|Year : 2017 | Volume
| Issue : 2 | Page : 81-86
Bacterial contamination of multi-dose eye drops at ophthalmology department, University of Gondar, Northwest Ethiopia
Asegedech Tsegaw1, Asamere Tsegaw2, Tefera Abula3, Yared Assefa2
1 Department of Pharmacology, School of Pharmacy, University of Gondar, Gondar, Ethiopia
2 Department of Ophthalmology, University of Gondar, Gondar, Ethiopia
3 Department of Pharmacology, School of Pharmacy, Addis Ababa University, Addis Ababa, Ethiopia
|Date of Web Publication||7-Sep-2017|
Department of Ophthalmology, University of Gondar, P.O. Box 196, Gondar
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Purpose: Ophthalmic solutions used for both diagnostic and therapeutic purposes were found to be contaminated with bacteria pathogens and caused serious ocular infections such as keratitis and endophthalmitis. The objective was to assess the magnitude and pattern of bacterial contamination of multi-dose ophthalmic medications and investigate the drug susceptibility pattern of the isolates in the Department of Ophthalmology at Gondar University Teaching Hospital.
Methods: A total of 100 ophthalmic medications in-use by patients and eye-care workers have been taken and cultured for potential bacterial contamination in the Microbiology Department after 1 week and >1 week of use. The dropper tip and the residual eye medications were examined for contamination. The contaminating bacteria were identified using a standard procedure and drug susceptibility testing to selected antimicrobial agents was done.
Results: Eleven ophthalmic medications were contaminated by different bacterial species with a prevalence of 11%. Multi-use and longer duration of use of eye medications were associated with higher rate of contamination. The contamination level ranges from 0% for antibiotics, 20% for local anesthetics, and 40% for povidone iodine. Among bacteria identified, Staphylococcus aureus and coagulase-negative Staphylococcus species were resistant to methicillin while others were sensitive to the antibiotics tested.
Conclusion: The prevalence of contamination was low, but methicillin-resistant Staphylococcus was a potential risk. It is recommended that the Department of Ophthalmology should design set of rules about duration of use and safe handling of ophthalmic medications by the staff and patients.
Keywords: Bacterial contamination, drug susceptibility, Ethiopia, topical ophthalmic medications
|How to cite this article:|
Tsegaw A, Tsegaw A, Abula T, Assefa Y. Bacterial contamination of multi-dose eye drops at ophthalmology department, University of Gondar, Northwest Ethiopia. Middle East Afr J Ophthalmol 2017;24:81-6
|How to cite this URL:|
Tsegaw A, Tsegaw A, Abula T, Assefa Y. Bacterial contamination of multi-dose eye drops at ophthalmology department, University of Gondar, Northwest Ethiopia. Middle East Afr J Ophthalmol [serial online] 2017 [cited 2021 Apr 13];24:81-6. Available from: http://www.meajo.org/text.asp?2017/24/2/81/214179
| Introduction|| |
Contaminated ophthalmic solutions represent a potential cause of avoidable ocular infections. Ophthalmic solutions used for both diagnostic and therapeutic purposes have been found to be contaminated with bacteria pathogens and to be associated with ocular infections. Published rates of bacterial contamination in ophthalmic solution bottles are reported to be anywhere from 2.3% to 70% and commonly isolated bacteria include coagulase-negative Staphylococcus, Staphylococcus aureus, Pseudomonas, Bacillus, Proteus, Haemophilus, Enterobacter, Serratia, and Klebsiella spp.,,,,,,, Infections of the eye, from contaminated medications or other possible reasons, can rapidly damage the important functional structures and may lead to permanent vision loss and blindness.,, Serious eye infections such as bacterial keratitis and endophthalmitis were found to be associated with the use of contaminated topical medications,,
Bacterial keratitis refers to bacterial infection of the cornea and can cause corneal opacity and perforation, which leads to severe visual loss and blindness. It is the leading cause of monocular blindness in the developing world.,
The common risk factors for infectious keratitis include contaminated ocular medications, contact lens wear, recent ocular surgery, preexisting ocular surface disease, dry eyes, lid deformity, corneal sensational impairment, chronic use of topical steroids, and systemic immunosuppressant.
