2 - B-lactam ABX & B-lactamase Inhibitors Flashcards by Patricia Lovina

4 classes of B-lactam antibiotics

Penicillin
Cephalosporin
Monobactam
Carbapenem

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B-lactam MOA

Inhibition of peptidoglycan synthesis by binding to transpeptidase enzyme, preventing NAM amino acids to form crosslinks.

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4 causes of B-lactam resistance

1) B-lactamase production
2) Modification of target PBPs
3) Impaired penetration of drug
4) Drug efflux

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What structure does all B-lactam have in common?

B-lactam ring

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How does resistance happen through B-lactamase production?

B-lactamase enzyme degrade the B-lactam ring

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Structure of Penicillin?

B-lactam ring attached to thiazolidine ring. Different R groups yield derivatives of Penicillin.

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Penicillin Classification?

Narrow spectrum
penicilinase-resistant penicillins (resistant to staphylococcal b-lactamases)
extended spectrum penicillins

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Example of narrow spectrum penicillin

Penicillin G = Benzylpenicillin (iv)

Penicillin V = phenoxymethyl penicillin (oral)

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Example of Penicillinase-resistant penicillins (resistant to staphylococcal B-lactamase)

Methicillin
Nafcillin
Isoxazoyl penicillins (oxacillin, cloxacillin, dicloxacillin)

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Example of extended-spectrum penicillins

Amoxicillin
ampicillin
piperacillin
ticarcillin

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Previously, the activity of penicillin G was defined in units. Semisynthetic penicillins are prescribed by?

Weight

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Define penicillin stability in dry and solution state

dry crystalline –> years

solution –> degrade very rapidly (24 hours at 20C)

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Which factors affect oral absorption of Penicillin?

Acid stability and protein binding

ex: dicloxacillin, ampicillin, amoxicillin are acid stable and well absorbed

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All oral penicillin absorption are impaired by food except?

amoxicillin

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When should oral penicillin be administered?

1-2 hours before or after a meal

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Which penicillin derivative causes irritation and local pain if administered in a large dose through IM?

Penicillin G. That’s why IV is prefer

red

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Which penicillin derivative are formulated to delay absorption (repository)? How long can it last?

Benzathine and procaine. One dose can last for 10 days.

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Which body part receives a higher distribution of penicillin?

None, its equally distributed throughout the body.

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Therapeutic concentration of penicilllins are achieved in tissue and secretions (joint fluid, pericardial fluid, bile). Which cell and 2 tissues don’t it penetrate?

Living phagocytic cells

1) brain tissue penetration
2) intraocular fluid

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Penicillin is excreted into the sputum (dahak) and milk up to 15% levels present in the serum. true or false?

True. 3-15% of serum levels

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Excretion of penicillin through the kidneys occur in 2 places, one contributing 10%, one 90%. Which pathways are those?

10% - glomerular filtration

90%- renal tubular secretion

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A penicillinase resistant penicillins (resistant to staph b-lactamase) is primarily cleared by biliary excretion. Which is it?

Nafcillin.

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Which penicillin are eliminated by both kidney and biliary excretion?

Isoxazolyl penicillins (oxacillin, cloxacillin, and dicloxacillin)

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Why is dose adjustment of penicillin (not just by weight) required in newborns?

Penicillin clearance is less efficient in newborns.

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Which narrow spectrum penicillin is the drug of choice for infections caused by streptococci, meningococci, penicillin-susceptible pneumococci, clostridium, treponema, non b-lactamase producing gram - anaerobic organisms

Penicillin G

Which narrow spectrum penicillin is indicated only in minor infections, and has a narrow antibacterial spectrum? How many times is it used in a day

Penicillin V, 4x a day

Which narrow spectrum penicillin is indicated for infection caused by syphillis and b-hemolytic streptococcal pharyngitis?

Benzathine penicillin G

Which narrow spectrum penicillin is formerly used for treating uncomplicated pneumococcal pneumonia or gonorrhea, but is now rarely used due to resistance?

