ID: cell wall inhibitors Flashcards
1
Q
Gram +
- peptidoglycan layer?
- retain stain?
- stain color
A
thick peptidoglycan wall
- retain/absorbs stain
- purple
- easier to kill vs negative
2
Q
gram -
- peptidogucan layer?
- retain stain?
- stain color
A
thin peptidoglycan wall
- washes away in acid
- pink
3
Q
acid fast bacteria
- can appear how.. + or - ?
- outer bacterial envelope contains?
A
gram + or -
outer envelope contains glycolipids
4
Q
what is harder to kill? + or -
A
gram -
- covered by multiple thin layer of membrane that eject toxins
- lipopolysaccharide layer
5
Q
which is quicker to develop resistance?
A
gram -
6
Q
mycobacteria
- pos or neg
- stain on?
A
weakly gram +
but stain on a special stain called acid-fast
-TB
7
Q
Spirochetes
- pos or neg
- how is it visualized
A
gram -
very small and visualized on a darkfield micrscope
-lyme
8
Q
mycoplasma
- pos or neg
- cell wall and membrane?
A
not gram + or -
NO cell wall
only a cell membrane
9
Q
anaerobic bacteric
- ex of where to find
- pos or neg?
- uni or multi cellular?
A
- thrive and grow when oxygen is not present
- mostly unicelluarl
- can be + or -
EX: GI tract
10
Q
aerobic bacteria
pos or neg?
-ex dz caused by them
A
live and grow where oxygen is presnt
need it to survive
a
+ or -
EX: tonsillitis
11
Q
cell wall inhibitors intefere with?
- work best when ?
- do not work on?
A
synthesis of bacterial cell wall
- work best when bacteria are actively proliferating
- do not work on mycoplasma AND human cells do not have cell walls–>makes them relatively safe abx
12
Q
why are cell wall inhibs as a class relatively safe?
A
bc they attack the cell wall—- and human cells do not have cell walls
13
Q
list of cell wall inhibs (5)
A
- PCNs
- cephalosporins
- carbapenenms
- monobactams
- beta-lactamase inhibitor combinations
14
Q
cephalosporins start wht
A
CEF-
15
Q
CEF-
A
cephalosporins
16
Q
all penicilins have what in their structure
A
beta lactam rings
17
Q
PCNs inhibt what enzyme
A
Transpeptidase
18
Q
PCNs are ___ dependent
A
TIME
19
Q
PCNs are ___ soluble
A
water
20
Q
PCNs end in?
A
-cillin
21
Q
PCN G and V
- which is only PO and only IM/IV
- spectrum?
- cover mainly?
DOC for?
A
NATURAL PCNs!!!
V: PO
G: IM/—— comes in depot forms that make t1/2 longer
Spectrum: narrow and penicillinase sensitive
gram (+) cocci (pneumococci, beta-hemolytic streptococcus), gram (+) rods (Listeria),
gram (-) cocci (Neisseria meningitidis) and Treponema pallodum, most anaerobes, *only bacteriostatic for enterococci
beta lactamase sensitive* so does not kill as many staphylococcus bc they produce beta lactamases
INDS:
- DOC: Treponema pallodum–syphilis
- PCN G Benzathine: prophylaxis for Rheumatic fever.. IM q 21-28 days
22
Q
Second Generation aminopeniclins
list them and routes
A
Ampicillin–IV
Amoxicillin–PO
23
Q
Adv rxn to PNCs
A
generally well-tolerated and safe vs other ABX
- hypersensitivity
- diarrhea
- nephritis
- neurotoxicity
- hematologic–
24
Q
what enzyme is involved in construction of cell wall (peptidoglycan layer)
A
transpeptidase or penicillin binding protein
25
gram pos cell wall:
- thick or thin
- lipid content low/high
- yes/no endotoxin
- yes/no periplasmic space
- yes/no porin channels
- yes/no penetrable by PCN
thick cell wall
low lipid content
no endotoxin
no periplasmic space
no porin channel
easily penetrable by PNC
26
gram neg cell wall:
- thick or thin
- lipid content low/high
- yes/no endotoxin
- yes/no periplasmic space
- yes/no porin channels
- yes/no penetrable by PCN
thin cel wall
outer lipopolysaccharide membrane
yes endotoxins
yes periplasmic space
yes porin channel
harder for PCN to access
27
streptococci pos or neg
+
28
enterococci pos or neg
+
29
staphlyococci pos or neg
+
30
cornebacterium pos or neg
+
31
Listeria pos or neg
+
32
bacillus pos or neg
+ and spore forming
33
Clostridium pos or neg
+ and spore forming
34
PCNs kill which type of bacteria
Mainly gram +
*harder for them to cross lipopolysaccharide layer surrounding gram -
35
how does the PCNs kill gram -?
