Antibacterials 3 Flashcards
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
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)
List 1st generation cephalosporins
Cefazolin, Cephalexin
Define 1st generation cephalosporins
Penicillin G substitutes
• Resistant to staphylococcal penicillinase
• Activity against Gram-positive cocci, P.mirabilis, E.coli, &
K.pneumoniae
What are 1st generation clinical applications?
Rarely DOC for any infections
• Cefazolin = DOC for surgical prophylaxis
List 2nd generations cephalosporins?
Cefaclor, Cefoxitin, Cefotetan, Cefamandole
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
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)
List 3rd generation cephalosporins
Ceftriaxone, Cefoperazone, Cefotaxime, Ceftazidime,
Cefixime
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
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)
Which two 3rd generation cephalosporins have activity against p. aeruginosa?
Cefaperazone, ceftazidime
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
Clinical applications of Cefipime
• Treatment of mixed infections with susceptible
organisms
eg, complicated UTI’s, complicated intra-abdominal
infections, febrile neutropenia
Define and identify 5th generation cephalosporins
Ceftaroline
Parenteral admin. only
• Activity against MRSA !
• Similar spectrum of activity to 3rd generatio
Clinical application of Ceftaroline?
Skin and soft tissue infection due to MRSA,
particularly if Gram-negative pathogens are coinfecting
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
