Antibiotics 1 Flashcards

1
Q

gram positive organisms have:

A

cell wall:

  1. 20-80 nm think (much thicker than gram-neg cell wall);
  2. has peptidoglycan (backbone with alternating subunits of N-acetylglucosamine and N-acetylmuramic acid with beta1to4 linkages), identical tetrapeptide side chains attached to NAM, identical peptide cross-bridges
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2
Q

gram negative organisms have

A
  1. outer membrane (semipermeable lipid bilyaer with phospholipids, lipoproteins, LPS, and proteins)
  2. porins
  3. surface proteins (work as enzymes, adhesins)
  4. periplasmic space (site of BETA-LACTAMASE)
  5. peptidoglycan cell wall (2-3 layers thick with 2-3 nm)
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3
Q

Beta lactams: structural features, MOA, mechs of resistance

A
  1. beta-lactam ring for antibacterial activity; look at side chain as well
  2. binds penicillin binding proteins (PBPs): PBPs catalyze polymerization of the glycan strand (transglycosylation) and the cross-linking b/w glycan chains (transpeptidation); with peptidoglycan precursor buildup autolysins are triggered
  3. think beta-lactamase (expressed outside of cell in gram positive, in periplasmic space for gram negatives); alteration in porin channels and beta-lactams can’t penetrate outer membrane of gram-neg bacteria; low affinity binding of antibiotic to target PBPs (MRSA alters PBP2a, S pneumoniae alters PBP2x and PBP2b)
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4
Q

Beta lactam characteristics:

A
  1. Prevent transpeptidation (cross-linking) of peptidoglycan layers in the cell wall by binding to penicillin-binding proteins
  2. Most with short half-lives (maybe 20 minutes)
  3. Time-dependent pharmacodynamics (T > MIC)
  4. Most eliminated via renal route (adjust with renal insufficiency)
  5. Hypersens reactions and GI effects!!
  6. Lacks activity against organisms w/o cell wall: Mycoplasma pneumoniae, chlamydophilia pneumoniae
  7. Exception for MRSA activity: CEFTAROLINE!!!
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5
Q

Natural Penicillin quick facts (Penicillin V and Penicillin G):

A

Spectrum: effective against non-beta-lactamase producing bacteria: think strep, and anaerobes (actinomyces, prevotella, Clostridium except difficile); select gram neg bacteria (Neisseria), Syphilis
Place in therapy: oral strep infection, non-purulent cellulitis, syphilis
SE’s: hypersens reaction, GI SE’s, seizures at high doses (particularly with renal dysfunction)

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6
Q

Antistaph penicillin quick facts (Oxacillin, Nafcillin, Dicloxacillin):

A

Spectrum: MSSA, strep;
Place in therapy: MSSA infection (better than vanco)
SE’s: Nafcillin with thrombophlebitis and neutropenia, oxacillin with hepatotoxicity and neutropenia;
PEARLS: bulky side chain shields beta-lactam ring from penicillinase, but too big to get entry into gram-neg cell)

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7
Q

Aminopenicillin quick facts (Ampicillin, amoxicillin)

A

Spectrum: strep, enterococci (ampicillin DOC here), LIsteria; some gram negs (proteus mirabilis, E coli, Listeria);
Place in therapy: amoxicillin (comm-acquired URTI’s), IV ampicillin (DOC for enterococcal infections), IV ampicillin (listeria meningitis), IV ampicillin with aminoglycosides (enterococcal endocarditis);
SE’s: hypersens rxn with non-IgE rash (type IV hypersens) and IgE rxn (type I hypersens)
Pearls: susceptible to effects of beta-lactamse produced by staph and other gram-neg organisms, and increased risk of cross-reactivity with cefadroxil and cefprozil due to identical side chain

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8
Q

Extended spec penicillin-beta-lactamase inhibitor combos (amp/sulbactam, amoxicillin/clavulanate, piperacillin/tazobactam, ticarcillin/clavulanate):

A

Spectrum: enhanced gram-neg acitivity (enterobacteriaceae), enhanced gram-positive activity (MSSA), anaerobes like B fragilis; retained activity against strep and enterococci;
Place in therapy: Pip/taz and ticar/clav active against nosocomial infections like pneumonia, intra-abdo infections, wounds (PSEUDOMONAS); amox/clav and amp/sulb against aniaml and human bites, URI’s, and diabetic foot infection;
SE’s: non-IgE rash, hypersens rxns, amox/clav with diarrhea, pip/taz: thrombocytopenia and interstitial nephritis

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9
Q

Cephalosporin characteristics:

A
  1. Generally more resistant to beta-lactamases than penicillins (susceptible to cephalosporinases)
  2. lacks activity against MRSA and enterococcus, EXCEPT ceftaroline (5th gen)
  3. Lacks activity against B fragilis
  4. can cause hypersens rxns similar to penicillins (some cross-reactivity with penicillin)
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10
Q

1st gen cephalosporin facts (cefazolin and cephalexin):

