Bronchitis,Chronic Bronchitis - Fluoroquinolone Antibiotics Classification, Uses and Side Effects
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Fluoroquinolone Antibiotics Classification, Uses and Side Effects

The fluoroquinolones are a relatively new group of antibiotics. Fluoroquinolones were first introduced in 1986, but they are really modified quinolones, a class of antibiotics, whose accidental discovery occurred in the early 1960.

The fluoroquinolones are a family of synthetic, broad-spectrum antibacterial agents with bactericidal activity. The parent of the group is nalidixic acid, discovered in 1962 by Lescher and colleagues. The first fluoroquinolones were widely used because they were the only orally administered agents available for the treatment of serious infections caused by gram-negative organisms, including Pseudomonas species.


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 The newer fluoroquinolones have a wider clinical use and a broader spectrum of antibacterial activity including gram-positive and gram-negative aerobic and anaerobic organisms. Some of the newer fluoroquinolones have an important role in the treatment of community-acquired pneumonia and intra-abdominal infections.

Fluoroquinolones disadvantages:


Tendonitis or tendon rupture
Multiple drug interactions
Not used in children
Newer quinolones produce additional toxicities to the heart that were not found with the older agents


Fluoroquinolones advantages:


Ease of administration
Daily or twice daily dosing
Excellent oral absorption
Excellent tissue penetration
Prolonged half-lives
Significant entry into phagocytic cells
Efficacy
Overall safety


Classification of Fluoroquinolones

As a group, the fluoroquinolones have excellent in vitro activity against a wide range of both gram-positive and gram-negative bacteria. The newest fluoroquinolones have enhanced activity against gram-positive bacteria with only a minimal decrease in activity against gram-negative bacteria. Their expanded gram-positive activity is especially important because it includes significant activity against Streptococcus pneumoniae.

First Generation. The first-generation agents include cinoxacin and nalidixic acid, which are the oldest and least often used quinolones. These drugs had poor systemic distribution and limited activity and were used primarily for gram-negative urinary tract infections. Cinoxacin and nalidixic acid require more frequent dosing than the newer quinolones, and they are more susceptible to the development of bacterial resistance.

Second Generation. The second-generation fluoroquinolones have increased gram-negative activity, as well as some gram-positive and atypical pathogen coverage. Compared with first-generation quinolones, these drugs have broader clinical applications in the treatment of complicated urinary tract infections and pyelonephritis, sexually transmitted diseases, selected pneumonias and skin infections.

Second-generation agents include ciprofloxacin, enoxacin, lomefloxacin, norfloxacin and ofloxacin. Ciprofloxacin is the most potent fluoroquinolone against P. aeruginosa. Ciprofloxacin and ofloxacin are the most widely used second-generation quinolones because of their availability in oral and intravenous formulations and their broad set of FDA-labeled indications.

Third Generation. The third-generation fluoroquinolones are separated into a third class because of their expanded activity against gram-positive organisms, particularly penicillin-sensitive and penicillin-resistant S. pneumoniae, and atypical pathogens such as Mycoplasma pneumoniae and Chlamydia pneumoniae. Although the third-generation agents retain broad gram-negative coverage, they are less active than ciprofloxacin against Pseudomonas species.

Because of their expanded antimicrobial spectrum, third-generation fluoroquinolones are useful in the treatment of community-acquired pneumonia, acute sinusitis and acute exacerbations of chronic bronchitis, which are their primary FDA-labeled indications. The third-generation fluoroquinolones include levofloxacin, gatifloxacin, moxifloxacin and sparfloxacin.

Fourth Generation. The fourth-generation fluoroquinolones add significant antimicrobial activity against anaerobes while maintaining the gram-positive and gram-negative activity of the third-generation drugs. They also retain activity against Pseudomonas species comparable to that of ciprofloxacin. The fourth-generation fluoroquinolones include trovafloxacin (Trovan).

Because of concern about hepatotoxicity, trovafloxacin therapy should be reserved for life- or limb-threatening infections requiring inpatient treatment (hospital or long-term care facility), and the drug should be taken for no longer than 14 days.

Side effects

The fluoroquinolones as a class are generally well tolerated. Most adverse effects are mild in severity, self-limited, and rarely result in treatment discontinuation. However, they can have serious adverse effects.

Fluoroquinolones are approved for use only in people older than 18. They can affect the growth of bones, teeth, and cartilage in a child or fetus. The FDA has assigned fluoroquinolones to pregnancy risk category C, indicating that these drugs have the potential to cause teratogenic or embryocidal effects. Giving fluoroquinolones during pregnancy is not recommended unless the benefits justify the potential risks to the fetus. These agents are also excreted in breast milk and should be avoided during breast-feeding if at all possible.


