Term
| What is the MoA of penicillins? |
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Definition
Bacterium cannot make cell walls - necessary for shape - Specifically inhibits transpeptidase resulting in a weak cell wall.
**Contains peptidoglycans, alternating NAM and NAGs |
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Term
| What enzyme crosslinks cell walls in bacteria? |
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Definition
| transpeptidase - necessary to form a rigid cell wall |
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Term
| What is the difference between gram(+) and gram(-) bacteria? |
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Definition
- gram(+) - The cell wall lies above the cell membrane and has THICK peptidoglycan.
- gram(-) - Has 2 phospholipid membranes than surround the cell wall, and a single sheet of PG. A drug must be HYDROPHILIC to get through porins |
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Term
| What does a gram(-) cell look like? |
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Definition
Outer layer - LPS, an endotoxin
Lower layer - plasma membrane
Porins allow passage to plasma membrane |
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Term
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Definition
Differentiates between gram(+) and gram(-)
Crystal Violet --> Iodine --> alcohol --> Safranin |
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Term
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Definition
Penicillin binding proteins, usually transpeptidase, that when binding penicillin lead to death of the cell.
**Penicillins permanently bind PBPs, neutralizing them |
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Term
| What are mechanisms of resistance? |
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Definition
- Intrinsic - lack PBPs or porin channels (P. aerug)
- Acquired - mutation to PBPs, can no longer bind
- Efflux of antibiotics in gram(-) bacteria
**MRSA has heavier PBPs that penicillin cannot bind to |
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Term
| Why do some antibiotics need to be reconstituted? |
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Definition
| Beta lactams will hydrolyze |
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Term
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Definition
| An enzyme that HYDROLYZES the beta lactam ring, inactivating penicillin. Resembles transpeptidase, rapidly regenerates. |
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Term
| What to penicillin G and V treat? |
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Definition
ALL gram(+) and 3 gram(-) - N. gonorrhoeae, N. meningtidis, H. influenzae.
**Most strep - S. viridans, S. pyogenes. Listeria. Gas gangrene and anthrax now resistant. |
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Term
| What are aspects of Pen G and Pen VK? |
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Definition
- Pen G - only 1/3 is absorbed in GI. Not acid stable. DO NOT TAKE WITH FOOD. Does not cross meninges
- Pen VK - increased oral bioavailability, less potency
**Probenecid increases half life |
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Term
| What are the indications for Pen G/VK? |
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Definition
- Strep Throat - S. pyogenes
- Strep endocarditis - S. viridans
- Meningococcal infections - better agents available
- Syphilis and Anthrax - T. pallidum (gram-) and B. anthracis
- Listeriosis - L. Monocytogenes |
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Term
| What are different types of streptococcal species? |
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Definition
- Alpha hemolytic - reduce heme
- Beta hemolytic - rupture RBCs, most common
- Group A - contain A carbs. M antigen is most antigenic. S pyogenes
- Group B - S. agalactieae, test pregnant women |
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Term
| What is the pathophysiology of S. pyogenes? |
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Definition
- hemolysins rupture cells
- Exotoxins express a red color
- Breakdown of DNA
- Streptokinases alter clotting
**Tx is always penicillin |
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Term
| What is the function of normal flora? |
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Definition
- Secrete vitamins - K and B12
- Prevent Colonization **
- Antagonize other species
- tissue development
- natural antibodies
**S. epidermidis most common. Bacteroides in the appendix |
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Term
| What flora are found in cows milk? |
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Definition
Bacteroides, lactobacillus, enterococci
**Clostridium species can overgrow in the colon |
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Term
| How do antibiotics affect oral contraceptives? |
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Definition
Penicillins and tetracyclines specifically, Rifampin and griseofulvin ABSOLUTELY.
**Normal flora allows more EE to be available in the gut. If this is wiped out, contraceptive doesn't work. |
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Term
| What are penicillinase resistant penicillins? |
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Definition
Resistant to beta lactams - restrict to STAPH infections that express this. Less active against organisms that do not express beta lactamase
**Still don't work against MRSA |
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Term
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Definition
Resistant to penicillin/cephalosporins - pervasive in nosocomial.
**Larger PBPs |
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Term
| What are features of methicillin? |
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Definition
| Bulky methoxy groups limit spectrum of activity to Staph species ONLY. |
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Term
| What is Nafcillin/Nafcil or Unipen or Nalpen used to treat? |
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Definition
| Bulky ring is resistant to beta lactamase - MSSA and S. epidermidis |
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Term
| What are the isoxozalyl penicillins? |
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Definition
Oxacillin, Cloxacillin, and Dicloxacillin
Have NO gram(-) coverage, but can be used for S. aureus |
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Term
| What are aminopenicillins? |
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Definition
Broader spectrum, but no resistance to beta lactamase
- Ampicillin/Omnipen or polycillin - chiral center, increased ACID stability and water solubility
- Amoxicillin - greater H. pylori coverage, incr blood levels. more potent!
