Med-Chem/Pharmacology 2: Antibiotics Part 1 (Continued - EXAM 4) -27Q's
KNOW and identify the group "oxime" as being responsible for 3rd generation cephalosporins being highly resistant to beta-lactamases (shields beta-lactam ring).
"oxime = N-OCH3 = increases stability against BL's"
KNOW and identify the difference between the ring structure of cephalosporins/cepham and cephamycins.
(-OCH3 is present in cephamycins & -H is present in cephalosporins)
*KNOW* All the following 3rd generation cephalosporins are eliminated renally EXCEPT ________ which is eliminated mostly through the biliary route. A. Ceftriaxone B. Cefotaxime C. Ceftazidime D. Ceftazidime + Avibactam E. Cefpodoxime F. Cefixime
A *can cause biliary sludging in neonates*
*KNOW* Which of the following 2nd generation cephalosporins contains the "oxime" group that shields the drug from beta-lactamases? A. Cefuroxime B. Cefaclor C. Cefproxil D. Cefotetan E. Cefoxitin
A *more resistant to BL*
Which of the following 3rd generation Cephalosporins is susceptible to *Borrelia (lyme disease)?* select all that apply A. Ceftriaxone B. Cefotaxime C. Ceftazidime D. Ceftazidime + Avibactam E. Cefpodoxime F. Cefixime
A & B
Vaborbactam is a non-beta lactam beta-lactamase inhibitor that inhibits most: *select all that apply* A. ESBL strains B. KPC strains C. MBL strains
A & B *NO effect on MBL strains*
*QUIZ Q* Select all the bugs that covered by Aztreonam: A. Listeria B. Klebsiella C. Pseudomonas aeruginosa D. E-coli E. E-coli (KPC positive) F. Mycoplasma pneumonia
B, C, D
*KNOW* Methyl substitution of which of the following carbapenems makes it stable against the peptidase (does NOT require cilastatin)? *select all that apply* A. Imipenem B. Meropenem C. Doripenem D. Ertapenem
B, C, D *Methyl group protects drug from breakdown by kidney enzyme dipeptidase*
*KNOW* Oral vancomycin (PO) is indicated for: A. Diarrhea B. C.diff colitis C. Both A & B
C
*QUIZ Q* Cefepime has poor coverage of: A. Gram negatives B. Gram positives C. Anaerobes D. Pseudomonas
C
*QUIZ Q* The major advantage of Ceftazidime over Ceftriaxone is that Ceftazidime has an excellent coverage of: A. Resistant streptococci B. Neisseria gonorrhoeae C. Pseudomonas
C
*QUIZ Q* Which of the following BEST describes the coverage of Ceftaroline? A. Excellent coverage of gram negatives including Pseudomonas but not KPC B. Excellent coverage of gram negatives including Pseudomonas and KPC C. Excellent coverage of gram positives including MRSA & VRSA D. Excellent coverage of gram positives including MRSA but not VRSA
C
*QUIZ Q* Which of the following lacks the coverage of Pseudomonas? A. Imipenem B. Meropenem C. Ertapenem D. Doripenem
C
Due to both the "oxime" group and "N-methylpyrrolidine" group, Cefepime (4th gen) is: A. Broad spectrum B. Highly stable against beta-lactamases C. Has better gram positive and gram negative coverage D. All the above
D
Fosfomycin: A. Binds and inhibits enolpyruvate transferase B. Inhibits the conversion of NAG to NAM C. Inhibits cell wall synthesis D. All the above
D
Which of the following agents offer the BEST gram POSITIVE coverage? A. Ceftriaxone B. Cefpodoxime C. Cefditoren D. All the above
D
Which of the following carbapenems has the longest half-life? A. Imipenem B. Meropenem C. Doripenem D. Ertapenem
D
Which of the following is TRUE regarding carbapenems? A. Penetrate the BBB well B. Can be used for meningitis due to good BBB penetration C. Possible seizures as an adverse effect (CNS toxicity) D. All the above
D
Ceftriaxone has EXCELLENT activity against: A. N. gonorrhoeae B. N. meningitides C. Resistant streptococci D. All the above
