Clinical comparison of 0.6%
besifloxacin ophthalmic suspension and 1.5% azithromycin ophthalmic
suspension in acute bacterial conjunctivitis
Meena
R1, Gupta ML2
1Dr. Ravindra Kumar Meena, Assistant Professor, Jhalawar Medical
college, Jhalawar, Rajasthan, India, 2Dr. M. L. Gupta, Associate
Professor, Department of Ophthalmology, Jhalawar Medical college,
Jhalawar, Rajasthan, India.
Address for correspondence: Dr. Ravindra Kumar Meena, Email:
drravindrameena@gmail.com
Abstract
Introduction:
Acute bacterial conjunctivitis is one of the most common ocular
infection seen in day to day clinical practice. Our purpose to conduct
this study was to compare the outcome and efficacy of 0.6% besifloxacin
ophthalmic suspension and 1.5% azithromycin ophthalmic suspension in
acute bacterial conjunctivitis. Method: This is a Prospective,
randomized, parallel-group, clinical study of acute bacterial
conjunctivitis Conducted From July 2015 to Sept 2015 on 200 patients in
the department of Ophthalmology at Jhalawar Medical College,
Jhalawar.(raj.) All selected patients were divided into two groups of
100 each. Group A was treated by besifloxacin 0.6% ophthalmic
suspension,where as group B was treated by 1.5% azithromycin ophthalmic
suspension three times a day for 7 day. Observation was done on 3, 7
day regarding clinical resolution and side effect of these drugs in
both groups. Result: Clinical resolution, complication , and side
effects of these two drugs were analysed on day 3 and day 7 and found
that 0.6% besifloxacin is significantly better than 1.5% azithromycin
eye drop on day 3 and day 7 (p value<0.5) and also have less
side effect (p value<0.5).Conclusion: 0.6% besifloxacin is safe
and efficacious in acute bacterial conjunctivitis in all age group.
Key words: Azithromycin,
Besifloxacin, Conjunctivitis, Clinical Resolution
Manuscript received: 30th
Oct 2015, Reviewed:
8th Nov 2015
Author Corrected:
20th Nov 2015, Accepted
for Publication: 2nd Dec 2015
Introduction
Acute Conjunctivitis is one of the most common eye infection in which
the eyes become red and inflamed Bacterial infection accounts for up to
50% of all conjunctivitis cases in adults and as many as
70–80% of cases in children. Bacterial conjunctivitis is
characterised by mucopurulent discharge and conjunctival hyperaemia.
Acute bacterial conjunctivitis is an infective condition that is not
normally serious [1, 2].
In the developed world, the syndrome of acute ‘red
eye’ accounts between 1% and 4% of consultations with primary
care physicians and in the majority of cases an acute bacterial
conjunctivitis is diagnosed [3].
Bacterial conjunctivitis can often be distinguished from viral
conjunctivitis by signs such as mucopurulent discharge, chemosis,
conjunctival congestion and crusting with mucopurulence being a key
distinguishing factor. The most common causative microbes in adults
include gram-positive: Staphylococcus aureus, Staphylococcus
epidermidis and Streptococcus pneumonia and the gram-negative pathogen
Haemophilus influenza. S. aureus is the most common in adults, while
children are most prone to infection by H. Influenza [4].
Mild cases are generally considered to be self‐limiting, resolving in 5
to 10 days. However, current consensus supports the use of topical
antibiotics as they (1) provide symptomatic relief, (2) hasten
microbial remission (3) shorten disease duration, (4) reduce risk of
developing sight‐threatening complications, (5) reduce rate of
re‐infection, (6) prevent infection spread. Recent meta‐analysis and a
clinical trial showed that antibiotics provide significantly better
rates of early clinical remission, and both early and late
microbiological remission than placebo [5].
As treatment of bacterial conjunctivitis is often empirical and
initiated before speciation of the ocular pathogen (that is,
bacteriological culture), it is important to prescribe an antibiotic
with a broad spectrum of antimicrobial activity. In this regard,
topical fluoroquinolones have gained increasing use for the treatment of
acute bacterial conjunctivitis. The fluoroquinolone family of
antibiotics exhibits bactericidal activity by inhibiting two essential
bacterial topoisomerase enzymes, DNA gyrase (topoisomerase II) and
topoisomerase IV [6].
