Treatment for Acute Infective Conjunctivitis in Children

7/30/2019 Treatment for Acute Infective Conjunctivitis in Children

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JOURNAL CLUBPRESENTATION

fromDR. M. Atiq ur Rahman



• CHLORAMPHENICOL TREATMENTFOR ACUTE INFECTIVECONJUNCTIVITIS IN CHILDREN IN

PRIMARY CARE : A RANDOMISEDDOUBLE - BLIND PLACEBO -CONTROLLED TRIAL By Peter,

Anthony, Angela, Rafael, Aziz, et al.



• INTRODUCTION Acute infective conjunctivitis has a substantial effect on the health-

service work load despite its low morbidity.

The disease accounts for up to 1% of consultations in primary care.

In U.K., more than 1 million episodes, & in

U.S.A. 5 million ( i.e. 1 in 8 children have conjunctivitis every year).Most of family doctors recognise the difficulty of differentiating a viral

from bacterial cause.

In England, topical ocular antibiotic prescriptions is large (around 2.3million are issued every year in primary care ).

Acute conjunctivitis often has a bacterial cause and therefore

prescription of antibiotics seems rational.



• A Cochrane systematic review of treatment showed thattopical Abx resulted in significantly greater clinical andmicrobiological remission than placebo, but also showeda high rate of resolution with placebo.

• However, the included trials were all based onsecondary-care populations, with exclusively bacterialinfections and in which disease severity was probablyincreased.

• So, they designed a randomised trial to investigate theeffectiveness of topical chloramphenicol for childrenpresenting with acute infective conjunctivitis presentingin primary care.



• METHODS• The study was a placebo-controlled, double-blind, randomised

controlled trial consisting of 326 children with a clinical diagnosis of conjunctivitis.

• Children were randomly assigned to receive chloramphenicol ( n=

163) or placebo eye drops ( n= 163).• Chloramphenicol was chosen because it is the most commonpreparation used by family doctors and has a low rate of resistancein common organisms.

• Previous fears about the drug’s safety have not been proven(Lancaster, Swart, Jick, BMJ I998; 316:667)

• This study was approved by the Oxfordshire clinical research ethicscommittee with 12 practices in Oxxfordshire, U.K., recruited byOxford Childhood Infection Study (OXCIS).



• Children aged between 6 months and12 years with a working diagnosis of acute

infective conjunctivitis.

• Exclusion criteria was – a).allergic to

chloramphenicol, b) current Abx within the

previous 48 h. c) immunocompromised. d)

had evidence of severe infection ( e.g.periorbital cellulitis ).



• PROCEDURES

• Recruitement occurred between October and april in2001 -02, 2002 – 03, and 2003 – 04 , because moreinfective events rather than allergic conjunctivitis arise

during these months.• The recruiting family doctors gave parents a standard

information sheet, with written information designed for children.

• Children were seen by a research nurse within 4 hoursof recruitement.

• The study was explained to parents and children, andthose agreeing to participate signed a consent form.



• They undertook an audit of the medical records of allchildren consulting family doctors and period was for 1week every month during recruitement with acuteinfective conjunctivitis.

• For baseline assessments, a research nurse assessedclinical severity, including the degree of redness of theeye, by comparison with validated photographs.

• Two conjunctival swabs were taken from the worst – affected eye by use of a cotton swab for bacterial culture

and a Dacron swab for viral PCR assays.

• All research nurses trained in proper conjunctivalsampling techniques from Oxford Eye Hospital, U.K.



• Identical bottles were prepared containing either 0.5% chloramphenicol eye drops or distilledwater with the excipients boric acid (1.5%) andborax (0.3%).

• The active and placebo drops were randomisedcentrally by use of random number tables inblocks of ten.

• patients were given a bottle of eye drops by the

recruiting nurse with instructions to put one dropin each of their child’s affected eye every 2 h for the first 24 h and then four times daily until 48 hafter the infection resolved.



• At 7 days follow-up, the child was seen again bya research nurse after recruitement when aclinical assessment was made and two swabswere taken from the same eye as the first swab.

