CWSI Flashcards
1
Q
Target of CWSI
A
Penicillin-binding-proteins (PBP)
2
Q
CMSI are
A
cidal
3
Q
Peptidoglycan is composed of
A
- alternating sugar backbone (NAG and NAM)
- chain of four AA extending from backbones (NAM)
- peptide bridge that corss-links peptide chains
4
Q
Last AA on NAM chain, that can be modified for resistance
A
D-alanine
5
Q
Peptidoglycan
A
assembled in cytoplasm, transported through membrane to cell surface, cross-linking is driven by cleavage of terminal AA (D-alanine)
6
Q
5 Targets of CWSI
A
- Transglycosylation - joining NAG-NAM (performed by PBP)
- Transpeptidation- (cross links pentapeptides (performed by PBP)
- NAG reduction to NAM
- Transport across membrane
- AA mimicry - pentapeptide chain
7
Q
Job of PBP
A
transglycosylation and transpeptidation
8
Q
inhibits one of the first steps of CWS
A
fosfomycin
9
Q
MOA of fosfomycin
A
inhibits peptidoglycan synthesis resulting in accumulation of nucleotide precursors and subsequent cell death (acts as PEP to inactivate enzyme) (prevents NAG –> NAM)
10
Q
MOA of beta-lactams
A
prevent transpeptidation and transglycosylation; beta-lactam ring irreversibly bind to PBP; susceptible to penicillinases
11
Q
Types of beta-lactams
A
penicillins, cephalosporins, carbapenems, and monobactams
12
Q
Bactiracin MOA
A
blocks transport of peptidoglycan subunits from cytoplasm to cell exterior; cell-wall subunits accumulate in the cytoplasm and cannot be added to growing chain
13
Q
Glycopeptides (Vancomycin) MOA
A
bind to D-alanine while subunits are external to the cell membrane but still linked to lipid carrier; binding sterically inhibits the addition of subunits to peptidoglycan backbone
14
Q
Autolysins
A
cleave peptidoglycan bonds in normal course of cell growth
15
Q
CWSI require
A
autolysins; cell in GROWING PHASE
16
Q
CWSI inhibitors can’t be used with
A
protein-synthesis inhibitors (Chloramphenicol) because the cell won’t be growing then
17
Q
Antagonism for CWSI
A
CWSI + Protein synthesis inhibitor (ex. PCN + choramphenicol)
18
Q
PBP MOA
A
removes D-alanine to form crosslink w/ nearby peptide
19
Q
Natural Peniciilin drugs
A
- Pen G (IV)
- Benzathine PCN (IM)
- Procaine PCN G (IM)
- Pen V (oral)
20
Q
Spectrum of natural PCN
A
Best G (+) (especially cocci); some G- and anerobic coverage;
inactivated by beta-lactamases;
no antipseudomonal
elimination- kidney (probenicid reduces elimination);
poor CNS penetration (except inflammation- N. meningitides)
21
Q
DOC of natural PCN
A
N. meningitides, S. pneumoniae, strep A, B, enterococcus, actinomyces, leptospira, treponema
22
Q
DOC for syphilis
A
Penicillin
23
Q
Silver nitrate drops
A
PCN drops in eyes to prevent gonorrhea opthamolgia in newborns
24
Q
Penicillinase resistant drugs
A
Nafcillin (IM/IV)
Oxacillin (IV/IM, ORAL)
Dicloxacillin (oral)
Methicillin*
25
Penicillinase resistant drug characteristics
lower G+, some G-
resistant to penicillinase
some acid stable and highly protein bound
hepatic metabolism and renal excretion
26
DOC of penicillinase resistant drugs
MSSA (penicillinase producing stap aureus)
27
Methicillin resistance
due to altered PBP; no beta-lactam will work (can't bind) except for ceftaroline
28
Only beta-lactam that works against MRSA
ceftaroline
29
Extended spectrum PCN
```
better G-, less G+
no anti-pseudomonal activity
resistance is frequent
susceptible to beta-lactamases
URINARY EXCRETION
```
30
Extended spectrum PCN drugs
Ampicillin (oral)
| Amoxicillin (oral)
31
Ampicillin and amoxicillin DOC for
Listeria (ampicillin)
H. pylori (amoxicillin in combo)
B. burgdorferi (early; can also use doxycline)
32
Ampicillin rash