D *1st gen can cover regular streptococci* *2nd gen Cefuroxime can also cover N.meningitides*
Combination Ceftazidime + Avibactam covers? A. ESBL strains B. KPC strains C. Amp C cephalosporinases D. All the above
D *2nd gen Cefotetan & Cefoxitin cover ESBL strains only*
Which of the following 2nd generation cephalosporins is associated with adverse effects due to presence of MTT side chain? A. Cefuroxime B. Cefaclor C. Cefproxil D. Cefotetan E. Cefoxitin
D *Be able to IDENTIFY the MTT structure feature responsible for the adverse effects*
Which of the following groups of Ceftazidime make the drug highly effective against gram negatives, particularly Pseudomonas? A. "oxime" group B. "carboxyl" containing group (modified oxime) C. "pyridinium" group D. B & C
D *KNOW & identify groups*
*KNOW* Which of the following carbapenems does NOT have reliable coverage of Pseudomonas, Acinetobacter and Enterococci? A. Imipenem B. Meropenem C. Doripenem D. Ertapenem
D *PAE not Ertapenem*
*QUIZ Q* Which generation of cephalosporins are LEAST useful for treating meningitis? A. 4th B. 3rd C. 2nd D. 1st
D *Remember for CSF penetration; 4th=3rd>2nd>1st*
*KNOW* Which of the following cephalosporins are used for Borrelia (lyme disease)? A. Cefuroxime axetil (2nd) B. Cefotaxime (3rd) C. Ceftriaxone (3rd) D. All the above *which one is ORAL?*
D *cefuroxime axetil = only ORAL cephalosporin used for borrelia*
KNOW and identify the side chain within Cefazolin that's responsible for the adverse effects. (MTD)
*Cefazolin is associated with adverse effects due to MTD structure*
1st generation cephalosporins coverage:
*Good gram positive coverage* -MSSA -Staphylococci saprophyticus (UTI) -Streptococcus pneumoniae (TOO much resistance) - Other streptococci *Gram negative (PEK)* -Proteus (indole -) -E-coli -Klebsiella *Nafcillin & 1st gen cephalosporins = good for MSSA* *NO Morexella OR H.Influenza coverage*
Coverage for 2nd generation cephalosporins:
*Gram positive is similar as 1st generation* -MSSA -Streptococci -Staphylococci saprophyticus (UTI) *Gram negative coverage* -(HNPEK + Morexella) -H.Influenzae -N.meningitides *(cefuroxime)* -Proteus (indole -) -E-coli -Klebsiella *Cefoxitin & Cefotetan* -have additional gram negative coverage (ESBL strains) -Bacteroides
3rd generation cephalosporins coverage:
*Gram positive* (not as good as 1st gen) - MSSA - Viridans - Streptococcus pneumoniae *BEST gram positive: Ceftriaxone, Cefpodoxime, Cefditoren* *Better HNPEK coverage* -H.Influenzae -Neisseria gonorrhoeae, meningitis) -Proteus (indole -) -E-coli -Klebsiella *CAPES (but 4th gen more reliable - since these induce BL's)* -Citrobacter -Acinetobacter -Providencia -Enterobacter -Serratia *Borrelia (lyme disease): Ceftriaxone & Cefotaxime ONLY*
Carbapenem coverage: (broad spectrum)
*gram positive (all gram positive EXCEPT MRSA)* -MSSA -Enterococcus faecalis (NOT covered by Ertapenem) -Listeria -Strep pneumoniae -Viridans *gram negative* -Enterics -H.Influenzae -Morexella -Neisseria (gonorrhea & meningitis) -Pseudomonas** (NOT covered by Ertapenem) -ESBL strains ONLY (not KPC/CRE) *anaerobes* -Bacteroides -Clostridium (NOT C.diff) *NOT covered* (BuY Atypical H T V) -Borrelia (lyme disease) -Yersinia -Atypicals (Chlamydia, Mycoplasma,Rickettsia, Legionella) -H.pylori -Treponema -Vibrio
Coverage for Cefepime (IV/IM):
*gram positive coverage (similar to 3rd gen but more effective since no BL producers)* -MSSA -Strep pyogenes -Viridans -Strep pneumoniae (NOT the resistant ones) *gram negative coverage* -HNPEK -CAPES -Pseudomonas *NO activity against ESBL, CRE/KPC or anaerobes* *Cefepime (4th gen) has greater affinity to PBP's & greater resistance to BL's*
