Antimicrobials Flashcards
What is the mechanism of action of penicillin?
Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall. Activate autolytic enzymes.
What are the clinical uses of penicillin?
Mostly used for gram positive organisms (*S. pneumoniae, S. pyogenes, Actinomyces). *
Also used for gram-negative cocci (N. meningitidis) and spirochetes (*T. pallidum). *
Bactericidal for gram-positive cocci, gram positive rods, gram-negative rods, gram-negative cocci and spirochetes.
Name two toxicities of **penicillin. **
Hemolytic anemia
Hypersensitivity reactions
What is the mechanism of penicillin resistance?
Penicillinase in bacteria (a type of ß-lactamase) cleaves ß-lactam ring.
Name two penicillinase-sensitive penicillins (aminopenicillins).
Ampicillin
Amoxicillin
What is the mechanism of action of the aminopenicillins (amoxicillin, ampicillin)?
Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall. Activate autolytic enzymes.
What are the clinical uses of the aminopenicillins (amoxicillin, ampicillin)?
Extended spectrum penicillins: H. influenzae, H. pylori, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, **enterococci. **
HHELPSS kill **enterococci. **
Give three toxicities of aminopenicillins.
Hypersensitivity reactions, rash, pseudomembranous colitis.
What is the mechanism of resistance for the aminopenicillins?
Penicillinase in bacteria (a type of ß-lactamase) cleaves ß-lactam ring.
Name 3 penicillinase-resistant penicillins.
Oxacillin
Nafcillin
Dicloxacillin
What is the mechanism of action of the penicillinase-resistant penicillins?
Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall. Activate autolytic enzymes.
What makes dicloxacillin, nafcillin, and oxacillin penicillinase-resistant?
These drugs have a bulky R group that blocks access of the ß-lactamase to the ß-lactam ring.
What is the clinical use of the penicillinase-resistant penicillins (dicloxacillin, nafcillin, oxacillin)?
S. aureus
(except MRSA–resistant because of altered penicillin-binding protein sight).
Give two toxicities of the penicillinase-resistant penicillins (dicloxacillin, nafcillin, oxacillin).
Hypersensitivity reactions and interstitial nephritis.
Name two antipseudomonals.
Ticarcillin
Piperacillin
What is the mechanism of action of the antipseudomonals (piperacillin, ticarcillin)?
Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptidoglycan in cell wall. Activate autolytic enzymes.
What are the clinical uses of piperacillin and ticarcillin?
**Pseudomonas **species and gram-natative rods. (Susceptible to penicillinase–use with ß-lactamase inhibitors).
Name a toxicity of the antipseudomonals (piperacillin, ticarcillin).
Hypersensitivity reactions
Name three ß-lactamase inhibitors.
Clavulonic Acid
Sulbactam
Tazobactam
What is the clinical use of clavulonic acid, sulbactam and tazobactam?
Added to penicillin antibiotics to protect the antibiotic from destruction by ß-lactamase (penicillinase).
Which drug can we combine with amoxicillin and ampicillin to protect against destruction by ß-lactamase?
Claculanic acid
What drug is the prototype ß-lactam antibiotic?
Penicillin
What is the mechanism of action of the cephalosporins?
These are bactericidal ß-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
Which organisms are generally not covered by the cephalosporins?
LAME: **Listeria, *Atypicals (Chlamydia, Mycoplasma*), MRSA and Enterococci.
[Exception: ceftaroline covers MRSA]
Name two first generation cephalosporins.
Cephalexin
Cefazolin
What are the clinical uses of the first generation cephalosporins?
Gram-positive cocci: Proteus mirabilis, E. coli, Klebsiella pneumoniae
[PEcK]
Which cephalosporin is used prior to surgery to prevent S. aureus wound infections?
Cefazolin
Name three second generation cephalosporins.
Cefaclor
Cefuroxime
Cefoxitin
What are the clinical uses of the second generation cephalosporins?
Gram positive cocci: Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens.
[HEN PEcKS]
Name three 3rd generation cephalosporins.
Ceftriaxone
Cefotaxime
Ceftazidime
What are the clinical uses of the third generation cephalosprins?
Serious gram-negative infections resistant to other beta-lactams.
Ceftriaxone: meningitis, gonorrhea, disseminated Lyme disease
Ceftazidime: Pseudomonas
Name one fourth generation cephalosporin.
Cefepine
What are the clinical uses of cefepime?
Gram negative organisms, with increased activity against Pseudomonas and gram-positive organisms.
Name a 5th generation cephalosporin.
Ceftaroline
What are the clinical uses of ceftaroline?
Broad gram-positive and gram-negative organism coverage, including MRSA.
[Exception: does not cover Pseudomonas]
Cephalosporin toxicities (4)
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfram like reaction, vitamin K deficiency.
Name two drug-drug interactions seen with cephalosporins.
Exhibit cross-reactivity with penicillins and increase nephrotoxicity of aminoglycosides.
What is the mechanism of resistance to cephalosporins?
Structural change in penicillin-binding proteins.
Name four carbapenems.
Imipenem, meropenem, ertapenem, doripenem.
What is the mechanism of action of imipenem?
Broad specturm, ß-lactamase-resistant carbapenem.
Which drug is always administered with imipenem, and why?
Given with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of the drug in the renal tubules.
What are the clinical uses of the carbapenems?
Gram positive cocci, gram-negative rods and anaerobes.
[Wide spectrum but many side effects–limit use to life-threatening infections/after other drugs fail]
Carbapenem toxicities?
GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels.
Which carbapenem has a lower risk of seizures and is stable to dehydropeptidase I?
Meropenem
Name a monobactam antibiotic.
Aztreonam
