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60-399: EHEC may mean: Enterohemorrhagic Escherichia coli , strain of bacteria Ethyl hydroxyethyl cellulose , a chemical compound Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title EHEC . If an internal link led you here, you may wish to change the link to point directly to

120-483: A hemorrhagic colitis with severe abdominal pain. Serotype O157:H7 may trigger an infectious dose with 100 bacterial cells or fewer; other strain such as 104:H4 has also caused an outbreak in Germany 2011. Infections are most common in warmer months and in children under five years of age and are usually acquired from uncooked beef and unpasteurized milk and juice. Initially a non-bloody diarrhea develops in patients after

180-655: A benzodiazepine-dependent individual can precipitate acute benzodiazepine withdrawal symptoms due to quinolones displacing benzodiazepines from their binding sites. Fluoroquinolones have varying specificity for cytochrome P450 , so may have interactions with drugs cleared by those enzymes; the order from most P450-inhibitory to least, is enoxacin > ciprofloxacin > norfloxacin > ofloxacin, levofloxacin, trovafloxacin, gatifloxacin, moxifloxacin. Quinolones are not recommended in people with epilepsy , Marfan's syndrome , Ehlers-Danlos Syndrome , QT prolongation , pre-existing CNS lesions, or CNS inflammation, or who have had

240-411: A stroke . They are best avoided in the athlete population. Safety concerns exist for fluoroquinolone use during pregnancy, so they are contraindicated unless no other safe alternative antibiotic exists. However, one meta-analysis looking at the outcome of pregnancies involving quinolone use in the first trimester found no increased risk of malformations. They are also contraindicated in children due to

300-440: A chemical distillate during an attempt at synthesis of the chloroquinoline antimalarial agent, chloroquine . Naphthyridone and quinolone classes of antibiotics prevent bacterial DNA replication by inhibition of DNA unwinding events, and can be both bacteriostatic and bacteriocidal. (See Mechanism of Action earlier.) The majority of quinolones in clinical use belong to the second generation class of "fluoroquinolones", which have

360-498: A first-line treatment for many infections, including very commons ones such as acute sinusitis, acute bronchitis, and uncomplicated UTIs. Reports of serious adverse events began emerging, and the FDA first added a black-box warning to fluoroquinolones in July 2008 for the increased risk of tendinitis and tendon rupture. In February 2011, the risk of worsening symptoms for those with myasthenia gravis

420-596: A history of aneurysms. Quinolones are associated with a small risk of tendonitis and tendon rupture; a 2013 review found the incidence of tendon injury among those taking fluoroquinolones to be between 0.08 and 0.20%. The risk appears to be higher among people older than 60 and those also taking corticosteroids; the risk also may be higher among people who are male, have a pre-existing joint or tendon issue, have kidney disease, or are highly active. Some experts have advised avoidance of fluoroquinolones in athletes. If tendonitis occurs, it generally appears within one month, and

480-491: A large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone . They are used in human and veterinary medicine to treat bacterial infections , as well as in animal husbandry, specifically poultry production. Nearly all quinolone antibiotics in use are fluoroquinolones , which contain a fluorine atom in their chemical structure and are effective against both Gram-negative and Gram-positive bacteria. One example

540-473: A quinolone, nalidixic acid is considered the first quinolone drug. It was introduced in 1962 for treatment of urinary tract infections (UTIs) in humans. Nalidixic acid was discovered by George Lesher and coworkers in a distillate during an attempt at chloroquine synthesis. Nalidixic acid is thus considered to be the predecessor of all members of the quinolone family, including the second, third and fourth generations commonly known as fluoroquinolones. Since

600-558: A true quinoline framework, maintain the C-3 carboxylic acid group, and add a fluorine atom to the all-carbon containing ring, typically at the C-6 or C-8 positions. Quinolones can be classified into generations based on their antibacterial spectrums. The earlier-generation agents are, in general, more narrow-spectrum than the later ones, but no standard is employed to determine which drug belongs to which generation. The only universal standard applied

