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2014 via the internet survey tool SurveyMonkey obtained from the University of California, San
(surveymonkey.com; Palo Alto, California), with one Francisco Committee on Human Research. The study
reminder on 26 August 2014. Data collection was adhered to the Declaration of Helsinki and all federal
closed in October of 2014. and state laws.
The survey consisted of seven questions (figure 1).
Respondents were presented with the clinical scenario
of a patient with a large, central, bacterial corneal ulcer RESULTS
and were asked what their empirical antibiotic treat- A total of 1009 cornea specialists were members at the
ment would be, why they chose that regimen and time the survey was sent out. One hundred forty
whether they would obtain cultures prior to instituting responses to the survey were received, for a response
rate of 14%. Respondents were mostly from the USA
treatment. Specific antibiotic regimens given as options
(n=104), with the remaining international respondents
included fourth-generation fluoroquinolones (such as
(n=36) coming from 17 countries on six continents
moxifloxacin and gatifloxacin) and fortified antibiotics
(table 1). Many respondents had greater than 20 years
(including tobramycin, vancomycin and cefazolin).
of clinical experience (n=62, 44%), followed by
Respondents were also queried regarding their demo- 10–20 years in practice (n=33, 24%), 5–10 years in
graphics including their geographic location, the practice (n=30, 21%) and 0–5 years in practice (n=15,
average number of corneal ulcers seen per month as 11%). In general, the international respondents
well as the number of years they had been in practice. encountered more cases of infectious keratitis per
Finally they were asked what percentage of Staphylo- month, with 42% seeing more than five cases per
coccus aureus in the community would have to be month versus 24% of US respondents (p=0.05). When
methicillin-resistant Staphylococcus aureus (MRSA) for asked if they would culture a large central ulcer, all
them to cover MRSA empirically. international respondents (n=36) and 98% (n=101) of
Responses were collected and analysed using descrip- US respondents reported that they would (two US
tive statistics with Stata V.14.0. 2 test was used to respondents, or 2%, said they would not).
compare responses between international and US Respondents were asked about their empirical treat-
respondents, and logistic regression models were used ment of bacterial keratitis, and their responses
to assess the relationship between specific concerns, revealed marked differences in practice patterns
such as toxicity or antibiotic resistance and choice of between clinicians in the USA and in other countries,
antibiotic. Institutional review board exemption was as seen in figure 2. In the USA, the majority of
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Figure 2 Graph showing antibiotic choice of US and international cornea specialists for empirical treatment of bacterial
keratitis.
Concern over ocular toxicity was the second strongest Fluoroquinolone antibiotics penetrate ocular tissues
predictor of fluoroquinolone use in our study. Forti- well and have good safety profiles with minimal toxicity
fied antibiotics and in particular fortified vancomycin to the ocular surface. They also exhibit broad coverage
are known to cause significant ocular surface toxicity, of bacterial organisms implicated in bacterial ulcers.
such as increasing epithelial defect size or conjunc- The primary target of fluoroquinolones is DNA gyrase,
tival injection, which can sometimes be difficult to an essential bacterial enzyme. There is reason to believe
distinguish from progression of the corneal infection. that because of this mechanism of action, they may be
Some have advocated using topical linezolid as an more susceptible to the development of resistance than
alternative to vancomycin, which has less toxicity but other antibiotics.11 Rates of MRSA infection have been
still covers resistant organisms including MRSA.9 increasing in North America, and ocular isolates in the
Interestingly, no one in our survey reported using USA have been reported to be resistant to fluoroquino-
linezolid. Our observation that those concerned with lones approximately 80% of the time.12–14 In our study
broad-spectrum coverage were more likely to choose concern for antibiotic resistance and broad spectrum
fortified antibiotics and those favouring a low toxicity coverage were highly predictive of choosing fortified
profile were more likely to choose a single agent vancomycin after controlling for location. The fact that
could be influenced by the availability of particular international cornea specialists both have a lower
antibiotics. threshold for MRSA coverage and are less likely to be
using fortified antibiotics suggests that they consider the
prevalence of MRSA to be relatively low in their
Table 2 Threshold for empirical methicillin-resistant population.
