Levofloxacin


Article Author:
Vivek Podder


Article Editor:
Nazia Sadiq


Editors In Chief:
Kranthi Sitammagari
Mayank Singhal


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
8/17/2019 9:22:50 PM

Indications

Levofloxacin is a broad-spectrum, third-generation fluoroquinolone antibiotic, used to treat bacterial infections. Levofloxacin is a safe and effective medicine on the World Health Organization's essential medicines list. It was patented in 1987 and subsequently received FDA-approval in 1996 for medical use in the United States.[1]

Levofloxacin is FDA-approved for the treatment of nosocomial pneumonia, community-acquired pneumonia, acute bacterial rhinosinusitis, acute bacterial exacerbation of chronic bronchitis, prostatitis, acute pyelonephritis, urinary tract infection (uncomplicated or complicated), skin or skin structure infections, prophylaxis and treatment of plague due to Yersinia pestis, and to reduce the incidence of disease progression of inhalational anthrax. Due to increased risk of severe side effects (e.g., tendinitis and tendon rupture, peripheral neuropathy, and CNS effects), levofloxacin is used only in patients with acute exacerbation of chronic bronchitis, acute bacterial sinusitis, and uncomplicated urinary tract infections, who do not have alternative treatment options. Ophthalmic levofloxacin also has a use in the treatment of bacterial conjunctivitis. To decrease the development of drug-resistant bacteria, the FDA has recommended using levofloxacin only for strongly suspected bacterial infections. Also, levofloxacin should not be used empirically in patients at risk of multidrug-resistant Escherichia coli.[2] 

Mechanism of Action

Levofloxacin is a bactericidal antibiotic of the fluoroquinolone drug class that directly inhibits bacterial DNA synthesis. Levofloxacin promotes the breakage of DNA strands by inhibiting DNA-gyrase in susceptible organisms, which in turn inhibits the relaxation of supercoiled DNA. Of the fluoroquinolone class, levofloxacin has the most enhanced activity against gram-positive penicillin-sensitive and resistant organisms notably, Streptococcus pneumoniae), and reduced action against gram-negative bacilli notably, Pseudomonas aeruginosa compared to ciprofloxacin. Levofloxacin has effectiveness against other common respiratory organisms; notably, Haemophilus influenzaeMoraxella catarrhalis, Legionella sppMycoplasma spp, and Chlamydia pneumoniae.[2] Levofloxacin also has a higher in-vitro activity against Mycobacterium tuberculosis and is preferred over the other fluoroquinolones as second-line antitubercular therapy.[3] There is a growing concern of drug resistance to fluoroquinolones worldwide, which can occur through chromosome-encoded or plasmid-mediated mechanisms. Levofloxacin is rapidly absorbed and widely distributed in the body. The bioavailability of levofloxacin is 99%; therefore, the intravenous and oral preparations of levofloxacin are usable interchangeably. Levofloxacin clearance is primarily via the renal route (87%).[4]

Administration

Levofloxacin is available both for oral tablets and solution, and intravenous administration. Levofloxacin is not available for administration through intramuscular, intrathecal, or subcutaneous route. The available oral dosage strengths for levofloxacin are 250 mg, 500 mg, and 750 mg.

Oral dosing with tablets can be without regard to meals. However, the oral solution should be taken 1 hour before or 2 hours after meals. Patients should avoid using antacids, or levofloxacin should be administered two hours before or two hours after taking antacids containing magnesium or aluminum. It is essential to maintain proper hydration to prevent crystalluria.  

