Antibiotics Final Flashcards
Bacteriocidal
Kill
Bacteriostatic
Prevent growth
Describe penicillin
Thiazolidine ring with beta Lactation rings with R groups(for modifications)
Inhibit cell wall synthesis by inhibiting penicillin binding protein/transpeptidase, inhibiting peptidoglycan cell wall cross linking
ONLY WORKS ON ACTIVELY GROWING CELLS
How become resistant to penicillin
Alter porins, alter structure of Pbp/transpeptidase, upregulate penicillin pumps
Porins are how they get into bacteri a
Pump get them out
Penicillin G
1st
Competitively compete with transpeptidase->bacteriocidal
Many organisms resistant
Use on-S pneumonia, s pyogenes, viridans, N mengitidites, spirochetes, C perfrigens
(Gram positive organisms, gram negative cocci, non beta lactamase producing anaerobes
Can get hypersensitivity reactions
Amino penicillins
Increased binding affinity to transpeptidase to increase gram negative coverage
Ampicillin and amoxicillin
Use on E. coli, enteric, W/beta lactamase inhibitor on H influenza, E. coli, klebsiella, protussus, and b fragilis
Hypersensitivity
Penicillinase resistant penicillins
Methicillin, nafcillin, oxacilin, dicloxallin
Competitive inhibition of transpeptidase stop cell wall synthesis
Primary antibiotic for staph a and staph e
What is Mersa
Methicillin resistant staph a
Antipseudomonal penicillins
Competitive inhibitors of pbp and target PSEUDOMONAS A
Piperacillin , usually with tazobactam (beta lactamase inhibitor )
Broadest spectrum of penicillin
Hypersensitivity to beta lactamase ring
Use on staph e and a , enterococcus faecalis, p aeruuginosa
Cephalosporins
7 aa cephalosporin acid base with R 1 and R2 to enhance antibacterial
BACTERICIDAL by binding and inhabiting transpeptidase
Resistance-beta lactamase
Can’t use on klebsiella or coli due to b lactamase
Bacteria can alter structure of transpeptidase or upregulate cephalosporin efflux pumps
Broader spectrum than penicillin
1st gen-s aureus +
2nd gen-ok of pos and neg
3rd gen-e coli -
Hypersensitivity to beta lactamase ring rash several days after therapy
1st generation cephalosporins
Cefazolin and cephalexin Cell wall synthesis inhibitors Get hypersensitivity Use on A aureus, enterococcus and s epidermis Not MRSA
OK against gram negative
2nd generation cephalosporins
Cefotaxime, cefixime, chef dining, ceftibuten, ceftazimide, ceftriaxone,, cefpodoxime proxetil, cefditoren pivoxil
BACTERICIDAL bind transpeptidase
Same as first PLUS gram negative like klebsiella
H influenza, n meningitidis, s pneumonia,
NOT SERRATIA or STAPH A
Cefoxitin and cefotetan against b fragilis and some serratia but not h influenza
3rd generation cephalosporins
Ceftizoxime and cefoperazone (prodrugs hydrolyzed to active) FOR NEGATIVE less on positive
Cefpodozime proxetil__>cefpodoxime
Neusseria , haemophilus
NOT enterobacter, citrobacter, serratia, acinobacter (beta lactamase)
Ceftazidime for P aeruginosa
E. coli, h influenza, p miribalis, s pyogenes
Fourth generation cephalosporins
Cefepime
Enterobacter and pseudomonas bc resistant to their beta lactamase s
Efflux can make resistant to it though!!
