|Ahead of print publication
Multi-use of single use unims: Does economic burden outweigh contamination risk?
Richa Sharma1, Abadan K Amitava1, Mehar Rizvi2, Sadat AO Bani1
1 Institute of Ophthalmology, Jawaharlal Nehru Medical College, AMU, Aligarh, India
2 Department of Microbiology, Jawaharlal Nehru Medical College, AMU, Aligarh, India
Abadan K Amitava,
Institute of Ophthalmology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Gandhi Eye Hospital, Aligarh, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Aim: To assess if residual drops of unims can be used after single use to cut down economic load. Setting: Laboratory setting. Materials and Methods: This study was done to determine the possibility of multi-use of such unims. Ten unims of Acuvail (ketorolac tromethamine 0.45%) were opened simultaneously to culture a single drop from each unim daily for 7 days and growth was studied at 24 h (group 1); a similar study was done taking extra aseptic precautions (group 2), and with another set of 10 unims, with one drop twice a day for 3 days (group 3). Results: 20% unims showed growth on the 1st day and 60% on the 6th day. The growth consisted of Staphylococcus aureus. No growth was found in the second part of the study. Two drops per day arm showed incremental growth from the 3 rd dose (2 nd day). Conclusion: Even though unims contain more than one drop, patients should be strictly instructed for single use of such vials because there is potential risk of transmitting pathogens and a serious threat to post-cataract surgery patients.
Keywords: Contamination, eye drops, unims
Contaminated eye drops may lead to avoidable infections. Prevalence of contamination of ophthalmic drugs varies from 0.07 to 35.8%. , Contaminated drops have been associated with keratitis, corneal ulcers and may transmit opportunistic pathogens. ,,, In addition, contamination alters the pH and reduces the drug efficacy.  Flora from patients' eyes often contaminates multi-dose vials (MDVs). , Organisms have been recovered from both antibiotic and non-antibiotic eye drops, in both a hospital setting and when patients self-administer. Myriad factors can lead to drop contamination. A study in Iran demonstrated a significant risk of contamination with the duration of use.  Brudieu et al. found a significantly lower rate of contamination in vials used by ophthalmic patients (17.7%) compared to that used by medical and gerontological patients (35.8%), highlighting the importance of instructions and training in instilling eye drops.  Another study comparing pipette dispensers with squeeze bottles showed that cap of squeeze bottles could serve as potential reservoir for bacterial contamination. 
In the past, preservatives and anti-bacterial substances were added to drops to reduce or eliminate contamination. Examples of such preservatives include EDTA, oxychloro complex, phenylethyl alcohols, parabens, and chlorobutanol.  Minimizing contamination is vital in ophthalmology. Several options have been tried, such as discarding eye drops from MDVs within 4 weeks of opening in a domestic setting and within a week in hospital wards.  Single Dose Dispensers (SDDs) were also an effort to reduce contamination. Although meant for single use, they contain enough drug to permit 5-6 instillations. One study in England found that up to 79% hospitals were actually using single-use "unims" till the drops finished, for economic reasons. 
Recently, pharmaceutical companies (e.g. Allergan) have introduced unims (0.4 ml of ketorolac tromethamine 0.45%) with caps which can be replaced, which translates into 7-8 drops (assuming a drop size of 50 μl). Although not explicitly stated on the unims container or in the accompanying literature, the company representative subtly suggests that the replaceable caps offer the possibility of multi-use. This raises the risk of contamination, whether from the environment or from the patient.
