08 Antibacterial- cell wall synthesis inhibitors Flashcards
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Bactericidal Drugs<!--EndFragment-->
what they do and example of these drugs
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Bactericidal Drugs<!--EndFragment-->
Cause death of the microorganism
Eg:
Penicillins
Aminoglycosides
Cephalosporins
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Bacteriostatic Drugs and what they do
Bacteriostatic Drugs and what they do
Inhibit the growth of the microorganism
E.g. Sulfonamides, Tetracyclines, Erythromycin
Drugs for Inhibition of cell wall systhesis
Inhibition of cell wall systhesis
Penicillins**
Cephalosporins**
Carbapenems
Monobactum
Vancomycin**
Bacitracin
Cycloserine
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Drugs for Inhibition of protein synthesis
Inhibition of protein synthesis
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Tetracyclines
Macrolides
Chloramphenicol
Aminoglycosides
Streptogramins
Linezolid
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Drugs for Inhibition of nucelic acid synthesis
Inhibition of nucelic acid synthesis
Fluroquinolones
Rifampin
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Drugs for Inhibition of folic acid synthesis
Inhibition of folic acid synthesis
Sulfonamides
Trimethoprim
Pyrimethamine
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Beta lactam antibiotics
Beta lactam antibiotics
- Penicillins **
- Cephalosporins**
- Carbapenems
- Monobactum
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Cross linking is catalyzed by what bacterial enzymes? mention all known names
Cross linking is catalyzed by what bacterial enzymes?
Transpeptidases** AKA penicillin-binding proteins (PBPs)**** because they can be bound by beta-lactam antibiotics (e.g. penicillin)
- they bind to and inactivate penicillin binding proteins (PBP) e.g. transpeptidase***
What are Penicillinase? It acts on what to confer resistance? example?
Penicillinase act on what to confer resistance?
Penicillinase are enzymes produced by the bacteria
They act on the four-member nitrogen-containing b-lactam ring** of b-lactam drugs.
Eg: Penicillinases** (b-lactamases) break the betalactam ring
- eg. Staphylococci
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Side effects of Penicillins<!--EndFragment-->
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Side effects of Penicillins<!--EndFragment-->
Hypersensitivity reactions – rare
- Skin rashes
- Acute anaphylactic shock***
Alter bacterial flora of the gut***
- GI disturbances (esp broad spectrum) -> Clostridium difficle overgrowth
Cross-sensitivity is possible***
- (allergic to one may also be allergic to others)
Types of penicillins
Types of penicillins
- Narrow Spectrum penicillin (Penicillinase susceptible)
- Narrow Spectrum (Penicillinase resistant) penicillins
- Broad spectrum (Penicillinase susceptible) penicillins
- Extended spectrum or antipseudomonal
- Beta-lactam with beta lactamase inhibitor
Broad spectrum penicillins
Broad spectrum
(Penicillinase susceptible) penicillins
Includes: Ampicillin**, amoxicillin**
Spectrum of activity:
- Activity against gram positive cocci
- Active against some gram negative rods**
Uses:
- Infections due to Haemophilus influenzae, E. coli Listeria monocytogenes, Proteus mirabilis,, Salmonella, Shigella
- (Coverage: ampicillin/amoxicillin HELPSS kill enterococci)
note: Activity enhanced if used in combination with beta lactamase inhibitors (clavulanic acid, sulbactum)- widens the spectrum
What is Amoxicillin? What is it used for?
Amoxicillin
- Amoxicillin is a broad spectrum penicillins that is Penicillinase susceptible.
- It’s effective against gram positive cocci and **some **gram negative rods**
Amoxicillin is also use to:
- prevent bacterial endocarditis* before major surgical procedures
- used in H.pylori infection (peptic ulcers)
Main uses of Amoxicillin and other broad spectrum are:
Infections due to Haemophilus influenzae, E. coli Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella
(Coverage: ampicillin/amoxicillin **HELPSS **kill enterococci)
Note: Activity enhanced if used in combination with beta lactamase inhibitors (clavulanic acid, sulbactum)- widens the spectrum
Toxicity:
Hypersensitivity reactions
Pseudomembranous colitis****
Note: broad spectrum penicillins Includes: Ampicillin**, amoxicillin**
Extended spectrum or antipseudomonal penicillin
Extended spectrum or antipseudomonal penicillin
Includes:
Ticarcillin, piperacillin***, azlocillin
Mechanism:
- Same as penicillin, extended spectrum
Spectrum:
- Gram –ve rods including
- Pseudomonas aeruginosa***
Penicillinase sensitive→ use with Beta lactamase inhibitors.