Expand gram - coverage
Enterobacter, p aeruginosa,
Poor b fragilis
Get hypersensitivity
Fifth generation cephalosporins
Ceftaroline fosamil—>ceftaroline
Ceftozane ( with tazobactam)
Ceftaroline-MRSA with increased binding to transpeptidase and penicillin resistant S pneumonia
Ceftolozane-pseudomonas
Ok gram negative but not fragilis
Carbapenenems
Have beta lactamase ring
Imipenem(first and more severe side effects also needs renal dipeptidase inhibitor, celastatin), ertapenem, meropenem, doripenem
Bind inhibit transpeptidase
RESISTANT TO LACTAMASE DEGRADATION unlike penicillin and cephalosporin
Also smaller structure so can pass through portions better (gram -)
Resistance-lactamase, shrink portions , degrade carbapenem
For gram negative
Impenem-listeria, staph (not mrsa), enterococci(not faecium), strep, enterobacteriacae, acinetobacter, B FRAGILIS,
Not for c deficit like , MRSA, enterococcus faecium
Meropenem and doripenem better with negatives and worse with positive
But NOT DEGRADED by dipeptidase and don’t need dipeptidase inhibitor
Ertapenem no P aeruginosa or acinetobacter or enterococcus
Hypersensitivity to beta lactamase
Monobactams
Monolithic beta lactamase ring
Aztreonam
Bind transpeptidase
Stable to beta lactamase (still susceptible though)
NOT FOR GRAM POSITIVE OR ANAEROBES (for aerobes)
Same gram - spectrum as ceftazidime since same structure
Enterobacteriacae and P aeruginosa, H influenza
If allergic to penicillin or other can tolerate azetreonam
But caution if giving to a ceftazidime allergic patient
Gram negative bacteria when cant tolerate others
Skin rash or increased serum aminotransferases (hepatoma it you)
Glycopeptides and Lipoglycopeptides
Glycopeptide vancomycin 1st but not engineer lipoglycopeptides called telavancin, dalbavancin and oritavancin
Cell wall synthesis inhibitor-bind D-alanyl-D-alanine and prevent extension and cross linking of peptidoglycan which also damages cell wall
Lipoglycopeptides further improve this by dimerizing and imbedding in their lipid into the cell membrane for improved binding —rapid (oritavin and telavancin do this more rapid than vancomycin or dalbavancin)
E faecium is resistant since transposoning which changes glycopetpide binding site bind bad
Lipo better at overcoming this resistance
Vancomycin glycopeptide-ampicillin resistant enterococci, penicillin resistant strep, MRSA
Everything else resistant and gram - due to size too big to penetrate gram negative bacteria
Telavancin, dalbavancin and oritavancin -same but ok against some enterococci that are resistant to v
IV given…..orally not absorbed
Nephrotoxicity from fast infusion-hypotension, tachycardia, flushing RED MAN SYNDROME not allergy just direct action with mast cells and degranulation and histamine release
Take antihistamine
Beta lactamase inhibitors
Not antibiotics, resemble beta lactamase molecules
Weak antibacterial
Clavulanic acid , sulbactam, tazobactam,
Resistance-differ binding affinity
Extend spectrum of aminopenicillins to include h influenza, E. coli and klebsiella, proteus and B fragilis
Piperacillin is always coformuatied with the beta lactamase inhibitor tazobactam to give best gram - coverage
Well tolerated -minimal but sometimes to people with lactamase problem
Oxazolidinones
Protein synthesis inhibitor (bind to 50s ribosomal subunit, cant protein synthesisinhibit fMET tRNA complex-of AUG no start codon cant be INITIATED)
Linezolid, tedizolid
Gram positive
Bacteriostatic but BACTERICIDAL for strep
Resistance-point mutation 23s rna binding site on 50s , methyltransferase can modify the ribosome and alter binding (TRANSFERABLE BETWEEN BACTERIA_
Gram positive -not for gram negative
For vancomycin resistant enterococci, penicillin resistant s pneumonia, and mrsa
ADVERSE-
Myelosuppression-thrombocytopenia 7-10 days
Lactic acidosis, optic neuritis, peripheral neuropathy from INHIBITION of MITOCHONDRIAL PROTEIN SYNTHESIS
