Apr24 M3,4-Antimicrobial antibiotics Flashcards
important nose and sinus bacterial pathogens
- Strep pneumoniae
- group A strep (GAS)
- Staph aureus
- Haemophilus influenza
important throat and pharynx bacterial pathogen
group A strep
important middle ear bacterial pathogen
Strep pneumoniae
important urinary tract bacterial pathogen
-enterobacteriaceae
-enterococcus
(would come from gut)
important CNS bacterial pathogens
- Neisseria meningitidis
- Haemophilus influenzae
- Strep pneumoniae
- Listeria
important eye bacterial pathogens
- Haemophilus
- Moraxella
- Neisseria gonorrhoeae
- Strep pneumoniae
important wound infection bacterial pathogens
- Staph aureus
- Group A strep
important bone and joint bacterial pathogens
- Staph aureus
- GAS
- Kingella kingae
important blood bacterial pathogens
anything can cause that except the non invasive bacteria
Abx that have the same bioavailability if taken po or IV
- clindamycin
- fluoroquinolones
- septra
- tetracyclines
- metronidazole
- linezolid
what is the rate limiting step in giving Abx po (for Abx what are equally good po and IV)
- GI tolerance
- GI absorption (if diarrhea or nauseated, colitis, gastritis)
how time-dependent (conc independent) antibodies work
activity dependent on the AMOUNT OF TIME spent above the MIC of the organism
classic type of Abx that is time-dependent
beta-lactams (penicillins, cephalosporins, carbapenems)
how concentration dependent antibodies work
activity is dependent on CONCENTRATION above the MIC
classic type of Abx that is concentration dependent
aminoglycosides
beta lactam Abx (penicillin and derivatives) molecular structure
- have a beta-lactam ring in their molecular strcture
- this ring looks like the peptidoglycan wall (looks like the 2 acids in the wall, N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM))
mechanism of action of beta lactams
picked up by penicillin binding protein and inhibition of cell wall synthesis. wall is weak when enough penicillin in it and it bursts
how resistance to beta lactams develops
- formation of enzymes that inactivate penicillin (penicillinase precisely or beta lactamase in general): destroy the beta lactam ring (happens in MSSA)
- mutated penicillin binding protein (e.g. in MRSA and strep pneumoniae). don’t recognize beta lactams
- decrease in Abx penetration in bacteria
how can we fight the resistance of bacteria that make beta-lactamases (like MSSA)
add beta lactamase inhibitors to the Abx regimen
what beta lactamase inhibitors do
bind beta-lactamases of bacteria and rid them so a beta-lactam Abx can work
penicillin general coverage
especially for gram positive anaerobes but gram negative too (including anaerobes, gram+ and -)
problems encountered with penicillin
- MSSA (resistant S aureus that developed a penicillinase)
- resistant gram negative enterobacteriaceae (developed beta-lactamases)
- new pathogens that are resistant (pseudomonas spp)
name of specific penicillins designed to target MSSA (penicillinase S aureus) + disadvantage
- methicilin
- cloxacilin
- problem = loss of anaerobic activity
penicillins created to extend their coverage ot gram negatives and one bacteria it helps for specifically
- ampicillin IV
- amoxicilin (Amoxil) po (are both in the aminopenicillins family)
- good for E.coli
penicillins designed to expanded gram negative coverage including Pseudomonas aeruginosa (and wound infection and sepsis caused by this organism)
- ticarcillin
- piperacillin
(EXAM) combination in which penicillins are given + side effect
- penicillin + beta-lactamase inhibitor combination
- diarrhea SE bc of beta-lactamase inhibitors
(EXAM) penicillin + bli coverage
- most gram + (including S. aureus, Enterococcus, Listeria)
- most gram - RESPIRATORY pathogens (haemophilus and moraxella spp) and ENTERIC pathogens
- most anaerobes (gram+ and gram-)
- NO PSEUDOMONAS COVERAGE
(EXAM) only two penicillin + bli combinations that have the usual penicillin + bli coverage but also pseudomonas spp coverage
- ticarcillin + clavulanic acid (Timentin IV)
- piperacillin + tazobactam
(EXAM) perfect situations for using broad spectrum penicillin + bli combinations
very sick, immunosuppressed patients in hospital, with sepsis or dying
(EXAM) specific advantage that beta lactamase inhibitors add (in the penicillin + bli combination)
anaerobic coverage
cephalosporins: something they have that penicillins don’t have
resistance to beta-lactamases
main gram + organism that is covered with cephalosporins
MSSA (staph aureus)
cephalosporins how gram+ and gram- coverages vary with generation
gram+ : decreasing until 3rd. then increases again until 5th. 5th covers MRSA
gram- : coverage increases until 4th generation. 5th gen loses pseudomonas activity (only 3rd and 4th gen had pseudomonas activity)
gram positive organisms that cephalosporins can treat
- MSSA
- strep pneumoniae
- group A strep
one gram negative that cephalosporins can’t treat
campylobacter
cephalosporins (are beta lactams) that have pseudomonas (gram-) activity
ceftazidime (3rd gen) and the 4th generation cephalosporins
two gram+ organisms that cephalosporins don’t cover
- enterococcus spp
- listeria spp
carbapenems (are beta lactams) coverage and advantage they have that cephalosporins also have
- broad spectrum (like beta-lactam + bli combination): gram+ (with MSSA), gram-, anaerobes.
