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| Journal of the New Zealand Medical Association,
21-January-2011, Vol 124 No 1328
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The utility of routine conjunctival swabs in
management of conjunctivitis
Although infective conjunctivitis is in most cases a mild
and self-limiting condition, a recent meta-analysis and review show that topical
antibacterial treatment shortens the duration of symptoms and accelerates
bacteriologic cure.1,2 Not surprisingly,
randomized controlled trials have shown the greatest benefit when topical
antibacterial treatment is given to patients with proven bacterial
conjunctivitis: compared with placebo, topical antibacterial treatment improved
clinical cure or improvement rates from 61% to 78% (levofloxacin; cure at day 6
to 10),3 from 63% to 93% (moxifloxacin; cure at
about 1 week),4 from 28% to 62%
(polymyxin-bacitracin; cure at day 3 to 5),5
and from 22% to 64% (ofloxacin; improvement at day
2).6
In a large recent randomized controlled trial in acute
probable infective conjunctivitis, topical chloramphenicol reduced duration of
moderate symptoms from 4.8 days to 3.3 days.7
If these benefits are desired then clinicians should ideally
prescribe topical antibacterial treatment to patients with bacterial
conjunctivitis and not to patients with viral or non-infectious conjunctivitis.
Approximately half of cases of acute infective conjunctivitis are caused by
bacteria, irrespective of age.2,7
Clinical predictors of bacterial infections have been
evaluated in three recent studies.8–10
Reitveld found that both eyes being glued on waking correlated significantly
with bacterial conjunctivitis whereas a history of previous conjunctivitis
correlated significantly with non-bacterial
conjunctivitis.8 Reitveld used these risk
factors to develop a clinical scoring system, which has a sensitivity of 67% and
specificity of 73% at a cut-off of +2 and a sensitivity of 84% and specificity
of 38% at a cut-off of +1.8
Patel et al studied a group of children with a high
proportion of Haemophilus influenzae conjunctivitis and found that
gluey or sticky eyelids and mucoid or purulent discharge were predictive of
bacterial infection.9 Meltzer and colleagues in
New York found in children that no or watery discharge, no glued eyes in the
morning, presentation in summer and age 6 years or older correlated with
negative bacterial culture.10
Some Ophthalmologists claim that adenoviral conjunctivitis
has a distinct clinical pattern but provide no supportive data for
this.11 Based on these studies, glued eyes on
waking and purulent discharge correlate consistently with bacterial infection
but do not as single or even combined variables have sufficient predictive value
to accurately distinguish bacterial from viral conjunctivitis.
Conjunctival swab culture is the gold standard diagnostic
test for bacterial conjunctivitis. Testing is recommended for conjunctivitis in
neonates, contact-lens wearers, outbreaks, suspected venereal infections and
those not responding to treatment, all circumstances in which the microbial
cause is relatively uncertain or could have specific management implications.
For routine cases of conjunctivitis, however, conjunctival swab culture has been
said to play a limited role.
Conjunctival swab cultures have been described as
uncomfortable, impractical (due to the long turnaround time) and expensive. In
one recent report the results of conjunctival swab cultures had no impact on
patient outcome but in this study there was no prospective rational protocol for
when and how to collect the samples or use the
results.7
We prospectively identified all conjunctival swabs submitted
in the Nelson region during a 6-month period. To examine the issue of turnaround
time we measured the accuracy of preliminary (next day) results as a predictor
of final results. To examination their potential utility in routine management
of conjunctivitis we modeled the potential impact of preliminary and final swab
results on treatment and clinical outcome.
MethodsEvaluation of microscopy and preliminary
culture results—We prospectively identified the results of all
eye swabs submitted for bacterial culture between 1 January and 30 June 2009 to
Medlab South, the sole laboratory provider to Nelson city and surrounding
regions. Approximately 90,000 people live in this geographically isolated region
of the South Island of New Zealand. We excluded samples from non-conjunctival
sources and children under 3 weeks of age.
An episode of conjunctivitis was defined as the
submission of 1 or more conjunctival swabs from an individual patient in a
21-day period. In the laboratory, all eye swabs underwent Gram-stain microscopy
followed by inoculation onto sheep blood and chocolate agars and incubation for
48 hours in a CO2 atmosphere. At 24 hours,
potential eye pathogens were identified by colony morphology and microscopy and,
if appropriate, oxidase, butyrate disk and rapid antigen tests.