Staphylococcus aureus coverage (MRSA). Percentage of The strengths of this study include the geographic
MRSA in the community necessary to change the default diversity of respondents, providing both US and inter-
corneal ulcer treatment to include MRSA coverage. national perspectives and representing a broad range
% MRSA USA, N International, p Value of experience. In addition, a large number of our
(%) N (%) respondents were experienced physicians and seeing
ulcers frequently in clinical care. Limitations include
5%–15% 14 (14) 15 (42) p<0.001 the fact that we only surveyed members of the Cornea
15%–30% 30 (29) 7 (19) Society listserv, therefore our results may not be gener-
alisable to all ophthalmologists. Additionally the survey
30%–50% 6 (6) 5 (14)
did not ask respondents about their practice setting,
>50% 7 (7) 1 (3) which may be related to empirical antibiotic choice
Default MRSA 46 (45) 8 (22) since those in academic settings may have more access
coverage to fortified antibiotics. Another limitation would be the
multiple-choice format of our question about antibiotic
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Table 3 Reasons for antibiotic of choice. Logistic regression models predicting likelihood of choosing fluoroquinolone
monotherapy and fortified vancomycin, correcting for location.
Fluoroquinolone monotherapy
Efficacy 1.05 0.91 0.45 to 2.46
Coverage 0.30 0.02 0.11 to 0.81
Availability 20.86 <0.001* 6.79 to 64.13
Toxicity 7.48 <0.001* 2.53 to 22.09
Synergy 0.16 0.08 0.02 to 1.23
Resistance 0.39 0.08 0.13 to 1.11
Fortified vancomycin
Efficacy 1.96 0.06 0.97 to 3.92
Coverage 7.10 <0.001* 2.44 to 20.61
Availability 0.20 <0.001* 0.09 to 0.44
Toxicity 0.10 0.003* 0.02 to 0.45
Synergy 0.75 0.56 0.29 to 1.95
Resistance 12.51 <0.001* 4.97 to 31.45
preference because other options such as vancomycin Funding There are no conflicts of interest to declare. Corresponding author
monotherapy were not listed (in this case, we listed Dr Jennifer Rose-Nussbaumer contributed to study design and
implementation, data analysis, and writing of this manuscript. Ariana Austin
vancomycin only in conjunction with other antibiotics contributed to data analysis and writing of the manuscript. Dr Julie Schallhorn
because it only covers Gram-positive bacteria). We and Dr Mike Geske were involved in design and implementation of this study.
attempted to address this by giving respondents the Dr Mark Mannis contributed to study design and implementation as well as
option to write in their own preferred antibiotic, but it editing of the manuscript. Dr Tom Lietman contributed to the design of the
study, data analysis, and editing of the manuscript.
is possible the question format affected responses
Ethics approval University of California, San Francisco Institutional Review
given.
Board.
Practice patterns for the initial treatment of bacterial
Provenance and peer review Not commissioned; externally peer reviewed.
keratitis vary with clinicians in the USA more likely to
use fortified antibiotics versus fluoroquinolone mono- Open Access This is an Open Access article distributed in accordance with
the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,
therapy and more concerned with resistant organisms which permits others to distribute, remix, adapt, build upon this work non-
than their international peers. These differences may commercially, and license their derivative works on different terms, provided
be due to multiple factors, including varying preva- the original work is properly cited and the use is non-commercial. See: http://
lence of resistant organisms, lack of availability of creativecommons.org/licenses/by-nc/4.0/
fortified antibiotics and concerns for ocular toxicity. © Article author(s) (or their employer(s) unless otherwise stated in the text of
Determining which of these factors impact clinical the article) 2016. All rights reserved. No commercial use is permitted unless
otherwise expressly granted.
outcomes, such as visual acuity, should be an important
focus of future research. Open Access This is an Open Access article distributed in accordance with
the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build upon this work non-
commercially, and license their derivative works on different terms, provided
Acknowledgements Individual support for this study came from K23 the original work is properly cited and the use is non-commercial. See: http://
EY025025 (JRN), an unrestricted grant from the Peirles Foundation (JRN) and creativecommons.org/licenses/by-nc/4.0/
an unrestricted grant from Research to Prevent Blindness (JRN).
Contributors Corresponding author JR-N contributed to study design and
implementation, data analysis and writing of this manuscript. AA contributed REFERENCES
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References This article cites 14 articles, 0 of which you can access for free at:
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provided the original work is properly cited and the use is
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Notes