Original article

Adult bacterial conjunctivitis:

resistance patterns over 12 years in
patients attending a large primary eye
care centre in the UK
Alexander Silvester,1 Timothy Neal,2 Gabriela Czanner,3 Michael Briggs,1
Simon Harding,3 Stephen Kaye1

To cite: Silvester A, Neal T, ABSTRACT Key messages

Czanner G, et al. Adult Purpose: To determine whether there was a change
bacterial conjunctivitis:
in the resistance pattern of bacteria isolated from cases What is already known about this subject?
resistance patterns over 12
of conjunctivitis following the introduction of over-the- Bacterial conjunctivitis is common and often treated
years in patients attending a
large primary eye care centre counter availability of chloramphenicol in 2005. empirically with topical antimicrobials. Inappropriate
in the UK. BMJ Open Ophth Design and setting: Retrospective review of use of antimicrobials has led to increased bacterial
1:e000006. doi:10.1136/ laboratory records for adult patients with suspected resistance.
bmjophth-2016-000006 bacterial conjunctivitis between 2001 and 2012 What are the new findings?
" Prepublication history and attending the Royal Liverpool University Hospital. Among Gram-positive bacteria, the most prevalent
additional material is Participants: Patients with suspected bacterial cause of bacterial conjunctivitis, chloramphenicol
available. To view please visit conjunctivitis. Organisms were identified by standard sensitivity remains high.
the journal (http://dx.doi.org/ laboratory methods. Scanty growth and normal flora How might these results change the focus of
10.1136/bmjophth-2016- were considered as a negative result. For positive research or clinical practice?
000006). results, susceptibility testing was undertaken as per Topical chloramphenicol remains a suitable first-line
British Society for Antimicrobial Chemotherapy treatment for bacterial conjunctivitis.
Received 02 June 2016
Revised 19 October 2016 guidelines.
Accepted 22 October 2016 Main outcome measures: Prevalence of groups of
bacteria associated with acute conjunctivitis and their
resistance to chloramphenicol, ciprofloxacin, secondary damage to the ocular surface. A
gentamicin, and methicillin. meta-analysis2 concluded that while bacte-
Results: A total of 8209 conjunctival swabs were rial conjunctivitis is often self-limiting, anti-
reviewed; 1300 (15.8%) were considered positive, of microbial use is associated with improved
which 977 (75.2%) and 323 (24.8%) bacteria were rates of clinical and microbiological
identified as Gram positive and Gram negative, remission. Inappropriate use of antimicro-
respectively. Staphylococcus aureus was the most bials, however, is associated with increased
prevalent organism identified. Resistance of all
bacterial resistance, and in recent years
bacterial isolates to chloramphenicol was 8.4% varying
from 3.0% to 16.4% while that for ciprofloxacin and
there has been a global drive to reduce the
gentamicin was 16.4% and 14.0%, respectively. prescribing of antimicrobials. While pre-
Methicillin resistance among S. aureus was 8.3%. scribing chloramphenicol for conjunctivitis
1
Conclusion: Resistance to chloramphenicol has among general practitioners in the UK has
St Paul’s Eye Unit, Royal
remained stable since being made available over the fallen,3 its use has increased several fold
Liverpool University Hospital,
Liverpool, UK
counter. Among Gram-positive bacteria, the most since 2005, when it became the first antibi-
2
Department of Medical prevalent causative agent of bacterial conjunctivitis, otic available over the counter.4 Surveillance
Microbiology, Royal chloramphenicol sensitivity remains high. of causative organisms and resistance sus-
Liverpool University Hospital,
ceptibility patterns are important in guiding
Liverpool, UK
3
Department of Eye and antimicrobial selection. While large studies
Vision Science, Institute of BACKGROUND in the USA5 6 have investigated trends in
Ageing and Chronic Disease, bacterial resistance to antimicrobials over
Acute infective conjunctivitis is an inflam-
University of Liverpool,
mation of the conjunctiva secondary to a the last decade, these have limited applica-
Liverpool, UK
bacterial or viral infection. It is a common tion in the UK as chloramphenicol, an anti-
condition with bacterial conjunctivitis hav- biotic very commonly used in the UK, is not
Correspondence to
Dr Alexander Silvester; alex. ing an estimated incidence of 135 per used in the USA due to the rare purported
[email protected], 10 000 in the USA.1 In severe cases, it may association between topically administered
[email protected] result in conjunctival scarring and chloramphenicol and aplastic anaemia. A

