Cell Wall Active Antimicrobials

Question 1

1,3. Explain the mechanism of action B-lactams: penicillins and cephlosporins.

Answer 1

1. penetrate cell wall (Gram neg- pass through the porin and gram + diffuse across the peptidoglycan) and bind to penciling binding proteins
2. antibiotic inhibits transpeptidation so that peptidoglycan cross-linking doe snot occur; integrity of cell wall is lost
3. leakage or inhibition of substance that normally acts to inhibit autolysis

note penicillins and cephalsporins are time-dependent killers meaning that time above MIC is the most important parameter for optimizing bacterial killing- frequent dosing

Question 2

2. Describe the major mechanisms by which bacteria develop resistance to cell wall active agents. (5)

Answer 2

enzyme activation (beta-lactamases or extended-spectrum beta lactamases [ESBL])
alteration in target site
altered bacterial membrane
efflux pumps
(environmental?)

cephalosporins show low toxicity and limited cross-reactivity with penicillins
rash
diarrhea

Question 3

4. List the major adverse drug reactions associated with beta-lactam antimicrobials, vancomycin and daptomycin.

Answer 3

beta-lactams: rash/hypersensitivity, antibiotic associated diarrhea, cytopenias, renal impairment

Question 4

5. Discus the summarizing statements, part 1

Answer 4

Learn@UW

Question 5

1,3. Explain the spectrum of activity of penicillin G and its formulations.

Answer 5

gram-positive: streptococci, most enterococci, most pneumococci, peptostretococcus, Listeria, Clostridia
Gram neg: pasturella, Neisseria meningitdis
Spirochetes: Treponema pallidum (syhpilis) and Borrelia species (Lyme disease)

DOC with streptococcal, syphilis
Gas gangrene, periodontal infection and enterococcal infections

Penicillin G is the intravenous formulation
Benzathine penicillin G is the IM form (low over weeks)
Penicillin VK is the oral formulation

Question 6

1,3. Explain the spectrum of activity of amoxicillin and its formulations.

Answer 6

same spectrum of activity as penciling while adding some Gram negatives including most E.coli, Proteus mirablia dn Haemophilus

Upper and lower respiratory infections, uncomplicated UTI and enterococcal infections

DOC for nonMRSA/MRSE staph infection

Amoxicillin is the oral formulation
Ampicillin is used as the IV formulation

Question 7

1,3. Explain the spectrum of activity of dicloxacillin and its formulations.

Answer 7

niche antibiotics for staphylococci; excellent activity against staphylococci and streptococci, no activity for gram neg, enteroccocci or anaerobes

dicloxacillin is the oral form (cellulitis)
oxacillin is the IV form (endocarditis or osteomyelitis)

Question 8

1,3. Explain the spectrum of activity of extended spectrum penicillin and its formulations.

Answer 8

better activity against Gram negative aerobes and pseudomonas, more commonly use as a combo with beta-lactamase inhibitor

gram negative aerobes, pseudomas, some strep and staph, peperacillin covers enterococci

sued in pseudomas infections and mixed infections with gram negatives and enterococci

Question 9

1,3. Explain the spectrum of activity of penicillin/beta-lactamase inhibitor and its formulations.

Answer 9

spectrum: S. aureus, E. coli, H. influenzae, Moraxella catarrhalis, Klesiella, Bacteroids and other anaerobes

Used: upper and lower respiratory tract infections, celulitis, animal and human bites, intra abdominal infections, nosocomial infections including pseudomonas (popular for outpatient infection and nosocomial infections)

oral: amoxicillin/clavulanic acid
IV: piperacillin/taxobactam

Question 10

1,3. Explain the spectrum of activity of 1st generation cephalosporins and its formulations.

Answer 10

Gram positive cocci, E. coli and Klebsiella (widely used for Gram Positive skin and soft tissue infections due to strep or staph and pre-op prophylaxis)
cephalexin- oral

cefazolin- IV: used often for perioperative antibiotic prophylaxis

Question 11

1,3. Explain the spectrum of activity of 2nd generation cephalosporins and its formulations.

Answer 11

cephamycins subgroup is only with significant amount of anaerobic activity

Cefuroxime group: 1st gen+ Haemophilus and Moraxella– used for upper and lower respiratory infections
Cephamycin group: 1st gen+ anaerobes and more gram neg.– used for intra abdominal and pelvic infections

cefoxitin- IV agent

Question 12

1,3. Explain the spectrum of activity of 3rd generation cephalosporins and its formulations.

Answer 12

ceftriaxone- long half life, large spectrum
ceftriaxone- niche treating Pseudomonas infections (no meaningful gram positive activity

excellent gram neg. and streptococcal activity, DOC for N. gonrrhoeae (ceftriaxone) and pseudomonas (cetrazadime); can achieve excellent levels in CSF, used in management of meningitis

meningitis (ceftriaxone)
CAP (both)
UTI (all)
gonorrhea (ceftriaxone)
Pseudomonas (ceftazadime)
viridans strep endocarditis (ceftriaxone)
intra-abdominal (ceftriaxone + metronidazole for anaerobes)

Question 13

1,3. Explain the spectrum of activity of 4th gen. cephalosporins and its formulations.

