|Year : 2020 | Volume
| Issue : 4 | Page : 1237-1245
A comparative randomized study to evaluate the effect of azithromycin 1.5% eyedrops versus moxifloxacin 0.5% eyedrops on bacterial conjunctivitis
Hesham M. F El Maraz1, Sameh S Mandour1, Soha S. F Abd-El Maksoud2
1 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Ophthalmology, Ministry of Health, Zagazig, Egypt
|Date of Submission||29-Jun-2020|
|Date of Decision||20-Aug-2020|
|Date of Acceptance||30-Aug-2020|
|Date of Web Publication||24-Dec-2020|
Soha S. F Abd-El Maksoud
BSC, Department of Ophthalmology, Ministry of Health, Zagazig, Sharqia
Source of Support: None, Conflict of Interest: None
To evaluate the effect of azithromycin 1.5% eyedrops versus moxifloxacin 0.5% eyedrops on bacterial conjunctivitis.
Purulent bacterial conjunctivitis affects all ages, with high frequency in newborns and children. This study evaluates the effect of azithromycin 1.5% eyedrops with moxifloxacin 0.5% eyedrops in treatment of bacterial conjunctivitis.
Patients and methods
A prospective comparative randomized controlled clinical trial was conducted that included 100 participants with purulent bacterial conjunctivitis at Menoufia outpatient clinic. Patients received either azithromycin 1.5% eyedrops twice daily for 7 days or moxifloxacin 0.5% eyedrops three times per day for 7 days. The primary variable was clinical cure at days 3 and 7 on the worst eye. The cure was defined as absence of purulent discharge and bulbar conjunctivitis.
Overall, 88% of patients in the azithromycin group and 90% in the moxifloxacin group were clinically cured at D7. Clinical cure with azithromycin was not inferior to moxifloxacin at day 7, and discharge was absent in 92% of patients treated with azithromycin and 94% with moxifloxacin. Azithromycin and moxifloxacin were well tolerated.
Azithromycin 1.5% for 7 days was as effective as moxifloxacin for 7 days. Furthermore, patients on azithromycin presented clinical cure on day 3 as patients on moxifloxacin.
Keywords: azithromycin, bacterial conjunctivitis, moxifloxacin, purulent and mucopurulent discharge, red eye
|How to cite this article:|
El Maraz HM, Mandour SS, Abd-El Maksoud SS. A comparative randomized study to evaluate the effect of azithromycin 1.5% eyedrops versus moxifloxacin 0.5% eyedrops on bacterial conjunctivitis. Menoufia Med J 2020;33:1237-45
|How to cite this URL:|
El Maraz HM, Mandour SS, Abd-El Maksoud SS. A comparative randomized study to evaluate the effect of azithromycin 1.5% eyedrops versus moxifloxacin 0.5% eyedrops on bacterial conjunctivitis. Menoufia Med J [serial online] 2020 [cited 2021 Apr 19];33:1237-45. Available from: http://www.mmj.eg.net/text.asp?2020/33/4/1237/304492
| Introduction|| |
Bacterial infection accounts for up to 50% of all conjunctivitis cases in adults and as many as 70–80% of cases in children. Conjunctivitis is one of the most common eye infections in childhood and a common cause of pediatric primary care visits and ocular complaints in pediatric emergency departments. Bacterial conjunctivitis is characterized by mucopurulent discharge and conjunctival hyperemia. It is an extremely contagious disease caused by one or more bacterial species and affects both sexes and all ages and countries. It can also cause epidemics among people in close quarters, including nursery, school, and student populations. Mild cases are generally considered to be self-limiting, resolving in 5–10 days. However, the current consensus supports the use of topical antibiotics, as they provide significantly better rates of early clinical cure and microbiological resolution compared with artificial tears. Topical antibiotics are also known to reduce the rate of reinfection and prevent the spread of infection.
As most topical antibiotics are prescribed empirically without diagnostic bacteriological profiling, these findings emphasize the importance of an etiological approach to determine the best possible initial treatment for eradication of the causative microbes.
