Tropical Medicine and International Health

volume 10 no 2 pp 190197 february 2005

Topical quinolone vs. antiseptic for treating chronic suppurative

otitis media: a randomized controlled trial
Carolyn Macfadyen1, Carrol Gamble2, Paul Garner1, Isaac Macharia3, Ian Mackenzie1, Peter Mugwe3, Herbert
Oburra3, Kennedy Otwombe1, Stephen Taylor2 and Paula Williamson2
1 International Health Research Group, Liverpool School of Tropical Medicine, Liverpool, UK
2 Centre for Medical Statistics and Health Evaluation, School of Health Sciences, University of Liverpool, Liverpool, UK
3 Section of Ear, Nose and Throat Diseases, University of Nairobi, Kenyatta National Hospital, Nairobi, Kenya

Summary

objective To compare a topical quinolone antibiotic (ciprofloxacin) with a cheaper topical antiseptic
(boric acid) for treating chronic suppurative otitis media in children.
design Randomized controlled trial.
setting and participants A total of 427 children with chronic suppurative otitis media enrolled from
141 schools following screening of 39 841 schoolchildren in Kenya.
intervention Topical ciprofloxacin (n 216) or boric acid in alcohol (n 211); child-to-child
treatment twice daily for 2 weeks.
main outcome measures Resolution of discharge (at 2 weeks for primary outcome), healing of the
tympanic membrane, and change in hearing threshold from baseline, all at 2 and 4 weeks.
results At 2 weeks, discharge was resolved in 123 of 207 (59%) children given ciprofloxacin, and in
65 of 204 (32%) given boric acid (relative risk 1.86; 95% CI 1.482.35; P < 0.0001). This effect was
also significant at 4 weeks, and ciprofloxacin was associated with better hearing at both visits. No
difference with respect to tympanic membrane healing was detected. There were significantly fewer
adverse events of ear pain, irritation, and bleeding on mopping with ciprofloxacin than boric acid.
conclusions Ciprofloxacin performed better than boric acid and alcohol for treating chronic
suppurative otitis media in children in Kenya.
keywords randomized controlled trial, otitis media, suppurative, fluoroquinolones, antiseptics,
eardrops, instillation, drug, hearing impairment, developing countries

Introduction
Chronic suppurative otitis media (CSOM) is a common
cause of hearing impairment in low- and middle-income
countries [Berman 1995; World Health Organization
(WHO) 1998]. It is defined as chronically discharging ears
(for at least the preceding 2 weeks) associated with
persistent eardrum perforations. Data on prevalence of
CSOM are uncommon, although one study estimated it at
1.1% in Kenyan schoolchildren (Hatcher et al. 1995).
Treatment aims to eradicate infection, prevent complications, heal the tympanic membrane, and improve hearing.
Treatment options include dry mopping, ear wicking,
gentle syringing, or suctioning; systemic antibiotics; and
topical treatment with either antiseptics or antibiotics,
sometimes with steroids. A Cochrane Review published in
190

1998 (Acuin et al. 2004) concluded that topical treatment

with antibiotics or antiseptics is more effective than
systemic antibiotics, aural toilet alone, or no treatment at
all; and topical quinolones were better than topical
non-quinolone antibiotics.
Antiseptic drops, such as boric acid, are cheap and listed
in country guidelines of some low-income countries; e.g. in
Papua New Guinea (Standard Treatment for Common
Illnesses of Children in Papua New Guinea 1993). The
Cochrane Review identified three small studies (n 126)
comparing topical antiseptics with topical antibiotics, and
did not demonstrate a difference for the outcome wet ear
(Acuin et al. 2004).
Topical ciprofloxacin, a quinolone antibiotic, has
recently become available, is licensed in the European
Union, but is expensive: 5 per 5 ml bottle in the UK. The

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Tropical Medicine and International Health

volume 10 no 2 pp 190197 february 2005

C. Macfadyen et al. Topical quinolone vs. antiseptic for chronic suppurative otitis media

Cochrane Review found quinolones superior to other

topical antibiotics for CSOM; we conducted a randomized
trial to evaluate this expensive but apparently effective
drug against topical antiseptics in Kenyan schoolchildren.