660-489: Is ciprofloxacin , one of the most widely used antibiotics worldwide. Fluoroquinolones are often used for genitourinary infections and are widely used in the treatment of hospital-acquired infections associated with urinary catheters. In community-acquired infections, they are recommended only when risk factors for multidrug resistance are present or after other antibiotic regimens have failed. However, for serious acute cases of pyelonephritis or bacterial prostatitis where

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720-529: Is caused by multidrug-resistant bacteria , or when alternative treatment options require parenteral administration and oral therapy is preferred. While typical drug side effects reactions are mild to moderate, sometimes serious adverse effects, such as suicide, occur. Fluoroquinolones can increase the risk of psychiatric symptoms, including depression and psychotic reactions. These may potentially lead to thoughts of suicide or suicide attempts. For example, recent reports from senior coroners on two suicides show

780-599: Is closer to the Shiga toxin. Practically, the choice of words and categories is not as important as the understanding of clinical relevance. The infectivity or the virulence of an EHEC strain depends on several factors, including the presence of fucose in the medium, the sensing of this sugar and the activation of EHEC pathogenicity island . Shiga toxins are a major virulence factor of EHEC. The toxins interact with intestinal epithelium and can cause systematic complications in humans like HUS and cerebral dysfunction if they enter

840-536: Is the grouping of the non- fluorinated drugs found within this class (quinolones) within the first-generation heading. As such, a wide variation exists within the literature dependent upon the methods employed by the authors. The first generation is rarely used. Frequently prescribed drugs are moxifloxacin , ciprofloxacin , levofloxacin . Structurally related first-generation drugs, but formally not 4-quinolones, include cinoxacin , nalidixic acid , and piromidic acid , pipemidic acid The second-generation class

900-483: Is the target, whereas topoisomerase IV is the target for many Gram-positive bacteria. Eukaryotic cells are not believed to contain DNA gyrase or topoisomerase IV. However, debate exists concerning whether the quinolones still have such an adverse effect on the DNA of healthy cells. Some compounds in this class have been shown to inhibit the synthesis of mitochondrial DNA . The basic pharmacophore , or active structure, of

960-469: The quinoline ring system. The addition of the fluorine atom at C6 distinguishes the successive-generation fluoroquinolones from the first-generation of quinolones. The addition of the C6 fluorine atom has since been demonstrated not to be required for the antibacterial activity of this class ( circa 1997). Because the use of broad-spectrum antibiotics encourages the spread of multidrug-resistant strains and

1020-408: The FDA issued a drug safety communication advising that fluoroquinolones should be reserved for these conditions only when no other options are available due to potentially permanent, disabling side effects occurring together. The drug safety communication also announced the required labeling updates to reflect this new safety information. The FDA put out another label change in July 2017, strengthening

1080-666: The GABA A receptor complex within the central nervous system, leading to excitotoxic type effects and oxidative stress. Products containing multivalent cations , such as aluminium- or magnesium-containing antacids , and products containing calcium, iron, or zinc invariably result in marked reduction of oral absorption of fluoroquinolones. Other drugs that interact with fluoroquinolones include sucralfate , probenecid , cimetidine , theophylline , warfarin , antiviral agents , phenytoin , cyclosporine , rifampin , pyrazinamide , and cycloserine . Administration of quinolone antibiotics to

1140-501: The LEE) and QseF. QseE phosphorylates QseF. The products QseBC and QseEF repress the expression of FusK and FusR. FusK and FusR are the two components of a system to repress the transcription of the LEE genes. FusK is a sensor kinase which is able to sense many sugars among which fucose. When fucose is present in the medium FusK phosphorylates FusR which represses LEE expression. Thus when EHEC enters

1200-505: The Shiga toxins cannot pass through the intestinal epithelium into circulation. EHEC becomes pathogenic through the expression of the locus of enterocyte effacement (LEE) encoded on its pathogenicity island. However, when EHEC is not in a host this expression is a waste of energy and resources, so it is only activated if some molecules are sensed in the environment. When QseC or QseE bind with one of their interacting signalling molecule, they autophosphorylate and transfer its phosphate to

1260-521: The Stx-bearing bacteriophage and cause increased production of toxins. Attempts to block toxin production with antibacterials which target the ribosomal protein synthesis are conceptually more attractive. Plasma exchange offers a controversial but possibly helpful treatment. The use of antimotility agents (medications that suppress diarrhea by slowing bowel transit) in children under 10 years of age or in elderly patients should be avoided, as they increase