Moxifloxacin 0.5% ophthalmic solution is a fourth-generation fluoroquinolone currently indicated for 13 isolates of bacterial conjunctivitis. It is a broad-spectrum, concentration-dependent, bactericidal antibiotic. Conversely, azithromycin is derived from the parent class of macrolides known to be bacteriostatic and time dependent. Although it is suggested that concentration is a factor in the antibacterial effect of azithromycin, given the current high level of gram-positive resistance patterns, this agent demonstrates a time-dependent, bacteriostatic effect. Azithromycin 1% is currently indicated for five bacterial isolates. The aim of this study was to evaluate the effect of azithromycin 1.5% eyedrops versus moxifloxacin 0.5% eyedrops on bacterial conjunctivitis.
| Patients and methods|| |
This is a prospective comparative randomized controlled clinical trial conducted in Ophthalmology Outpatient Clinic at Menoufia University between September 2019 and March 2020 in accordance with Good Clinical Practices, the International Conference on Harmonization guidelines, the Declaration of Helsinki, and the Health Insurance Portability and Accountability Act guidelines. All patients, or their legal guardians, provided informed consent, and the study was approved by the local ethical committee (820/7/3/2019). Patients were eligible for participation if they were at least 6 year of age, in good health, and had a clinical diagnosis of bacterial conjunctivitis, as evidenced by mucopurulent or purulent conjunctival discharge, bulbar conjunctival injection in at least one eye, crusty or sticky eyelids, and/or ocular surface redness. Patients had to be willing to discontinue contact lens use during the study and to avoid disallowed medications (systemic or topical antimicrobial medications, and any medication that the investigator believed could interfere with the study parameters). Females of child-bearing potential had to use a reliable means of contraception and had negative pregnancy test results at baseline. Patients were excluded if they were using contact lens, systemic or ocular antibiotics, anti-inflammatory or immune-suppressive treatments, and if bacterial conjunctivitis was diagnosed more than 7 days earlier, as well as if association was noted with trauma or foreign body, dacryocystitis, keratitis, viral ocular infection, significant ocular abnormality, and amblyopia. Randomization was performed using a sealed envelope system, where 100 shuffled envelopes designating the treatment to either azithromycin ophthalmic solution Cyanaro (Rameda Pharmaceutical Company, Cairo, Egypt) or moxifloxacin ophthalmic solution (Vigamox; Alcon Laboratories Inc., Fort Worth, Texas, USA) were opened by every patient before starting the study. On day 0, eligible patients were randomly allocated (1:1 ratio) to one of the two investigator-masked study treatments. Patients were divided into two groups, with 50 patients in each group (one group received azithromycin 1.5% eyedrops twice daily, morning and evening) for 7 days, and the other group received moxifloxacin 0.5% eyedrops three times per day for 7 days. All patients attended three visits (days 0, 3, and 7). A 'first ophthalmologist investigator' who was masked to the treatment performed the ophthalmologic examination, whereas a second investigator was responsible for dispensing medications and assessing tolerance and safety.
