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A. Introduction

  1. Potent cytolytic anti-bacterials
  2. Inhibit bacterial DNA gyrase (a type II topoisomerase)
  3. Agents primarily available as oral compounds; intravenous formulations for some
    1. Peak drug levels appear to be most important deterimnant of clinical efficacy [2]
    2. Drug exposure (area under the curve) also highly correlated with clinical efficacy
  4. Major acitivity is against Gram negative bacilli
    1. Aerobic enterics: E. coli, Klebsiella, Enterobacter
    2. Pathogenic: Salmonella, Shigella, Vibrio
    3. Some of these agents have good anti-pseudomonal activity
  5. Moderate activity against Gram Positive organisms
    1. Initial good anti-staphylococcal activity with development of resistance
    2. Enterococcal coverage is generally good
    3. Mediocre activity of older quinolones against pneumococcus
    4. Newer quinolones have improved anti-pneumococcal activity
  6. Newer fluoroquinolones have good activity against atypical pathogens
    1. Legionella pneumophila
    2. Mycoplasma pneumoniae
    3. Chlamydia species
  7. Rapid cytolytic activity against susceptible organisms (within hours of IV dosing)
  8. Utility
    1. Excellent for urinary tract infections (usually for TMP/SMX resistance)
    2. Second line for sinus infections and community acquired pneumonia (CAP)
    3. May be effective for chronic bronchitis in smokers
    4. Newer agents have good coverage of pneumococcus, including PCN resistant strains
    5. Certain agents have superb anaerobic coverage (similar to metronidazole)
    6. Ciprofloxacin and other second/third generation quinolones active against anthrax [3]
    7. Fluoroquinolone antibiotics reduced risk of death 48% in fever and neutropenia [15]
    8. Antibiotic prophylaxis with a fluoroquinolone should be used in neutropenic patients
  9. Resistance to Fluoroquinolones [4]
    1. Chromosomal mutations that modify DNA gyrase or DNA topoisomerase IV
    2. Plasmid resistance reported for Klebisiella and E. coli
  10. Contraindications
    1. Allergies
    2. Pregnancy / Lactation
    3. Children and adults under 18 years old - causes cartilage development defects
    4. Gatifloxacin can cause hypoglycemia in elderly diabetics taking hypoglycemic agents [13]

B. Norfloxacin (Noroxin®)

  1. Oldest quinolone in current use
  2. Rapid urinary excretion with little systemic efficacy indicated for:
    1. Uncomplicated and complicated UTI
    2. Uncomplicated urethral and cervical gonorrhea
    3. Prostatis due to E. coli
  3. Covers some resistant enterococcal strains
  4. Dose 400mg po bid (q12 hours)

C. Ciprofloxacin (Cipro®)

  1. Available po (500-750 mg bid) or iv (400mg iv q12 hours)
  2. Moderate staphylococcal coverage, but resistance develops rapidly
  3. Enterococcal coverage may be excellent, but varies by institution and locality
  4. Streptococcal (pneumococcal) coverage is unreliable
  5. Gram negative coverage is excellent (including severe infections)
  6. General Utility
    1. Second Line (resistant) urinary tract infections (UTI, cystitis), prostatitis
    2. Superior to amoxicillin-clavulanate (Augmentin®) for acute uncomplicated UTI [8]
    3. Second Line Bronchitis (particularly in smokers) or sinusitis
    4. Skin infections not due to streptococci in penicillin allergic patients
    5. With oral rifampin in staphylococcal endocarditis due to susceptible organisms
  7. FDA approved for prevention and treatment of anthrax [3]
  8. Active against plague (Yersinia pestis) and tularemia as well [3]

D. Ofloxacin (Floxin®)

  1. Excellent chlamydia and gonorrhea coverage (not seen with ciprofloxacin)
  2. Approved for general gynecologic infection treatment (400mg po bid x 7 days)
  3. Improved streptococcal coverage over ciprofloxacin
  4. Reasonable bronchitis and sinusitis coverage in penicillin allergic patients
  5. Oral ofloxacin 400mg qd x 10 days reduced time on ventilator and in hospital, and reduced mortality rate in COPD exacerbation [9]
  6. Dose is 400mg twice daily (oral and intravenous same dose)

E. Fleroxacin (Magalone®)

  1. Good UTI agent
  2. 400mg po single dose for uncomplicated gonorrhea

F. Sparfloxacin (Zagam®)

  1. Once daily oral quinolone
  2. FDA approved for CAP and chronic bronchitis
  3. Activity against nearly all classes of bacteria
    1. S. pneumoniae, including pencillin resistant strains
    2. H. influenzae, M. catarrhalis, including ß-lactamase producing strains
    3. Atypicals: C. pneumoniae, Mycoplasma pneumoniae, Legionella (in vitro)
  4. Dose: 400mg po x 1 loading dose, then 200mg po qd x 9 days thereafter (10 day course)
  5. Photosensitivity reactions have been reported