Endophthalmitis is an infection and inflammation of all internal and external structure of the eye ball that potentially is the most devastating of ocular infections and a vision-threatening ocular emergency that mandates immediate and aggressive antibiotic therapy. During infection, irreversible damage to delicate structures of the eye occurs. Despite aggressive therapeutic and surgical intervention, endophthalmitis generally results in partial or complete loss of vision, often within a few days of inoculation.,,
Apart from the risk of infection, bacterial contamination of ophthalmic preparations may alter the pH of the preparation and therefore reduce the efficacy of the medication in the treatment of the intended diagnosis. To prevent microbial contamination, most preparations contain preservatives unless the drug itself has an antimicrobial effect. These preservatives are used to prevent or inhibit the growth of microorganisms which increase the risk of infection or degradation of the drug so that sterility is assured at the time of first use and maintained during use. The role of preservatives is not sufficient to ensure the sterility of multi-dose eye drops during their use, and this justifies the need for safer use of eye drop vials.,,,,,,,
Available research evidence about the level of contamination of ophthalmic medications is mainly from more developed countries' eye-care settings. One can expect the level of microbial contamination of eye drops in African eye-care settings and its associated consequence to be worse than in the more developed western ophthalmic centers. However, there is not enough research evidence conducted in African ophthalmic care settings so far. To our knowledge, there is no published evidence that described the level of contamination of eye drops in Ethiopian eye-care centers. Therefore, this study attempted to assess the magnitude and pattern of bacterial contamination of multi-dose ophthalmic medications and drug susceptibility pattern at the University of Gondar Hospital, Northwest Ethiopia.
| Methods|| |
Study design period and area
A cross-sectional study was conducted on topical ophthalmic medications used by patients at the University of Gondar Teaching Hospital, Ophthalmology Department, from January 2013 to April 2013.
All topical ophthalmic medications on-use at the Ophthalmology Department, Gondar University Hospital, were the study population.
Sample size and sampling technique
The sample size was determined with the assumption of 6% prevalence taken from a similar study in Kenya on the contamination of topical ophthalmic medications, and convenient sampling technique was used.
(n = the sample size to estimate a single population proportion)
- Z α/2 = standard score corresponding 95% of certainty (=1.96)
- P = 0.06 (taken from similar study in Kenya)
- d = 0.05 (absolute precision)
- 15% = contingency.
n = 87
15% contingency = 13
n = 87 + 13 = 100
- Single-user medication = Topical ophthalmic drug used by a single patient
- Multi-user medication = Topical ophthalmic drug used for more than one patient.
Sample collection procedures
All eye medications in-use were collected during the study period from single-user and multi-user patients at the Departments of Ophthalmology, Gondar University Hospital, after <7 days of use and >7 days of use. All the collected samples were recorded for their active ingredients as well as their duration of uses. The residual contents and droppers of the eye samples immediately examined for possible microbial contamination under aseptic conditions.
The microbial analysis was performed on both the dropper tip and the residual eye drops for each container. The specimens were obtained and cultured according to the standard procedures. A sterile cotton swab was moistened in sterile saline before wiping the nozzle tip of the eye drop containers and then used to inoculate on the culture plates. The vials were then inverted and one drop directly inoculated on each of the media (chocolate agar plate, blood agar plate, MacConkey agar plate). A flame sterilizes loop was then allowed to cool and used to spread the inoculation systematically. This ensured single colony growth. Inoculated media were incubated as soon as possible. MacConkey agar and blood agar plates were incubated over night at 37°C aerobically. To enhance the growth of those bacterial pathogens that need 5%–10% CO2, they were cultured to chocolate agar plate with in a candle jar. The saline broth was also incubated at 37°C and subcultured on blood agar. After overnight incubation, plates were examined for the growth of bacteria colonies. Plates which did not show any growth were further incubated for additional 24 h. For plates which had bacteria colonies, Gram stain was performed and their Gram reaction was observed using a microscope. Gram-negative and Gram-positive bacteria were identified. Gram-negative bacteria were further identified with a series of biochemical tests using triple sugar iron, urea, citrate, motility, and lysine deoxy carboxylase reagents by their color change reactions produced. Appropriate flowchart was used to make decisions in the identification of the bacteria. Gram-positive cocci were identified based on their catalase and coagulase tests.