- Specimen collection was performed by the ophthalmologist investigator. A bacteriologic specimen was taken from each infected eye using an alginate swab passed along the cul-de-sac to the temporal margin and back to the nasal margin at least three times rotating the swab at 180°. The swab was introduced into the tube containing 2.4 ml of alginate-dissolution transport medium with Calgon. Then, after vortexing, 0.5 ml of this transport medium was plated on Columbia-agar medium (with 5% sheep blood) and 0.5 ml was plated on chocolate-agar medium. Delay between sampling and plating had to be as short as possible. A conjunctival swabbing was taken from each infected eye on at time of examination (day 0). Sample was cultured within 2 h and cultured on blood agar and MacConkey at laboratory of El Menoufia University. The microbes isolated from patients were reported. The bacteriological status was confirmed by an independent central review using the modified Cagle's classification. A bacteriological sample was considered positive if bacteria isolated after culture were above the pathogenic thresholds following Cagle's microbiological criteria. Cardinal clinical signs of bacterial conjunctivitis (bulbar injection and purulent discharge) were assessed for each eye under slit lamp and scored using a four-point ordinal scale (0 = absent; 1 = mild; 2 = moderate; and 3 = severe). Clinical signs were evaluated on days 0, 3, and 7. Second swab was taken at day 7, and microbiological resolution (i.e., absence of bacteria or their reduction below the pathogenic threshold) was assessed on day 7. The primary variable was the clinical cure (as defined by the absence of purulent discharge and bulbar conjunctivitis on days 3 and 7 in group receiving azithromycin eyedrops and on days 3 and 7 in group receiving moxifloxacin eyedrops). The secondary variables included clinical cure and negative culture on day 7, as well as other ocular signs (folliculo-papillary reaction of palpebral conjunctiva, eyelid erythema, eyelid swelling). Regarding safety assessment analysis, it was based on the evaluation of adverse events (AEs), symptoms related to study medication instillation that is, burning/stinging/itching, stickiness, foreign body sensation and blurred vision, ocular signs at slit lamp examination, visual acuity, and treatment tolerability by the investigator and patient or parent/guardian. If an exacerbated reaction was noted by the parent/guardian upon instillation of the study medication to his/her child, the symptoms of itching/burning/stinging, stickiness, foreign body sensation, and blurred vision were recorded. Visual acuity was done by the random E test, in which patient identified the direction the letter 'E' is facing. Looking at the letter on a chart or projection, patient pointed in the direction the letter is facing: up, down, left, or right
- Slit lamp examination was done as follows:
- Lid to assess discharge in lower fornix
- Sclera to exclude scleritis and episcleritis.
- Iris to exclude uveitis
- Cornea to exclude corneal ulcer by fluorescein stain
- Lacrimal gland to exclude lacrimal gland obstruction by negative regurge test
- Pupil (rapid, reactive, and round)
- Anterior chamber to exclude flare and hypopyon.
- Intraocular pressure was assessed to exclude glaucoma
- Fundus examination was done to exclude glaucoma.
Data were analyzed using the Statistical Package for Social Sciences (SPSS), version 20 (IBM, Armonk, New York, USA). Data showing normal distribution were presented as the means and SD. The nonparametric values were tested using the Mann–Whitney U test. Qualitative data are represented by frequency and relative percentage, and χ2 test was used for testing the association of the qualitative data. In all analyses, P value less than 0.05 were considered statistically significant.
| Results|| |
There were no statistical significance differences between the studied groups in age or sex distribution [Table 1].
There was no statistical significance difference between groups I and II in disease duration or side. Moreover, there was no statistically significant difference between groups I and II in frequency of itching or foreign body sensation [Table 2].
There was no statistically significance difference between groups I and II in severity of mucopurulent discharge or bulbar injection in any of the follow-up days. However, there was a highly statistically significance difference in severity of both mucopurulent discharge and bulbar injection in different days in each group [Table 3].
|Table 3: Follow-up of symptoms among the studied groups at days 0, 3, and 7 of infection|
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There was no statistically significant difference between groups I and II in culture results in days 0 or 7. Moreover, there was no statistically significant difference between the two groups in frequency of improvement in day 3 or 7. However, there was a highly statistically significant difference in culture results when comparing day 0 with day 7 in both groups, and there was a highly statistically significant difference in frequency of improvement when comparing day 3 with day 7 in both groups [Table 4].
|Table 4: Culture results and improvement among the studied groups at different days of follow-up|
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There was no statistically significant difference between groups I and II in frequency of different ocular and nonocular adverse effects [Table 5].
