intro to Abx,Cell wall/membrane attackers Flashcards
bactericidal
DNA replication (fluroQ + metronizadole) RNA replication (rifampin) cell wall attackers (except beta lactamase) cell membrane (polymixins, daptomycin) proteins: ONLY macrolides, streptoGs,aminoGs
batcteriostatic
"ECSTaTiCO about bacteriostatic" to be alive :) Erythromycin Clindamycin Sulfonamides Trimethoprim Tetracyclines Oxazolianones (linezolid)
combination therapy:syngery
increase killing power:
Utilize this when organism is unknown or special indications such as infectious endocarditis or tuberculosis
Concerns for combination therapy include:
Development of resistance
One drug interfering with the action of another
Tetracycline (bacteriostatic) interfering with penicillins (bactericidal)
ex/ PCN (cell wall) and aminoglycoside (protein synthesis): can get into cell wall to target ribosome.
combination therapy: antagonism
dont combine bactericidal and bacteriostatic- can use 2 Cidals or 2 Statics (slow growth inhibits cidal)
PCN: MOA, Adverse effects
MOA: crosslinking of cell wall (peptidoglycan)
Adverse: NEPHRITIS, hematologic (bleeding and clotting), NEUROTOXICITY, secondary infections, hypersensitivity
PCN: spectrum, clinical uses
spectrum: Gram + (cocci, rods, anerobes), Gram - (cocci), spirochete.
uses: syphilis, gangrene
PCN: 3 types and spectrum differences
natural
antistaph (B Lactamase resistant): add MSSA, Streptococcus A and B
extended spectrum: Add gram - (can get through outer membrane) .
–>Amp/Amox: add + and -, subtract MSSA
–>Piper/Tic: add + (including pseudomonas, Klebsiella, Enterobacter)
PCN- natural group
“Natural Voluptous Girls Benza-yonce”
G, V, Benzathine
PCN- AntiStaph
"you take drug test for staff?" - "Nah im chillin, Oxy and Meth Dictate" Naficillin Oxacillin Methacillin Dicloxacillin
PCN- extended spectrum
Ampicillin/Amoxicillin
Pipercillin/Ticarcillin
Abx that attack cell wall synthesis
Beta Lactams (PCNs, Cephalosporins, Monobactams, Carbopenems)
–>Beta Lactamas inhibitors (“CAST”: Clavulanic Acid,
Avibactam, Sulfabactam, Tazobactam)
Glycopeptides
Bacitracin
Fosfomycin
cycloserine (not as important)
Abx that attack protein synthesis
50s subunit: Macrolides, Clindamycin, Streptogramins, Oxazolidones
30s Subunit: Tetracyclines, Aminoglycosides
Abx that attack cell membrane integrity
Polymixins
Daptomycin
Abx that attack metabolic pathways (folate synthesis)or action
sulfanomide, trimethoprim
(PABA- folate- purines)
Abx that attack Nucleic acid synthesis
fluoroquinolones and metronizadole - DNA
Rifampin- RNA
only place in the body where you shouldnt have normal flora
lungs
common offenders with no cell wall (aka can’t use cell wall attacker)
TB, mycoplasm pneumoniae, chlamydia pneumoniae, legionella pneumoniae
difficult areas to determine if normal flora is a problem
sputum, urine from women (dirtier areas)
empiric treatment
Selecting an agent to treat an ill patient based on presumed infection (signs and symptoms). dont wanna wait for C&S- either critically ill pt, immunosuppressed, easy to identify
=treat with broad spectrum right away, then maybe do C&S
min. inhibitory conc. vs. min bactericidal conc.
Minimum Inhibitory Concentration
Lowest antimicrobial concentration that prevents growth of an organism 24 hours after administration
Minimum Bactericidal Concentration
Lowest antimicrobial concentration that kills 99.9% of bacteria
minimum inhibitory conc- goes along with bacteriostatic - can use these at lower agents and increase it to become bactericidal
factors that affect effective conc of drug
Impacted by:
Capillaries ability to carry drug to tissue site
Natural barriers: CNS, placenta, vitreous body of eye
Blood Brain Barrier (BBB)- very tight junctions
For agent to cross BBB is must possess the following:
High lipid solubility
Low molecular weight
Low protein binding
reasons to give drugs parenterally
-For increased bioavailability
Drug is avoiding first pass metabolism by liver
-Need increased absorption due to gut malabsorption issue
-Necessary for high concentrations (meningitis & endocarditis)
-Also give IV or IM if can’t take oral medications
Vomiting or drug not absorbed orally
when can you change IV or oral medication?
