antibiotics, drug safety, fluoroquinolones, infections



  1. Kidd, Tara PharmD
  2. Mitchell, Stephanie
  3. Dehays, Julie
  4. Wibberley, Erica PharmD


Abstract: Fluoroquinolones (FQs) are highly effective, well-tolerated, broad-spectrum antibiotics, making them desirable treatment options for infections. However, their adverse reactions as well as recent trends in antibiotic susceptibility must be considered. This article discusses the spectrum of activity and adverse reactions of FQs to guide nurses in caring for patients receiving this class of antibiotics.


Article Content

Fluoroquinolones (FQs) are highly effective systemic antibacterial agents that may be used to treat common respiratory, urinary, skin, and soft tissue infections. In the US, the FQs available are ciprofloxacin, levofloxacin, moxifloxacin, delafloxacin, and ofloxacin. These antibiotics offer many therapeutic advantages, including a large volume of distribution and high oral bioavailability. The large volume of distribution results in high medication concentrations in many organs, including the kidneys, gallbladder, liver, lung, skin, and prostate. FQs are also well-absorbed from the upper gastrointestinal (GI) tract, with high bioavailability that ranges from 59% to over 99%, depending on the specific FQ and patient age. These properties make FQs desirable for treating infections, but their adverse reactions and current susceptibility trends need to be considered as well.1-5

Figure. No caption a... - Click to enlarge in new windowFigure. No caption available.

Spectrum of activity

FQs are bactericidal antibiotics that work by inhibiting DNA gyrase (topoisomerase II) and DNA topoisomerase IV, which are necessary for transcription and DNA replication. With the cessation of DNA replication, FQs damage bacterial DNA, and, ultimately, cause cell death.1-5 This results in a wide spectrum of antimicrobial activity, ranging from Gram-negative bacilli to Gram-positive and atypical pathogens. (See FQ coverage of select organisms.1-5) Delafloxacin has activity against methicillin-resistant Staphylococcus aureus, but the best FQ agents for Gram-positive organisms are levofloxacin and moxifloxacin.6 Moxifloxacin is also the only drug in the class that is active against anaerobic organisms, but it lacks activity against Pseudomonas species (spp.). Moxifloxacin does not achieve adequate concentration in the urine, making it ineffective for the treatment of urinary tract infections.6


FQs are versatile and commonly chosen when a more broad-spectrum antibiotic is required. Respiratory FQs (levofloxacin, moxifloxacin, and delafloxacin) are used as the first-line treatment for infections such as pneumonia, chronic obstructive pulmonary disease exacerbations, and bronchitis because they are highly active against common and atypical respiratory pathogens. Ciprofloxacin and ofloxacin achieve high concentrations in lung tissue, but they are not considered respiratory FQs due to their weak activity against S. pneumoniae.1 FQs may also be used as first-line options for intra-abdominal infections, prostatitis, typhoid fever, and pyelonephritis.


While FQs provide broad empiric coverage, bacterial resistance typically increases rapidly, resulting in the reduced utility of FQs.1 Consult local susceptibility data (antibiogram) when possible to ensure local resistance rates do not preclude the use of FQs as empiric treatment. Additionally, the FDA recommends reserving FQs only for patients who have no alternative treatment options in uncomplicated infections such as chronic bronchitis exacerbation, uncomplicated cystitis, and acute sinusitis.1-4


Adverse reactions

Although a majority of the general population tolerates FQs with minimal to no adverse reactions, increasing reports of serious adverse reactions make FQs a less attractive treatment option.7 Risks and benefits must be weighed for each patient situation. Significant adverse reactions and important considerations are detailed below.



Administration of FQs is associated with prolonged QT interval through inhibition of cardiac potassium voltage-gated channels. On rare occasions, this can lead to a life-threatening ventricular dysrhythmia called torsades de pointes. FQs should be avoided in patients taking other QT-prolonging drugs or in patients with long QT syndromes, especially if alternative antibiotics are available. Medications commonly associated with QT prolongation include antiarrhythmics, antimicrobials, antidepressants, antipsychotics, and others like ondansetron or methadone.8 (See Commonly prescribed QT-prolonging medications.8)


If an FQ must be used, QT intervals should be monitored via ECG. Potassium and magnesium levels should also be repleted to maintain concentrations in the high-normal range when needed for cardioprotection.8


FQs must be avoided in patients with or at risk for aortic aneurysm or dissection. A US FDA review concluded that FQs can increase the occurrence of aortic dissections or aortic aneurysm ruptures. It is hypothesized that FQs cause excess activity of matrix metalloproteinases (MMP), which help prevent the degradation of collagen when balanced appropriately with tissue inhibitors of MMP.9 The imbalance of MMP with tissue inhibitors degrades the integrity of the vessel, leading to an increase in aortic diameter and wall stress.9 FQs should be avoided in patients with known aortic aneurysms or those with risk factors for aneurysm such as Marfan syndrome, Ehlers Danlos syndrome, peripheral atherosclerotic vascular diseases, uncontrolled hypertension, and advanced age.1-4



