Fluoroquinones

Question 1

1. Describe the mechanism of action of the fluoroquinolones.

Answer 1

They bind DNA gyrase (G-) and topoisomerase IV (G+), halting DNA synthesis and killing the bacteria

Question 2

2. Describe the 4 mechanisms by which bacteria develop resistance to the fluoroquinolone antibiotics.

Answer 2

Altered binding sites – chromosomal mutations in the genes that lead to decreased binding affinity of the FQs to their target sites.
1. S. aureus and P. aeruginosa require only a single mutation in the genes
encoding for the topoisomerases to become resistant.
2. E. coli and S. pneumoniae often require more than one mutation to become
resistant to the newer FQs.

Expression of active efflux - reported in P. aeruginosa and S. pneumoniae.

Altered cell wall permeability – decreased porin expression (rare).

Cross-resistance is usually observed between the FQs.

Question 3

List the spectrum of activity of the ciprofloxacin

Answer 3

Gram + (exception): B. antracis

Gram – aerobes: Enterobacteriaceae, H. influenzae, M catarrhalis, Neisseria, P. aeruginosa (cipro>levo)

Atypical bacteria- Legionella pneumophilia (DOC), Chlamydophila and Chlamydia, Mycoplasma, Ureaplasma urealyticum

Question 4

List the spectrum of activity of the levofloxacin

Answer 4

Gram + aerobes- MSSA, Strep pneumo

Gram – aerobes: P. aeruginosa (cipro>levo), Enterobacteriaceae, H. influenzae, M catarrhalis, Neisseria

Atypical bacteria- Legionella pneumophilia (DOC), Chlamydophila and Chlamydia, Mycoplasma, Ureaplasma urealyticum

Other: M. tuberculosis, B. anthracis

Question 5

List the spectrum of activity of the moxifloxacin

Answer 5

Gram + aerobes- MSSA, Strep pneumo

Anaerboes- Bacteroides (30% resistance with B. Fragilis)

Atypical bacteria- Legionella pneumophilia (DOC), Chlamydophila and Chlamydia, Mycoplasma, Ureaplasma urealyticum

Other: mycobacterium tuberculosis

Question 6

Which fluoroquinolones that have the best activity against Staphylococcus aureus?

Answer 6

MSSA: Levofloxacin and moxifloxacin

Question 7

Which fluoroquinolones that have the best activity against Streptococcus pneumoniae?

Answer 7

Levofloxacin and moxifloxacin

Question 8

Which fluoroquinolones that have the best activity against Pseudomonas aeruginosa?

Answer 8

Ciprofloxacin (levofloxacin works but is not preferred)

Question 9

Which fluoroquinolones that have the best activity against atypical bacteria?

Answer 9

Cipro, levo and moxi

Question 10

Which fluoroquinolones that have the best activity against anaerobes?

Answer 10

Moxifloxacin has some activity

Question 11

Discuss the main clinical uses of ciprofloxacin,

Answer 11

Acute exacerbations of chronic bronchitis and sinusitis,
Bacterial exacerbations in cystic fibrosis (P. aeruginosa),
Nosocomial pneumonia (anti-pseudomonal FQ’s),
Urinary tract infections (cystitis, pyelonephritis),
Chronic Bacterial Prostatitis,
Bone/Osteomyelitis,
intraabdominal infections (with metronidazole),
Traveler’s diarrhea
Tuberculosis
STDs

Question 12

Discuss the main clinical uses of levofloxacin

Answer 12

Community-acquired pneumonia
Acute exacerbations of chronic bronchitis and sinusitis
Nosocomial pneumonia (anti-pseudomonal FQ’s)
Urinary tract infections (cystitis, pyelonephritis)
Chronic Bacterial Prostatitis
Bone/Osteomyelitis
intraabdominal infections (with metronidazole),
Tuberculosis
STDs

Question 13

Discuss the main clinical uses of moxifloxacin

Answer 13

Community-acquired pneumonia
Acute exacerbations of chronic bronchitis and sinusitis
Bone/Osteomyelitis
intraabdominal infections (with metronidazole),
Tuberculosis
STDs

Question 14

List the major adverse effects associated with fluoroquinolone therapy

Answer 14

Major:
A. Gastrointestinal (5%) – nausea, vomiting, diarrhea, dyspepsia, Clostridium difficile colitis
B. CNS – headache, confusion, agitation, insomnia, dizziness, rarely hallucinations and seizures

C. Hepatotoxicity – transaminase elevation; moxifloxacin has been associated with a few cases of liver failure
D. Phototoxicity – patients should to avoid exposure to sunlight or UV light. Sunscreen containing UVA blockers may help.
E. Cardiac – FQs may cause slight prolongation in QTc interval, excessive prolongation can lead to Torsades. FQs should be used with caution in patients with
HYPOKALEMIA or in patients who already have a prolonged QTc interval. Avoid concomitant use with class III antiarrhythmics (amiodarone, sotalol), or with
other drugs that can prolong the QTc.
F. Articular Damage – arthropathy (articular cartilage damage, arthralgias and joint swelling) observed in young experimental animals led to the contraindication in PEDIATRIC PATIENTS, PREGNANT AND BREASTFEEDING WOMEN
G. Tendonitis and Tendon Rupture – Higher risk in patients over 60 years of age receiving corticosteroids, or who have undergone a renal, heart or lung transplant; patient should avoid exercise if tendon pain develops while on therapy

Question 15

Explain the major drug interactions that may occur with the fluoroquinolone antibiotics.

Answer 15

A. Divalent and trivalent cations (Zinc, Iron, Ca, Al, Mg– including antacids, ddI, Sucralfate, enteral feeds) may impair the absorption of ANY ORAL fluoroquinolones through chelation leading to clinical failure; doses should be administered at least 2 to 4 hours apart (tube feedings must be stopped for several hours surrounding FQ administration); give FQ first

B. Warfarin – idiosyncratic interaction leading to increased prothrombin time and potential bleeding; has been reported with most FQs

C. Theophylline – inhibition of theophylline metabolism leading to increased serum theophylline concentrations and potential toxicity; may occur with ciprofloxacin, but does not occur with levofloxacin or moxifloxacin

D. Cyclosporine – ciprofloxacin may inhibit cyclosporine metabolism leading to increased cyclosporine levels and potential toxicity