Levofloxacin; Uses, Dosage, Side Effects, Interactions, Pregnancy

Levofloxacin
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Levofloxacin is a broad-spectrum, third-generation fluoroquinolone antibiotic and optically active L-isomer of ofloxacin with antibacterial activity. Levofloxacin diffuses through the bacterial cell wall and acts by inhibiting DNA gyrase (bacterial topoisomerase II), an enzyme required for DNA replication, RNA transcription, and repair of bacterial DNA. Inhibition of DNA gyrase activity leads to blockage of bacterial cell growth.
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Levofloxacin is a third generation fluoroquinolone that is widely used in the treatment of mild-to-moderate respiratory and urinary tract infections due to sensitive organisms. Levofloxacin has been linked to rare instances of clinically apparent hepatic injury marked by a short latency period and a hepatocellular pattern of enzyme elevations, similar to what has been described with ciprofloxacin.
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Levofloxacin belongs to the class of medications called quinolones. Levofloxacin is a broad-spectrum antibiotic of the fluoroquinolone drug class.It usually results in death of the bacteria. It is the left-sided isomer of the medication ofloxacin. It is an antibiotic used for the treatment of certain bacterial infections. It is most commonly used to treat infections of the bladder, kidney, prostate, sinus, skin, and lung.

Mechanism of Action of Levofloxacin

Levofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. Like all quinolones, it functions by inhibiting the DNA gyrase and topoisomerase IV. Topoisomerase IV is necessary to separate DNA that has been replicated (doubled) prior to bacterial cell division. With the DNA not being separated, the process is stopped, and the bacterium cannot divide. DNA gyrase, on the other hand, is responsible for supercoiling the DNA, so that it will fit in the newly formed cells. Both mechanisms amount to killing the bacterium. Levofloxacin acts as a bactericide.

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Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels, especially the rapid component of the delayed rectifier potassium current I(Kr), expressed by HERG (the human ether-a-go-go-related gene). According to the available case reports and clinical studies, moxifloxacin carries the greatest risk of QT prolongation from all available quinolones in clinical practice and it should be used with caution in patients with predisposing factors for Torsades de pointes (TdP).

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Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer. The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination.

Indications of Levofloxacin

Levofloxacin is used to treat bacterial infections in adults. These include:

  • Pneumonia
  • Sinus infection
  • Worsening of chronic bronchitis
  • Skin infections
  • Chronic prostate infection
  • Urinary tract infections
  • Pyelonephritis (kidney infection)
  • Inhalational anthrax
  • Plague
  • Bacterial Infection
  • Urinary Tract Infection
  • Anthrax
  • Anthrax Prophylaxis
  • Bladder Infection
  • Bronchitis
  • Chlamydia Infection
  • Epididymitis, Sexually Transmitted
  • Gonococcal Infection, Disseminated
  • Gonococcal Infection, Uncomplicated
  • Kidney Infections
  • Nongonococcal Urethritis
  • Nosocomial Pneumonia
  • Otitis Media
  • Pelvic Inflammatory Disease
  • Plague
  • Sinusitis
  • Skin or Soft Tissue Infection
  • Streptococcal Infection
  • Tuberculosis, Active
  • For the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms: Corynebacterium species, Staphylococus aureusStaphylococcus epidermidisStreptococcus pneumoniaeStreptococcus (Groups C/F/G), Viridans group streptococci, Acinetobacter lwoffiiHaemophilus influenzaeSerratia marcescens.
  • Indicated in adults for the treatment of Respiratory Tract Infections (RTIs), Urinary Tract ,Infections (UTIs);
  • Skin and soft tissue infections (SSTIs);Anthrax curative treatment;Quinsair is indicated for the management of chronic pulmonary infections due to Pseudomonas aeruginosa in adult patients with cystic fibrosis. Consideration should be given to official guidance on the appropriate use of antibacterial agents.
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Therapeutic Indications of Levofloxacin