Methods
Study site
Rural primary schools in Kisumu District, West Kenya: we
visited 165 of the 186 total. The District has the highest
infant (116.7/1000) and under 5-year (194.7/1000)
mortality in Kenya, and ear infection is common (Ministry
of Planning and National Development 2004).
Participants
School children aged 5 years and older, with (a) purulent,
aural discharge for 14 days or longer; (b) pus in the
external canal on otoscopy; and (c) perforation of the
tympanic membrane. We excluded children who had been
treated for ear infection or received antibiotics for any
other disorder in the previous 2 weeks, or who had other
ear problems (pre-existing disease, complicated otitis
media, anatomical abnormalities) or allergy to study drugs.
Interventions
Topical eardrops were given twice daily, after dry mopping, for 10 consecutive school days (no treatment at
weekends) with either ciprofloxacin eardrops (Ciloxan
0.3%; Alcon), or antiseptic eardrops (2% boric acid in
45% alcohol). Older children were appointed as ear
monitors and trained to clean and treat the infected ears,
under the supervision of trained teachers, as described in
Smith et al. (1996).
Randomization and masking
Children were randomized in a 1:1 ratio using computergenerated block randomization, stratified by school. Each
treatment pack contained two bottles of randomized
treatment and remained sealed until allocated to a child;
packs and the bottles were identical in appearance and
both treatments identical in colour and smell. Participants,
carers, and outcome assessors remained blind to the
treatment allocated throughout the study.
Field procedures
Four trained teams [each consisting of an Ear Nose and
Throat (ENT) registrar, clinical officer, and a nurse

2005 Blackwell Publishing Ltd

experienced in ENT] screened children by class, inviting

children with CSOM and their guardians to an induction
visit, usually two school days later. At induction, a childs
legal guardian(s) provided signed informed consent before
assessments. After consent, but before randomization,
teams performed baseline and eligibility assessments.
Demographic data and a medical history were taken.
Nurses established pure tone hearing threshold for air
conduction, in decibels at 500 Hz, 1 kHz, 2 kHz, 4 kHz
and 8 kHz, in a quiet location and by a standard technique
using portable Kamplex screening audiometers (AKM KS8
MP, battery operated); they recorded ambient noise levels
using sound level meters. After audiometry, registrars and
clinical officers swabbed infected ears (for bacteriology and
sensitivity analysis in Kisumu), then examined both ears for
presence and degree of discharge, tympanic membrane
perforation, and any other otoscopic findings using Earlite
Kite and Heine mini otoscopes.
After completing all induction assessments, eligible
children were allocated their sequential treatment pack;
clinical officers trained children and teachers and supervised the first dose. Every child was given a treatment
record to complete to monitor treatment administration.
Follow-up and outcomes
Children were seen at 2 and 4 weeks to collect data. Where
children were absent, we revisited the school the next day.
All teams rotated schools for follow-up visits, to avoid
them assessing children they had previously seen. Outcomes were (a) resolution of aural discharge; (b) healing of
tympanic membrane; and (c) change in hearing threshold.
The primary outcome was resolution of aural discharge at
2 weeks. We also recorded adverse events.
Children with persistent discharge at week 2 were
instructed to dry mop the ear(s) until week 4; those
discharging at week 4 were also instructed to dry mop, and
given a new bottle of eardrops and referred, with children
with persistent perforation or other ear pathology, to the
ENT surgeon in Kisumu. Children with other illnesses were
referred to the nearby clinic or hospital. Any children
referred during the study, remained in the study, and details
of their referral and subsequent treatment were collected.
Sample size
Rates of CSOM may be higher in Kisumu than the 1.1%
found other parts of Kenya, with its higher infant mortality
rates (http://www.cbs.go.ke) and higher rates of ear diseases
estimated by local medical staff and local surveys conducted
in 2000 (Educational Assessment and Resource Centre
Kisumu, and New Nyanza Provincial General Hospital
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C. Macfadyen et al. Topical quinolone vs. antiseptic for chronic suppurative otitis media