[Table 6] shows there were no statistically significant relation between culture results and different variables in day 0, but in day 7, there were statistically significant increases in mean age, frequency of age group more than 50 years, bilateral, presence of mucopurulent discharge, bulbar injection, and ocular adverse effect among nonimproved cases.
|Table 6: Relation between culture results and different variables among group I patients|
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[Table 7] shows there were statistically significant increases in frequency of severe mucopurulent discharge among gram-positive cases compared with negative ones on day 0. On day 7, there were statistically significant increases in frequency of presence of mucopurulent discharge, bulbar injection, worsening of bacterial conjunctivitis, and fever among nonimproved cases [Figure 1],[Figure 2],[Figure 3].
|Table 7: Relation between culture and different variables among group II patients|
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|Figure 1: Culture results among the studied groups at different days of follow-up.|
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| Discussion|| |
Purulent bacterial conjunctivitis, characterized by mucopurulent discharge and hyperemia, affects both sexes and all ages, ethnicities, and countries. It represents one of the most common ocular diseases. It may cause epidemics among people in close quarters, such as in nursery, school, and student populations.
Topical fluoroquinolones are a pharmacological group that has shown an increase in the number of molecules since 1990. Their broad-spectrum allows them to be considered the first-line therapy for bacterial conjunctivitis. Moxifloxacin is the most potent fluoroquinolones evaluated in ophthalmic presentation. They are active in killing gram-positive and some gram-negative bacteria.
Azithromycin is a second-generation macrolide that has rapid tissue distribution, sustained high tissue levels and rapid uptake and transport by phagocytic cells. This drug has a wide in vitro antimicrobial spectrum against gram-positive and gram-negative bacteria.
In the present study, there was no statistically significant difference between groups I and II in severity of mucopurulent discharge in any of the follow-up days. However, there was a highly statistically significant difference in severity of mucopurulent discharge in different days in each group. Moreover, in the present study, mucopurulent discharge was the most common symptom. This came in agreement with Bremond-Gignac et al. and Tarabishy and Jeng, who found that typical symptoms of bacterial conjunctivitis are a red eye and purulent discharge.
In the current study, there was no statistically significant difference between both groups in severity of bulbar injection in any of the follow-up days. However, there was a highly statistically significant difference in severity of bulbar injection in different days in each group.
Moreover, in the present study, there was no statistically significant difference between both groups in culture results on day 0 or day 7. Moreover, there was no statistically significant difference between the two groups in frequency of improvement on day 3 or 7. However, there was a highly statistically significant difference in culture results when comparing day 0 with day 7 in each group, and there was a highly statistically significant difference in frequency of improvement when comparing day 3 with day 7 in each group.
In the current study, the most common organisms isolated from bacterial conjunctivitis patients were Haemophilus influenzae (23%), followed by Staphylococcus aureus and Streptococcus pneumoniae (19%).
In agreement with our study, Stroman et al. found that 75% of H. influenzae, 18% of S. pneumoniae, and 30% of S. aureus were isolated from patients with conjunctivitis.
Gupta found that the most frequent causative microbes isolated from patients at inclusion were Hemophilus (31.5%), S. aureus (17.7%), S. pneumoniae (14.8%), and coagulase-negative staphylococcus (12.8%).
In the present study, 90% had microbiologically confirmed recovery at day 7 in patients with acute bacterial conjunctivitis receiving azithromycin 1.5% ophthalmic solution. Clinical recovery or significant improvement at day 7 was observed in 90% at day 7.
This came in agreement with Abelson et al. who found that 1% azithromycin ophthalmic solution eradicated more than 90% of H. influenzae, S. pneumoniae, Staphylococcus epidermidis, and Streptococcus mitis group pathogens isolated from the per-protocol population.
In the present study, 92% had microbiologically confirmed recovery at day 7 in patients with acute bacterial conjunctivitis receiving moxifloxacin 0.5% ophthalmic solution. Clinical recovery or significant improvement at day 7 was observed in 92% at day 7.
Baiza-Durán et al. , Wong et al. , McDonald et al. , and Scoper found that moxifloxacin is the most potent fluoroquinolone evaluated in ophthalmic presentation, with eradication rate more than 90%. It is active in killing gram-positive and some gram-negative bacteria.
