By: Ron Melton, OD, FAAO
ABSTRACT Bacterial conjunctivitis is a common ocular infection that, although usually self-limited, can result in severe cases and develop vision threatening complications. Diagnosis of bacterial conjunctivitis is generally clinical, and most cases can be managed with empirical antibiotic therapy. Use of a potent, broad spectrum topical antibiotic maximizes the chances of rapid, successful resolution. BESIVANCE® (besifloxacin ophthalmic suspension) 0.6%, a fluoroquinolone developed specifically for topical ocular use and approved for the treatment of bacterial conjunctivitis, provides such an antibiotic choice. BESIVANCE® is a quinolone antimicrobial indicated for the treatment of bacterial conjunctivitis caused by susceptible isolates of the following bacteria: Aerococcus viridans*, CDC coryneform group G, Corynebacterium pseudodiphtheriticum*, Corynebacterium striatum*, Haemophilus influenzae, Moraxella catarrhalis*, Moraxella lacunata*, Pseudomonas aeruginosa*, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis*, Staphylococcus lugdunensis*, Staphylococcus warneri*, Streptococcus mitis group, Streptococcus oralis, Streptococcus pneumoniae, Streptococcus salivarius*.
*Efficacy for this organism was studied in fewer than 10 infections.
As a double halogenated topical chlorofluoroquinolone, BESIVANCE® demonstrates potent activity against a range of important ocular pathogens, including strains of methicillin-resistant staphylococci, and susceptible isolates of Pseuedomonas aeruginosa. Formulated in a mucoadhesive vehicle, BESIVANCE® also has excellent ocular surface residence time, making it a superb choice for the treatment of bacterial conjunctivitis.
Important Risk Information for BESIVANCE®
- BESIVANCE® is for topical ophthalmic use only, and should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye.
- As with other anti-infectives, prolonged use of BESIVANCE® may result in overgrowth of nonsusceptible organisms, including fungi. If super-infection occurs, discontinue use and institute alternative therapy.
- Patients should not wear contact lenses if they have signs or symptoms of bacterial conjunctivitis or during the course of therapy with BESIVANCE®.
- The most common adverse event reported in 2% of patients treated with BESIVANCE® was conjunctival redness. Other adverse events reported in patients receiving BESIVANCE® occurring in approximately 1-2% of patients included: blurred vision, eye pain, eye irritation, eye pruritus and headache.
- BESIVANCE® is not intended to be administered systemically. Quinolones administered systemically have been associated with hypersensitivity reactions, even following a single dose. Patients should be advised to discontinue use immediately and contact their physician at the first sign of a rash or allergic reaction.
- Safety and effectiveness in infants below one year of age have not been established.
Bacterial conjunctivitis is a common ocular surface infection. Each year, one in every eight US children comes down with acute conjunctivitis, most of which is bacterial; and bacterial conjunctivitis accounts for about 1% of all primary care office visits.1 In the US, the incidence of bacterial conjunctivitis is estimated at about 1.3%.2
Typically, bacterial conjunctivitis is acute and self-limited. It can resolve spontaneously, but topical antibiotic therapy offers a number of benefits.3 Antibiotic treatment can shorten the course of the disease, enabling a faster return to school or work. Faster resolution also reduces the risk of transmission and the potential for a lingering moderate or severe bacterial conjunctivitis causing serious complications.
Spectrum of Activity and Potency
The organisms that most often cause bacterial conjunctivitis include Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and Staphylococcus epidermidis.4 Among these, S. aureus is typically the most aggressive organism, and the combination of virulence and drug resistance makes methicillin-resistant S. aureus (MRSA) an organism of great concern. Although MRSA has moved out into the community, healthcare workers remain at high risk of MRSA colonization because of its prevalence in hospital settings.5
When confronted by a case of bacterial conjunctivitis, the gold standard for determining the causative pathogen is to culture the conjunctiva. Routine culture of every case of conjunctivitis is impractical in general practice settings, however; and patients with bacterial conjunctivitis diagnosed from signs and symptoms are typically treated empirically with topical ophthalmic antibiotics.
To achieve quick and effective bacterial eradication with empirical therapy, it is critical to choose an agent with a wide spectrum of antimicrobial activity.
A Powerful Fluoroquinolone
Current generation fluoroquinolones are the antimicrobial agents most often used to manage ocular infections, including bacterial conjunctivitis, in large part because they have a broad spectrum of activity and are generally well tolerated. Despite overall effectiveness of the class, fluoroquinolone resistance is a growing problem, and there has been a concerning rise in the prevalence of MRSA-caused ocular infections.6 To meet the long-term threat of bacterial resistance, a continuous stream of novel agents will be necessary. In the short term, clinicians can be advised to treat bacterial conjunctivitis empirically with currently available agents that have the potency necessary to neutralize even resistant organisms.
