This past fall, I had the opportunity to lecture again at the Tasmania Lifestyle Congress in Hobart, Tasmania, Australia. I enjoy lecturing abroad because it gives me the opportunity to meet colleagues the world over and to see how optometry is practiced elsewhere.
From a therapeutic perspective, optometrists in both Australia and New Zealand are very sophisticated and keep abreast of the literature when delivering care to their patients. Our therapeutic options in the U.S. are very similar. In fact, we use the same glaucoma medications. But, there is one area where I see a major difference: topical antibiotics.
In the U.S., we have a plethora of later-generation fluoroquinolones, such as moxifloxacin, gatifloxacin, levofloxacin and besifloxacin. However, these medications are not available in Australia––and it is unclear if they ever will be. In Australia, the only fluoroquinolones available are ofloxacin and ciprofloxacin, and these medications typically are reserved for cases of bacterial keratitis.1 Of course, these fluoroquinolones are still available as generics in the U.S., but are not often used because of the availability of newer alternatives as well as concerns of bacterial resistance.2,3
Bacterial keratitis is as common in Australia as in the U.S., with contact lens wear and ocular surgery as precipitating events.4,5 Despite the absence of the later-generation fluoroquinolones, Australian eye care providers and their patients do not seem to be suffering. Interestingly, there are low resistance rates of Pseudomonas aeruginosa and Staphylococcus aureus to ciprofloxacin in Australia.1 You have to wonder how clinicians Down Under can be so successful, yet we in America seem to have significant issues with resistance and consistently need to develop new drugs to combat these heartier microbes.
Emerging Resistance
Antibiotic resistance among ocular pathogens seems to be increasing in correlation with the prevalence of resistant bacteria associated with systemic infections. In other words, systemic treatment of bacterial infections seems to be promoting the development of organisms that are heartier and more resistant to antimicrobial therapy.6 So, when one of these heartier organisms infects the conjunctiva or cornea, there may be fewer therapeutic options.
We have always looked upon heavy systemic use of antibiotics as well as antibiotic treatment of livestock feed as primary culprits for ophthalmic resistance. And, although the rise in resistant ocular bacteria is apparently linked to the increase in resistant systemic pathogens, recent evidence has identified the emergence of resistant bacteria in the eye to prior topical antibiotic therapy.6 In any case, either of these postulations contributes to the emergence of resistance among ocular pathogens. (To that end, besifloxacin is one of the latest fluoroquinolones that has no systemic counterpart. It was developed exclusively for ophthalmic use with the hope that it will decrease the development of resistant microbes because of no systemic use.)
The author making friends with some of the locals.
A recent surveillance study saw that a large proportion of S. aureus and coagulase-negative staphylococci isolates were resistant to oxacillin/methicillin, azithromycin and fluoroquinolones.7 Another study indicated that methicillin-resistant staphylococci were more likely to be resistant to fluoroquinolones, aminoglycosides and macrolides.8
There are two schools of thought regarding antibiotic choice and the development of resistance.
• High risk. This concept involves using the most potent antibiotics only in high-risk cases, such as bacterial keratitis. In most countries outside the U.S., topical fluoroquinolones––particularly those recently approved by the European Medicines Agency, including levofloxacin and moxifloxacin––rarely are used. The strategy of using topical fluoroquinolones as a last resort reflects a belief that the agents may enhance the development of resistance, jeopardizing future availability of antibacterial treatment for ocular infections.9
• High concentration. The other school of thought suggests that the use of topical fluoroquinolones, which results in antibacterial concentrations at the ocular surface that can significantly exceed mutant prevention concentrations (approximately 10 times the minimum inhibitory concentration), should be preferentially used in order to prevent the development of resistance. In the case of later-generation fluoroquinolones such as topical moxifloxacin, a dual-step mutation is required for resistance to emerge. Moxifloxacin restricts the selection of resistant mutants, meaning that emergence of resistance is unlikely.9
It is not clear which strategy is most appropriate. Despite the availability of just two fluoroquinolones in Australia, resistance rates are quite low. A study from New South Wales, Australia, indicated that ocular infections––both conjunctivitis and keratitis––involving S. aureus in the U.S. exhibited greater resistance to antibiotics than those in Australia.10 Additionally, the researchers noted that isolates from corneal infections were more resistant to antibiotics than those from conjunctival infections, with isolates from the U.S. demonstrating the greatest resistance levels.10
Nonetheless, there have been some issues with bacterial resistance in Australia. For example, there is an emerging resistance to cefazolin, which commonly is used as a first-line antibiotic for gram-positive cocci.11 However, most microorganisms isolated from patients with bacterial keratitis in Australia showed susceptibility to ciprofloxacin and aminoglycosides.12
So, if clinicians in Australia typically restrict their use of the two available fluoroquinolones to cases of bacterial keratitis, what do they use for other conditions?
Chloramphenicol Revisited
In the
January 2008 column, I discussed the widespread use of topical chloramphenicol in New Zealand. In Australia, as in New Zealand, topical chloramphenicol is the most widely used ophthalmic antibiotic. Moreover, it is used extensively throughout the world (except in the U.S.) for the treatment of acute bacterial infections and corneal trauma. Also, due to its excellent ocular penetration, chloramphenicol is very popular in surgical prophylaxis.