• Every 6 weeks , parents were telephoned toidentify any further eye problems since the endof the trial.

• The primary outcome measure was the clinical

cure at 7 days, as stated by parents.• The time of cure was the first recorded time inthe diary after which none of three symptoms(pain, redness, or discharge) was recorded.



• For microbiological outcome measures, conjunctivalswabs were taken to the laboratory immediately after sampling and processed on arrival.

• Blood agar and chocolate agar plates were inoculated.

Agar plates were incubated at 37.C in 5% CO2 for atleast 48 h, and all morphollogically different bacterialtypes were identified by standard clinical microbiologicaltechniques.

• They used molecular assays to detect the presence or

absence of adenovirus, picornavirus, herpes simplexvirus , and Chlamydia trachomatis.



• Regarding bacteria , other than Hemophilusinfluenzae and Streptococcus pneumoniae, stilldebate as pathogenic in childhood conjunctivitis.

• They undertook a meta-analysis to compare the

bacteria cultured from the conjunctivae of 518children with conjunctivitis and283 healthycontrol children, aggregating data from twoprevious studies.

• The most common organisms in conjunctivitissamples compared with controls wereH.influenzae, S.pneumoniae, and Moraxellacatarrhalis.



Colony counts were grouped as follows :100 or more colonies = 3,11 – 99 = 2 ,

1 – 10 = 1,and no growth = 0.The outcome was the difference betweencolony count classifications on the

recruitement and swabs at day 7 for H.influenzae, S. pneumoniae, and M.catarrhalis identified in every case.



• Zero colony counts on the second swab werelabelled as cured, reduced colony countslabelled as improved , same colony countslabelled as unchanged, and increased colonycounts labelled as worse.

• If H. influenzae, S.pneumoniae, or M.catarrhaliswere detected concomitantly, the final outcomewas taken as the worst outcome among themultiple bacteria.

• According to this outcome, children werecompared.



• STATISTICAL ANALYSIS For all dichomotous outcomes, the riskdifference between the chloramphenicol andplacebo groups with 95% CIs was calculated.

• For clinical cure outcome at day 7 , an estimateof the number of children was obtained.

• Clinical cure rates in the two groups werecompared with the log-rank test and Kaplan-

Meier survival statistics.• Individuals lost to follow-up were treated as stillnot cured by the end of day 7 ( i.e. intention totreat analysis ).



• A 19% difference in cure rate at 7 days hadbeen previously reported (Gigliotti, Hendley,Morgan, et al. J.Pediatrics 1984; 104:623-626 ).

• However , the sample size was recalculated(without breaking the randomisation code) whenthese later assumptions clearly did not hold –almost 80% of events were bacterial and theoverall 7- day cure rate was more than 80%.

• This study showed a 12- 14% difference incomparison with previous reports.



• RESULTS

Chloramph- Placebo Non-random-

nicol(n=163) (n=163) ised (n=30)

Age(years)

Mean(SD) 3.3(2.8) 3.3(2.6) 3.7(2.9)

Median(IQR) 2.4(1.2-4.3) 2.6(1.3-4.3) 2.9(1.4-4.9)

Sex

No. of male 83(51%) 87(53%) 19(63%)

Clinical features

Moderate or severe

redness 36/153(24%) 39/152(26%) 10(33%)

Purulent discharge 136/162(83%) 130/161(81%) 28(93%)

Pain or soreness 81/163(50%) 77/162(48%) 22(73%)

Unilateral 58(36%) 50(31%) 11(37%)

Social class (as mother’s profession)

Profession or managerial 90/161(56%) 77/157(49%) 16(53%)

TABLE: Baseline characteristics of eligible children



chloramphenicol placebo Total

(n=162) (n=163) (n=325)

Bacteria

Total 126(78%) 126(77%) 252(78%)

H.influenzae 99(61%) 98(60%) 197(61%)

S.pneumoniae 32(20%) 32(20%) 64(20%)

