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Essay: Understanding Fluoroquinolones: How These Antibiotics Treat Infections and Their Importance in Medicine

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  • Published: 1 April 2019*
  • Last Modified: 23 July 2024
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  • Words: 1,171 (approx)
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Fluoroquinolones are types of antibiotics which are useful in treating a wide range of infectious diseases in the human body, and these antibiotics stem from the general classification of Quinolone.  There are a total of four generations of Fluoroquinolone which have been used for medicinal purposes.  Not all of the antibiotics classified in these four generations are currently in use in clinical settings since some have been discontinued and are not being prescribed or used to treat patients any longer.  As mentioned before, Fluoroquinolone antibiotics are known to be a type of Quinolone, and they were created in order to be more effective in antibiotic use than Quinolones through the alteration of the backbone as a nitrogen and fluorine atom were added (Redgrave, Sutton, Webber, & Piddock, 2014).  This structure of the antibiotic is important to the function and capability of Fluoroquinolones, and the creation of new generations has helped in creating stronger antibiotics which can further withstand resistance of certain infections to these antibiotics and which can prove to be more effective against gram-positive and gram-negative bacteria.  

When a Fluoroquinolone is introduced into the body to fight an infection, the antibiotic localizes bacterial type II topoisomerases in order to prevent DNA gyrase and topoisomerase IV from assisting in the DNA replication process (2014).  DNA gyrase and topoisomerase IV are type II topoisomerases, and they both work to unwind supercoiled DNA, so fluoroquinolones’ objective is to restrict these type II topoisomerases from continuing the DNA replication process (2014).  In order to do this, the Fluoroquinolone binds first to the DNA in order to be able to specifically bind to either DNA gyrase or topoisomerase IV after passing through the DNA which was fragmented.  The binding of the antibiotic to either DNA gyrase or topoisomerase IV depends on whether the bacteria is gram-positive or gram-negative.  The antibiotic will bind to DNA gyrase in a bacteria which is gram-negative whereas in a gram-positive bacteria, the antibiotic will bind to topoisomerase IV (2014).  This bound Fluoroquinolone will disable the DNA from winding back or closing off after the antibiotics entrance, and the DNA which is fragmented in order for the Fluoroquinolone to reach the type II topoisomerases is known as a cleaved complex (2014).  Therefore, when working to stop an infection, Fluoroquinolones disrupt not only the replication of DNA but the restoration of the DNA to the proper form as well (Bolon, 2009).

The last Fluoroquinolones which have been introduced are the fourth generation Fluoroquinolones.  These have proven to be effective in their use against both gram-positive and gram-negative bacteria, being able to perform the antibiotic abilities of previous generations while simultaneously excelling in ability compared to those used previously, showing how these antibiotics have been created and altered through generations in order to be able to fight infections and resistance coming from mutations (Mather, Karenchak, Romanowski, & Kowalski, 2002).  Previously, the antibiotics introduced were those in the first, second, and third generations.  The Fluoroquinolones present in the first generation included nalidixic acid and cinoxacin while those in the second generation included norfloxacin, ciprofloxacin, lomefloxacin, ofloxacin, and levofloxacin (Redgrave, Sutton, Webber, & Piddock, 2014).  Although many Fluoroquinolones were created, not all are still in use today.  For example, the antibiotics in the third generation include three antibiotics by the names of sparfloxacin, gatifloxacin, and grepafloxacin, and none of these are currently being used in clinical settings (2014).  The fluoroquinolone antibiotics which are currently still being utilized are nalidixic acid, norfloxacin, ciprofloxacin, ofloxacin, levofloxacin, and two antibiotics in the fourth generation which are moxifloxacin and gemifloxacin, excluding a third fourth generation antibiotic of trovafloxacin (2014).  These fluoroquinolone antibiotics, along with a few others, have advanced after each generation through alterations which make them more effective, and they have also proven to be more effective when there is proper selection of these antibiotics by those individuals administering them (Ball, 2000).  The table below from a journal published by the University of Birmingham provides a list of the four generations of fluoroquinolones as well as a description as to whether they are still in use in clinical settings and in what form they are being utilized.

When analyzing the generations of fluoroquinolones, Peter Ball of the University of St. Andrews provides information on what each generation, up to the third-generation, was capable of doing, and Maureen K. Bolon of the Northwestern University Feinberg School of Medicine also provides insight into this and includes the fourth-generation through a journal published after that of Andrews.  Andrews mentions how the first-generation of fluoroquinolones were mainly utilized in order to treat urinary tract infections (2000).  In a later study, Bolon mentions how the first-generation of fluoroquinolones focused mainly on combating gram-negative bacteria with little focus on gram-positive bacteria (2009).  Further information shows how the second-generation of fluoroquinolones were developed in order to enhance the capability of the first generation antibiotics with a focus on increasing the potency or resistance against gram-negative bacteria with a small improvement when it comes to gram-positive bacteria (2009).  The third-generation of fluoroquinolones were adapted and created to be used for respiratory tract infections, and this generation was the first to specifically provide a greater amount of defense when it comes to gram-positive bacteria.  Previous generations were mainly focused on attacking gram-negative bacteria with a slight focus on gram-positive bacteria.  This changed with the introduction of the third-generation of fluoroquinolones.  Both the second and third generations have two different agents each, so there are 2A, 2B, 3A, and 3B agents with a slight variance in the activity performed by each.  The fourth-generation of fluoroquinolones, as mentioned previously, perform the same antibiotic abilities as previous generations with a focus on a greater amount of ability to fight pneumococci and anaerobes (2009).

Another aspect which was subject to change through these generations was the dosage amount given to individuals.  As newer fluoroquinolones were developed, this allowed the potency and strength of these antibiotics to increase and simultaneously permit for the antibiotics to be given to patients less often, enabling them to be given to patients on a daily basis instead of more than once a day.  The table below, from a journal by Maureen K. Bolon, shows the dosages along with the bioavailability, protein binding, half-life, elimination, and formulation of four different fluoroquinolones, with Ciprofloxacin being from the second generation and the antibiotic having to be given to the patient most often from the table provided (2009).  

The fluoroquinolones which have been developed have proven to advanced after each generation both in their capabilities and the amount having to be given to patients in need of the antibiotic.  Along with these advances, the newer generations of fluoroquinolones have also been developed in response to fluoroquinolone resistance which has occurred in previous generations.  This resistance can be due to different types of a certain bacteria arising, from the over use of a certain antibiotic along or mutations which can occur in certain genes.  Fluoroquinolone resistance occurs through different mechanisms which include target-site mutation, transmissible resistance, membrane permeability, and efflux (Redgrave, Sutton, Webber, & Piddock, 2014).  Each of these mechanisms and the reason for resistance will be explained further throughout the essay.  

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