Bacteriology 6: Antiboiotics Flashcards by Anaili Abreu

In dentistry, prophylactic agents on used on patients who:

before the patients procedure
-amoxicillin or clindamycin
-endocarditis risk
-facial fractures, compound skull fractures, and cerebral rhinorrhea
-immunocompromised
-recently received radiotherapy to the jaws
-prosthetic hip replacements, ventriculoatrial shunts, insertion of implants or bone grafting

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Which is the antimicrobial drug of choice (DOC) for prophylaxis of infectious endocarditis?

Amoxicillin

clindamycin is used when patients are allergic to amoxicillin

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Why would there be failure of antimicrobial therapy?

-inadequate drainage of pus/debriddement before administering prescription
-inappropriateness of the antimicrobial agent
-impaired host response
-poor patient compliance
-poor blood supply to tissues
-possibility of an unusual infection or that the disease has no infective etiology
-presence of local factors such as foreign bodies, which may act as reservoirs of reinfection

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Mechanisms of action for folic acid metabolism medications

Medications:
-trimethoprim
-sulfonamides

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Mechanisms of action for cell wall synthesis medication (8)

inhibit the PG’s
-vancomycin
-bacitracin

inhibit the crosslinking of PG’s (B-lactams)
-penicillins
-monobactams
-carbapenems
-cephalosporins

-cycloserine

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Mechanisms of action for cell membrane medications

Polymyxins

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Mechanisms of action for protein synthesis (30s inhibitors)

Prevent the tRNA from entering the A- site of the ribosome by blocking it (tetracycline) or Some change the shape of the 30S subunit, causing misreading of the codons (streptomycin)

-tetracyclines (Doxycyline, minocycline) intracellular pathogens
-Aminoglycosides (streptomycin, gentamicin)

bactericidal

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Mechanisms of action for protein synthesis (50s inhibitors)

-erythromycin
-chloramphenicol
-clindamycin

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Mechanisms of action for DNA-dependent RNA polymerase

Rifampin

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Mechanisms of action for DNA replication (DNA gyrase)

-nalidixic acid
-quinolones

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Why is bactericidal a good selective toxicity?

B/c Eukaryotic cells lack peptidoglycan

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What do cell wall agents do?

They either prevent the synthesis of wall components or the assembly of the synthesized precursors of the wall components.
-bactericidal = good selective toxicity b/c eukaryotic cells lack a cell wall (peptidoglycan)

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Penicillin structure and target

structure
All have a thiazolidine ring joined to a B-lactam ring to which the side chain is attached
-the side chain dictates susceptibility to B-lactamase and spectrum of activity.

target
penicillin will inhibit the transpeptidase (referred to as penicillin-binding protein) which is the last step of the peptidoglycan synthesis (cross-linking the polymer)

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Where in the carbohydrate backbone of the peptidoglycan cell wall structure does the alternating D/L amino acid peptide chain bind?

The peptide chain (D/L aa) will bind to **NAM **
D-ala being the terminal aa
Peptide Inter bridge is formed by the transpeptidase… this is what causes the cross-linking

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Penicillins-resistance

Bacteria will have enzymes such as B-lactamase or penicillinase causing penicillin resistance by hydrolyzing the drug ineffective by opening the B-lactam ring in penicillin converting it to penicilloic acid (ineffective penicillin)

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There are two forms of naturally occurring penicillin (Narrow spectrum)

Pen G = degraded by stomach acid thus requires injection administration (painfully b/c given intramuscular)
Pen V = taken orally = It was developed to be more stable in acidic conditions, making it suitable for oral administration.

nature INVENTED penicillin, someone DISCOVERED penicillin

Penicillin G is effective against a broad range of Gram-positive bacteria and some Gram-negative bacteria.

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Penicillins - B-lactamase resistant

Synthetic penicillin generated to be Resistant to the B-lactamase of staphylococci

-oxacillin
-methicillin
-dicloxacillin
-Nafcillin
-Cloxacillin
-Flucloxacillin

Natural penicillin (like Penicillin G) mainly targets Gram-positive bacteria. Synthetic penicillins were created to extend activity to Gram-negative bacteria as well.

Synthetic penicillins like Methicillin, Oxacillin, and Nafcillin were designed to be resistant to β-lactamase, making them effective against penicillin-resistant bacteria, such as Staphylococcus aureus

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Penicillins- broad spectrum/ aminopenicillins
-sensitive to B-lactamase

B-lactam antibiotics
ampicillin
amoxicillin

More effective on gram (-)
These are also synthetic penicillin

Many Gram-negative bacteria produce β-lactamase in the periplasmic space, but not all of them produce high enough levels to completely degrade amoxicillin before it can act on the bacteria.
Amoxicillin can still be effective against Gram-negative bacteria that either:
Produce low amounts of β-lactamase, or
Do not produce the specific types of β-lactamase that efficiently break down amoxicillin (some broad-spectrum or extended-spectrum β-lactamases).