(NNPGH) ENT Clinic, Kisumu, unpublished data; and

Dr David Odeny, personal communication) we therefore
used a higher estimate than that of Hatcher et al. 1995, but
more conservative than the local Kisumu estimates, 15.1%,
which were judged to be overestimated as they were based
on 900 students screened in three schools selected following
high referral numbers to the education assessment and
rehabilitation centre in Kisumu and rates may not be
limited to CSOM. Assuming a prevalence of 2%, and a total
of 46,116 children in 186 schools in February 2002 (Office
of the District Education Officer 2002), we estimated that
920 children would be potentially eligible for the study.
Assuming 750 agreed to participate and an estimated 50%
resolution rate at 2 weeks in the antiseptic group (Acuin
et al. 2004), we calculated the study would have a power of
79% to detect the defined minimum clinically worthwhile
absolute difference in resolution rates of 10%, at a twosided significance level of 5%.
An interim analysis was carried out for the first 200
study participants to check the estimated resolution rate for
the control group. The results indicated a resolution rate at
2 weeks of 0.31 (95% CI 0.220.40) in the boric acid
group. Although the original estimate of 0.5 was excluded
from the confidence interval, further sample size calculations assuming, in turn, the limits of this interval to be the
true proportion (i.e. 0.22 and 0.40 respectively), showed
our original numbers would still be sufficient to provide
approximately 80% power to detect an absolute difference
of 10% in either of these scenarios. Thus our target sample
size seemed compatible with the plausible estimates for the
control group resolution rate from our interim analysis. As
this calculation did not involve any comparison between
the two groups, the overall type 1 error rate is unaffected
(Wittes et al. 1999).
Statistical methods (analyses)
All analyses followed the intention-to-treat principle and
were conducted using SAS v8.2 2001. For bilateral disease,
resolution and healing were considered to occur when both
ears were resolved or healed. We also carried out sensitivity
analyses defining bilateral resolution and healing to have
occurred when either or both ears resolved or healed.
For audiometry readings, a single reading was taken
from the diseased ear in unilateral cases, whilst the average
across the two ears was calculated for bilateral disease.
Hearing threshold was recorded in dBHL and was
averaged across the 500 Hz, 1 kHz, 2 kHz and 4 kHz
frequency range.
For resolution and healing outcomes, ciprofloxacin was
compared with boric acid using the relative risk (RR) and
95% confidence interval. We assessed the statistical signi192

ficance using the Pearsons chi-square statistic. We used

logistic regression for resolution at 2 weeks, to assess
whether the age of the child, bilateral disease, length of
current CSOM episode and degree of perforation at
induction affected the relative treatment effect. Results are
expressed as odds ratio (OR).
For audiometry, analysis of covariance (ancova) was
undertaken for hearing threshold, according to the study
protocol. The WHO classifications were also used to
describe hearing impairment levels and Fishers exact test
was used consider changes between levels.
We report adverse events, notably local symptoms such
as pain, irritation or bleeding (for example on mopping), as
a secondary outcome.
Ethical approval
We obtained ethical approval from the Ministries of
Education and Health, the Provincial Ethical Review
Committee, the Kenyatta National Hospital Institutional
Review Board in Kenya, and the Liverpool School of
Tropical Medicine Research Ethics Committee in the UK.
We received consent for the study from local education and
medical staff, from head teachers of the schools, who
informed students, and parents. We obtained informed
parental consent from eligible childrens legally acceptable
representatives.
Results
We conducted the study in 165 of the 186 Kisumu rural
primary schools in the May to August 2002 school term.
Twenty-one schools were not reached in the time
available. We reviewed 39 266 children at the screening
visit, plus an additional 575 children seen at the
induction visit. We found eligible children in 141
schools, and randomized a total of 427 children (Figure 1). At the week 4 visit, three subjects in the boric
acid group and one in the ciprofloxacin group were seen
1 week late. Seven children received some or all of the
wrong treatment because of switching with other participants bottles at allocation or during treatment
(Figure 1). All participants were analysed in the group
they were initially randomized to. The groups were
comparable with respect to baseline data (Table 1).
Outcomes
Resolution of aural discharge is higher with ciprofloxacin
at 2 and 4 weeks (Table 2). Sensitivity analyses allowing
for varying outcome definition in bilateral disease did not
significantly affect the results. The estimated treatment

