What are 4 common methods of AB resistance?
- Decreased permeability of cell
- Alteration of target site
- Enzyme inactivation
- Efflux of drug
To what protein do penicillins bind to exert their effect?
Penicillin binding protein
What is the structural difference b/w Gram (+) and Gram (-) organisms?
Gram (+) cells have a rigid cell wall made of peptidoglycan layers while Gram (-) cells have a multilayered cell wall that contains lipopolysaccharide (LPS)
Where is the site of bacterial hydrolysis of penicillins that lead to resistance?
Hydrolysis of the Beta lactam ring with beta lactamase
Describe the mechanism of beta lactamase resistance
Beta-lactamase breaks down beta lactam ring of penicillins, cephalosporins, monobactams, and carbepenems and therefore the drugs cannot bind to the penicillin binding protein
Describe the mechanism of cancomycin resistance involving cell walls
- The peptidoglycans of the cell wall acquire a terminal lactate and therefore vancomycin cannot bind
- OR the cell wall of the bug can become so thick that the vancomycin gets caught and cannot exert its effect
What is an important resistance mechanism that all Staphylococcus aureus has acquired?
Penicillinase! All SA is penicillin reisistant
What are the two most common penicillin binding proteins?
PBP2b and PBP2x
What drugs bind to PBP2b?
Penicillins and first generation cephalosporins
What drugs bind to PBP2x
All non-first generation cephalosporins, the carbapenms, and monobactams
What is the bacterial function of PBP?
Anchor and orient the native bacterial transpeptidase which is required to cross-link cell walls
What type of mutation would confer resistance to all lactam drugs?
Concurrent alterations in PBP2b and PBP2x would confer resistance to all lactam ABs
What characteristic of lactams make them very susceptible to hydrolysis
High-tension 90 degree angle bond
Are carbepenems susceptible to penicillinase?
No because carbepenems are not penicillins
What are the two ways to protect penicillins from hydrolysis?
- Adding bulky aromatic groups around the ring to sterically inhibit penicillinase
- Combine penicillins with suicide inhibitor from the clavam class of drugs
Why are neither penicillins nor cephalosporins effective against Extended spectrum beta lactamase gram negative species?
These bugs produce an abundance of of lactamase
What is the typical presentation from a lactam-induced allergy?
Either anaphylaxis (hives, angioedema, respiratory stridor, hypotension) or Maculo (flat/red)-papular (lumpy/bumpy) skin eruption
What is a serious allergic complication of lactams?
Interstitial nephritis, toxic epidermal necrolysis, cytopenia)
What is the antigenic focux responsible for essentially all cases of drug allergy to lactams?
5/6 member ring adjacent to lactam ring
What is the cause of allergic cross reactivity b/w penicillins and cephalosporins?
The similarity b/w the functional groups b/w penicillins and cephalosporins at R1 position
What immune reaction causes the maculopapular rash from aminopenicillins?
Antigenic reaction with an IgM Ab (NOT IgE) and occurs in 100% of patiets with acute infectious mononucleosis from EBV
What are the lactam drugs?
Penicillins, Cephalosporins, carbepenems, monobactam
What are the penicillins?
- penicillin g, penicillin v
- penicillinase-resistanat penicillins [oxacillin, dicoxacillin]
- Amniopenicillins [ampicillin, amoxicillin]
- Extended spectrum penicillins [piperacillin]
- Penicillins w/ suicide inhibitors [Piperacillin-tazobactam, amoxicillin-clavulanate]
What are the Cephalosporins?
- First generation [cefazolin, cephalexin]
- Second generation [cefuroxime]
- Third generation [ceftriaxone and ceftazidime, cefpodoxime]