- resistant to beta-lactamases, like cephalosporins
carbapenems good situation to use
multiple resistant organisms, very sick patients, sepsis
carbapenems emerging resistance situation
gram negative rods in our gut are developing carbapenemases (resistance)
mild side effects of all beta lactams
- GI upset
- diarrhea (bc of beta-lactamase inhibitors and also in cefixime (Suprax), a 3rd gen cephalosporin))
- neutropenia
serious side effects of beta lactams
- seizures (lower threshold with all beta lactams and some lower the threshold more, but need many grams to have seizure)
- anaphylaxis (also, if already had anaphylaxis with one penicillin, higher risk of reacting with another penicillin. less risk with cephalosporins and <5% cross-reactivity with carbapenems)
Abx used when someone is allergic to penicillin
high generation cephalosporin (as move up the classes, R chains are complicated and cover the beta lactam ring from the immune system)
(important) which beta-lactams cross the BBB and can be used to tx meningitis
- Penicillin IV high dose
- Ampicillin IV high dose
- 3rd gen cephalosporins IV (high dose) (including cefepime)
- carbapenems
(important) which beta lactams have activity against MSSA (staph aureus)
- cloxacillin po/IV and methicillin
- beta-lactam + bli combinations (po/IV)
- 1st and 2nd gen cephalosporins (po/IV) (3rd gen IV also works but less)
- cefepime (a 3rd gen cephalosporin)
- carbapenems
(important) which beta-lactams have activity against pseudomonas
- Ticarcillin and Piperacillin (IV)
- Timentin (Ticarcillin + clavulanic acid) and Piperacillin+Tazobactam (IV)
- Ceftazidime (3rd gen cephalosporin) (IV)
- cefepime (3rd gen cephalosporin) (IV)
- carbapenems (IV)
(important) route of administation of beta-lactams for them to act on pseudomonas
IV
(important) beta-lactams with anaerobes activity
all
vancomycin (a glycopeptide Abx) mechanism of action
acts on the cell wall and inhibits cross-linking and chain formation
vancomycin coverage
ONLY gram + (anaerobes included)
vancomycin: organism that it covers very well and important thing about route of administration
- clostridium difficile (vanco po)
- doesn’t matter if po bc want effect in gut anyways)
vancomycin: special regions that it can reach
with higher doses
- crosses BBB, mainly with inflammation**
- reaches bone cartilage
- reaches heart tissue
evolution of vancomycin resistance
- MIC of vanco is going up
- will eventually deal with VISA (vanco works) and VRSA (are two kinds of vanco resistant S. aureus)
specific S. aureus for which you may use vancomycin
MRSA (but will need higher levels of vancomycin)
how to make sure vancomycin reaches the needed levels (to get MRSA coverage, BBB and bone cartilage penetration)
peak levels of the drug are measured
adverse reactions with vancomycin
- nephrotoxicity when given with other drugs (with accumulation, IV*** vanco has a high trough level. meaning a high residual concentration)
- if given in <1hr, get histamine release (Red-man syndrome), but is not anaphylaxis or allergy. get flushing, hives, hypotn
tx of histamine release (flusing, hives, hypotn) caused by vancomycin
Benadryl + give vancomycin over a longer course
macrolides and ketolides coverage
- gram+ (S pneumoniae, GAS)
- gram- (campylobacter, bordetella pertussis)
- atypical (mycoplasma spp, chlamydia spp, clamydophila spp)
- non-TB mycobacteria
main use of macrolides and ketolides
treat atypical infections and non-TB mycobacteria infections
macrolides used to treat non-TB mycobacteria infections
- calrithromycin
- azythromycin
do macrolides cross the BBB, can you use them to treat meningitis
no