Once antibiotics are clinically indicated, the standard of care for
bacterial conjunctivitis is broad-spectrum topical ophthalmic
antibiotic eye drops. Various classes of antibiotics have been used
including aminoglycosides, polymyxin B combinations, macrolides,
sulfonamides and fluoroquinolones. Aminoglycosides (tobramycin and
gentamycin) require frequent dosing (1–2 drops every four to
six hours for ten days), which can lead to poor patient compliance. In
addition, despite their frequent use, aminoglycosides demonstrate poor
antimicrobial activity against Streptococci, which limits their use as
a broad-spectrum treatment for conjunctivitis. Azithromycin is also
less preferred due to its unequal gram-negative and positive coverage.
Erythromycin is no longer recommended because its activity against
S.aureus has diminished. Fluoroquinolones are still considered by many
to be the antibiotics of choice for ocular infections on account of
their broad-spectrum potency and low toxicity.
Besifloxacin ophthalmic suspension 0.6% is fourth generation topical
fluoroquinolone recently approved for treatment of bacterial
conjunctivitis in adults and children older than 1 year. Besifloxacin
is the only fluoroquinolone specifically designed for ocular use.
Unlike older antibiotics of this class, besifloxacin is not used for
systemic infections. Restriction to topical use only, renders
besifloxacin unique in its class and theoretically reduces the risk for
the development of resistance due to decreased systemic exposure
[4,7,8].
Besifloxacin binds to DNA gyrase and topoisomerase IV, two enzymes that
are critical for DNA replication in bacteria. Unlike previous
generation in this class besifloxacin has a relative affinity for
inhibiting the above enzymes [9]
Material
and Methods
Design and Patients: This is a Prospective, randomized, parallel-group,
clinical study of Acute bacterial conjunctivitis conducted From July
2015 to September 2015 on 200 patients in the department of
ophthalmology at Jhalawar medical college, Jhalawar, Rajasthan
All selected patients were divided into two groups of 100 each.
1. Group A
0.6% besifloxacin ophthalmic suspension
group .
2. Group B
1.5% azithromycin ophthalmic suspension group.
Inclusion Criteria:
All patients of acute bacterial conjunctivitis as defined by mild to
severe bulbar/fornices conjunctival congestion, discharge and
stickiness in at least one eye for last 1 to 2 days.
Exclusion Criteria:
Patients were excluded
1. If they were associated with other ocular pathologies like chronic
dacryocystitis, trichiasis, entropion
2. Patients having previous infection, and already on drug.
3. Patients having diabetes mellitus, using systemic
corticosteroids.
4. Those had dry eye problem and who gave history of previous
ocular surgery, laser treatment or trauma.
5. Systemic or ocular antibiotics, anti-inflammatory or
immunosuppressive treatments were not authorised for use during the
study.
The study was conducted in accordance with Good Clinical Practice.
Written informed consent was obtained from all patients.
A detailed follow up was carried out at the Day1 , Day3 and Day7 with
regards to the :- Congestion, discharge, clinical resolution,
complication
Study design and method: All
the patients of acute bacterial conjunctivitis were allocated randomly
in 1:1 ratio to one of the study group. We divided the work between two
ophthalmologist, one of us had to performed the ophthalmologic
examination, while a second was responsible for dispensing medications
and assessing outcome,tolerance and safety.
Clinical feature
assessments: The cardinal clinical signs of acute
bacterial conjunctivitis (bulbar/fornices congestion and discharge)
were assess for each eye by slit lamp and graded by a four point
ordinal scale (0=absent; 1=mild; 2=moderate; 3=severe;)
Microbiological
observation: A conjunctival swab was taken from
each infected eye on day1 and day7. Bacterial specimens were analysed
by giemsa staining in the department of ophthalmology, Jhalawar medical
college.
