Antibiotics (Quinolone )

antibiotic .(quinolone group):-



The newer fluoroquinolones have broad-spectrum bactericidal activity, excellent oral bioavailability, good tissue penetration and favorable safety and tolerability profiles. A new four-generation classification of the quinolone drugs takes into account the expanded antimicrobial spectrum of the more recently introduced fluoroquinolones and their clinical indications. First-generation drugs (e.g., nalidixic acid) achieve minimal serum levels. Second-generation quinolones (e.g., ciprofloxacin) have increased gram-negative and systemic activity. Third-generation drugs (e.g., levofloxacin) have expanded activity against gram-positive bacteria and atypical pathogens. Fourth-generation quinolone drugs (currently only trovafloxacin) add significant activity against anaerobes. The quinolones can be differentiated within classes based on their pharmacokinetic properties.

Overview of Fluoroquinolones:-

The fluoroquinolones are broad-spectrum antibiotics with particular activity against gram-negative organisms, especially Pseudomonas aeruginosa. These agents are well absorbed when given orally. Because tissue and fluid concentrations often exceed the serum drug concentration, these antibiotics are particularly useful for certain infections, such as pneumonia.4–6 Fluoroquinolones are usually well tolerated, with few side effects. However, they can have serious adverse effects

SIDE EFFECTS:-

The most common adverse effects of the fluoroquinolones are nausea, vomiting and diarrhea, which occur in 3 to 6 percent of recipients.5 Other more serious but less common side effects are central nervous system effects (headache, confusion and dizziness), phototoxicity (more common with lomefloxacin [Maxaquin] and sparfloxacin [Zagam]), cardiotoxicity (sparfloxacin) and hepatotoxicity (trovafloxacin .

CLINICALLY IMPORTANT PHARMACOKINETIC:-

The newer fluoroquinolone antibiotics also have improved pharmacokinetic parameters compared with the original quinolones. They are rapidly and almost completely absorbed from the gastrointestinal tract. Peak serum concentrations obtained after oral administration are very near those achieved with intravenous administration.3 Consequently, the oral route is generally preferred in most situations, and hospitalized patients should be switched from intravenous to oral formulations as soon as oral medications can be tolerated.

Absorption of orally administered fluoroquinolones is significantly decreased when these agents are coadministered with aluminum, magnesium, calcium, iron or zinc, because of the formation of insoluble drug–cationic chelate complexes in the gastrointestinal tract.3,10 The problem can be overcome largely by administering products containing these metal ions at least four hours before or two hours after oral administration of a fluoroquinolone. Because sucralfate (Carafate) contains aluminum, it can also reduce absorption of the quinolones. Adequate spacing of administration times has not been determined, and coadministration of quinolones and sucralfate should be avoided.

1.ciproflaxacine 

2.enoxicine

3.levoflaxacine

5.noreflaxacine

6.oflaxacine

7.travaflaxacine

the above 7 drugs have same group but different chemical structures & mechanism of actions.

New Classification of Quinolones

FIRST GENERATION

The first-generation agents include cinoxacin and nalidixic acid, which are the oldest and least often used quinolones. Because minimal serum levels are achieved, use of these drugs has been restricted to the treatment of uncomplicated 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. These agents are not recommended for use in patients with poor renal function because of significantly decreased urine concentrations.

SECOND GENERATION

The second-generation quinolones have increased gram-negative activity, as well as some gram-positive and atypical pathogen coverage. Compared with first-generation drugs and considered as a group, these agents 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.21,22 Because of its good penetration into bone, orally administered ciprofloxacin is a useful alternative to parenterally administered antibiotics for the treatment of osteomyelitis caused by susceptible organisms.

Although the FDA has labeled some second-generation quinolones for the treatment of lower respiratory tract infections and acute sinusitis, it should be stressed that S. pneumoniae is frequently resistant to agents in this class. Consequently, second-generation quinolones are not the drugs of first choice for lower respiratory tract infections and acute sinusitis.

Of the second-generation agents, ofloxacin has the greatest activity against Chlamydia trachomatis.

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 quinolones currently include levofloxacin, gatifloxacin, moxifloxacin and sparfloxacin. These agents 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.6,12,19 Although the third-generation quinolones retain broad gram-negative coverage, they are less active than ciprofloxacin against Pseudomonas species.

Because of their expanded antimicrobial spectrum, third-generation quinolones are useful in the treatment of community-acquired pneumonia, acute sinusitis and acute exacerbations of chronic bronchitis, which are their primary FDA-labeled indications. Gatifloxacin also has FDA-labeled indications for urinary tract infections and gonorrhea.20 Levofloxacin (the more active component of the ofloxacin racemic mixture12,21) and gatifloxacin are available in oral and intravenous formulations.

Sparfloxacin carries a significant risk of phototoxicity.21,23 Grepafloxacin, sparfloxacin and moxifloxacin have been reported to cause prolongation of the QT interval; gatifloxacin has not. However, the FDA recommends that all of these drugs should be avoided in patients who are taking drugs that are known to prolong the QT interval, such as tricyclic antidepressants, phenothiazines and class I antiarrhythmics.24 In contrast, levofloxacin does not affect the QT interval.

FOURTH GENERATION:-

Trovafloxacin, currently the only member of the fourth-generation class, adds significant antimicrobial activity against anaerobes while maintaining the gram-positive and gram-negative activity of the third-generation quinolones. It also retains activity against Pseudomonas species comparable to that of ciprofloxacin.17,18

Trovafloxacin is available in an oral tablet and as the prodrug alatrofloxacin (Trovan IV) in an intravenous formulation. Although the findings of few clinical trials on trovafloxacin have been published, the drug was originally labeled by the FDA for the treatment of a wide spectrum of infectious diseases.18 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.