Silvester A, et al. BMJ Open Ophth 1:e000006. doi:10.1136/bmjophth-2016-000006 1

 Open Access

review of its use in the UK concluded that topical Susceptibility testing was carried out as per British
chloramphenicol was not a significant risk factor for Society for Antimicrobial Chemotherapy (BSAC) guide-
inducing dose-related bone marrow toxicity.7 To deter- lines,9 and BSAC templates were used to interpret zone
mine resistance patterns of bacteria isolated from cases inhibition diameters for the following antimicrobials:
of conjunctivitis to commonly prescribed antimicro- chloramphenicol, ciprofloxacin and gentamicin.
bials, laboratory reports of patients presenting with sus-
pected acute conjunctivitis were reviewed. The
ANALYSIS
prevalence of the organisms causing acute bacterial
The data are time series and are analysed using linear
conjunctivitis and their sensitivities to chloramphenicol
regression models. We investigated for a possible
and other commonly used topical antimicrobials were
cycling changes in data via a polynomial component of
examined between 2001 and 2012.
second, third or fourth order. The order was chosen to
maximize the adjusted coefficient of determination.
The statistical significance of trend and cycles was
METHODS
judged at level 0.05.
Laboratory records for all bacterial swabs taken from
adult patients with suspected bacterial conjunctivitis
presenting to the Royal Liverpool University Hospital, RESULTS
UK, between 2001 and 2012 were reviewed. A total of 8209 conjunctival swab results were reviewed,
Conjunctival samples were collected using cotton of which 1300 (15.8%) were considered bacterial cul-
swabs from the inferior conjunctival fornix as per local ture positive. The isolation rate by year ranged from
protocol. Samples were inoculated onto chocolate agar, 9.8% to 25.2%, and 977 (75.2%) and 323 (24.8%) of
Columbia agar with 5% horse blood and MacConkey bacterial isolates were identified as Gram-positive and
agar plates, and placed in a 5% CO2 incubator at Gram-negative organisms, respectively (table 1). All
37 or in air at 37 (MacConkey agar plate). Plates were organisms isolated have been listed in box 1. Between
examined after 24 and 48 hours of incubation for the 2006 and 2011, 3293 viral conjunctival samples were
presence of pathogens associated with collected. An adenovirus was identified in 707 of these,
conjunctivitis. Organisms were identified by standard and 21 (2.97%) of which were also bacterial culture
laboratory methods. A negative result was defined as positive.
either a scanty growth of bacteria or those that were In bacterial culture-positive samples, resistance to
considered as part of the ‘normal conjunctiva flora’ chloramphenicol varied from 3.0% to 16.4% (table 1)
such as coagulase-negative staphylococci, diphtheroids and was predominantly among Gram-negative
and alpha-haemolytic streptococci. Because of the diffi- organisms. There was no significant change in resis-
culty in distinguishing clinically between bacterial and tance to chloramphenicol over the study period; in
viral conjunctivitis, samples were also often taken for particular, there was no change after 2005. Resistance
viruses, in particular adenovirus and herpes simplex to ciprofloxacin and gentamicin over the period
virus. Samples for viruses were analysed by real-time of 2001–2012 was found in 16.4% and 14.0% of iso-
PCR.8 Data for viral isolates were only available from lates, respectively, predominantly among Gram-posi-
2006 onwards. tive organisms (80.1% and 69.2%). There was no

Table 1 Bacterial isolates from adults with suspected bacterial conjunctivitis attending Royal Liverpool University Hospital
(2001–2012) and their resistance to chloramphenicol

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

Positive isolates 115 152 135 161 110 85 90 66 86 84 100 116

All isolates resistant to 12 7 9 18 18 9 5 2 5 5 14 5
chloramphenicol (%) (10.4) (4.6) (6.7) (11.2) (16.4) (10.6) (5.6) (3.0) (5.8) (6.0) (14.0) (4.3)
No. of Gram-positive 95 105 96 101 75 70 70 59 79 66 70 91
isolates (%) (82.6) (69.1) (71.1) (62.7) (68.2) (82.4) (77.8) (89.4) (91.9) (78.6) (70.0) (78.4)
Gram-positive isolates 6 1 3 3 6 1 3 0 2 0 1 2
resistant to chloramphenicol (6.32) (1.0) (3.1) (3.0) (8.0) (1.4) (4.2) (0) (2.5) (0) (1.4) (2.2)
(%)
No. of of Gram- negative 20 47 39 60 35 15 20 7 7 18 30 25
isolates (%) (17.4) (30.9) (28.9) (37.3) (31.8) (17.7) (22.2) (10.6) (8.1) (21.4) (30.0) (21.6)
Gram-negative isolates 6 6 6 15 12 8 2 2 3 5 13 3
resistant to chloramphenicol (30.0) (12.8) (15.4) (25.0) (34.3) (53.3) (10.0) (28.6) (42.9) (27.8) (43.3) (12.0)
(%)