Not used long term is alternate treatment available
Inhibits monomania oxidase -drug drug interactions antidepressants and serotonin reputable inhibitors
Do not coal minister with bc will get serotonin syndome, life threatening headache, palpitations, HTM crisis
Macro lines and ketolides
Macrocyclic lactose ring with deoxycholic sugars
Erythromycin, clarithromycin, azothromycin, fidaxomicin (C dificile by not systemically absorbed-just fidaxomicin)
Ketaloid-telithromycin
Bind 50s prevent translocation of tRNA from a site to p site also cause conformational change in ribosome
Which indirectly inhibit pbp
Bacteriostatic
Resistance-efflux, ribosome can make methylated enzymes which modify binding site on ribsome, degradation(esterases by enterobacteriacae), 50s mutations (campylobacter and bacillus )
Erythromycin-streptococci, pneumococci, staphylococci, C jejuni, M pneumonia, C trachomatis, H pylori, gram positive bacilli, bartonalle, neisseria, rickettsia, treponema pallidus
Not for aerobic gram negative bacilli
Azithromycin-moraxella catarrhalis , chlamydia, , h pylori ,
Clarithromycin-better for strep and staph and h influenza
Fidaxomicin-c difficult
Ketolide-withstand resistance to S pneumonia and S aureus bc poor substrates for drug efflux
Adverse-diarrhea nausea vomiting anorexia —erythromycin acts on motility receptors that stimulate GI motility , prolonged hepatotoxicity
Hypersensitivity skin eruptions , eosinophilia, fever
Streptogramins
Streptogramin a-dalfopristin 70%
Streptogramin b-quinupristin 30%
COMBINED - bind 50s SYNERGYSTICALLY
Q bind 50s induces early termination of protein synthesis
D-enhance bind 50s nearby conformational change enhance binding of Q
BACTERICIDAL
Resistance-enzymatic deactivation D, binding site altered, efflux,
Gram positive cocci (resistant strep, penicillin resistant s pneumonia, MRSA) M pneumonia, C pneumonia, Legionella Staph strep BACTERICIDAL Bacteriostatic with E faecium Not foR -
Well tolerated pain at infusion site
Tetracyclines and glycycylines
T-four membered ring -doxycycline, minocycline, tetracycline, demeclocycline
G-broader spectrum in tetracycline resistant -tigecycline
Bind 30s prevent aminoaciduria tRNA from entering a site
Bacteriostatic
Resistance-influx reduced or efflux up , (glycylcylines overcome the efflux sometimes), upregulationof a preotein that dislodges tetracyclines or glycylcylines(. G have higher affinity bind0, enzymatically deactivated
Tetracyclines0gram positive anaerobes, chlamydia, mycoplasms, rickettsias, MRSA, strep pyogenes UREAPLASMA, mycoplasma pneumonia’s, rickettsia, chlymidia legionells plasmodium , t pallidus spirochete
G-all and enterococci, enterobacteriacae, acinobacter, b fragilis,
Pseudomonas proteus are resistant
Adverse-GI irritation and bone and teeth bind calcium deform, enamel
Can get C dificille
Aminoglycosides
Streptomycin, gentamicin, tobramycin, amikacin, neomycin, paromycin, kanamycin, netilmicin
Often combined
Bind 30s inhibit initiation, continuation, premature termination
BACTERICIDAL
Enter gram - by porin and then electrical gradient which needs o2 don’t work on anaerobes
Synergy if add penicillin or vancomycin on getting in there
SYNERGYYYY
Resistant-enzymatic inactivation , decreased transport from porin change, (streptomycin)gram negative aerobes
Enterobacter, E. coli, klebsiella, pneumonia, pseudomonas, serratia, acinetobacter
Not used alone to treat gram positive add with beta lactamase antibiotic to exapsd coverage to gram negative
To work on listeria, viridans, streptococci enterococci staphylococci
Adverse-nephrotoxic and ototoxic
Balance ataxia
Fluoroquinolones
Morflaxin and ciproflacin second group better for gram positive cocci
Gemifloaxin, moxifocin, gatifloxacin-gram positive
Moxifloxacin-anaerobes
