Beta-Lactam Antibiotics & Other Cell Wall Synthesis Inhibitors Flashcards by VERNARD DOMINIC ALOYON

what are the similarities of bactericidal and bacteriostatic?

they are both antimicrobial drugs

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What are the differences of bactericidal ang bacteriostatic?

Bactericidal - eradicate infection without host defense mechanism
Bacteriostatic - inhibits antimicrobial growth, need host defense mechanism to eradicate infection

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Drugs with structures containing a beta-lactam ring: includes the penicillins, cephalosporins and carbapenems. This ring must be intact for antimicrobial action

Beta-lactam
antibiotics

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Bacterial enzymes (penicillinases, cephalosporinases) that hydrolyze the beta-lactam ring of certain penicillins and cephalosporins

Beta-lactamases

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Potent inhibitors of some bacterial beta-lactamases used in combinations to protect hydrolyzable penicillins from inactivation

Beta-lactamase
inhibitors

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Lowest concentration of antimicrobial drug capable of
inhibiting growth of an organism in a defined growth
medium

Minimal
inhibitory
concentration
(MIC)

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Bacterial cytoplasmic membrane proteins that act as the initial receptors for penicillins and other beta-lactam antibiotics

Penicillin-binding
proteins (PBPs)

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Chains of polysaccharides and polypeptides that are
cross-linked to form the bacterial cell wall

Peptidoglycan

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More toxic to the invader than to the host; a property of
useful antimicrobial drugs

Selective
toxicity

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Bacterial enzymes involved in the cross-linking of linear peptidoglycan chains, the final step in cell wall synthesis

Transpeptidase

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Types of Microbial resistance:

1.Production of antibiotic-inactivating enzymes
2.Changes in the structure of target receptors
3.Increased efflux via drug transporters
4. Decreases in the permeability of microbes’ cellular membrane to antibiotics

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Strategies to combat Microbial resistance

Use of adjunctive agents that can protect against antibiotic inactivation
Use of antibiotic combinations
Introduction of new chemical derivatives of establish anibiotics
Efforts to avoid indiscriminate use or misuse of anitbiotics

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the major antibiotics that
inhibit bacterial cell wall synthesis:

Penicillins
Cephalosporins

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Why are they called beta-lactams

Because of their 4-member ring

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include some of the most
effective, widely used, and well-tolerated agents available for
the treatment of microbial infections.

beta-lactams

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also inhibit cell wall synthesis but are not nearly as important as the beta-lactam drugs:

Vancomycin
Fosfomycin
Bacitracin

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The selective toxicity
of the drugs discussed in this chapter is mainly due to specific
actions on the _________ that is unique to the microorganism.

synthesis of a cellular structure

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how many antibiotics that act as cell wall synthesis inhibitors are currently available, with individual
spectra of activity that afford a wide range of clinical applications

More than 50

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2 types of Narrow spectrum Penicillins

Penicillinase susceptible
Penicillinase resistant

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What generation is included in narrow spectrum cephalosporins?

1st generation

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What generation is included in wider spectrum cephalosporins?

2nd, 3rd, 4th generation

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3 miscellaneous Bacterial cell-wall inhibitors

Carbapenems
Aztreonam
Vancomycin

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Penicillins are derivatives of what?

6-aminopenicillanic acid

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What does all penicillins contain that is esential for antibacterial activity

beta-lactam ring

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Penicillin subclasses have additional chemical substituents that confer differences in:

- antimicrobial activity - susceptability to acid and enzymatic hydrolysis - biodisposition