Antibiotic susceptibility pattern
The identified bacteria were tested for susceptibility to antibacterial agents by the disc diffusion method using Mueller-Hinton agar as media and antibacterial discs. Tetracycline (30 μg), penicillin (10 μg), erythromycin (15 μg), clindamycin, oxacillin, methicillin (5 μg) trimethoprim/sulfamethoxazole (30 μg), vancomycin (30 μg), ampicillin (10 μg), cefotaxime, ceftriaxone (30 μg), gentamicin (10 μg), chloramphenicol (30 μg), and ciprofloxacin (5 μg) were used for testing.
The identified bacteria were separately cultured on nutrient agar for 24 h. Using a sterile wire loop, three to four isolated overnight cultured colonies were transferred to a tube containing sterile saline. The bacterial suspension was compared to the 0.5 McFarland standard.
Using a sterile swab, the bacterial suspension was inoculated on a plate of Muller-Hinton agar. Excess fluid by pressing and rotating the swab against the side of the tube above the level of the suspension was removed. The swab was streaked evenly over the surface of the medium in three directions rotating the plate to ensure even distribution. With the Petri dish lid in place, the surface of the agar was allowed for 3 min to dry. Using sterile forceps, the appropriate antimicrobial discs were placed evenly on the inoculated plate. Within 30 min of applying the discs, the plates were inverted and incubated aerobically at 35°C for 18 h. After overnight incubation, the plates were examined. Using a ruler, the diameter of each zone of inhibition in mm on the underside of the plate was measured. The endpoint of inhibition was where growth starts. Using the interpretative chart, the zones sizes of each antimicrobial were interpreted and reported the organisms classified as “resistant,” intermediate (moderately sensitive), or “sensitive” (susceptible).
To get reliable and valid result, the following quality control measures were taken; avoidance of contamination, avoidance of delay in specimen examination, use of quality reagents, and proper reporting, and recording of the results. Culture media were tested for sterility and performance. Standard reference strains of Escherichia coli American Type Culture Collection (ATCC)-25922, S. aureus (ATCC-25923), and Pseudomonas aeruginosa (ATCC-27853) were used as a quality control throughout the study for culture and antimicrobial susceptibility testing. To standardize the inoculum density of bacteria suspension for susceptibility, a 0.5 McFarland standard was used.
Data were entered and analyzed using the Statistical Package for Social Sciences (SPSS) version 20. Differences in proportions were evaluated by Pearson's Chi-square test; P < 0.05 was considered to be statistically significant.
| Results|| |
A total of 100 eye medications were microbiologically evaluated from bottle tips and residual contents. Overall, 11 eye drops from the total of 100 analyzed eye medications were contaminated by various species of bacteria. This represents a prevalence of 11% bacterial contamination. All of the contaminations of the eye medications were found from the dropper tips. None of the eye medications was contaminated from the residual contents. The rate of contamination ranges from 0% for antibiotics and 20% for local anesthetics. However, there was no significant difference found within the categories of drugs used (P > 0.05) [Table 1]. All local anesthetic eye drops studied were used by eye care professionals to anesthetize patients' eyes during procedures.
|Table 1: Bacterial contamination of eye medications in Ophthalmology Department, University of Gondar Hospital, Northwest Ethiopia, January-April 2013|
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4% Povidone iodine as compared with other medications had the highest overall rates of contamination which was 40% from the five samples taken, followed by tropicamide which was 29.4% and tetracaine which was 20% [Table 2].
|Table 2: Bacterial contamination of individual eye medications and their preservatives in Ophthalmology Department, University of Gondar Hospital, Northwest Ethiopia, January-April 2013|
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Among the total of 100 eye medications studied, 66 eye medications had <7 days of use whereas the rest 34 had >7 days of use as of their first opening. Hence, the bacterial contamination rate was found to be 2/66 (3.2%) for medications with <7 days of use and 9/34 (24.3%) for medications with duration >7 days of use. This difference in contamination rate with duration of use of eye drops was found to be significant (P < 0.003).