Coverage of Fosfomycin includes:
*gram positive* -Staphylococci -MSSA -MRSA -Enterococci (some) *gram negative* -ESBL, KPC, some MBL strains
KNOW the core ring structure of carbapenems and be able to compare it with Penem structure. (Carbapanem vs penem (penicillins)
*having a carbon instead of a sulfur makes the ring more strained & reactive*
KNOW and identify the structure of Fosfomycin:
*looks like a triangle with phosphate group*
KNOW and identify Aztreonam as a Monobactam. (know monobactam structure)
*not fused to a second ring; just a mono-beta lactam ring*
Vancomycin coverage:
*only gram positive cocci and anaerobic coverage* -MSSA -MRSA**** -Streptococci (most) -Enterococci faecalis -Clostridium (including C.diff) *TOO Big for gram negative coverage*
Coverage of Aztreonam (Monobactam):
*similar to aminoglycosides (gram negative coverage)* -H.Influenzae -Morexella -Neisseria (gonorrhea & meningitis) -Enterics -Pseudomonas (NOT all strains) *KNOW: does NOT cover ~ESBL, KPC/CRE or R-MBL strains*
Coverage for Ceftolozane:
-Mostly complicated infections involving resistant gram negative -Pseudomonas (resistant strains) -ESBL strains *NOT KPC/CRE*
KNOW & Identify the 2 structures that make Ceftolozane highly effective against Pseudomonas (even resistant strains):
-modified oxime group -pyrazole + urea
1. Rank the COVERAGE of cephalosporins based on generation for gram POSITIVE bacteria (BEST to WORST). 2. Rank the COVERAGE of cephalosporins based on generation for gram NEGATIVE bacteria (BEST to WORST). 3. Rank the CSF penetration of cephalosporins based on generation. (BEST to WORST) 4. Rank the SENSITIVITY to B-lactamases of cephalosporins based on generation (MOST susceptible to LEAST susceptible)
1. 1st > 4th > 2nd = 3rd 2. 4th > 3rd > 2nd > 1st 3. 4th = 3rd > 2nd > 1st 4. 1st > 2nd > 3rd > 4th
1. Which of the following Cephalosporins is used mostly for resistant gram POSITIVE infections (Staph & strep)? A. Ceftaroline B. Ceftolozane 2. Which of the following cephalosporins is used mostly for resistant gram NEGATIVE infections (Pseudomonas)? A. Ceftaroline B. Ceftolozane
1. A 2. B
*KNOW* Match the following: 1. Ceftaroline 2. Ceftolozane A. Mostly for resistant gram positive infections (MRSA, VRSA) B. Mostly for resistant gram negative infections (Pseudomonas, ESBL strains)
1. A (Rol* is +) 2. B (Loz* is -)
1. Aztreonam (Monobactam) is administered? A. Orally B. Parentrally (IV/IM) 2. Aztreonam (Monobactam) is eliminated? A. Renally (changed form) B. Renally (unchanged form)
1. B 2. B
3rd generation cephalosporins include:
1. Ceftriaxone (IV/IM) 2. Cefotaxime (IV/IM) 3. Ceftazidime (IV/IM) 4. Ceftazidime + Avibactam (IV/IM) 5. Cefixime (PO) 6. Cefpodoxime (PO) 7. Cefdinir (PO) 8. Cefibuten (PO) 9. Cefditoren pivoxil (PO)
2nd generation cephalosporins include:
1. Cefuroxime (IM/IV/PO) 2. Cefaclor (PO) 3. Cefprozil (PO) (RTI's) *Cephamycins* 4. Cefotetan (IM/IV) 5. Cefoxitin (IV) (UTI's) *KNOW difference in structures (-OCH3 is present in cephamycins & -H is present in cephalosporins)*
1st generation cephalosporins include:
1. Cephazolin (IV/IM) 2. Cephalexin (PO) 3. Cefadroxil (PO)
Carbapenems include:
1. Imipenem 2. Meropenem 3. Doripenem 4. Ertapenem *resistant to most beta-lactamases EXCEPT carbapenemases*
*KNOW* Stereochemistry of carbapenems is important for binding to most PBP's. A. True B. False
A
*KNOW* Which of the following glycopeptides covers C.diff? A. Vancomycin B. Teicoplanin C. Telavancin D. Oritavancin E. Dalbavancin
