Mid Beta-Lactam Antibiotics And Vancomycin Ii

Front 1

Whats the difference in structure between penicillins and cephalosporins?

Back 1

Penicillins have 5 member ring and cephalosporins have a six membered ring.Whats the difference in structure between penicillins and cephalosporins?

Front 2

Describe the structure of cephalosporins

Back 2

The basic structure consists of a 6 membered dihydrothiazine ring with substituations at the 3 position generally affecting their pharmacological properties and changes at the 7 position affecting antimicrobial activity.

Front 3

Describe Cephalosporin C

Back 3

It has broad activity against both gram positive and gram negative bacteria, and was resistant to degratation by staphylococcal penicillinases. Unfortunately, it did not cross the BBB and was ineffective for meningococcal meningitis.

Front 4

Describe the properties of Cephalothin

Back 4

Less painful to inject IM, longer half-life

Front 5

What is cephalosporin activity a function of?

Back 5

-Their affinity for PBPs
-Their permiability properties
-Their stability to beta-lactamases

Front 6

Which type of bacteria can cephalosporins not bind the PBP of?

Back 6

Enterococci

Front 7

Describe induction of gram negative chromosomal beta-lactamases by cephalosporin

Back 7

The cephalosporins, as a group, are much more potent inducers of the Gram negative chromosomal ß-lactamases, the members of the ampC family, which (ironically) have cephalosporin activity. Thus, if there are sizable populations of bacteria present, sub-inhibitory levels of cephalosporins may well select out mutants with derepressed chromosomal ß-lactamase activity resulting in clinical failures of therapy.

Front 8

What are the first generation cephalosporins - "house cephalosporins"? How are they administered?

Back 8

Cefazolin - parenteral
Cephalexin - oral

Front 9

Describe the use of first generation cephalospotins

Back 9

-Excellent activity against community acquired bacteria
-Often used for surgical prophylaxis
-Used for skin and soft tissue infections (but not bites)
-Poor activity against anaerobes in the gut
As more resistant Gram negative infections became common, and the importance of ß-lactamase producing anaerobes in the bowel was appreciated, the use of second generation cephalosporins increased.

Front 10

What are the second generation cephalosporins?

Back 10

Cefoxitin
Cefotetan
Cefuroxime

Front 11

Describe cefoxitin and cefotetan

Back 11

-Very ß-lactamase stable (due to methoxy group)
-Active against many aerobic and anaerobic Gram negative rods, but they have somewhat less activity against Gram positive organisms than the first generation cephalosporins
-Primarily use to treat infections arising from the bowel flora.
(Note as cephalosporins they do not have activity against enterococci, also common in the gut flora.)
-Cefoxitin can induce the chromosomal beta-lactamase and it is a cephalosporinase then cefoxitin can induce its own destruction.

Front 12

Describe cefuroxime

Back 12

-Excellent against many gram positive bacteria
-Improved beta-lactamase stability
-Active against gram negatives in the respiratory tract (Hemophilus)

Front 13

What are the third generation cephalosporins?

Back 13

Cefotaxime
Ceftriaxone
Ceftazidime

Front 14

Describe cefotaxime and ceftriaxome

Back 14

-Originally for resistant gram negative rods
-Due to enhanced activity, high blood levels, and pharmacokinetic properties, they are used for many infections
-Can get into the CSF and are good for the common causes of meningitis

Ceftriaxome:
-Exceptionally active and can get into the CSF with a single IM dose
-Highly protein bound
-Long half life

Front 15

Describe ceftazidime

Back 15

-Used for P. aeruginosa infection
-Has the piperazine side chain from piperacillin
-Active againsts other gram negative enteric and opportunistic pathogens
-Limited gram positive activity
-Can induce chromosomal beta-lactamases (though less so than others)

Front 16

What is the fourth generation drug?

Back 16

Cefipime

Front 17

Describe cefipime

Back 17

-Increased gram positive as well as gram negative activity
-Used in settings where broad spectrum coverage is needed
-Active against P. aeruginosa and many of the other opportunistic gram negative pathogens found in hospitalized patients.
-Low induction of chromosomal cephalosporinases
-Increased beta lactamase stability

Front 18

What are the carbapenems?

Back 18

Imipenem
Meropenum
Ertapenem

Front 19

What is the target of carbapenems?

Back 19

PBP2, which is present in low copy number

Front 20

Describe the permiability of carbapenems

Back 20

-Improved permeability properties
-Use a porin channel that is not usually activated by the more common efflux pumps
-Huge spectrum

Front 21

What organisms are susceptible to carbapenems?

Back 21

These are very very broadly active drugs and it is easier to remember the organisms that are not killed: Stenotrophomonas and Burkholderia (opportunistic Gram negatives) and Enterococci.

Front 22

Describe the effect of carbapenems on the CNS

Back 22

-Penetrate the CNS
-May have CNS toxicity (Imipenem, not meropenem)

Front 23

Describe the stability of carbapenems

Back 23

While they lack a ß-lactam
ring and were initially thought to be entirely ßlactamase stable, there have been organisms that have developed enzymes to break down these agents as well.

Front 24

What monobactams are available?

Back 24

Aztreonam

Front 25

Describe aztreonam

Back 25

-Only binds to gram negative PBPs
-No beta-lactam ring, so stable to beta lactamases
-Narrow spectrum - only aerobic gram negative rods
-Can be removed by some efflux pumps

Front 26

Describe the resistance mechanisms against aztreonam

Back 26

They are basically the same as for the penicillins. Some species, notably the Enterococci, are inherently resistant to the cephalosporins
due to structural differences in their PBP’s.

Front 27

Describe cefotaxime metabolism

Back 27

Cefotaxime is metabolized and des-acetyl cefotaxime is
excreted into the gut.

Front 28

How does vancomycin work?

Back 28

Targets the cell wall, interacting with the D-ala-D-ala portion of the pentapeptide side chain of staphylococci. It blocks both the carboxypeptidase activity as well as the transpeptidase. Once vancomycin resistance is established it can be a significant problem in a given setting.

Front 29

What type of bacteria is vancomycin good for?

Back 29

Gram positives, Streptococci, Clostridia, Listeria, and Bacillus. It does not get into gram negatives. It is active agains tthe highly penicillin resistant S. pneumonie, and is used for pneumonoccal meningitis until the susceptibilities of the infecting organism are known.