Abx Flashcards
What is pharmacokinetics?
all of the ways a body manipulates the drug
What is pharmacodynamics
the biochemical and physiological effects of a drug and its MOA
What is the difference between bactericidal and a bacteriostatic antibiotic?
Bactericidal kills bacteria. Bacteriostatic inhibits growth of bacteria and the immune system kills infections
What does MIC stand for?
Minimum inhibitory concentration
What is the difference in time dependent and concentration dependent killing? Explain in terms of MIC?
- Time dependent; 2 - 4x MIC (time above MIC = killing) 2. Concentration dependent; high concentrations (often 10x MIC) to get bactericidal effect
With serious infections (meningitis, osteomyelitis, endocarditis, bacteria c. neutropenia) what type of abx is preferred?
bactericidal
What are 5 examples of bactericidal abx?
Quinolones, aminoglycosides, penicillins, cephalosporins, rifampin
What are 9 examples of bacteriostatic abx?
tetrocyclines, macrolides, clindamycin, septra, chloramphenicol, dapsone, isoniazid, vanco, linezolid
What are 5 examples of time dependent abx?
penicillin, clindamycin, linezolid, cephalosporins, macrolides
what are two examples of concentration dependent abx?
aminoglycosides, quinolones
Gram +ve bacteria have a thick outer wall composed of _______.
peptidoglycan layer
Gram -ve bacteria have a thin inner wall of ________ and an outer membrane composed of _____ & _______.
peptidoglycan, lipopolysaccharide & protein
What happens to gram +ve and -ve bacteria during gram staining?
Gram +ve purple. Gram -ve pink (accept counter stain)
What are 4 examples of gram +ve cocci?
Staphylcoccus aureus, Streptococcus, enterococcus, peptostreptococcus
What are 5 examples of gram +ve bacilli?
bacillus sp, clostidia, listeria, corynebacterium, actinomyces
What is an example of gram -ve cocci?
neisseria
What is an examples of gram -ve bacilli?
e coli, shigella, salmonella, citrobacter, klebsiella, yersinia, morganella, proteus, serratia, enterobacter
Which bacteria cause the majority of skin and soft tissue infections? (particularly cellulitis)
staphylcoccus aureus, streptococci sp
What is the MOA of penicillins
inhibit cell wall synthesis by binding to PBPs (which aid in cell wall synthesis)
What are two mechanisms of resistance to penicillins?
beta lactamases (enzymes which break down beta lactam ring), Altered PBPs
cell wall synthesis inhibitors are ______ (type of abx) except for ______
beta lactam abx, except for vanco
Which organisms are covered by pen G?
Streptococci, peptostreptococci, coynebacterium (diptheria), clostridium (except c diff), neisseria, trep pallidum, erysipelothix, actinomyces
What organism is rarely covered by PenG due to resistance?
staph
Ampicillin (IV) or amoxicillin (PO) covers everything Pen G covers plus what?
some gram -ve, enterococcal, listeria & shigella [ enterococci, h influenza, listeria, e coli, proteus, salmonella, shigella]
Piperacillin covers everything ampicillin covers plus what? (3)
Gram -ve (klebsiella, serratia, B fragilis), pseudomonas, anaerobic (enterobacter, citrobacter)
What is cloxacillin?
beta lactamase resistant penicillin
What does cloxacillin (beta lactamase resistant penicillin) cover?
strictly gram +ve. designed specifically to cover S aureus (not MRSA), no gram -ve or anaerobic.
What are the three most common pathogens related to UTIs?
E coli (58.3%), Enterococcus (11.3%), Klebsiella pneumoniae (8.5%)
What must you factor into your emperic tx choice for UTIs?
community ecoli resistance drives emperic tx (allergy to sulfa important)
Which meds would you use based on community ecoli resistance?
20% resistance to septra (Use Nitrofurantoin/quinolone)
What is the duration of therapy for acute and uncomplicated UTIs?
3 days (if unsuccessful tx for 7 - 10 days)
What is the duration of therapy for a pregnant pt with uncomplicated UTIs?
7 days (avoid septra near term to avoid kernicterus; bilirubin induced brain dysfunction)
what is the class of abx that ciprofloxacin, levofloxacin and moxifloxacin belong to?
Fluoroquinolones
What does ciprofloxacin cover?
excellent gram -ve
What does levofloxacin cover?
Cipro (gram -ve) PLUS gram +ve/ atypicals
What does moxifloxacin cover?