A
*QUIZ Q* Based on the given structures, which of the following is TRUE: (structure A has amino group, structure B has -OCH3 & no amino group) A. Drug A is more stable in stomach acid and can be given as an oral drug B. Drug A has better gram negative coverage than drug B C. Drug A is more stable against beta-lactamases than drug B D. Drug A penetrates the blood brain barrier better than drug B
A
*QUIZ Q* Which of the following BEST describes the coverage of Ceftolozane + Tazobactam? A. Excellent gram negative coverage including Pseudomonas and ESBL strains B. Excellent gram negative coverage including Pseudomonas but NOT ESBL strains C. Excellent gram positive coverage including MRSA and VRSA D. Excellent gram positive coverage including MRSA but not VRSA
A
*QUIZ Q* Which of the following does NOT have significant oral bioavailability? A. Cefazolin B. Cephalexin C. Cefadroxil
A
Cefepime (4th gen) does NOT induce beta-lactamase production. A. True B. False
A
Cefotetan & cefoxitin have a BETTER gram negative coverage than cefuroxime, cefaclor or cefprozil. A. True B. False
A
Ceftolozane is often combined with Tazobactam (Ceftolozane + Tazobactam) for maximum effectiveness against beta-lactamases producers. A. True B. False
A
The methoxy substituent in cephamycins (cefotetan & cefoxitin - IV) _________ susceptibility to beta-lactamases. A. Decrease B. Increase
A
The presence of AMINO groups enhance stability of drug against hydrolysis/acid in the stomach thus can be taken: A. PO (orally) B. IV/IM (parenterally)
A
Vancomycin and Teicoplanin are large molecules (>1400 Da). This suggests: A. They are useful for ONLY gram positive bacteria B. They are useful for ONLY gram negative bacteria C. They are useful for both gram positive and gram negative bacteria
A
Which of the following carbapenems is easily broken down by renal dihydropeptidase so it requires coadministration of Cilastatin, which inhibits the dipeptidase? A. Imipenem B. Meropenem C. Doripenem D. Ertapenem
A
*KNOW* Which of the following 2nd generation cephalosporins has the BEST CSF penetration (useful for N. Meningitis)? A. Cefuroxime B. Cefaclor C. Cefproxil D. Cefotetan E. Cefoxitin
A *But 3rd gen is better*
Which of the following 3rd generation Cephalosporins is susceptible to *N.meningitis?* A. Ceftriaxone B. Cefotaxime C. Ceftazidime D. Ceftazidime + Avibactam E. Cefpodoxime F. Cefixime
A *Ceftriaxone is BEST for Neisseria* other is 2nd generation Cefuroxime
Ceftaroline was designed so that it could bind to the PBP's in MRSA despite changes. A. True B. False
A *Identify group responsible for affinity to PBPs*
Ceftaroline fosamil is a prodrug that contains a phosphate group that is removed by plasma phosphatases. A. True B. False
A *Identify phosphate group*
Methyl substitution on the beta-lactam ring of Aztreonam (Monobactam) renders the drug: A. Highly resistant to many beta-lactamases B. Highly susceptible to many beta-lactamases
A *NOT ESBL, KPC/CRE or MBL strains*
*QUIZ Q* Which generation cephalosporin is the BEST choice for treating MSSA? A. 1st B. 2nd C. 3rd
A *Remember for gram positive: 1st>4th>2nd=3rd*
The potential side effect associated with Cefazolin due to MTD ring is? A. Bleeding B. Nephrotoxicity
A *b/c it inhibits vitamin K production*
*QUIZ Q* All third and fourth generation cephalosporins contain an "aminothiazole" moiety. What are the advantages of this group?(see structure) *select all that apply* A. Increased resistance to beta-lactamases B. Increased porin penetration C. Increased affinity for PBP's D. Increased oral bioavailability
