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Inhibitors of Cell Wall Synthesis
inhibitors of cell wall
57
Accounting
Pre-School
09/29/2014

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Term
Normal transpeptidation
Definition
When cross linking of polymers occurs, one D-ala-D-ala group comes up to 5 glycines and one D-ala is booted off and links to it
Term
B lactamases cause bacterial suicide
Definition
Fluid can enter the cell - swell and lyse
Term
General effects of B lactams
Definition

Good tissue penetration, time dependent, most are renally eliminated

Class adverse effects: hypersensitivity: nausea/vomiting/diarrhea/seizures at high doses

Differences in transpeptidases and hydrophilicity make differences in B-lactams 

Term
Cross Reactivity of Aztreonam
Definition
with Ceftazidime
Term
Desensitization
Definition
The process involves exposing a patient over hours to days to gradually increasing doses of a medication to which the patient has an allergic history. The purpose of this procedure is to attempt to build up tolerance to the medication and blunt the allergic response by inhibiting the release of mast cell mediators though prevention of IgE crosslinking.
Term
Penicillin G
Definition

Natural Penicillin

IV only

Renal elimination

Very short half life (~30 minutes)

Most bacteria are resistant

Useful spectrum: streptococci, enterococci, Treponema palldium

Main uses: susceptible streptococcal infections, syphillis

Term
Natural Penicillins Indications
Definition
Streptococcus, enterococcus, Treponema pallidum
Term
Penicillin V
Definition

phenoxymethylpenicillin

By mouth only

Renal elimination

Very short half life (~30 minutes; frequent dosing required)

Most bacteria are resistant 

Useful spectrum: streptococcus, enterococcus, Treponema pallidum

Main uses: susceptible streptococcal infections, syphillis

Term
Methicillin, nafcillin, oxacillin, dicloxacillin, and cloxacillin
Definition
Anti-staph penicillins (penicillinase resistant penicillins)
Term
Anti-staph Penicillins
Definition

Penicillinase resistant penicillins

Methicillin, nafcillin, oxacillin, dicloxacillin, and cloxacillin 

Contain bulky R group that will inhibit many B-lactamases

Dicloxacillin and cloxacillin are oral

Methicillin: acute interstitial nephritis (removed from market), nafcillin is hepatically eliminated and has high incidence of phlebitis

Useful spectrum: MSSA, streptococci

Main use: susceptible staphylococcal infections (endocarditis, cellulitis) 

Term
Methicillin
Definition

High incidence of acute interstitial nephritis

Anti-staphlycococcal Penicillin ("penicillinase resistant" penicillins)

Term
Nafcillin
Definition

Anti-staphylcoccal penicillin

Hepatically eliminated

has a high incidence of phlebitis 

Term
Anti-staphylococcal Penicillin Spectrum
Definition

MSSA, streptococci

Main use: susceptible staphylococcal infections (cellulitis, endocarditis)

 

Staph can still be resistant to them via their PBP 

Anti-staphylococcals kill staph susceptible to them better than vancomycin

Term
Aminopenicillins
Definition

Ampicillin, Amoxicillin, Bacampicillin

Ampicillin = IV, PO; Amoxicillin = PO (better bioavailability)

Susceptible to B-lactamases

Amino group confers improved gram negative specificity

Useful spectrum: streptococci, enterococci, non-b-lactamase producing GNR: listeria, H pylori

Main Uses: URIs, UTIs, PUD, enterococcal infections 

Term
Aminopenicillin spectrum
Definition

Streptococcus, enterococci, some non-B-lactamase producing GNR - Listeria, H pylori

Main Uses: URIs, UTIs, PUD, enterococcal infections 

Term
Antipseudomonal Penicillins
Definition

Ureidopenicillins (piperacillin, mezlocillin, azlocillin) - ureidocillins have saturable renal and biliary excretion

Carboxypenicillins (carbenicillin -- oral; rest are IV, ticarcillin)

AE: thrombocytopenia

Useful spectrum: as aminopenicillins, plus pseudomonas, better coverage againsts GNR 

Susceptible to B lactamases

Penetrate cell wall of pseudomonas, unlike aminopenicillins

Main uses: HAP, nosocomial infections 

Term
Antipseudomonal Penicillins SE
Definition
thrombocytopenia
Term
Spectrum of Antipseudomonal pencillins
Definition

As aminopenicillins, pseudomonas, better coverage vs GNR

Main Uses: HAP, nosocomial infections 

Term
Zosyn
Definition
Piperacillin + Tazobactam
Term
Timentin
Definition
Ticarcillin + Clavulonate
Term
Unasyn
Definition
Ampicillin + Sulbactam
Term
Augmentin
Definition
Amoxicillin + Clavulanate
Term
B-lactam/beta-lactamase inhibitor combinations
Definition