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1320-408: The U.S. FDA added black box warnings on all fluoroquinolones, advising of the increased risk of tendon damage. In 2016, the FDA found that systemic use (by mouth or injection) of fluoroquinolones was associated with "disabling and potentially permanent serious side effects" involving the tendons, muscles, joints, nerves, and central nervous system, concluding that these side effects generally outweigh

1380-469: The UK due to ongoing safety concerns. In a study comparing the safety and efficacy of levofloxacin to that of azithromycin or ceftriaxone in 712 children with community-acquired pneumonia, serious adverse events were experienced by 6% of those treated with levofloxacin and 4% of those treated with comparator antibiotics. Most of these were considered by the treating physician to be unrelated or doubtfully related to

1440-440: The acquisition and outgrowth of a particularly virulent Clostridium strain. More generally, fluoroquinolones are tolerated, with typical drug side effects being mild to moderate. Common side effects include gastrointestinal effects such as nausea, vomiting, and diarrhea, as well as headache and insomnia. Postmarketing surveillance has revealed a variety of relatively rare but serious adverse effects associated with all members of

1500-587: The action of quinolones. Finally, mutations at key sites in DNA gyrase or topoisomerase IV can decrease their binding affinity to quinolones, decreasing the drugs' effectiveness. Quinolones are chemotherapeutic bactericidal drugs. They interfere with DNA replication by preventing bacterial DNA from unwinding and duplicating. Specifically, they inhibit the ligase activity of the type II topoisomerases , DNA gyrase and topoisomerase IV, which cut DNA to introduce supercoiling, while leaving nuclease activity unaffected. With

1560-533: The ambulatory treatment of community-acquired pneumonia only after other antibiotic classes have been tried and failed, or in cases with demonstrated drug-resistant Streptococcus pneumoniae . Resistance to quinolones can evolve rapidly, even during a course of treatment. Numerous pathogens , including Escherichia coli , commonly exhibit resistance. Widespread veterinary usage of quinolones, in particular in Europe, has been implicated. Fluoroquinolones had become

1620-560: The bacterial nucleotide pool, and that this process contributes to the cytotoxicity of these agents. The incorporation of oxidized guanine nucleotides into DNA could be bactericidal. Bacterial cytotoxicity could arise from incomplete repair of closely spaced 8-oxo-2'-deoxyguanosine in the DNA resulting in double-strand breaks. Fluoroquinolones can enter in cells easily via porins , so are often used to treat intracellular pathogens such as Legionella pneumophila and Mycoplasma pneumoniae . For many Gram-negative bacteria, DNA gyrase

1680-1098: The bacterium attaches to the epithelium of the terminal ileum , cecum , and colon . The subsequent production of toxins mediates the bloody diarrhea. In children, a complication can be hemolytic uremic syndrome which then uses cytotoxins to attack the cells in the gut, so that bacteria can leak out into the blood and cause endothelial injury in locations such as the kidney by binding to globotriaosylceramide (Gb3). EHECs that induce bloody diarrhea lead to HUS in 10% of cases. The clinical manifestations of postdiarrheal HUS include acute renal failure , microangiopathic hemolytic anemia , and thrombocytopenia . The verocytotoxin (shiga-like toxin) can directly damage renal and endothelial cells. Thrombocytopenia occurs as platelets are consumed by clotting. Hemolytic anemia results from intravascular fibrin deposition, increased fragility of red blood cells, and fragmentation. Antibiotics are of questionable value and have not shown to be of clear clinical benefit. Antibiotics that interfere with DNA synthesis, such as fluoroquinolones , have been shown to induce

1740-579: The benefits for people with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections when other treatment options are available. Concerns regarding low blood sugar and mental health problems were added in 2018. In December 2018, the FDA issued a warning regarding an increased risk of aortic aneurysms and aortic dissections associated with fluoroquinolone use. This warning specifically targeted older adults and patients with conditions such as hypertension, Marfan syndrome, Ehlers-Danlos syndrome, atherosclerosis, peripheral vascular disease, and

