Antibacterials 3 Flashcards by Shahryar Farooq

Describe Cephalosporins

• beta-lactam antibiotics
• Bactericidal
• Same MOA as penicillin's
• Affected by similar resistance mechanisms but less
susceptible to beta-lactamases
• Classified into generations

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What are cephalosporins inactive against?

All 1st-4th generation cephalosporins are considered
inactive against MRSA,
• All cephalosporins are considered inactive against
Actinotobacteria, Listeria, Legionella, Chlamydia,
Mycoplasma, and Enterococci species (mnemonic :
LAME)

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List 1st generation cephalosporins

Cefazolin, Cephalexin

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Define 1st generation cephalosporins

Penicillin G substitutes
• Resistant to staphylococcal penicillinase
• Activity against Gram-positive cocci, P.mirabilis, E.coli, &
K.pneumoniae

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What are 1st generation clinical applications?

Rarely DOC for any infections

• Cefazolin = DOC for surgical prophylaxis

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List 2nd generations cephalosporins?

Cefaclor, Cefoxitin, Cefotetan, Cefamandole

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Define 2nd generations cephalosporins

Extended Gram-negative coverage
• Greater activity against H.influenzae, Enterobacter
aerogenes and some Neisseria species
• Weaker activity against Gram-positive organisms

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2nd generation Cephalosporins clinical applications?

Primarily used to treat sinusitis, otitis & lower
respiratory tract infections
• Cefotetan & cefoxitin = prophylaxis & therapy of
abdominal and pelvic cavity infections (increased risk of
Gram negative bacteria being present)

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List 3rd generation cephalosporins

Ceftriaxone, Cefoperazone, Cefotaxime, Ceftazidime,

Cefixime

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Define 3rd generation cephalosporins

Enhanced activity against Gram-negative cocci
• Highly active against enterobacteriacae, Neisseria, &
H.influenzae
• Cefotaxime, ceftazidime and ceftriaxone = usually active
against pneumococci

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Clinical Applications of Ceftriaxone?

DOC for gonorrhea
• DOC for empiric treatment of meningitis
• Prophylaxis of meningitis in exposed individuals
• Treatment of disseminated Lyme disease (CNS or
joint infection)

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Which two 3rd generation cephalosporins have activity against p. aeruginosa?

Cefaperazone, ceftazidime

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Identify 4th generation cephalosporin, ROA, and define 4th generation Cephalosporin activity

Cefipime, Parenteral admin. Only
• Wide antibacterial spectrum eg, enterobacter,
Haemophilis, Neisseria, E.coli, pneumococci, P.mirabilis
& P.aeruginosa

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Clinical applications of Cefipime

• Treatment of mixed infections with susceptible
organisms
eg, complicated UTI’s, complicated intra-abdominal
infections, febrile neutropenia

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Define and identify 5th generation cephalosporins

Ceftaroline
Parenteral admin. only
• Activity against MRSA !
• Similar spectrum of activity to 3rd generatio

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Clinical application of Ceftaroline?

Skin and soft tissue infection due to MRSA,

particularly if Gram-negative pathogens are coinfecting

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Cephalosporins PK?

Most administered parenterally (exceptions =
cephalexin, cefaclor, cefixime)
• Only 3rd generation reach adequate levels in CSF
• Mainly eliminated via kidneys (exceptions = ceftriaxone &
cefoperazone excreted in bile)

Cephalosporins Adverse events?

Allergic reactions (cross-sensitivity with penicillins can
occur)
However, minor penicillin allergic patients often
treated successfully with a cephalosporin
• Pain at infection site (IM), thrombophlebitis (IV)
• Superinfections (eg, C.difficile)
Kernicterus (pregnancy)

Cefamandole, cefoperazone & cefotetan contain

methyl-thiotetrazole group, all can cause:

• hypoprothrombinemia (Vit. K1 admin can prevent)
&
• disulfiram-like reactions (avoid alcohol)

List of Carbapenems

Define Carbapenems

Doripenem, Ertapenem, Imipenem & Meropenem
• Synthetic beta-lactam antibiotics
• Resist hydrolysis by most beta-lactamases

Describe Carbapenems antibacterial spectrum

Very broad spectrum of activity
Ertapenem = less broad, not active against P.aeruginosa
• Active against -lactamase-producing Gram-positive &
negative organisms; aerobes & anaerobes; P.aeruginosa
• Not active against carbapenemase producing
organisms eg, carbapenem-resistant enterobacteriaceae,
carbapenem-resistant klebsiella
• Not active against MRSA

Carbapenems Clinical Applications?