Levofloxacin (gram -ve, gram +ve, atypicals) PLUS anaerobic
What is the MOA for fluoroquinolones?
- DNA gyrase (topoisomerase II) prevents supercoiling of bacterial DNA. 2. Topoisomerase IV allows for separation of the two rings of DNA following replication. 3. Flouroquinolones inhibit both topoisomerase II & IV. (II target in gram -ve/ IV target in gram +ve)
What do fluoroquinolones inhibit? What organism does that target
inhibit topoisomerase II & IV. Target Gram -ve (II) and gram +ve (IV)
What med does tendinopathy occur in 1% of patients?
ciprofloxacin
What increases the risk of developing tendinopathy on ciprofloxacin?
DM and steroid use
What are indications for the use of ciprofloxacin?
- Broad spectrum (GU infections, pseudomonas resp infections) 2. Soft tissue infections (DM, infections where gram -ve or pseudomonas may be involved) 3. Gonorrhea 4. Travellers diarrhea
What are the indications for levofloxacin?
Resp infections, sinusitis, CAP, UTis, exacerbations of chronic bronchitis
What are the indications with moxifloxacin?
Resp infections, sinusitis, exacerbations of chronic bronchitis, CAP (all Levo minus UTIs)
What ECG changes are seen with moxifloxacin?
QT prolongation
Do not use moxifloxacin in those with severe ___________insufficiency?
hepatic insufficiency (only 20% excreted renal)
What is the most common pathogen associated with CAP?
Streptococcus pneumoniae (40% of known)
_____ to ____ % of cases of pneumonia ave an unknown cause
40 - 50%
Who can be treated empirically for CAP? (which groups)
those with no modifying RF and those with COPD who have not been on abx or oral steroids x 3 months
What is the empiric tx of pneumonia?
macrolide abx
Those with COPD and past abx o steroid use are more likely to harbour gram _____ organisms as well as ______ organisms
Gram -ve, resistant pathogens
Your first line abx for COPD c. abx or steroids in past 3 months is?
resp fluoroquinolones (levofloxacin, moxifloxacin)
Second line abx for COPD c. abx or steroids in past 3 months is?
Beta lactam (amoxicillin/clavulanate) OR cephalosporin (2nd Gen) & macrolide
If a patient with CAP has a suspected micro aspiration, you will need to use an Abx with ______ coverage. What is your first choice?
anaerobic coverage. First choice = amoxicillin/clavulanate & macrolide
Which 4 classes of abx have decreased protein synthesis as part of their MOA?
Macrolides, tetracyclines, aminoglycosides, clindamycin
What is the MOA for macrolide abx?
decreased protein synthesis (50s ribosomal subunit)
What are 3 mechanisms of resistance to macrolides?
decreased permeability, altered ribosomal subunits, enzymatic hydrolysis
What do macrolide abx cover?
broad coverage of gram +ve and -ve, atypical coverage (mycoplasma, chlamydia), mycobacterial coverage
What do macrolides NOT cover?
anaerobes
What are 3 examples of macrolide abx?
Erythromycin. Clarithromycin. Azithromycin
What two macrocodes are available in daily dosing with less GI SE?
Clarithromycin and azithromycin
What is the MOA for tetrocyclines?
binds to 30s ribosomal sub unit to inhibit protein synthesis
What is the resistance mechanism for tetracyclines?
Resistance by efflux pump or by ribosomal protection
What are the SE of tetrocyclines?
SE; GI upset, photosensitivity (redness in sun exposed areas), teeth/bone problems (grey, yellow, brown discolouration)
What is the MOA of aminoglycosides
Interfere with protein synthesis, bind to amnoacyl site of 16s ribosomal RNA with the 30s sub unit
What are examples of amino glycosides?
Gentamycin, tobramycin, amikacin, streptomycin
When do you need to adjust amino glycoside dosing?
renal failure dose adjustment
What do amino glycosides cover?
aerobic gram -ve bacilli (including pseudomonas), staph aureus, enterococci
What toxicities can occur with amino glycosides?
tubular necrosis, renal failure, cochlear toxicity (deaf), vestibular toxicity (vertigo)
What are some bacterial causes of meningitis?
Strep pneumoniae (gram+ diplococci), neisseria meningiditis (gram - diplococci), Haemophilus influenza, listeria moncytogenes (very young, very old), lyme disease, gram -ve bacilli, staphylococcal
The first gen cephalosporins have good gram ____ coverage.
first gen = good gram +ve
As you move to 2nd, 3rd, 4th gen. Cephalosporins tend to lose _____ coverage and gain ____ coverage.
lose +ve and gain -ve coverage
What are two examples of first gen cephalosporins? (one IV, one PO)
Cefazolin (ancef) IV and Cephalexin (keflex) PO
when are first gen cephalosporins (cefazolin, cephalexin/ ancef, keflex) typically used?