BESIVANCE® (besifloxacin ophthalmic suspension) 0.6% was developed specifically for ophthalmic use and approved for the treatment of bacterial conjunctivitis in 2009.7 Like other fluoroquinolones, its bactericidal activity is a result of inhibitory effects on topoisomerase II (DNA gyrase) and topoisomerase IV, two bacterial enzymes that are essential for DNA replication.7 Older fluoroquinolones targeted primarily topoisomerase IV, whereas later generation fluoroquinolones have increased affinity for topoisomerase II.8
Similar to gatifloxacin and moxifloxacin, which are cyclopropyl fluoroquinolones, the BESIVANCE® molecule contains an N-cyclopropyl group that confers broad-spectrum antimicrobial activity.9 It acts against gram-positive and gram-negative organisms commonly associated with bacterial conjunctivitis.4
What sets BESIVANCE® apart is the addition of a chlorine atom at the C-8 position, which makes BESIVANCE® an 8-chlorofluoroquinolone. It is the first and only double-halogenated ocular fluoroquinolone available in the US. The chlorine addition provides improved potency against both bacterial topoisomerases.9,10 This more balanced dual-binding mechanism may also increase its potency across the bacterial spectrum.10 Additionally, BESIVANCE® has no systemic equivalent, eliminating the risk of resistance from systemic use.9 In vitro resistance to BESIVANCE® occurs at a general frequency of < 3.3 × 10–10 for S. aureus and < 7 × 10–10 for S. pneumonia.7
BESIVANCE® demonstrates efficient killing of the common isolates in bacterial conjunctivitis.11 A review of minimum inhibitory concentration (MIC) values indicates that BESIVANCE® has excellent potency against both gram-positive and gram-negative bacteria.4
In vitro studies find BESIVANCE® also has significant potency against resistant strains, including MRSA and ciprofloxacin-resistant staphylococci, which is not true of all common topical antibiotics or even of all other fluoroquinolones.4,12
Besifloxacin demonstrates low MIC50 and MIC90 values against MRSA (0.5 μg/mL and 4 μg/mL, respectively), which are comparable to those of vancomycin (MIC50 = 1 μg/mL; MIC90 = 4 μg/mL), a glycopeptide antibiotic regularly used for the treatment of MRSA infections because of its potency against the highly resistant organism.6
While it is not always possible to establish the clinical significance of in vitro data, bacterial conjunctivitis clinical trials have shown excellent therapeutic efficacy and tolerability of BESIVANCE® in adults and children of at least 1 year of age.13-16
In one recent study, treatment with besifloxacin brought about rapid microbial eradication in cases of bacterial conjunctivitis culture-positive for MRSA and methicillin-resistant S. epidermidis (MRSE) - even where isolates were also ciprofloxacin-resistant.17 Microbial eradication does not always correlate with clinical outcome in an antiinfective trial. In vitro reports from this study found the MIC90 values for besifloxacin to be 2 μg/mL against ciprofloxacin-resistant MRSA isolates, and 4 μg/mL against ciprofloxacin-resistant MRSE isolates.17 The clinical significance of in vitro data has not been established.
In my experience, BESIVANCE® is highly effective in treating bacterial conjunctivitis, which I see as a reflection of its potent activity against both susceptible and resistant bacterial strains (see Case Study box).
BESIVANCE® is formulated in a mucoadhesive polymer that enhances drug retention on the ocular surface.18 Extended residence time may result in increased drug concentration on the surface of the eye, and, consequently, improved efficacy for concentration-dependent antibiotics like BESIVANCE®, whose efficacy is greatest when concentrations are high at the site of infection.
Measurement of human tear concentration after a single instillation has shown that BESIVANCE® remains on the ocular surface through 24 hours; at 12 hours after instillation, of one drop in the affected eye(s) 3 times a day, 4 to 12 hours apart, for 7 days.
In 2012, the US FDA granted additional labeling indications for BESIVANCE® (besifloxacin ophthalmic suspension) 0.6%, including indications to treat bacterial conjunctivitis caused by susceptible isolates of Aerococcus viridians, Moraxella catarrhalis, Pseudomonas aeruginosa, and Staphylococcus warneri.7 BESIVANCE® provides practitioners a potent topical antibiotic indicated for most of the pathogens relevant to bacterial conjunctivitis. The approval for P. aeruginosa, in particular, should be reassuring to practitioners, as it represents an official recognition of the activity BESIVANCE® shows against this often highly virulent gram-negative organism.
P. aeruginosa is a concern not just because of its virulence but because of its ability to invade the cornea, particularly in contact lens wearers.19 BESIVANCE® offers proven activity against P. aeruginosa conjunctivitis. Indeed, a recent post hoc analysis of four clinical studies showed that treatment with BESIVANCE® leads to fast microbial eradication and high rates of clinical resolution in patients with bacterial conjunctivitis caused by P. aeruginosa.19 Clinical resolution was defined as the absence of both ocular discharge and bulbar conjunctival injection.