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Penicillins- extended spectrum/anti-pseudomonal

Sensitive to B-lactamase
-mezlocillin
-piperacillin
-ticaracillin
-carbenicillin

More effective against gram (-) RODS
-P.aeruginosa
-E.coli
-H.influenza
-K.pneumoniae

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Cephalosporins
-structure

Have a B-lactam ring and a dihydrothiazine ring. It also contains 2 R groups that determine the pharmacological properties

Instead of a pentagon attached to the B-lactam ring like in penicillin is a hexagon attached to the B-lactam ring in cephalosporin antibiotics. They utilize the same mechanism of action

some bacterias produce cephalosporinases which make them resistant

-resistant to inactivation by certain B-lactamases (S.aureus)

Gram-Positive Bacteria:
Gram-positive bacteria, such as Staphylococcus aureus, can produce β-lactamase enzymes that break down β-lactam= making them resistant.
In Gram-positive bacteria, β-lactamases are secreted outside the cell, into the surrounding environment. Since Gram-positive bacteria do not have an outer membrane, their cell wall is directly exposed to the external environment.

Gram-Negative Bacteria:
In Gram-negative bacteria, β-lactamases are often found in the periplasmic space (the area between the outer membrane and the cell wall). Here, they break down β-lactam antibiotics after they pass through the outer membrane but before they can reach PBPs in the periplasmic space.

What type of antibiotics have increased generations and why?

The generations of cephalosporin antibiotics were increased to expand their spectrum of activity and to improve their effectiveness against resistant bacteria.

Cephalosporins are classified into “generations” based on their susceptibility, potency, and spectrum (activity)

First Generation:
Mostly active against Gram-positive bacteria (e.g., Staphylococcus and Streptococcus).
Examples: Cefazolin, Cephalexin.
Limited activity against Gram-negative bacteria.

Second Generation:
Expanded activity against Gram-negative bacteria HEN PEcKS (e.g., Haemophilus influenzae, Enterobacter aerogenes Neisseria, serratia).
Examples: Cefuroxime, Cefoxitin, cefprozil
Decreased against many Gram-positive bacteria

**Third Generation:
Further expanded activity against Gram-negative bacteria, including HEN PEcKS, salmonella, S.pneumoniae
Better CNS penetration, useful for treating meningitis.
Examples: Ceftriaxone, Cefotaxime, Ceftazidime, cefdinir
Less effective against Gram-positive bacteria compared to first-generation drugs.

Fourth Generation:
Broad-spectrum coverage of both Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa.
Enhanced resistance to enterobacter β-lactamases.
Example: Cefepime, cefozopran

Fifth Generation
Active against methicillin-resistant Staphylococcus aureus (MRSA) and other resistant Gram-positive organisms, in addition to Gram-negative bacteria.
Example: Ceftaroline, ceftolozane, ceftobiprole

Carbapenems

Makes them active against most bacteria
-consists of a B-lactam ring but has an semisynthetic ring attached to it (imipenem, meropenem, ertapenem, doripenem)
Poor oral bioavailability - given I.V.

Resistant to most B-LACTAMASES

Monobactams

Aztreonam

Narrow spectrum of activity
Mostly against gram (-) = aerobes
Used as a last resort when bacteria is pretty much resistant to everything, and allergic to penicillin

Resistant to most B-lactamases and cephalosporinases

Monobactams have a monocyclic β-lactam ring, which is different from the bicyclic structure of penicillins and cephalosporins. This unique structure makes them resistant to certain types of β-lactamase enzymes.

B-lactamase inhibitors

Bind more efficiently to the B-lactamase enzymes, allowing B-lactam antibiotics to be more effective

CA = Clavulanic acid
Sulbactam
Tazobactam

These have little antimicrobial activity and must be combined with a B-lactan antibiotic

Combos in a single pill
Augmentin = CA + amoxicillin
Unasyn = Sulbactam + ampicillin
Zosyn = Tazobactam + piperacillin
Zerbaxa = Tazobactam + ceftolozane

Amoxicillin is broken down by B-lactamase of bacteria,
to penicilloic acid. If Clavulanic acid is incorporated with amoxicillin, it inhibits the B-lactamase activity.

