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The New Zealand Medical Journal

 Journal of the New Zealand Medical Association, 21-January-2011, Vol 124 No 1328

The utility of routine conjunctival swabs in management of conjunctivitis
Richard J Everts, Tony Barnett, Ben R Lahood
Abstract
Aim To determine the accuracy of preliminary results of conjunctival swab culture and to evaluate the utility of preliminary and final conjunctival swab culture results in the routine management of conjunctivitis.
Methods We prospectively identified 164 conjunctival swabs from adults and children over 3 weeks of age and compared preliminary (next day) with final culture results. We modelled the would-be effect on treatment and clinical outcome of three strategies (indiscriminant, delayed and targeted) for management of acute conjunctivitis.
Results In total, 54 of 164 (33%) samples yielded significant bacterial growth. Compared to final culture, preliminary culture had a sensitivity of 86%, positive predictive value of 98% and specificity of 99%. Modelling showed that an indiscriminant approach to management (all patients given topical antibacterial treatment, no swabs taken) was the most effective at reducing symptoms but led to substantial unnecessary use of topical antibacterial treatment. Modelling showed that a delayed treatment strategy (patients start topical antibacterial treatment only if not improving satisfactorily after 2 days, no swabs taken) was the least effective at reducing symptoms and lead to moderate unnecessary use of topical antibacterial treatment. The targeted treatment strategy (topical antibacterial treatment given to those with clinical predictors of bacterial infection on day 0, positive preliminary culture results on day 1 and positive final culture results on day 2) was highly effective at reducing symptoms and potentially the least wasteful of topical antibacterial treatment.
Conclusion Preliminary (next day) conjunctival swab culture results are highly predictive of the final result and could be used by practitioners to guide prescription of topical antibacterial treatment.

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.

Methods

Evaluation 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
Strategy
Description
Indiscriminant
No conjunctival swab taken. Topical antibacterial eye treatment given to all patients on day 1.
Delayed treatment
No conjunctival swab taken. Patient educated and reassured about benign and self-limited nature of conjunctivitis. No antibacterial eye treatment given for first 2 days. If not improving at day 3 then start antibacterial eye drops.7
Targeted treatment (T1 and T2)
At first assessment (day 1), conjunctival swab collected for culture from all cases. Patients prescribed topical antibacterial treatment on day 1 if they have a Reitveld’s clinical score of +1 or more (group T1) or +2 or more (group T2).8 Then use preliminary microbiology results (day 2) and final results (day 3) to guide offer of topical antibacterial treatment to patients who still have symptoms.
Assumptions made and methods applied in modelling:
  • The population used for modelling was our own cohort of 157 patient episodes, including 53 episodes of bacterial conjunctivitis and 104 episodes of non-bacterial conjunctivitis.
  • In the indiscriminant treatment strategy, all patients comply with topical antibacterial treatment, irrespective of symptom resolution, for the first few days.
  • In the delayed treatment strategy, 53% patients collect a prescription for topical antibacterial treatment on day 3, irrespective of cause of conjunctivitis (53% chose to take treatment on day 3 in the Everitt study and the cause of conjunctivitis in these patients was not described).7
  • In the targeted treatment strategy, the proportion of patients given topical antibacterial treatment on day 1 (subgroups T1 and T2) is based on the proportion of patients with these scores in Reitveld’s published cohort.8
  • In the targeted treatment strategy, the proportion of patients with positive Gram-stain microscopy and preliminary culture results on day 2 was based on the results in our cohort of actual patients.
  • In the targeted treatment strategy, all patients are contacted on day 2 with the preliminary results of their conjunctival swab culture and treatment advice is based on that result (and the presence of any residual symptoms, see below); patients whose final result is different from the preliminary result are contacted again on day 3 and treatment advice is based on that result (and the presence of any residual symptoms, see below). On each day, the treatment advice supersedes that of the previous day; for example, if a patient is started on topical antibacterial treatment on day 1 based on clinical variables but the preliminary laboratory results do not indicate a bacterial infection, the patient is advised to stop treatment.
  • Based on the reported clinical outcomes for patients with proven bacterial conjunctivitis who were randomized to placebo treatment in the studies by Gross et al, Gigliotti et al and the Ofloxacin Study Group III, the symptoms and signs spontaneously resolve in 10% of bacterial conjunctivitis patients per day.4-6 Therefore, in the targeted treatment strategy, 10% of patients on day 1 and 20% of patients on day 2 are not offered topical antibacterial treatment even if their laboratory results indicate bacterial infection.
  • Efficacy of topical antibacterial treatment for bacterial infections is estimated to be 1 day fewer symptoms, irrespective of when treatment was started.

Results

Over 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
Result
Number of cases (%)
No microbial growth
Mixed skin flora
Significant bacterial growth
Streptococcus pneumoniae
Staphylococcus aureus
Haemophilus influenzae
Moraxella catarrhalis
Others*
52 (32)
58 (35)
54 (33)
15
12
10
4
13
*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)
Variables
Bacterial conjunctivitis
Non-bacterial conjunctivitis
Microscopy positive*
Microscopy negative
14
38
2
107
* 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)
Variables
Bacterial conjunctivitis
Non-bacterial conjunctivitis
Preliminary culture positive*
Preliminary culture negative
42
7
1
109
* 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
Management strategy
Indiscriminant
Delayed
Targeted (T1)
Targeted (T2)
Day 1*
Day 2
Day 3
53
53
53
0
0
28
45
41
42
36
41
42
* 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
Management strategy
Indiscriminant
Delayed
Targeted (T1)
Targeted (T2)
Day 1
Day 2
Day 3
104
104
104
0
0
55
65
2
0
28
2
0
* Day 1: the day the patient presents to his or her doctor for assessment.

Discussion

We 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.

Conclusion

Preliminary (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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  2. Epling J. Bacterial conjunctivitis. BMJ Clin Evid 2007;10:704
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