1800-422: The circulation. In EHEC, Shiga toxins are encoded by lysogenic bacteriophages. The toxins bind to cell-surface glycolipid receptor Gb3, which causes the cell to take the toxin in via endocytosis . The Shiga toxins target ribosomal RNA , which inhibits protein synthesis and causes apoptosis . The reason EHEC are symptomless in cattle is because the cattle do not have vascular expression of Gb3 unlike humans. Thus,

1860-799: The class of antibiotics most commonly prescribed to adults in 2002. Nearly half (42%) of these prescriptions were for conditions not approved by the U.S. FDA, such as acute bronchitis , otitis media , and acute upper respiratory tract infection, according to a study supported in part by the Agency for Healthcare Research and Quality . In addition, they are commonly prescribed for medical conditions, such as acute respiratory illness, that are usually caused by viral infections. Three mechanisms of resistance are known. Some types of efflux pumps can act to decrease intracellular quinolone concentration. In gram-negative bacteria, plasmid-mediated resistance genes produce proteins that can bind to DNA gyrase , protecting it from

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1920-619: The damage may be delayed several months after stopping treatment. The overall rate of adverse events in people treated with fluoroquinolones is roughly similar to that seen in people treated with other antibiotic classes. A U.S. Centers for Disease Control and Prevention study found people treated with fluoroquinolones experienced adverse events severe enough to lead to an emergency department visit more frequently than those treated with cephalosporins or macrolides , but less frequently than those treated with penicillins , clindamycin , sulfonamides , or vancomycin . Fluoroquinolones prolong

1980-561: The development of Clostridioides difficile infections, treatment guidelines often recommend minimizing the use of fluoroquinolones and other broad-spectrum antibiotics in less severe infections and in those in which risk factors for multidrug resistance are not present. It has been recommended that fluoroquinolones not be used as a first-line agent for community-acquired pneumonia, instead recommending macrolide or doxycycline as first-line agents. The Drug-Resistant Streptococcus pneumoniae Working Group recommends fluoroquinolones be used for

2040-510: The difference is negligible. Following this view, all "VTEC" (blue) should be called "STEC" (red). Historically, a different name was sometimes used because the toxins are not exactly the same as the one found in Shigella dysenteriae , down to every last amino acid residue, although by this logic every "STEC" would be a "VTEC". The line can also be drawn to use "STEC" for Stx1 -producing strains and "VTEC" for Stx2 -producing strains, since Stx1

2100-522: The epithelium, then the expression of LEE genes will not be repressed by FusR, and KpdE will strongly activate them. In summary, the combined effect of the QseC/QseF and FusKR provide a fine-tuning system of LEE expression which saves energy and allow the mechanisms of virulence to be expressed only when the chances of success are higher. There are rare STEC without LEE, see PMID   19239748 . Fluoroquinolones Quinolone antibiotics constitute

2160-753: The fluoroquinolone antibacterial class. Among these, tendon problems and exacerbation of the symptoms of the neurological disorder myasthenia gravis are the subject of "black box" warnings in the United States. A 2018 EU-wide review of fluoroquinolones concluded that they are associated with serious side effects including tendonitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders, and impaired hearing, vision, taste and smell. Tendon damage (especially to Achilles tendon but also other tendons) can occur within 48 hours of starting fluoroquinolone treatment but

2220-431: The fluoroquinolone class is based upon the quinoline ring system. Various substitutions made to the quinoline ring resulted in the development of numerous fluoroquinolone drugs. The addition of the fluorine atom at C-6 distinguishes the successive-generation fluoroquinolones from the first-generation quinolones, although examples are known that omit the atom while retaining antibacterial activity. Although not formally

2280-405: The gastrointestinal tract of cattle and sheep, and can infect humans. They are globally-occurring bacteria. The best known of these strains is O157:H7 , but non-O157 strains cause an estimated 36,000 illnesses, 1,000 hospitalizations and 30 deaths in the United States yearly. Food safety specialists recognize "Big Six" strains: O26; O45; O103; O111; O121 ; and O145. A 2011 outbreak in Germany