We compared the results of microscopy and preliminary
culture to the results of final conjunctival swab culture. Positive microscopy
was defined as at least 1+ leukocytes and at least 1+ microorganisms resembling
a common conjunctival pathogen (e.g., gram-positive cocci or gram-negative
bacilli, not gram-positive bacilli.)
Positive preliminary culture was defined as a pure or
predominant growth of any quantity of proven or probable eye pathogen. Bacterial
conjunctivitis was defined as a pure or predominant growth of any eye pathogen
(does not include coagulase-negative staphylococci or non-pneumococcal
alpha-haemolytic streptococci.) Normal skin flora was defined as a mixture of
diphtheroids, viridans-group streptococci or coagulase-negative
staphylococci.
Modelling utility of conjunctival swab culture
results—We modelled the effect of three strategies (see Table 1)
on treatment and clinical outcome in conjunctivitis.
Table 1. Management strategies for
conjunctivitis
Assumptions made and methods applied in modelling:
ResultsOver the 6-month period we processed 164 conjunctival
samples representing 157 patient episodes of conjunctivitis. Of the samples
received, 88 (54%) were from female patients and 138 (84%) were requested by
community general practitioners. Forty samples (24%) were from patients aged 3
to 51 weeks; the other 124 samples were from patients aged 1 to 95 years old and
the age distribution of these patients was fairly even across this range. The
final results of culture are presented in Table 2.
Table 2. Final results of 164 conjunctival
cultures
*E. coli, Proteus
mirabilis, Haemophilus parainfluenzae, Pseudomonas aeruginosa.
Comparisons of gram-stain microscopy and preliminary culture
to final culture results are presented in Tables 3 and 4 respectively. Compared
to final culture, microscopy had a sensitivity of 27%, specificity of 98%,
positive predictive value of 87.5% and overall accuracy of 75%. Compared to
final culture, preliminary culture had a sensitivity of 86%, specificity of 99%,
positive predictive value of 98% and overall accuracy of 95%.
Table 3. Comparison of immediate gram-stain
microscopy to final conjunctival swab culture result (n=161)
* Contains at least 1+
leukocytes and at least 1+ microorganism compatible with an eye pathogen.
Table 4. Comparison of preliminary (next day)
culture result to final conjunctival swab culture result (n=159)
* A pure or
predominant growth of any quantity of proven or probable eye pathogen.
The results of modelling three different management
strategies are displayed in Tables 5 and 6. According to the results in Table 5
and the assumptions used for modeling, the days of symptoms saved by topical
antibacterial therapy for the patients in each management group are estimated as
follows: indiscriminant strategy = 53 days, delayed strategy = 28 days, targeted
strategy - T1 and T2 = at least 42 days. According to the results in Table 6,
the number of days of topical antibacterial treatment used for non-bacterial
conjunctivitis in each management group during the first 3 days are as follows:
indiscriminant strategy = 312 days, delayed strategy = 55 days, targeted
strategy - T1 = 67 days and T2 = 30 days.
Table 5. The number of patients (modelled) with
bacterial conjunctivitis (n=53) who would take topical antibacterial treatment
(appropriately) in each management strategy
* Day 1 = the day the
patient presents to his or her doctor for assessment.
Table 6. The number of patients (modelled) with
non-bacterial conjunctivitis (n=104) who would take topical antibacterial
treatment (unnecessarily) in each management strategy
* Day 1: the day the
patient presents to his or her doctor for assessment.
DiscussionWe have shown that preliminary conjunctival swab culture
results accurately predict final results and that these results could be used to
guide prescription of the correct treatment to the majority of patients with
conjunctivitis within a day after presentation.
When applied to our study cohort of patients presenting with
routine conjunctivitis, modeling showed that a targeted management strategy
involving a clinical algorithm and routine conjunctival swab cultures resulted
in a high reduction in patient symptom days and strategy T2 led to the lowest
number of inappropriate days of topical antibiotic use. The targeted approach
therefore achieves the aims of high patient medical benefit and minimal
unnecessary antibacterial use.
In our model the indiscriminant strategy (prescribing
topical antibacterial treatment to all patients with conjunctivitis, without
conjunctival culture) was the simplest and most effective approach to management
of routine conjunctivitis. This strategy could be rationalized a little by
applying a clinical prediction algorithm to determine which patients to treat on
day 1.
In New Zealand and Australia, where chloramphenicol is the
standard recommended topical antibacterial agent for
conjunctivitis,12,13 there is little incentive
to avoid the unnecessary use of topical antibacterial treatment as serious
adverse reactions to topical chloramphenicol are rare and resistance to
chloramphenicol amongst eye isolates is rare despite its widespread use for
decades. 14-16 In New Zealand a course of
chloramphenicol eye ointment or drops costs less than $2.50.