Useful spectrum = parent drug + most b-lactamase producing bacteria 

- streptococci, MSSA, enterococci

- better GNR coverage than parent drugs alone

- anaerobes (like to make B lactamase) 

 

Amp/sublactam + amox/clav are not active against pseudomonas 

 

Broad spectrum leads to good empiric coverage for nosocominal organisms

Less potential to induce resistance compared to cephalosporins, but does occur

Main uses: GI infections, abcesses, HAP, serious nosocomial infections, diabetic wound infections 

Term
Cephalosporin General Activity
Definition

All have 6 membered rings attached to B-lactam ring

All have same MOA as other B lactams

Less B-lactamase susceptible than most penicillins

Classified by generations

Term
1st Generation Cephalosporins
Definition

Cefazolin (IV), Cephalexin (PO)

Cephalexin and Cefadroxil are PO 

Cephadrine is both IV and PO 

 

Eliminated renally

No CNS penetration

Useful spectrum: MSSA, streptococci, some GNR

Main uses: Surgical prophylaxis, cellulitis, UTIs

Term
2nd Generation Cephalosporins
Definition

Cefuroxime (PO/IV)

PO: Cefaclor, Loracarbef, cefprozil, cefdinir

Somewhat worse gram positive coverage, but somewhat better gram - coverage including Neisseria

Cefotetan and Cefoxitin have anaerobic activity

Main use: URTIs, surgical prophylaxis (cefotetin, cefoxitin), gonorrhea 

 

Term
1st Generation Cephalosporin Spectrum
Definition

MSSA, streptococci, some GNRs

Surgical prophylaxis, cellulitis URIs

cefazolin, cephalexin (PO)

Term
PO 2nd generation cephalosporins
Definition
Cefaclor, loracarbef, cefprozil, cefdinir
Term
2nd generation cephalosporin anaerobic activity
Definition

cefotetan, cefoxitin

Main Uses: URTIs, surgical prophylaxis, gonorrhea 

Term
3rd Generation Cephalosporins
Definition

Ceftriaxone, Cefotaxime, Cetazidime

Cefpodoxime, cefixime, ceftibuten (PO), the rest are all IV 

Decreased antistaph activity but increased antistrep except ceftazidime, cefixime (PO), and ceftibuten (PO) which have little or no useful gram positive activity -- better gram negative activity

 

Ceftazidime, cefoperazone active vs pseudomonas aeruginosa

 

Eliminated renally, except ceftriaxone and cefoperazone; ceftriaxone has dual elimination and can cause biliary sludging in neonates 

 

Main Uses: meningitis, CAP/HAP, lyme disease, SSSIs, UTIs, febrile neutropenia 

Term
3rd generation Cephalosporins PO
Definition
Cefpodoxie, Cefixime, Ceftibuten
Term
Exceptions to 3rd generation cephalosporin about having little or no useful gram positive activity
Definition

Ceftazidime, cefixime (PO), and ceftibuten (PO)

little or no useful gram positive coverage

better gram negative coverage

Term
3rd generation cephalosporins active against Pseudomonas
Definition
Ceftazidime and cefoperazone
Term
3rd Generation cephalosporins are eliminated renally except
Definition

Cefoperazone and ceftriaxone

 

-- Ceftriaxone has dual elimination and can cause biliary sludging in neonates 

Term
3rd Generation Cephalosporins Main Uses/Spectrum
Definition
Main Uses: meningitis, CAP/HAP, lyme disease, SSSis, UTIs, febrile neutropenias
Term
4th Generation Cephalosporin
Definition

Cefepime (IV only)

Eliminated renally

useful spectrum: MSSA, streptococci, GNR including pseudomonas

Main uses: HAP, nosocomial infections, febrile neutropenia

Term
5th Generation Cephalosporins
Definition

Cetraroline (IV only)

Anti MRSA cephalosproin

Useful spectrum: MRSA and MSSA, streptococci, enteric GNR

Not useful against pseudomonas

Susceptible to B lactamases

Indicated Uses: SSSIs, CAP 

Term
Monobactam
Definition

Aztreonam (IV only) 

Only active vs gram - rods, including Pseudomonas

Renally eliminated

Not cross reactive with other beta lactam allergies, except ceftazidime

Main use: gram negative infections in patients with allergies to other beta lactams 