-Bacampicillin/Spectrobid - incr blood levels
**Broad spectrum = wipes out normal flora |
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Term
| What bacterium does ampicillin cover? |
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Definition
Gram + organisms
Gram -: Everything except P. aeruginosa |
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Term
| What are indications for aminopenicillins? |
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Definition
- Respiratory: S. pyogenes, S. pneumoniae (Amox!), H. influenzae
- UTI: E. coli, P. mirabilis, Enterococci
- Meningitis: Listeria monocytogenes
- Lyme disease: Borrelia burgdorferi |
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Term
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Definition
Congestion and swelling in the eustachian tube: S. pneumoniae and H. influenzae, both gram(-)
**Delay antibiotic tx for 72 hours, then treat for 7-10 days |
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Term
| What are beta lactamase inhibitors? |
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Definition
Clavulanic acid irreversibly inhibits, a suicide substrate
Also Sulbactam w/ Ampicillin |
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Term
| What are antipseudomonal penicillins? |
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Definition
The broadest spectrum, work against P. aeruginosa:
- Carbenicillin/Geopen or Geocillin
- Ticarcillin/Ticar
- Mezlocillin/Mezlin*
- Piperacillin/Pipracil*
**Still don't work against MRSA, beta lactamase |
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Term
| What is the difference between Carboxypenicillins and Ureidopenicillins? |
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Definition
- Carboxy - Acid instability. Enhanced gram(-) activity. Carbenicillin is rapidly metabolized, Ticar is not. Used in UTI, RTI and osteomyelitis from P. aerug, P. vulgaris
- Ureido - gram(-) wound infections, UTIs
**Zosyn: Piperacillin+Tazobactam, a beta lactamase inhibitor. Broadest spectrum. Also works against Bacteroides and Clostridium |
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Term
| What antibiotic can be used against Bacteroides? |
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Definition
| Zosyn/Piperacillin+Tazobactam |
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Term
| What are adverse effects of penicillins? |
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Definition
Hypersensitivity! The penicilloyl is reactive. Immune system reacts w/ haptens.
Sensitization from antibiotic treated food. |
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Term
| What are the features of 1st generation cephalosporins? |
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Definition
Good against gram(+), modest against gram(-) - E. coli, K. pneumoniae, P. mirabilis
**Not for MRSA |
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Term
| What are the features of 2nd generation cephalosporins? |
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Definition
Increased gram(-) activity: E. coli, Klebsiella, Proteus, H. influenzae
**Bacteroides fragilis |
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Term
| What are the features of 3rd generation cephalosporins? |
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Definition
More active against Enterobacteriaceae, including those w/ beta lactamase.
Some w/ pseudomonas
Enterobacteria: Salmonella, Shigella, Escherichia, Klebsiella |
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Term
| What are the characteristics of 4th generation cephalosporins? |
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Definition
| resists hydrolysis and beta lactamase - works against resistant organisms |
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Term
| What do cephalosporins not work against? |
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Definition
- MRSA
- MRSE
- L. monocytogenes |
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Term
| What cephalosporins can be used to treat meningitis? |
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Definition
| Cefuroxime, Cefotaxime, Ceftriaxone, Cefepime, Ceftizoxime |
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Term
| What are 1st generation cephalosporins? |
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Definition
- Cephalexin/Keflex - amino group increases absorption. Works on E. coli, Klebsiella, P. vulgaris/mirabilis
- Cefadroxil/Duricef - similar to amoxicillin
- Cefazolin/Ancef - longer half life |
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Term
| What is Clostridium difficile? |
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Definition
Antibiotic associated colitis --> pseudomembraneous colitis. Antibiotic wipes out normal flora results in C. diff overgrowth.
**Caused by FQNs, clinda, cephalosporins |
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Term
| What increases the risk of a C. diff infection? |
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Definition
Tx with antibiotics: FQNs, cephalosporins, clindamycin
PPIs |
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Term
| How do C. diff toxins work? |
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Definition
| Translocation domain moves toxin to Rho GTPase, then transfer of glucose inactivates. Actin no longer works and cell dies |
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Term
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Definition
- Discontinue causing antibiotic
- Avoid anti-diarrheals |
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Term
| Why are 2nd gen cephalosporins resistant to beta lactamase? |
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Definition
| Bulk is pointing towards the molecule (SYN), prevents beta lactamase from working |
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Term
| What are 2nd generation cephalosporins? |
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Definition
- Cefuroxime/Ceftin - penetrates CSF
- Cefoxitin/Mefoxin - Bacteroides
- Cefotetan/Cefotan - good bacteroides
- Cefaclor/Ceclor - less gram(-) activity, but works against H. influenzae
- Loracarbef/Lorabid
- Cefprozil/Cefzil - less gram(+) |
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