The situation is different in other parts of the world where
fluoroquinolines and aminoglycosides are recommended first-line antimicrobial
agents for conjunctivitis – these products are not only four- to five-fold
more expensive than chloramphenicol but the agents have major roles in the
treatment of systemic infections. Unnecessary or widespread use of topical
antibacterial fluoroquinolones or aminoglycosides for conjunctivitis may
contribute to the development of resistance, which threatens the use of these
agents in more important clinical situations.
In our model both the targeted strategy and the
indiscriminant strategy were more effective at preventing days of symptoms than
the delayed treatment strategy studied by Everitt et al and recommended by
others.2, 7,17 This is consistent with the
results presented in Everitt’s study, which showed that those patients
randomized to delayed topical antibacterial treatment had a longer mean duration
of moderate symptoms (3.9 days) than those randomized to immediate antibiotics
(3.3 days).7
The major disadvantage in delaying treatment for all cases
is that those with bacterial infections lose an opportunity for 2 days of active
treatment, which could have shortened their symptoms, potentially allowed them
to return to work or school earlier and reduced the transmission of bacterial
eye pathogens to others. Moreover, approximately half of those who decide to
start antibacterial therapy after 2 days of persistent symptoms could be
ineffectively treating a viral infection.
Advantages of the delayed approach include relatively low
usage of topical antibacterial treatment and empowerment of the patient to make
their own decision on topical antibacterial treatment (which many will decline
if told that their infection is a benign and self-limited condition, even if it
means more days of symptoms).18
In a recent Cochrane review the authors commented on the
lack of cost-effectiveness data for treatment of
conjunctivitis.1 We found there were too many
intangible variables and outcomes and too much uncertainty in our assumptions to
be able to model cost. For example, although the targeted approach has up-front
additional costs for a conjunctival swab (approximately $20 per patient),
frequent initial prescription of topical antibacterial treatment (approximately
$2.40 per patient) and the time taken for at least one follow-up contact
(approximately $5 for a phone call), these may be offset by increased diagnostic
certainty (reducing the need for repeat medical assessments), savings in reduced
days off work or school for some patients and reduced antibiotic resistance
pressure in your community.
Cost-effective analyses are complex and region-specific - a
recent North American report, for example, concluded that US$24 point-of-care
adenovirus testing on conjunctival samples was cost-effective, despite that test
providing less useful information to guide management than a swab
culture.19
Our study samples were not collected routinely or
deliberately for the purposes of this analysis but were collected when thought
to be clinically indicated and therefore do not represent all cases of
conjunctivitis presenting for care. Our patient population, however, is similar
to that in other reports, which should allow most readers to apply our results
to their circumstances. Provided there is co-operation by the local laboratory
(e.g., phoning or electronic transmission of provisional results) and education
and motivation of local practitioners, a targeted strategy similar to our model
could be implemented in primary-care (community) or hospital settings.
Our results indicate that such a strategy would be effective
and ecologically friendly and could lead to improved quality of care. To improve
the cost effectiveness of the targeted strategy, clinicians could apply it only
to patients for whom the conjunctivitis is preventing attendance at paid
employment (like a health-care worker) or school.
A targeted approach may also have additional value in
patients with severe symptoms, patients who have less predictive clinical
features (for example a Rietveld score of +1 to +3) or patient groups from parts
of the world or circumstances (e.g., hospital-acquired) where the ratio of
bacterial to non-bacterial conjunctivitis is higher or where microbial causes of
simple conjunctivitis are less predictable or less susceptible to local topical
antibacterial agents.
ConclusionPreliminary (next day) conjunctival swab culture results are
highly predictive of the final result and could be used by practitioners to
guide use of topical antibacterial treatment.
Author information: Richard J Everts,
Infectious Diseases Specialist and Clinical Microbiologist, Nelson Hospital,
Nelson; Tony Barnett, Laboratory Scientist, Medlab South, Nelson; Ben R Lahood,
Resident Medical Officer, Nelson Hospital, Nelson
Acknowledgement: We thank Hazel Everitt for
reviewing the manuscript.
Correspondence: Richard Everts, Nelson
Hospital, Private Bag 18, Nelson, New Zealand. Fax: +64 (0)3 5461288.
Email: richard.everts@nmdhb.govt.nz
References:
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