Eye infections

What are the key principles of preventing eye infections?

What infection control procedures should be followed in the outpatient clinic?

Hand washing/sanitizing should be routinely performed in between each patient. Using gloves during examination of suspected infectious conjunctivitis cases is highly recommended.
Clinicians should use single use eye drops or minimum volume multi-dose vials that are discarded after contact with a patient’s eye or after a specified number of days.
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Local area surface disinfection of exam rooms and instruments with patient contact (e.g., tonometer, slit lamp chin rest, indirect ophthalmoscope, chairs, exam tables, door handles) should be completed in between patients.
Exam room environments (e.g., counter surfaces, chairs, exam tables, door handles, sinks, light switches) should be routinely disinfected with a terminal disinfection at the end of each clinic day.
In the case of suspected adenoviral conjunctivitis, terminal disinfection of exam room after care of suspect case should be undertaken.
Cohorting of patients with suspected adenovirus conjunctivitis to separate waiting and exam rooms should be undertaken.
Staff should be educated on proper infection control procedures at regular time-points and during outbreaks of adenovirus conjunctivitis.
All patients, especially those with suspected adenovirus conjunctivitis, should be informed about how to reduce transmission of infections.

How should the exam room be sterilized after routine patients, and after suspected adenoviral conjunctivitis?

Routinely, exam rooms (e.g., counter surfaces, chairs, exam tables, door handles, sinks, light switches) should be wiped down with a disinfectant (e.g., bleach/chlorine based solution, PDI Sanicloth germicidal wipes) approved by your institutional infection control committee in between patients and a terminal clean with bleach solution (1000 ppm) should be performed at the end of the day.
Following a case of suspected adenoviral conjunctivitis, exam rooms (e.g., counter surfaces, chairs, exam tables, door handles, sinks, light switches) should be wiped down with a bleach solution (1000 ppm).
Waiting areas (counter surfaces, chairs, tables, door handles, light switches, toys) should be routinely cleaned once daily with an infection control committee approved disinfectant. Reading materials available in the waiting room and exam rooms should be removed weekly.
In the event of an outbreak of adenoviral conjunctivitis, all reading materials and toys should be removed from the waiting area and exam rooms.

How should equipment be sterilized after routine patients, and after suspected adenoviral conjunctivitis?

Reusable ophthalmologic instruments and other non-sterile equipment (e.g., tonometer, indirect ophthalmoscope) should be routinely disinfected for 5-10 minutes with 70% ethyl alcohol or ~5,000 ppm chlorine (whichever is compatible with equipment according to manufacturer’s instructions) between patients. After disinfection, equipment should be rinsed in water and air dried. Clinics routinely use 70% isopropyl alcohol swabs due to the convenience; however several studies suggest that 70% isopropyl alcohol does not eliminate adenovirus from instruments and the environment.
After suspected adenoviral conjunctivitis: If possible, avoid procedures where reusable equipment contacts mucous membranes of infected/exposed patients. If your clinic routinely uses 70% isopropyl alcohol swabs, additional sterilization may be required, particularly in the context of an outbreak of conjunctivitis.

Should patients with suspected adenovirus conjunctivitis be isolated in the outpatient clinic? What procedures should be in place for suspected adenovirus conjunctivitis?

Patients with suspected adenovirus conjunctivitis should be isolated in both the waiting areas and exam rooms. Receptionists should inquire about exposure to people with red eyes and fever in the preceding 10 days and note eye redness or discharge. A specific exam room should be designated for patients with suspected adenovirus conjunctivitis.
In the setting of an outbreak, increased control of common areas and increased patient education may be required.
Standard isolation may not be feasible in all clinics. If this is the case, isolation of patients with suspected adenovirus conjunctivitis should be initiated in the setting of a community or nosocomial outbreak.

Perioperative Infection Prophylaxis for Ophthalmic Surgery

What are the key concepts related to Perioperative Infection Prophylaxis for Ophthalmic Surgery and implications for infection control?

