There are four generations of quinolones:
First generation: nalidixic acid, nitrofurantoin. Usually used in urinary tract infection. This group was called old quinolones.
Second generation: ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, and lomefloxacin. From this generation on, the next groups are called new quinolones/fluoroquinolones; due to their systemic effect.
Third generation: gatifloxacin, gemifloxacin, grepafloxacin, sparfloxacin
Fourth generation: moxifloxacin, trovafloxacin
Out of this classification, there is a group named respiratory quinolones; which contains fluoroquinolones that can be used to treat respiratory tract infections besides urinary tract infections and abdominal infections. Examples are: levofloxacin, gatifloxacin, and moxifloxacin.
Fluoroquinolones are different in indications due to their different structure, thus differing their spectrum. First generation quinolones have poor serum and tissue concentrations, have only small activity against Pseudomonas and Gram-positive bacteria. But the second generation has activity against Pseudomonas, the third one has activity against Gram-positive bacteria, and the fourth generation has activity against anaerob bacteria.
Fluoroquinolones have broad spectrum based on the organ/system of human body: respiratory tract infections, skin and soft tissue infections, digestive system, tuberculosis, anthrax, typhoid fever, etc. The broader spectrum, combined with convenient dosage (1-2 times daily) makes fluoroquinolones the perfect choice for many infectious diseases in adult.
Ciprofloxacin
The first quinolone which possesses systemic effect, not limited only in urinary tract. Until today, this is the most used fluoroquinolones. Ciprofloxacin works well against intestinal infections (including typhoid fever) and urinary tract. Some cases of respiratory also can be covered by ciprofloxacin. Ciprofloxacin can penetrate bone and skeletal muscle tissue, thus it can be used in osteomyelitis treatment.
Ciprofloxacin is often used for typhoid fever, even though this indication is still off-label in several countries. In Southern Asia, bacterial resistance against ciprofloxacin is getting higher.
Ofloxacin
Ofloxacin is effective for intestinal infection, urinary tract infection, gonorrhea (once it is recommended, but now not anymore), typhoid fever, and ear infection (otitis media).
Ofloxacin is recommended as first-line antibiotic for typhoid fever, based on WHO document in 2003 [for further information, see References]. Ofloxacin also had been proved as equally effective amongst 3-day course, 5-day course, and 10-day course against typhoid fever, in a study from Phillippines. [Tayag et al, 1997] But ofloxacin still possesses several weaknesses; such as interaction with theophylline. Ofloxacin itself is a racemic antibiotic, consists of L-enantiomer (later became levofloxacin) and R-enantiomer.
Levofloxacin
The next generation of fluoroquinolone, is the first member of respiratory quinolone and also suitable for skin infection. It is levofloxacin, L-enantiomer of ofloxacin. This fluoroquinolone is still effective against typhoid fever with faster defervescence (Read http://bit.ly/agP02U and http://bit.ly/8XzowY). Levofloxacin is has more convenient dose than ofloxacin and ciprofloxacin, with once-daily dose.
Moxifloxacin
Fourth generation of quinolone, is also a respiratory quinolone, and cure respiratory infections faster than other previous quinolones. Moxifloxacin's study from Keating et al (2006) has proved that bacterial rhinosinusitis could be cured with moxifloxacin in only 10 days, meanwhile levofloxacin needed 14 days. Moxifloxacin also showed lower recurrence rate than levofloxacin.
Gatifloxacin
Gatifloxacin, a new fluoroquinolone with stronger efficacy, had left fluoroquinolone market since 2006. Now it is only available as ophthalmic solution. A study from NEJM in 2006 proved that gatifloxacin was associated with higher risk of serious diabetes mellitus. Finally the medicine was pulled from the market since May 2006. Some sources suspected that the pull was caused by decreased market value, but many believed that diabetes risk was the real culprit.
Others
Trovafloxacin had been pulled from market since 2000 due to its evident hepatotoxicity effect. Sparfloxacin is also not available anymore in several countries due to its controversial cardiotoxic effect. Lomefloxacin is associated with higher phototoxicity effect, while besifloxacin, so far, is only available as ophthalmic solution 0.6% for bacterial conjunctivitis.
In Tuberculosis
For tuberculosis, fluoroquinolone is one of the second-line antibiotics, even though several of them are still not approved for this indication. Some suitable fluoroquinolones are levofloxacin and moxifloxacin (formerly, gatifloxacin too). Several literatures do not support ciprofloxacin in this indication. Usually fluoroquinolone is used when a TB patient is resistant against at least one of first line medicines (isoniazid, rifampicin, ethambutol, atau pyrazinamide). [Moadebi et al, 2007]
Black Box Warning and Contraindications
All fluoroquinolones have black box warning on their label: should not be given to children and adolescent under the age of 18 years old and pregnant women; due to arthropaty risk; should be given carefully to elderly due to risk of tendinitis, steroid users, and post-transplant patients.
About the use of fluoroquinolones in children, we have discussed about ciprofloxacin in previous article [click here]. Previous study also proved that the use fluoroquinolone in children with pneumonia due to cystic fibrosis was not associated with growth disturbance [Read http://bit.ly/br39Ab]. Ciprofloxacin, or all other fluoroquinolones; are suitable for this case, even when the involved bacterium is Pseudomonas.
About the use of fluoroquinolone and children, WHO has announced a statement circa 2010-2011 [Read http://bit.ly/cL52M7]. In this report, incidence of arthropathy due to quinolone treatment did not differ significantly with the use of azithromycin (a new macrolide). From these facts, we concluded that even though there has not been any absolute universal statement or consensus about the use of quinolones in children, physicians should be still carefully choose which group of children to be treated with fluoroquinolone. They also have to follow the local consensus of treatment.
Other "weakness" for fluoroquinolones, is that they are contraindicated in G6PD-deficient patients. This group of medicine causes hemolysis in these patients.
Adverse Effects and Interactions
Main adverse effect of fluoroquinolones is associated with gastrointestinal tract: nausea, vomiting, and diarrhea (for about 3-6%). Fluoroquinolones are often advised to be taken after meals to minimize this adverse effect. Other adverse effect is elevated blood glucose; which is more evident with gatifloxacin. The remainders are: headache, confusion, dizziness, and peripheral nerve symptoms.
Pharmacokinetic of fluoroquinolones are affected by antacids, sucralfate, or multivitamin with earth alkaline ion or transitional metals. These ions and fluoroquinolone form complex and this decreases effectivity of fluoroquinolone. If you have to take both of these medicines, the administration should be separated by at least 4 hours.
Next interaction of fluoroquinolone is that theophylline can decrease the clearance of fluoroquinolone, especially in high dose; due to the shared metabolism pathway (CYP1A2). But in newer fluoroquinolones, this effect is not very obvious.
Other interactions that should be warranted is with erithromycin and antiarrhythmic medicines.
As usual, your comments are welcomed!
References
Gurwitz JH. N Engl J Med 2006; 354: 1413-1415
Keating KN et al. Curr Med Res Opin 2006; 22(2): 327-33
Moadebi S et al. Drugs 2007; 67 (14): 2077-2099
Tayag EA et al. Phil J Microbiol Infect Dis 1997; 26 (3): 129-132
World Health Organization. The Diagnosis, treatment, and prevention of typhoid fever, 2003. Available from http://whqlibdoc.who.int/hq/2003/WHO_V&B_03.07.pdf
Yee CL et al. Pediatr Infect Dis J 2002; 21 (6): 525-9
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