Gastrointestinal effects. The most common adverse events experienced with fluoroquinolone administration are gastrointestinal (nausea, vomiting, diarrhea, constipation, and abdominal pain), which occur in 1 to 5% of patients.
CNS effects. Headache, dizziness, and drowsiness have been reported with all fluoroquinolones. Insomnia was reported in 3-7% of patients with ofloxacin. Severe CNS effects, including seizures, have been reported in patients receiving trovafloxacin. Seizures may develop within 3 to 4 days of therapy but resolve with drug discontinuation. Although seizures are infrequent, fluoroquinolones should be avoided in patients with a history of convulsion, cerebral trauma, or anoxia. No seizures have been reported with levofloxacin, moxifloxacin, gatifloxacin, and gemifloxacin. With the older non-fluorinated quinolones neurotoxic symptoms such as dizziness occurred in about 50% of the patients.
Phototoxicity. Exposure to ultraviolet A rays from direct or indirect sunlight should be avoided during treatment and several days (5 days with sparfloxacin) after the use of the drug. The degree of phototoxic potential of fluoroquinolones is as follows: lomefloxacin > sparfloxacin > ciprofloxacin > norfloxacin = ofloxacin = levofloxacin = gatifloxacin = moxifloxacin.
Musculoskeletal effects. Concern about the development of musculoskeletal effects, evident in animal studies, has led to the contraindication of fluoroquinolones for routine use in children and in women who are pregnant or lactating.
Tendon damage (tendinitis and tendon rupture). Although fluoroquinolone-related tendinitis generally resolves within one week of discontinuation of therapy, spontaneous ruptures have been reported as long as nine months after cessation of fluoroquinolone use. Potential risk factors for tendinopathy include age >50 years, male gender, and concomitant use of corticosteroids.
Hepatoxicity. Trovafloxacin use has been associated with rare liver damage, which prompted the withdrawal of the oral preparations from the U.S. market. However, the IV preparation is still available for treatment of infections so serious that the benefits outweigh the risks.
Cardiovascular effects. The newer quinolones have been found to produce additional toxicities to the heart that were not found with the older compounds. Evidence suggests that sparfloxacin and grepafloxacin may have the most cardiotoxic potential.
Hypoglycemia/Hyperglycemia. Recently, rare cases of hypoglycemia have been reported with gatifloxacin and ciprofloxacin in patients also receiving oral diabetic medications, primarily sulfonylureas. Although hypoglycemia has been reported with other fluoroquinolones (levofloxacin and moxifloxacin), the effects have been mild.
Hypersensitivity. Hypersensitivity reactions occur only occasionally during quinolone therapy and are generally mild to moderate in severity, and usually resolve after treatment is stopped.

 
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Conditions treated with Fluoroquinolones: indications and uses

The newer fluoroquinolones have a wider clinical use and a broader spectrum of antibacterial activity including gram-positive and gram-negative aerobic and anaerobic organisms. Some of the newer fluoroquinolones have an important role in the treatment of community-acquired pneumonia and intra-abdominal infections. The serum elimination half-life of the fluoroquinolones range from 3 -20 hours, allowing for once or twice daily dosing.

All of the fluoroquinolones are effective in treating urinary tract infections caused by susceptible organisms. They are the first-line treatment of acute uncomplicated cystitis in patients who cannot tolerate sulfonamides or TMP, who live in geographic areas with known resistance > 10% to 20% to TMP-SMX, or who have risk factors for such resistance.


Urinary tract infections (norfloxacin, lomefloxacin, enoxacin, ofloxacin, ciprofloxacin, levofloxacin, gatifloxacin, trovafloxacin)
Lower respiratory tract infections (lomefloxacin, ofloxacin, ciprofloxacin, trovafloxacin)
Skin and skin-structure infections (ofloxacin, ciprofloxacin, levofloxacin, trovafloxacin)
Urethral and cervical gonococcal infections (norfloxacin, enoxacin, ofloxacin, ciprofloxacin, gatifloxacin, trovafloxacin)
Prostatitis (norfloxacin, ofloxacin, trovafloxacin)
Acute sinusitis (ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin (Avelox), trovafloxacin)
Acute exacerbations of chronic bronchitis (levofloxacin, sparfloxacin (Zagam), gatifloxacin, moxifloxacin, trovafloxacin)
Community-acquired pneumonia (levofloxacin, sparfloxacin, gatifloxacin, moxifloxacin, trovafloxacin)




Yury Bayarski is the author of OriginalDrugs.com - website, offering patches and natural health products. More information about antibiotic medications is available on author's website.

 
 
     
 
 





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