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 Open Access

susceptibility and resistance trends is therefore

Box 1 Organisms identified from bacterial isolates from
adults with suspected bacterial conjunctivitis attending important. It is of interest, therefore, that over the
Royal Liverpool University Hospital (2001–2012) study period there was no evidence of an increase in
antimicrobial resistance to commonly prescribed topi-
Haemolytic streptococcus cal antimicrobials. BSAC breakpoints used for suscepti-
Haemophilus influenzae bility testing are derived for systemically delivered
Moraxella catarrhalis
antimicrobials. Caution is, therefore, needed interpret-
Morganella morganii
Neisseria gonorrhoeae ing resistance patterns to topically applied agents.
Neisseria meningitidis Although models for topical breakpoints for cases of
Pseudomonas sp. keratitis are becoming available,11 there are currently
Staphylococcus aureus no interpretative breakpoints for topical antimicrobials
Streptococcus pneumoniae for cases of conjunctivitis.
Based on the systemic breakpoints, chloramphenicol
resistance has remained stable since 2005 when chlor-
significant association between antimicrobial resistance amphenicol was made available over the counter.
and isolation rate for each year under study Among Gram-positive bacteria, chloramphenicol sensi-
(p=0.58). There was a significant reduction in methicil- tivity remains high. Compared with many topical anti-
lin resistance among Staphylococcus aureus isolates bacterial agents, chloramphenicol has excellent
(mean 8.3%, minimum 1.3%, maximum 13.4%, intraocular penetration following topical application.12
p=0.038) over the 12-year period (figure 1). Similar to that reported in studies from the USA,5 6 S.
aureus was the most prevalent organism. The preva-
DISCUSSION lence of methicillin-resistant S. aureus (MRSA) was,
Acute infective conjunctivitis is a common however, much lower than reported in Japan13 and
condition. Although cases of viral and bacterial con- USA5 6 and also significantly reduced over the time
junctivitis have some clinically distinguishing features, period of this study. A reduction of MRSA infections
it is not always easy to differentiate them. It is not sur- over this period of time has been demonstrated in
prising, therefore, that in the majority of patients stud- other infections,14and this has been attributed to
ied, the aetiological agent was an enhanced screening and decolonisation of patients
adenovirus. Although antibacterial agents would not with MRSA in recent years.
be indicated in a viral conjunctivitis, because of the A limitation to this study was the low-positive isola-
difficulty in distinguishing bacterial and viral causes, it tion rate. Other papers have shown variable rates of
is not unreasonable to prescribe broad-spectrum anti- positive isolates,15and one study had a similar isolation
microbials prior to obtaining culture results. It is of rate to this paper (15.8%).16 This difference might be
note, therefore, that while prescribing of chloram- explained by the inclusion of all bacteria isolated in
phenicol has fallen, its use has increased due to its some studies rather than pathogenic bacteria
availability over the counter. only. In addition, our isolation rate might be lower as
In non-ocular infections, over and inappropriate use bacterial swabs were taken from all patients with sus-
of antimicrobials has led to an increase in resistant pected conjunctivitis including those with viral
organisms10 and the monitoring of antimicrobial conjunctivitis. Many patients present after they have
already started topical antibiotic treatment, this may
have reduced the positive isolation rate.
Although chloramphenicol remains a useful agent for
bacterial conjunctivitis, in particular for cases of Gram-
positive conjunctivitis, it should not be used if contact
lens related or if Pseudomonas aeruginosa is suspected.17
Despite the ready availability of chloramphenicol
over the counter during the last 7 years, there has been
no increase in chloramphenicol resistance nor a
change in the bacterial spectrum in this cohort of
patients.

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
Figure 1 Percentage of Staphylococcus aureus isolated the original work is properly cited and the use is non-commercial. See: http://
creativecommons.org/licenses/by-nc/4.0/
resistant to methicillin

Silvester A, et al. BMJ Open Ophth 1:e000006. doi:10.1136/bmjophth-2016-000006 3

 Open Access

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4 Silvester A, et al. BMJ Open Ophth 1:e000006. doi:10.1136/bmjophth-2016-000006