Cell Wall Synthesis Inhibitors (CWSIs)  First Generation

 Cefazolin
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 Cephalexin
 Beta Lactams
 Second Generation
o Penicillins
 Cefaclor
 Natural (nature-made)
 Cefamandole
 Penicillin G (oral)
 Cefoxitin
 Penicillin V (IV)
 Third Generation
 Penicillinase Resistant
 Cefotaxime
 Methicillin
 Ceftazidime
 Cloxacillin
 Ceftriaxone
 Dicloxacillin
 Fourth Generation
 Nafcillin
 Cefepine
 Oxacillin
 Cefpirone
 Aminopenicillins

 Amoxicillin
o Carbapenems

 Ampicillin  Imipenem + cilastatin

 Extended Spectrum  Ertapenem

 Azlocillin  Meropenem

 Carbenicillin o Monobactams
 Mezlocillin  Aztreonam
 Piperacillin
 Polypeptides
 Ticarcillin
o Vancomycin
o Cephalosporins
 o Bacitracin
o Fosfomycin
o Daptomycin
Cell wall synthesis inhibitors (CWSIs) block transpeptidation, the final step
in the formation of the bacterial cell wall. (Transpeptidation is the cross-
linking of adjacent peptidoglycan strands.)
Beta Lactams
 Includes: Penicillins, Cephalosporins, Carbapenams, Monobactams
 Cell Wall Synthesis Inhibitors (CWSIs).
 Inhibit enzyme required for transpeptidation, the final step in
bacterial cell wall synthesis.
 Bacteria have developed resistance by creating beta lactamase
(penicillinase for penicillin, cephalosporinase for cephalosporins).
 Beta lactamase inactivates the drug by opening the beta lactam ring
in the drug's structure.
 Some people have allergies to any drug that has a beta lactam ring.
3 ways to overcome beta lactamase:
 Give a lactamase inhibitor with the Beta Lactam drug
o Clavulanic acid
o Sulbactam
o Tazobactam
 Find a modified Beta Lactam that is resistant to lactamase
 Don't use a Beta Lactam as your antibiotic
Pneumonic: CAST - Beta Lactamase inhibitors include Clavulanic Acid,
Sulbactam, Tazobactam
Clavulanic Acid
 Beta Lactamase inhibitor. Beta lactamase inactivates beta lactam
drugs by opening the beta lactam ring in the drug's structure.
 Given with Beta Lactamase drugs (penicillin, cephalosporin) to
overcome bacterial resistance to these drugs
 Not an antibiotic, but given with antibiotics to avoid resistance
Sulbactam
 Beta Lactamase inhibitor. Beta lactamase inactivates beta lactam
drugs by opening the beta lactam ring in the drug's structure.
 Given with Beta Lactamase drugs (penicillin, cephalosporin) to
overcome bacterial resistance to these drugs
 Not an antibiotic, but given with antibiotics to avoid resistance
Tazobactam
 Beta Lactamase inhibitor. Beta lactamase inactivates beta lactam
drugs by opening the beta lactam ring in the drug's structure.
 Given with Beta Lactamase drugs (penicillin, cephalosporin) to
overcome bacterial resistance to these drugs
 Not an antibiotic, but given with antibiotics to avoid resistance
Question: You've decided to culture a wound while working at the
wound care center. Which of the following drugs should you use if the
bacterial isolate produces a lactamase enzyme?
A. Penicillin B. Cephalosporin C. Cephalosporin + sulbactam
D. Vancomycin E. C and D
Answer: E. You could also use any of the penicillinase resistant drugs (ex. methicillin)
