One of the most crucial quinolone group members was Nalidixic Acid. The Problem with this compound was that it was a narrow spectrum, and it has moderate gram-negative activity, but it has no gram-positive activity. Apart from this issue, the nalidixic acid was poorly distributed in the body.so; over time, scientists added fluorine with mother compound, i.e. Nalidix acid so “a group of antibiotics which are fluorinated analogs of nalidixic acid are called fluoroquinolones.”
Why are they so important?
A)Very Good Oral Absorption.
B)Perfect distribution means deep penetration in the tissues very efficiently.because of their deep penetration they can kill intracellular organisms.e.g chlamydia,TB,Legionella,Brucella.
C)Newer agents are a vast spectrum.
D)They have high potency.
E)They are very well tolerated (Very safe drugs compare to antibiotic other medicines)
Mechanism of action of quinolones :
These drugs are bactericidal, But the question is how they kill the bacteria?
They are working on enzymes called topoisomerases or DNA Gyrase.
Quinolones and fluoroquinolones inhibit bacterial replication by blocking their DNA replication pathway. DNA is the core genetic material of the cells and is responsible for the cell’s proper functioning. During protein synthesis and DNA replication, the double-stranded DNA needs to unwind into a single-stranded structure, which allows for complementary base pairing to occur and synthesis of mRNA to proceed. Typically, enzymes in the bacteria called DNA gyrase or DNA topoisomerase do this unwinding of DNA in the bacteria. DNA gyrase is a topoisomerase II type enzyme that unwinds the DNA by introducing negative supercoils and relaxing positive supercoils. Quinolones and fluoroquinolones inhibit this enzyme by binding to the A-subunit of the enzyme due to which the bacteria are unable to replicate or even synthesize proteins.
When we give the patient fluoroquinolones, they approach the topoisomerase enzyme and work on ligase point and make it dysfunctional.
Initially, the quinolone and fluoroquinolones first and second-generation drugs were the best work on gram-negative bacteria.but the newer group work on both grams negative and gram-positive.
Classification of quinolones and fluoroquinolones
The first generation, i.e., Nalidix acid is the only quinolone other three classes are fluoroquinolones. Other compounds are the derivatives of nalidixic acid. Following are some classes of quinolones and fluoroquinolones ;
- (A)First Generation e.g., Nalidixic acid
- (B)Second Generation, e.g, Ciprofloxacin (Ciproxin), Norfloxacin, and ofloxacin.
- Norfloxacin doesn’t absorb very well, and they are not used most commonly, While ciprofloxacin is the most widely used drug in this class.
- (C)Third Generation e.g., Levofloxacin
- (D)Fourth Generation: Moxifloxacin
The spectrum of activity:
- 1)First Generation Nalidix acid is moderately effective (Not very useful) against gram-negative bacteria. This drug is not used these days because of poor distribution in the body, so it is used in rare uncomplicated urinary tract infections. This drug is eliminated from the body through the renal system, and it concentrates on the urinary system.
- They become more efficient against gram-negative as compare to Nalidixic acid. And Also, have some less gram-positive coverage but keep in mind it doesn’t work on streptococcus pneumonia.
- Ciprofloxacin (Ciproxin) is also effective against atypical organisms like chlamydia,mycoplasma. Both of these organisms cause respiratory tract infections.
- This means the second generation has expanded its spectrum from moderate to more effective against gram-negative bacteria, some added benefits to gram-positive bacteria, and atypical organisms.
Uses / Indications
Where not to use this antibiotic?
- Don’t use this antibiotic more often because of the development of resistant strain, and due to over usage, ciprofloxacin is failing against bacteria because of the development of resistance.
- Every doctor knows there is one resistance type of organism, i.e, MRSA (Methicillin resistance staphylococcus aureus ). It is resistant to many other antibiotics, and the latest news is that even ciprofloxacin (Ciproxin) is failing.
- Don’t use this drug in Pneumococcus and Enterococcus infections.
Where to Use Ciprofloxacin?
- A)GIT: Its very effective in traveler diarrhea caused by toxic ecoli.
- B)Ciprofloxacin is more effective in cystic fibrosis due to infection by pseudomonas auregenosa.
- Usually, fluoroquinolones are contraindicated in children under the age of 18 because, in the animal model, it is approved that fluoroquinolones can damage the cartilages and produce arthropathy, so it should not be used in pregnant women.
3)Third Generation: Levofloxacin
- Good against gram-negative but has more activity against gram-positive, including streptococcus pneumonia, means levofloxacin can be used in pneumonia. That is why this is also called respiratory quinolones.
- Levofloxacin is also effective against chlamydia, mycoplasma, and atypical pneumonia.
- DON’T Use this antibiotic
- If you are allergic to this drug or other drugs of this class like ciprofloxacin, norfloxacin, and moxifloxacin.
- Avoid taking antacids, vitamin or mineral supplements, sucralfate (Carafate), or didanosine (Videx) powder or chewable tablets within 2 hours before or after taking levofloxacin.
- Before taking levofloxacin, tell your doctor if you have muscle weakness, kidney or liver disease, or trouble breathing, seizures, joint problems, diabetes, myasthenia gravis, a history of head injury of brain tumor, a condition called pseudotumor cerebri, a personal or family history of Long QT syndrome, low levels of potassium in your blood, or if you have ever had an allergic reaction to an antibiotic.
- Levofloxacin may cause swelling or tear of a tendon, especially in the Achilles’ tendon of the heel. These effects may be more likely to occur if you are over 60 or have had a kidney, heart, or lung transplant.
- If you take steroid medication, Stop taking levofloxacin and call your doctor at once if you have sudden pain, swelling, tenderness, stiffness.
- Levofloxacin is used to treat bacterial infections that cause bronchitis or pneumonia, which means that this drug’s action is more extended against pneumococci and used to treat people who have been exposed to anthrax or plague.
- Levofloxacin is also used to treat bacterial infections of the sinuses, skin, kidneys, bladder, or prostate.4)Fourth Generation.Moxifloxacin
- Levofloxacin and moxifloxacin are both called respiratory quinolones.
- Its spectrum of activity further broadens against gram-positive cocci and gram-positive bacilli.
- Moxifloxacin can kill the anaerobic organisms, and this can be used in mixed infection.
- Moxifloxacin is used to treat a variety of bacterial infections. It works by stopping the growth of bacteria.
- Moxifloxacin is used to treat bacterial infections, including:
- community-acquired pneumonia, throat, sinus, and lung infections, stomach infections, and skin infections
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