Ofloxacin

Article Author:
Derrick Graham
Article Editor:
Jayson Tripp
Updated:
12/30/2019 11:05:11 PM
PubMed Link:
Ofloxacin

Indications

Ofloxacin is an antimicrobial drug in the fluoroquinolone family that is effective in treating a wide variety of bacterial infections. It received FDA approval in 1990 as a “1C" drug, categorizing it as a new molecular entity offering little or no therapeutic advantage over existing therapies, namely, ciprofloxacin. Yet, despite its insignificant therapeutic benefit, ofloxacin earned support for its improved oral bioavailability, longer half-life, and expanded applications to certain sexually transmitted infections compared to its counterpart, ciprofloxacin. 

The following are FDA-approved indications for ofloxacin use: 

  • Otitis externa from infection with Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus
  • Chronic suppurative otitis media due to Proteus mirabilis, Pseudomonas aeruginosa, or Staphylococcus aureus
  • Acute otitis media from Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa Staphylococcus aureus, or Streptococcus pneumonia
  • Conjunctivitis due to Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Enterobacter cloacaeHaemophilus influenzae, Proteus mirabilis, or Pseudomonas aeruginosa
  • Corneal ulcers due to infection with Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Enterobacter cloacae, Haemophilus influenzae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens, or Cutibacterium acnes
  • Acute bacterial exacerbations of chronic bronchitis resulting from Haemophilus influenzae or Streptococcus pneumoniae
  • Community-acquired pneumonia due to Haemophilus influenzae or Streptococcus pneumoniae
  • Uncomplicated skin and skin structure infection due to methicillin-susceptible Staphylococcus aureus, Streptococcus pyogenes, or Proteus mirabilis
  • Acute, uncomplicated urethral and cervical gonorrhea from Neisseria gonorrhoeae infection
  • Nongonococcal urethritis and cervicitis due to Chlamydia trachomatis
  • Mixed infections of the urethra and cervix with Chlamydia trachomatis or Neisseria gonorrhoeae
  • Acute pelvic inflammatory disease (includes severe infection) due to Chlamydia trachomatis or Neisseria gonorrhoeae
  • Uncomplicated cystitis as a result of Citrobacter diversus, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa
  • Complicated urinary tract infections from infection with Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter diversusor Pseudomonas aeruginosa
  • Prostatitis resulting from Escherichia coli

Additionally, traveler’s diarrhea, leprosy, epididymitis, and spontaneous bacterial peritonitis are non-FDA approved indications for ofloxacin use.[1][2][3]

Mechanism of Action

As with other second-generation fluoroquinolone drugs, ofloxacin is a broad-spectrum antibiotic that exhibits a bactericidal effect. It works by binding to and inhibiting bacterial topoisomerase II (DNA gyrase), an enzyme that relaxes supercoiled DNA, and topoisomerase IV, an enzyme that separates linked daughter chromosomes following replication. These inhibitory effects interrupt DNA replication, transcription, and repair, thereby preventing cell division in bacterial cells.[4]  

Administration

Ofloxacin administration can be in oral, intravenous, or topical forms. General infections receive oral or intravenous ofloxacin. In instances of severe infection, intravenous administration is preferable as it allows higher dosing that leads to higher drug concentrations, ultimately leading to an increase in clinical cure rates.[5]

Topical preparations exist for specific cases. For otitis externa and otitis media, patients have treatment with an ofloxacin otic drop solution. Topical ofloxacin penetrates the tympanic membrane, achieving similar middle ear concentrations through topical or by systemic administration.[6]  For bacterial conjunctivitis and corneal ulcers, patients can receive an ofloxacin ophthalmic drop solution. An animal study demonstrated that topical ofloxacin permeates the cornea, achieving therapeutic levels in the anterior and posterior chambers of the eye while sparing the retina from any toxic effects.[7]

Fluoroquinolones chelate di- and trivalent metal cations, thus antacids or vitamins containing calcium, magnesium, aluminum, iron, and zinc should be avoided during ofloxacin therapy, as these reduce the amount of drug that gets absorbed.[8] 

Adverse Effects

The most characteristic adverse effect of ofloxacin treatment, along with other fluoroquinolone treatments, is tendinopathy, typically presenting as pain or swelling along a tendon’s path. Such injury has been observed both during drug administration and up to several months after. In patients receiving corticosteroid therapy or engaging in strenuous physical activity with concurrent ofloxacin administration, there is a particularly high risk of tendon rupture. This injury primarily affects the Achilles tendon and necessitates surgical repair.  

