Quinolone

WikiDoc Resources for Quinolone

Articles

Most recent articles on Quinolone

Most cited articles on Quinolone

Review articles on Quinolone

Articles on Quinolone in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Quinolone

Images of Quinolone

Photos of Quinolone

Podcasts & MP3s on Quinolone

Videos on Quinolone

Evidence Based Medicine

Cochrane Collaboration on Quinolone

Bandolier on Quinolone

TRIP on Quinolone

Clinical Trials

Ongoing Trials on Quinolone at Clinical Trials.gov

Trial results on Quinolone

Clinical Trials on Quinolone at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Quinolone

NICE Guidance on Quinolone

NHS PRODIGY Guidance

FDA on Quinolone

CDC on Quinolone

Books

Books on Quinolone

News

Quinolone in the news

Be alerted to news on Quinolone

News trends on Quinolone

Commentary

Blogs on Quinolone

Definitions

Definitions of Quinolone

Patient Resources / Community

Patient resources on Quinolone

Discussion groups on Quinolone

Patient Handouts on Quinolone

Directions to Hospitals Treating Quinolone

Risk calculators and risk factors for Quinolone

Healthcare Provider Resources

Symptoms of Quinolone

Causes & Risk Factors for Quinolone

Diagnostic studies for Quinolone

Treatment of Quinolone

Continuing Medical Education (CME)

CME Programs on Quinolone

International

Quinolone en Espanol

Quinolone en Francais

Business

Quinolone in the Marketplace

Patents on Quinolone

Experimental / Informatics

List of terms related to Quinolone

Nalidixic acid

Ciprofloxacin

Levofloxacin

Trovafloxacin

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]

## Overview[edit | edit source]

The quinolones are a family of broad-spectrum antibiotics. The parent of the group is nalidixic acid. The majority of quinolones in clinical use belong to the subset of fluoroquinolones, which have a fluoro group attached the central ring system, typically at the 6-position.

## Mechanism[edit | edit source]

Quinolones and fluoroquinolones are bactericidal drugs, actively killing bacteria. Quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription. Quinolones can enter cells easily and therefore are often used to treat intracellular pathogens such as Legionella pneumophila and Mycoplasma pneumoniae. For many gram-negative bacteria DNA gyrase is the target, whereas topoisomerase IV is the target for many gram-positive bacteria. Eukaryotic cells do not contain DNA gyrase or topoisomerase IV.

## Adverse effects[edit | edit source]

Quinolone antibiotics were once considered relatively safe, but several side-effects have become evident with experience. For example, numerous case reports have implicated their use since 1965 in spontaneous tendon ruptures or damage, especially with the concurrent use of a systemic corticosteroid. In the fall of 2004, the Food and Drug Administration upgraded the warnings found within the package inserts for all drugs within this class regarding such serious adverse reactions. It is important to note, however, that the incidence of this is quite rare, with occurrences at less than one per ten thousand person-years.[1]

* Peripheral neuropathy (nerve damage): "Rare cases of sensory or sensor motor axonal polyneuropathy affecting small and or large axons resulting in paresthesias, hypoaesthesias, dysesthesias, and weakness have been reported in patients taking quinolones. Therapy should be discontinued if the patient experiences symptoms of neuropathy, including pain, burning, tingling, numbness and/or weakness, or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength in order to prevent the development of an irreversible condition."

* Tendon damage: "Ruptures of the shoulder, hand, Achilles tendon, or other tendons that require surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones. Post-marketing surveillance reports indicate that this risk may be increased in patients receiving concomitant corticosteroids, especially the elderly. Fluoroquinolone therapy should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients should rest and refrain from exercise until diagnosis of tendinitis or tendon rupture had been excluded. Tendon rupture can occur during or after therapy with quinolones."

Other problems include:

* Heart problems (prolonged QT Interval / Torsades de pointes)
* Pseudomembranous colitis
* Rhabdomyolysis (breakdown of muscle tissue)
* Stevens-Johnson syndrome
* Lowered seizure threshold
* Hypoglycemia
* Kidney stones due to loss of Oxalobacter formigenes[2]

## Resistance[edit | edit source]

Resistance to quinolones can develop rapidly, even during a course of treatment. Numerous pathogens, including Staphylococcus aureus, enterococci, and Streptococcus pyogenes now exhibit resistance worldwide.[3] Widespread veterinary usage of quinolones, in particular in Europe, has been implicated.

