CWSI Flashcards
Target of CWSI
Penicillin-binding-proteins (PBP)
CMSI are
cidal
Peptidoglycan is composed of
- alternating sugar backbone (NAG and NAM)
- chain of four AA extending from backbones (NAM)
- peptide bridge that corss-links peptide chains
Last AA on NAM chain, that can be modified for resistance
D-alanine
Peptidoglycan
assembled in cytoplasm, transported through membrane to cell surface, cross-linking is driven by cleavage of terminal AA (D-alanine)
5 Targets of CWSI
- 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
Job of PBP
transglycosylation and transpeptidation
inhibits one of the first steps of CWS
fosfomycin
MOA of fosfomycin
inhibits peptidoglycan synthesis resulting in accumulation of nucleotide precursors and subsequent cell death (acts as PEP to inactivate enzyme) (prevents NAG –> NAM)
MOA of beta-lactams
prevent transpeptidation and transglycosylation; beta-lactam ring irreversibly bind to PBP; susceptible to penicillinases
Types of beta-lactams
penicillins, cephalosporins, carbapenems, and monobactams
Bactiracin MOA
blocks transport of peptidoglycan subunits from cytoplasm to cell exterior; cell-wall subunits accumulate in the cytoplasm and cannot be added to growing chain
Glycopeptides (Vancomycin) MOA
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
Autolysins
cleave peptidoglycan bonds in normal course of cell growth
CWSI require
autolysins; cell in GROWING PHASE
CWSI inhibitors can’t be used with
protein-synthesis inhibitors (Chloramphenicol) because the cell won’t be growing then
Antagonism for CWSI
CWSI + Protein synthesis inhibitor (ex. PCN + choramphenicol)
PBP MOA
removes D-alanine to form crosslink w/ nearby peptide
Natural Peniciilin drugs
- Pen G (IV)
- Benzathine PCN (IM)
- Procaine PCN G (IM)
- Pen V (oral)
Spectrum of natural PCN
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)
DOC of natural PCN
N. meningitides, S. pneumoniae, strep A, B, enterococcus, actinomyces, leptospira, treponema
DOC for syphilis
Penicillin
Silver nitrate drops
PCN drops in eyes to prevent gonorrhea opthamolgia in newborns
Penicillinase resistant drugs
Nafcillin (IM/IV)
Oxacillin (IV/IM, ORAL)
Dicloxacillin (oral)
Methicillin*
Penicillinase resistant drug characteristics
lower G+, some G-
resistant to penicillinase
some acid stable and highly protein bound
hepatic metabolism and renal excretion
DOC of penicillinase resistant drugs
MSSA (penicillinase producing stap aureus)
Methicillin resistance
due to altered PBP; no beta-lactam will work (can’t bind) except for ceftaroline
Only beta-lactam that works against MRSA
ceftaroline
Extended spectrum PCN
better G-, less G+ no anti-pseudomonal activity resistance is frequent susceptible to beta-lactamases URINARY EXCRETION
Extended spectrum PCN drugs
Ampicillin (oral)
Amoxicillin (oral)
Ampicillin and amoxicillin DOC for
Listeria (ampicillin)
H. pylori (amoxicillin in combo)
B. burgdorferi (early; can also use doxycline)
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
Antipseudomonal PCN drugs
Piperacillin (IV/IM)
Ticarcillin (IV/IM)
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
DOC for antipseudomonal PCN drugs
P. aeruginosa (in combo w/ aminoglycoside to avoid resistance)
Beta-lactamase inhibitors
clavulanic acid
Sulbactam
Tazobactam
Beta-lactamase inhibitors used with
ampicillin, amoxicillin, ticarcillin, piperacillin
role of beta-lactamase inhibitors
block penicillinase activity; extend spectrum of drug
PCN resistance
- Penicillinase
- altered PBP
- autolytic enzymes not active (not growing)
- lack of cell wall/not peptidoglycan cell wall (mycoplasma; chlamydia)
what bacteria have penicillinase activity
Staphylcocci and other Gram-negative
Tranpeptidase
PBP