Antibiotics - bacterial Flashcards
4 types of antimicrobials?
bacterial
fungal
viral
other: mycobacterium, parasites
two ways to classify antibiotics by scope?
narrow spectrum: relatively small # of specific organisms will be sensitive to that agent (ex. penicillin)
broad spectrum: broad range of organisms will be sensitive to that agent (ex. piperacillin/tazobactam)
5 MOAs for antibiotics?
- inhibition of cell wall synthesis (penicillin, bacitracin, cephalosporin, vancomycin)
- disruption of cell membrane function (polymyxin)
- inhibition of protein synthesis (tetracycline, erythromycin, streptomycin, chloramphenicol)
- inhibition of nuclei acid synthesis (rifamycin, quinolones, metronidazole)
- action as antimetabolites (sulfonilamide, trimethoprim)
two ways to categorize abx by their killing capabilities?
bacteriostatic: keep at the # that is there
bactericidal: kill the bacteria off
two ways to categorize antimicrobials by pharmacodynamic profiles?
time dependent
concentration dependent
different categories of bugs?
gram (+): streptococci, staphylococci, enterococci
gram (=): enterobacteriaceae, pseudomonas
anaerobes: bacteroides fragilis
general bacterial classifications?
aerobe vs anaerobe
gram (+) vs gram (=)
shapes of bac?
cocci or rods
important aerobic gram (+) cocci?
staphylococci: s. aureus, coag-negative staph
streptococci: s. pneumoniae, group B strep, viridans strep
enterococci: e. faecalis, e. faecium
important aerobic gram (=)?
gram (=) rods: e. coli, k. pneumoniae, serratia, enterobacter, h. influenze, p. aeruginose
gram (=) cocci: m. catarrhalis, m. gonorrhoeae, n. meningitidis
important atypical respiratory aerobes? what makes them atypical?
legionella spp, mycoplasma pneumonia, chlamydia pneumoniae
lack a cell wall, intracellular organisms & can’t be seen w/gram staining process
where do true anaerobes generally live?
the gut!
bacteroides fragilis
clostridium difficile (causes diarrhea)
two oral anaerobes?
prevotella
peptostreptococcus
what is sensitivity in relation to abx?
the degree to which microbial organisms are killed or their proliferation is arrested by the drug
4 factors that determine sensitivity of microbes?
- reach microorganism
- bind to or enter the microorganism
- interfere w/vital microbial fxn
- remain chemically intact while acting upon the microorganism
how to test a bugs sensitivity to a drug?
done in vitro
dilution tests: minimum inhibitory concentration; minimum bactericidal concentration
disk-diffusion technique
7 ways to categorize abx via chemical structure?
- sulfonamides
- penicillins
- cephalosporins
- macrolides
- tetracyclines
- quinolones
- others
what is the main structure that inhibits cell wall synthesis?
beta-lactam ring structure
MOA of penicillin? two ways for bugs to have resistance?
MOA: B-lactam inhibits cell wall synthesis by binding to penicillin binding proteins
resistance via B-lactamases & altered PBPs
is penicillin time or dose dependent? bacteriostatic or bacteriocidal?
time dependent
bacteriocidal
4 different types of penicillins and penicillin congeners?
natural penicillin (penicillin G and penicillin VK)
aminopenicillins (amoxicillin, ampicillin)
penicillinase-resistance penicillins (methicillin, where we hear about MRSA)
extended spectrum PCNs + beta-lactamase inhibitor (piperacillin, tazobactram)
effective uses of penicillin? bioavailability? spectrum of use? given how?
often resistant b/c bacterial have evolved so only a few we can treat w/penicillin: gram (+) streptococci, oral anaerobes
drug of choice for N. meningitidis, syphilis
poor bioavailability, narrow spectrum of use
give per IV
penicillinase-resistant penicillin use?
naficillin
major drug used for MSSA
can be used to tx gram (+) strep and MSSA and oral anaerobes
two examples of aminopenicillins? aminopenicillins MOA? used to tx what?
ampicillin, amoxicillin
MOA: binds to PBPs and inhibits synthesis of cell wall
used to tx respiratory infxn (not as common anymore),, sinusitis, otitis, lower respiratory tract infxns, endocarditis from enterococcus
can be used to tx gram (+) strep and enterococci; some gram (=)s, oral anaerobes
ex of extended-spectrum penicillins?
spectrum? bugs it can treat? how to use?
piperacillin
broad spectrum, severe infections
gram (+) strep, staph, possibly eneterococci
gram (=)- excellent- pseudomonas aeruginosa
given in combo w/B-lactamase inhibitor so it can act on those bugs which produce the B-lactamase
MOA of B-lactamase inhibitors?
increase treatment capacity against MSSA and enterobactieraceae and anaerobes
bugs pencillin/B-lactamase inhibitor can be used on?
gram (+) strep, MSSA, maybe enterococci
gram (=) P. aeurginosa
all anaerobes
possible adverse rxns with penicillins?
allergic reaction: anaphylaxis, rash, urticaria, fever
5-20% report allergy, <20% who think they have an allergy actually have an allergy
diarrhea
type I allergic reaction? common to see in what type of abx?