Among the total of 100 medications analyzed, 63 were single user and 37 were multi user. The prevalence of contamination was 2/63 (3.2%) for single-use and 9/37 (24.3%) for multi-use medications. This variation of rate of bacterial contamination among single-use and multi-use medications was found to be statistically significant (P < 0.005).
S. aureus was observed in five of the contaminated medications; two tropicamide 1%, two dexamethasone 0.1%, and one povidone iodine 4% preparations. Coagulase-negative Staphylococcus species were isolated from two medications (dexamethasone 0.1% and tetracaine 1%), two Bacillus species were obtained from tropicamide1%, and one E. coli and one Enterobacter species were grown from tetracaine1% and povidone iodine 4%, respectively. None of the medications grew more than one bacterium. Overall, Gram-positive bacteria were cultivated from nine of the 11 contaminated medications and two contaminated medications grew Gram-negative bacteria.
Antimicrobial susceptibility tests
Bacterial susceptibility test was performed for most of the identified bacteria with the commonly used antibiotics. Among the Gram-positives, S. aureus showed resistance to methicillin (80%), penicillin (20%), tetracycline (60%), chloramphenicol (20%) and ampicillin (20%) and sensitive to clindamycin (100%), erythromycin (100%), vancomycin (100%), cefotaxime (100%), and cotrimoxazole (100%). Coagulase-negative Staphylococcus species showed resistance to methicillin (100%), tetracycline (100%), and chloramphenicol (50%) and resistance to the other antibiotics tested. Enterobacter species were resistant to tetracycline (100%) and ampicillin (100%). E. coli were resistant to chloramphenicol (100%) and ampicillin (100%).
| Discussion|| |
Ophthalmic medications are presumed sterile when first opened. Therapeutic and diagnostic medications of the eye have also been found to be contaminated with reported rates as high as 70% and such contamination has resulted in keratitis or endophthalmitis. Our data show a contamination rate of 11% which is in the lower range of data published on the contamination of eye drops elsewhere, i.e., 2.3%–70%. Our study also indicated all of the contaminations of the eye medications were found from the dropper tips, and none were contaminated from the residual contents. These results are in line with findings reported in the earlier studies.,,, The reason for such findings might be due to the fact that the moist tips may serve as a reservoir for microbial contamination, and there is always risk that eye drop products will become contaminated with bacteria as a result of touching the dropper tips while opening it for usage, contact of dropper with the ocular tissues, and environmental factors. This can also be attributed to the fact that the tips of bottles of eye medications have direct contacts with the ocular structures as compared to the contents of the bottles.
In this study, contamination of therapeutic and diagnostic ophthalmic medications was observed predominantly in local anesthetics (20%) and mydriatics (18.5%) in the outpatient department. However, no bacterial contamination was noticed from antibiotics. Although the contamination rate ranges from 0% to 20% for category of drugs (i.e., mydriatics, antibiotics, steroids, and local anesthetics), this difference was proved to be statistically nonsignificant. This finding is in accordance with a study done in Kenya that indicated the highest contamination rates were observed in local anesthetics (10%) and mydriatics (7%), but a study by Jokl et al. showed that steroid solutions were 5.8 times more likely to be contaminated than others. The absence of bacterial contamination in eye medications containing antibiotics may be due to the antibacterial effect of the drugs, and this supports the self-sterilizing effect of many antibiotics. Among individual eye medications studied, 4% povidone iodine was found to be at high rate of contamination (40%). This fact contradicts with the broad spectrum antibacterial effect and antiseptic use of povidone iodine. However, the authors of this paper suggest the reason might be poor aseptic condition during the local preparation of this product.
This study shows that the prevalence of bacterial contamination increased as the duration of use of medications increased from 1 week to >1 week and the difference was found to be significant (P < 0.003). This finding was found to be in agreement with the results of other similar studies.,, Such studies indicated that there is clear-cut association between contamination rate of tips and contents with the length of time that they are used. These findings can be attributed to the fact that as the length of time of use is prolonged, frequency of contact of the eye medication with ocular surfaces will be increased and thus the probability of getting contamination will be enhanced. Conversely, in some other reports, it has been claimed that duration of use does not influence the degree of contamination.,, However, such findings of nonsignificant difference of contamination rate with duration were observed when the length of days of used to compare was relatively short.