they have to go through the porins because they cannot cross the lipoplysaccharide layer
36
beta-lactamases are also called?
penicillinases
37
Beta lactamases
enzymes that break the beta-lactam ring-- casing the ABX to lose its bactericidal effect
-some bacteria produce this enzyme
38
PCNs are bacterialcidal or bacteriostatic?
bacteriocidal
39
solution to beta-lactamase producitng bacteria?
beta-lactamase inhibitors
| PCN + BLI added together to make one drug and more effective
40
name the combination drugs that make up beta-lactamase inhibitors (4)
1. Ampicillin + Sulbactam
2. Amoxicilin + Clavulanate= Augmentin ****
3. Ticarcillin + Clavulanate
4. Piperacillin + tazobactam
41
list the three ways bacteria are resistant to beta-lactam antibitotics
1. prod of beta-lactamase enzymes
2. decreased penetration-- of cell wall and LPS layer and efflux pumps
3. Modified penicillin binding proteins (lower affinity of antibiotics to target)
42
list the 5 ways you can classify PCNs
1. source--natural or semi-synthetic
2. Route of admin: PO only vs PArenteral only
3. Spectrum of activity: Narrow spectrum to broad to intermediate to extended
4. Resistance to beta-lactamase or non-resistance
5. resistance to acids: acid stable vs acid unstable
43
PCN G
- list the two types
- routes of admin
Procaine PCN G and Benzathine PCN G
| IM ONLY****
44
what happens if you give PCN G IV?
cardiac arrest
| IM ONLY**
45
which drug if given IV can cause cardiac arrest?
PCN G benzathine procaine
46
what does PCN G and V fight
Gram + cocci: pneumococci, beta-hemolytic streptococcus (strep pharyngitis)
Gram + rods: listeria
Gram - cocci: Neisseria
Most anaerobes
Enterococci: but only has bacteriostatic effect not bacteriocidal
DOC for syphilis
IM PCN G for rheumatic fever prophylaxis
47
which bacteria has become very resistant to PCN G and V
staph aureus-- over time 90% of the strains have developed beta lactamase
48
Anti Staphylococcal Penicillins
- list them and routes (4)
- spectrum?
- potency compared to natural PCNs
- resistant to?
- indications?
- not effective for?
- adv rxns
Methicillin (not avail in US bc causes acute interstitial nephritis)
Nafcillin (IV ONLY)
Oxacillin (IV, IM)
Dicloxacillin (PO)
* beta lactamase resistant penicillins
* potency: less potent vs natural PCNs
very narrow spectrum: for staph A infections w/o MRSA
INDS:
- cellulitis
- beta-lactamase producing staph infections (NOT MRSA)
NOT FOR:
- gram neg
- listeria
- Enterococci
ADV RXN:
- N/V/D
- Neurotoxicity
- acute interstitial nephritis--- from methicillin**
- thrombocytopenia
- neutropenia
- methemoglobinemia
49
which drug causes acute interstitial nephritis
Methicillin-- anti-staphylococcal penicillin
| *why it is no longer avail in US
50
Second Generation Aminopenicillins
- list them
- spectrum
- structure
- treats?
- not good for?
- can be added to?
- adv eff
Ampicillin and Amoxicillin
SPECTRUM: extended/broad
* great gram + and gram- bacilli coverage
* including H. influenzae
* E. coli
* Listeria
* Proteus
* Salmonella
* respiratory infections
* dental infections
* UTI pregnancy
* otitis media
Semi-synthetic
* can be added to beta-lactamase inhibitors for better gram - coverage:
1. ampicillin + sulbactam
2. Amoxicillin + clavulanate
not good for tx beta-lactamase producing staphylococci
skin rashes with ampicilin-- 9%
51
anti-pseudomonal penicillins
- generatoni?
- list the drug names
- which is not avail in us?