  • Levofloxacin is used for the treatment of acute bacterial sinusitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.
  • Levofloxacin is used for the treatment of community-acquired pneumonia caused by susceptible S. aureus (oxacillin-susceptible strains), S. pneumoniae (including penicillin-resistant strains (penicillinMIC of 2 ug/mL or greater)), H. influenzae, H. parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, M. catarrhalis, Chlamydophila pneumoniae (formerly Chlamydia pneumoniae), or Mycoplasma pneumoniae.
  • Levofloxacin is used for the treatment of mild to moderate complicated urinary tract infections caused by susceptible E. faecalis, Enterobacter cloacae, E. coli, K. pneumoniae, P. mirabilis, or Ps. aeruginosa and acute pyelonephritis caused by susceptible E. coli, including cases with concurrent bacteremia.
  • Levofloxacin is used for the treatment of mild to moderate uncomplicated urinary tract infections caused by susceptible E. coli, K. pneumoniae, or S. saprophyticus.
  • Levofloxacin is used for the treatment of mild to moderate uncomplicated skin and skin structure infections caused by susceptible S. aureus (oxacillin-susceptible strains) or S. pyogenes (group A beta-hemolytic streptococci) and for the treatment of complicated skin and skin structure infections caused by susceptible S. aureus (oxacillin-susceptible strains), Enterococcus faecalis, S. pyogenes, or Proteus mirabilis.
  • Levofloxacin is used for the treatment of nosocomial pneumonia caused by susceptible S. aureus (oxacillin-susceptible strains), S. pneumoniae, H. influenzae, Escherichia coli, K. pneumoniae, Ps. aeruginosa, or Serratia marcescens.
  • Levofloxacin is used for the treatment of acute bacterial exacerbations of chronic bronchitis caused by susceptible Staphylococcus aureus (oxacillin-susceptible (methicillin-susceptible) strains), S. pneumoniae, H. influenzae, H. parainfluenzae, or M. catarrhalis.
  • Levofloxacin is used for inhalational anthrax (postexposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis.1 Although the efficacy of levofloxacin for postexposure prophylaxis to prevent inhalational anthrax has not been evaluated in human clinical trials, the drug is labeled by the US Food and Drug Administration (FDA) for this indication based on a surrogate end point derived from a primate model of inhalational anthrax that predicts clinical benefit based on plasma levofloxacin concentrations achievable in humans with recommended oral or IV dosages.
  • Levofloxacin is used for the treatment of chronic prostatitis caused by susceptible E. coli, E. faecalis, or S. epidermidis (oxacillin-susceptible strains).
  • Oral levofloxacin is used for short-term treatment of travelers’ diarrhea or for the prevention of travelers’ diarrhea in adults traveling for relatively short periods of time to high-risk areas.
  • Fluoroquinolones (e.g., ciprofloxacin, levofloxacin, ofloxacin) have been suggested as alternative agents for the treatment of plague caused by Yersinia pestis and also have been recommended for postexposure prophylaxis following a high risk exposure to Y. pestis, including exposure in the context of biologic warfare or bioterrorism.
  • Levofloxacin is recommended as an alternative for the treatment of acute pelvic inflammatory disease (PID), but should not be used if quinolone-resistant N. gonorrhoeae may be involved or if in vitro susceptibility cannot be tested.
  • The CDC recommends oral levofloxacin as an alternative agent for the treatment of nongonococcal urethritis.
  • Fluoroquinolones, including levofloxacin, have been used in multiple-drug regimens for the treatment of active tuberculosis, usually in patients with infections caused by Mycobacterium tuberculosis resistant to first-line agents and in patients intolerant of some first-line agents.
  • Levofloxacin has been used in a limited of patients for the treatment of meningitis caused by susceptible organisms (e.g., Rhodococcus equi)64 and has been suggested as a possible alternative for use in conjunction with other anti-infectives for the treatment of meningitis caused by susceptible bacteria.
  • Levofloxacin is used for the treatment of epididymitis most likely caused by sexually transmitted enteric bacteria (e.g., E. coli) or when culture or nucleic acid amplification tests are negative for N. gonorrhoeae.
  • Levofloxacin has been used in the treatment of disseminated gonococcal infections caused by susceptible N. gonorrhoeae.
  • Levofloxacin has been used for the treatment of uncomplicated gonorrhea caused by susceptible Neisseria gonorrhoeae. Although fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin) were previously considered drugs of choice for the treatment of uncomplicated gonorrhea, the CDC currently states that fluoroquinolones should not be used for the treatment of gonorrhea or any associated infections that may involve N. gonorrhoeae (e.g., pelvic inflammatory disease (PID), epididymitis).
  • Levofloxacin is used as an alternative for treatment of native or prosthetic valve endocarditis caused by fastidious gram-negative bacilli known as the HACEK group (Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Haemophilus aphrophilus, H. influenzae, H. parainfluenzae, H. paraphrophilus, Kingella denitrificans, K. kingae).
  • Although levofloxacin has not been evaluated in clinical trials for the treatment of chlamydial infections, levofloxacin is considered an alternative agent for the treatment of urogenital infections caused by C. trachomatis.
  • Levofloxacin 0.5% ophthalmic solution is used for the treatment of conjunctivitis caused by susceptible strains of Acinetobacter lwoffii, Corynebacterium spp, Haemophilus influenzae, Serratia marcescens, Staphylococcus aureus, S. epidermidis, groups C, F, and G streptococci, viridans streptococci, or Streptococcus pneumoniae.
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Contra-Indications of Levofloxacin

