Drugs for bacterial infections 1 Flashcards
What type of pathogens are:
* strep
* staph
* entero
* listeria?
gram positive
What type of pathogens are
* clostridia
* bacteroides?
anaerobes
What type of pathogens are:
* chlamydiae
* mycoplasma
* legionella?
atypicals
What type of pathogens are:
* e. coli
* klebsiella
* proteus
* enterobacter
* pseudomonas
* acinetobacter
* h. influenzae
* moraxella catarrhalis
* neissera
* “bacters”
* “cocci”?
gram negative
What type of drug inhibits growth and replication of bacteria?
bacteriostatic
What type of drug actually kills bacteria and can be concentration OR time dependent?
bactericidal
What is essential to look at with time-dependent antibiotics?
time above lowest concentration of drug that can prevent growth of an organism (MIC = minimum inhibitory concentration)
What is essential to look at with concentration-dependent antibiotics?
Cmax/MIC ratio
AUC/MIC ratio
AUC = total amount of drug exposed to body over time
What is based on the time which bacteria are exposed to antibiotics at a concentration higher than MIC?
time-dependent abx
What is based on the rate and extent of killing increasing as peak drug concentration increases?
concentration dependent abx
What is the suppression of bacterial growth after limited exposure to abx?
post-antibiotic effect
What are common drugs that are concentration dependent abx?
aminoglycosides and fluoroquinolones
What are the first steps you need to take when addressing a pathogen?
- grow organism & evaluate w/ gram-stain
- identify specific organism
- determine sensitivity (MIC)
What type of antibiotic are PCNs, cephalosporins, carbapenems?
beta lactams
What type of abx MOA do
* beta lactams
* aztreonam
* glycopeptides
* lipopeptides
have?
cell wall inhibitors
Which drugs are bactericidal?
- beta lactams
- aztreonam
- glycopeptides
- lipopeptides
- sulfonamides & trimethoprim
- aminoglycosides
- quinupristin/dalfopristin
- fluoroquinolones
What type of abx MOA does sulfonamides/trimethoprim have?
folate antagonists
What type of abx MOA do
* aminoglycosides
* macrolides
* tetracyclines
* clindamycin
* linezolid
* quinupristin/dalfopristin
* chloramphenicol
* tigecycline
have?
protein synthesis inhibitors
What type of abx MOA does fluoroquinolones have?
inhibit DNA topoisomerases
We’re ECSTaTiC about bacteriostatic!
E - erythromycin
C-clindamycin
S-sulfamethoxazole
T- trimethoprim
a
T-tetracycline
i
C-chloramphenicol
Very Finely Proficient At Cell Murder
V-Vancomycin
F-fluoroquinolones
P-penicillin
A- aminoglycosides
C- cephalosporin
M- metronidazole
What type of spectrum are these drugs:
* 2nd gen cephs
* amoxicillin
* ampicillin
* metronidazole?
narrow
What type of spectrum are these drugs:
* 3rd gen cephs except ceftazidime
* amoxicillin/clauv
* ampicillin/sulbactam
broad
What type of spectrum are these drugs:
* ceftazidime
* 4th gen cephs
* anti-pseudomonal penicillins
* aztreonam
* ertapenem
* ceftraoline
* fluoroquinolones
* aminoglycosides
* colistimethate
extended
What type of spectrum are these drugs:
* anti-pseudomonal carbapenems
* tigecycline
* ceftazidime/avibactam
* ceftolozane/tazobactam
* impenem/cilastatin/relebactam
* meropenem/vaborbactam
* cefiderocol
* eravacycline
protected
Which drugs inhibit cell wall synthesis?
- penicillins
- cephalosphorins
- carbapenems
- monobactams
What is the MOA of beta lactams and monobactams?
competitive binding of transpeptidation enzymes which ultimately results in bacteria death. **Binds to penicillin binding proteins **
Are all beta lactams bactericidal?
Yes
How is resistance mediated through beta-lactams?
production of beta-lactamase (h.flu, MSSA, bacteroides, moraxella)
or alteration of PBPs (S.pneumoniae, MRSA)
What are ADRs of beta lactams/monobactams?