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Tropical Medicine and International Health

volume 10 no 2 pp 190197 february 2005

C. Macfadyen et al. Topical quinolone vs. antiseptic for chronic suppurative otitis media

Assessed for eligibility (n = 39 841*)

*39, 266 at screen + 575 at induction

Diagnosed with CSOM (n = 548*)

*489 at screen + 59 at induction
Children with CSOM not entered trial (n = 121)

Invited but absent at induction (n = 19)

Declined to give consent

(n = 2)

Did not meet inclusion criteria (n = 100)*

Dry perforation
(n = 40)
Other diagnoses (n = 19)
Other medications (n = 21)
Too young
(n = 14)
Other reasons
(n = 22)
*16 children met two exclusion criteria
Randomised (n = 427)

(n = 216)
Allocated to ciprofloxacin

(n = 212)
Received cipro only

Received cipro and boric (n = 3)

Received boric only

(n = 1)

(n = 211)
Allocated to boric acid

Received boric acid only (n = 208)

Received boric and cipro (n = 2)

Received cipro only

(n = 1)

Treat 10 schooldays (twice daily)

Child to child approach
Week 2 follow-up

Week 2 follow-up

Attended

(n = 207)

Attended

Absent but not withdrawn

(n = 3)

Absent but not withdrawn

(n = 2)

Absent and withdrawn at week 2

(n = 6)

Absent and withdrawn at week 2

(n = 5)

Lost to follow-up
(n = 5)
Consent withdrawn (n = 1)

Week 4 follow-up
(n = 200)
Attended:
Withdrawn at week 2
(n = 6)
Absent and withdrawn at week 4 (n = 10)

Lost to follow -up

(n = 10)

(n = 204)

(n = 5)
Lost to follow-up
Consent withdrawn (n = 0)

Week 4 follow-up
Attended
Withdrawn at week 2
Absent and withdrawn at week 4

Lost to follow -up

(n = 202)
(n = 5)
(n = 4)

(n = 4)

Figure 1 Flow of participants through the study.

effect for resolution of discharge did not differ substantially

after adjusting for age of the child, bilateral disease, length
of current CSOM episode and degree of perforation at
induction, using logistic regression: at 2 weeks, the results,

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expressed as OR, 95% CI were 3.13, 2.094.69 (unadjusted); 3.16, 2.044.93 (adjusted); and at 4 weeks were
2.86, 1.914.27 (unadjusted); and 2.91, 1.884.50
(adjusted).
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C. Macfadyen et al. Topical quinolone vs. antiseptic for chronic suppurative otitis media

Antibiotic (Cipro)

Antiseptic (Boric)

Characteristic

N*

N*

Total randomized

216

211

Age [mean (SD) (range)]

215

Male [n (%N)]

216

11.0 (3.15)
(5.119.0)
128 (59)

211
211

11.3 (3.15)
(4.119.3)
123 (58)

Bilateral [n (%N)]

216

48 (22)

211

58 (27)

Weeks since start of current episode

[median (IQR)]

196

8 (416)

194

8 (420)

Start of current episode [n (%N)]

Ear ache
Cough or cold
Fever
Other
Not known

216

Any treatment ever received for ear

problems [n (%N)]

214

117 (55)

210

122 (58)

Audiometry [mean (SD) (range)]

212

41.0 (13.3)
(16.9100)

209

42.3 (13.4)
(11.3100)

Table 1 Baseline comparison

211
127 (59)
75 (35)
61 (28)
50 (23)
39 (18)

126 (60)
75 (36)
54 (26)
65 (31)
26 (12)

Degree of perforation [n (%N)]

Unilateral disease (diseased ear)
Small
Medium
Large
Total
Bilateral disease (both ears)
Both small
Both medium
Both large
Both total
One small, one medium
One small, one total
One medium, one large
One large, one total

166

149
28
70
56
11

(17)
(42)
(34)
(7)

47

22
61
56
10

(15)
(41)
(38)
(7)

56
5 (11)
14 (30)
11 (23)
5 (11)
4 (9)
1 (2)
5 (11)
2 (4)

4 (7)
18 (32)
17 (30)
2 (4)
5 (9)
0
8 (14)
2 (4)

* N is the number available or eligible for each characteristic.