2340-418: The gut there is a competition between the signals coming from QseC and QseF, and the signal coming from FusK. The first two would like to activate virulence, but Fusk stops it because the mucous layer, which is a source of fucose, isolates enterocytes from bacteria making the synthesis of the virulence factors useless. However, when fucose concentration decreases because bacterial cells find an unprotected area of

2400-532: The heart's QT interval by blocking voltage-gated potassium channels. Prolongation of the QT interval can lead to torsades de pointes , a life-threatening arrhythmia , but in practice, this appears relatively uncommon in part because the most widely prescribed fluoroquinolones (ciprofloxacin and levofloxacin) only minimally prolong the QT interval. In 2019 study by Journal of the American College of Cardiology it

2460-444: The intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=EHEC&oldid=1082132528 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Enterohemorrhagic Escherichia coli Shiga toxin–producing Escherichia coli are zoonotic pathogens, in that they can be found in

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2520-404: The introduction of nalidixic acid, more than 10,000 analogs have been synthesized, but only a handful have found their way into clinical practice. The first generation also included other quinolone drugs, such as pipemidic acid , oxolinic acid , and cinoxacin , which were introduced in the 1970s. They proved to be only marginal improvements over nalidixic acid. These drugs were widely used as

2580-790: The ligase activity disrupted, these enzymes release DNA with single- and double-strand breaks that lead to cell death. The majority of quinolones in clinical use are fluoroquinolones, which have a fluorine atom attached to the central ring system, typically at the 6-position or C-8 position . Most of them are named with the -oxacin suffix. First and second generation quinolones are largely active against Gram-negative bacteria, whereas third and fourth generation quinolones have increased activity against Gram-positive and anaerobic bacteria. Some quinolones containing aromatic substituents at their C-7 positions are highly active against eukaryotic type II topoisomerase. It has also been proposed that quinolone antibiotics cause oxidation of guanine nucleotides in

2640-409: The most common spontaneous reports between April 2005 and March 2008. An estimated 130,000 pediatric prescriptions for levofloxacin were filled on behalf of 112,000 pediatric patients during that period. Meta-analyses conclude that fluoroquinolones pose little or no additional risk to children compared to other antibiotic classes. Fluoroquinolone use in children may be appropriate when the infection

2700-565: The most common tendon injured appears to be the Achilles tendon . The cause is not well understood. Fluoroquinolones can increase the rate of rare but serious tears in the aorta by 31% compared to other antibiotics. People at increased risk include those with aortic aneurysm, hypertension, certain genetic conditions such as Marfan syndrome and Ehlers-Danlos syndrome , and the elderly. For these people, fluoroquinolones should be used only when no other treatment options are available. One year after

2760-476: The person may need to be hospitalised, fluoroquinolones are recommended as first-line therapy. Due to people with sickle-cell disease being at increased risk for developing osteomyelitis from the Salmonella , fluoroquinolones are the "drugs of choice" due to their ability to enter bone tissue without chelating it, as tetracyclines are known to do. Fluoroquinolones are featured prominently in guidelines for

2820-618: The prescriber. A 2024 review from the UK’s Medicines & Healthcare Products Regulatory Agency examined the effectiveness of current measures to reduce these identified risks of fluoroquinolones. It concluded, “Systemic fluoroquinolones must now only be prescribed when other commonly recommended antibiotics are inappropriate.” Nervous-system effects include insomnia, restlessness, and rarely, seizure, convulsions, and psychosis. Other rare and serious adverse events have been observed with varying degrees of evidence for causation. In 2008,

2880-413: The red and blue have often been treated as synonyms of the purple. At least one reference holds "EHEC" to be mutually exclusive of "VTEC" and "STEC", but this does not match common usage, as many more publications lump all of the latter in with the former. The current microbiology-based view on "Shiga-like toxin" (SLT) or "verotoxin" is that they should all be referred to as (versions of) Shiga toxin , as

2940-444: The response regulator. QseC senses adrenaline , noradrenaline , and an Endonuclease I-SceIII, encoded by a mobile group I intron within the mitochondrial COX1 gene (AI3); whereas QseE senses adrenaline, noradrenaline, SO4 and PO4. These signals are a clear indication to the bacteria that they are no longer free in the environment, but in the gut. As a result, QseC phosphorylates QseB (which activates flagella), KpdE (which activates