Use is typically restricted to avoid resistance
• Use limited to life-threatening infections, especially if
broad-spectrum coverage is required
Commonly used for treatment of:
• extended-spectrum beta-lactamase producing Gramnegatives

Describe carbapenems PK?

IV
• Imipenem forms potentially nephrotoxic metabolite.
Combining with enzyme (dehydropeptidase I) inhibitor
Cilastatin prevents metabolism thus prevents toxicity
& increases availability.
• Doripenem, ertapenem and meropenem are not
metabolized by same enzyme (no need for Cilastatin)

Describe Carbapenems adverse effects

GI distress (nausea, vomiting, diarrhea)
• High levels of imipenem can cause CNS toxicity e.g.
seizures
• Allergic reactions
(partial cross-sensitivity with
penicillin’s)

What is a monobactam?

Aztreonam, ketone group on amide link

Monobactum antibacterial spectrum?

Aerobic Gram-negative rods ONLY (including pseudomonas) • No activity against Gram-positive bacteria or anaerobes • Resistant to action of -lactamases

Monobactum Clinical applications?

UTI’s, lower respiratory tract infections, septicemia, skin/structure infections, intraabdominal infections, gynecological infections caused by susceptible Gramnegative bacteria • Useful for treatment of Gram-negative infections in patients allergic to penicillin

Describe Monobactum Pharmacokinetics?

Mainly IV or IM • Can be given by inhalation in CF patients • Penetrates CSF when inflamed • Excreted primarily via urine

Monobactum Adverse Events?

Relatively nontoxic • Little cross-hypersensitivity with other beta-lactam antibiotics • Occasional skin rashes and GI upset

Define Vancomycin

Bacterial glycoprotein • Active against Gram-positive bacteria only • Virtually all Gram-negative organisms are intrinsically resistant • Effective against multi-drug resistant organisms (eg, MRSA, enterococci, PRSP)

Vancomycin MOA?

Binds to the D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide • Inhibits bacterial cell wall synthesis & peptidoglycan formation • Not susceptible to beta-lactamases

How does bacteria become resistant to vancomycin?

• Modification of the D-Ala-D-Ala binding site (D-Ala replaced by D-lactate) • Plasmid-mediated changes in drug permeability

Vancomycin Clinical Applications?

Treatment of serious infections caused by beta-lactam resistant Gram +ve organisms eg, MRSA • Treatment of Gram +ve infections in patients severely allergic to beta-lactams • In combination with an aminoglycoside for empiric treatment of infective endocarditis • In combination with an aminoglycoside for treatment of Penicillin Resistant Strep Pneumoniae (PRSP) Given orally for the treatment of staphylococcal enterocolitis or antibiotic-associated pseudomembranous colitis (C.difficile)

Vancomycin PK?

Poor oral absorption • Requires slow IV infusion (60-90 min) • Penetrates CSF when inflamed • 90-100% excreted via kidneys

Vancomycin AE?

• Mostly minor eg, fever, chills, phlebitis at infusion site • ‘Red man’ or ‘red neck’ syndrome (infusion-related flushing over face and upper torso) • Ototoxicity (drug accumulation) • Nephrotoxicity (drug accumulation)

Describe Daptomycin?

Bactericidal • Effective against resistant Gram-positive organisms (eg, MRSA, enterococci, VRE & VRSA) • Inactive against Gram-negative bacteria • Not effective in treatment of pneumonia

Daptomycin MOA?

• Novel mechanism of action -> useful against multi-drug resistant bacteria • Binds to cell membrane via calcium-dependent insertion of lipid tail • Results in depolarization of cell membrane with K+ efflux -> cell death

Daptomycin Clinical application?

Recommended for treatment of severe infections caused by MRSA or VRE • Treatment of complicated skin/structure infections caused by susceptible S.aureus

Daptomycin PK?

IV only | can accumulate in renal insufficiency

Daptomycin AE?

Constipation, nausea, headache, insomnia • Elevated creatine phosphokinases (recommended to discontinue coadmin. of statins)

Define Bacitracin?

* Unique mechanisms -> no cross resistance * Interferes in late stage cell wall synthesis * Effective against Gram-positive organisms * Marked nephrotoxicity -> mainly topical use

Define Fosfomycin

Inhibits cytoplasmic enzyme enolpyruvate transferase in early stage of cell wall synthesis • Active against Gram-positive and negative organisms • Oral • Used for treatment of uncomplicated lower UTI’s