In the current study, a short treatment regimen (3 days) with azithromycin 1.5% eyedrops provided a more rapid clinical cure in patients with purulent bacterial conjunctivitis. This came in agreement with Bremond-Gignac et al. , who found the same results.
In the current study, on day 3, the clinical cure rate for the worse eye increased in moxifloxacin group (52%). On day 7, clinical cure rates increased to 92%.
In agreement with our study, Gupta found that on day 3, the clinical cure rate for the worse eye was increased in moxifloxacin group (47.1%). On day 7, clinical cure rates increased to 89.2%.
In the current study, there was no statistically significant difference between both groups in frequency of different ocular and nonocular adverse effects.
In the present study, azithromycin 1.5% ophthalmic solution is well tolerated in patients with bacterial conjunctivitis, with the most commonly reported treatment-related AEs being ocular in nature (20%). Burning and redness occurred in 8% of patients of this group. This came in agreement with Garnock-Jones, who found that the most common (incidence 10%) AEs listed in the UK SPC as occurring during clinical trials and from postmarketing safety data are related to ocular discomfort (i.e., pruritus, burning, and stinging) upon instillation. Less common (incidence 1–10%) AEs include blurred vision, sticky eye sensation, and foreign body sensation upon instillation.
In the present study, moxifloxacin 0.5% ophthalmic solution was well tolerated in patients with bacterial conjunctivitis, with the most commonly reported treatment-related AEs being ocular in nature (14%). Burning and redness occurred in 10 and 6%, respectively. This came in agreement with Gillian, who found the same results.
In the current study, the frequency of different ocular adverse effects was higher in azithromycin group (20%) than in moxifloxacin group (14%) but did not reach statistical significance. Moreover, there was no statistically significant difference between both groups in frequency of different nonocular adverse effects.
Granet et al. found that ocular AEs (redness, irritation, stinging, burning, dryness, itching, and chemosis) were observed in 18 (17.3%) eyes receiving azithromycin and one (1%) eye receiving moxifloxacin. Moxifloxacin was significantly more tolerable than azithromycin in healthy adult and pediatric eyes. Tolerability and patient acceptance affect compliance; thus, these data should be of significance to the clinician. One nonocular AE was observed in a patient who received both antibiotics (postnasal drip).
In the present study, 92% of patients receiving moxifloxacin 0.5% ophthalmic solution were cured at day 7. This came in agreement with Alcon Inc., who recommended a 7-day treatment course of moxifloxacin 0.5% ophthalmic solution.
| Conclusion|| |
Our study shows that azithromycin 1.5% for 7 days was as effective as moxifloxacin for 7 days. Azithromycin 1.5% and moxifloxacin 0.5% ophthalmic solution were well tolerated in patients with bacterial conjunctivitis. Ocular AEs (e.g., burning and redness) were the most commonly reported treatment-related AEs, with the majority being of mild severity.