Table 2 Resolution of aural discharge at 2 and 4 weeks
Antibiotic (cipro)
[n/N (%)]

Antiseptic (boric)
[n/N (%)]

RR (95% CI)

P-value

Resolution at 2 weeks
1. Both ears resolve
2. Either or both ears resolve

123/207 (59.4)
132/207 (63.8)

65/204 (31.9)
77/202 (38.1)

1.86 (1.482.35)
1.67 (1.362.05)

<0.0001
<0.0001

Resolution at 4 weeks
1. Both ears resolve
2. Either or both ears resolve

130/196 (66.3)
143/197 (72.6)

90/198 (45.5)
105/198 (53.0)

1.46 (1.221.75)
1.37 (1.171.60)

<0.0001
<0.0001

Total randomized: N 216; N 211.

Results include all children, treated for unilateral disease and for bilateral disease. Only the study ear has been considered for children
with unilateral disease in all analyses. Two approaches for handling children treated for bilateral disease: counted as success where
(1) both ears resolve, or (2) either or both ears resolve.

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C. Macfadyen et al. Topical quinolone vs. antiseptic for chronic suppurative otitis media

Table 3 Complete healing of tympanic

membrane at 2 and 4 weeks

Healing at 2 weeks
1. Both ears healed
2. Either or both ears
healed
Healing at 4 weeks
1. Both ears healed
2. Either or both ears
healed

Antibiotic
(cipro)
[n/N (%)]

Antiseptic
(boric)
[n/N (%)]

RR (95% CI)

P-value

15/207 (7.2)
19/207 (9.2)

14/204 (6.9)
18/202 (8.9)

1.06 (0.522.13)
1.03 (0.561.90)

0.879
0.925

31/200 (15.5)
38/200 (19.0)

20/199 (10.1)
28/199 (14.1)

1.54 (0.912.61)
1.35 (0.862.11)

0.103
0.185

Total randomized: N 216; N 211.

Results include all children, treated for unilateral disease and for bilateral disease. Only the
study ear has been considered for children with unilateral disease in all analyses. Two
approaches for handling children treated for bilateral disease: counted as success where (1)
both ears healed, or (2) either or both ears healed.

Healing of the tympanic membrane at 2 and 4 weeks

showed no statistically significant difference between the
treatments (Table 3), although the estimated relative risk
suggests an effect in favour of ciprofloxacin at week 4.
Sensitivity analyses did not significantly affect the results.
Audiometry (controlling for baseline threshold with
ancova) showed a trend to improved hearing for
ciprofloxacin at 2 weeks and a significant effect at 4 weeks
(Table 4). The conclusions did not change when
controlling for background noise as an additional
covariate. Tables 5 and 6 show the WHO classifications
for the level and change in level of hearing impairment
by treatment group.
For adverse events of ear pain, irritation, and bleeding
on mopping, there was a significantly higher frequency in
the boric acid group (30/206, 14.6%) than in the ciprofloxacin group (17/210, 8.1%), giving a difference (95% CI)
of 6.5% (0.312.7%) (Pearsons chi-squared P-value
0.037).

Table 4 Audiometry average change in hearing from baseline at

2 and 4 weeks (dB averaged over 500, 1000, 2000 and 4000 Hz)

2 weeks:
Cipro
Boric
4 weeks
Cipro
Boric

dB mean
improvement
(SD)

Difference
(95% CI*)
(CiproBoric)

P-value*

201
202

4.32 (11.18)
2.69 (11.67)

2.17 (0.094.24)

0.0410

196
194

5.42 (11.03)
2.63 (12.18)

3.43 (1.345.52)

0.0014

* Results from ancova controlling for baseline audio level.

