Full Answer
What is fluoroquinolone antibiotic?
Fluoroquinolone antibiotics. The fluoroquinolones are a family of synthetic broad-spectrum antibiotics, which eradicate bacteria by interfering with DNA replication. However, the fluoroquinolones are relatively ineffective against intracellular pathogens. Fluoroquinolones can be used as an acute-phase antibiotic for patients on ...
Why are fluoroquinolones used in hospitals?
Fluoroquinolones are used by hospitals as “first-line” antibiotics. If a patient becomes sick with an opportunistic infection, it is not good to have encouraged the persistent bacteria to have developed a resistance to fluoroquinolones (potentially due to previous over-use of the drugs)
What is the association between oral fluoroquinolones and retinal detachment?
Association between oral fluoroquinolone use and the development of retinal detachment: a systematic review and meta-analysis of observational studies. A systematic review and meta-analysis of the association between systemic fluoroquinolones and retinal detachment.
Why are fluoroquinolones used as an acute-phase antibiotic?
Fluoroquinolones can be used as an acute-phase antibiotic for patients on the Marshall Protocol because they produce little or no immunopathology.
Do fluoroquinolones act in the same way?
All the fluoroquinolones are thought to act in a similar way.
Is fluoroquinolone as effective as minocycline?
Fluoroquinolones are only a fraction as effective as minocycline in killing intracellular bacteria. 1) When used frequently, undesirable side effects have been well-documented. One of the risks of fluoroquinolone antibiotics is that of tendon damage, however, this risk is reportedly relatively small for patients who are not taking steroids.
How are fluoroquinolones classified?
Fluoroquinolones are classified on the basis of their spectrum of activity [ Table 1 ]. [ 9 - 11]
What is a fluoroquinolone?
Fluoroquinolones are synthetic fluorinated analogues of nalidixic acid, a 1,8-naphthyridine and possess a 4-quinolone nucleus. [ 11] The quinolone structure consists of a bicyclic system with a substituent at position N-1, a carboxyl group at position 3, a keto group at position 4, a fluorine atom at position 6, and a substituent (often nitrogen heterocycle moiety) at the C-7. Normally, in position 2, there are no substituents, various 1-methyl-2-alkenyl-4 (1H). [ 12]
How does resistance to fluoroquinolones occur?
MECHANISM OF RESISTANCE. Resistance to fluoroquinolones mostly occurs by two mechanisms that are mutations in the both target enzymes DNA gyrase in Gram-negative bacteria and topoisomerase IV in Gram-positive bacteria. The second way that reduced accumulation of the fluoroquinolones can occur is through an efflux system.
How do fluoroquinolones work?
Fluoroquinolones show their action by inhibiting the replication and transcription of bacterial DNA that is responsible for proper functioning of the cell . [ 15, 16] During DNA replication and transcription, double-stranded DNA goes to uncoil into a single-stranded structure by enzymes called DNA gyrase or DNA topoisomerase. DNA gyrase is an essential adenosine triphosphate-hydrolyzing topoisomerase II enzyme that prevents the detachment of gyrase from DNA. It consists of two A subunits (gyrA) and two B subunits (gyrB). DNA gyrase establishes negative super-helical twists in the bacterial DNA [ Figure 1 ]. [ 17] 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. There is DNA-binding groove between the A and B subunits so that binding of the fluoroquinolones to this groove may conformity change the DNA gyrase molecule. Then, DNA becomes another binding site itself, as a result fluoroquinolones bind with both DNA and DNA gyrase. In many bacteria, DNA gyrase acts as the primary site of fluoroquinolone action, including E. coli. [ 18] Fluoroquinolones have also been found to inhibit the in vitro activities of topoisomerase IV, having structure similar to DNA gyrase. [ 2] The 2 nd target site for the fluoroquinolones is topoisomerase IV, this is made up from two ParC subunits (parC) and two ParE subunits (parE). The protein subunits coded for by parC (ParC) and parE (ParE) are homologous to the A and B subunits of DNA gyrase, respectively. Topoisomerase IV carries out decatenation and relaxation of DNA and assists with the segregation of replicating chromosomes or plasmids in bacteria. [ 19] The bactericidal activity of the fluoroquinolones is enhanced by inhibition of topoisomerase IV.
Why are quinolones restricted?
The key restriction to the use of quinolones for the treatment of community-acquired pneumonia and bronchitis had been observed because of poor in vitro activity of ciprofloxacin, ofloxacin, and norfloxacin against S. pneumoniae and anaerobic bacteria.
Why are fluoroquinolones not used clinically?
At present, these drugs not use clinically due to bacterial resistance of fluoroquinolones at molecular level by different mechanisms. The future directions of fluoroquinolones are on nucleus that may be valuable target site to increase the potency, efficacy, and decrease side effects of fluoroquinolones.
