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

08 Antibacterial- cell wall synthesis inhibitors Flashcards by Yvens Ulysse Jr.

Bactericidal Drugs

what they do and example of these drugs

Bactericidal Drugs

Cause death of the microorganism

Eg:

Penicillins

Aminoglycosides

Cephalosporins

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Bacteriostatic Drugs and what they do

Inhibit the growth of the microorganism

E.g. Sulfonamides, Tetracyclines, Erythromycin

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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

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

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***

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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

Side effects of Penicillins

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)

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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

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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

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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**

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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.

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Beta lactamase inhibitors

Include:*****
Clavulanic Acid
Sulbactum
Tazobactum
= (CAST)

Often added to penicillin antibiotics to protect the antibiotic from destruction by beta lactamase (penicillinase).

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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**

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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 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

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

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

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

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

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: ## Footnote –_Carbapenems_ like **Imipenem\*\*\***, Meropenem, Ertapenem –_Monobactams_ like **Aztreonam\*\***

Carbapenems

Carbapenems (one of the other beta lactam antibiotics) ## Footnote 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 **-N**ephrotoxicity, **O**totoxicity, **T**hrombophlebitis * 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 ## Footnote

\*\*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.