The study also revealed that although the medications are labeled to have preservatives, there was a contamination rate of 11%. Most of the medications found contaminated were having thimerosal or benzalkonium chloride as preservatives. These findings were in accordance with studies reported in similar studies., Thus, from the result of our study and other similar studies, it can be suggested that the role of preservatives is not sufficient to ensure the sterility of multi dose eye drops during their uses and this justifies use of single dose eye drops.
The prevalence of contamination was more in multi user medications (24.3%) than in single user (3.2%). This difference was significant with a P < 0.005. A similar result was obtained in other study but the result is different in a study done in Kenya. Probably, using a single bottle of medication for multiple patients exposes the medication to contamination from each patient and this may increase the overall contamination rate relative to single user scenario. This study also indicates that even in the presence of preservatives, multi-user eye medications could be potential vectors of bacterial contaminants from one patient to another, and thus care should be exercised in the drop application techniques even when instilled by health care professionals. Ideally, only unidrop disposable eye containers should be used but they can cost more than multi-drop bottles. For any patient who might be infected or have external eye disease, a unidrop dispenser should be used. Alternatively, the multi-drop bottle could be discarded after use with infected or potentially infected patient.
Most of the bacteria identified were Gram-positives which were S. aureus and coagulase-negative Staphylococcus species and Gram-negatives such as E. coli and Enterobacter species.
The resident flora of the conjunctiva and eyelid mainly comprises of Gram positive bacteria, including coagulase-negative staphylococci, Corynebacterium species, Propionibacterium species, as well as S. aureus, Bacillus species, Micrococcus species, and Enterobacter species. The kind of microorganisms found in the eye drops implies that the medications have come into contact with the eyelid of patients and/or hands of nursing staff during administration; furthermore, they may have been left without closure. Schein et al. believe the cycle of contamination between in-use medications and conjunctiva may represent an important risk factor for microbial keratitis in patients with ocular surface disease. The presence of Gram-negative bacteria, Enterobacteriaceae may be due to hand-fecal contamination. The identity of contaminating organisms found in this study is consistent with those of other studies,,, in which it has been demonstrated that Gram-positive cocci were the dominant contaminant of the eye drops. Most of the detected contaminants were Gram-positive organisms, in particular, S. aureus and coagulase-negative staphylococci that are indigenous to conjunctiva and skin. It should be taken into account that these organisms could be harmful to patients who have disrupted epithelial barriers or those who are immunocompromised.
The identified Gram-positive bacteria which were S. aureus and coagulase negative Staphylococcus species showed resistance to methicillin, tetracycline, and chloramphenicol. This shows that methicillin-resistant Staphylococcus is a potential risk in our setting. The coverage of vancomycin against coagulase negative Staphylococcus species and S. aureus was 100%. The coverage of ceftriaxone, cefotaxime, gentamicin, ciprofloxacin, and cotrimoxazole was 100% and tetracycline and ampicillin showed resistance to the Gram-negative bacilli. The emergency of bacterial resistance was due to characteristic of the pathogens, improper dosage regimen, misuse of antibiotics for viral and other nonbacterial infections, and extended duration of therapy. Resistance and sensitivity based on in vitro testing may not reflect true clinical resistance and response to an antibiotic because of the host factors and penetration of the drug. However, these results do provide information that allows a clinician to make rationale-based decision in choosing an initial regimen for ocular pathogens.
| Conclusion|| |
This study showed that the total rate of bacterial contamination of eye medications in-use by patients and eye-care professionals in the Ophthalmology Department at University of Gondar Teaching Hospital was 11%. Local anesthetic and mydriatic agents were found relatively highly contaminated for possible reason of longer duration of use for multiple patients. Multi-use eye medications were found to be contaminated at higher rates than single-use eye medications. The use of medications for longer duration was found to increase the rate of contamination of eye medications.
The findings of this study suggest that the Department of Ophthalmology of University of Gondar Teaching hospital should design a proper set of rules, guidelines for safer practice, duration of use, correct handling, and application of eye medications.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]