What is the main mechanism of fluoroquinolones?
The main mechanism fluoroquinolones is mutations that alter the accumulation of fluoroquinolones in bacteria. The broad use of the fluoroquinolones is discussed. They are useful in the treatment of urinary tract infections, prostatitis, sexually transmitted diseases, gastrointestinal infections, osteomyelitis, and respiratory tract infections.
Classification and Chemistry
Fluoroquinolones are a class of broad-spectrum antibiotics. The common medications in the class include:
Mechanisms of Action and Resistance
Topoisomerase II ( DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions.
Spectrum of Activity
Fluoroquinolones are considered broad-spectrum antibiotics: Ciprofloxacin covers gram-negative rods the best; Levofloxacin and moxifloxacin provide excellent coverage of most potential respiratory pathogens; Delafloxacin covers both P. aeruginosa and MRSA.
Indications
Compared to other antibiotics, fluoroquinolones are associated with a higher risk of potentially permanent and disabling adverse events. Therefore, fluoroquinolones are generally not used for uncomplicated infections
Adverse Effects and Contraindications
Fluoroquinolones carry higher risks than many other antibiotics, which limits the use. Although adverse effects are uncommon, some may be permanent or severe.
Comparison of Medications
Antibiotics can be classified in several ways. One way is to classify antibiotics by mechanism of action:
How do fluoroquinolones work?
These drugs work by targeting 2 bacterial enzymes responsible for notching, coiling, and sealing DNA during replication: DNA gyrase and topoisomerase IV. Because current fluoroquinolones bind ...
Which fluoroquinolones treat bacterial infections?
Here's a list of bacterial infections that fluoroquinolones like ciprofloxacin and levofloxacin treat:
How often can you take fluoroquinolone?
In addition to broad-spectrum bacterial coverage, fluoroquinolones also sport other properties that make them great antibiotics. First, they are taken by mouth (and not by injection). Second, they distribute well throughout various body compartments. Third, fluoroquinolones have a longer half-life which allows them to be dosed once or twice a day. Fourth, ciprofloxacin and levofloxacin are excreted mostly by the kidneys making them great at fighting urinary tract infections.
Why do you abandon fluoroquinolone treatment?
By abandoning treatment midway through—after you "feel" better—you contribute to the selection, survival, and spread of antibiotic-resistant bacteria which then become a serious public health concern. Remember that we're always fighting a war against antibiotics, and we lose battles once resistance emerges.
Is fluoroquinolone safe?
For the most part, fluoroquinolones are very safe medication. However, they can cause certain adverse effects including:
Is fluoroquinolone resistant to other antibiotics?
Although resistance to fluoroquin olones is less prevalent than resistance to some other antibiotics, it still happens especially among staphylococci (MRSA), Pseudomonas aeruginosa, and Serratia marcescens. And once a strain of bacteria is resistant against one fluoroquinolone then it's resistant to them all.
Is levofloxacin a fluoroquinolone?
If you're reading this article, you may have been prescribed ciprofloxacin (Cipro), levofloxacin (Levaquin) or some other type of fluoroquinolone for the treatment of a bacterial infection ( think respiratory or urinary tract infection ). Overall, these drugs are safe and effective against a wide array of gram-positive and gram-negative bacterial pathogens making them a good choice for systemic or body-wide treatment.
Which fluoroquinolone is the newest generation?
More recently, the molecule configurations of fluoroquinolones have been modified to produce new generations of antibiotics.5For example, sitafloxacin is the newest-generation fluoroquinolone.8–12The most frequently used fluoroquinolones include ciprofloxacin, levofloxacin, norfloxacin, ofloxacin, and gatifloxacin.13,14
How many nonrandomized studies have been published?
One of the seven non-randomized studies was published in 2019,28one in 2018,29one in 2017,30two in 2016,31,32one in 2015,33and one in 2014.34Six non-randomized studies were retrospective28–32,34and the other was prospective.33
Is sitafloxacin the same as plazomicin?
When patients with pyelonephritis or complicated UTIs were considered, sitafloxacin and levofloxacin were similarly effective as ceftrizxone and plazomicin respectively. However, ceftolozane-tazobactam was significantly more effective than levofloxacin in one non-randomized study.
Is ceftazidime more effective than ciprofloxacin?
In one randomized controlled trial, ceftazidime was more effective than ciprofloxacin in patients with acute obstructive pyelonephritis. However, ertapenem was significantly more effective than fluoroquinolones in complicated UTIs in one non-randomized study.
Where were nonrandomized studies conducted?
Two of the non-randomized studies were conducted in the US,30,32two in Taiwan,31,34one in the UK,28one in Germany,29and one in Switzerland.33
Can pregnant women take fluoroquinolone?