- MOAfor each drgu
- indications for each drug
3rd/4th gen aminopenicillins
Ticarcillin (3rd gen) and Piperacillin (4th gen)
Ticarcillin not avail in US
MOA: can penetrate porin channels of gram- at high doses and resistant to beta-lactamase activity
Indications: Pseudomonas aeurginosa
Piperacillin: aka zosyn
- Pseudomonas ****
- Klebsiella
- enterococcus
- Bacteriodes fragilis
Piperacillin + Tazobactam=zosyn
52
```
kinetics of PCNs
-routes
-abs
-t 1/2
-met
eliminatin
```
route depends on whether the drug is acid stable or not
abs: usually rapid
t1/2 is SHORT
well distributed--- crosses placenta and into B milk BUT cannot cross BBB unless there is inflammation present
met: kindye, liver
elimin: renal tubules,
53
is dicloxacillin's absoprtion decreased or increased with food
decreased
54
is amoxicillin's absoprtion decreased or increaesd with food
increased
55
can PCNs cross BBB?
no, only when there is inflammation present
56
what drug increases excretion and increases levels of PCNs
Probenecid
57
adv rxns for PCNs
-gen well tol and SAFE compared to other abx
- hypersensivity
- diarhea
- nephritis: only with methicillin
- neurotoxicity-- can lower seizure threshold
- hematologic: piperacillin, nafcillin, Pen G---can result in decreased coagulation, monitor for cytopenias after prolonged tx
58
which PCN can cause nephritis
Methicillin
59
```
General MOA for cephalosporins
ADV rxns for cephalosporins in general
-abs
-excretion
-contraindications
-which gen is highest cross reactivity
```
-beta-lactam ABX
-Bactericidal
-cell wall inhibs closely related to structure and function of PCN
-1-4 gens
-
Adv rxn: cross reactivity with PCNs--- hypersensitivy rxn 0-80%
Poorly absoproed PO-- why most is given IV or IM
Excretion: kidney, EXCEPT Ceftriaxone=liver
Generally well tolerated
CONTR:
*severe PCN allg--- can develop SJS, anaphy, TEN
*1st gens have the highest cross reactivity with PCN
60
which is more effective against beta- lactamase producting bacteria: PCNs or Cephalosporins
Cephs
61
first generation cephs
- list drugs and routes
- spectrum
- indications
* Cephalexin--PO--KEFLEX
* Cefazolin--IV
* Cefadroxil--PO... dont worry about this one...
spectrum: great coverage for gram+ cocci, some anaerobes and gram - rods
indiactions:
- skin and soft tissue infections : staph and strep--NOT MRSA
- surgical prophylaxsis=cefazolin
62
second generation cephs
-spectrum as a class
-indications as a class
-
Spectrum:
* broader gram- coverage since they are resistant to beta lactamases
* weaker gram + coverage
Indications:
1. Cefoxitin very good coverage for Bacteroids fragilis--anaerobic gram-
* skin infections
* respiratory/ENT
* UTI
* Cefoxitin is used for anaerobic infections abdominal
63
Third gen Cephs
- list drugs and routes
- spectrum
- indications
- resistance?
- can cause?
* Ceftriaxone--IM, IV
* Ceftazidime--IM, IV +/- avibactam
* Cefotaxime
spectrum: broader gram- coverage,
GOOD CNS PENETRATION** esp Ceftriaxone*****8
-good coverage for Serratia
Indications:
* Ceftriaxone, Cefotaxime - DOC Bacterial meningitis, gonorrhea
* Ceftazidime- Pseudomonas
* added with macrolide for CAP (but hospitalized)
* **resistance is building with this class
* ** can lead to C. Diff
64
Fourth Gen Cephs:
- drugs and routes
- spectrum
- indications
*Cefepime (IV)
Spectrum:
* Gram- for Pseudomonas
* Gram + for strep and staph only methicillin susceptible organisms
indications:
* Isolated infections with pseudomonas
65
Fith gen ceph:
- drugs and routes
- specturm
- does not cover?
- indications
Ceftaroline *IV*
spectrum:
* broad spectrum grm + including MRSA and gram-
DOES NOT COVER PSEUDOMONAS OR ANAEROBES
Indications:
- hosp aquired MRSA infections--skin, CAP
- never first line tho
66
```
Carbapenems
-drugs and routes
-MOA
-spectrum
-treats?
-any dose adjustmetns?
-
```
- PENEMS
* Imipenem--IV
* Meropenem--IV +/- vaborbactam
* ertapenem--IV, IM
MOA: beta-lactam wall inhibitor
Spectrum: tx beta-lactamase producing organisms that are resistant to other drugs BUT resistance to carbepenams is emerging
* Broad spectrum and saved only for serious infections:
* Gram (-)---H. influenzae, N. Gonorrhoeae, Enterobacteriaceae, Pseudomona
* anaerobes: B. fragilis
* Gram (+)-- Enterococcus, listeria
NOT FOR MRSA or MYCOPLASMA
all need renal dosing****
67
which ABX MUST MUST always be dose-adjusted for renal function?