- mild rashes to drug fever
- nephritis, anaphylaxis
- seizures from very high doses
- accumulation can occur when not adjusted for renal function
What are amino-PCNS and which is parenteral versus oral?
parenteral: ampicillin
oral: amoxicillin
What are amino-PCNs AND beta-lactamase inhibitors and which is parenteral vs oral?
parenteral: ampicillin-sulbactam
oral: amoxicillin-clavulanate
What are anti-staph PCNs?
oxacillin, nafcillin, dicloxacillin (oral)
In what bacteria are PCNs reliable?
streptococci and treponema pallidum
In what bacteria are PCNs moderate?
enterococci & s. pnuemoniae
When are PCNs DOC?
syphilis, streptococcal pharyngitis (GAS)
What make all staphylococci resistant to penicillin?
penicillinases
Are PCNs a reliable empiric antibiotic choice?
No
In what bacteria are aminopenicillins reliable in?
enterococci and streptococci
In what bacteria are aminopenicillins moderate in?
h. flu, gram negative rods, and s/ pneumoniae
In what clinical utility are aminopenicillins used?
susceptible GNRs, upper respiratory tract infections
When is amoxicillin your PO DOC?
otitis media
When is ampicillin IV your DOC?
susceptible enterococci, and listeria monocytogenes
What requires addition of an aminoglycoside for synergy to become bacteriacidal?
bacteriostatic activity against enterococci
What are anti-staph penicillins also called?
penicillinase resistant
When are anti-staph PCNs reliable?
MSSA and strep
When are anti-staph PCNs moderate?
s. pneumoniae
When are anti-staph PCNs your drug of choice?
skin and soft tissue infections and endocarditis caused by MSSA
Why are anti-staph PCNS prefered over vancomycin for MSSA?
more rapidly bactericidal
If staphylococcus is sensitive to oxacillin, what else is it sensitive to?
ALL anti-staph PCNs AND amino-PCNs + BL-inhibitor AND most cephs (1st gens preferred)
What are examples of aminopenicillins?
ampicillin and amoxicillin
What are examples of beta-lactams that are beta-lactamase inhibitors?
ampicillin/sulbactam, amoxicillin/clavulanate, piperacillin/tazobactam and ticarcillin/clavulanate
In what are beta-lactams/beta-lactamase inhibitors reliable?
many anaerobes, enteric GNRs, enterococci, H. flu, MSSA, pseudomonas aeruginosa (only pip/tazo and ticarc/clav), strep
In what are beta-lactams/beta-lactamase inhibitors clinically utilized?
empiric therapy for nosocomial infections including pneumonia (only pip/tazo and ticarc/clav), intra-abdominal infections, diabetic ulcers, and aspiration pneumonia
In what are beta-lactams/beta-lactamase inhibitors moderate?
s. pneumoniae
What beta-lactams/beta-lactamase inhibitors only have moderate activity against enterococci?
ticarcillin/clavulanate
How do beta-lactamase inhibitors work?
restore activity of the antibiotic against B-lactamases producing bacteria
NO EFFECT on resistance caused by other mechanisms like MRSA or PCN-resistant pneumococci
What are bacteriostatic oral MRSA treatment options?
- clindamycin
- doxycycline
- linezolid
- minocycline
- tedizolid
What are bacteriostatic IV MRSA treatment options?
- linezolid
- quinupristin/dalfopristine
- tedizolid
- tigecycline
- clindamycin
- doxycyline
What are bactericidal oral MRSA treatment options?
- trimethoprim/sulfamethoxazole
- delafloxacin
What are bactericidal IV MRSA treatment options?
- cetaroline
- dalbavancin
- daptomycin
- delafloxacin
- oritavancin
- telavancin
- trimethoprim/sulfa
- vancomycin
What is the most common allergy reported by patients?
PCN - rash, GI intolerance is often reported, but not an allergy
What is the MOA of cephalosporins?
binds to PCN binding proteins (PBPS)
What’s more stable than PCN and aminoPCNs to b-lactamases?
cephalosporins
How is resistance developed from cephalosporins?
altered PBPs = MRSA and B-lactamase degradation = GNRs
What cephalosporin generation have good CNS penetration?
