Antimicrobials: Antimetabolites Flashcards
T-F–antifolate antibiotics act in a single step to block bacterial folic acid synthesis? Does it inhibit, DNA, RNA, or protein synthesis?
- False-sequential steps
2. All three, reduce thymidine, purine, and methionine
What is a major synergistic combination of antifolate antibiotics? Are they cidal or static?
- sulfonamide+ trimethoprim
2. together they are bactericidal. Static alone.
What step do sulfonamides block?
1.competitively blocks DHPS (binding to PABA) which takes pteridine+PABA to dihydropteroic acid.
[first step to becoming methionine, thymidine, purine]
High levels of what block sulfa activity?
PABA pus
Does DHPS enzyme function in humans?
- No, bacteria must synthesize folic acid, but we obtain it from our diet.
How is sulfonamides administrated? Is it distributes to CNS and CSF? Metabolism? Excretion? Broad or narrow spectrum?
- orally but can be IV
- Yes
- Liver
- Kidney
- Broad (can target parasites)
What is sulfonamides not used for?
Rickettsia
What are the 3 mechanisms of antibacterial resistance in sulfonamides that is Common in Staph, Strep, Enterobacteriaceae, Neisseria?
1) Overproduction of PABA
2) Encode mutant DHPS enzyme with decreased affinity for
sulfas (often plasmid mediated)
3) Upregulation of efflux pumps
When is hemolytic anemia seen with sulfonamide use?
G6PD
What is kernicterus?
in infants, sulfa competes for
bilirubin binding sites on albumin and increases
levels of unconjugated bilirubin = CNS toxicity
What is stevens-johnsons syndrome?
Hypersensitivity
with mucosal sloughing, skin eruptions
When might sulfonamides be used alone because they usually aren’t because they are typically combined with trimethoprim in bacteria?
- malaria
2. CNS toxoplasmosis
What does trimethoprim block?
DHFR- which takes dihydrofolic acid to tetrahydrofolic acid–inhibits bacterial DHFR 100,000 times for than human DHFR
[STATIC ALONE!!]
How are Tmp-sulfa excreted? oral?
- in the urine
2. yes
Tmp-sulfa is a broad spectrum antibiotic used for multiple G+ and G-. What is it typically not used for in regards to bacteria/
- pseudomonas
- anaerobes
- atypical bacteria
What are the 2 major resistance pathways for trimethoprim? Is resistance dependent on location?
1) Overexpression of DHFR
2) Expression of mutant DHFR that is resistant to Tmp
(often plasmid-mediated)
YES
What is one of the most common seen severe side effects of TMP-sulfa?
bone marrow suppression with neutropenia
-can cause anti-folate effect.
Can TMP-sulfa be used for MRSA? what bacteria is efficacy decreasing in?
- Yes [also UTI, Pneumocytis, sinusitis and otitis media]
2. E. coli
Are quinolines bacteriostatic? Do they inhibit RNA synthesis? What proteins does it inhibit? reversible damage?
- Bactericidal
- No- DNA
- gyrase and topoisomerase [unwinding]
- No-irreversible
T-F–quinolones adhere to concentration dependent killing concepts?
True
How man more times is the AUC/MIC for the immunocompromised patient from the immunocompetent patient?
4 times
[100 vs. 25]
Do fluoroquinolones have great GI absorption? Do they get in CSF? what reduces its absorption? what type of elimination?
- YEs- same serum levels as IV
- CSF low
- Forms chelates with cations
- Hepatic or renal
What is the order of quinolones based on efficacy for G- and pseudomonas?
cipro > levo > moxi
What is the order of quinolones for G+ and strep in regards to efficacy?
moxi > levo > cipro
What are 3 methods of resistance for quinolines? What bacteria specifically?
- decreased permeability,
- Efflux pump
- mutation of the enzymes
[all MRSA, N. gonorrhea, Salmonella, Campylobacter]
T-F–fluoroquinolones majority of use considered inappropriate?
True