Carbapenems *****
| Monobactams aka Aztreonam
68
Imipenem
- inactivated where and how do we prevent this
- spectrum?
- adv rxns
- avoid in tx of which dz?
at the renal tubules
*prevent this by adding cilastatin to it
BROAD BROAD spectrum
* CNS toxicity--including seizures
* *AVOID IN MENINGITIS***
69
Meropenem
- adv rxns
- indications
-less CNS toxicity than Imipenem
inds:
- pediatric bacterial meningitis >3 MO of age
- intraabdominal infections
NOT inactivated at renal tubule
70
which carbapenem is inactivated and not inactivated at renal tubules
Meropenem NOT
| Imipenem YES inactivated
71
Ertapenem
- t1/2
- sepctrm
narrower spectrum (newer drug)
T1/2 LONG so advantage to taking this is once daily dosing
72
Doripenem
discontinued in US
73
Monobactams
- drugs and routes
- MOA
- special dosing?
- indications
- does not tx
- cross allergenicity with?
Aztreonam (IV)
- beta lactam cell wall inhibitor-- binds to penicilin-binding proteins
- effective against gram(-) and aerobes (enterobacteriaceae, Pseudomonas)
DOES NOT work on anaerones or gram+
yes renal dosing required
-cross allergenicity with Ceftazidime
good alterntive for PCN allergy
74
Vancomycin
- routes
- MOA/structure
- spectrum/indications
- adv rxns
IV, PO
*glycopeptide that binds to peptidoglycan precursors--interferring with polymerization and cross linking requried for stable bacterial cell wall
Spectrum:
* Gram + only
* mostly staphlyococci and streptococci--BACTERICIDAL
* bacteriostatic for enterococci
Indications:
* MRSA***** IV also bacteremia/sepsis, pneumonia
* C Diff ***** PO
ADV RXN:
* Vancomycin flushing syndrome aka red man syndrome
- flushing
- erythema
- pruritis of face/neck-->goes to lower body
- rarely cause cardiovascular collapse
- due to rapid infusion rates
* thrombophlebitis
* Nephrotoxicity--always check renal functions and check troughs
75
Lipoglycopeptides
- drugs
- MOA
- ____ dependent
- potency compared to vancomycin
- spectrum
- adv rxn
- t 1/2
- Telavancin
- Olivanic--inferes with cell wall synthesis
- Dalbavancin
* Bactericidial
* concentration dependent
* more potent than vancomycin
Spectrum: gram+
* staphylococci
* streptococci
* VRE
* MRSA
* VRSA
ADV RXN:
*Telavancin-- nephrotoxicity, teratogeniciy, coagulation disturbance, prolonged QTc
t 1/2 of Oritavancin and Dalbavancin-- very long half lives=--- 200 hours!!
76
Daptomycin
- rotue
- MOA
- spectrum
- cannot tx?
- adv rxn
IV
Cyclic lipopeptide causes rapid depol of the cell membrane and inhibits DNA, RNA and protein synthesis
Bactericidal and [ ] dependent
SPectrum:
* gram+
* MRSA
* VRE (vancomycin resistant enterococci)
* Skin infections
* bacteremia
Do not use for pneumonia bc it is inactivated by pulmonary surfactant
ADV RXN:
* elevated transaminases
* myalgia
* rhabdomyolysis
77
Fosfomycin
- routes
- MOA/structure
- bacteriostatic or cidal?
- inds
- dosing?
- abs?
- distrubtion
- ADV rxn
PO, IV
Phosphonic acid derivative, inhibits peptodoglycan synthesis needed for bacterial cell wall synthesis
bactericidal
INDS:
-UTIs caused by E. coli and E. Faecalis
SINGLE DOSE
abs: rapidly
distributed: kidneys well
ADV RXN
* gen well tol
* diarrhea/nausea
* vaginitis
* HA
78
Polymyxin B
- routes
- moa
- spectrum and inds
IM, IV, topical
* *IV: great risk of nephrotoxicity and neurotoxicity
* *topical not abs in GI tract
MOA: cation polypeptide binds to lipopolysaccharide membrane of gram-
*causing cell contents to leak out--- cell death
Spectrum:
- narrow: primarily gram- organisms
* Hops acquired multi-drug resistance organisms (i.e resistance to carbapenems)----PSEUDOMONAS, ACINETOBACTER
* topical is MC used--ophthalmic
79
adv rxn to Telavancin
nephrotoxicity, teratogeniciy, coagulation disturbance, prolonged QTc
80
-vancin
```
Lipoglycopeptides
*televancin
*olivanic
*delevancin
gram+ coverage
```