General rule: when seeing signs of improvement, fever down and focal symptoms better, and have an equivalent oral antibiotic then switch to it
A popular time to do this is once culture results back (48 hours) as culture will help tell you which oral antibiotic will be effective
conc dependent killing, time dependent killing, postantibiotic effect
-Concentration-dependent killing
Once daily dosing to achieve high peak levels
Leads to rapid killing of pathogen
Ex. Aminoglycosides, fluoroquinolones
-Time-dependent (concentration-independent) killing
Multiple doses or continuous IV infusion
Increased efficacy of antimicrobial when the blood conc. remain above MIC (min inhib conc.) for extended periods of time to kill more bacteria
Beta-lactams, macrolides
-Postantibiotic effect
Persistent suppression of microbial growth after antibiotic levels fall below MIC.
Ex. Aminoglycosides, fluoroquinolones
mechanisms of resistance to antibiotics (by bacteria)
(4 main)
Destruction or Inactivation of Drug Mutation of Target Site Efflux of Drug Genetic Transfer -Conjugation -Transformation -Transduction
common contributors to hypersensitivity (drug allergy)
beta lactams and sulfas
3 complications of antibiotics therapy
hypersensitivity, toxicity (adverse effect), superinfection
B lactamase inhibitors: function
Beta lactamases:source of resistance.
used in combo with abx
inhibit the enzyme produced by the bacteria (w/abx)= bacteria will not be as resistant to the antibiotic.
Available in fixed combinations (ex. amox/clav=augmentin)
The dose is based on the strength of the primary antibiotic – not the beta lactamase inhibitor.
Beta Lactamase inhibitors
"CAST" Clavulanic Acid Avibactram (w/ ceftazidime) Sulfabactam Taxobactam
cephalosporin generation categorizing
Five generations based on when they are made & what they kill.
When a significant modification was made to the group that really changed the spectrum it was called a new generation.
First generation the oldest
Currently on fifth generation
ceph 1st gen and their spectrum
cefazolim + cephalexin gram + cocci (strep and staph) "PEcK" Proteus mirabilis E. Coli Klebsiella
which cephalosporin is secreted by bile/feces?
ceftriaxone- so no dosage adjustment needed for renal/hepatic comprimised individuals
admin and distribution of cephalosporins
Administration: Many IV, fewer oral-poor oral absorption
Distribution: Good, but CSF penetration limited to
Ceftriazone, cefotaxime
All cross placenta
adverse effects of cephalosporins
- super infections
- low prothrombin
- disulfuram-like effect
- increase nephrotoxicity risk with aminoglycosides
common superinfections/secondary infections
Cdiff, Vaginal candidas, thrush
*all can occur with cephalosporins
klebsiella can cause what?
Klebsiella: Gram-negative
pneumonia, blood infections, wound or surgical site infections, meningitis, etc
cephalexin used for what?
UTIs, Skin infections, otitis media, pharyngitis
2nd gen cephalosporins
Cefaclor Cefoxitin Cefuroxime Cefprozil Cefotetan
“Fake Fox Fur ( is) Proper To Tan”
ceforoxime is good to use for what?
CAP (community acquired pneumonia- kills Hflu and strep pneumonia
2nd gen cephalosporin spectrum
PEcK.. add "HENS" H. Flu Enterobacter Neisseria Serratia mercescens
*good for lower respiratory infections
3rd gen cephalosporins
Cefdinir Ceftriaxone Ceftazidime Cefotaxime Cefpodoxime
“Dine Alone” all end in “ime”
*exceptions, cefepime (4th gen), ceforoxime (2nd gen)
“Ceftaz as tazmanian devil- potent and only one that gets pseudamonas)
what do we use to treat gonorrhea?