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Discussion
This study is the largest trial to date comparing an
antiseptic with a quinolone antibiotic. Our results show
better resolution and hearing threshold with a quinolone
antibiotic over antiseptic. Since the Cochrane Review,
which found no trials of quinolones, there have been four
additional trials with mixed results: a study in Malawi
suggested ofloxacin was better than 2% acetic acid in 25%
spirit and 30% glycerine (for dry ears at 2 weeks, RR 6.13;
95% CI, 2.5914.53; n 53 ears) (van Hasselt 1997),
while another Malawi study (van Hasselt 1998, cited in
van Hasselt & van Kregten 2002), found a single dose of
ofloxacin 0.075% in hydroxypropyl methyl-cellulose 1.5%
(HPMC) was better than one dose of povidone iodine 1%
in HPMC 1.5% (for dry ears after 1 week, RR 3.87, 95%
CI 2.316.47, n 170). However, two trials did not find a
significant effect in favour of topical quinolone antibiotics,
but numbers were small: a trial in Israel (Fradis et al. 1997)
compared ciprofloxacin hydrochloride eardrops with a
weak concentration of 1% Burow aluminium acetate
solution (results for dry ear 24 h after the end of 3 weeks
treatment, RR 2.01; 95% CI 0.765.36, n 36), while a
study in India (Jaya et al. 2003) compared 0.3% ciprofloxacin and 5% povidone iodine (results for participants
with inactive ears at 2 weeks, RR 1.02; 95% CI, 0.82
1.26; n 39 participants).
We took resolution of discharge as our primary outcome, as this indicates clearing of the current infection, and
minimizes the risk of progression of the disease. Ciprofloxacin also had an impact on hearing, which underlines the
long-term purpose of treating this infection appropriately,
as deafness caused by CSOM may contribute to delayed
learning and behavioural disturbance (Klein 2001).
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C. Macfadyen et al. Topical quinolone vs. antiseptic for chronic suppurative otitis media

Table 5 Levels of hearing impairment at each visit (dB averaged over 500, 1000, 2000 and 4000 Hz)
Level of hearing
impairment [n (%)]*
25 dB or better (no impairment)
2640 dB (mild)
4160 dB (moderate)
6180 dB (severe)
81 dB or worse (profound)
Chi-square (d.f.), P-value

Baseline

Week 2

Week 4

Boric

Cipro

Boric

14
91
88
14
2

17
95
82
16
2

24 (11.8)
38
97 (47.6)
98
65 (31.8)
62
16 (7.8)
4
2 (1.0)
2
10.437 (4), 0.034

(6.7)
(43.5)
(42.1)
(6.7)
(1.0)

(8.0)
(44.8)
(38.7)
(7.6)
(0.9)

Cipro
(18.6)
(48.0)
(30.4)
(2.0)
(1.0)

Boric

Cipro

30 (15.3)
39
81 (41.3)
102
70 (35.7)
52
11 (5.6)
4
4 (2.0)
1
11.296 (4), 0.023

(19.7)
(51.5)
(26.3)
(2.0)
(0.5)

* Level is according to WHO classification of grades of hearing impairment.

Difference in WHO grade of

hearing impairment [n (%)]*
Worse (two-step increment)
Worse (one-step increment)
No change
Improved (one-step decrement)
Improved (two-step decrement)
Improved (three-step decrement)
Chi-square (d.f.), Fishers exact
P-value

Week 2
Boric

Week 4
Cipro

3 (1.5)
1
26 (12.9)
28
116 (57.4)
98
53 (26.2)
62
4 (2.0)
11
0
1
7.557 (5), 0.161

(0.5)
(13.9)
(48.8)
(30.9)
(5.5)
(0.5)

Boric

Cipro

4 (2.1)
0
25 (12.9)
16
109 (56.2)
108
49 (25.3)
59
7 (3.6)
11
0
2
9.785 (5), 0.078

Table 6 Change in level of hearing

impairment from baseline (dB averaged
over 500, 1000, 2000 and 4000 Hz)

(8.2)
(55.1)
(30.1)
(5.6)
(1.0)

* An improvement in the level of hearing impairment means there was a decrease in the
average hearing threshold. WHO grades are as presented in Table 5.

