Antibiotics 101

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Antibiotics 101 Puja Van Epps 1/20/14

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Antibiotics 101. Puja Van Epps 1/20/14. Beta-lactams. Core PCN structure. Core Cephalosporin structure. Beta-lactams. Beta-lactamases are enzymes produced by some bacteria that provide resistance against beta lactams through hydrolysis of the β- lactam ring. Natural Penicillins. - PowerPoint PPT Presentation

Transcript of Antibiotics 101

Page 1: Antibiotics 101

Antibiotics 101

Puja Van Epps1/20/14

Page 2: Antibiotics 101

Beta-lactams

Core PCN structure

Core Cephalosporin structure

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Beta-lactams

Beta-lactamases are enzymes produced by some bacteria that provide resistance against beta lactams through hydrolysis of the β-lactam ring

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Natural Penicillins

Bicillin L-A (Penicillin G benzathine) – IM only

Penicillin G (IV) Penicillin V = PO

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Natural Penicillins- Spectra

Groups Important Organisms

Gram PositiveGroup A/B/C/G strep

S. pneumoniae* viridans streptococci gr.*, Strep milleri*

Enterococcus (feacalis>faecium)

Gram NegativeNeisseria meningitidis*Pasteuralla multocida Haemophilus ducreyi

AnaerobesActinomycesClostridial sp.

PeptostreptococcusFusobacterium

Other Treponema pallidum

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Natural Penicillins

Bicillin: Primary, secondary, latent and late latent syphillis

PCN G: Neurosyphillis; systemic infection due to susceptible bacteria (Streptococci)

PCN V: Group A strep pharyngitis

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Anti-staphylococcal Penicillins

Nafcillin, oxacillin, methicillin, dicloxacillin (PO) Penicillinase is a specific type of β-lactamase,

showing specificity for Penicillins First β-lactamase to be identified; PCN R in S.

aureus Major Uses: Methicillin-susceptible S. aureus or Coagulase

Negative Staph; PCN-susceptible strains of Streptococci

No gram negative activity

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Aminopenicillins

Ampicillin/amoxicillin; Augmentin (Amox-Clav); Unasyn (Amp-Sulbactam)

Amp/amox – Great for susceptible streps and enterococcus; very limited GN activity; cover anaerobes

Addition of Clavulanate or Sulbactam enhances Gram negative activity

No activity against MSSA without the beta-lactamase inhibitor.

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Aminopenicillins

Important holes in coverage Pseudomonas sp. Atypical gram negatives – mycoplasma

pneumoniae, chlamydia pneumoniae, legionella sp.

Enterobacter sp. If susceptible Ampicillin is the DOC

for Enterococcus and Listeria

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Anti-Pseudomonal Penicillins Ticarcillin, Ticar-Clav, Piperacillin, Pip-Tazo

Generally good gram positive, gram negative and anaerobic coverage

Ticarcillin and Piperacillin without their beta-lactamase inhibitor DO NOT cover MSSA

Important holes in coverage: MRSA (ESBL+, KPC+, or other resistant GN)

Stenotrophomonas maltophilia – Ticar-Clav is second line, Pip/Tazo does not cover.

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Cephalosporins

5 generations, increasing gram negative coverage with each generation

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First Generation Cephalosporins

Cefadroxil, Cephalexin (PO) Cefazolin (IV)

Gram PositiveGroup A, B, C, G Strep

Strep pneumoViridans strep

MSSA

Gram NegativeE. coli, Klebsiella sp.,

Proteus mirabilis

Anaerobes No activity

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First Generation Cephalosporins

Important holes in coverage – MRSA, Enterococcus, Pseudomonas,

anerobes

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Second Generation Cephalosporins

Cefuroxime (IV, PO), Cefotetan (IV), Cefoxitin (IV)

In addition to the coverage of 1st generation

- H. influenzae, M. catarrhalis, Neisseria sp., and anearobic coverage (variable)

Important holes in coverage: - MRSA, Enterococcus, Pseudomonas

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Third Generation Cephalosporins

Ceftriaxone, Cefotaxime, Ceftazadime (IV) Cefixime, Cefdinir (PO) In general less active against gram-

positive aerobes than previous generations, but have greater activity against gram-negatives

Cefotaxime and Ceftriaxone have the best gram + coverage in the group

Only Ceftazadime covers Pseudomonas

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Third Generation Cephalosporins

Major holes in coverage – - Enterococcus, MRSA, Pseudomonas

(except Ceftazidime), +/- Acinetobacter, Listeria

Ceftazidime crosses BBB, Ceftriaxone in inflamed meninges

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Fourth Generation Cephalosporins

Cefepime (IV)

gram-positives: similar to first generation

gram-negatives: broad, including Pseudomonas

Major holes: MRSA, poor anaerobic coverage, listeria

Crosses BBB

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Fifth Generation Cephalosporin

Ceftaroline (IV) Major advantage: - MRSAMajor holes in coverage: - Pseudomonas, enterococcus and

anaerobes CAP, SSTI

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Cephalosporin Review

Antipseudomonal – Ceftazadime and Cefepime Anti-MRSA – Ceftaroline Anti-Enterococcal – None (Ceftaroline has in-vitro activity against