Penicillins All end in "illin"
  Cell Wall Synthesis Inhibitors. Beta Lactams. Bacteria become
resistant by producing penicillinase (a beta lactamase which
inactivates penicillin by opening it's beta lactam ring).
 Excreted through the urine unchanged (adjust for Creatinine
Clearance)
 Lower dose can be used when given with probenecid. Probenecid
blocks renal tubular secretion of penicillins.
 ADRs include: Allergies (hypersensitivity reactions)
Penicillin Allergies:
 Immediate Reaction - IgE mediated. Within minutes of IV or IM
dose. Causes urtircaria (hives) through hypotension, shock and death.
 Accelerated Reaction - 1-72 hours post dose. Urtricaria
 Late Reaction - 72 hours to several weeks past dose. Rashes
Penicillin G, Oral penicillin
 Cell Wall Synthesis Inhibitor. Beta Lactam. Inhibits the enzyme
required for transpeptidation, the final step in cell wall synthesis.
 Bacteria resist penicillins by producing beta lactamase, an enzyme
which inactivates the drug by opening the beta lactam ring in the
drug's structure.
 Gram Pos (narrow spectrum)
 Natural, made by nature
Penicillin V, IV penicillin
 Cell Wall Synthesis Inhibitor. Beta Lactam. Inhibits the enzyme
required for transpeptidation, the final step in cell wall synthesis.
 Bacteria resist penicillins by producing beta lactamase, an enzyme
which inactivates the drug by opening the beta lactam ring in the
drug's structure.
 Gram Pos (narrow spectrum)
 Natural, made by nature
Methicillin
 Cell Wall Synthesis Inhibitor. Beta Lactam. Penicillinase resistant
semisynthetic penicillin. Inhibits the enzyme required for
transpeptidation, the final step in cell wall synthesis.
 Bacteria resist penicillins by producing beta lactamase, an enzyme
which inactivates the drug by opening the beta lactam ring in the
drug's structure.
 Methicillin is modified to resist beta lactamase
 Gram Pos, narrow spectrum
 Over prescribing in health care has lead to the evolution of
bacteria that have become resistant to Methicillin (and other
penicillinase-resistant drugs). Even though methicillin has been
modified to avoid beta lactamase, it is still not effective against
Methicillin-Resistant Staph Aureus (MRSA).
Amoxicillin
 Cell Wall Synthesis Inhibitor. Beta Lactam. Aminopenicillin.
Inhibits the enzyme required for transpeptidation, the final step in
cell wall synthesis.
 Bacteria resist penicillins by producing beta lactamase, an enzyme
which inactivates the drug by opening the beta lactam ring in the
drug's structure.
 Broad spectrum, Gram Pos and some Gram Neg
Ampicillin
 Cell Wall Synthesis Inhibitor. Beta Lactam. Aminopenicillin.
Inhibits the enzyme required for transpeptidation, the final step in
cell wall synthesis.
 Bacteria resist penicillins by producing beta lactamase, an enzyme
which inactivates the drug by opening the beta lactam ring in the
drug's structure.
 Broad spectrum, Gram Pos and some Gram Neg
 o Bleeding (inhibit Vitamin K)
Extended Spectrum Penicillins
 Azlocillin, Carbenicillin, etc. o Acetaldehyde accumulation (inhibit alcohol oxidation, like
 Little to no Gram Pos disulfiram)