It is also possible for ofloxacin treatment to cause increased intracranial pressure and toxic psychosis.[9] As ofloxacin may stimulate the central nervous system, neurological effects such as seizures, lightheadedness, hallucinations, restlessness, tremors, anxiety, depression, confusion, difficulty sleeping, nightmares, paranoia, or suicidal thoughts or acts may also occur. These effects may develop after as little as one dose and call for immediate termination of treatment. Caution is necessary when considering therapy for patients with preexisting conditions or risk factors that predispose to seizures or other CNS effects.  

Hypersensitivity reactions are another adverse effect occasionally observed with ofloxacin treatment, most frequently following the initial dose. This Type I hypersensitivity reaction is the result of some patients possessing preformed serum IgE against ofloxacin.[10] Reported signs of a hypersensitivity reaction include seizure, cardiovascular collapse, shock, loss of consciousness, airway obstruction, dyspnea, tingling, angioedema, urticaria, itching, and other allergic skin manifestations.  On rare occasion and following multiple doses, other serious and sometimes fatal hypersensitivity-associated events have been observed, involving fever, rash, severe dermatologic reactions, vasculitis, serum sickness, arthralgia, myalgia, allergic pneumonitis, interstitial nephritis, acute renal insufficiency or failure, acute hepatic necrosis or failure, hepatitis, jaundice, hemolytic or aplastic anemia, thrombocytopenia, leukopenia, agranulocytosis, pancytopenia, and other hematologic disorders. As with other hypersensitivity reactions, the earliest indication of these clinical manifestations calls for immediate discontinuation of treatment. 

Though uncommon, ofloxacin treatment has also led to reports of peripheral neuropathy, as manifest by pain, burning, tingling, numbness, weakness, and altered sensation. Exacerbation of muscle weakness in a patient with myasthenia gravis is a dangerous possibility. The earliest indication of these clinical manifestations calls for immediate discontinuation of treatment. 

Other rare and serious adverse effects include prolongation of the QT interval and aortic aneurysm.

Contraindications

Ofloxacin use is contraindicated in patients with a history of quinolone-associated hypersensitivity reactions, myasthenia gravis, and prolonged QT interval. Unless there is no other option, it is also contraindicated in patients with a history of or at increased risk for aortic aneurysm, Marfan syndrome, or Ehlers-Danlos syndrome.

Monitoring

In general, ofloxacin is regarded as a safe drug with a considerable safety margin.[11][12] For patients with an increased risk of adverse effects or in cases with a prolonged treatment course, useful values and tests for monitoring include creatinine levels, CBC, and liver function tests. The therapeutic index for ofloxacin varies by bacterial agent and indication.

Toxicity

Orally administered ofloxacin has a bioavailability of approximately 98% and reaches peak serum concentration one to two hours after administration. Elimination occurs primarily through renal excretion, although a small portion (4 to 8%) of the drug is excreted fecally as bile.[12] 

In cases of overdose, gastric lavage and sufficient hydration are recommended interventions. No antidotes yet exist, and dialysis treatments are not effective in reversing toxicity.[12] Activated charcoal may decrease ofloxacin absorption and reduce the likelihood of systemic toxicity.[13] 