3rd and 4th potentially
What are 3rd gen cephalosporins (CNS)?
ceftriaxone, ceftazidime, cefotaxime
meningitis
What are first gen cephalosporins?
cefazolin + cephalexin PO
What are second gen “respiratory” cephalosporins?
cefuroxime, cefuroxime axetil PO
What are second gen “enterics” cephalosporins?
cefoxitin and cefotetan
What are third gen cephalosporins?
ceftriaxone, cefixime PO,cefpodoxime PO, cefdinir PO, cefotaxime, ceftazidime
What’s a fourth gen cephalosporin?
cefepime
What’s a fifth gen cephalosporin?
ceftaroline
What clinical activity are 1st gen cephalosporins reliable for?
MSSA, streptococci
What clinical activity are 1st gen cephalosporins moderate for?
some enteric GNRs
How are 1st gen cephalosporins clinically utilized?
SSTIs and endocarditis caused by MSSA, surgical prophylaxis, susceptible GNRs
What should you NOT use for MSSA in the CNS?
1st gen cephalosporins
What are 2nd gen “resp” cephalosporins reliable for??
some enteric GNRs, H. flu
What are 2nd gen “resp” cephalosporins moderate for?
staph, strep
where are 2nd gen “resp” cephalosporins clinically utilized?
- activity against H. flu!! (differentiates)
- URTIs, community acquired pneumonia w/macrolide or doxy
What are 2nd gen enteric cephalosporins reliable for?
some enteric GNRs, h. flu
What are 2nd gen enteric cephalosporins moderate for?
anaerobes, staph, strep
Where are 2nd gen enteric cephalosporins clinically utilized?
abdominal and gynecologic infections, surgical prophylaxis
activity against bacteroides fragilis
What are ADRs for 2nd gen enteric cephalosporins?
disulfiriam-like reaction when w/ ethanol
What are 3rd gen cephalosporins reliable for?
enteric GNRs, pseudomonas (ceftazidime ONLY), strep
What are 3rd gen cephalosporins moderate for?
MSSA (NOT ceftazidime or ceftixime)
In what are 3rd gen cephs clinically utilized?
community acquired pneumonia (+macrolide and doxy), UTIs, lyme disease (ceftriaxone)
nosocromial infections, febrile neutropenia (ceftazidime ONLY)
When are 3rd gen cephalosporins your DOC?
gonorrhea and meningitis (ceftriaxone)
How are 3rd gen cephalosporins better?
more active against GNRs from previous generations and some PCN-resistant S.pneumoniae (NOT cefixime or ceftazidime)
What are 4th gen cephs reliable for?
enteric GNRs, MSSA, pseudomonas, strep and MRSA
What are 4th gen cephs moderate for?
acinetobacter
How are 4th gen cephs clinically utilized?
febrile neutropenia, nosocomial infections (pneumonia), meningitis
How are 4th gen cephs better?
better staph/strep activity, active against some PCN-resistant S. pneumoniae
Where are 5th gen cephs reliable?
enteric GNRs, MSSA, MRSA, strep
Where are 5th gen cephs moderate?
acinetobacter, enterococcus faecalis
How are 5th gen cephalosporins clinically utilized?
approved for SSTI and community-acquired pneumonia
How are 5th gen cephs better?
additional MRSA coverage and E.faecalis activity
What is ceftolozane-tazobactam used for?
intra-abdominal infections and UTIs
What does ceftolozane-tazobactam cover?
ESBL coverage and most active B-lactam for pseudomonas
no staph or entero coverage
What is ceftazidime-avibactam used for?
intra-abdominal infections and UTIs; new type of B-lactamase inhibitor
What are examples of carbapenems?
- imipenem/cilastatin
- meropenem
- doripenem
- etrapenem
Where are carbapenems clinically reliable?
- MSSA
- streptococci
- anaerobes
- enteric GNRs
- psuedomonas (NOT ertapenem)
- acinetobacter (not ertrapenem)
Where are carbapenems moderate?
enterococci (NOT ertapenem)
How are carbapenems clinically utilized?