Hearing in the diseased ear is usually significantly impaired

compared with the uninfected ear, and children with
unilateral disease, as for bilateral impairment, are likely to
have significant educational and social problems (Ballantyne & Martin 1984; Brookhouser et al. 1991). Longerterm follow-up would be needed to assess the impact of
treatment on hearing in the long-term and on behaviour
and learning.
Smith et al. (1996) found that healing of the tympanic
membrane was an important factor for improving hearing.
While we found few cases of complete healing with either
treatment, there was a trend towards a small benefit of
ciprofloxacin by week 4; the wide confidence intervals imply
a potentially clinically important benefit cannot be ruled out
for tympanic membrane healing with ciprofloxacin.
We followed up students for just 4 weeks, because of
logistic and financial constraints. However, longer followup would be needed to assess whether the differences found
here (for resolution, healing and hearing) remain over time.
The higher number of children reporting adverse events
related to ear pain, irritation, and bleeding on mopping
with boric acid in alcohol is probably because the alcohol
may sting. This finding is in line with other studies to date,
which have supported a good safety profile for quinolone
eardrops (Brownlee et al. 1992; Morpeth et al. 2001; Jaya
196

et al. 2003; Acuin et al. 2004; Acuin 2004). No formal

analyses were performed on any other safety findings in our
trial, which was not designed or powered to assess more
specific safety questions, as numbers were small and
specific adverse event information may not have been
systematically detected because of the open-ended nature
of the questioning.
Although ciprofloxacin remains more expensive than
antiseptics and other non-quinolone antibiotics (approximately 12 times the price of boric acid in Kenya), the
difference varies between countries. It is likely that the cost
of quinolone eardrops will fall with time, particularly if
generic preparations are available. In addition to direct
purchase costs, other treatment-related costs and practicalities for treatment preparation, transport and storage
must also be considered when comparing treatments.
Conclusions
In children with chronic suppurative otitis media, we have
found topical ciprofloxacin ear drops to be more effective
than boric acid at 2 and 4 weeks, for both resolution of
discharge and improvement in hearing. We also found
significantly fewer adverse events of ear pain, irritation, and
bleeding on mopping, with ciprofloxacin than boric acid.

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C. Macfadyen et al. Topical quinolone vs. antiseptic for chronic suppurative otitis media

Acknowledgements
We thank Dr AW Smith, World Health Organization, for
his advice; Dr David Odeny, consultant ENT surgeon, for
his help in Kisumu; and Zedekia Owira, Inspector for
Schools. The study was funded by a Project Grant from
The Wellcome Trust (UK Registered Charity Number
210183; Grant reference number: 056756/Z/99/Z). Alcon
(Denmark and Belgium) provided the Ciloxan supplies.
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Authors
Carolyn Macfadyen (corresponding author), Paul Garner, Ian Mackenzie, Kennedy Otwombe, International Health Research Group,
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. Fax: +44 (0) 151 705 3364; Tel: +44 (0) 151 708
9393, E-mail: cmacfadyenuk@yahoo.co.uk, pgarner@liverpool.ac.uk, macken34@liverpool.ac.uk, notwombe@yahoo.com
Carrol Gamble, Stephen Taylor, Paula Williamson, Centre for Medical Statistics and Health Evaluation, School of Health Sciences,
Shelleys Cottage, Brownlow Street, University of Liverpool, Liverpool L69 3GS. Tel.: 44 (0) 151 794 5121; Fax: +44 (0) 151 794 5130;
E-mail: c.gamble@liverpool.ac.uk, s.taylor01@liverpool.ac.uk, p.r.williamson@liverpool.ac.uk
Isaac Macharia, Peter Mugwe, Herbert Oburra, Section of Ear, Nose and Throat Diseases, Department of Surgery, University of
Nairobi, Kenyatta National Hospital, Nairobi, Kenya. E-mail: machariaim@wananchi.com, mugwe@wananchi.com, kansel@
insightkenya.com

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