Answer 13

important drug for nosocomial infections including Pseudomonas

excellent Gram positive (of 1st gen), excellent Gram neg. (of 3rd gen, including Pseudomonas) but no coverage for anaerobes and no MRSA

used for nosocomial infections, febrile neutropenia and Pseudomonas

IV: Cefepime

Question 14

1,3. Explain the spectrum of activity of ceftaroline and its formulations.

Answer 14

coverage of MRSA

excellent Gram pos., S. pneumonia, although activity against Gram negative and anaerobes is limited

used for SSTI and CAP

ceftaroline- IV

Question 15

1,3. Explain the spectrum of activity of carbapenems and its formulations. Note the mechanism of action and adverse reactions.

Answer 15

broadest spectrum activity used for serious infections, critically ill patients and highly resistant organisms

mechanism: inhibition of cell wall synthesis, time dependent

most bacteria except MRSA, Enterococus faecium, Clostriudium difficult, stenotrophomonas and Burkholderia

excellent Gram pos. almost all Gram neg and anaerobes
(ertapenem does not cover pseudomonas or Acinetobacter, long half life)

meropenem: (IV) better gram neg activity, crosses BBB, good for pediatric meningitis)

**resistance through alterations in porins and changes in PBP, 2014 carbapenem resistant enterobacteriaceae

***pay close attention to renal dose adjustments

adverse effects: rash, hypersensitive, cross rxn with penicillins, imipenem (high dose seizures)

Question 16

1,3. Explain the spectrum of activity of monobactam and its formulations. Note the mechanism of action and adverse reactions.

Answer 16

aztreanam- niche against Gram negative rods, including pseudomonas in case of penicillin allergy

mech: inhib cell wall synthesis, time dependent killing
resistance: beta-lactamases

adverse reactions: rash and hypersensitivity

limited to coverage of aerobic Gram-neg bacilli inclining Pseudomonas, no activity against gram positive anaerobes

Question 17

1,3. Explain the spectrum of activity of glycopeptide and its formulations. Note the mechanism of action and adverse reactions.

Answer 17

vancomycin important against antibiotic Gram positive bacteria esp MRSA and MRSE and enterococci or mod/severe C. difficicle; important role with penicillin allergy

mechanism: prevents transglycolation so disaccharide cannot be added to peptidoglyca by binding to peptide precursor units– considered “slow” cidal, does not cross BBB readily
spectrum: aerobic and anaerobic Gram positive bacteria, (staph, enterococci -not VRE- strep and corynebacteria) no gram neg activity
resistance: enterococcal resistance mediated by formation of peptidoglycan precursor the has decreased affinity for vancomycin, some VRSA; other organism through changes in peptidoglycan precursor

adverse reactions: neutropenia, renal impairment with other nephrotoxins
IV- used for systemic infections
Oral- only used of C. difficult because it is not readily absorbed in GI tract

Question 18

1,3. Explain the spectrum of activity of cyclic lipopeptide and its formulations. Note the mechanism of action and adverse reactions.

Answer 18

daptomycin put back into use because of MRSA and VRE, used in highly resistant gram pos. orgs. more rapid cidal activity and DO NOT use treating pneumonia

Mech: binds to membrane and causes rapid depolarization ; concentration-dependent killing

some resistance described in S. aureus and E. faecium

long half life, inactivated by pulmonary surfactant, IV only

adverse reactions: rash and hypersensitivity uncommon, must monitor for myopathy

Question 19

List the 3 ‘cardinal truths’ about antibiotics

Answer 19

the are a lot easier to start than to stop
most problems have >1 acceptable solution
some problems have only 1 acceptable solution

Question 20

What 4 families of antibiotics are classified as beta-lactams?

Answer 20

penicillins
cephalosporins
carbapenems
monobactams

cidal drugs, B-lactams interfere with the cross liking of peptidoglycan interfering with the integrity of bacterial cell walls

Question 21

Describe the drug class to which vancomycin belongs.

Answer 21

glycopeptide- complex molecule that inhibits synthesis of peptidoglycan (act an early stage of synthesis compared to b-lactams)

Question 22

Describe the class of drugs that daptomycin belongs to.

Answer 22

cyclic lipopeptides bind to the cell membrane of gram-positive organisms

Question 23

Give a short synapse of the 5 subfamilies of penecillins

Answer 23

1. penicillin: Streptococci, syphilis
2. aminopenicillin: better gram negative coverage: URTI and enterococcal
3. semi-synthetic: Staph that are not MRSA or MRSE
4. extended-spectrum penicillins only used in combo with beta-lactamase inhibitors
5. penicillin/beta lactamase inhibitor combo: community acquired and nosocomial infections

Question 24

Which generation of cephalosporin have activity against MRSA, anaerobes and listeria?

Answer 24

MRSA- 5th gen
anaerobic: 2nd gen
Listeria: none