Cell Wall Synthesis Inhibitors (CWSIs)

Cefpirone

Carbapenems

Beta Lactams
o

Penicillins
Natural (nature-made) Penicillin G (oral) Penicillin V (IV) Penicillinase Resistant Methicillin Cloxacillin Dicloxacillin Nafcillin Oxacillin Aminopenicillins Amoxicillin Ampicillin Extended Spectrum Azlocillin Carbenicillin Mezlocillin Piperacillin Ticarcillin First Generation Cefazolin Cephalexin Second Generation Cefaclor Cefamandole Cefoxitin Third Generation Cefotaxime Ceftazidime Ceftriaxone Fourth Generation Cefepine o

Imipenem + cilastatin Ertapenem Meropenem Aztreonam

Monobactams

Polypeptides
o o o o

Vancomycin Bacitracin Fosfomycin Daptomycin

Cell wall synthesis inhibitors (CWSIs) block transpeptidation, the final step in the formation of the bacterial cell wall. (Transpeptidation is the crosslinking of adjacent peptidoglycan strands.) Beta Lactams

Cephalosporins

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

Answer: E. You could also use any of the penicillinase resistant drugs (ex. methicillin)

Pneumonic: CAST - Beta Lactamase inhibitors include Clavulanic Acid, Sulbactam, Tazobactam Clavulanic Acid

Penicillins

All end in "illin"

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

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)

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

Penicillin Allergies:

Tazobactam

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

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

Penicillin G, Oral penicillin

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 D. Vancomycin E. C and D C. Cephalosporin + sulbactam

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. 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

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).

Extended Spectrum Penicillins

Azlocillin, Carbenicillin, etc. Little to no Gram Pos Good for Pseudomonas

Over prescribing in health care has lead to the evolution of bacteria that have become resistant to Methecillin (and other penicillinase-resistant drugs). Even though methecillin has been modified to avoid beta lactamase, it is still not effective against Methecillin-Resistant Staph Aureus (MRSA).

Cephalosporins
o o o o

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

First Generation: Cefazolin, Cephalexin Second Generation: Cefaclor, Cefamandole, Cefoxitin Third Generation: Cefotaxime, Ceftazidime, Ceftriaxone 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).

Ampicillin

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 o Bleeding (inhibit Vitamin K) o Acetaldehyde accumulation (inhibit alcohol oxidation, like disulfiram)

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.

First Generation Cephalosporins

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).

Narrow spectrum to broad spectrum Destroyed by lactamase

Second Generation Cephalosporins

Increased coverage of Gram Neg Increased stability to lactamases Some penetrate CNS (meningitis)

Third Generation Cephalosporins

More broad spectrum Increased resistance to lactamases Penetrates CNS (meningitis) Class used for prophylaxis in hospitalized patients

Carbapenems
Imipenem + cilastatin Ertapenem Meropenem

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 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.

Good for aerobic Gram Neg, including Pseudomonas Ineffective against Gram Pos Narrow spectrum, but resistant to beta lactamase

Polypeptides

Vancomycin Bacitracin Fosfomycin Daptomycin

Cilastatin

Polypeptide Cell Wall Synthesis Inhibitors

Inhibits the conversion of imipenem to a toxic metabolite in the kidney. Always given with imipenem

Since they're polypeptides, they must be given IV or topical, except fosfomycin. Include Vancomycin, Bacitracin, Fosfomycin, Daptromycin

Meropenem

Vancomycin

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)

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)

Monobactams : Aztreonam

Bacitracin

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.

Polypeptide Cell Wall Synthesis Inhibitor Used topical only, available over the counter Causes nephrotoxicity when taken orally.

Fosfomycin

Polypeptide Cell Wall Synthesis Inhibitor Inhibits the cell wall enzyme enolpyruvyl transferase, Used for uncomplicated urinary tract infections (UTIs). Available orally and parenterally

Daptomycin

Polypeptide Cell Wall Synthesis Inhibitor-acting Not a cell wall synthesis inhibitor, but acts like one. Binds to cell wall, causes depolarization of the cell which leads to death of the cell.