In clinical guidelines, fluoroquinolones are not recommended for children and pregnant women due to the potential adverse effects. A guideline by the National Institute for Health and Care Excellence (NICE) recommends ciprofloxacin for pyelonephritis for non-pregnant women and men aged 16 years and over. In the other three guidelines, both ciprofloxacin and levofloxacin are recommended for acute pyelonephritis.
What is a fluoroquinolone?
Douglas N. Fish. The fluoroquinolones are synthetically derived, broad-spectrum antibacterial agents designed for both intravenous (IV) and oral administration. Since the introduction of ciprofloxacin in the late 1980s, fluoroquinolones have assumed an important role in the treatment of infections in critically ill patients.
Why do people take fluoroquinolones?
Many authorities consider fluoroquinolones to be the drugs of choice for treatment of severe pneumonias caused by atypical pathogens, particularly Legionella, because of their very potent in vitro activity, bactericidal actions, and high serum and intracellular concentrations.
What is the resistance to fluoroquinolones?
aeruginosa has been particularly problematic since the introduction of these agents into clinical use. As fluoroquinolones have become more extensively used in the treatment of respiratory tract infections, reports of increasing resistance among S. pneumoniae have focused attention on newly recognized mechanisms of drug action and drug resistance. 19–22 Resistance to fluoroquinolones has tended to emerge rapidly in bacteria with lower intrinsic susceptibility (e.g., S. aureus, P. aeruginosa, and Acinetobacter spp.) because potentially fewer mutational steps are required to confer clinically relevant MIC changes. 26,31,32 However, fluoroquinolone resistance has also been noted to be an increasing problem among gram-negative bacilli such as Enterobacter spp., Klebsiella pneumoniae, and even E. coli, organisms that were originally considered to be highly susceptible to the drugs. 6,8,10 This problem is particularly an issue among isolates from ICUs. 10 Development of resistance is also accelerated by the use of drugs with lower in vitro activity, use of inappropriately low doses to treat infections caused by less susceptible organisms, and treatment of infection at sites where quinolone penetration may be decreased. 31–34 Development of resistance to one fluoroquinolone usually causes decreased susceptibility to all other agents in the class, although clinically relevant resistance may not necessarily occur. Of note, fluoroquinolone use has also been associated with high rates of cross-resistance among drugs of unrelated antibiotic classes such as the carbapenems, cephalosporins, and aminoglycosides. 33–35 Although not well understood, such cross-resistance is probably mediated by up-regulation and/or reduction in multiple efflux pump systems involved in passage of antibiotics through cell membranes and intracellular drug accumulation. 33–35 Although the fluoroquinolones remain highly active and clinically effective against a wide variety of important pathogens found in critically ill patients, increasing resistance is clearly an important issue in the clinical use of these drugs.
What are quinolone resistance determining regions?
Mutations in quinolone-resistance determining regions (QRDR) of topoisomerase enzymes prevent formation of drug/enzyme/DNA complexes, allowing DNA synthesis to occur in the presence of the drugs. Mutations in the genes encoding DNA gyrase ( gyrA and gyrB) have been most frequently identified. However, other quinolone-resistant mutations in parC and parE, the genes encoding topoisomerase IV, have also been identified. 1,2,17,19 Resistance to fluoroquinolones appears to arise in a stepwise manner. In some species (e.g., gram-negative bacteria), first-step mutations occur in gyrA and occasionally in gyrB, whereas in other species (e.g., S. aureus, S. pneumoniae) first-step mutations occur in parC and less often in parE.17,19 First-step mutations usually result in a low-level resistance (≤fourfold increased MIC), whereas additional mutations in either primary or secondary enzyme targets (second-step mutations) result in high-level resistance to drugs at clinically relevant concentrations. Dual gyrA and parC mutations have been described in clinical isolates of S. pneumoniae; however, it is thought that these strains were selected by fluoroquinolones with less potent antipneumococcal activity (e.g., ciprofloxacin). 19–22
What are the mechanisms of fluoroquinolone resistance?
Two basic mechanisms of fluoroquinolone resistance have been identified. One involves alteration of DNA gyrase and topoisomerase IV , whereas the other results in reduced drug accumulation within bacterial cells. 2,17 Plasmid-mediated resistance, once considered quite rare, appears to be spreading rapidly among enteric gram-negative bacilli in certain geographic regions. 18 However, plasmid-mediated resistance is relatively unusual compared with the more typical chromosomally mediated mechanisms of resistance.
Which fluoroquinolone is best for gram positive bacteria?