Treatment pattern:
After taken conjunctival swab all patients received antibiotic eyedrop
either 1.5% azithromycin ophthalmic suspension or 0.6% besifloxacin
ophthalmic suspension three times a day for 7 days.
All patients were advised to come on day 3 and day 7 for further follow
up and look for congestion,discharge,clinical resolution and
complication.
Safety and tolerance
analysis: It was based on the observation of side effect
related to study medication instillation like burning, stinging,
itching, foreign body sensation and blurred vision.tolerance was
assessed by asking the patients.
Results
In our study we enrolled 200 patients of acute bacterial
conjunctivitis, out of which 100 patients were treated with 0.6%
besifloxacin ophthalmic suspension(Group A) and 100 were with 1.5%
azithromycin ophthalmic suspension(Group B).
Table No. 1: Distribution
of cases according to age and gender
|
Age
in group(yrs.)
|
Besifloxacin
(100)
|
Total p value
|
Azithromycin
group
|
Total
|
p
value
|
|
M F
|
|
M
F
|
|
1-15
|
5
3
|
08 >0.05 NS
|
08
02
|
10
|
>0.05 NS
|
|
16-30
|
32 11
|
43 <0.05 SIG
|
35
04
|
39
|
<0.05 SIG
|
|
31-50
|
34 07
|
41 <0.05 SIG
|
28
13
|
41
|
<0.05 SIG
|
|
51+
|
06 02
|
08 > 0.05 NS
|
07
03
|
10
|
>0.05 NS
|
|
Total
|
77
23
|
100 <0.05 SIG
|
78
22
|
100
|
<0.05 SIG
|
Mean age of besifloxacin group =30.16 ±12.33 years
Mean age of azithromycin group=30.93 ± 13.16 years
The difference between the mean ages of both group was not significant.
In both groups p value was significant in 16-30, 31-50,and 51+
Table No. 2:
Distribution of cases according to bulbar/fornices congestion
|
|
Besifloxacin(100)
|
Azithromycin(100)
|
|
Absent
|
05(5%)
|
05(5%)
|
|
Mild
|
25(25%)
|
22(22%)
|
|
Moderate
|
52(52%)
|
58(58%)
|
|
Severe
|
18(18%)
|
15(15%)
|
|
Total
|
100
|
100
|
Group B patients had more fornices congestion.
Table No. 3: Distribution
of cases according to purulent discharge
|
|
Besifloxacin(100)
|
Azithromycin(100)
|
|
Absent
|
00
|
00
|
|
Mild
|
15(15%)
|
12(12%)
|
|
Moderate
|
55(55%)
|
58(58%)
|
|
Severe
|
30(30%)
|
30(30%)
|
|
Total
|
100
|
100
|
In this also Group B patients had more purulent discharge.
Table No. 4: Distribution
of cases according to clinical resolution
|
Day
|
Besifloxacin(100)
|
Azithromycin(100)
|
P
value
|
Z
score
|
Significance
|
|
3
|
65(65%)
|
48(48%)
|
.022
|
2.282
|
Significant
|
|
7
|
95(95%)
|
84(84%)
|
.021
|
2.307
|
Significant
|
Most of the patients in Group A cured on day 3 and day 7.
Table No. 5: Distribution
of cases according to complication
|
Complication
|
Besifloxacin(100)
|
Azithromycin(100)
|
P
value
|
Z
score
|
significance
|
|
Keratitis
|
05(5%)
|
10(10%)
|
.283
|
1.074
|
NS
|
|
Corneal opacity
|
03(3%)
|
04(04%)
|
.182
|
1.334
|
NS
|
Table No. 6: Distribution
of cases according to side effects of medication
|
|
Besifloxacin(100)
|
Azithromycin(100)
|
P
value
|
Z
score
|
Significance
|
|
Burning
|
35
|
50
|
0.045
|
2.003
|
Sig.
|
|
Itching
|
40
|
45
|
0.567
|
0.572
|
NS
|
|
Stickness
|
25
|
35
|
0.165
|
1.389
|
NS
|
|
Fb sensation
|
40
|
55
|
.047
|
1.982
|
Sig.
|
|
Blurred vision
|
05
|
10
|
.283
|
1.074
|
NS
|
Most of the patients had side effect of burning and foreign body
sensation.