G. Levofloxacin (Levaquin®) [2]

  1. S-isomer of racemic ofloxacin with improved anti-pneumococcal activity [12]
  2. FDA approved for UTIs, sinusitis, pneumonia, and chronic bronchitis
  3. Activity against gram positive, gram negatives, and atypical organisms
    1. S. pneumoniae, S. aureus
    2. H. influenzae, H. parainfluenzae, M. catarrhalis
    3. Mycoplasma, Chlamydia pneumoniae, and Legionella pneumophila
    4. Klebsiella pneumoniae
  4. Once daily dosing: 500mg qd (oral or IV)
  5. Oral or intravenous formulations are available
  6. Levofloxacin resistant pneumococcal pneumonia has been described [11]

H. Lomefloxacin (Maxaquin®)

  1. Approved for acute exacerbation of chronic bronchitis and for UTI
  2. Photosensitivity reactions have been reported
  3. Dose 400mg po qd

I. Trovafloxacin (Trovan®) [6]

  1. FDA approved for a large number of infections
  2. Coverage includes
    1. Pneumococcus, including penicillin resistant strains
    2. Gram negative rods including Pseudomonas
    3. Atypicals: Chlamydia pneumoniae, Legionella, Mycoplasma
    4. Anaerobes: approximately equivalent to metronidazole
  3. This is the only fluoroquinolone with excellent coverage of anaerobes
  4. Approved for mixed infections including abdominal
  5. Available in oral and intravenous (Trovan IV®) formulations
  6. Dose
    1. Oral 200mg po qd x 7-14 days depending on indication (100mg qd for COPD)
    2. Intravenous 300mg qd followed by oral qd when symptoms improve

J. Moxifloxacin (Avelox®) [7]

  1. Approved for CAP, chronic bronchitis, sinusitis
  2. Better activity against S. pneumoniae in vitro than levofloxacin
  3. Clinically significant QTc interval prolongation has been reported [10]
  4. Dose is 400mg po qd

K. Gemifloxacin (Factive®) [14]

  1. Approved for acute exacerbation chronic bronchitis and CAP
  2. Dose is 320mg po qd
  3. Activity spectrum similar to levofloxacin
  4. As active as other agents and priced initially higher than other fluoroquinolones
  5. Rash is main Adverse Event
    1. Incidence of rash 3%, higher than other fluoroquinolones
    2. In women <40 years old, ~32% had rash (versus <5% with ciprofloxacin)
    3. Rash usually resuolves in 1-2 weeks
    4. ~5% of rash patients required systemic glucocorticoids
    5. Progression to Stevens-Johnson syndrome not observed

L. Gatifloxacin (Tequin®) [7]

  1. Approved for CAP, chronic bronchitis, and sinusitis
  2. Also approved for urinary tract infections (UTI) and gonorrhea
  3. Single dose 400mg for uncomplicated UTI is very effective and relatively inexpensive
  4. Better activity against S. pneumoniae in vitro than levofloxacin
  5. Oral and intravenous forms available
  6. Dose is 400mg qd (IV or oral)
  7. Hypoglycemia [13,16,17]
    1. Increased risk, especially in elderly diabetics on oral hypoglycemic agents
    2. Overall risk ~4.3X for hypoglycemia
  8. Marked increase risk of hyperglycemia (16.7X) with general use [16,17]
  9. Other second generation fluoroquinolones are safer and as effective [16]

M. Grepafloxacin (Raxar®) [5]

  1. FDA approved for CAP, chronic bronchitis, urethritis
  2. Dose is 400-600mg po qd
  3. Activity spectrum similar to levofloxacin
  4. Less active against pseudomonas than ciprofloxacin
  5. More active against anaerobes than ciprofloxacin
  6. Superior activity in vitro against penicillin resistant pneumococci
  7. Withdrawn from market due to severe cardiovascular events, QT prolongation [10]

References

  1. Hooper DC. 1998. Ann Intern Med. 129(11):908 abstract
  2. Preston SL, Drusano GL, Berman AL, et al. 1998. JAMA. 279(2):125 abstract
  3. Drugs and Vaccines Against Biological Weapons. 2001. Med Let. 43(1115):87 abstract
  4. Martinez-Martinez L, Pascual A, Jacoby GA. 1998. Lancet. 351(9105):797 abstract
  5. Grepafloxacin. 1998. Med Let. 40(1019):17 abstract
  6. Trovafloxacin. 1998. Med Let. 40(1022):30 abstract
  7. Gatifloxacin and Moxifloxacin. 2000. Med Let. 42(1072):15 abstract
  8. Hooton TM, Scholes D, Gupta K, et al. 2005. JAMA. 293(8):949 abstract
  9. Nouira S, Marghli S, Belghith M, et al. 2001. Lancet. 358(9298):2020 abstract
  10. Khan IA. 2002. Am J Med. 112(1):58 abstract
  11. Davidson R, Cavalcanti R, Brunton JL, et al. 2002. NEJM. 346(10):747 abstract
  12. Sterioisomers. 2003. Med Let. 45(1159):51 abstract
  13. Hypoglycemia with Fluoroquinolones. Med Let. 45(1162):64 abstract
  14. Gemifloxacin. 2004. Med Let. 46(1192):78 abstract
  15. Gafter-Gvlli A, Fraser A, Paul M, Lelbovici L. 2005. Ann Intern Med. 142(12):679
  16. Hypo- and Hyperglycemia with Gatifloxacin. 2006. Med Let. 48(1230):24
  17. Park-Wyllie LY, Juurlink DN, Kopp A, et al. 2006. NEJM. 354(13):1352 abstract