Why do we have combinations in a single pill of B-lactam antibiotics with B-lactamase inhibitors?

Combining β-lactam antibiotics with β-lactamase inhibitors in a single pill addresses the challenge of bacterial resistance to β-lactam antibiotics.

β-Lactamases are enzymes produced by many bacteria that break down the β-lactam ring in antibiotics like penicillins and cephalosporins, making them ineffective.
By combining a β-lactam antibiotic with a β-lactamase inhibitor, the inhibitor can neutralize the β-lactamase enzyme, allowing the β-lactam antibiotic to remain effective against the bacteria.

Amoxicillin is broken down by B-lactamase of bacteria,
to penicilloic acid. If Clavulanic acid (CA) is incorporated with amoxicillin, it inhibits the B-lactamase activity.
Amoxicillin + CA = augmentin

Non-B-lactam cell wall inhibitors
-medication
-mechanism

Bacitracin

Targets the lipid carrier that transports the peptidoglycan precursors across the cytoplasmic membrane where they are assembled
Toxicity limits it to topical use only = neosporin

Vancomycin
Forms hydrogen bonds with D-ala terminus. This stabilize the vancomycin, preventing the transglycosylation and transpeptidation steps of cell wall synthesis, thereby inhibiting cell wall formation.

Transglycosylation: The enzyme responsible for adding the NAG-NAM-peptide precursor to the growing peptidoglycan chain is blocked, preventing polymerization.
Transpeptidation: This step, in which transpeptidase enzymes cross-link peptidoglycan strands, is also blocked because Vancomycin prevents access to the D-Ala-D-Ala dipeptide.

Cell wall inhibitors for mycobacteria
-medication

Isoniazid
ethionamide
These medication interfere with the synthesis of mycolic acids (a unique component of mycobacterial cell walls)

Called “mycobacteria” b/c of observations of their fungal-like appearance and rod shape (bacteria)
Typically also involves a multi-drug therapy

Treating mycobacterial infections, such as those caused by Mycobacterium tuberculosis (which causes tuberculosis) and Mycobacterium leprae (which causes leprosy), requires specific antibiotics that target their unique cell wall components. Mycobacterial cell walls have distinctive features, including a high lipid content and mycolic acids, which make them different from the cell walls of other bacteria.

Cell membrane agents

Polymyxin
Disrupts the cell membrane!!!!! By inserting themselves (a fatty acid portion) into the outer bacterial membrane (onto LPS) disrupting its structure and function. Causing cell death

Polymyxin B is effective against Gram-negative bacteria, such as Escherichia coli and Pseudomonas aeruginosa.

Due to possibility of nephrotoxicity- used topically

What’s in neosporin?

This is a triple antibiotic therefore it will have 3 things
-Bacitracin (inhibiting cell wall synthesis by preventing a lipid carrier that transports peptidoglycan precursors across the cytoplasmic membrane where they are assembled)
-Polymyxin B (A polymyxin antibiotic that disrupts the bacterial cell membrane.)
- Neomycin (An aminoglycoside antibiotic that inhibits protein synthesis in bacteria.)

Capsule
Outter membrane
Perplasmic space
Cell wall
Inner membrane
Cytosol

Why add Polymyxin B into Neosporin?

Polymyxin B is effective against Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa. Including it in Neosporin helps cover a broader range of potential pathogens.

Polymyxin B disrupts the cell membrane!!!!! By inserting themselves (a fatty acid portion) into the outer bacterial membrane (onto LPS) disrupting its structure and function. Causing cell death

What do you have to consider before prescribing an antimicrobial agent?

infective etiology, specimen, when to start treatment, which agent

Why selective toxicity is important during antimicrobial therapy?

So it does not harm anything else BUT the target microorganism

Bactericidal, selective toxicity, active in body/even when diluted, does not make susceptible bacteria become resistant, no side effects (ideally), not metabolize too fast, stable, soluble

Quinolones - Fluorooquinolones
-medications
-mechanism

Nucleic acid interacting agents
-Ciprofloxacin
-Levofloxacin
-Norfloxacin
-Moxifloxacin
-Sparfloxacin

good choice for intracellular pathogens b/c of their good penetration of macrophages and neutrophils

These are going to inhibit DNA replication by interfering w/ DNA gyrase (the enzyme responsible for uncoiling/relaxing DNA) these are working with topoisomerases

Metronidazole
-medication
-mechanism
-bacteria

Bactericidal
Breaking DNA braches by increasing free radicals.
Anaerobic bacteria

Protein synthesis agents