Discussion
In our study both groups had more male patients than female
particularly in 16- 50 years age group because in our area males were
more prone to do outdoor work which was supported by Eping et al,
Abrahamian et al, Feingold et al, Buck et al [10-13]. Although the
literature on the epidemiology of bacterial conjunctivitis contains
several references to its highly contagious nature [10-13] no overall
population-based data exists on the incidence of bacterial
conjunctivitis. In the United States it is estimated that 23% of
bacterial conjunctivitis cases occur in the 0-2 year age range, 28%
occur in the 3-9 year range, 13% occur in the 10-19 year range with the
remaining 36% of cases occurring in adults. [14]
Mean age of besifloxacin group.was 30.16±12.33, Mean age of
azithromycin group was 30.93±13.16 which was also not
significant.
73% Patients (Table no.2) showed moderate to severe bulbar congestion
in azithromycin group,70% patients shows moderate to severe bulbar
congestion in besifloxacin group which did not had any significant
value .
85% patients in besifloxacin group and 88% patients in azithromycin
group ( Table no. 3) showed moderate to severe purulent discharge. The
severity of both these cardinal sign was not significantly different
between these two group which was supported by Bremond gignac et al. [1]
In clinical resolution rate besifloxacin group had significantly high
value in comparison to azithromycin group (p value 0.022)(p value
0.021) on day 3 and day 7 respectively which was supported by, Tepedino
et al [15] , Karpecki et al[16].
A 2009 multicenter, randomized Phase III study involving 390 patients
demonstrated superior clinical resolution and bacterial eradication
with besifloxacin. All patients had culture-confirmed bacterial
conjunctivitis. Patients receiving besifloxacin demonstrated
significantly more clinical resolution than patients receiving the
vehicle at day 5 (45.2% vs. 33.0%, p = 0.008) and day 8 (84.4% vs.
69.1%, p = 0.0011). In addition, besifloxacin-treated patients had
significantly higher rates of microbial eradication at day 5 (91.5% vs.
59.7%, p=0.0001) and 8 (88.4% vs. 71.7%, p = ,0.0001) supported by,
Tepedino et al, Karpecki et al[15,16].
Complication like keratitis and corneal opacity both remained non
significant in both group(p value>0.05) (Table No.5).
Table No. 6 shows the side effects of both eye drops in which burning
sensation and foreign body sensation was significantly higher in
azithromycin group than besifloxacin group supported by Comstock T Let
al[17] which showed that Systemic exposure of besifloxacin was
negligible and the most common adverse events in patients receiving
topical besifloxacin were local and included blurred vision (2.1%), eye
pain (1.8%), eye irritation (1.4%), nonspecific conjunctivitis (1.2%)
and eye pruritis (1.1%). Besifloxacin topical administration did not
affect visual acuity [18].
Results from this prospective, randomized, parallel-group, clinical
study of acute bacterial conjunctivitis which included 200 subjects
provides evidence of the safety of besifloxacin given three times daily
for 7 days in the treatment of bacterial
conjunctivitis.
Conclusion
In summary, 0.6% besifloxacin ophthalmic suspension is an effective and
safe therapeutic option for acute bacterial conjunctivitis in
comparison to 1.5% azithromycin ophthalmic suspension. 0.6%
Besifloxacin provided a superior clinical cure rate on day 3 compared
with 1.5% azithromycin ophthalmic suspension in all age group in acute
bacterial conjunctivitis.
Funding:
Nil, Conflict of
interest: None initiated.
Permission
from IRB:
Yes
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How to cite this article?
Meena R, Gupta ML. Clinical comparison of 0.6% besifloxacin ophthalmic
suspension and 1.5% azithromycin ophthalmic suspension in acute
bacterial conjunctivitis. Int J Med Res Rev 2015;3(11):1288-1293. doi:
10.17511/ijmrr.2015.i11.234.