  • History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of betalactam antibacterial agent (penicillins, monobactams and carbapenems).
  • Hemolytic anemia
  • Liver problems
  • Interstitial nephritis
  • Subacute cutaneous lupus erythematosus
  • Systemic lupus erythematosus
  • use should be avoided in pregnant or lactating women, and in children with developing teeth because they may result in permanent staining (dark yellow-gray teeth with a darker horizontal band that goes across the top and bottom rows of teeth), and possibly affect the growth of teeth and bones.
  • Allergy
  • Avoid taking this medicine if you have a known allergy to it or any other fluoroquinolones.
  • Avoid if you have a past history of tendinitis or tendon rupture after using this medicine.
  • Myasthenia Gravis

Dosage of Levofloxacin

Strengths: 250 mg; 500 mg; 750 mg, 25 mg/mL; 750 mg/150 mL; 250 mg/50 mL; 500 mg/100 mL

Nosocomial Pneumonia

  • 750 mg orally or IV every 24 hours for 7 to 14 days

Pneumonia

  • For 7- to 14-day regimen: 500 mg orally or IV every 24 hours for 7 to 14 days
  • For 5-day regimen: 750 mg orally or IV every 24 hours for 5 days

For the treatment of community-acquired pneumonia

  • For 7- to 14-day regimen: Due to methicillin-susceptible S aureus, S pneumoniae (including MDRSP), H influenzae, H parainfluenzae, K pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumonia
  • For 5-day regimen: Due to S pneumoniae (excluding MDRSP), H influenzae, H parainfluenzae, M pneumoniae, or C pneumonia

Skin and Structure Infection

  • Complicated infection: 750 mg orally or IV every 24 hours for 7 to 14 days
  • Uncomplicated infection: 500 mg orally or IV every 24 hours for 7 to 10 days

Duration of Therapy

  • Postexposure prophylaxis for B anthracis infection: 60 days

Systemic anthrax

  • With possible/confirmed meningitis: At least 2 to 3 weeks or untilthe the patient is clinically stable (whichever is longer)
  • When meningitis has been excluded: 2 weeks or until patient is clinically stable (whichever is longer)
  • Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial regimen of 60 days from onset of illness.

Cutaneous anthrax without systemic involvement

  • Bioterrorism-related cases: 60 days
  • Naturally-acquired cases: 7 to 10 days

Side Effects of Levofloxacin

The most common 

More common

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Rare

Drug Interactions of Levofloxacin

Levofloxacin may interact with following drugs, supplyments, & may change the efficacy of drugs

Pregnancy and Lactation of Levofloxacin

FDA Pregnancy Category B 

Pregnancy

There are a limited amount of data with respect to the use of levofloxacin in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. However in the absence of human data and due to that experimental data suggest a risk of damage by fluoroquinolones to the weight-bearing cartilage of the growing organism, levofloxacin must not be used in pregnant women.

Lactation

This medication may pass into breast milk. If you are a breast-feeding mother and are taking levofloxacin, it may affect your baby . Levofloxacin tablets are contraindicated in breast-feeding women. There is insufficient information on the excretion of levofloxacin in human milk; however other fluoroquinolones are excreted in breast milk. In the absence of human data and due to that experimental data suggest a risk of damage by fluoroquinolones to the weight-bearing cartilage of the growing organism, levofloxacin must not be used in breastfeeding women.

References

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