Chloramphenicol has a broad spectrum of both gram-positive and gram-negative antibacterial activity, and it is effective against anaerobic organisms, Mycoplasma, Rickettsia and Chlamydia. Especially noteworthy is its low rate of clinical and microbiologic resistance as well as its ability to conquer organisms that are resistant to more common antibiotics.13-16 Chloramphenicol’s efficacy against ocular methicillin-resistant Staphylococcus aureus (MRSA) infections has also been documented in several investigative reports.17-20
To date, there have been 23 cases of aplastic anemia (the majority were not fatal) reported in the U.S. that possibly were associated with the use of topical chloramphenicol.13 This purported association with aplastic anemia has curtailed use of the drug in the U.S.
We have long shied away from topical chloramphenicol due to its perceived threat to patient health and risk of death. But, are Australian optometrists and ophthalmologists worried about chloramphenicol use? Doesn’t seem so. How do I know? Because, in Australia, topical chloramphenicol is sold over the counter without a prescription!
Dr. Sowka has no direct financial interests in any of the products mentioned.
1. Willcox MD. Review of resistance of ocular isolates of Pseudomonas aeruginosa and staphylococci from keratitis to ciprofloxacin, gentamicin and cephalosporins. Clin Exp Optom. 2011 Mar;94(2):161-8.
2. Alexandrakis G, Alfonso EC, Miller D. Shifting trends in bacterial keratitis in south Florida and emerging resistance to fluoroquinolones. Ophthalmology. 2000 Aug;107(8):1497-502.
3. McDonald M, Blondeau JM. Emerging antibiotic resistance in ocular infections and the role of fluoroquinolones. J Cataract Refract Surg. 2010 Sep;36(9):1588-98.
4. Stapleton F, Keay L, Edwards K, et al. The incidence of contact lens-related microbial keratitis in Australia. Ophthalmology. 2008 Oct;115(10):1655-62.
5. Green M, Apel A, Stapleton F. A longitudinal study of trends in keratitis in Australia. Cornea. 2008 Jan;27(1):33-9.
6. Sharma S. Antibiotic resistance in ocular bacterial pathogens. Indian J Med Microbiol. 2011 Jul-Sep;29(3):218-22.
7. Bradley JS, Jackson MA; Committee on Infectious Diseases; American Academy of Pediatrics. The use of systemic and topical fluoroquinolones. Pediatrics. 2011 Oct;128(4):e1034-45.
8. Haas W, Pillar CM, Torres M, et al. Monitoring antibiotic resistance in ocular microorganisms: results from the Antibiotic Resistance Monitoring in Ocular micRorganisms (ARMOR) 2009 surveillance study. Am J Ophthalmol. 2011 Oct;152(4):567-74.
9. Benitez-Del-Castillo J, Verboven Y, Stroman D, Kodjikian L. The role of topical moxifloxacin, a new antibacterial in Europe, in the treatment of bacterial conjunctivitis. Clin Drug Investig. 2011;31(8):543-57.
10. Schubert TL, Hume EB, Willcox MD. Staphylococcus aureus ocular isolates from symptomatic adverse events: antibiotic resistance and similarity of bacteria causing adverse events. Clin Exp Optom. 2008 Mar;91(2):148-55.
11. Leibovitch I, Lai TF, Senarath L, et al. Infectious keratitis in South Australia: emerging resistance to cephazolin. Eur J Ophthalmol. 2005 Jan-Feb;15(1):23-6.
12. Ly CN, Pham JN, Badenoch PR, et al. Bacteria commonly isolated from keratitis specimens retain antibiotic susceptibility to fluoroquinolones and gentamicin plus cephalothin. Clin Experiment Ophthalmol. 2006 Jan-Feb;34(1):44-50.
13. McGhee CN, Anastas CN. Widespread ocular use of topical chloramphenicol: is there justifiable concern regarding idiosyncratic aplastic anaemia? Br J Ophthalmol 1996 Feb;80(2):182-4.
14. Egger SF, Ruckhofer J, Alzner E, et al. In vitro susceptibilities to topical antibiotics of bacteria isolated from the surface of clinically symptomatic eyes. Ophthalmic Res 2001 Mar-Apr;33(2):117-20.
15. Altaie R, Fahy GT, Cormican M. Failure of Listeria monocytogenes keratitis to respond to topical ofloxacin. Cornea 2006 Aug;25(7):849-50.
16. Cimolai N. Ocular Methicillin-resistant Staphylococcus aureus Infections in a Newborn Intensive Care Cohort. Am J Ophthalmol 2006 Jul;142(1):183-4.
17. Fukuda M, Ohashi H, Matsumoto C, et al. Methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococcus ocular surface infection efficacy of chloramphenicol eye drops. Cornea. 2002 Oct;21(7 Suppl):S86-9.
18. Walvick MD, Amato M. Ophthalmic methicillin-resistant Staphylococcus aureus infections: sensitivity and resistance profiles of 234 isolates. J Community Health. 2011 Dec;36(6):1024-6.
19. Elsahn AF, Yildiz EH, Jungkind DL, et al. In vitro susceptibility patterns of methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus corneal isolates to antibiotics. Cornea. 2010 Oct;29(10):1131-5.
20. Lam RF, Lai JS, Ng JS, et al. Topical chloramphenicol for eye infections. Hong Kong Med J 2002 Feb;8(1):44-7.