# Pharmacokinetics Since penicillins vary in their resistance to gastric acid, therfore they vary in their __________

Oral Bioavailability

# Pharmacokinetics Why are penicillins not metabolized extensively?

because they are polar compounds

# Pharmacokinetics What are the penicillin parenteral formulations that are available for injections?

- Ampicillin - Piperacillin - Ticarcillin

# Pharmacokinetics Penicillins are usually unchange in the urine via:

- glomerular filtration - tubular secretion

# Pharmacokinetics The tubular secretion of penicillins are inhibited by?

Probenecid

# Pharmacokinetics What kind of penicillin is mainly excreted in the bile?

Nafcillin

# Pharmacokinetics What kind of penicillin undergoes enterohepatic cycling?

ampicillin

# Pharmacokinetics Half life of most penicillins?

30 mins to 1 hour

# Pharmacokinetics Forms of penicillin G that are administered intramuscularly and have longer half lives

- procaine - benzathine

# Pharmacokinetics Why do procaine and benzathine have longer plasma half-lifes?

because the active drug is released vrey slowly to the bloodstream

# Pharmacokinetics When does most penicillins cross the blood-brain barrier?

When the meniges are inflamed

# Mechanisms of Action What kind of drugs are beta-lactams?

Batericidal drugs

# Mechanisms of Action Steps on how beta-lactams inhibit cell wall synthesis:

1. Bind to specific receptors (penicillin-binding proteins) 2. Inhibition of transpeptidation reaction 3. Activation of autolytic enzymes

# Mechanisms of Action Where are PBPs located?

in the bacterial cytoplasmic membrane

# Mechanisms of Action the reaction that cross-links the linear pe[tidoglycan chain constituents of the cell wall

Transpeptidation reaction

# Mechanisms of Action Enzymes that causes lesions in the bacterial cell wall

Autolytic enzymes

# Resistance If this happens to the beta-lactam ring, it will result in the loss of antibacterial activity

Enzymatic hydrolysis

# Resistance Is the major mechanism of bacterial resistance

Formation of beta-lactamase (penicillinase)

# Resistance What organisms use the formation of penicillinase as resistance?

- staphylococci - gram negative organisms

# Resistance What inhibitors of penicillinase are often used in combination with penicillin to prevent their inactivation?

- cluvanic acid - sulbactam - tazobactam

# Resistance Structural change in target PBPs of staphylococci is responsible for?

methicillin resitance

# Resistance Structural change in target PBPs of pneumococci and enterococci is responsible for?

penicillin G resistance

# Resistance Example of pneumonococci

Penicillin resistant Streptococcus pneumoniae (PRSP)

# Resistance What organisms use changes in the porin structure as resistance

Gram negative rods (Pseudomonas aeruginosa)

# Resistance changes in the porin structures in the outer cell wall membrane may contribute to resistance by what?

impeding access of penicillins to PBPs

# Clinical Uses Narrow-spectrum penicillinase-susceptible agents

- Penicillin G - Penicillin V

# Clinical Uses the prototype of a subclass of penicillins that have a limited spectrum of antibacterial activity and are susceptible to beta-lactamases.

Penicillin G

# Clinical Uses Penicillin G theraphy of infections include?

1. common streptococci 2. miningcocci 3. gram-positive bacilli 4. spirochetes

# Clinical Uses Strains of pneumococci that are now resistant to penicillins

Penicillin resistant S. pneumoniae (PRSP)

# Clinical Uses Strains that are resistant to penicillin via beta-lactamase:

- Stapphylococcus aureus - Neisseria gonorrhoeae

# Clinical Uses Penicillin G is the suitable drug for?

Syphilis

# Clinical Uses Penicillin G is not the suitable drug for?

gonorrhea

# Clinical Uses Activity of penicillin G against enterococci is enhanced by?

coadministration of aminoglycosides

# Clinical Uses oral drug mainly used in oropharyngeal infections

Penicillin V

# Clinical Uses Very-narrow-spectrum penicillinase-resistant drugs:

- methicillin - nafcillin - oxacillin

# Clinical Uses Very-narrow-spectrum penicillinase-resistant drug that is a prototype but rarely used because of its nephrotoxic potential

methicillin

# Clinical Uses The primary use of Very-narrow-spectrum penicillinase-resistant drugs is in the treatment of known or suspected _________

staphylococcal infections

# Clinical Uses are resistant to all penicillins and are often resistant to multiple antimicrobial drugs.

Methicillin-resistant (MR) staphylococci - S. aureus (MRSA) - S. epidermis (MRSE)

# Clinical Uses Wider-spectrum penicillinase-susceptible drugs:

- Ampicillin and Amoxicillin - Piperacillin and Ticarrcillin

# Clinical Uses Ampicillin and amoxicillin therapy of infections include?

1. similar to penicillin G 2. enterococci 3. Listeria monocytogenes 4. Escherichia coli 5. Proteus mirabilis 6. Haemophilus influenzae 7. Moraxella catarrhalis

# Clinical Uses Piperacillin and ticarcillin have activity against:

gram-negative rods - Pseudomonas - Enterobacter - Klebsiella sps

# Clinical Uses Most drugs in this subgroup have synergistic actions with aminoglycosides against such organisms.

Piperacillin and ticarcillin

# Clinical Uses What penicillinase inhibitors are used with piperacillin and ticarcillin to ennhance their activity?

- tazobactam - clavulanic acid

# Toxicity Allergic reactions to penicillin include:

- urticaria - severe pruritus - fever - joint swelling - hemolytic anemia - nephritis - anaphylaxis

# Toxicity How many percent of people with history of penicillin reaction have a allergic response when given penicillin again?

