Fluoroquinolones Flashcards
Nalidixic acid was a byproduct of
chloroquine synthesis
Nalidixic acid was used for treatment of ____ due to high urinary concentration but poor absorption
UTI
Nalidixic acid spectrum of activity included
gram - but not pseudomonas
Quinolone pharmacophore at position 6
fluorine was added leading to a 10 fold increase in DNA gyrase inhibition
Substitutions on the main quinolone core alter the____ properties and microbiologic activity
PK
Fluoroquinolone MOA
- separate the double helix
- As DNA helices pulls strands apart, positive supercoiling occurs, putting pressure on the strands
- DNA gyrase removes the supercoils to relieve torsional stress
Following complete replication the cells need to be separated
- topoisomerase IV is responsible for separating interlinked DNA and allows for the development of 2 daughter cells
- similar in structure to DNA gyros, topoIV is made of 4 sub its and encoded by ParC and ParE genes
Fluoroquinolones interfere with ______ to disrupt DNA development and daughter cell formation
DNA gyrase and topoisomerase IV
DNA gyrase is the primary target in
Gram -
Topoisomerase IV is the primary target in
Gram +
Fluoroquinolones include
ciprofloxacin
levofloxacin
moxifloxacin
delafloxacin
Ciprofloxacin oral absorption
high
Ciprofloxacin 1/2 life
4 hours
Ciprofloxacin elimination
50% renal
Levofloxacin oral absorption
high (IV:PO)
Levofloxacin 1/2 life
7 hours
Levofloxacin elimination
87% renal
Moxifloxacin oral absorption
high (IV:PO)
Moxifloxacin 1/2 life
12 hours
Moxifloxacin elimination
20% renal; low
Delafloxacin oral absorption
high but lowest out of FQ
Delafloxacin 1/2 life
4 hours
Delafloxacin elimination
65% renal
FQs distribute _____ into tissues including _____
well; CNS
FQ’s are mostly _______ eliminated
renally
Moxifloxacin is mostly metabolized by the
liver
Moxifloxacin needs/does not need a renal adjustment
does not
Ciprofloxacin spectrum coverage
GRAM - ONLY
dark red: Neisseria, h. influenzae, m. catarrhalis, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia, p. aeriginosa
light red: E. coli
Levofloxacin spectrum coverage
dark purple: streptococcus, s. pneumoniae, viridans, MSSA
dark red: Neisseria, h. influenzae, m. catarrhalis, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia
light red: E. coli, p. aeruginosa
Levofloxacin and moxifloxacin are
respiratory agents
Moxifloxacin spectrum coverage
dark purple: streptococcus, s. pneumoniae, viridans, MSSA
light purple: MRSA
dark red: Neisseria, h. influenzae, m. catarrhalis, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia
light red: E. coli
Misc: anaerobes
Delafloxacin spectrum coverage
dark purple: streptococcus, s. pneumoniae, viridans, MSSA, MRSA
light purple: e. faecalis
dark red: Neisseria, h. influenzae, m. catarrhalis, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia
light red: E. coli, p.aeruginosa
Misc: anaerobes
Which FQ covers MRSA?
Delafloxacin
Which organisms do FQ not cover at all
e. faecium and acinetobacter
FQ cover atypicals:
++ (oral and gut)
chlamydia
mycoplasma
legionella
FQ also cover
s. maltophilia, vibrio, yersinia, bacillus anthracis, mycobacterium, nocardia
There is a high frequency of FQ resistance in
ESBL-producing gram - bacteria
Dosing is dependent on
indication
Levofloxacin and Moxifloxacin dosing is
QD
Mechanisms of resistance for FQ
alterations to target sites DNA grease (gyrA or gryB) and topoIV (parC or parE)
primary mutation will occur at the drugs primary target
gram - is usually at DNA gyrase
gram + is usually at topoIV
reduction in intracellular concentrations (efflux pumps)
reduction in number of porin channels (decreased entry)
FQ/AG modifying enzymes
Adverse effects with FQ
nausea diarrhea dizziness rash headache vaginitis
FQ use is associated with higher risk of
C. difficile infection
FDA warnings for FQ
tendinitis/tendon rupture
peripheral neuropathy
restricting use for sinusitis, bronchitis, uncomplicated UTI
decrease in blood sugar and entrain mental health side effects
aortic aneurysm and dissection
Quinolone-induced arthropathy/tendinopathy is a
class effect
In peds we worry about FQ causing
developmental issues in cartilage and joints
In adult patients ____ is most common musculoskeletal disorder
Achille’s tendon rupture
FQ musculoskeletal disorders potential mechanism may involve
chelating properties- interact with regulating proteins of tenocytes
Magnesium deficient has a
synergistic effect on tendonopathy
FQ have been associated with
aortic aneurysm and rupture of aortic aneurysm
Risk factors for aortic aneurysm associated with FQ use
age > 70 and course >14 days
FQ should be avoided in patients who have existing____unless no other options available
aortic aneurysms
FQ can cause ___prolongation
QTc/QT
QT prolongation is a risk factors for
arrhythmias
torsades de pointes (ventricular tachycardia)
can lead to ventricular fibrillation and death
Avoid FQ with other _____ medications
QT prolonging
FQ have also been associated with disturbances of blood glucose causing
hyperglycemia and hypoglycemia
Risk of _____ is greater in diabetic patients, the elderly, and those with organ dysfunction
hypoglycemia
____occurs more often although is still relatively infrequent. May occur in diabetic or non-diabetic patients and at any time in therapy
hyperglycemia
FQ drug-drug interactions
warfarin-increased effect
anti diabetic agents
chelation agents: antacids, sucralfate, metal cations, multivitamins (separate by 2 hours before or 6 hours after FQ)
QT prolonging agents
NSAIDs (increase risk for seizures)
Ciprofloxacin specific (CYP1A2 inhibitor): theophylline, cyclosporine, methotrexate
FQ indications
CA pneumonia (moxi, levo, dela) UTI, acute exacerbation of chronic bronchitis, sinusitis
decreasing use in many health systems but frequently prescribed despite warnings for UTI and intra-ab (caution with E. coli resistance)
Fluoroquinolones are bactericidal/bacteriostatic
bactericidal