Enhancing Healthcare Team Outcomes

By supporting patients with diverse interprofessional teams of healthcare providers, many severe adverse effects of ofloxacin treatment are avoidable. A nurse or physician taking the patient’s history may identify patients at high risk due to previous histories of hypersensitivity reactions, tendon disorders, cardiovascular disorders, Marfan syndrome, Ehlers-Danlos syndrome, or risk factors that lower the seizure threshold. Pharmacists may notice red flags for patients who are already taking corticosteroids, antiarrhythmics, or CNS medications whose adverse effects would be compounded by ofloxacin treatment. In these cases, the patients benefit from proactive interprofessional teams capable of working together to devise alternative drug treatment plans or ensuring that proper monitoring was available to ensure successful treatment and avoid adverse effects.  The pharmacist should assist the team by verifying dosing, and in severe cases, and infectious disease board-certified pharmacist can provide antibiogram data to direct agent selection. Nursing can monitor for adverse events and treatment effectiveness. This type of interprofessional team paradigm enhances positive results while minimizing adverse effects. [Level 5]


References

[1] Ta┼čkiran B,Colako─člu O,Sözmen B,Unsal B,Aslan SL,Buyraç Z, Comparison of cefotaxime and ofloxacin in treatment of spontaneous bacterial peritonitis. The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology. 2004 Mar;     [PubMed PMID: 15264119]
[2] Kumar A,Girdhar A,Girdhar BK, A randomized controlled trial to compare cure and relapse rate of paucibacillary multidrug therapy with monthly rifampicin, ofloxacin, and minocycline among paucibacillary leprosy patients in Agra District, India. Indian journal of dermatology, venereology and leprology. 2015 Jul-Aug;     [PubMed PMID: 26144850]
[3] Vieler E,Jantos C,Schmidts HL,Weidner W,Schiefer HG, Comparative efficacies of ofloxacin, cefotaxime, and doxycycline for treatment of experimental epididymitis due to Escherichia coli in rats. Antimicrobial agents and chemotherapy. 1993 Apr;     [PubMed PMID: 8494382]
[4] Levine C,Hiasa H,Marians KJ, DNA gyrase and topoisomerase IV: biochemical activities, physiological roles during chromosome replication, and drug sensitivities. Biochimica et biophysica acta. 1998 Oct 1;     [PubMed PMID: 9748489]
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[6] Koulich E,Roland PS,Pawlowski KS, Comparison of systemic and otic administration of ofloxacin. The Laryngoscope. 2010 Oct;     [PubMed PMID: 20830758]
[7] Cohen RG,Raizman M,Callina C,Lahav M, Retinal safety of oral and topical ofloxacin in rabbits. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 1997 Aug;     [PubMed PMID: 9261772]
[8] Pitman SK,Hoang UTP,Wi CH,Alsheikh M,Hiner DA,Percival KM, Revisiting Oral Fluoroquinolone and Multivalent Cation Drug-Drug Interactions: Are They Still Relevant? Antibiotics (Basel, Switzerland). 2019 Jul 31;     [PubMed PMID: 31370320]
[9] Zaudig M,von Bose M, Ofloxacin-induced psychosis. The British journal of psychiatry : the journal of mental science. 1987 Oct;     [PubMed PMID: 3482162]
[10] Nam YH,Kim JE,Kim SH,Jin HJ,Hwang EK,Shin YS,Ye YM,Park HS, Immunologic evaluation of ofloxacin hypersensitivity. Allergy, asthma     [PubMed PMID: 23115735]
[11] Tack KJ,Smith JA, The safety profile of ofloxacin. The American journal of medicine. 1989 Dec 29;     [PubMed PMID: 2690623]
[12] Todd PA,Faulds D, Ofloxacin. A reappraisal of its antimicrobial activity, pharmacology and therapeutic use. Drugs. 1991 Nov;     [PubMed PMID: 1723377]
[13] Stass H,Kubitza D,Möller JG,Delesen H, Influence of activated charcoal on the pharmacokinetics of moxifloxacin following intravenous and oral administration of a 400 mg single dose to healthy males. British journal of clinical pharmacology. 2005 May;     [PubMed PMID: 15842551]