Cell Wall Antibiotics Flashcards Preview

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Flashcards in Cell Wall Antibiotics Deck (25):
1

Environment for metronidazole
Use

Anaerobic
Good for brain or abdomen

2

Environment for Aminoglycosides

Aerobic

3

"The Usual" AB treatment

Combo of extended spectrum penicillin, beta lactamase inhibitor, and vancomycin

4

General mechanisms of resistance

Enzyme inactivation, alteration of target site, altered bacterial membrane, efflux pumps, and environmental

5

What type of bacteria is resistant to almost all AB's?

Carbapenem resistant enterobacteriacae
Most common in Klebsiella
Klebsiella producing carbapenemase (KPC)
New Delhi Metallo-beta-lactamase 1 (NDM)

6

What is mechanism of methicillin resistance?

Altered PBPs

7

Which bugs use efflux pumps?
Against which drugs?

Gram Neg and S pneumoniae
Tetracyclin, quinolones, and macrolides

8

4 families of beta lactams

penicillins, cephalosporins, carbapenems, and monobactams

9

Penicillins
Type of killing
Subtypes
Resistance due to?
Adverse rxns

Time-dependent killing (short half life)
Natural penicillins, aminopenicillins, Semi-synthetic penicillins, extended spectrum penicillins, penicillin / beta lactamase inhibitor combinations
Resistance caused by beta lactamase, changes in outer membrane porins, or altered PBPs
Advers rxns: rash, hypersensitivity, diarrhea, cytopenia, renal impairment.

10

Natural penicillins
Drugs
Spectrum
DOC for which conditions?

•Penicillin G Benzathine (IM) – Low concentrations over many weeks. Tx syphilis.
•Penicillin G (IV) – High serum concentrations. Tx endocarditis or brain abscess.

SPECTRUM
•Gram-positives: streptococci (DOC), most enterococci, most pneumococci, Peptostreptococcus, Listeria, Clostridia (gas gangrene, add clindamycin)
•Gram-negatives: Pasturella (caused by animal bites), Neisseria meningitidis
•Spirochetes: Treponema pallidum (syphilis), Borrelia species (Lyme disease)
•Periodontal infections

DOC for Streptococci and Syphillis

11

Aminopenicillins
Comparison to natural penicillins
Drugs
Spectrum
Resistance
Use

Better Gram (-) coverage than natural penicillins.
•Amoxicillin (oral)
•Ampicillin (IV) – not on list
•Spectrum same as natural penicillins + some Gram Neg (E coli, Proteus mirablis, Haemophilus).
Does not work for bugs w/ beta-lactamase.
•Use – Upper and lower respiratory infections (pharyngitis, otitis, sinusitis, pneumonia), UTI, enterococcus, listeria, endocarditis prophylaxis for dental work

12

Semi-synthetic penicillins
Drugs
Use
Spectrum

Dicloxacillin (oral) – tx mild infections such as cellulitis
Oxacillin (IV) – tx more severe Staph infections such as endocarditis or osteomyelitis. Good CNS penetration
DOC for Staph (non-MRSA or MRSE). Treat bacteria w/ beta-lactamase properties, such as Staph aureus, which are resistant to natural penicillins.
•Spectrum – Narrow. Only used for Staph.

13

Penicillin / Beta-Lactamase Inhibitors
Drugs
Spectrum
What if H influenzae does not make beta lactamase?
Use

•Amoxicillin-clavulanic acid (oral) – Tx outpatient infections. Bites.
•Piperacillin-tazobactam (IV) – Tx nosocomial infections. Pseudomonas.
•Spectrum – Same as penicillin + beta-lactamase organisms: S aureus, E coli, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella, Bacteriodes, anaerobes
•70% of H influenzae does NOT make beta-lactamase. Use amoxicillin.
•Use – Upper and lower respiratory tract infections, head / neck infections, SSTI’s (cellulitis), animal / human bites, intraabdominal infections, pseudomonas

14

Cephalosporins
Type of killing
Mechanism
Resistance
Adverse effects
Which bugs do cephalosporins NOT work for?
Which drugs do / do not enter CSF?

Time-dependent killing
Beta lactam inhibits cell wall synthesis
Resistance due to beta lactamase, changes in outer membrane porins, or altered PBP
Adverse Rxns - Few. Rash, cross-rxn w/ penicillin, diarrhea
Do NOT work for enterococci, Listeria, Chlamydia, or Mycoplasma
3rd gen (Ceftriaxone and Ceftazadime) and 4th ten (Cefepime) enter CSF. 1st and 2nd generation do not.