 Good for Pseudomonas First Generation Cephalosporins

 Narrow spectrum to broad spectrum
Over prescribing in health care has lead to the evolution of bacteria that have  Destroyed by lactamase
become resistant to Methecillin (and other penicillinase-resistant drugs).
Even though methecillin has been modified to avoid beta lactamase, it is still Second Generation Cephalosporins
not effective against Methecillin-Resistant Staph Aureus (MRSA).  Increased coverage of Gram Neg
 Increased stability to lactamases

 Some penetrate CNS (meningitis)

Cephalosporins
o First Generation: Cefazolin, Cephalexin
o Second Generation: Cefaclor, Cefamandole, Cefoxitin
o Third Generation: Cefotaxime, Ceftazidime, Ceftriaxone
o Fourth Generation: Cefepime, Cefpirone
Note: "Memorize the two or three most common drugs in each class and the
difference between classes." (12, statement applies to Cephalosporins).
 Cell Wall Synthesis Inhibitors. Beta Lactams.
 Bacteria resist Beta Lactam drugs by producing beta lactamase, an
enzyme which inactivates the drug by opening the beta lactam ring in
the drug's structure.
 Through each generation of cephalosporins, the drugs have been
modified for increased coverage and increased resistance to beta
lactamase.
 All the drugs start with "ceph" or "cef". Fourth generation drugs have
a "p" in them.
 ADRs:
o Cross allergy with penicillins
Third Generation Cephalosporins
 More broad spectrum
 Increased resistance to lactamases
 Penetrates CNS (meningitis)
 Class used for prophylaxis in hospitalized patients
Fourth Generation Cephalosporins
 Gram Pos and Gram Neg, Pseudomonas aeruginosa
 Good for Gram neg with resistance to other drugs
 Class designed to treat organisms with resistance to multiple other
drugs.
Cefepime
 Cell Wall Synthesis Inhibitor antibiotic. Beta Lactam. Fourth
Generation Cephalosporin.
 Bacteria can resist beta lactam drugs by producing beta lactamase,
which inactivates the drug by open the beta lactam ring in it's
structure. Fourth Generation cephalosporins resist beta lactamase,
and have increased coverage over previous generations.
 Gram Pos, Gram Neg and Pseudomonas aeruginosa
  Good for gram neg with resistance to other drugs.
 Has "cef" in the name like many cephalosporins and has a "p" which
helps to recognize it as fourth generation.
Question: Which of the following drugs is used for P. aeruginosa infection?
A. Cyclobenzaprine
B. Cefaclor
C. Cefepime
D. Student-resistant profesorius
E. Cefotaxime
Answer: C. Remember the cephalosporins have "cef" or "ceph" and the
fourth generation (which covers Pseudomonas aeruginosa) have a "p" in
them. Other drugs which cover Pseudomonas are extended spectrum
penicillins (above) and aztreonam (below).
Carbapenems
 Imipenem + cilastatin
 Ertapenem
 Meropenem
 Cell Wall Synthesis Inhibitors. Beta Lactams. Inhibit
transpeptidation, the final step in cell wall synthesis.
 Bacteria can resist beta lactams by producing beta lectamase, an
ezyme which deactivates the drug by opening the beta lactam ring in
it's structure.
 Given by IV only
 All have "penem" in their name
Imipenem
 Cell Wall Synthesis Inhibitors. Beta Lactams. Inhibit
transpeptidation, the final step in cell wall synthesis.
 Bacteria can resist beta lactams by producing beta lectamase, an
ezyme which deactivates the drug by opening the beta lactam ring in
it's structure.
 Given by IV only.
 Converted by the kidney to a toxic metabolite. Cilastatin inhibits this
biotransformation, so Imipenem is always given with cilastatin.
Cilastatin
 Inhibits the conversion of imipenem to a toxic metabolite in the
kidney.
 Always given with imipenem
Meropenem
 Cell Wall Synthesis Inhibitors. Beta Lactams. Inhibit
transpeptidation, the final step in cell wall synthesis.
 Bacteria can resist beta lactams by producing beta lectamase, an
ezyme which deactivates the drug by opening the beta lactam ring in
it's structure.
 Given by IV only.
 Unlike imipenem, meropenem is more stable when converted in the
kidney. Meropenem is not given with cilastatin (which inhibits toxic
transformation of imipenem)
Monobactams : Aztreonam
 Cell Wall Synthesis Inhibitors. Beta Lactams. The only
Monobactam. Inhibit transpeptidation, the final step in cell wall
synthesis.
 Bacteria can resist beta lactams by producing beta lectamase, an
ezyme which deactivates the drug by opening the beta lactam ring in
it's structure. Aztreonam is highly resistant to beta lactamase.
 Good for aerobic Gram Neg, including Pseudomonas
 Ineffective against Gram Pos
  Narrow spectrum, but resistant to beta lactamase  Inhibits the cell wall enzyme enolpyruvyl transferase, Used for
uncomplicated urinary tract infections (UTIs).
Polypeptides  Available orally and parenterally
 Vancomycin
 Bacitracin Daptomycin
 Polypeptide Cell Wall Synthesis Inhibitor-acting
 Fosfomycin
 Not a cell wall synthesis inhibitor, but acts like one. Binds to cell
 Daptomycin wall, causes depolarization of the cell which leads to death of the
cell.
Polypeptide Cell Wall Synthesis Inhibitors
 Since they're polypeptides, they must be given IV or topical, except
fosfomycin.
 Include Vancomycin, Bacitracin, Fosfomycin, Daptromycin

Vancomycin
 Polypeptide Cell Wall Synthesis Inhibitor
 Poor oral absorption, given IV only

 Gram Pos only

 Requires peak and trough measurements

 ADRs:

o Dose-related high tone deafness

o Kidney failure

o Red Man Syndrome (histamine release)

Bacitracin
 Polypeptide Cell Wall Synthesis Inhibitor
 Used topical only, available over the counter

 Causes nephrotoxicity when taken orally.

Fosfomycin
 Polypeptide Cell Wall Synthesis Inhibitor