- mixed aerobic/anaerobic infections, infections caused by ESBL organisms, intra-abdominal infections
- nosocomial pneumonia, febrile neutropenia, other nosocomial infections (NO ERTAPENEM)
When are carbapenems your DOC?
ESBL-producing GNRs
does aztreonam have gram positive activity?
NO
What’s an example of a monobactam?
aztreonam
What are monobactams reliable for?
most GNRs, pseudomonas
What are monobactams moderate for?
acinetobacter
When are monobactams clinically utilized?
gram negative infections, pseudomonas, often used in patients with severe allergies to B-lactams
When shoud you avoid all PCNS?
in setting of anaphylaxis and up to 40% cross in rash/hives
What are the best to use with side chain cross-reactivity?
monobactams
What cephalosporins should be avoided in patients with true PCN allergies?
- cefaclor
- cefadroxil
- cefatrizine
- cefprozil
- cephalexin
- cephradine
If a patient can safely recieve a cephalosporin, should you give that or carbapenem?
cephalosporin! carbapenem should be reserved.
What are oral psuedomonas treatment options?
- ciprofloxacin
- levofloxacin
- norfloxacin
- ofloxacin
What are IV pseudomonas treatment options?
- aminoglycosides
- piperacilling-tazobactam
- ceftazidime/ceftazidime
- cefepime
- ceftolazoane
- impenem, meropenem, doripenem
- colostin
What are nebulized pseudomonas treatment options?
- aztreonam
- colistin
- tobramycin
Which drugs have no need for renal dose adjustment?
ceftriaxone and nafcillin
What’s a glycopeptide?
vancomycin
What’s a lipopeptide?
daptomycin
What are glycopeptides MOA?
- bactericidal (Conc. dependent)
- inhibits cross-linking of linear peptidoglycans
- MONITOR DRUG LEVELS
What are ADRs of glycopeptides?
nephrotoxicity, red man syndrome, rare ototoxicity
When are glycopeptides reliable?
MSSA (not first choice), MRSA, strep, c. diff
When are glycopeptides moderate?
enterococci
When are glycopeptides clinically utilized?
empiric treatment for pneumococcal meningitis, MSSA (allergy)
When are glycopeptides the DOC?
all MRSA, or empiric MRSA coverage, severe C.diff
PO = not absorbed by GI tract, not systemically distributed
What are lipopetide MOA?
bactericidal - conc dependent
binds to membrane, depoloarizes, loss of membrane potential
Avoid in pneumonia
What are ADRs of lipopeptide?
rhabdomyolosis (check CK), hepatic effects (dose dependent)
avoid with statins!!
When are lipopeptides clinically reliable?
MSSA, MRSA, strep
When are lipopeptides reliable to moderate?
enterococci (VRE)
When are lipopeptides clinically utilized?
SSTIs and staphylococcal bacteremia/endocarditis
Buy AT 30, CCELL for 50 dollarS
“Protein synthesis inhibitors”
Inhibitors of 30
* aminoglycosides
* tetracyclines
inhibitors of 50
* clindamycin
* chloramphenicol
* erythromycin
* linomycin
* linezolid
* streptogramins
What are protein synthesis inhibitors of 30s?
- aminoglycosides
- tetracyclines
What are protein synthesis inhibitors of 50s?
- clindamycin
- chloramphenicol
- erythromycin
- lincomycin
- linezolid
- streptogramins
What are major toxic effects of aminoglycosides?
ototoxicity and nephrotoxicity
What are examples of aminoglycosides?
getamicin, tobramycin, amikacin
What’s the MOA of aminoglycosides?
inhibit protein synthesis with 30s unit
Must monitor drug levels
rarely used as single drug therapy!
bactericidal conc dependent
What should you do for long term AG use?
baseline and follow up with audiology
Can neuromuscular blockade occur with AGs?
Yes, in high doses
When are aminoglycosides reliable?
GNR, pseudomonas
When are aminoglycosides utilized clinically?
combo w/ other abx for serious infections: febrile neutropenia, sepsis, CF, ventilator-associated pneumonia
What’s used for synergy with B-lactams or vanc for gram+ infections (no coverage as mono)?
aminoglycosides