Inhibit transcription and replication of bacterial dna by inhibiting bacterial topoisomerase 2 (gyrase)and bacterial topoisomerase 4. We have 2 but ok and dna gyrase
Resistance- mutation in quinolone binding region on dNA grasses or topoisomerase , efflux
Gram pos and neg
Gram negative aerobes
Not gram positive cocci
Well tolerated GI side effects C dificille induced colitis tendon rupture, AT prolongation from moxifloxacin
Sulfonamides and benzylpyrimidines
Co formulated
Sulfamethoxazole and trimethoprim
TMP/SMX
Synergistic -disrupt different steps of THF biosynthetic pathway
For purine synthesis
PABA-THF-purine
Trimethoprim-dihydrofolatereductase inhibitor
Sulfamethoxazole-analog of PABA competitive inhibitor for dihydropteroate synthesis
Resistance-change in THF synthetic path , overproduce PABA, upregulate mutated dihydropteroate synthase that has reduced binding for sulfamethoxazole. Permeability
Permeability, upregulate DHF reductase,
Combo-staph epidermidis, s aureus, MRSA, S pyogenes, viridans, strep, serratia, shigella, salmonella, enterobacter, proteus m, nocardia, p jiroveci, haemophilus
Anemia leukoplakia
Nausea vomit urticaria rash Stevens Johnson syndrome -mucous membrane skin eruption
Polymyxins
Basic peptides
Polymyxin B and colistin (polymixin E)
Polymyxin E-topical
Adverse effects not used as much
Gram negative
But used again to combat resistance
Disrupts membrane cationic detergent due to amphipathic properties
Disrupt outer membrane gram negative
And can inactivate endotoxins!!!! Prevent fever, diarrhea, shock, BACTERICIDAL
Resistance is rare-klebsiella and acinetobacter , p aeruginosatopical on scrape well tolerated. But systemic parenteral administration is toxic NEPHROTOXICITY slurred speech, vertigo, parenthesis, apnea, muscle weakness
Only for gram negative
Why are penicillins called “beta-Lactam antibiotics”?
They all have a beta-Lactation ring
Is penicillin bateriostatic or bactericidal?
Bactericidal
Steps in penicillin action
- Penetrate cell layers
- Keep beta-Lactam ring in tact
- Bind transpeptidase (Pbp)
How can a bacteria be resistant to penicillin
- Outer membrane (gram negative) must be right size and charge to enter
- Beta lactamase(gram - and +) cleave CN bond in the beta Lactation ring (staph a secretes penicillinase, NOTE: gram negative with beta lactamase destroy in the periplasmic space)
- Later transpeptidase
- Pump it out with the “effluent pump”
Sensitivity to penicillin
Anaphylactic “allergic” reaction
IgE mediated
Bronchospasm, urticaria, anaphylactic Shock)
C. difficile
Type G penicillin
Fleming original
Mold penicillium notatum made a chemical that inhibited Steph a growth
1941
Oral (penicillin V is acid stable), IM, IV (cryastalline to increase HL)
USE ON : streptococcus pharygitis (oral )
Aminopenicillins
Better coverage of gram -
Better penetration through outer membrane and better binding to transpeptidase
Still problems with penicillinase
‘USE ON : E. coli, proteus, salmonella, shigella) ENTEROCOCCUS
Resistance: H influenza and many gram - have penicillinase
Ampicillin(oral) , amoxicillin(oral, better absorbed so for bronchitis, otitis media, sinusitis)
DRUG OF CHOICE FOR LISTERIA
*AMP-GENT IV ampicillin with others (gentamicin) for broad spectrum gram ———-UTI bc often has gram negative enteric or enterococcus
Penicillinase resistant penicillins
Wider gram - (including pseudomonas )
Methicillin, nafcillin, oxacilin (IV)
(I met a nasty ox)
Staph Aureus, but not MRSA
Naficillin-S. Aureus (cellulitis, endocarditis, sepsis)
Cloxacillin and dicloxacillin
Oral beta lactamase resistant penicillins
Only for gram + (staph a)
Patient has cellulitis or impetigo?
Staph a or b hemolytic steptococcus
CLOCK
Penicillin g or v-not for staph a
Penicillinase resistant agents-give bc cover staph a (produces beta lactamase)
Anti pseudomonas penicillins (carboxypenicillins and ureidopenicillins )
Expanded gram - rod coverage
Pseudomonas a, b fragilis, and many gram +