Moxifloxacin has the best overall activity against staphylococci and streptococci, followed by levofloxacin and more distantly by ciprofloxacin. 12,13 Levofloxacin and moxifloxacin are reliably active against penicillin-susceptible strains of S. pneumoniae; this activity is also retained against strains of S. pneumoniae resistant to other drug classes including penicillins, macrolides, and sulfonamides. Although ciprofloxacin has only moderate activity against methicillin-susceptible S. aureus (MSSA), newer agents have excellent activity against this organism. None of the fluoroquinolones is reliably active against methicillin-resistant S. aureus (MRSA), and rates of fluoroquinolone resistance among MRSA are quite high. Fluoroquinolones as a class also have only moderate activity against enterococci, with great variability seen among the various agents and specific bacterial strains. 11–13 Fluoroquinolones have consistently excellent activity against Listeria monocytogenes.11–13
Which fluoroquinolone is the least active?
Levofloxacin tends to be slightly more active against Acinetobacter spp., whereas moxifloxacin usually displays the best activity and ciprofloxacin is consistently the least active agent against Stenotrophomonas maltophilia.6,11–13 However, resistance to these latter organisms is quite common, and even agents with the best relative in vitro activity are not reliably clinically effective against many isolates. 6,11–13
What is the fourth generation of fluoroquinolones?
These fourth-generation fluoroquinolon es are the result of extensive scientific research and reflect significant progress in our understanding of pharmacology and clinical therapeutics. The new antibiotics represent a major advance in the management of infectious ocular disease. They are not just big guns that we should reserve only ...
Which is more potent, fourth or third generation fluoroquinolone?
The researchers conclude that fourth-generation fluoroquinolones are more potent than second- and third-generation medicines for gram-positive bacteria, and are equally as potent for gram-negative bacteria. The fourth-generation fluoroquinolones appear to cover second- and third-generation fluoro- quinolone resistant organisms.
How does moxifloxacin help bacteria?
Bacteria may also develop fluoroquinolone resistance through efflux mechanisms that effectively pump antibiotic out of the cell. As an example of fourth-generation engineering, moxifloxacin was created with a bulky bicyclic amine side chain at the C-7 position that serves to block the bacterial membrane-associated efflux pump. This provides an additional line of defense against resistance. Of particular clinical relevance, the fourth-generation agents show no cross-resistance with bacteria resistant to second-and third-generation fluoroquinolones.
Why do moxifloxacin and gatifloxacin attack both topoisomerases?
Because moxifloxacin and gatifloxacin attack both topoisomerases, simultaneous independent mutations in two bacterial genes would have to occur to enable resistancean event far less likely than the single mutation necessary for a mutation to overcome prior-generation fluoroquinolones.
Why are fluoroquinolones used for keratitis?
Because bacteria l keratitis is potentially devastating and yet is usually treated empirically, the fourth-generation fluoroquinolones may rapidly become the drugs of choice for infectious keratitis due to their excellent penetration, rapid kill rate and broad spectrum of activity.
What happened due to the high rate of empirical success with fluoroquinolone monotherapy?
What also happened due to the high rate of empirical success with fluoroquinolone monotherapy was a significant decrease in the number of clinicians who routinely cultured ulcers. Soon after topical fluoroquinolones were introduced, standards of care shifted away from the routine culturing of suspected microbial keratitis.
How many corneal infiltrates did the control group have?
On day three, the control group had eight corneal infiltrates and all control eyes had positive cultures. The ciprofloxacin group had seven infiltrates, and six of eight eyes had positive cultures. The gatifloxacin eyes had three areas of 1mm central corneal haze and no infiltrates.
What is the purpose of fluoroquinolones?
Quinolones and fluoroquinolones may also be used to treat unusual infections such as anthrax or plague. Doctors may also decide to use them for other types of infection when other alternative treatment options have failed or cannot be used.
How do fluoroquinolones differ from quinolones?
Quinolones and fluoroquinolones also differ in the way they are absorbed, metabolized and excreted in the body.
What are Quinolones?
Quinolones are a type of antibiotic. Antibiotics kill or inhibit the growth of bacteria.
What are quinolones and fluoroquinolones used for?
Quinolones and fluoroquinolones are considered broad-spectrum antibiotics. This means that they are effective against a wide range of bacteria.
What are the side effects of quinolones and fluoroquinolones?
The most commonly reported side effects include diarrhea, nausea, abnormal liver function tests, vomiting, and rash.
What are the effects of quinolones on DNA?
Quinolones and fluoroquinolones detrimentally affect the function of two enzymes produced by bacteria, topoisomerase IV and DNA gyrase, so that they can no longer repair DNA or help in its manufacture.
Can you take fluoroquinolone with quinolone?
Quinolones and fluoroquinolones should be avoided in children under the age of 18 years unless they have a serious infection that cannot be treated with any other antibiotic. This is because they can damage the weight-bearing joints in children, and children are also more susceptible to other adverse effects of quinolones and fluoroquinolones, including tendinitis and tendon rupture.