The recommended oral dose regimen is 750 mg once daily to treat nosocomial pneumonia, complicated skin and skin structure infections (7 to 14 days), community-acquired pneumonia, acute bacterial sinusitis, complicated urinary tract infection or acute pyelonephritis (five days). The daily dosing of 500 mg once daily is recommended to treat nosocomial pneumonia (7 to 14 days), acute bacterial sinusitis (10 to 14 days), acute bacterial exacerbation of chronic bronchitis (seven days), uncomplicated skin and skin structure infections (7 to 10 days), chronic bacterial prostatitis (28 days), and post-exposure inhalational anthrax (60 days). The daily dosing of 250 mg once daily is recommended for patients with complicated urinary tract infections or acute pyelonephritis (10 days) or uncomplicated urinary tract infections (3 days).[1] 

Levofloxacin injection should be administered to both adult or pediatric patients by slow intravenous infusion over 60 minutes (for 250 to 500 mg) and over 90 minutes (for 750 mg). Due to an increased risk of hypotension, bolus, or rapid intravenous administration should be avoided. It should not be infused through a solution containing multivalent cations. The ophthalmic solution is safe and an effective antibiotic used for seven days in the treatment of bacterial conjunctivitis. 

A 50% reduction in the total daily dosage is recommended in patients with renal impairment (glomerular filtration rate between 10 and 50 mL/min) and extended to every 48 hours if glomerular filtration rate falls less than 10 mL/min).[1]

Adverse Effects

The primary adverse effects of levofloxacin include photosensitivity, nausea, diarrhea, headache, tendinitis, tendon rupture, hyper-hypoglycemia, seizures, prolonged QT interval, and peripheral neuropathy.[5] Clinicians should prescribe levofloxacin to patients with a history of a prolonged QT interval carefully. It is advisable to minimize or avoid exposure to natural or artificial sunlight while taking levofloxacin to reduce the occurrence of phototoxicity. FDA has alerted a black box warning for using levofloxacin and other fluoroquinolones due to increased risk of disabling and irreversible side effects including tendinitis and tendon rupture, peripheral neuropathy, and CNS effects (e.g., seizures, increased intracranial pressure) in all ages.[6] However, older patients (older than 60 years), those patients taking corticosteroids and with kidney, heart, or lung transplants are at increased risk of severe tendon disorders. Research has determined that prolonged use of levofloxacin is associated with increased risk of fungal or bacterial superinfection (e.g., pseudomembranous colitis).[7] Due to the increased risk of hepatotoxicity, patients should be educated on signs or symptoms of liver injury so they can discontinue treatment. 

Contraindications

The concurrent administration of levofloxacin with drugs that prolong QT interval is contraindicated. It is also contraindicated in patients with documented hypersensitivity to the drug or its components, in pregnancy, nursing mothers, and in children younger than 18 years of age due to possible risk of cartilage damage. It is recommended to avoid levofloxacin and other fluoroquinolone antibiotics in patients with myasthenia gravis due to increased risk of exacerbating existing muscle weakness. Unlike ciprofloxacin, levofloxacin does not inhibit drug-metabolizing enzyme CYP1A2; however, due to its weak inhibiting potential on CYP2C9 enzyme, bleeding can occur with concurrent administration of warfarin.[8] Careful monitoring of blood glucose is recommended for patients taking concurrent antidiabetic agents due to the risk of glucose dysregulation. 

Monitoring

Providers should monitor patients who are taking levofloxacin, for crystalluria, signs, and symptoms of tendonitis and disordered glucose regulation, altered mental status, white blood cells, and signs of infections. It is also essential to evaluate organ system functions (hepatic, renal, hematopoietic) periodically during treatment. It is also necessary to monitor for evidence of bleeding because of drug interaction of levofloxacin with warfarin, which acts on the CYP2C9 enzyme and raises warfarin levels.[9] Unlike, ciprofloxacin, monitoring of patients concurrently taking theophylline is not necessary as levofloxacin does not inhibit the enzyme CYP1A2. 

