poor activity against Enterococcus sp. and P. aeruginosa
What are monobactams?
They are characterized by monocyclic beta-lactam ring
Resistant to most beta-lactamases (Not active against ESBLs or AmpC b-lactamases)
Need Special Drug Acess to recieve Azteonam, but it is active against gram negative bacilli including P. aeruginosa
What are macrolides?
They are generally bacteriostatic and work by attaching to bacterial ribosomes and inhibiting protein synthesis.
ex. Erythromycin, clarithromycin, and azithromycin
These drugs are reserved for penicillin allergic patients die to side effect profile
Resistance:
Methylated rRNA receptor
Inactivating enzymes
Active Efflux
What is the spectrum of activity for macrolides?
Gram positive:
pneumococci, streptococci, and corynebacteria
ex. M. pneumoniae, Chlamydia trachomatis, C. pneumonophillia
Bordatella pertussis, Campylobacter jejuni, and Helicobacter pylori
What is erythromycin?
It is a macrolide and it is available as an IV or oral drug. IV formulations can cause phlebitis (burned veins)
Adverse effects:
GI (patients vomit out doses)
Cholestatic hepatitis (especially increased with estolate formulation of erthryomycin)
