5 questions answered about antibiotic resistance in eye care

The world has been plagued by the COVID-19 pandemic caused by a novel pathogen that was predicted by various public health specialists, agencies, and even Hollywood years prior.^1-3 However, when COVID-19 appeared, the world was woefully unprepared.

A possibly larger threat to global health, according to the World Health Organization (WHO), is antibiotic resistance, a subcategory of antimicrobial resistance.⁴ Alexander Fleming, who discovered penicillin in 1928, warned that bacteria can become resistant to this wonder drug during his Nobel Prize acceptance speech in 1945.⁵

Since then, doctors have seen bacteria develop resistance to many new antibiotics at an alarmingly faster rate.⁶ This adaptability of bacteria has led to the development of superbugs, such as carbapenem-resistant Enterobacteriaceae, methicillin resistant Staphylococcus aureus (MRSA), and multidrug-resistant Pseudomonas aeruginosa, that are resistant to numerous categories of antibiotics.⁷

If the rate of antibiotic resistance continues unabated, the WHO warns that “it is compromising our ability to treat infectious diseases and putting people everywhere at risk.”⁸ In a report by the United Nations, it is estimated that drug-resistant diseases could cause 10 million deaths each year by 2050, outpacing cancer at 8.3 million lives taken annually.⁹

Related: How antibiotic resistance happens

What is antibiotic resistance, and how does it develop?

Good and bad bacteria exist in human bodies. Among them are drug-resistant strains. Use of broad-spectrum antibiotics kills beneficial bacteria that protect and pathogenic ones that harm. Unfortunately, this selective process benefits those bacteria with antibiotic resistance, and they survive and thrive without competition.¹⁰ Some bacteria are able to share their drug-resistant trait with other bacteria that are not its own offspring through a process called horizontal gene transfer.^2,11

How does antibiotic-resistant bacteria develop in humans?

These bacteria develop via 2 main methods. One way occurs when broad-spectrum antibiotics kill both helpful and harmful bacteria in the body and leave behind resistant bacteria to proliferate in an altered microbiome. Therefore, prophylactic antibiotic use can be dangerous.

The second method is tied to the popular farming and agricultural habit of adding antibiotics to animal feed with the aim of promoting faster and larger animal growth. By consuming these food-source animals, products made from them, and vegetative produce grown on the same farms, individuals are at risk of contracting antibiotic-resistant bacteria if food is not properly prepared.¹² Illnesses spread between animals and people are called zoonotic diseases.¹³ When infected individuals seek medical care at clinics and hospitals, health care workers and other patients are exposed to possible community spread.¹² Antibiotic resistance is not only a personal but a societal concern.²

How do ODs combat antibiotic resistance?

ODs can help prevent antibiotic resistance through several mechanisms:

• Education. Physicians must address educational gaps in proper antibiotic use. For example, discourage antibiotic use for viral flu infections; do not discontinue antibiotics early or use in low doses; resistance lives at the bacterial level not the individual level; and antibiotic resistance can affect anyone.¹⁴

• Surveillance. Without rapid bacteria testing options, physicians are not able to use antibiotic resistance surveillance programs to guide prescribing practices.¹⁴

• Antibiotic stewardship. Physicians and patients must adopt more care when prescribing and using antibiotics. Inappropriate antibiotic use in food source animals, which has already proven effective in other countries, is being adopted in some states.^14,15

• Hygiene. Proper disinfection and hygiene protocols reduce community spread.¹⁴ With COVID-19, everyone is more cognizant about the important role of hygiene in transmission.

• Lab testing. Rapid and specific lab tests are needed to quickly identify the cause of an infection so physicians can target prescribing based on specific bacteria and their resistance traits (Figure 1).¹⁴

• Investment in new antibiotic treatment and strategy. The last time a new class of antibiotic was introduced to market was almost 15 years ago.^2,16 New drug research and development is costly, and antibiotics have a lower return on investment than chronic-use medications. Commitments are needed from private and government partners to invest in new antibiotic research.^14,17

How do ODs’ actions affect antibiotic resistance?