15

1st Generation Cephalosporins
Drugs
Spectrum
Use

•Cephalexin (oral)
•Cefazolin (IV) – perioperative AB prophylaxis
•Spectrum – Gram Pos cocci including Strep and MSSA
•Use – SSTI from Strep and Staph. Perioperative AB prophylaxis

16

2nd Generation Cephalosporins
Unique feature
Drugs, spectrum, and uses

Only cephalosporin w/ anaerobic activity
•Cefuroxime group – Used for upper / lower respiratory infections
•Cefoxitin – same as 1st gen + anaerobes and some Gram Neg. Used for intra-abdominal / pelvic infections

17

3rd Generation Cephalosporins
Drugs w /uses and side effects
Spectrum
DOC for what?

•Ceftriaxone (IV) – long half life allows for once daily dosing. Good for gonorrhea. May cause biliary sludging w/ long term use. Used for seriuous infections such as meningitis, CAP, viridans strep endocarditis, intra-abdominal (need to add drug for anaerobes, such as metronidazole), UTIs.
•Ceftazadime (IV) – works against Pseudomonas
•Spectrum – Gram negative, Strep, N gonorrhoeae
DOC for gonorrhea

18

4th Generation Cephalosporins
Drugs w/ uses and side effects
Spectrum

•Cefepime – very broad spectrum. Tx serious nosocomial infections caused by Pseudomonas as well as febrile neutropenia. May cause mental status changes (be careful w/ elderly)
•Spectrum – Gram Pos and Neg including S aureus, Strep, GNR aerobes, Pseudomonas and ESBL (extended spectrum beta lactamase). Not MRSA or anaerobes.

19

5th Generation Cephalosporins
Drugs
Spectrum
Use

•Ceftaroline (IV) – only cephalosporin that treats MRSA (except CAP)
•Spectrum – Mainly Gram Pos. Some Gram Neg and anaerobes. MRSA, MRSE (coag-neg), strep.
•Use – SSTI’s, CAP (not MRSA for this)

20

Which class has broadest spectrum of all AB's?

Carbapenems

21

Carbapenems
Drugs
Mechanism
Reason they're so good
Spectrum
Resistance
Adverse rxns

Meropenem
•Mechanism – inhibits cell wall synthesis (beta lactam). Time dependent killing.
•Reason they’re so good: molecules are small so can get through porins of Gram Neg, resistant to most beta-lactamases, and have high affinity for PBPs
•Spectrum – Most Gram Pos, Gram Neg (including ESBL), Pseudomonas, and anaerobes. Not MRSA, MRSE, Enterococcus faecium, C diff, Stenostrophomas, or Burkholderia
•Resistance – beta-lactamases, alterations in porins, changes in PBPs.
•Adverse effects – rash, hypersensitivity, cross-rxn w/ penicillins, seizures

22

Monobactam
Drugs
Mechanism
Spectrum
Resistance
Adverse Rxns

Aztreonam
•Mechanism – inhibits cell wall synthesis (beta lactam). Time dependent killing.
•Spectrum – Aerobic Gram Neg Rods, such as Pseudomonas aeruginosa. Can be used in pxs allergic to penicillin or other beta-lactams.
•Resistance – beta-lactamases
•Adverse rxns – rash and hypersensitivity

23

Vancomycin
Type of AB
Mechanism
Spectrum
Resistance
Uses
Adverse Rxns

Glycopeptide
•Mechanism – Binds d-alanyl-D-alanine peptide precursor to prevent peptidoglycan polymerase / transpeptidation → autolysis. Slowly cidal (slower than beta-lactams). Time-dependent killing.
•Spectrum – Aerobic and anaerobic Gram Pos including MRSA, MRSE (Coag-Neg Staph), enterococci (not VRE), Strep, and corynebacteria.
•Resistance – Enterococcal resistance (VRE) due to peptidoglycan precursor w/ lower affinity for vancomycin. Some Staph aureus resistance as well (VRSA)
•Uses – IV form used for systemic infections. Oral form is not absorbed well in gut, which is good for C diff. MRSA, Coag-Neg Staph, Enterococcal infections that are resistant to ampicillin, P pneumoniae meningitis, penicillin allergy.
•Adverse rxns – neutropenia, renal impairment (monitor trough levels), ototoxicity, Red Man Syndrome

24

Daptomycin
Type of AB
Mechanism
Dosing
Spectrum
Resistance
Uses
Adverse Rxns

Cyclic lipopeptide
•Mechanism – lipid portion inserts into cell membrane and causes rapid depolarization → protein inhibition and DNA synthesis inhibition → cell death (“blows up” cells). Concentration-dependent killing.
•Llong half life allows for once daily dosing (IV only).
•Spectrum – Gram (+). Does NOT work for CAP due to inactivation by pulmonary surfactant
•Resistance – some Staph aureus and E faecium. Does not work for CAP.
•Uses – Serious MRSA, VRE, Coag-Neg Staph, including bacteremia and endocarditis
•Adverse Rxns – Myopathy. Elevated CK.

25

Pseudomonal agents (7)

Pipericillin, ceftazidime (3rd gen), cefepime (4th gen), aztreonam, merapenem, aminoglycoside, quinolone (ciprofloxacin)