IgE
occur w/in 1 hr of dose
urticarial rash, pruritis, flushing, angioedema of face or laryngeal tissues, wheezing, hypotension
anaphylaxis
common to see w/B-lactam drugs; ~5% cross reactivity w/cephalosporins if true allergy
4 less common adverse penicillin rxns?
hematologic: anemia, thrombocytopenia
hepatitis w/nafcillin/oxacillin
interstitial nephritis: nafcillin/oxacillin
seizures: high doses, renal failure
SEs of amoxicillin and clavulanate/augmentin?
notable increased SEs from clavulanic acid, clavulanate alone has very little antimicrobial activity but causes copious GI distress and diarrhea
what is the most severe cause of abx induced diarrhea?
pseudomembranous colitis (c. difficile colitis)
most of the abx are cleared in which way?
most are cleared renally
what is the only major interaction w/amoxicillin?
acacia
MOA of cephalosporins?
binds to beta-lactam ring of cell wall and inhibits organisms ability to form new cell walls
between 1st, 2nd, 3rd and 4th generation cephalosporins, which have the greatest activity against gram (+)s, against gram (=)s?
1st and 2nd have greatest activity against gram (+)s
3rd and 4th have greatest activity against gram (=)s
what bug do cephalosporins NEVER cover??
enterococcus
1st generation cephalosporins use? what bugs does it cover?
indications: UTIS, skin infxns, some respiratory and prophylaxis surgically
used against gram (+) strep, MSSA; gram (=) e. coli, klebsiella; oral anaerobes
can be used as an alternative to penicillin allergic pts
2nd generation cephalosporins use? what bugs does it cover?
indicated in some respiration and GI infections
gram (+) strep, MSSA
gram (=)- good coverage overall
oral anaerobes + b. fragilis
3rd generation cephalosporin use? bugs it covers?
use: respiratory infxns, serious infxns gram (+) strep, MSSA gram (=): very good, p. aeruginosa oral anaerobes some are able to cross BBB
4th generation cephalosporin use? what bugs?
serious hospital infxns
gram (+) strep and MSSA
gram (=): excellent, p. aeruginosa
oral anaerobes only
what can 5th generation cephalosporins cover?
MRSA
strep pneumonia
covers GNR, but not pseudomonas
exceptions of cephalosporins that are not cleared renally?
ceftriaxone so don’t need to adjust for reduced renal fxn
ADRs of cephalosporins?
allergic rxns: anaphylaxis, rash, urticaria, fever, 3-7% cross resistance with penicillin allergy
diarrhea
less common: anemia, thrombocytopenia, seizures when given at high doses
two other beta-lactam drugs? MOA? what can provide bugs w/resistance?
monobactams and carbapenems
MOA: inhibit cell wall synthesis
resistance via B-lactamases, outer membrane protein mutations
very broad spectrum, sever infxns in hospital
macrolides use? bugs it covers?
erythromycin, azithromycin
good coverage of respiratory infections, chlamydia, syphilis, gonorrhea, sinusitis, bronchitis, COPD
gram (+) strep, MSSA, pneumococci
gram (=) minimal w/h. flu
oral anaerobes
useful in treating atypical respiratory pathogens such as legionella, chlamydia, mycoplasma
ADRs of macrolides?
GI: n/v, diarrhea b/c cause direct (+) motility of gut; erythro is worse than clarithro which is worse than azithro
phlebitis with IV erythro
less common: prolonged QT interval
hepatotoxicity
what enzyme do macrolides inhibit?