3000-410: The risk of HUS with EHEC infections. Names of the group and its subgroups include the following. There is some polysemy involved. Invariable synonymity is indicated by having the same color. Beyond that there is also some wider but variable synonymity. The first two (purple) in their narrowest sense are generally treated as hypernyms of the others (red and blue), although in less precise usage

3060-410: The risks of damage to the musculoskeletal system. Their use in children is not absolutely contraindicated, however for certain severe infections where other antibiotics are not an option, their use can be justified. Quinolones should also not be given to people with a known hypersensitivity to the drug class. The basic pharmacophore , or active structure, of the fluoroquinolone class is based upon

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3120-479: The risks of fluoroquinolones in everyday life. Neither victim had a history of depression or mental health problems. However, both men had been prescribed ciprofloxacin shortly before they killed themselves. In a “Report to Prevent Future Deaths,” mandated by UK law, one of the coroners noted that there is no compelling reason why patients should expect to risk becoming suicidal from an antibiotic unless this fact and potential symptoms were brought to their attention by

3180-468: The same time and causing the potential for irreversible impairment. The advisory committee concluded that the serious risks associated with the use of fluoroquinolones for these types of uncomplicated infections generally outweighed the benefits for patients with other treatment options. The 21-member joint committee overwhelmingly recommended stronger label warnings on the containers because of rare but sometimes devastating side effects. On 12 May 2016,

3240-426: The study drug. Two deaths were observed in the levofloxacin group, neither of which was thought to be treatment-related. Spontaneous reports to the U.S. FDA Adverse Effects Reporting System at the time of the 20 September 2011 U.S. FDA Pediatric Drugs Advisory Committee included musculoskeletal events (39, including five cases of tendon rupture) and central nervous system events (19, including five cases of seizures) as

3300-497: The treatment of hospital-acquired pneumonia. In most countries, fluoroquinolones are approved for use in children only under narrowly defined circumstances, owing in part to the observation of high rates of musculoskeletal adverse events in fluoroquinolone-treated juvenile animals. In the UK, the prescribing indications for fluoroquinolones for children are severely restricted. Only inhalant anthrax and pseudomonal infections in cystic fibrosis infections are licensed indications in

3360-494: The warning announcement, prescribing behaviors were reported to have remained unchanged. Clostridioides difficile colitis may occur in connection with the use of any antibacterial drug, especially those with a broad spectrum of activity such as clindamycin, cephalosporins, and fluoroquinolones. Fluoroquinoline treatment is associated with risk that is similar to or less than that associated with broad spectrum cephalosporins. Fluoroquinolone administration may be associated with

3420-432: The warnings about potentially disabling adverse effects and limiting use of these drugs to second-line treatments for acute sinusitis, acute bronchitis, and uncomplicated UTIs. The first generation of the quinolones began following introduction of the related, but structurally distinct naphthyridine-family nalidixic acid in 1962 for treatment of UTIs in humans. Nalidixic acid was discovered by George Lesher and coworkers in

3480-497: Was added to the warning. In August 2013, the agency required updates to the labels to describe the potential for irreversible peripheral neuropathy (serious nerve damage). In November 2015, an FDA Advisory Committee discussed the risks and benefits of fluoroquinolones for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated UTIs based on new safety information. The new information focused on two or more side effects occurring at

3540-472: Was caused by another STEC, O104:H4 . This strain has both enteroaggregative and enterohemorrhagic properties. Both the O145 and O104 strains can cause hemolytic-uremic syndrome (HUS); the former strain shown to account for 2% to 51% of known HUS cases; an estimated 56% of such cases are caused by O145 and 14% by other EHEC strains. The clinical presentation in humans ranges from a mild and uncomplicated diarrhea to

3600-467: Was discovered that fluoroquinolones could increase the risk for heart valve diseases. Events that may occur in acute overdose are rare, and include kidney failure and seizure. Susceptible groups of patients, such as children and the elderly, are at greater risk of adverse reactions during therapeutic use. The mechanisms of the toxicity of fluoroquinolones have been attributed to their interactions with different receptor complexes, such as blockade of

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