generalized, dull red maculopapular rash, usually 3-14 days after starting tx; not allergic and does not preclude future use of PCN; many patients with EBV (mono) develop rash
33
Antipseudomonal PCN drugs
Piperacillin (IV/IM)
| Ticarcillin (IV/IM)
34
Antipseudomonal PCN drug properties
bacteria covered by extended spectrum (good G-) + additional enteric Gram (-) (proteus, enterobacter, providencia and serratia);
major use: pseudomonas aeurginosa
susceptible to beta-lactamase
only available in combo with B-lactamase inhibitors
parenteral
renal excretion
35
DOC for antipseudomonal PCN drugs
P. aeruginosa (in combo w/ aminoglycoside to avoid resistance)
36
Beta-lactamase inhibitors
clavulanic acid
Sulbactam
Tazobactam
37
Beta-lactamase inhibitors used with
ampicillin, amoxicillin, ticarcillin, piperacillin
38
role of beta-lactamase inhibitors
block penicillinase activity; extend spectrum of drug
39
PCN resistance
1. Penicillinase
2. altered PBP
3. autolytic enzymes not active (not growing)
4. lack of cell wall/not peptidoglycan cell wall (mycoplasma; chlamydia)
40
what bacteria have penicillinase activity
Staphylcocci and other Gram-negative
41
Tranpeptidase
PBP
42
Toxicity of PCN
1. ALLERGY (safest drug besides this)
2. electrolyte imbalance
3. GI
4. Superinfections
43
Hypersensitivity drugs
PCN, sulfa, cephalosporins, etc.
44
Pharmacokinetics of PCN
```
good tissue penetration
poor CNS penetration
mostly renal elimination (extended spectrum is urinary)
filtration and tubular excretion
probenecid inhibits renal elimination
```
45
Probencid
inhibits renal elimination; increases half-life of PCN
46
Benzathine Penicillin
longest acting, low blood levels
47
Pen G
mild/moderate infections
48
Pen G DOC
rheumatic fever, syphilis
49
Excretion of PCN
most rapidly excreted by kidney; most is tubular secretion (can be partially blocked by probenecid)
50
Cephalosporins MOA
activate cell wall autolytic enzymes through blocking terminal cross-linking of peptidoglycan (PBP)
51
Advantage of cephalosporins over penicillins
7-methyl group that increases resistance to beta-lactamases
52
1st generation cephalosporins (narrow spectrum) drugs
cefazolin (IV/IM)
| Cephalexin (oral)
53
1st gen properties
good G+
moderate G - (e. coli, klebsiella, proteus)
MSSA susceptible
Resistant (entercocci, MRSA, s. epidermis)
Alternative for PCN-allergic individuals
increased beta-lactamase resistance
Renal excretion
54
DOC for surgical prophylaxis
cefazolin
55
2nd gen cephalosporin drugs (intermediate spectrum)
Cefaclor (oral)
Cefuroxime (IV/IM)
Cefprozil (oral)
56
2nd gen properties
lower G+, somewhat increase G-
no antipseudomonal activity
mostly renal excretion
VERY SIMILAR TO FIRST GEN EXCEPT SOME MORE G-
57
All cephalosporins lack activity against
enterococci, listeria, MRSA
58
DOC of 1st gen cepahlosporin
E. coli, Klebsiella, proteus; cefazolin for surgical prophylaxis
59
DOC of 2nd gen cephalosporin
E. coli, Klebsiella, proteus, moraxella
60
Only 2nd gen ceph that can cross BBB
cefuroxime
61
3rd gen ceph drugs
Ceftriaxone (IV/IM)
Ceftaxime (IV/IM)
Ceftazidime (IV/IM)
Cefixime (oral)
62
Ceftriaxone
CNS penetration, N. gonorrhea
63
Cefotaxime
CNS penetration
64
Ceftazidime
P aeruginosa (if ticarcillin or piperacillin can't be used)
65
Cefixime
gonorrhea, but ceftriaxone IM is better
66
3rd gen ceph properties
less active against G+
much more active against Enterobacteriaceae (penicillinase producing)
Kidney excretion
67
Ceftriaxone contraindication
neonates or jaundiced; bilirubin displacement
68
4th gen ceph drug
Cefepime (BROAD SPECTRUM)
69
4th gen ceph properties (cefepime)
better G+
ANTIPSEUDOMONAL
renal excretion
BROADEST COVERAGE: enterobacter, MSSA< pseudomonas