Topical antibiotic therapy is beneficial in patients with bacterial conjunctivitis. In empirical therapy - the typical treatment for bacterial conjunctivitis - it is important to use a potent, broad-spectrum agent. BESIVANCE® has demonstrated excellent therapeutic efficacy in the treatment of bacterial conjunctivitis.14-16,19 The potent bactericidal activity of BESIVANCE® against a wide range of significant ocular pathogens, including resistant strains, makes it a valuable component of the ocular antibiotic armamentarium.
BESIVANCE is a registered trademark of Bausch & Lomb Incorporated. All other product/brand names are trademarks of their respective owners.
- Hovding G. Acute bacterial conjunctivitis. Acta Ophthalmologica. 2008;86:5-17.
- Smith AF, Waycaster C. Estimate of the direct and indirect annual cost of bacterial conjunctivitis in the United States. BMC Ophthalmol. 2009;9:13.
- Sheikh A, Hurwitz B, van Schayck CP, et al. Antibiotics versus placebo for acute bacterial conjunctivitis. Cochrane Database of Systematic Reviews 2012, Issue 9. No.: CD001211.
- Haas W, Gearinger LS, Usner DW, et al. Integrated analysis of three bacterial conjunctivitis trials of besifloxacin opthalmic suspension, 0.6%: etiology of bacterial conjunctivitis and antibacterial susceptibility profile. Clin Ophthalmol. 2011;5:1369–79.
- Byrne FM, Wilcox MH. MRSA prevention strategies and current guidelines. Injury. 2011;42 Suppl 5:S3-6.
- Haas W, et al. Monitoring antibiotic resistance in ocular microorganisms: results from the Antibiotic Resistance in Ocular Microorganisms (ARMOR) 2009 Surveillance Study. Am J Ophthalmol. 2011;152(4):567-74.
- BESIVANCE® package insert. Tampa, FL: Bausch & Lomb Incorporated; 2012.
- Carter NJ, Scott LJ. Besifloxacin ophthalmic suspension 0.6%. Drugs. 2010;70(1):83-97.
- Ward KH, Lepage J-F, Driot J-Y. Nonclinical pharmacodynamics, pharmacokinetics, and safety of BOL-303224-A, a novel fluoroquinolone antimicrobial agent for topical ophthalmic use. J Ocul Pharmacol Ther. 2007;23:243–56.
- Cambau E, Matrat S, Pan X, et al. Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli. J Antimicrob Chemother. 2009;63(3):443-50.
- Morris TW, Gearinger LS, Usner DW, et al. Integrated analysis of three bacterial conjunctivitis trials of besifloxacin ophthalmic suspension, 0.6%: microbiological eradication outcomes. Clin Ophthalmol. 2011;5:1359-67.
- Silverstein BE, Allaire C, Bateman KM, et al. Efficacy and tolerability of besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days in the treatment of bacterial conjunctivitis: a multicenter, randomized, double-masked, vehicle-controlled, parallel- group study in adults and children. Clin Ther. 2011;33(1):13-26.
- Comstock TL, Paterno MR, Usner DW, et al. Efficacy and safety of besifloxacin ophthalmic suspension 0.6% in children and adolescents with bacterial conjunctivitis: a post hoc, subgroup analysis of three randomized, double-masked, parallel-group, multicenter clinical trials. Paediatr Drugs. 2010;12(2):105-12.
- McDonald MB, Protzko EE, Brunner LS, et al. Efficacy and safety of besifloxacin ophthalmic suspension 0.6% compared with moxifloxacin ophthalmic solution 0.5% for treating bacterial conjunctivitis. Ophthalmology. 2009;116 (9): 1615-23.
- Karpecki P, DePaolis M, Hunter JA, et al. Besifloxacin ophthalmic suspension 0.6% in patients with bacterial conjunctivitis: a multicenter, prospective, randomized, double-masked, vehicle-controlled, 5-day efficacy and safety study. Clin Ther. 2009; 31 (3): 514-26.
- Tepedino ME, Heller WH, Usner DW, et al. Phase III efficacy and safety study of besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis. Curr Med Res Opin. 2009; 25 (5): 1159-69
- DeCory HH, Comstock TL, Gearinger LS, Morris TW. Clinical efficacy of besifloxacin ophthalmic suspension, 0.6% against MRSA and MRSE. Poster presented at the annual meeting of the Association for Research in Vision and Ophthalmology; Fort Lauderdale, FL; May 6-10, 2012.
- Protzko E, Bowman L, Abelson M, et al; for the AzaSite Clinical Study Group. Phase 3 safety comparisons for 1.0% azithromycin in polymeric mucoadhesive eye drops versus 0.3% tobramycin eye drops for bacterial conjunctivitis. Invest Ophthalmol Vis Sci. 2007;48:3425–9.
- Silverstein BE, Morris TW, Gearinger LS, et al. Besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis patients with Pseudomonas aeruginosa infections. Clin Ophthalmol. 2012;6:1987-96.