Procaine penicillin G

Which penicillin class is indicated for b-lactamase-producing staphylococci, but not for listeria monocytogenes, enterococci, and methicillin resistant strains of staphylococci?

penicillinase-resistant Penicillins

Extended-spectrum penicilins are further classified into 3 groups, which are:

Aminopenicillins, carboxypenicillins, ureidopenicillins

Extended-spectrum penicilins have greater activity than penicillin G against gram - bacteria because?

They have enhanced ability to penetrate the outer membrane.

Name 2 aminopenicillins

Ampicillin | Amoxicillin

Name 2 Carboxypenicillins

Carbenicillin, Carbenicillin indanyl sodium Ticarcillin

Name 3 ureidopenicillins

Piperacillin Mezlocillin Azlocillin

Which aminopenicilin is better absorbed orally?

Amoxicillin. amoxicillin 3x a day ~ = 4x ampicilin

Name 4 aminopenicillin indications

UTI, meningitis, salmonella, upper respiratory tract infections

Which aminopenicillin is effective for shigellosis?

Ampicillin

Can aminopenicillins be used in empirical therapy of UTI, meningitis, and typhoid?

No.

Which aminopenicillin can treat serious infections cased by enterococci, listeria monocytogenes, b-lactamase-negative strains of gram - cocci such as e coli and salmonella, and anaerobes (all penicillin susceptible) ?

Ampicillin

Which drug is not active against microbes causing commonly encountered in hospital-acquired infections, such as klebsiella, enterobacter, p.aeruginosa, etc?

ampicillin

Which carboxypenicillin is obsolete?

carbenicillin. It's the 1st antipseudomonal carboxypenicillin

Which drug class is active against some isolates of P.aeruginosa resistant to ampicillin?

Carboxypenicillin (ext. spect peni)

Are carboxypenicillins effective for most strains of Klebsiella, Enterococcus faecalis, and S. aureus?

Which drug class is effective to treat gram (-) bacilli, such as Klebsiella pneumoniae?

Ureidopenicillins

Which drug combination produces the broadest antibacterial spectrum of penicillins?

Piperacillin (ureidopenicillin, ext. spectrum pen)+ Tazobactam (cephalosporin)

Which drug class can aminoglycosides / fluoroquinolone be combined with to overcome resistant pseudomonal infections outside urinary tract?

ureidopenicillins (etx. spec peni)

Most common adverse reaction of penicillin is due to?

hypersensitivity. - Antigenic determinants: products of penicillin (penicilloic acid, products of alkaline hydrolysis) All are cross-sensitizing and cross reacting. This extends to other b-lactam abx

Hypersensitive incidence % of penicillin?

0.7 - 10%

Name at least 3 manifestations of hypersensitivity to penicillin.

Maculopapular rash, urticarial rash, fever, bronchospasm, vasculitis, serum sickness, exfoliative dermatitis, stevens-johnson syndrome, shock anaphylaxis

Aside from hypersensitivity reactions, are there other adverse reactions of penicillin?

-Toxic effects (bone marrow depression, granulocytopenia, hepatitis) -impaired hemostasis in association with penicillin G, carbenicillin, piperacillin, or ticarcillin -IM penicillin = pain IV penicillin = phlebitis / thrombophlebitis -Large dose orally may lead to GIT upset, nausea, vomitting, diarrhea

Core nucleus structure of cephalosporins?

7-aminocephalosporanic acid R1 side chain - B lactam ring - dihydrothiazine ring - R2 side chain

Cephalosporins has a broad spectrum of activity. Why?

They're more stable against b-lactamases. extended spectrum b lactamases can still hydrolyze most cephalosporins.

Name 2 1st gen Cephalosporin

Cefazolin | Cefadroxil

Name 2 2nd gen Cephalosporin

Cefuroxime | cefamandole

Name 2 3rd gen Cephalosporin

Ceftriaxone | Cefotaxime

Name a 4th gen cephalosporin

cefepime

Which class of beta-lactam is more acid stable?

Cephalosporins

Which class of beta lactam antibiotic has low intrinsic antimicrobial activity, but attachment of R groups in 3rd and 7th position yields potent compounds of low toxicity?

Cephalosporins

What differentiates different generations of cephalosporin?

Increasing generation --> 1. increase activity against gram - bacteria and anaerobe 2. increase resistance to b-lactamases 3. Increase ability to reach CSF and BBB

Route of Administration for 1st Gen Cephalosporin?

