Fluoroquinolones and Drugs for UTI Flashcards by Brendan Davis

Fluoroquinolone Drugs

Ciprofloxacin
Ofloxacin
Levofloxacin
Moxifloxacin
Gatifloxacin
Gemifloxacin
"COLe Might Get Goals"

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Fluoroquinolone MOA

Inhibition of DNA GYRASE (main target) - prevents relaxation of supercoiled DNA for transcription/replication
BACTERICIDAL

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Fluoroquinolone Spectrum

Aerobic G- rods
Good G+ coverage
Exception: Moxifloxacin and Gemifloxacin are effective against ANAEROBES

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Fluroquinolones effective against anaerobes

Moxifloxacin and Gemifloxacin

Only fluoroquinolones with “m” in the name

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Ciprofloxacin Use

UTIs (2nd line, Bactrim is DOC), ANTHRAX prophylaxis, P. aeruginosa, systemic infections

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Ofloxacin Use

PROSTATITIS, STDs (except syphilis), TB

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Levofloxacin Use

CAP alternative (Macrolide is DOC)

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CAP treatment

Macrolide (DOC) > Levofloxacin (or Gemifloxacin) > Telithromycin (has severe hepatotoxicity)

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Moxifloxacin

PCN-resistant S. pneumoniae

ANAEROBES

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Gatifloxacin

OCULAR application only

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Gemifloxacin

PCN-resistant S. pneumonia
ANAEROBES
CAP alternative (Macrolide is DOC)

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Fluoroquinolone Pharmacokinetics

Well absorbed ORALLY
Decreased absorption with CA, Mg, Al (antacids)
Widely distributed, EXCELLENT TISSUE PENETRATION
Poor CNS penetration
Excreted through kidney (can be blocked by probenecid)

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Fluoroquinolone Adverse Effects

GI disturbances
QT PROLONGATION
Cartilage erosions
Tendon rupture (more likely in men >50 w/ previous use of inhaled corticosteroids)
Photosensitivity
etc...

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Fluoroquinolone Contraindication

Pregnant
Nursing
Children <18 years old (cartilage damage)

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Fluoroquinolone Resistance

Plasmid mediated resistance:
Target site mutations (DNA gyrase/topoisomerase IV)
Reduced permeability
MDR efflux pump over-expression

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What is a prodrug?

Drug that must be metabolized or altered to be effective

Antibiotics that are prodrugs

METRONIDAZOLE - non-enzymatically reduced by reacting with reduced ferredoxin (only in anaerobes).
NITROFURANTOIN - reduced in bacterial cells to a highly reactive intemediate
METHENAMINE - decomposes to formaldehyde and ammonia in the acid medium of the urinary tract

Metronidazole Spectrum

ANAEROBES only! (G- and G+ bacilli)

Metronidazole Uses

Indicated for anaerobic or mixed intra-abdominal infections
VAGINITIS (bacterial vaginosis)
C diff (DOC, also oral vancomycin)
Endocarditis
RTI (respiratory tract infection)
H. pylori therapy (multi drug regimen)

Metronidazole Administration

Oral, IV, or topical

Metronidazole Metabolism

Liver metabolism

Eliminated in the urine

Metronidazole Adverse Reactions

DISULFIRAM-LIKE RXN
Disgeusia (Metallic taste)
GI disturbances
Central and peripheral nervous system toxicity: seizures and peripheral neuropathy with prolonged use
Hypersensitivity

Exclusive UTI Drugs

Nitrofurantoin

Methenamine

UTI Common Pathogens

E. coli (most community acquired infections: 70-80%)
Staph saprophyticus, G+ organism causes 10-15%
Proteus, Klebsiella, Seratia, Pseudomonas (G- from catheter-associated UTIs)

Why are nitrofurantoin and methenamine good for UTIs?

Renally excreted (where infection is) Concentration-dependent cidal activity: Achieve high urinary concentrations Bactericidal activity in the urine (do NOT achieve therapeutic concentrations anywhere else in body)

Nitrofurantoin MOA

Reduced to highly reactive intermediate in bacterial cells to attack ribosomes, DNA, metabolism, and other macromolecules (PRODRUG)

Nitrofurantoin Spectrum

WIDE Spectrum against G+ and G-: E. coli, S. pyogenes, Citrobacter, Klebsiella, Enterobacter, Salmonella, Shigella, Serratia, and indole positive Proteus Most PROTEUS and PSEUDOMONAS organisms are resistant!

Nitrofurantoin Use

Alternative uncomplicated UTI treatment (E. coli resistant to Bactrim and Fluoroquinolones)

Uncomplicated UTI Treatment

Bactrim > Fluoroquinolones > Nitrofurantoin

Nitrofurantoin Pharmacokinetics

Rapid and complete oral absorption Acidic urine (pH<5.5) increases therapeutic action Activity decreased when glomerular filtration impaired - can't get to site of action.

Nitrofurantoin Contraindication

Creatinine clearance is less than 50 mL/min Impaired renal function (abx can't get to site of infection) End of term Pregnancy (don't know babies G6PD status) <1 month of age Allergy

Nitrofurantoin Adverse Effects

Colors the urine brown! (normal, but tell patient) GI upset Allergic reactions HEMOLYTIC ANEMIA and hepatocellular damage in G6PD deficiency Pulmonary fibrosis with chronic usage Neurological disorders (demyelination and degeneration of neurons)

Methenamine MOA

Decomposes to formaldehyde and ammonia in the acid medium of the urinary tract --> Must be in ACIDIC environment to work.

Methenamine Administration

Oral. Well absorbed orally but some decomposition occurs in the stomach.

Methenamine Resistance

NONE!!! Only drug with no resistance. | Bacterial resistance to formaldehyde does not develop.

Methenamine Spectrum

Nearly all bacteria are SENSITIVE, but those that increase the pH of the urine inhibit the release of formaldehyde. Therefore, PROTEUS is resistant - should combine with a weak organic acid (hippuric acid)

Methenamine Toxicity

Essentially NON-TOXIC b/c little decomposition takes place until it is in the acidic urine. May cause GI distress Occasional Allergic Rxns

Methenamine Contraindications

Hepatic insufficiency - Liver can't deal with ammonia | Renal insufficiency - Can't get to site of infection