A, B, C
Which of the following cephalosporin generations INDUCE beta-lactamase production? *select all that apply* A. 1st B. 2nd C. 3rd D. 4th
A, B, C
*QUIZ Q* Which of the following are covered by cefazolin (assuming susceptible strain)? *select all that apply* A. Staphylococcus saprophyticus B. E-coli C. Proteus (indole -) D. Proteus (indole +) E. Morexella F. Serratia G. Klebsiella H. MSSA
A, B, C, G, H
*QUIZ Q* These are two different core structures for 2nd generation cephalosporins . Which of the following statements are TRUE regarding these drugs? *select all that apply* (structure A has -H and structure B has -OCH3) A. Drugs with core structure B are intrinsically resistant to beta-lactamases B. Drugs with core structure A have better gram negative coverage C. Drugs with structure B are considered to be cephamycins D. Drugs with core structure B have better anaerobic coverage E. Drugs with core structure B are oral drugs F. Drugs with core structure B have a better gram negative coverage
A, C, D, F
*QUIZ Q* Which of the following statements are TRUE regarding Fosfomycin? *select all that apply* A. Inhibits cell wall synthesis B. Covers gram negatives but not gram positives involved in UTI's C. Covers major gram negative and gram positive species involved in UTI's D. Can be used for treatment of pyelonephritis if the species is susceptible to the drug E. Can be used safely during pregnancy
A, C, E
Which of the following 3rd generation Cephalosporins is susceptible to *N.gonorrhoeae*? *select all that apply* A. Ceftriaxone B. Cefotaxime C. Ceftazidime D. Ceftazidime + Avibactam E. Cefpodoxime F. Cefixime
A, E, F *one IV/IM (best - Ceftriaxone) & two oral (Cefixime & Cefpodoxime)*
*KNOW* Which of the following generations of cephalosporins has improved gram negative activity to include Morexella and H.influenzae? A. 1st generation B. 2nd generation
B
*QUIZ Q* Which of the following has the best gram negative coverage? A. Cefuroxime B. Cefoxitin C. Cephalexin D. Cefaclor
B
The recently approved Vabomere is a combination of __________ and vaborbactam. A. Imipenem B. Meropenem C. Doripenem D. Ertapenem
B
All carbapenems are administered: A. Orally B. Parenterally
B *poorly absorbed orally*
*KNOW* Which of the following "ORAL" 3rd generation cephalosporins cover N.gonorrhoeae? *select all that apply* A. Cefdinir B. Cefixime C. Cefibuten D. Cefpodoxime E. Cefditoren
B & D *Ceftriaxone (IV/IM) covers N.gonorrhoeae also*
Cefaclor and cefprozil are oral drugs because: A. They contain an amino group B. They do NOT have leaving groups C. Both A & B
C
Cephalosporins are divided into 5 groups or "generations" based on: A. Antimicrobial activity B. Susceptibility to beta-lactamases C. Both A & B
C
Mechanism of action of vancomycin: A. Binding to D-Ala-D-Ala terminus of NAM-pentapeptide and prevent its transfer by the peptidoglycan synthase B. Bactericidal action C. Both A & B
C
Seizures due to carbapenems are more likely to occur in patients with? A. Renal insufficiency B. CNS disease C. All the above
C
Which of the following 3rd generation Cephalosporins is susceptible to *Pseudomonas*? A. Ceftriaxone B. Cefotaxime C. Ceftazidime D. Ceftazidime + Avibactam E. Cefpodoxime F. Cefixime
C
Which of the following groups of Cefotaxime makes the drug effective but also decreases its in-vivo stability (easily hydrolyzed)? A. "oxime" group B. "aminothiazole" group C. "acetoxy" group
C *KNOW & identify group*
