Chapter 178 - Fluoroquinolones Flashcards
How do you qualify the enteral absorption, volume of distribution and elimination half-lives of fluoroquinolones?
Fluoroquinolones are well absorbed after oral and parenteral administration, have a large volume of distribution, and have extended elimination half-lives
Are fluoroquinolones bactericidal or bacteriostatic?
Bactericidal
What properties make fluoroquinolones good antibiotics for infectious prostatitis?
Weak acids
Lipophilic
Low protein binding
Are fluoroquinolones soluble in alkaline, acidic solutions or both?
Both (amphoteric molecule)
What is the generation of enrofloxacin, ciprofloxacin and marbofloxacin?
2nd-generation
What is the percentage of enrofloxacin metabolized in ciprofloxacin?
40%
What is the percentage of marbofloxacin excreted unchanged in the urine?
40%
Give one antibiotics from the third generation of fluoroquinolones
Pradofloxacin
What properties did these additions bring to the fluoroquinolones?
- Fluorine at position 6
- Piperazine at position 7
- Pyrrolidine group at position 7
- Halide, fluorine, or methoxy group at position 8
- Fluorine at position 6: enhanced drug penetration into the bacterial cell as well as increased efficacy against gram-negative bacteria
- Piperazine at position 7: increased antipseudomonal activity
- Pyrrolidine group at position 7: improves activity against gram-positive organisms.
- Halide, fluorine, or methoxy group at position 8: increase the drug’s half-life, absorption,
and efficacy against anaerobic bacteria
What is the activity of third generation fluoroquinolones?
Third-generation drugs (e.g., pradofloxacin) have the activity of the 2nd generation against aerobic gram-negative, and expanded activity against gram-positive bacteria, atypical pathogens, and some anaerobes
What is the mechanism of fluoroquinolones?
Inhibition of two bacterial enzymes of the topoisomerase class: DNA gyrase (formerly called topoisomerase II) responsible for the opening of the 2 strands of duplex DNA (primarily gram negative), and topoisomerase IV, responsible for the removal of the interlinking of daughter chromosomes (primarily gram positive) –> inhibiting normal bacterial DNA synthesis
What is the minimal bactericidal concentrations
of quinolones in relation to the minimum inhibitory concentration (MIC)
Minimal bactericidal concentrations of quinolones are usually within 2-fold to 4-fold of the minimum inhibitory concentration (MIC)
T/F Most fluoroquinolones are effective against Streptococcus spp
F - Only a small subset of the newer agents
What are the effects of oral antacids containing polyvalent cations (magnesium, aluminum,
calcium, iron, and zinc) on Fluoroquinolones?
Oral antacids containing polyvalent cations (magnesium, aluminum, calcium, iron, and zinc) decrease absorption
What are the effects of administration of food on Fluoroquinolones?
Food does not tend to decrease total serum concentrations of fluoroquinolones, but may lengthen the time to peak serum concentrations
T/F: Quinolone concentrations achieved in bile and urine are often 10 to 20 times greater than those in serum
T
T/F: Quinolone concentrations achieved in saliva, prostatic fluid, bone, and cerebrospinal fluid are often 10 to 20 times greater than those in serum
F: Concentrations of quinolones in saliva, prostatic fluid, bone, and cerebrospinal fluid are usually lower than drug concentrations in serum, although they are often adequate for killing susceptible organisms, particularly in the presence of inflammation
What is the recommended AUC/MIC24hr ratios for gram-positive and gram-negative bacteria
Streptococcus pneumoniae and most other gram-positive bacteria are rapidly killed by quinolones at a
24-hour AUC/MIC (AUC/MIC24hr) ratio of 30 to 40 or higher, whereas others, like P. aeruginosa and most other aerobic gram- negative bacteria, require much greater exposure over time to quinolones (AUC/MIC24hr ratios of ≥100 to 125).
For how long does the postantibiotic effect last after elimination?
Fluoroquinolones exhibit a marked postantibiotic
effect (PAE) in which they continue to inhibit bacterial growth for up to 8 hours after elimination from the body
What are the 3 bacteria most likely to be resistant to fluoroquinolones?
Staphylococcus, Pseudomonas, and E. coli
What are the mechanisms of fluoroquinolones bacterial resistance?
- Chromosomal point mutations in the genes encoding DNA gyrase and topoisomerase IV
- Expression of energy-dependent efflux systems that prevent the accumulation of effective intracellular concentrations of quinolones via active pumping of drug across the cell membrane (ex. multidrug efflux system AcrA-AcrB-TolC).
- Gram-negative bacteria can regulate membrane permeability by altering the levels of outer
membrane porins that form the channels responsible for passive diffusion.
Why are fluoroquinolones of later generation less prone to bacterial resistance?
Later-generation fluoroquinolone compounds with equal activity against DNA gyrase and topoisomerase IV would require simultaneous mutations in the bacteria at both sites to be rendered ineffective (double mutation rarely happens)
How is fluoroquinolone resistance transmitted to other antibiotics?
Via the transmission of plasmids
T/F:
Plasmid-mediated mechanisms typically confer high levels of resistance to fluoroquinolones
F - Plasmid-mediated mechanisms typically confer low levels of resistance to fluoroquinolones, but importantly, they favor the selection of bacteria possessing additional chromosome-encoded resistance mechanisms.