Toxicity

The elimination half-life of levofloxacin ranges from 27 to 35 hours in adults with renal impairment depending on severity, as compared with six to eight hours in healthy adults. This prolonged half-life indicates that dosing adjustment is necessary for these patients. Levofloxacin has a low potential for acute toxicity; however, during an acute overdose, the stomach needs to be emptied, and the patient should be under observation with adequate maintenance of hydration. It is important to note that hemodialysis or peritoneal dialysis can not adequately remove levofloxacin. The role of enhancing drug elimination with forced dilution is not clear. Activated oral charcoal administration is also a recommended approach with appropriate conditions.[10] Clinical data indicate that breast milk has a low concentration of levofloxacin, which is unlikely to cause adverse effects in breastfed babies. Use of levofloxacin with breastfeeding mothers is acceptable with monitoring of the infant for possible GI adverse effects (diarrhea or candidiasis).[10] 

Enhancing Healthcare Team Outcomes

Levofloxacin is a widely prescribed respiratory fluoroquinolone by many healthcare professionals for a broad spectrum of bacterial infections. Levofloxacin is well-known to increase the risk of tendinitis and tendon rupture in all ages, especially in patients over 60 years old, taking corticosteroids, and with a history of kidney, heart, or lung transplants. It not only extends hospital stay but increases the cost of healthcare. All healthcare workers who prescribe this agent should stratify patients earlier for risk of these complications and should sparely use the drug for patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections. Patients should be asked to maintain adequate hydration to prevent crystalluria and avoid antacids to ensure proper bioavailability. As levofloxacin excretion is primarily via the kidney, providers should carefully adjust the dose in the presence of renal insufficiency to prevent the accumulation of levofloxacin.  

Healthcare providers should monitor patients for changes in bowel frequency, fever, abdominal cramps, and loss of appetite, nausea, vomiting, right upper quadrant tenderness, jaundice, dark-colored urine, or palpitations. Levofloxacin is well known to cause pseudomembranous colitis, hepatotoxicity, and QT prolongation; therefore, patients should be educated to discontinue treatment when the clinical features develop. If diarrhea develops, it is essential to manage fluid and electrolyte replacement in this patient population adequately. Healthcare workers should limit the duration of levofloxacin therapy and abstain from empirical prescribing of this agent due to the growing worldwide concern of drug resistance to levofloxacin and other fluoroquinolones.

Clear communication between physicians and nurses is necessary so that levofloxacin is administered by slow infusion to avoid the risk of hypotension. Pharmacists need to verify dosing and treatment duration, as well as checking for drug-drug interactions. Nursing is on the front lines for observing adverse effects and will report these to the rest of the team promptly. TO achieve improved patient outcomes with reduced risk of side effects and increased patient satisfaction, a concerted and collaborative interprofessional team effort between patients, physicians, nurses, pharmacists, and other healthcare providers is necessary. [Level V]


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Levofloxacin - Questions

Take a quiz of the questions on this article.

