cell wall synthesis inhibitors Flashcards
What is the difference between g+ and g- bacteria cell wall
g+ have a thick cell wall which is comprised of peptidoglycan and lipoteichoic acid, absence of outer membrane
g- have a thin cell wall, but have an outer membrane consisting of LPS
What are beta lactam
4 membered ring
can be fused to 5 membered or 6 membered ring
how does B lactam interfere with cell wall synthesis
they bind to active site of transpeptidase, which catalyses the cross linking of terminal peptide components of linear polymer chains
This weakens the cell wall structure of actively growing bacterial cells, lead to build up in intracellular osmotic pressure and lysis of bacterial cells
what type of natural penicillins are there
pen g
pen V
what is pen g and pen v used for
against B lacatamase negative strains of G+ and G-. for G+ is strep and bacillus diphtheriae. For Gi is gonococci, meningococci, treponema palladium
what is natural penicillins not useful for
-> amoebae, plasmodia, rickettsiae, fungi or virus
how is natural pen excreted
renally
which has better oral bioavailability, pen g or pen v, and why
pen V, more acid stable
what first line treatment is pen V used in
in the management of orofacial infections
what are examples of penicillinase resistant penicillins
cloxacillin, oxacillin, flucloxacillin
what is penicillinase resistant penicillins most potent against
inhibitors of most penicillinase producing staphylococci
what is PRP ineffective against
G-ve organisms. all are less effective against microorganisms susceptible to pen G
how is PRP excreted by
renal clearance
why is PRP resistant to b-lactamase
bulky side group confers protection by limiting their accessibility to the catalytic site of action
What are some examples of broad spectrum penicillins ( aminopenicillins)
amoxiciliin, ampicillin
what is the route of administration for aminopenicillins
Oral, IV, Oral for amoxicillin is better than ampicillin
what is aminopenicillins indicated for
B-lactamase negative strains of microogranisms
In UTI against ecoli
prophylaxis against infective endocarditis
detal abscesses
in URI against S. pneumoniae, H. influenzae
Ampicillin in bacterial meningitis, caused by salmonella, E.coli, neisseria meningiditis. S. pneumoniae etc
what does Aminopenicillins not cover
pseudomonas, klebsiella
what is an example of anti psuedomonal penicillin
piperacillin
what coverage does piperacillin have
greater activity against g- bacteria like pseudomonas, proteus and some species of klebsiella.
has been used against non B lactamase g+ like staphylococcus spp, s. pyogenes, enterococcus
how is piperacillin administered
IV
how does piperacillin cleared
primary renal clearance, dose adjustment required with renal dysfunction
how does B- lactamase inhibitors work
binds to b- lactamses, protecting other B lactams antibiotics from being targeted by B lacatamase
clavulanic acid is a suicide inhibitor. Explain
they covalently bond to B lactamase and restructure it permanently inactivating it
when is zosyn used ( tazobactam + piperacillin)
broadest antibacterial spectrum. Used to treat severe cases of nosocomial pneumonia
What are some mechanisms to resistance to penicillins
- penicillin binding protein ( transpeptidase can be altered, reducing affinity for penicillin)
- efflux pump
3.production of B-lactamase
- when bacteria decrease porin production, decreased ability of antibiotic to reach PBP
what is resistant to penicillins
MRSA
what are some adverse effect to penicillin
hypersensitivity
cdad with ampicillin
neurotoxicity
hepatotoicity
anosmia
which cephalosporin have excellent CSF penetration
3,4 and 5 gen
what is 1st and 2nd gen cephs not active against
enterococci or P. aeruginosa
what are the egs of 1st gen cephs and what is it active against
cefazolin (iV), cephalexin, cefadroxil, cephradine.
Mostly taken orally
Very active against gram positives streptococci, staph aureus
example of gen 2 cephs and its usage
cefuroxime,
used for e coli, klebsiella, proteus, haemophilus influenzae
example of gen 3 cephs and its uses
cefotaxime, ceftriaxone,ceftazidime
used for p. aeruginosa, neisseria gonorrhoeae, enterobacteriaceae.
Activity for s aureus, strep pneumoniae, strep pyogenes comparable to first generation agents
example of 4th gen ceph and their uses
cefepime . covers pseudomonas, more resistance to some B-lactamases. Comparable to 3rd gen
example of 5th gene, and uses
Ceftaroline.ONLY ONE TAHT COVERS MRSA.
covers VRSA, strep pneumoniae, haemophilus influenzae, moraaxella catarrhalis. DOes not cover ESBL producing strains
Which ceph is most active against s. aureus and s. pyogenes
cefotaxime
how is ceph eliminated, what is the exception
renally, except ceftriaxone through hepaticd
what are some adverse reactions of ceph
hypersensitivity
GIT, CDAD
Thrombophlebitis
What is carbapenem first line agent
ESBL producing bacteria
what are the types of carbapenem
imipenem, meropenem, ertapenem
which is the more limited spectrum of carbapenem and why
ertapenem, lacks activity against p. aeruginosa and enterococcus
how is carbapenem excreted
imipenem hydrolysed rapidly by DHP-1 found in brush borer of proximal renal tubules. cilastatin added to recover more of the active form
meropenem and ertapenem excreted renally. stable against hydrolysis by DHP-1
what is resistant to carbapenem
MRSA
what are some adverse effects of carbapenem
GIT
Rashes
neurotoxicity at high blood concentrations
cross hypersensitivity with penicillins
What is the example of monobactam
aztreonam
what is monobactam used for
only for gram negative bacteria, useful against many B-lactamase producing gram negative bacteria
like
enterobacteriaceae, p. aeruginosa, h. influenzae. n. gonorrhoeae
Indicated for
UTI by enterobacteriaceae
LRTI due to E. coli, Klebsiella, P. aeruginosa, Haemophilus influenzae
Septicemia and intra abdominal infections by E. coli, Klebsiella pneumoniae, enterobacter and P. aeruginosa
how is azteronam administered
IV, IM, penetrates BBB in patients with inflammed meninges
What are the adverse effects of aztreonam
generally well tolerated, can cause occasional skin rash and transaminasemia.
Little or no cross sensitivity with other penicillin
What does vancomycin covers
primarily acts on gram positive bacteria
How is vancomycin administered
orally and IV, but oral administration poor
what is vancomycin used to treat
CDAD( the oral prep), or antibiotic associated pseudomembranous colitis
common indication is osteomyelitis, endocarditis
infections caused by susceptible organisms in individuals with penicillin allergy
Prophylaxis treatment where MRSAis expected
how does vancomycin works
interferes with transglycosylation of cell wall precursor units, inhibiting bacterial cell wall synthesis
what are some adverse reactions of vancomycin
red man syndrome
- can be prevented by prolonging duration of infusion to 1-2 hrs
thrombophlebitis with fever chills
nephrotoxicity and ototoxicity which is rare but can be increased when used with other agents that cause this as well like aminoglycoside
what is the pregnancy category for vancomycin
Cat C for parentral, cat B for oral
how can vancomycin face resistance
- emergence of s aureus that expresses reduced susceptibility to vancomycin
- expression of enyme that modify the cell wall precursore, substituting terminal D-alanine for D-lactate or D-serine, reducing vancomycin binding affinity