Although systemic use of antibiotics plays a much bigger role, resistance occurs in eye care, and reports exist of increasing ocular infection treatment failures.^19,20 One study looked at the effects of topical antibiotics on resistance patterns of ocular surface flora after repeated exposure.²¹ Investigators in another study found the prophylactic use of topical antibiotics after intravitreal injections in age-related macular degeneration (AMD) patients resulted in significant changes in ocular surface antibiotic resistance profile. The percentage of S. epidermidis isolated from the conjunctival flora surface significantly increases after repeated exposure to different antibiotics at the expense of other commensal flora.^21,22 Although Staphylococcus epidermidis can have probiotic function, it is also an opportunistic pathogen and one of the most common causes of endophthalmitis.²³ Investigators concluded that “recommend that routine use of prophylactic antibiotics after [intravitreal] injection be discouraged.”²⁰

From 2000 to 2006, the Ocular Tracking Resistance in US Today (Ocular TRUST) program found high levels of antibiotic resistance in certain ocular isolates (approximately 50% S. aureus-MRSA, 62% Coagulase-negative Staphylococci [CoNS], approximately 20% Streptococcus pneumonia) with many strains resistant to multiple drug categories. The 6-year Ocular TRUST program discovered a 12.1% increase in incidence of MRSA strains over the course of the study.¹⁹ In 2009 Bausch + Lomb initiated and continues to support the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) project that is the only ongoing nationwide antibiotic resistance surveillance program focused on 5 common ocular pathogens (S. aureus, CoNS, S. pneumoniae, P. aeruginosa, and Haemophilus influenzae).²⁴

Recently published is ARMOR 10-year cumulative data.²⁵ It reported on the differences in antibiotic resistance of the 5 pathogens across 10 different drugs representing the main categories of antibiotics. Overall, “antibiotic resistance may be prevalent among staphylococcal isolates, particularly among older patients. In this study, a few small differences in antibiotic resistance were observed by geographic region or longitudinally.”²⁵

How should ODs apply surveillance data to clinical practice?

In clinical practice, I use the findings of ARMOR’s charts about specific antibiotic resistance rates for the different pathogens when I make empirical prescribing decisions in initial and subsequent antibiotic treatments. Here are clinical examples.

• Blepharitis. I typically treat this condition with vigorous lid hygiene as first-line therapy (eg, lid scrubs, hypochlorous acid, tea tree oil, etc.), but if refractory I will prescribe an effective antibiotic. Several studies have reported that up to 95% of blepharitis cases are caused by S. epidemidis (CoNS).^26,27 Looking at the ARMOR chart for CoNS, vancomycin and besifloxacin (Besivance; Bausch + Lomb) have the lowest minimum inhibitory concentration (MIC90) (2 ug/mL) against all CoNS isolates collected and besifloxacin’s MIC90 (4 ug/mL) is second to only vancomycin (2 ug/mL) for methicillin-resistant CoNS (MRCoNS) isolates.²⁵ Given this data, I would prescribe commercially available besifloxacin 4 times a day for 1 week in stubborn cases of blepharitis.

• Corneal ulcers in contact lens wearers. The most common bacterial agent is P. aeruginosa in this scenario.²⁸ According to ARMOR, the antibiotic with the lowest MIC90 against P. aeruginosa ciprofloxacin (0.5 µg/mL) followed by levofloxacin, gatifloxacin (Zymaxid 0.5%, Zymar 0.3%; Allergan) and tobramycin (Tobrex, Novartis) (all at 1 µg/mL). This helps to guide my prescribing of ciprofloxacin (Ciloxan; Novartis) drops every 1 to 2 hours, and if that is not available, levofloxacin or gatifloxacin alternating with tobramycin every 1 to 2 hours would be my next best option.²⁵ See Figure 2.

Until researchers develop a rapid point-of-care test and newer antibiotics, ODs can rely on surveillance data to guide in decisions on which antibiotic to prescribe.

Effects of COVID-19
The WHO warned on June 1, 2020, that the “COVID-19 pandemic has led to an increased use of antibiotics, which ultimately will lead to higher bacterial resistance rates that will impact the burden of disease and deaths during the pandemic and beyond.”

Only a small number of COVID-19 patients need antibiotics to treat subsequent bacterial infections. The WHO issued guidance to medics to stop prophylaxis antibiotic therapy in patients with mild to moderate COVID-19 without a clinical suspicion of bacterial infection.²⁹

References

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2. Xue K. Superbug: an epidemic begins. Harvard Magazine. May 2014. Accessed April 7, 2021. https://www.harvardmagazine.com/2014/05/superbug.

