Sulfas, Antifolates, Fluoros - Fitzpatrick Flashcards
Sulfamethoxazole-Trimethoprim (TMP-SMZ) - Main uses in this section (3)
- PREVENTING or treating Toxoplasmosis in immunosuppressed patients
- PREVENTING or treating Pneumocystis jiroveci pneumonia in immunosuppressed patients
- H. influenza sinusitis
Adverse effects of TMP-SMZ (5)
Seen ESPECIALLY in who?
- Rash (Steven-Johnson) - LIFE THREATENING
- Kernicterus (and jaundice) - NEWBORNS
- Hemolysis in G6PD deficiency patients
Especially seen in AIDS patients
Sulfadiazine-Pyrimethamine is used clinically for what?
TOXOPLASMOSIS
Sulfonamide drugs - MoA
Competitive inhibition of DIHYDROPTEROATE SYNTHASE (resembles PABA) –> inhibits bacterial folic acid synthesis –> inhibits nucleic acid synthesis and replication
TMP-SMZ is a classic example of _____
Antibiotic synergy
Trimethoprim - MoA
How is this synergistic w/ Sulfamethoxazole?
Dihydrofolate reductase inhibitor
This is the 2nd enzyme in the folic acid synthesis pathway in bacteria. Thus, the TMP-SMZ combo inhibits BOTH of the steps.
Organisms that are sensitive to Sulfonamides must do what?
Are humans sensitive? Why or why not?
Build folic acid DE NOVO
NO - we get our folate from diet
Organisms sensitive to TMP-SMZ (+ condition caused) (7)
- E. coli (cystitis, prostatitis)
- Proteus (cystitis, prostatitis)
- Salmonella (diarrhea)
- Shigella (diarrhea)
- H. influenza (sinusitis)
- Pneumocystis jiroveci (pneumonia)
- Toxoplasma (encephalitis)
3 ways for resistance to TMP-SMZ
- Dihydropteroate synthase mutation
- DHFR mutation
- DHFR overexpression
Can you use TMP-SMZ for MRSA?
- Yes, but only in the community in areas where it is known that the MRSA strain is susceptible to it
A pregnant woman takes TMP-SMZ for an infection. At birth, the baby appears yellow and shows signs of neurologic deficit. Explain.
SMZ displaces bilirubin from albumin. In baby, bilirubin cannot be broken down, thus builds up in skin (jaundice) and brain (kernicterus).
SMZ is contraindicated in who?
Near-term pregnant women, neonates
A patient is taking a Sulfonamide for an infection, and soon develops weakness, hematuria, jaundice, etc. The patient remembers that she has a deficiency in G6PD. Explain.
Sulfonamides cause increased reactive oxidants (oxidative stress). In G6PD deficiency, glycolysis cannot be used to turn NADP+ into NADPH, and thus glutathione. As a result, the oxidants and H2O2 build up, causing hemolytic anemia.
TMP is contraindicated in who? Why?
Pregnant women at months 2-3 (end of 1st trimester)
- High folate need by fetus at that time
- Without it –> CV defects and oral clefts
Fluoroquinolones - MoA
DNA gyrase (topoisomerase 2) and topoisomerase 4 inhibition –> DNA dysruption
- DNA gyrase = gram (-) - Topoisomerase 4 = gram (+)
Mechanisms of resistance to Fluoroquinolones (3)
- DNA gyrase / topoisomerase mutation
- Cellular membrane efflux mechanisms
- Decreased porins - MULTI-DRUG RESISTANCE
3 ways that porins can be decreased and lead to multi-drug resistance in a bacterial strain
- Loss completely
- Mutation (non-functional)
- Decreased expression of the porin
Difference in a bacterial strain being COMPLETELY resistant to a Fluoroquinolone vs. being PARTIALLY resistant
Complete = no active porins Partial = decreased expression/production of porins
2nd generation Fluoroquinolone - drug
Ciprofloxacin
3rd generation Fluoroquinolone - drug
Levofloxacin
4th generation of Fluoroquinolone - drug
Moxifloxacin
Choosing a fluoroquinolone, even for an unusual bacteria, is often due to what characteristic of the infection?
Localized in BONE
Due to its penetration into bone, Fluoroquinolone is used to treat what?
Osteomyelitis
Atypical organisms covered by Fluoroquinolones
- Mycoplasma
- Chlamydia
- Mycobacteria
- Legionella