We therefore designed a study to evaluate the risk of contamination if such unims were used to dispense one drop daily over 7 days. In how many days did bacterial contamination show up? What were the organisms found and what was their antibiotic susceptibility? And did a heightened sterile approach reduce contamination? We re-evaluated contamination rates using a two drops a day approach to mimic the recommended dosing schedule of the unims under study.
| Materials and Methods|| |
We opened a sealed package of 10 unims of 0.4 ml of Ketorolac (group 1) in the laboratory and labeled them serially from 1 to 10. Consecutively, for the next 7 days, a single drop from each unim was inoculated on blood agar, and streaked with a heat-sterilized platinum loop and incubated for 24 h. Unims were recapped and stored in a refrigerator. Culture was considered positive if colonies grew over the streaks within 24 h; they were then counted, the organism was identified by microscopy and biochemical tests, and sensitivity testing was carried out. In addition, on the 7th day, a swab from the investigator's hands was inoculated onto blood agar. To assess whether extra aseptic precautions altered the contamination rate, the entire procedure was repeated, but this time ensuring daily diligent washing of hands, followed by gloving, and alcohol (70%) swabbing the cap prior to instilling a drop onto blood agar (group 2). In addition, another of set of 10 unims was used instilling one drop twice a day onto culture media; due to the limited drug, we could instill a total of 6 drops over 3 days (group 3).
| Results|| |
In group 1, the number of unims which showed positive growth over 7 days ranged from 20 to 60% [Figure 1]. Of the six unims which finally yielded growth, there was a steady increase in the number of colonies over the subsequent days [Figure 2] and [Figure 3].
|Figure 1: Graph showing number of unims with growth over a period of 7 days|
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|Figure 2: Graph showing number of colonies in each unim showing growth over 7 days|
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|Figure 3: Graph showing total number of colonies in all unims over 7 days|
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Every growth consisted of Staphylococcus aureus [Figure 4] and [Figure 5]. These were catalase, coagulase, and mannitol positive. The organism was susceptible to Amikacin, Ofloxacin, Clindamycin, Sparfloxacin, Cephazoline, Gatifloxacin, Erythromycin, Gentamycin, and Vancomycin.
|Figure 4: Photograph of isolated colony of Staphylococcus aureus in our study|
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In group 2, no growth was seen over 7 days.
With group 3 approach, we noticed growth of Staphylococcus colonies of about 20% with the 3 rd drop, 30% with the 4 th and 5 th drops, and 60% with the 6 th drop. There was a steady increase in the number of colonies for each subsequent drop once contamination was observed in a particular unim [Table 1].
The culture from researcher's hands grew the same coagulase-positive S. aureus.
| Discussion|| |
Our study shows that there is a 20% (95% CI: 4.8-44.8%) risk of contamination of eye drops even from the first day while using unims. This can go as high as 60% (95% CI: 29.6-90%) by the 6th drop. In our experiment, the growth was invariably of S. aureus, fortunately susceptible to numerous antibiotics. Extremely careful attention to sterility can prevent contamination even up to a week after the unims have been opened. But such a milieu will not be the environment in which most patients would be using them; thus, contamination is likely to be higher with patient use.
Like in our study, Gram-positive cocci were the dominating contaminating organisms of the eye drops in many previous studies; most of them were of skin flora, which implies that medication has come in contact with eyelid of the patient and/or hands of nursing staff during administration. ,,, Although the pathogens in our study were susceptible to numerous antibiotics, it is evident that they can seriously compromise ocular health in situations of disrupted epithelial barriers or postoperatively, as also in immunocompromised patients.
A study from England by Qureshi et al. showed that 86% of practitioners were using SDDs for multi-use on patients in their clinics.  It is likely that such practice would be higher in a domestic environment, especially in a developing country like ours.
A study using combined fluorescein-proparacaine unims for applanation tonometry in the OPD revealed a 17% risk of picking up contaminating organisms from the patient's conjunctiva and lids; i.e. in 17% cases, the last drop grew coagulase-negative S. aureus which is considered as normal flora of the skin and conjunctiva.  In the same paper, the authors analyzed that according to the NHS hospital statistics (2005-2006), the cost of using new unims on every patient would be £2,125 079 as compared to £765 028 on using each unim on five patients.
It is common knowledge that eye dropper tips often make contact with the patients' hands - a situation made worse with the small size of unims and their caps. As revealed in our study, the source of the organisms is often the instillers' hands, and we stand a fair chance of risking contamination in the patients' home environments, especially since none will follow the stringent precautions we included in the second part of our research.
We feel that despite obvious economic benefits, we should desist from suggesting that the unims can be used over a couple of days.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]