There are three known mechanisms of resistance.[4] Efflux pumps can be used to decrease intracellular drug concentration. In gram-negative bacteria, plasmid-mediated resistance genes produce proteins that can bind to DNA gyrase, protecting it from the action of quinolones. Finally, mutations at key sites in DNA gyrase or topoisomerase IV can decrease their binding affinity to quinolones, decreasing the drug effectiveness.

## Generations[edit | edit source]

The quinolones are divided into generations based on their antibacterial spectrum. The earlier generation agents are, in general, more narrow spectrum than the later ones.

### 1st generation[edit | edit source]

* cinoxacin (Cinoxacin®)
* flumequine (Flubactin®) (Veterinary use)
* nalidixic acid (NegGam®, Wintomylon®)
* oxolinic acid
* piromidic acid
* pipemidic acid (Dolcol®)

### 2nd generation[edit | edit source]

* ciprofloxacin (Ciprobay®, Cipro®, Ciproxin®)
* enoxacin (Enroxil®, Penetrex®)
* fleroxacin (Megalone®) (withdrawn)
* lomefloxacin (Maxaquin®)
* nadifloxacin
* norfloxacin (Lexinor®, Noroxin®, Quinabic®, Janacin®)
* ofloxacin (Floxin®, Oxaldin®, Tarivid®)
* pefloxacin
* rufloxacin (Uroflox®)

### 3rd generation[edit | edit source]

* balofloxacin
* grepafloxacin (Raxar®) (withdrawn)
* levofloxacin (Cravit®, Levaquin®)
* pazufloxacin Mesilate
* sparfloxacin (Zagam®)
* temafloxacin (Omniflox®) (withdrawn)
* tosufloxacin

### 4th generation[edit | edit source]

* clinafloxacin
* gemifloxacin (Factive®)
* moxifloxacin (Avelox®)
* gatifloxacin (Tequin® (withdrawn), Zymar®)
* sitafloxacin
* trovafloxacin (Trovan®) (withdrawn)

### In development[edit | edit source]

* ecinofloxacin
* prulifloxacin

## Veterinary use[edit | edit source]

The quinolones have been widely used in agriculture and several agents exist which have veterinary but not human use.

* danofloxacin (Advocin, Advocid) (for veterinary use)
* difloxacin (Dicural, Vetequinon)
* enrofloxacin (Baytril) (for veterinary use)
* marbofloxacin (Marbocyl, Zenequin) (for veterinary use)
* orbifloxacin (Orbax, Victas) (for veterinary use)
* sarafloxacin (Floxasol, Saraflox, Sarafin) (for veterinary use)

## External links[edit | edit source]

* Fact Sheet: Quinolones
* The Flox Report An investigative approach to the true toxicity of quinolone antibiotics.
* Research on Adverse Effects of Fluoroquinolones
* Fluoroquinolone-Induced Tendinopathy: What do we know? Richard M. Harrell, MD.
* Fluoroquinolones "Family Practice Notebook" entry page for Fluoroquinolones
* Structure Activity Relationships "Antibacterial Agents; Structure Activity Relationships," André Bryskier MD

## References[edit | edit source]

1. ↑ Maury M. Breecher, PhD, MPH (October 17, 2003). "IDSA: Achilles Tendon Rupture after use of antibiotics". Doctor's Guide, Global Edition.CS1 maint: Multiple names: authors list (link)
2. ↑ [1] \- Interim reference; cites Troxel SA, Low RK. Intestinal Oxalobacter Formigenes Colonization Urinary Oxalate Levels in Calcium Oxalate Stone Formers. Journal of Urology 165:245A, 2001. (Please replace with that citation if the full text of the article agrees with the linked summary)
3. ↑ M Jacobs, Worldwide Overview of Antimicrobial Resistance. International Symposium on Antimicrobial Agents and Resistance 2005.
4. ↑ A Robicsek, GA Jacoby and DC Hooper, The worldwide emergence of plasmid-mediated quinolone resistance. 2006. The Lancet Infectious Diseases 6-10:629-640

Template:QuinoloneAntiBiotics

de:Fluorchinolone eu:Kinolona fo:Quinolon it:Chinoloni nl:Fluoroquinolone no:Quinoloner sk:Chinolón

Template:WikiDoc Sources