Authors' contributions: H.M.F. contributed to data collection, analysis and wrote the manuscript. S.S.M. and S.S.F. provided patient data and contributed to data analyses and interpretation; they critically reviewed the manuscript. S.S.F. performed microbiology testing. All authors read and approved the final manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gupta K. Effcacy and safety of moxifloxacin 0.5% eye drops versus tobramycin 0.3% eye drops in pediatric population with purulent bacterial conjunctivitis. Int J Sci Study 2019; 7
Martin M, Turco JH, Zegans ME, Facklam RR, Sodha S, Elliott? JA, et al
. An outbreak of conjunctivitis due to atypical Streptococcus pneumoniae
. N Engl J Med 2003; 348
Bremond-Gignac D, Nezzar H, Bianchi PE, Messaoud R, Lazreg S, Voinea L, et al
. Efficacy and safety of azithromycin 1.5% eye drops in paediatric population with purulent bacterial conjunctivitis. Br J Ophthalmol 2014; 98
Shrestha SP, Khadka J, Pokhrel AK, Sathian B. Acute bacterial conjunctivitis–antibiotic susceptibility and resistance to commercially available topical antibiotics in Nepal. Nepalese J Ophthalmol 2016; 8
Granet D, Lichtenstein SJ, Onofrey B, Katz JA. An assessment of the tolerability of moxifloxacin 0.5% compared to azithromycin 1.0% in DuraSite®. Clin Ophthalmol 2007; 1
Utine CA. Update and critical appraisal of the use of topical azithromycin ophthalmic 1%(AzaSite®) solution in the treatment of ocular infections. Clinical Ophthalmology (Auckland, NZ). 2011;5
Denis F, Chaumeil C, Goldschmidt P, Delval L, Pouliquen P, Cochereau I, et al
. Microbiologic efficacy of 3-day treatment with azithromycin 1.5% eyedrops for purulent bacterial conjunctivitis. Eur J Ophthalmol 2008; 18
Schwab IR, Friedlaender M, McCulley J, Lichtenstein SJ, Moran CT, Levofloxacin Bacterial Conjunctivitis Active Control Study Group. A phase III clinical trial of 0.5% levofloxacin ophthalmic solution versus 0.3% ofloxacin ophthalmic solution for the treatment of bacterial conjunctivitis. Ophthalmology 2003; 110
Yeu E, Hauswirth S. A review of the differential diagnosis of acute infectious conjunctivitis: implications for treatment and management. Clin Ophthalmol 2020; 14
Heller W, Cruz M, Bhagat YR, De Leon JM, Felix C, Villanueva L, et al
. Gatifloxacin 0.5% administered twice daily for the treatment of acute bacterial conjunctivitis in patients one year of age or older. J Ocul Pharmacol Ther 2014; 30
Jaruratanasirikul S, Hortiwakul R, Tantisarasart T, Phuenpathom N, Tussanasunthornwong S. Distribution of azithromycin into brain tissue, cerebrospinal fluid, and aqueous humor of the eye. Antimicrob Agents Chemother 1996; 40
Tarabishy AB, Jeng BH. Bacterial conjunctivitis: a review for internists. Cleve Clin J Med 2008; 75
Stroman DW, Cupp GA, Schlech BA. Resistance patterns in conjunctivitis and blepharitis in 2006. Investig Ophthalmol Vis Sci 2007; 48
Abelson MB, Heller W, Shapiro AM, Si E, Hsu P, Bowman LM, et al
. Clinical cure of bacterial conjunctivitis with azithromycin 1%: vehicle-controlled, double-masked clinical trial. Am J Ophthalmol 2008; 145
Baiza-Durán L, Olvera-Montano O, Mercado-Sesma AR, Oregon-Miranda AA, Pazufloxacin Study Group. Efficacy and safety of 0.6% pazufloxacin ophthalmic solution versus moxifloxacin 0.5% and gatifloxacin 0.3% in subjects with bacterial conjunctivitis: a randomized clinical trial. J Ocul Pharmacol Ther 2018; 34
Wong CA, Galvis V, Tello A, Villareal D, Rey JJ. In vitro
antibiotic susceptibility to fluoroquinolones. Arch Soc Esp Oftalmol 2012; 87
McDonald MB, Protzko EE, Brunner LS, Morris TW, Haas W, Paterno MR, et al
. Efficacy and safety of besifloxacin ophthalmic suspension 0.6% compared with moxifloxacin ophthalmic solution 0.5% for treating bacterial conjunctivitis. Ophthalmology 2009; 116
Scoper SV. Review of third-and fourth-generation fluoroquinolones in ophthalmology: in-vitro and in-vivo efficacy. Adv Ther 2008; 25
Garnock-Jones KP. Azithromycin 1.5% ophthalmic solution. Drugs 2012; 72
Gillian M. Moxifloxacin 0.5% ophthalmic solution in bacterial conjunctivitis. Drugs 2011; 71
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]