E. faecalis) Enterobacter sp. can develop resistance to

cephalosporins during treatment, therefore not the treatment of choice

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Carbapenems

Ertapenem, Doripenem, Imipenem, Meropenem Broadest spectrum of activity Have activity against gram-positive and gram-

negative aerobes and anaerobes Bacteria not covered by carbapenems include

MRSA, VRE, MR coagulase-negative staph Additional ertapenem exceptions:

Pseudomonas, Acinetobacter, Enterococcus

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Carbapenems

Major holes in coverage: - Atypicals (Legionella, Mycoplasma) ,

MRSA, VRE, Stenotrophomonas maltophilia, KPC+

Ertapenem does not cover: - Pseudomonas, Acinetobacter,

Enterococcus

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Monobactam

Aztreonam: binds preferentially to PBP 3 of gram-negative aerobes

No gram positive or anaerobic activity Major uses – Hospital acquired infections

in patients with anaphylaxis to any beta lactams (does not have cross reactivity)

Important gram neg holes: Acinetobacter, ESBL+, KPC+

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Fluoroquinolones Ciprofloxacin, Levofloxacin, Moxifloxacin Broad spectrum of activity, excellent

bioavailability, tissue penetration Cipro has poor gram + coverage Disadvantages: resistance, expense, C

diff Advantages: Atypical coverage,

Antipseudomonal (Cipro, Levo)

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Aminoglycosides

Gentamicin, Tobramycin, Amikacin inhibit protein synthesis by irreversibly

binding to 30S ribosome, bactericidal For gram + use in combination with cell

wall agents Broad spectrum gram neg coverage

including Pseudomonas and Acinetobacter

Also have mycobacterial coverage

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Aminoglycosides – adverse effects

Nephrotoxicity– Nonoligouric renal failure from damage to the proximal

tubules– Underlying CKD, Age, other nephrotixins, duration,

high troughs Ototoxicity

– 8th cranial nerve damage - vestibular and auditory toxicity; irreversible

– Related to duration of therapy (>2wks)

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Macrolides

Clarithromycin, Erythromycin, Azithromycin

Inhibit protein synthesis by reversibly binding to the 50s ribosomal unit

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Macrolides Gram-Positive Aerobes –

Clarithro>Erythro>Azithro Gram-Negative Aerobes –

Azithro>Clarithro>ErythroNo activity against any Enterobacteriaceae or Pseudomonas

Anaerobes – activity against upper airway anaerobes Atypical Bacteria – Excellent Also cover – Mycobacterium avium complex,

Campylobacter, Borrelia, Bordetella, Brucella.

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Anti-MRSA drugs

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Vancomycin Inhibits synthesis and assembly of the

second stage of peptidoglycan polymers Gram-positive bacteria: excellent coverage Major uses: MRSA, MSSA (in PCN all), PCN R

streptococci No activity against gram-negatives or

anaerobes If MIC to Vancomycin in MRSA is ≥ 2, Do not

use

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Vancomycin

Red-Man Syndrome– flushing, pruritus, rash– related to rate of infusion– resolves spontaneously – may lengthen infusion

NOT AN ALLERGY

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Daptomycin Lipopeptide; binds to components of the cell

membrane and causes rapid depolarization, inhibiting intracellular synthesis of DNA, RNA, and protein

Major uses - SAB, Right-sided IE caused by S. aureus, VRE

Indicated for SSTI, R sided IE

Do not use for lung infections including MRSA PNA – pulmonary surfactant inhibits Daptomycin

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Linezolid Binds to the 50S ribosomal subunit near the

surface interface of 30S subunit – causes inhibition of 70S initiation complex which inhibits protein synthesis

Active against wide range of Gram + bacteria, limited to no Gram negative or anearobic activity

Major uses – MRSA, VRE. Major problem thrombocytopenia with prolonged use (>2wks),

bacteriostatic (cidal against Enterococcus)

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Tigecyline Binds to the 30S ribosomal subunit of susceptible bacteria,

inhibiting protein synthesis. Broad spectrum of activity including – - MRSA, VRE, gram negatives (including resistant GN) Major holes- The 3 P’s – Pseudomonas, Proteus and doesn’t get in the

urine Indicated for complicated SSTI, intra-abdominal infections,

CAP Major problems: GI issues, and shown to have increased

mortality in serious infections – monotherapy only as a last resort.

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Clindamycin

Inhibits protein synthesis by binding exclusively to the 50S ribosomal subunit

Major uses - MRSA (some isolates), anaerobic

coverage

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Clindamycin

A positive D test indicates the presence of macrolide-inducible resistance to clindamycin produced by an inducible methylase that alters the common ribosomal binding site for macrolides, clindamycin

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Tetracylines

Doxycyline, Minocyline Good gram pos, neg and anaerobic

coverage Major uses MRSA, anti-malarial prophylaxis,

rickettsial infections, Borrelia burgdorferi

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Trimethoprim, TMX-Sulfa

Inhibit various steps within the folic acid biosynthetic pathway

Good gram pos and gram neg coverage (CA-MRSA)

Important uses: Pneumocystis, Stenotrophomonas maltophilia, Nocardia

Major holes Pseudomonas, anaerobes