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10. How antibiotic resistance happens. Centers for Disease Control and Prevention. Updated February 10, 2020. Accessed May 6, 2021. https://www.cdc.gov/drugresistance/about/how-resistance-happens.html

11. Bello-Lopez JM, Cabrero-Martinez OA, Ibáñez-Cervantes G, et al. Horizontal gene transfer and its association with antibiotic resistance in the genus Aeromonas spp. Microorganisms. 2019;7(9):363. doi:10.3390/microorganisms7090363

12. Antibiotic resistance and NARMS surveillance. Centers for Disease Control and Prevention. Updated November 21, 2019. Accessed May 6, 2021. https://www.cdc.gov/narms/faq.html

13. Zoonotic diseases. Centers for Disease Control and Prevention. Updated July 14, 2017. Accessed May 6, 2021. https://www.cdc.gov/onehealth/basics/zoonotic-diseases.html

14. Lack of new antibiotics threatens global efforts to contain drug-resistant infections. News release. World Health Organization. January 17, 2020. Accessed May 6, 2021. https://www.who.int/news-room/detail/17-01-2020-lack-of-new-antibiotics-threatens-global-efforts-to-contain-drug-resistant-infections

15. Martin MJ, Thottathil SE, Newman TB. Antibiotics overuse in animal agriculture: a call to action for health care providers. Am J Public Health. 2015;105(12):2409-2410. doi:10.2105/AJPH.2015.302870

16. Conly JM, Johnston BL. Where are all the new antibiotics? The new antibiotic paradox. Can J Infect Dis Med Microbiol. 2005;16(3):159-160. doi:10.1155/2005/892058

17. Lack of new antibiotics threatens global efforts to contact drug-resistant infections. World Health Organization. January 17, 2020. Accessed May 6, 2021. https://www.who.int/news-room/detail/17-01-2020-lack-of-new-antibiotics-threatens-global-efforts-to-contain-drug-resistant-infections

18. Dang, S. Understanding antibiotic resistance and eye infections. American Academy of Ophthalmology. September 21, 2014. Accessed May 6, 2021. https://www.aao.org/eye-health/news/antibiotic-resistance-eye-infections

19. Asbell PA, Colby KA, Deng S, et al. Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates. Am J Ophthalmol. 2008;145(6):951-958. doi:10.1016/j.ajo.2008.01.025

20. Yin VT, Weisbrod DJ, Eng KT, et al. Antibiotic resistance of ocular surface flora with repeated use of a topical antibiotic after intravitreal injection. JAMA Ophthalmol. 2013;131(4):456-461. doi:10.1001/jamaopthalmol.2013.2379

21. Kim SJ, Toma HS. Antimicrobial resistance and ophthalmic antibiotics: 1-year results of a longitudinal controlled study of patients undergoing intravitreal injections. Arch Ophthalmol. 2011;129(9):1180-1188. doi:10.1001/archophthalmol.2011.213

22. Dave SB, Toma HS, Kim SJ. Changes in ocular flora in eyes exposed to ophthalmic antibiotics. Ophthalmology. 2013;120(5):937-941. doi:10.1016/j.ophtha.2012.11.005

23. Gentile RC, Shukla S, Shah M, et al. Microbiological spectrum and antibiotic sensitivity in endophthalmitis: a 25-year review. Ophthalmology. 2014;121(8):1634-1642. doi:10.1016/j.ophtha.2014.02.001

24. Asbell, PA Sanfilippo CM, Pillar CM, DeCory HH, Sahm DF, Morris TW. Five-year results from the antibiotic resistance monitoring in ocular microorganisms (ARMOR) surveillance study. JAMA Ophthalmol. 2015;133(12):1445-1454. doi:10.1001/jamaophthalmol.2015.3888

25. Asbell PA, Sanfilippo CM, Sahm DF, DeCory HH. Trends in antibiotic resistance among ocular microorganisms in the United States from 2009 to 2018. JAMA Ophthalmol. 2020;138(5):439-450. doi:10.1001/jamaophthalmol.2020.0155

26. Groden LR, Murphy B, Rodnite J, Genvert GI. Lid flora in blepharitis. Cornea. 1991;10(1):50-53.

27. Ficker L, Ramakrishnan M, Seal D, Wright P. Role of cell-mediated immunity to staphylococci in blepharitis. Am J Ophthalmol. 1991;111(4):473-479. doi:10.1016/s0002-9394(14)72383-9

28. Cheng KH, Leung SL, Hoekman HW, et al. Incidence of contact-lens-associated microbial keratitis and its related morbidity. Lancet. 1999;354(9174):181-185. doi:10.1016/S0140-6736(98)09385-4

29. Record number of countries contribute data revealing disturbing rates of antimicrobial resistance. News release. World Health Organization. June 1, 2020. Accessed May 6, 2021. https://www.who.int/news-room/detail/01-06-2020-record-number-of-countries-contribute-data-revealing-disturbing-rates-of-antimicrobial-resistance