3rd gen cephalosporins
…” cause once you have gonorrhea, you Dine Alone”
4th gen cephalosporins
cefepime - think “prime”-alone
spectrum: add- stronger against pseudomonas
- more resistant to beta lactamases
treatment for meningitis
ceftriaxone or cefotaxime b/c can get into CNS
3rd gen cephalosporins
5th gen cephalosporin and spectrum
ceftaroline Broad spectrum Add: gram + and - "LAME" Listeria Atypical (chlamydia, mycoplasma) MRSA Enterococci faecalis
SUBTRACT: pseudomonas
monobactams: abx w/in, MOA, spectrum
Aztreonam
MOA: cell wall synthesis (less susceptible to beta lactamases than PCN)
Spectrum:
Great Gram neg. aerobic rods & Pseudomonas aeruginosa
Hospital drug for serious gm – infections that are resistant to other drugs or if penicillin allergic and can’t use other drugs
carbapenems
"DIME" Doripenem Imipenem Meropenem Ertapenem
carbapenems: MOA and Spectrum
MOA: cell wall
Spectrum: BROADEST of all beta lactams
gram +, -, anerobes
for life threatening infections
what is the broadest spectrum of beta lactams?
carbapenems the “DIME” of the dozen
carbapenems: adverse effects
CNS toxicity (risk for seizure) @ high plasma conc.- highest in meropenem
renal excretion of PCN is inhibited by what drug?
probenecid
Vancomycin is used to treat what major infections?
Cdiff, MRSA, Enterococci
bacitracin is used primarily for what?
topically for infections caused by gram + cocci
fosfomycin is used for what?
uncomplicated UTIs (from Ecoli or enterococci)
Abx that attack cell wall but have no B Lactam ring
glycopeptides, bacitracin, fosfomycin
cycloserine, not in slideshow
Vancomycin: what group?
MOA, bactericidal?, spectrum
glycopeptide cell wall- D-ALA-D-ALA (growing peptide) = inhibition of transpepsidase- preventing crosslinking Bactericidal: yes- time-dependent Spectrum: gram + (MRSA, enterococcus, Cdiff)
vancomycin PK
Not absorbed from GI tract, given IV
If given orally it is not being absorbed and giving it to act topically in the GI tract (C. diff)
Slow administration – 1 hour
*significant renal excretion
vancomycin: adverse rxns
“Well tolerated but NOT trouble free”
-Nephrotoxicity – especially if given with other nephrotoxic drugs (aminoglycosides)
-Ototoxicity - especially if given with other ototoxic drugs (aminoglycosides)
-Thrombophlebitis
Irritates tissue at site of injection
And-redman’s syndrome
skin flushing low BP from histamine release when give IV too fast
cell membrane attacking abx
daptomycin, polymixin B and E
Daptomycin: bactericidal? Spectrum? clinical uses?
adverse effects?
yes- conc. dependent
MRSA, enterococcus (including VRE)
uses:
sepsis, endocarditis, complicated skin and soft tissue infections
toxicity: skeletal muscle- myalgia and weakness
polymixin B and E: MOA, bactericidal, spectrum
MOA: cell membrane
bactericidal: YES, time-dependent
spectrum: gram neg. (pseudomonas, E. Coli, Klebsiella)
polymixin B and E: adverse effects
nephrotoxicity and neurotoxicity
fosfomycin: MOA, bactericidal
“cell membrane” category - targets early cell wall synthesis
bactericidal: YES
fosfomycin: spectrum and uses
spectrum: Gram + and - in urine only
uses: uncomplex UTI only
two Abx ecreted via biliary
ceftriaxone and nafcillin
treatment for pharyngitis?
PCN V - bacteria is form of streptococci
PCN will generally treat what?
aminoglycoside will generally treat what?
PCN: gram + (streptococci, staphylococci), syphilis, gangrene
AmG: gram - (pseudomonas, enterobacter)
cephalexin generally used to treat what?
skin and soft tissue infections
nafcillin, oxacillin generally treat what?
staph aureus (osteomyelitis, endocarditis, etc)
cefazolin generally used for what?
perioperative prophylaxis (staphylococci, Ecoli)
ceftotetan generally used to treat what?
intra-ab, gyn, biliary infections (aerobic and anaerobic bacilli)
cefdinir, cefprozil, ceforoxime generally used to treat what?
respiratory tract, skin and soft tissue infections (pneumococci, H Flu)
ceftriaxone generally treats what?
gonorrhea (gonococci), UTI, meningitis (meningococci)
go to treatment for endocarditis?
amoxicillin