empirical therapy when Beta-lactamases are anticipated
70
5th gen ceph drug
Ceftaroline
71
Ceftaroline (5th gen) properties
no antipseudomonal activity
active against G+/G-
renal excretion
MRSA and VRSA coverage; only beta-lactam active against MRSA (can bind to PBP2A with high affinity)
72
DOC for cephalosporins
moraxella (2nd/3rd gen)
N. gonorrhea (cetriaxone, cefixime)
E.coli, Klebsiella, Proteus (1st/2nd gen)- UTI
Salmonella- 3rd gen
PCN resistant strep pneumonia (cetriaxone)
Borellia- ceftriazone (late disease)
73
Borellia tx
Early: amoxicillin, doxycycline
Late: cetriaxone
74
Toxicity of cephalosporins
```
superinfection
DISULFIRAM-LIKE RXN
ALLERGY (don't give if PCN allergy)
positive Coomb's test
Diarrhea
DOSE DEPENDENT RENAL TUBULAR NECROSIS (synergistic nephrotoxicity with aminoglycosides)
```
75
Monobactam drug
Aztreonam (IM/IV)
76
Aztreonam (monobactam) properties
similar to 3rd gen ceph
relatively resistant to beta-lactamases
Spectrum: AEROBIC GRAM - (including pseudomonas)
no activity against G+ or anaerobes
renal excretion
no cross-sensitivity to beta lactams (good alternative for PCN allergic people)
77
Side effects of aztreonam
phlebitis, skin rash, abnormal liver function
78
Aztreonam not effective against
G+ or anaerobes
79
Aztreoname spectrum
G- aerobes only
80
Good alternative for penicillin allergic pt. w/ gram-negative infection
Aztreonam
81
Carbapenem drugs
Imipenem + cilastin (primaxin) (IV)
meropenem (IV)
ertapenem (IV/IM)
82
Carbapenem indications
organisms resistant to other antimicrobias and for MIXED AEROBC/ANAEROBIC infections; one of best classes for broad spectrum coverage
83
Imipenem administration
must be given with cilastin: imipenem is inactivated in renal tubule by dihydropeptidase, which results in low urinary concentrations
84
Cilastin
dihydropeptidase inhibitor; given with imipenem
85
Imipenem and Meropenem
highly stable against beta-lactamases (including extended spectrum lactamases)
broad spectrum activity (anaerobes, G+, G-, rods)
Pseudomonas may develop resistance rapidly (use with aminoglycosdie) renal excretion
86
Broadest coverage of beta-lactams
carbapenems
87
Causes seizures
Imipenem
88
Ertapenem
stable against beta-lactamses
Spectrum: G+, G0 and anerobic (Enterobacter)
IV/IM
Should not be used for pseudomonas
89
DOC of imipenem or meropenem
Serratia, Enterobacter (beta-lactamase producing)
90
Pseudomonas drug order
anti-pseudomonal PCN --> Cefepime (4th gen) --> Aztreonam --> Imipenem/meropenem
91
non-beta lactam ICWS
vancomycin
Fosfomycin
Bacitracin
92
MOA of vancomycin
prevents transpeptidation by binding to D-ala; bactericidal
93
Resistance to vancomycin
mutation of D-ala site
94
DOC of vancomycin
PCN and MRSA infections; G+ infections to allergic patients;
| Superinfections (Oral): staph, c. diff
95
Vanco is only effective against
G+
96
VRE
vancomycin resistant enterococci (drug of last resort)
97
Adverse effects of vancomycin
OTOTOXIC, NEPHROTOXIC, RED MAN SYNDROME, thrombophlebitis at injective site
98
red man syndrome
Rxn to vancomycin; flushing from histamine release
99
Fosfomycin MOA
analog of PEP (prevents NAG to NAM reduction); early inhibitor of CWS
100
Fosfomycin properties
Spectrum: G+/G-
oral; excreted by kidney
used for uncomplicated UTI's
Synergism: beta-lactam, aminoglycoside or fluorquinolone
101
Synergism of fosmomycin
beta-lactam, aminoglycoside or fluorquinolone
102
Bacitracin MOA
interferes with final dephosphorylation step in phospholipid carrier cycle; can't tranport NAG-NAM across inner membrane
103
Bacitracin properties
parenteral (rare) and TOPICAL
Spectrum: G+
Used in combo with neomycin and polymyxin (G-) (neosporin)
Nephrotoxicity in parenteral