Which of the following 1st generation cephalosporins lacks an amino group in its structure thus cannot be taken orally due to lack of stability in the stomach (must be taken parenterally)? A. Cephalexin B. Cefadroxil C. Cefazolin
C *NO amino group = NO stability in the stomach = NO PO administration*
*QUIZ Q* Which generation of cephalosporins has the best gram negative coverage? A. 1st B. 2nd C. 3rd
C *Remember for gram negative: 4th>3rd>2nd>1st*
*QUIZ Q* Generally speaking, cephalosporins are NOT useful in? A. Gram positive B. Gram negative C. Listeria D. Pseudomonas
C *Remember: Listeria & Enterococci*
Esterification of cefuroxime (cefuroxime axetil) leads to: A. Increased lipophillicity B. Increased oral bioavailability C. Both A & B
C *cefuroxime axetil = oral*
Changes in PBP's in ________ led to resistance to beta-lactamases. A. MRSA B. Strep. pneumoniae C. Both A & B
C *enzyme could not be inactivated*
Which of the following are natural glycopeptides? A. Vancomycin B. Teicoplanin C. Both A & B
C *glycopeptides are NOT orally bioavailable (IV delivery)*
*QUIZ Q* Which of the following would be the best option for treating lyme disease? A. Cefotetan B. Cephalexin C. Cefuroxime D. Cefazolin
C *others: Cefotaxime (3rd) & Ceftriaxone (3rd)*
Which of the following groups of Ceftriaxone makes the drug highly effective against many species, increases its in-vivo stability and half-life? A. "oxime" group B. "aminothiazole" group C. "thiotriazinedione" group
C Ceftriax*one* = thiotriazinedi*one* *KNOW & identify group*
*QUIZ Q* Unlike Imipenem, Meropenem contains a methyl substitution on the core ring structure. What is the major consequence of this methyl substitution? (what is the advantage of having this methyl group?) *see structure* A. Makes the drug more stable in stomach acid and thus increases oral bioavailability B. Makes the drug more resistant to beta-lactamases C. Increases the affinity for PBPs in Pseudomonas D. Makes the drug stable against renal dihydropeptidase
D
Aztreonam (monobactam): A. Has an excellent safety profile B. Is a good alternative to aminoglycosides C. Has no cross-reaction in penicillin-allergic patients D. All the above
D
The *aminothiazole* moiety in place of furan or benzene ring in 3rd generation cephalosporins: A. Increases porin penetration B. Increases gram negative coverage C. Increases affinity for PBP's D. Promotes further resistance to beta-lactamases E. All the above
E
*KNOW* Vancomycin is majorly associated with: A. Red man syndrome B. Myelosuppression C. Nephrotoxicity D. Ototoxicity & phlebitis E. All the above
E *red man syndrome: pruritus, erythematous rash on face, neck & upper torso*
Cefepime (4th gen cephalosporin) is used for: A. Pneumonia (HAP) B. Complicated UTI's & intraabdominal infections C. Febrile neutropenia (empiric treatment) D. Multi-drug resistant species E. All the above
E *reserved for serious infections*
Which of the following is TRUE regarding Fosfomycin? A. Its used synergistically with beta-lactams or aminoglycosides B. Its used as a urinary antibiotic C. Its used for uncomplicated lower UTI's in women D. Its safe to use in pregnancy E. It has poor tissue distribution F. All the above
F *Used as a urinary antibiotic b/c it does NOT penetrate the tissues well*
*KNOW* Which bugs are NOT covered by any of the Cephalosporins?
Listeria & Enterococci infections
Coverage for Ceftaroline:
Mostly complicated infections involving resistant gram positive. *excellent gram positive coverage* -MRSA**** -VRSA (Vancomycin Resistant Staph aureus)**** -Strep. pneumoniae (resistant) -Viridans *gram negative (similar to Ceftriaxone* *NO Pseudomonas, Amp C, ESBL or KPC/CRE strains*