Beta lactamase inhibitors
Beta lactamase inhibitors
Include:*****
Clavulanic Acid
Sulbactum
Tazobactum
= (CAST)
Often added to penicillin antibiotics to protect the antibiotic from destruction by beta lactamase (penicillinase).
penicillins with beta lactamase inhibitor combinations
penicillins with beta lactamase inhibitor combinations
- Piperacillin + tazobactum**
- Ampicillin + sulbactum
- Amoxicillin + clavulanate
- Ticracillin+ clavulanate
Spectrum of activity:
- Activity similar to natural beta lactams, plus, improved activity against beta lactamase producing staphylococci and selected gram negative rods.
- Piperacillin + tazobactum is the most active**
Prophylactic uses of Penicillins
Prophylactic (a medicine or course of action used to prevent disease) uses of Penicillins
Rheumatic fever- is an inflammatory disease that may develop after an infection with group A Streptococcus bacteria (such as strep throat or scarlet fever)
- Benzathine penicillin
Gonorrhoea & Syphillis in sexual partner
- Benzathine penicillin
Bacterial endocarditis prophylaxis
- Amoxicillin or ampicillin
- In patients with prosthetic heart valves, cyanotic heart disease, previous diagnosis of endocarditis- who are planning to undergo dental or respiratory tract or genitourinary or gastrointestinal procedures
Cephalosporins
Cephalosporins
Cephalosporins
- Cephalosporins are beta lactam antibiotics***
- Cephalosporins inhibits cell wall synthesis but are less susceptible to penicillinases.
- Cephalosporins are Bactericidal
- Cephalosporins Have the same MOA (mechanism of action) as penicillins, however they have wider* antibacterial spectrum
- Are resistant* to many beta lactamases
- have longer half lives*
Resistance to cephalosporins is due to :
- Production of Beta-lactamases* (cephalosporinases)
1st generation cephalosporins
1st generation cephalosporins
Includes:
- Cephalexin (oral), cefazolin (parenteral)
Spectrum of activity:
- Active against Gram positive cocci
- Some gram negative activity
- Proteus, E.coli, Klebsiella pneumoniae
- = PEcK**
Use:
- Cefazolin used prior to surgery to prevent S.aureus wound infections**
2nd generation Cephalosporins
2nd generation Cephalosporins
Includes:
- Cefoxitin*, Cefuroxime* ,Cefaclor,
Spectrum of activity:
-
Improved gram negative activity***
- Haemophilus influenza, Enterobacter, Neisseria, Proteus, E.coli, Klebsiella pneumoniae, Serratia (HEN PEcKS) ***
Active against gram positive cocci and some anaerobe e.g. Bacteroides fragilis*
Uses:
Cefoxitin, cefotetan- Bacteroids fragilis*
Cefuroxime, cefaclor, cefamandole – H.influenza*
Note:
Except Cefuroxime others do NOT enter CSF
3rd generation cephalosporins
3rd generation cephalosporins
Includes:
- Ceftriaxone(IM)**, Cefotaxime**, Cefixime (oral) ,Ceftazidime and cefoperazone,
Spectrum:
- Active against gram positive bacteria*
- Improved gram negative activity* to include Pseudomonas
- Can cross BBB** (except Cefoperazone & Cefixime)
Clinical uses:
- Serious gram negative infections- not responding to other beta lactams
- Bacterial Meningitis*: Ceftriaxone*****
- Acute cholecystitis*: Cefotaxime, Ceftriaxone
- Pseudomonas infections*: Ceftazidime***
- Gonorrhoea*: Ceftriaxone**** (parenteral) & Cefixime
- Salmonella typhi infections*: Ceftriaxone, cefaperazone
4th generation cephalosporins
4th generation cephalosporins
Includes:
- Cefepime(IV)**, cefpirome
- Resistant to inactivation by beta lactamases*
- Excellent penetration into gram negative bacteria – increased activity against pseudomonas aeruginosa*
- Wider spectrum than 3rd generation (both Gram positive & negative)
- 4th generaion cephalosporins are Reserve drugs*** and to be used only if the other drugs fail to produce any response.
Cephalosporins
Side effects
Cephalosporins
Side effects
Hypersensitivity reactions- rashes, fever
Cross-reaction between penicillins and cephalosporins
- History of anaphylaxis to penicillin is a contraindication for cephalosporin
Superinfection- diarrhea
note: If given with aminoglycosides- Increased chances of nephrotoxicity
Cefamandole, Cefoperazone & Cefotetan contain methylthiotetrazole group (MTT group) may cause dusulfiram like reactions with ethanol
Vitamin K deficiency causing hypoprothrombinemia and bleeding disorder
Organisms not covered by cephalosporins:
Organisms not covered by cephalosporins are LAME!