5-10%

# Toxicity Methicilin causes?

interstitial nephritis

# Toxicity nafcillin is associated with?

neutropenia

# Toxicity Ampicillin frequently causes?

maculopapular skin rash

# Toxicity What are the antigenic determinants that causes allergic reactions to penicillin

Penicilloic acid

# Toxicity Degration product of penicillin

penicilloic acid

# Toxicity occur with oral penicillins, especially with ampicillin.

Nausea and diarrhea

# Toxicity Toxicity of penicillins:

- Allergy - Gastrointestinal disturbances

# Toxicity Gastrointestinal upsets from penicillin may be caused by:

- direct irritation - overgrowth of gram + organisms or yeast

# Toxicity Ampicillin has been implicated in what disease?

pseudomembranous colitis

The cephalosporins are derivatives of what?

7-aminocephalosporanic acid

1st generation Cephalosporins

1. cephalexin 2. cefazolin 3. cefadroxil 4. cephalotin 5. cephadrine 6. cephapirin

2nd generation cephalosporins

1. cefuroxime 2. cefoxitin 3. cefotetan 4. cefamandole 5. cefaclor

3rd generation cephalosporins

1. ceftriazone 2. cefotaxime 3. cefoperazone 4. ceftazidime 5. cefixime 6. cefnidir 7. moxalactam

4th genaration cephalosporins

1. cefepime 2. ceftaroline

# Pharmacokinetics Several cephalosporins are administered via

oral

# Pharmacokinetics Most cephalosporin are administered via?

parenterally

# Pharmacokinetics Major elimination mechanism of cephalosporins?

renal exretion via active tubular secretion

# Pharmacokinetics What kind of elimination mechanism cephalosporins with side chains may undergo?

hepatic metabolism

# Pharmacokinetics Type of cephalosporin excreted mainly in the bile?

- cefoperazone - ceftriazone

# Pharmacokinetics What generation of cephalosporins do not enter the cerebrospinal fluid even when the miniges are inflamed?

First and second generation

# Resistance Structural differences from penicillins render cephalosporins less susceptible to penicillinases produced by __________

staphylococci

# Resistance Many bacteria are still resistant to cephalosporins through?

production of other beta-lactamase that can inactivate cephalosporins

# Resistance Resistance to cephalosporins can also resukt from:

- decrease of permeability to cephalosporins - changes in PBPs

# Resistance Are Methicillin-resistant staphylococci resistant to cephalosporins?

yups

# Clinical Uses Cefazolin is administered via

parenteral

# Clinical Uses cephalexin is administered via?

oral

# Clinical Uses First generation drugs are active againts:

- Gram positive cocci (staphylococci and common streptococci) - E. coli - K. pneumoniae

# Clinical Uses Clinical uses of 1st generation drugs

- treatment of infection - surgical prophylaxis (selected conditions)

# Clinical Uses First generation drugs have limited activity against:

- gram-negative cocci - enterococci - methicillin-resistant staphylococci - gram negative rods

# Clinical Uses Drugs in this subgroup usually have slightly less activity against gram-positive organisms than the first-generation drugs but have an extended gram-negative coverage.