A

Spectrum: strep and MSSA, some gram-negatives (beta-lactamase limits gram-neg spectrum), NO ANAEROBES OR ENTEROCOCCI;
Place in therapy: definitive therapy based on cultures (E coli, kelb UTI and MSSA with cefazolin); surgical prophylaxis with cefazolin
SE’s: Less antigenic than penicillins, but more cross reactivity with them than other cephalosporins;
Misc: NOT for CSF infection

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11
Q

2nd gen cephalosporin (cefuroxime, cefaclor, loracarbef, cefprozil are true; cephamycins with cefoxitin and cefotetan):

A

Spectrum: true cephalosporins with better activity against S pneumoniae than first gen and better gram neg activity than first gen (H influenzae, N gonorrheae, some enterobacteriaceae); CEPHAMYCINS: better activity against E coli and kleb, and has ACTIVITY AGAINST ANAEROBES;
Place in therapy: true cephs for CA respiratory tract infections, and cephamycins mostly surgical prophylaxis colon surgery;
Pearls: DON’T USE against ESBL-producing enterobacteriaceae

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12
Q

3rd gen cephalosporin (cefotaxime, ceftriaxone, ceftazidime, cefdinir, cefpodoxime, ceftibutin, cefixime)

A

Spectrum: activity against enterobacteriaceae increased;
ceftriaxone and cefotaxime against S pneumoniae, H influenzae, M catarrhalis, but less active against MSSA than first gen, and
ceftazidime for P aeruginosa, with poor activity against gram-pos organisms (S pneumoniae, MSSA), and both with NO ACTIVITY AGAINST enterococcus or anaerobes;

Place in therapy: ceftriaxone (adults) and cefotaxime (infants): good for CAP, meningitis when S pneumoniae or H influenze, or good when enteric gram-negs are likely (intraabdo infections and UTI’s); ceftriaxone good for lyme;
ceftazidime and cefepime: nosocomial infections where Pseudomonas is a concern, and Ceftas with poor gram-positive activity;
Pearls: no renal dosing required for ceftriaxone: can get biliary sludging and Ca crystals with infants

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13
Q

4th gen cephalosporin (zwitterion cefepime):

A

Spectrum: excellent gram-neg activity including Pseudomnoas, better activity against gram pos organisms than ceftazidime; cefepime is piperacillin/tazobactam without anaerobic activity; NO ACTIVITY AGAINST enterococcus or anaerobes;
Place in therapy: nosocomial infections, monotherapy for febrile neutropenia, post-neurosurg meningitis, nosocomial pneumonia;
SE”s: similar to other beta lactams

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14
Q

5th gen cephalosporin (ceftaroline, ceftobiprole)

A

Spectrum: similar gram neg activity to ceftriaxone (NO PSEUDOMONAS), S aureus INCLUDING MRSA, some enterococcus activity (unlike the other cephalosporins), and STILL NO ACTIVITY AGAINST ANAEROBES);
Place in therapy: monotherapy for complicated skin and soft tissue infections;
Pearl: some reports of ceftaroline-resistant MRSA

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15
Q

Monobactam quick facts (Aztreonam):

A

Spectrum: gram negs including P aeruginosa, NO ACTIVITY AGAINST gram-pos and anaerobes; very similar to aminoglycosides;
Place in therapy: usually used in combo with other agents for nosocomial infections especially in patients with penicillin allergy or renal dysfunction;
Pearls: shares same side chain as CEFTAZIDIME (maybe allergic cross-reactivity)

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16
Q

Carbapenem quick facts (imipenem/cilastatin, meropenem, ertapenem, doripenem):

A

Spectrum: broad-spectrum activity INCLUDING anaerobes; ertapenem less broad (no P aeruginosa), NO MRSA, and enterococcal coverage relatively poor
Place in therapy: Nosocomial infections, especially polymicrobial ones; ERTAPENEM: CA intra-abdo infection, polymicrobial infections not involving Pseudomonas, and convenient dosing regimen for outpatient use;
SE’s: similar to other beta-lactams; imipenem: SEIZURES (renal dysfunction)

17
Q

Regarding allergies, what is most important in identifying? What is the pathogenesis:

A

Patients with IgE-mediated allergy or history of severe reaction (Anaphylaxis, SJS, TEN, drug-induced hypersens syndrome);
major is penicilloyl, while R-group side chain is less common

18
Q

Vancomycin quick facts:

A

MOA: binds D-Ala-D-Ala end of pentapeptide which prevents elongation of peptidoglycan and cross-linking
Mech of resistance: VISA-rare (thickened cell wall), VRE: synthesis of abnormal peptidoglycan precursors (D-Ala-D-Lac)
Spectrum: gram pos including MRSA, coag-negative staph, strep, enterococcus
Place in therapy: serious MRSA infection; DOC for coag-negative staph infections, enterococcal infections;
SE’s: renal dysfunction, Redman syndrome (NOT a hypersens reaction but is histamine release due to high osmolarity of vanco solution), but true hypersens rxns can occur