Term
Carbapenems
Definition

Imipenem/Cilastatin, Meropenem, Doripenem, Ertapenem

IV only

Renally eliminated

Additional AEs: higher incidence of seizures (especially imipenem); nausea

Stable to most B lactamases

 

Term
Imipenem
Definition

metabolized by renal dihydropeptidase; cilastatin inhibits this

 

Term
Imipenem, meropenem, doripenem useful spectrum
Definition

MSSA, streptococci, E faecalis, anaerobes

Many GNR including P aeruginosa

Term
Ertapenem
Definition
MSSA, streptococci, anaerobes, inactive vs enterococci, P. aeruginosa, Acinetobacter sp.
Term
Carbapenems are drugs of choice for
Definition

B lactatmase producing GNR 

- Carbapenemaes now exist and are spreading

Main uses: nosocomial infections, mixed aerobic/anaerobic infections, febrile neutropenia

Term
Glycopeptides MOA
Definition

Vancomycin; Teicoplanin

Bind to terminal D-ala-D-ala chain of peptidoglycan, halting cell wall synthesis

Time dependent, poor availability

Spectrum: gram positive aerobes and anaerobes, including MRSA

Do not kill b lactam susceptible staph as quickly as b lactams

**drugs of choice for MRSA infections**

Term
Glycopeptides check value when
Definition

Pharmacokinetic levels (Vancomycin)

- Overutilized

- Traditional peak (25-40), trough (5-15) (now higher bc resistance)

Levels not well correlated to efficacy or toxicity

Main value: checking for appropriate dosing in patients with renal dysfunction/altered volumes of distribution 

 

Term
Glycopeptide Adverse Effect
Definition

Red-man Syndrome: when infused quickly, not an allergy

Nephrotoxicity, ototoxicity

Largely a problem with older formulations (mississippi mud)

Increased renal damage possible with concurrent nephrotoxins

Main uses: MRSA infections, gram positive infections in patients with severe beta lactam allergy 

Term
Lipoglycopeptides MOA
Definition

Telavancin (Oritivancin, dalbavancin)

Bind to terminal D-ala-D-ala portion of peptidoglycan AND disrupts cell membrane (lipophilic chain helps)

effective against some vancomycin resistant strains

AE: taste disturbances, headache, dizziness, foamy urine, injection site reaction

Indications: cSSSIs; also studied in HAP

Term
Lipoglycopeptide AEs and Indications
Definition

taste disturbances, headache, dizziness, foamy urine, injection site reaction, nephrotoxicity worse than vancomycin

Indication: cSSSIs, also studied in HAP

Term
Bacitracin MOA
Definition

Peptide antibiotic

Interpheres with dephosphorylation of bactoprenol pyrophosphate, disrupting peptidoglycan translocation 

Highly nephrotoxic, virtually always used topically

Useful spectrum: gram positive cocci and bacilli (topical infections)

Main use: minor skin infections 

Term
Bacitracin AE
Definition
Highly nephrotoxic
Term
Bacitracin spectrum and use
Definition

Spectrum: gram positive cocci and bacilli

main use: minor skin infections

Term
Fosfomycin
Definition

Inhibits peptidoglycan monomer synthesis

Use: UTIs

Available IV in Europe

Used for multi drug resistant infections

Term
Cycloserine
Definition

Inhibits the enzyme that links D-ala molecules

Use: TB 

Term
Daptomycin
Definition

cyclic lipopeptide

MOA: inserts into cell membrane of gram positive oranisms, leading to cation leak, depolarization, and cell death

Bactericidal 

Concentration dependent, Poorly absorbed so IV only

Inactive in lungs (inactivated by surfactant)

Exceted renally

Term
Daptomycin Spectrum
Definition

Gram positive aerobes and anaerobes, including MRSA and VRE 

Anaerobic activity poorly studied

AE: CK kinase elevation - rhabdomyolysis possibility

Uses: bacteremia, skin and soft tissue infections, endocarditis 

Term
Daptomycin AE
Definition

Creatinine Kinase Elevation - possiblity of rhabdomyolysis 

 

Term
Polymyxins
Definition

Colistin (polymyxin E)

Polymyxin B

MOA: bind to cell membrane of gram negative organisms, ad disrupts permeability; rapidly bactericidal

AE: nephrotoxicity (common), neurotoxicity (uncommon)

Concentration dependent

Excreted renally (PK not well studied)

Given by inhalation (CF), IV, or topically

Gram - organisms, including MDR strains of Pseudomonas, Acinetobacter, Klebsiella 

Uses: treatment of MDR GNR infections, topical infections, and prophylaxis of pneumonia in CF patients 

Inactive againsts Serratia, Providentia 

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