Take Quiz
A 20-year-old female presents to the emergency department with complaints of painful urination, fever with rigors, and malaise. She reports these symptoms have been recurring three to four times since last year. She does not have a history of any other comorbid conditions. On examination, her temperature is 39°C (102.2°F), the pulse is 85/min, respirations are 21/min, and blood pressure is 105/55 mm Hg. Her cardiac and abdominal examination findings are non-contributory. Her urine was sent for urinalysis and culture with susceptibility testing. She is then given a course of antibiotics by mouth daily for three days. She is advised to take this drug with adequate water to prevent crystalluria. What is the mechanism by which this medication has likely exerted its antibacterial effect?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 48-year-old male patient is brought to the emergency department due to sudden-onset of high-grade fever and shaking chills. He also reports shortness of breath and cough, 14 hours before the onset of the fever and chills. He denied any past illicit drugs or alcohol use. The patient has smoked one pack of cigarettes daily for 20 years. On examination, her temperature is 39.5°C (103.1°F), the pulse is 102 bpm, respirations are 27 bpm, and blood pressure is 100/65 mmHg. Examination shows dullness to percussion on the right side. Chest x-ray reveals audible crackles in the left upper lobe. Gram stain of the sputum shows gram-positive diplococci. A slow intravenous infusion of levofloxacin 750 mg is ordered over 90 minutes. Which of the following is likely to be prevented with a slow infusion of the antibiotic?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 54-year-old male presents to the emergency department for fever with chills, and dysuria with a change in urine color and foul odor for 4 hours. He also reports the right loin pain associated with malaise. He has a history of long-standing uncontrolled diabetes mellitus. On examination, his temperature is 39°C (102.2°F), the pulse is 95/min, respirations are 21/min, and blood pressure is 110/60 mm Hg. On palpation, the abdomen is found soft and lax, but the right renal angle tenderness is noted. The cardiac findings are noncontributory. His laboratory investigation shows a total leucocyte count of 16000/mm3 with predominant neutrophils and urinalysis shows 20/hpf pus cells in the urine. He was prescribed with an antibiotic that works by inhibiting bacterial DNA synthesis. Which of the following class is that antibiotic likely to be categorized?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 62-year-old male patient presents with fever, pleuritic chest pain, and a productive cough for two days. He also reports of chewing difficulty for the last five years. The patient has smoked three packs of cigarettes daily for 40 years. He has a history of diabetes, hypertension, and coronary artery disease. On examination, his temperature is 39.1°C (102.3°F), the pulse is 87/min, respirations are 27/min, and his blood pressure is 115/70 mmHg. Respiratory examination reveals decreased breath sounds on the left side. Chest x-ray reveals a left lower lobe infiltrates. Gram stain of the sputum shows numerous lancet-shaped gram-positive diplococci. He needs to be given levofloxacin 750 mg by mouth for five days. Which of the following should be ruled out before prescribing this antibiotic to the patient?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 70-year-old female patient with a history of chronic obstructive pulmonary disease is brought to the emergency department for sudden onset of shortness of breath, and cough with mucopurulent sputum. She reports a recurrence of these symptoms since a year for which she has been taking inhaled steroids. She also has a history of chronic renal failure. On examination, her temperature is 38 C (100.4 F), the pulse is 80/min, respirations are 25/min, and blood pressure is 110/70 mm Hg. Lung auscultation reveals prolonged expiratory wheezing. She is empirically treated with a course of an oral antibiotic for seven days and improves. Two weeks later, she presents to the outpatient with pain and swelling over the left heel. She denies any recent traumatic injury to the foot. Which of the following antibiotic is likely responsible for the new symptoms in this patient?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Levofloxacin - References

References

Bush LM,Chaparro-Rojas F,Okeh V,Etienne J, Cumulative clinical experience from over a decade of use of levofloxacin in urinary tract infections: critical appraisal and role in therapy. Infection and drug resistance. 2011;     [PubMed]
Yew WW,Chan CK,Chau CH,Tam CM,Leung CC,Wong PC,Lee J, Outcomes of patients with multidrug-resistant pulmonary tuberculosis treated with ofloxacin/levofloxacin-containing regimens. Chest. 2000 Mar;     [PubMed]
Anderson VR,Perry CM, Levofloxacin : a review of its use as a high-dose, short-course treatment for bacterial infection. Drugs. 2008;     [PubMed]
Fish DN,Chow AT, The clinical pharmacokinetics of levofloxacin. Clinical pharmacokinetics. 1997 Feb;     [PubMed]
Zhang L,Wei MJ,Zhao CY,Qi HM, Determination of the inhibitory potential of 6 fluoroquinolones on CYP1A2 and CYP2C9 in human liver microsomes. Acta pharmacologica Sinica. 2008 Dec;     [PubMed]
Ball P, Efficacy and safety of levofloxacin in the context of other contemporary fluoroquinolones: a review. Current therapeutic research, clinical and experimental. 2003 Nov;     [PubMed]
Jones CB,Fugate SE, Levofloxacin and warfarin interaction. The Annals of pharmacotherapy. 2002 Oct;     [PubMed]
Tanne JH, FDA adds     [PubMed]
Levofloxacin 2006;     [PubMed]
Fish DN, Fluoroquinolone adverse effects and drug interactions. Pharmacotherapy. 2001 Oct;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of PA-Hospital Medicine. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for PA-Hospital Medicine, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in PA-Hospital Medicine, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of PA-Hospital Medicine. When it is time for the PA-Hospital Medicine board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study PA-Hospital Medicine.