Gram +ve infections (strep, staph). Perioperatively
What are examples three examples of 2nd gen cephalosporins?
Cefuroxime IV (oral form = cefitin), Cefaclor, Cefoxitin
What does cefuroxime and cofactor cover (2nd gen cephalosporins)
gram -ve
What does cefoxitin cover?
gram -ve and anaerobic
What are three examples of non pseudomonal 3rd gen cephalosporins?
CefTRIAXone, CefoTAXime (IV typically used as empiric tx of bacterial meningitis), CeFIXime
What is an example of a 3rd gen cephalospoin that has pseudomonal coverage
cefTAZidime
What is an example of a 4th gen cephalosporin?
Cefepime
What does cefepime (4th gen cephalosporin) cover?
gram -ve and pseudomonas
What is the only cephalosprin with anaerobic coverage?
ceFOXitin
which two cephalosporins have pseudomonas coverage?
CefTAZadime (3rd gen) Cefepime (4th gen)
This class of abx is broad spectrum and typically used only for serious infection with are often polymicrobial
Carbapenems
What are 4 examples of carbapenems?
Imipenem + cilastatin. Meropenum. Ertapenem, Doripenem.
All of the carbapenems (imi+cilastatin, mero, efta, dori) cover pseudomonas except for ________
Ertapenem
What else do carbapenems cover?
Gram +ve, Gram -ve, Anaerobes
Seizures are a SE of _______?
Imipenem (seizures)
N&V, diarrhea, headache a SE of ________?
Doripenem (N&V,Diarrhea, HA)
What is the MOA of carbapenems?
class of beta lactams which are highly resistant to beta lactamasses
Which abx have anaerobic coverage? (7)
Metronidazole (flagyl). Clindamycin. Clavulin. Piperacillin/Tazobactam. carbapenems. cefoxitin. Moxifloxacin
What is the MOA for metronidazole
a nitromidazole abx which is reduced to toxic compounds that kill bacteria (bactericidal)
What does metronidazole cover?
covers anaerobes and parasitic infections (C diff as well)
What are the SE of metronidazole?
Seizures, peripheral neuropathy, must avoid ETOH, metallic taste in mouth
What is the only non B-lactam abx to have its effect at the cell wall level?
Vancomycin
Vancomycin only covers ______.
Gram +ve
Vancomycin is not orally absorbed, so why do they make an oral form of it?
oral formulation to treat C Diff Colitis
What are the clinical uses of vancomycin?
Gram +ve infection with severe pen allergy, MRSA and enterococcal infection (endocarditis), C Diff (oral vanco)
What are the SE of vancomycin?
Ototoxicity, nephrotoxicity, allergy, redman syndrome (flushing/redness of face); rapid infusion related
What are 8 mechanisms of abx resistance?
- enzymatic inactivation 2. decrease permeability of bacterial membranes (change in porin layers of LPS in gram -ve) 3. Anx efflux 4. Altered target sites (altered ribosomal units or PBPs) 5. Altered target enzymes 6. Protected target sites 7. Overproduction of target 8. Bypass of abx inhibition
” The combined effects are greater than the sum of their independent activities” What word is used to describe this effect when using a combo of abx?
synergistic
“The activity of the combination of 2 abx is less than the sum of each of their additive products” What is the term used to describe this?
antagonistic effect
Explain why penicillin and gentamycin are used together to treat enterococcal endocarditis?
Pen alone typically does not work due to resistance. But pen damages the cell wall which allows more gentamycin to enter the cell to work @ the ribosomal level
How does clindamycin work?
Inhibits protein synthesis (lincosamide antibiotic)
How does resistance occur?
resistance altered by 50s receptor sites or by enzymatic inactivation
What are the indications for clindamysin
anaerobic infections, staph or strap, pen allergic patients (gram +ve & anaerobes)
Which abx have anti-pseudomonal properties? which is the only po med?
Ciprofloxacin (ONLY PO), Pipercillin/tazobactam, carbapenems, aminoglycosides, ceftazidime, cefepime
What meds can be used in tx of MRSA?
Vancomycin, rifampin, trimethoprim/sulfamethoxazole, clindamycin, linezolid, daptomycin, Quinupritin -dalfopristin