= LAME
- *L**isteria monocytogenes
- *A**typical bacteria (Chlamydia, Mycoplasma)
- *M**RSA (exception; ceftaroline coveres MRSA)
- *E**nterococci
Other beta lactam antibiotics
Other beta lactam antibiotics Include:
–Carbapenems like Imipenem***, Meropenem, Ertapenem
–Monobactams like Aztreonam**
Carbapenems
Carbapenems (one of the other beta lactam antibiotics)
Include:
Imipenem***, Meropenem, Ertapenem
Are broad spectrum* antibiotics
Beta lactamases resistant**
Always used with cislastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules
Virtually active against all groups of organisms
Wide activity against Gram positive cocci, Gram negative rods and anaerobes
**Drug of choice in the Rx of Enterobacter infections
Reserve drugs**: used only when other antibiotics not effective
Monobactams
Monobactams (one of the other beta lactam antibiotics)
Includes:
- **Aztreonam** **
- Resistant to beta lactamases
- No cross allerginenicity with penicillins
- Narrow* spectrum antibiotic
- Only active against Gram negative* rods
- Anaerobic and gram positive bacteria are resistant
- *-Can be given to patients who are allergic to penicillin*****
Vancomycin
Vancomycin (classified as the Other Cell wall synthesis inhibitors)
- Vancomycin is a bactericidal glycoprotein***
- Mechanism of action:***
- Binds to D-Ala-D-Ala terminal of peptidoglycan side chain. this leads to Inhibition of cross linking** of the peptidoglycan chains.
-Narrow spectrum
-Used for serious infections* caused by drug-resistant Gram positive organisms especially:
- MRSA**,
- Penicillin resistant pneumococci and
- Clostridium difficile**
**Oral vancomycin is given for refractory C. difficile pseudomembranous colitis
- Initial treatment of choice for pseudomembranous colitis is Metronidazole
____________________________
notes:
- Acts by binding to D-Ala-D-Ala terminal of the nascent peptidoglycan pentapeptide side chain
- This leads to inhibition of transglycosilation
- This in turn prevents the peptidoglycan chain elongation
- All this leads to inhibition of cross linking of the peptidoglycan chains
Mechanism of Resistance to Vancomycin ***
Mechanism of Resistance ***
- Occurs in bacteria via amino acid modification of D-ala D-ala to D-ala D-lac
- decreased affinity of vancomycin for the binding site
- Occurs in strains of enterococci and staphylococci (VRE and VRSA)
Vancomycin
Adverse Effects
Vancomycin
Adverse Effects
-Nephrotoxicity, Ototoxicity, Thrombophlebitis
- remember noooo, NOT vancomycin .vancomycin is a red mon bad mon…. because of its many adverse effects.
-Red man syndrome ***
- because of release of histamine (flushing, redness of face, hypotension),
- this can be prevented by pre-treatment with **antihistamines. **
- resolves spontaneously after discontinuation
Other cell wall synthesis inhibitors
Other cell wall synthesis inhibitors
Bacitracin
- Very nephrotoxic
- Acts by inhibiting cell wall synthesis
- Used topically for its antibacterial property
**Cycloserine **
- inhibits many gram-positive and gram-negative organisms
- Used almost exclusively to treat tuberculosis*** caused by strains of M tuberculosis resistant to first-line agents
Rx of syphilis
Rx of syphilis is penecillin G*
Rx of gonorrhea
Rx of gonorrhea is ceftriaxone*
Rx of MRSA
Rx of MRSA is vancomycin*
Rx of C. difficile
Rx of C. difficile - metronidazole* or vancomycin*
Rx of acute ottitis media
Rx of acute ottitis media (inflammation of the middle ear) – ceftriaxone single dose*
Rx of Meningitis
Rx of Meningitis – ceftriaxone, Cefotaxime*
Rx of Pseudomonas
Rx of Pseudomonas – Cefoperazone*, Ceftazidime*, piperacillin***
Cefazolin is used for?
Cefazolin used prior to surgery to prevent S.aureus wound infections**
**Drug of choice in the Rx of Enterobacter infections
**Drug of choice in the Rx of Enterobacter infections (gram-negative facultative anaerobe. rod-shaped)
Carbapenems drugs (includes imipenem)
Note: carbapenems are always used with cislastatin to decrease inactivation of carbapenems in renal tubule.
