Penicillins Flashcards
What year and by who were penicillins discovered
1928, Alexander Flemming
What are 4 ways abx resistance is mediated(caused)?
1.Production and excretion of an enzyme that hydrolyzes the antimicrobial
2.Genetic alteration of the microbial site where antimicrobial binds
3.Alteration in cellular membrane proteins that prevent antimicrobials from penetrating into microbial cells
4.Transmembrane efflux pumps that transport antimicrobials from interior to exterior of the microbial cells
What is VRE and when did it emerge
vancomycin-resistant enterococci - emerged in 1980
What is CRE and when did it emerge
carbapenem-resistant enterobacterales - emerged in 2000s
Leading Risk Factors for having a drug-resistant pathogen:
Recent use of antimicrobials
Multiple medical comorbidities
Recent hospitalization or other skilled healthcare contact
Antibiotic Stewardship Strategies
Treatment for specific infectious disease
Formulary restrictions
Dose optimization
Prospective audits
Continuing education for prescribers
Define Antimicrobial:
The entire arsenal of drugs that have the activity to inhibit or kill microbes.
Define Antibiotic or Antibacterial
Specifically refers to antimicrobials that target bacteria
Define Bactericidal
Refers to 99.9% eradication of a bacterial colony in vitro in 24 hrs by an antimicrobial.
-No clinical utility in the designation. Not to be used for clinical decision-making.
Define Bacteriostatic:
Refers to an abx that kills bacteria but the result is less than 99.9% eradication in a 24hr period.
-No clinical utility in the designation. Not to be used for clinical decision-making.
What are Beta Lactams and what are they most effective at treating
Super class of abx and contains the most abx’s of any class. Most effective against rapidly replicating organisms.
What are the 4 major groups of abx within beta-lactams
Penicillins
Cephalosporins
Carbapenems
Monobactams
What is the active part of the beta-lactam abx
a 4-member ring known as the beta-lactam ring
What is the MOA of all beta-lactam abxs
B-lactams inhibit the biosynthesis of the bacterial cell wall by binding to bacterial enzymes, specifically the peptidoglycan structure, and leading to cell lysis.
What are three bacterial enzymes that help create cell wall/peptidoglycan synthesis
Transpeptidase
Carboxypeptidase
Endopeptidase
What is peptidoglycan?
a rigid envelope surrounding the cytoplasmic membrane of most bacterial species
What is minimum inhibitory concentration (MIC)?
the lowest concentration of an antimicrobial agent that will inhibit the visible growth of a microorganism after overnight incubation.
What are the 4 penicillin subclasses?
- Natural penicillins
- Aminopenicillins
- Antistaphylococcal penicillins
- Antipseudomonal or Extended-Spectrum penicillins
What are the four natural penicillins and how are they administered
Penicillin V - administered PO
Procaine penicillin - administered IM
Benzathine penicillin - administered IM
Penicillin G - administered IV
Penicillin G is reliable for treating which bacteria
reliable for treating Listeria monocytogenes
What is penicillinase?
the vast majority of organisms produce and excrete an enzyme called penicillinase. this enzyme hydrolyzes the beta-lactam ring of natural penicillins rendering them completely ineffective
Why has Penicillin-resistant Streptococcus pneumoniae had a decreased in prevalence ?
widespread vaccination for Streptococcus pneumoniae (PCV-13, -15, -20)
Why do only 5% to 15% of community-acquired Staphylococcus aureus remain susceptible to natural penicillins?
the vast majority of organisms produce and excrete an enzyme commonly known as penicillinase
A Penicillin-resistant s. pneumoniae is also likely to be resistant to?
cephalosporins, macrolides, and sulfonamides, and, to a lesser extent, clindamycin; therefore, they are commonly called drug-resistant S. pneumoniae (DRSP)
What are the two most common aminopenicllins?
Ampicillin
Amoxicillin
Aminopenicllins are often paired with what to increase their effectiveness
Often paired with beta-lactamase inhibitors to prevent the destruction of beta-lactam antibiotics by serving as a competitive inhibitor of beta-lactamase. (sulbactam and clavulanate)
What are three Antistaphylococcal Penicillins and how are they administered?
Nafcillin (only available IV)
oxacillin (only available IV)
dicloxacillin (only available PO)
Are Antistaphylococcal penicillins stable in the presence of penicillinase produced by staphylococci?
yes
What is the difference between penicillinase and beta-lactamase?
Penicillinase is a specific subtype of β-lactamase, showing specificity to pencillins
What is the Antipseudomonal Penicillin abx
Piperacillin/tazobactam
comprised of a single combination product: piperacillin and a beta-lactamase inhibitor, tazobactam.
Piperacillin/tazobactam is active against?
Pseudomonas aeruginosa, Enterobacter, Escherichia coli, Klebsiella species.
What is the the most common mechanism of resistance to penicillins?
Beta-lactamase production. large group of enzymes with diverse ability to inactivate beta-lactams
What are extended-spectrum beta-lactamases (ESBLs)? What is the consequence of this.
have broader activity and not generally inhibited by beta-lactamase inhibitors.
Which natural penicillin can be given PO
Penicillin V
Which penicillins should be given IM, with a long half life
Penicillin G procaine and penicillin G benzathine
What could cause a cardiac arrest regarding penicillin administration
IM administration of Penicillin G procaine and penicillin G benzathine near a vein or artery
How are penicillins distributed throughout body
Varying degrees of plasma protein bonding
Can penicillins cross the placenta or be in breast milk?
Yes and Yes
Do penicillins readily cross the BBB?
No
What percent of renal excretion of penicillins is by active tubular secretion
90%
How readily are penicillins metabolized?
Excluding nafcillin and oxacillin, penicillins undergo negligible metabolism and are excreted primarily as unchanged drugs in the urine, achieving high urinary concentrations.
How should you treat C.Diff? What is the criteria for stool sampling?
if definitive diagnosis is made, treatment with oral vancomycin or fidaxomicin is required.
more than three watery, unformed stools per day or blood in the stool warrant stool testing to detect C. difficile toxin.
Piperacillin/tazobactam, when combined with vancomycin, leads to higher-than-expected rates of?
nephrotoxicity
the most commonly prescribed antibiotic in the United States
Amoxacillin
cross-sensitivity between penicillins and cephalosporins, carbapenems, or beta-lactamase inhibitors was thought to be much higher, data suggest that the rate is closer to?
1%
less than what percent of patients are truly allergic to penicillins?
1%
Type 1 rxns of penicillins usually occur within how much time post administration
2-30min
4 steps for Abx selection
Make clinical diagnosis
Obtain culture/specimens if able
Make microbial dx
Select drug based on sensitivity or usual susceptibility
Which 6 drugs are known to interact with penicillins
Diuretics
Methotrexate
Oral contraceptives
Probenecid
Tetracyclines
Warfarin
Ampicillin can interact with which two drugs
beta blockers and allopurinol
a rapid strep test, is testing for which organism
Group A Streptococcus Bacteria