Second-generation drugs

# Clinical UsesClinical Uses Second generation drugs that can treat infections caused by the anaerobe Bacteroides fragilis

- cefotetan - cefoxitin

# Clinical Uses Second-generation drugs that can treat sinus, ear, and respiratory infection caused by H. influenzae or M catarrhaliss

- cefamandole - cefuroxime - cefaclor

# Clinical Uses Feature of this subgroup include increased activity against gram-negative organisms resistant to other beta-lactam drugs and ability to penetrate the blood-brain barrier

Third generation drugs

# Clinical Uses 3rd generations drugs that cannot penetrate the blood-brain barrier

- cefoperazone - cefixime

# Clinical Uses 3rd generation drugs are active against:

- Providencia - Serratia marcescens - beta-lactamase producing strains (H. influenza and Neisseria)

# Clinical Uses 3rd generation drugs are less active against?

Enterobacter strains that produce extended-spectrum beta-lactamases

# Clinical Uses Currently the most active cephalosporins against penicillin-resistant pneumonococci (PRSP strains) | but resistance is reported

Ceftriaxone and cefotaxime

# Clinical Uses 3rd generation drugs that have activity against Pseudomonas

- cefoperazone - ceftazidime

# Clinical Uses 3rd generation drugs that have activity against B. fragilis

ceftizoxime

# Clinical Uses Drugs in this subclass should usually be reserved for treatment of serious infections

3rd generation drugs

# Clinical Uses Ceftriaxone is adminstered via?

parenteral

# Clinical Uses cefixime is administered via?

oral

# Clinical Uses Drugs of choice for gonorrhea?

- ceftriaxone - cefixime

# Clinical Uses In acute otitis media, a single injection of ceftriaxone is usually as effecetive as?

10-day course treatment of amoxicillin

# Clinical Uses Cefepime is more resistant to beta-lactamases produced by gram-negative organism including:

- Enterobacter - Haemophilus - Neisseria - penicillin-resistant pneumococci

# Clinical Uses combines the gram-positive activity of first-generation agents with the wider gram-negative spectrum of third-generation cephalosporins

Cefepime

# Clinical Uses has activity in infections caused by methicillin-resistant staphylococci.

Ceftaroline

# Toxicity Allergic reaction of cephalosporins:

- skin rashes - anaphylactic shock

Allergic reactions occur less frequently in penicillins than with cephalosporins

that is not factual

Does complete cross-hypersensitivy exist in different cephalosporins

yups

Does complete cross-reactivty exist between penicillins and cephalosporins?

nope

Should patients with history of anaphylaxis to penicillins be treated with cephalosporins?

no way

Cephalosporins may cause pain at __________

intramuscular injection sites

Cephalosporins may cause _______ after intravenous administration

phlebitis

What will happen if you administer cephalosporin with aminoglycosides?

increase nephrotoxicity

may cause hypoprothrombinemia and disulfiram-like reactions with ethanol.

Drugs containing a methylthiotetrazole group - cefamandole - cefoperazone - cefotetan

Is a monobactam that is resistant to beta-lactamases produced by certain gram-negative rods

Aztreonam

What are the certain gram negative rods that aztreonam are resistant to

- Klebsiella - Pseudomonas - Serratia

Aztreonams have no activity against?

Gram-positive bacteria or anaerobes

Where does aztreonam prefer to bind?

PBP3

Aztreonam are synergistic with what?

Aminoglycosides

Aztreonam is administered via?

Aztreonam is eliminated via?

Renal tubular secretion

Aztreonam’s half life is prolonged in what situation?

Renal failure

Adverse effects of aztreonam:

- gastrointestinal upset with possible superinfection - vertigo - headache - hepatoxicity (rare)

Can Skin rash occur in aztreonam?

Yeah

Cross-allergenity of aztreonam with penicillin is possible?

Nope

Examples of carbapenems

- imipenem - doripenem - meropenem - ertapenem

Drugs that are chemically different from penicillins but retaining the betalactam ring structure with low susceptanility to beta-lactamases

Carbapenems

Carbapenems have wide activity against:

- gram-positive cocci (penicillin resistant pneumococci) - gram-negative rods - anerobes

Carbapenems are used in combination with what in pseudomonal infections

Aminoglycosides

Carbapenems are administered via?

Parenterally

Drugs that are useful for infections caused by organisms resistant to other antibiotics

Carbapenems

Organisms that are resistant to carbapenems

MRSA strains of staphylococci

Carbapenems are currently co-drugs of choice for infections caused by:

- enterobacter - citrobacter - serratia

Imipenem is rapidly inactivated by what?