M.catarrhalis 20(12%) 16(10%) 36(11%)Virus

Total 24(15%) 19(12%) 43(13%)

Adenovirus 11(7%) 8(5%) 19(6%)

Picornavirus 13(8%) 11(7%) 24(7%)



Chloramphenicol Placebo Difference(95%CI)

(n= 163) (n=163)

Time to cure (days)

Median (IQR) 5(3 to 6) 5(4 to 7) 0

Clinical cure at day 3

Intention to treat

comparison 64(39%) 54(33%) 6.2%(-4.3%to16.5%)

Clinical cure at day 7

Intention to treat comp. 140(86%) 128(79%) 7.4%(-o.9 to 15.6%)Excl. of pts.lost to F.U. 140/162(86%) 128/155(83%) 3.8%(-4.1 to 11.8%)

Pts. With bacterial only 101/119(85%) 94/117(80%) 4.6%(-5.1 to 14.2%)

Microbiological cure at day 7

Cure 50/125(40%) 29/125(23%) 16.8%(5.5 to 28%.1)

Improvement 31/125(25%) 40/125(32%) -7.2%(-18.3to3.9%)



• Relapse rate

Further episode of

conjunctivitis within 6 weeks 7(4%) 5(3%) 1.2%(-2.9 to 5.3%)

Adverse clinical eventsDay 1-7 3(2%) 3(2%) 0%(-2.9 to 2.9%)

(Chloramphenicol group: one child developed eyelid and facialoedema, one admitted with bronchiolitis, and one subsequently

diagnosed with keratitis.

Placebo group : two children developed a generalised rash and

one developed otitis media

TABLE: Main outcomes in treated children



• DISCUSSION• They have shown that symptoms resolve without Abx

in most children with acute infective conjunctivitis.

. In their intention to treat analysis, they recorded a modestimprovement in symptom resolution at day 7 in the groupreceiving chloramphenicol.

. About half a day was gained in time to resoluton betweenchildren treated with Abx and those with placebo.

. Their microbiology results confirm that chloramphenicoldoes reduce the number of pathogenic bacteria in theeye, but eradication is not essential for a clinical cure.



. Follow up for 6 weeks after diagnosis showed that

complications and relapse were uncommon , even

without treatment.

. Overall quality of the trial was good.

.The randomisation method was robust, and masking was

maintained.

. The dropout rate was low – nearly 95% of children were

followed up for 6 weeks after recruitment.

.The microbiological quality better than previous work.

. By use of a combination of culture and PCR, they could

identify a microbiological cause in 80% of children.



• They recorded lower colony counts for M.catarrhalis than for H.influenzae andS.pneumoniae, but exclusion of M. catarrhalis asa pathogen in their analysis made no substantialdifference to the results.

• The health economic argument against Abxprescription for acute conjunctivitis is compelling.

• The cost of 1 million general practiceconsultations and Abx prescriptions every year is substantial.



• Their study design could not assess the effect of

non-prescriptions on transmission rates.

• Acute infective conjunctivitis is regarded as

potentially transmissible, especially in childrenyounger than 5 years.

• They recorded no evidence to suggest that

microbiological investigation to distinguish viral

from bacterial causes with an immediate result,

would be helpful.



• Bacterial eradication was unimportant-clinical cure wasreported by parents even if bacteria could still berecovered at day 7.

• The relapse rate after Abx treatment stopped was low

and irrespective of the randomisation group.• They did not identify any children with C.trachomatis

infection in their cohort study.

• They chose to assess the effectiveness of chloramphenicol because this drug is the mostcommonly used topical Abx for conjuntivitis in the U.K.,where resistance to chloramphenicol is rare – noresistant isolates were detected in the study.



• MESSAGE

• This results show that healthy children with

acute conjunctivitis do not need an ocular

antibiotic at first presentation to primary care .• Parents should be encouraged to treat children

themselves without medical consultation, unless

their child develops unusual symptoms persist

for more than a week.



•

• THANK YOU

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Treatment for Acute Infective Conjunctivitis in Children