CYP450-3A4
4 major interactions with azithromycin?
all possibly prolong the QT segment
cesium, ephedra, oleander, sida cordifolia
MOA of tetracyclines?
inhibit protein synthesis by binding to the 30s ribosomal subunit (inhibits translation)
bacteriostatic
what can tetracyclines be used to tx?
increased resistance limits their use
respiratory, intracellular infxns, acne and rosacea, chlamydia, SSTI
gram (+) strep, MSSA
gram (=) h. flu, rickettsiae, other gram (=)s often resistance
oral anaerobes
atypical respiratory pathogens such as legionella, clamydia pneumonia, mycoplasma pneumonia
ADRs of tetracyclines?
photosensitivity nausea diarrhea tooth discoloration in children (C/I in children less than 8 and PG) less common: esophagitis, leukocytosis
what can tetracyclines not be given with? can be used in what populations?
do not give with Ca2+ supplements as it causes chelation of calcium ions
can be used in those who are PNC allergic
can be used in renal failure
MOA of sulfonamids?
inhibits folic acid synthesis via enzyme inhibition
bacteriostatic
can combine sulfamethoxazoe w/what other abx? what will this combo cover? what can this combo be used to tx?
can be combined with trimethoprim/bactrim
variable wide activity when used in combo
gram (+) strep, MSSA, CAMRSA
gram (+) most enterobacteriaceae
oral anaerobes
indications: UTI, otitis media, sinusitis, bronchitis, pneumocystitis prophylaxis, community acquired MRSA, SSTI
there is however increasing resistance
ADRs of bactrim? what drug does it specifically act with to increase its effects?
allergic rxns, rash, fever, photosensitivity, urticaria, GI effects, neutropenia, thrombocytopenia (folate deficiency)
rare: Steven Johnsons Syndrome (severe rash)
increases effects of warfarin!
MOA of fluroroquinolones? resistance mechanisms?
MOA: inhibits bacterial DNA gyrase, inhibiting DNA replication and transcription, bactericidal
resistance: mutations at target sites, efflux pumps
bugs fluoroquinolones can act against?
potent broad-spectrum agent, most gram (=): p. aerugonisa
atypical pathogens: community acquired pneumonia- legionella, clamydia pneu, mycoplasma pneu
indications for fluoroquinolones? problems?
UTI, pyleo, upper and lower respiratory tract infxns, SSTI, joint infxns
increasing resistance
increase evidence of adverse rxns
ADRs of fluoroquinolones?
GI: nausea
CNS: h/a, dizziness, insomnia
less common: cartilage toxicity, AVOID use in children and PG, CNS: confusion, seizures; prolonged cardiac QT interval
interactions w/fluoroquinolones? need to be taken away from what items?
any drug that can prolong the QT interval
like the macrolides
cesium, ephedra, grapefruit, sidea cordifolia, sweet orange
need to take away from calcium, iron, antacids, enteral feeding
MOA of anti-anaerobes (metronidazole and clindamycin)? resistance how?
metronidazole: inhibits nucleic acid synthesis
clindamycin: ribosomal protein synthesis inhibitor
resistance: rare w/metron, mutations in ribosomes w/clinda
use metronidazole against what?
only anaerobes!
indications: vaginitis, h.pylori in PUD, c. difficle, associated diarrhea, intra-abdominal abscess, lung abscess, peritonitis
use clindamycin against what?
gram (+) and anaerobes
NO GRAM (=)s
indications: SSTI, anaerobic infxns, topical available for acne vulgaris, bacterial vaginosis
ADRs of metronidazole?
nausea, diarrhea, metallic taste
drug interaction: disulfiram rxn: flushing, sweating, nausea w/EtOH, can persist a few days after
ADRs of clindamycin?
diarrhea, nausea, c. difficile
indication of nitrofurantoin/macrobid? MOA?
indication: lower UTIs but NOT for pyelonephritis, considered safe before 38 wks gestation
MOA: disrupts both DNA and RNA of bacteria which are sensitive to the drug
SEs of nitrofurantoin/macrobid?
n/v, diarrhea
less common: fever, chills, pulmonary fibrosis
not recommended for pyelonephritis and not effective in significant renal impairment
additional abx classes for hospital severe infxns? MOA? what bugs can they be used against?
aminoglycosides
MOA: bactercidial, inhibit protein synthesis
can be used against gram (=0 such as pseudomonas auerginosa
6 abx that can be used effectively to treat MRSA?
IV vancomycin daptomycin telavancin ceftaroline tigecycline linezolid
3 abx to use for community acquired MRSA (CAMRSA)
clindamycin
tetracycline
bactrim
6 drugs that cover pseudomonas?
aminoglycosides ciprofloxacin, levofloxacin ceftazidime, defepime, ceftolozane/tazobactam piperacillin, ticarcillin aztreonam imimpenem, meropenem, doripenem
what abx provide true anaerobic coverage?
metronidazole B-lactam/B-lactamase inhibitors carbapenems moxifloxacin clindamycin cefoxitin/cefotetan
topical abx?
mupirocin/bactroban
bacitracin
polysporin OTC (combo of bacitracin and polymyxin)
neosporin OTC (combo of bacitracin along with neomycin and polymyxin B
probiotic strains which have been proven to prevent c. difficile?
lactobacillus combos or single agent regiments