Renal dehydropeptidase I

An inhibitor of the enzyme renal dehydropeptidase

Cilastatin

Imipinem is always administered with this

Cilastatin

Increases the half life of imipenem and inhibits the formation of a potentially nephrotoxic metabolite

Cilastetin

Adverse effects of imimpenem-cilastetin:

- gastrointestinal distress - skin rash - very high plasma levels - cns toxicity (confusion, enchepalopathy, seizures)

Does Imipenem-cilastatin have partial allergenicity with penicillins

Yups

Is similae to imipenem except that it is not metabolized by renal dehydropeptidases and is less likey to cause seizures

Meropenem

Type of carbapenem that has a long half life but is less active against enterococci and Pseudomonas and its intramuscular injection causes pain and irritation

Ertapenem

Examples of beta-lactamase inhibitors

- clavulanic acid - sulbactam - tazobactam

Are used in fixed combinations with certain hydrolyzable penicillins

Beta-lactamase inhinbitors

Beta-lactamase inhibitors are most active against:

Plasmid-encoded beta-lactamase produced by: - gonococci - streptococci - e. coli - h. influenzae

Beta-lactamse inhibitors are not good inhibitors of what?

Inducible chromosomal beta-lactamases formed by - enterobacter - pseudomonas - serratia

Is a bactericidal glycoprotein that binds to the D-Ala-D-Ala terminal of nascent peptidoglycan pentapeptide side chain

Vancomycin

Drug that inhibit transglycosylation

Vancomycin

Drug that prevents elongation of the peptidoglycan chain and interferes with cross linking

Vancomycin

Strains that are resistan to vancomycin

- vancomycin-resistant enterococci (VRE) - vancomycin-resistant S. aureus

How does VRE and VRSA resist vancomycin?

Replacement of the terminal D-ala by D-lactate

Vancomycin are used for serious infections caused by?

Drug-resistant gram-positive organisms - methicilin-resistan staphylococci (MRSA) - penicillin-resistan pneumococci - c. difficile

Vancomycins are used in combination with what for treatment if penicillin resistan pneumococci (PRSP)?

3rd generation cephalosporin (ceftriaxone)

Vancomycin is also a backup drug for treatment of infections caused by?

Clostridium difficile

Drugs that similar characteristics to vancomycin

Teicoplanin and telavancin

Vancomycin is not absorbed from the

Gastrointestinal tract

Vancomycin may be given orally for what disease?

Bacterial enterocolitis

When given this way, vancomycin penetrates most tissues and is eliminated unchanged in the urine

Parenterally

This mandatory in patients with renal impairment taking vancomycin

Dosage modification

Toxic effects of vancomycin:

- chills - fever - phlebitis - ototoxicity - nephrotoxicity

Rapid intavenous infusion of vancomycin may cause

Diffuse flushing (red man syndrome) from histamin release

Is an antimetabolite inhibitor of cytosolic enolpyruvate transferase

Fosfomycin

Prevent formation of N-acetylmuramic acid

Fosfomycin

An esential precursor molecule for peptidoglycan chain formation

N-acetylmuramic acid

Resistance to fosfomycin occurs via

Decreased intracellular acumulation of the drug

Fosfomycin is excreted via?

Kidney

Fosfomycin urinary levels exceed what for many urinary tract pathogens

Minimal inhibitory concentrations (MICs)

In a single dose, this drug is less effective than a 7-day course of treatment with flouriquinolones

Fosfomycin

With multiple dosing of this drug, resistance emerges rapidly and diarrhea is common

Fosfomycin

Fosfomycin may be synergistic with these drug in specific infections

Beta-lactam and quinolone antibiotics

Is a peptide antibiotic that interferes with a late stage in cell wall synthesis in gram-positive organisms

Bacitracin

Because of its marked nephrotoxicity, the drig is limited to topical use

Bacitracin

An antimetabolite that blocks the incorporation of D-ala into the pentapeptide side chain of peptidoglycan

Cycloserine

Bacause of its potential neurotoxicity, it is only used to treat tuberculosis caused by organisms resistant to first line antituberculosis drugs

Cycloserine

Is a novel cyclic lipopeptide with spectrum similar to vancomycin but active against vancomycin-resistant strains of enterococci and staphylococci

Daptomycin

Daptomycin is eliminated via

Kidney

This should be monitored since daptomycin may cause myopathy

Creatine phosphokinase

CYLCOSERINE toxic effects

potential neurotoxicity - tremors - seizure - psychosis

Beta-Lactam Antibiotics & Other Cell Wall Synthesis Inhibitors Flashcards

(189 cards)