Fluoroquinolones & Metronidazole Flashcards
Fluoroquinolones
Developed in response to growing resistance.
Are FLUORINATED quinolones, hence the name.
Examples:
Ciprofloxacin
Levofloxacin
Moxifloxacin
Gemifloxacin
Fluoroquinolones Mech of Action
INHIBITION OF DNA SYNTHESIS by binding to/inhibiting topoisomerases.
FQs target DNA GYRASE (aka topoisomerase type II, required to undue supercoiling during replication; PRIMARY TARGET IN GRAM (-)) and TOPOISOMERASE IV (required to separate DNA into daughter cells; PRIMARY TARGET IN GRAM (+))
Fluoroquinolones- Bactericidal or Bacteriostatic
Concentration-dependent bactericidal;
AUC/MIC correlates w/ efficacy
Mechanisms of Resistance to Fluoroquinolone Abx
ALTERED BINDING SITES- decreased binding affinity of FQs to target sites
EXPRESSION OF ACTIVE EFFLUX- enhances transfer of FQs out of cell
ALTERED CELL WALL PERMEABILITY- decreased FQ accumulation w/i the cell (rare)
CROSS-RESISTANCE IS USUALLY OBSERVED BETWEEN THE FQs
The Available Fluoroquinolones
The main question is "Do they have activity against pneumococcus?" Older FQs: CIPROFLOXACIN Newer FQs (Respiratory FQs): LEVOFLOXACIN MOXIFLOXACIN
Fluoroquinolones Spectrum of Activity Gram (+)
Gram (+) Aerobes: older agents w/ poor activity; newer respiratory FQs w/ enhanced activity STREP. PNEUMO, INCL. PRSP MSSA (NOT MRSA) Group & Viridans Strep (limited) Enterococcus Spp. (limited)
Fluoroquinolones Spectrum of Activity Gram (-)
Gram (-) Aerobes: some FQs have excellent activity (CIPRO=LEVO>MOXI)
PSEUDOMONAS AERUGINOSA- significant resistance has emerged, cipro & levo have best activity, NOT MOXI
Enterobacter
H. influenzae
M. catarrhalis
Neisseria spp.
Fluoroquinolones Spectrum of Activity Anaerobes, Atypical bacteria, and others
Anaerobes:
ONLY MOXIFLOXACIN have adequate activity against Bacteroides spp.
Atypical bacteria: ALL FQs HAVE EXCELLENT ACTIVITY, INCL. LEGIONELLA PNEUMOPHILA- DOC CHLAMYDOPHILA AND CHLAMYDIA SPP. MYCOPLASMA SPP. UREAPLASMA UREALYTICUM
Other: TB, Bacillus anthracis
Fluoroquinolones- PAE?
FQs have post-antibiotic effect for both Gram (-) and Gram (+) bacteria
Fluoroquinolones Absorption
Have GOOD BIOAVAILABILITY after oral or IV administration
Fluoroquinolones Distribution
Extensive distribution, incl: LUNG BONE URINARY TRACT & PROSTATE (CIPRO, LEVO ONLY, THUS NOT MOXI FOR UTIS) MINIMAL CSF PENETRATION
Fluoroquinolones Elimination
Renally: CIPRO, LEVO, dosage adjustments necessary w/ renal insufficiency
Hepatically: MOXI
NONE OF THE FQs ARE REMOVED DURING HEMODIALYSIS!!!
Fluoroquinolones Clinical Uses- Upper Respiratory Infections (Sinusitis, ABECB)
LEVO
MOXI
GEMI
CIPRO
Fluoroquinolones Clinical Uses- Community-acquired pneumonia
LEVO
MOXI
GEMI
Fluoroquinolones Clinical Uses- Nosocomial pneumonia
LEVO
CIPRO
Fluoroquinolones Clinical Uses- Bacterial exacerbations in cystic fibrosis
CIPRO
Fluoroquinolones Clinical Uses- UTIs (cystitis, pyelonephritis, prostatitis)
LEVO
CIPRO
Fluoroquinolones Adverse Effects
G.I. CNS Hepatotoxicity (TROVA) Phototoxicity (uncommon) Cardiac (FQs USED W/ CAUTION W/ HYPOKALEMIA, CLASS III ANTIARRHYTHMICS, PREEXISTING QT PROLONGATION) Articular Cartilage Damage Tendonitis/Tendon Rupture DYSGLYCEMIAS (GATI removed from market)
Fluoroquinolones Drug Interactions
DIVALENT & TRIVALENT CATIONS- ALL PO FQs; IMPAIR ABSORPTION OF PO FQs, MAY LEAD TO CLINICAL FAILURE
Wafarin- ALL FQs
Theophylline & Cyclosporin- CIPRO
Metronidazole
First found active against protozoa, then against anaerobes where it is still extremely useful.
Metronidazole Mech of Action
INHIBITS DNA SYNTHESIS
- a prodrug activated by reduction
- selective toxicity against anaerobic and microaerophilic bacteria due to ferredoxins w/i these bacteria
Metronidazole- Bactericidal or Bacteriostatic?
Concentration-dependent Bactericidal
Mechanisms of Resistance against Metronidazole
ALTERED GROWTH REQUIREMENTS- organism grows in higher local oxygen [ ]s
ALTERED FERREDOXIN LEVELS
- well documented but uncommon
Metronidazole Spectrum of Activity
Anaerobic bacteria:
BACTEROIDES SPP. (ALL)
CLOSTRIDIUM (ALL)
others
Anaerobic Protozoa: Trichomonas vaginalis Entamoeba histolytica Giardia lamblia Gardnerella vaginalis
