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Flashcards in Fluoroquinolones Deck (36):

fluoroquinolones are derivates of

nalidixic acid


when fluoroquinolones were developed their main benefits were

Broad spectrum of activity
Improved PK properties – excellent oral bioavailability, tissue penetration, long half-lives


fluoroquinolones mechanism of action

Inhibit DNA synthesis by inhibiting bacterial topoisomerases necessary for DNA synthesis

FQs display rapid, concentration-dependent bactericidal activity


primary target of fluoroquinolones in gram (-) bacteria

DNA gyrase (topoisomerase II) – removes excess positive supercoiling in the DNA helix
- FQs form stable complex with DNA and DNA gyrase, which blocks DNA replication
- Primary target in gram-negative bacteria


primary target of fluoroquinolones in gram (+) bacteria

Topoisomerase IV – essential for separation of interlinked daughter DNA molecules
-FQs interfere with separation of daughter cells
-Primary target for many gram-positive bacteria


Mechanisms of Resistance of fluoroquinolones

• Altered target sites – chromosomal mutations in genes that code for DNA gyrase or topoisomerase IV lead to decreased binding affinity
-Most important and most common
• Expression of active efflux – transfers FQs out of cell
• Altered cell wall permeability – decreased porin expression
• Plasmid mediated resistance
• Cross-resistance occurs between FQs (if resistant to one it will be resistant to them all)


The Available FQs

Ciprofloxacin (Cipro®) – PO, IV

Levofloxacin (Levaquin®) – PO, IV
Moxifloxacin (Avelox®) – PO, IV


which FQs have the best gram positive aerobe activity

Moxifloxacin and levofloxacin


target organism for newer FQs

Streptococcus pneumoniae (including PRSP)*


which FQs have activity against Pseudomonas?

ciprofloxacin and levofloxacin with best activity but significant resistance has evolved (originally was the target organism)

NOT moxi


which FQs have the best activity against Enterbacteriaceae and H. influenzae

cipro and levo (best gram - aerobe activity)


which FQ is best for anaerobes

Moxifloxacin (but more and more resistance is developing)


which FQs have the best activity against atypically bacteria such as

Legionella pneumophila – DOC*
Chlamydophila and Chlamydia spp.
Mycoplasma spp.
Ureaplasma urealyticum

All have good activity


FQ absorption

very good bioavailability when given orally


FQ distribution

Extensive tissue distribution – lung; skin/soft tissue and bone; urinary tract and prostate (cipro, levo)

Moxi has good CSF penetration


FQ elimination

Renally eliminated: levofloxacin (90%), ciprofloxacin (60%), gemifloxacin (36%)
Dosage adjustment required in the presence of renal insufficiency

Hepatically eliminated: moxifloxacin (80%)


Fluoroquinolones most common clinical use

respiratory tract infections

Upper Respiratory Tract Infections
Sinusitis, bronchitis– levo, moxi, gemi, cipro

Lower Respiratory Tract Infections
• Community-acquired pneumonia - levo, moxi, gemi (Not cipro due to poor gram + coverage)
• Nosocomial (hospital acquired) pneumonia – anti-pseudomonal FQ’s: cipro (in combination with Gram + agent) & levo
• Exacerbations in cystic fibrosis - cipro


clinical uses for FQs

• Respiratory tract infections
• Urinary tract infections pyelonephritis, prostatitis – cipro, levo
• Other: bone, intraabdominal (with metronidazole), STDs, TB (levo, moxi)


 Adverse Effects

MANY - At least 7 FQs have been removed from the market due to adverse effects

Most common are GI and CNS
Prolongation on QTc interval
Tendonitis, tendon rupture
Hepatotoxicity, photosensitivity, hypersensitivity, rash, articular damage


cardiac adverse effects for FQs

• Prolongation of QTc interval – may lead to Torsades
• Use with caution in patients with hypokalemia, preexisting QT prolongation, concomitant antiarrhythmics
• Use caution in combination with other drugs that prolong the QT (effects can be additive)

get a baseline Ekg before starting


which patient populations are FQs contraindicated for

contraindication in pediatric patients and pregnant or breastfeeding women due to the articular cartilage damage


important drug interactions with FQs

• Divalent and trivalent cations – ALL PO FQs
Zinc, Iron, Calcium, Aluminum, Magnesium
Antacids, sucralfate, didanosine, enteral feedings, calcium-rich foods (orange juice)
Impair absorption of orally-administered FQs – may lead to CLINICAL FAILURE
Administer doses 2 to 4 hours apart; administer the FQ first
• Warfarin – idiosyncratic, all FQs
• Theophylline and Cyclosporine - cipro
Inhibition of metabolism → ↑ levels, ↑ toxicity


best FQs for community acquired pneumonia

levo, moxi, gemi


best FQs for healthcare associate pneumonia

cipro (w/ another antibiotic for gram + coverage), levo

HCAP needs to cover pseudomas


which FQs are good for Sinusitis, bronchitis



which FQs are good for UTI, prostatitis

cipro, levo


what is Metronidazole active against

protozoa and anaerobes


what is metronidazones mechanism of action

given as a prodrug that ultimatly becomes activated and inhibits DNA synthesis of the bacteria

Metronidazole displays concentration-dependent bactericidal activity


mechanisms of resistance for metronixazone

both are fairly uncommon

1. Altered growth requirements – organisms grows in higher local oxygen concentrations causing decreased activation of metronidazole
2. Altered ferredoxin levels – reduced transcription of the ferredoxin gene; less activation of metronidazole


target organisms for metronidazones

bacteroides ssp. and clostridium spp


metronidazone absorption

available IV and PO
Rapidly and completely absorbed (F > 90%); food with minimal effect on absorption


metronidazone distribution

Good serum concentrations with PO or IV
Well absorbed into body tissues and fluids; **DOES penetrate the CSF


metronidazone elimination

Metronidazole is primarily metabolized by the liver (metabolites excreted in urine); 6 to 15% excreted in the feces; half-life is 6 to 8 hours

Metronidazole is removed during hemodialysis


clinical uses of metronidazone

Anaerobic Infections (including in the CNS)
Intraabdominal, pelvic, skin/soft tissue, diabetic foot and decubitus ulcer infections; brain abscess

Pseudomembranous colitis due to C. difficile
Metronidazole is the drug of Choice for MILD to MODERATE c.dif disease
PO or IV

Bacterial vaginosis, Trichomonas, Amebiasis, H. pylori, Rosacea, Gingivitis


adverse reactions to metronidazone

• Gastrointestinal- Most common ADR
Nausea, vomiting, stomatitis, metallic taste
• CNS – most serious
Peripheral neuropathy*, seizures, encephalopathy
Use with caution in patients with preexisting CNS disorders
Requires discontinuation of metronidazole
• Mutagenicity, carcinogenicity
Avoid during pregnancy and breastfeeding*


metronidazone drug interactions

warfarin- ↑ Anticoagulant effect
alcohol - sever nausea and flushing (Disulfiram reaction)