One of the more severe effects of FQs is tendon rupture or tendonitis secondary to damage of extracellular matrix components such as collagen and elastin. Patients may present with pain, swelling, inflammation, or a rupture usually of the Achilles tendon or in other joint areas such as the rotator cuff, hand, or shoulder. These adverse reactions have been reported in 1%-4% of patients, and may occur within hours of starting an FQ or up to several months after completion of therapy.1-5 Individuals at a higher risk for tendonitis or tendon rupture include older adults, organ transplant recipients, and patients with diabetes. Additional risk factors include patients receiving high doses or a long duration of FQ or concomitantly taking corticosteroids. Activities that may further increase the risk of tendinopathies include strenuous activity, renal failure, or other previous tendon disorders. If a patient presents with any sign of tendinopathy such as pain or swelling, FQ treatment should be discontinued immediately and the healthcare provider must be notified.10


Arthralgia and myalgia are frequent complaints among those taking FQs. Symptom onset typically occurs within 3 days of therapy initiation and often resolves 7 to 8 days after therapy is discontinued. Though this can be extremely bothersome to the patient, it is not recommended to discontinue therapy.1-5

Commonly prescribed ... - Click to enlarge in new windowCommonly prescribed QT prolonging medications.


Another undesirable effect of FQs and antibiotics in general is the alteration of the normal colonic flora, causing an overgrowth of Clostridioides difficile. Signs and symptoms can range from mild diarrhea (5%) to severe colitis (<1%), and may occur 24 hours after antibiotic initiation or up to 3 months following treatment. Patient risk factors for C. difficile-associated disease include previous antibiotic exposure, long length of stays at a healthcare facility, older age, immunocompromise, prior GI surgery, gastric acid suppression (with proton pump inhibitors or histamine 2 receptor antagonists), or chemotherapy.1-5 If a patient is found to have C. difficile-associated diarrhea, the offending antibacterial should be discontinued if possible and C. difficile treatment should be initiated as indicated.10


Central nervous system

FQs can cause mild neurologic adverse reactions in patients after only a single dose. The most notable symptoms include headache, dizziness, sleeping difficulties, and memory issues. More serious but less common neurologic effects include delirium, disorientation, and major mood changes.1-5 Consider discontinuing FQ treatment if patients experience any of the more serious neurologic effects.


FQs have neuromuscular-blocking activity and may exacerbate muscle weakness, including muscles of respiration, in patients with myasthenia gravis.1-5 Symptoms typically occur about 1 day after initial administration. FQs are discouraged in patients with this autoimmune disorder.


Peripheral neuropathy symptoms include numbness, tingling, or burning, shooting pain in the arms and legs. It could also present as a change in sensation to light, touch, pain, or temperature. Although rare, peripheral neuropathy will typically develop within the first few days of FQ use and may last for months or even years after the discontinuation of the medication.1-5 If a patient develops symptoms of peripheral neuropathy, the medication should be discontinued immediately and the patient should be provided symptomatic care.


Other effects

FQs have also been shown to cause photosensitivity, an immune skin reaction presenting as an erythematous rash or hyperpigmentation. This may occur as quickly as 24 hours following FQ administration and occurs independently of dose. Cystic fibrosis increases the risk of photosensitivity, as does increased duration and intensity of sun exposure. Photosensitivity prevalence varies within the drug class based on structural molecule differences. The range of incidence is as follows: ciprofloxacin > levofloxacin > ofloxacin > moxifloxacin, with the risk at less than 1% for ciprofloxacin. When taking these medications, patients should be advised to use sunscreen containing UVA blockers or to avoid sun exposure if possible.10


FQs can cause hypo- or hyperglycemia in patients with or without diabetes.11 They should be used with caution in older adults and those with diabetes, and blood glucose levels should be closely monitored.1-5


Drug interactions

FQs interact with many drugs based on their pharmacokinetic profile. Multivitamins and minerals have the potential to decrease the serum concentration of FQs by reducing the absorption of orally administered quinolones. To ensure appropriate drug concentration, best practice involves administration of FQs at least 2 hours before or 6 hours after any doses of a multivitamin, supplement, or antacid that contains polyvalent cations (such as calcium, iron, magnesium, zinc, selenium, aluminum).1-5


When used in combination with nonsteroidal anti-inflammatory drugs, the central nervous stimulant effects of FQs may be amplified. This interaction has the potential to lower the seizure threshold, increasing the likelihood of seizure activity. It is important to monitor for any seizure-like activity in patients taking these medications concurrently. Avoid coadministration in patients with a seizure history.1



FQs are highly effective, well-tolerated, broad-spectrum antibiotics, making them desirable treatment options for many types of infections. However, its widespread use has led to a high rate of resistance, reducing their utility. Additionally, recent research has revealed more concerns regarding the safety profile of FQs, including rare but serious adverse reactions.


Considering the risks associated with FQs, drug interactions, and increasing resistance rates, the use of FQs should be reserved only for serious infections and situations without alternative antibiotic options. Healthcare professionals must monitor for adverse reactions, especially in populations with increased risks.




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