Parenteral (cefadroxil), and orally

Excretion route for 1st , 2nd, 3rd, 4thgen cephalosporin?

Kidneys

1st gen cephalosporin treats?

Staphylococcus and streptococcus skin, soft tissue infections, and UTI

Which route of administration should be avoided for 2nd Gen cephalosporin?

intramuscular. It's painful

2nd gen cephalosporin treats?

sinusitis, otitis, lower respiratory tract infections

Which 2nd gen cephalosporin can cross the BBB?

Cefuroxime

Which 3rd gen cephalosporin can treat meningitis?

Ceftriaxone and Cefotaxime

3rd gen cephalosporin is not used to treat?

Infections caused by organisms expressing extended-spectrum b-lactamase. Ex: enterobacter infections

Which generation of cephalosporin have true broad spectrum activity?

4th gen

Which gen of cephalosporin is used in empirical treatment of serious infections acquired in the hospital (nosocomial infections)?

4th gen

Name 2 examples of 5th gen cephalosporin

Ceftabiprole, Ceftaroline

Which generation of cephalosporin is active against MRSA (Methicillin-resistant Staphylococcus aureus)?

5th gen

Name 2 adverse effect of cephalosporins!

1. Allergy - hypersensitivity reaction ex: anaphylaxis, fever, skin rash, hemolytic anemia tolerable for individuals with penicillin allergy. But if patient experience anaphylaxis to penicillin, avoid ceph! 2. Toxicity appear as: - local irritation after i.m injection (severe pain), thrombophlebitis (blood clot in vein) after iv injection -renal toxicity ceph containing menthylthiotetrazole group: - hypoprothrombinemia (deficiency of prothrombin), bleeding disorder. disulfiram reaction (due to blocking of alcohol oxidation).

Which class of b-lactam antibiotics are active against anaerobic gram - rods, but no activity against gram + or anaerobes?

Monobactam

Monobactams can penetrate well into the CSF. T/F?

Patients that are allergic to penicillin can tolerate monobactams without any reactions. T/F, why?

T, because its structure is made up of only one ring structure, unlike the other b-lactam antibiotics that has a b-lactam ring and an additional ring structure attached to it.

Name a side effect of monobactam. Does it have any major toxicity?

No major toxicity. Side effects: occasional skin rash and elevation of serum aminotransferases

Which antibiotic has the broadest antimicrobial spectrum? Which organisms can it inhibit?

Carbapenems. Gram - and +, and anaerobes, except for organisms producing metallo-b-lactamase and carbapenemase

2 examples of carbapenems are?

Imipenem and meropenem

What are the differences between meropenem and imipenem?

imipenem is inactivated by dehydropeptidases (DHP) in renal rubules, while meropenems are not.

Can carbapenems penetrate the body tissues, including CSF?

Yes

How are carbapenems excreted?

Renally

Carbapenem indication?

Infections resistant to other drugs (ex: pneumonia and sepsis). Infections caused by extended-spectrum b-lactamase-producing gram -

State 4 common side effects of carbapenem

Nausea, vomiting, diarrhea, skin rashes, and reaction at infusion site.

Side effect of imipenem?

seizure, especially in renal failure patients

Patients allergic to penicillin may be allergic to?

carbapenem, cephalosporin,

3 examples of b-lactamase inhibitors?

Clavulanic acid, sulbactam, tazobactam

b-lactamase inhibitor is combined with extended spectrum penicillins because? Give examples.

the combination extends the activity of the penicillin to include b-lactamase producing strains of S aureus and some gram - bacteria. Ex: Ampicillin - sulbactam amoxicillin - clavulanic acid piperacillin - tazobactam

B lactamase inhibitors are effective on serratia. T/F?

State 3 common features of b-lactam antibiotics

1. B-lactam ring 2. MoA 3. Immunological property (cross sensitivity reaction)

Why does Imipenem need to be combined with cilastin?

Cilastin inhibits renal dehydropeptidase (DHP) which could inactivate the imipenem.

Which b-lactam class does not share resistance and cross-sensitivity with other beta lactam?

Monobactam