One of the most feared complications of intraocular surgery is endophthalmitis. Rates of this infection following cataract surgery, the most common ophthalmic surgery and one of the most common surgeries performed in the world, have recently been reported to be between 0.2% and 0.3% These low rates make interventional studies difficult and expensive to do. This potentially visually devastating infection can also occur after glaucoma surgeries, vitrectomies, pars plana intraocular injections, cornea transplants, and other less common ocular surgeries in which the eye wall is violated. Surgeries of the conjunctiva, sclera, and cornea that do not violate the eye wall may result in ocular surface infections of clinical significance or may proceed to endophthalmitis. Perioperative infection prophylaxis for ophthalmic surgery is a collection of strategies for decreasing the risk of these postoperative ocular infections.

There are 3 main strategies ophthalmic surgeons employ for the prophylaxis of infection:

1. the use of povidone iodine 5% solution as an ocular surface prep just prior to surgery

2. the use of perioperative antibiotic drops

3. the use of antibiotic solutions either diluted in the infusion solutions used during surgery or in a higher concentration given as a bolus at the end of the procedure (i.e. “intracameral antibiotics”).

Many eye surgeons will use a combination of these 3 strategies to avoid post-operative infections.

The use of intracameral antibiotics at the end of cataract surgery reduced the rates of endophthalmitis in a large prospective European clinical trial

Perioperative antibiotic drops reduce the bacterial load on the eye surface, penetrate into the anterior chamber, and reduce the risk of endophthalmitis.

The key conclusions of perioperative infection prophylaxis for ophthalmic surgery are:

Povidone iodine 5% solution used immediately preoperatively on the eye surface reduces rates of endophthalmitis post-operatively.
Certain surgical conditions (complicated case, longer operative time, older patient age) increase the risk of a post-operative infection
Most post-operative ocular infections involve bacteria that can be cultured from the patient’s periocular tissue before surgery.

The Role of Oral Antibiotics Perioperative Infection Prophylaxis for Ophthalmic Surgery:

There does not appear to be a role for oral antibiotics in Perioperative Infection Prophylaxis for Ophthalmic Surgery as the intraocular and eye surface concentrations of antibiotics achieved using eye drops or intracameral antibiotics is much higher than that which can be obtained by oral antibiotics. Also there is a blood-intraocular space barrier that makes it hard for systemic antibiotics to penetrate the eye. This barrier also makes the incidence of systemic seeding from intraocular infections rare. Some surgeons advocate the use of oral fluoroquinolones prior to surgery for severe ocular trauma as the normal anatomic barriers and physiology of the eye is disturbed.

What are the conclusions of clinical trials and meta-analyses regarding the control of eye infections?

Table I summarizes important studies related to infection prevention in ophthalmology.

Table I.

Author	Year	Location	Study Design	Number of Cases	Findings
Warren et al.	1985-1986	Chicago, United States	Case-control	401	Pneumotonometry was significantly associated with epidemic keratoconjunctivitis (EKC).In one nosocomial case, the patient received laser treatments immediately after a patient who was later found to have EKC. The lens, which had been used for both patients, was not disinfected between patients; the same physician performed both treatments.Initial infection control measures were not successful in halting transmission. Nosocomial infections did not stop until a strict triage and cohorting plan was implemented.
Montessori et al.	1995	Vancouver, British Columbia	Case-Control	39	Infections were associated with 4 of 20 physicians, 61% of cases linked to 1 physicianSubsequent outbreaks suggested that poor compliance with infection control measures, especially glove use, hand washing and equipment/room sterilization, was an issue.
Uchio et al.	2002	Japan	Case series	26	Multi-dose eye drop bottles used by infected patients are a possible vector for up to 9 weeks. 73% of eye drop bottles (inside of cap, rim of bottle, dispensing tip and fluid) were positive for adenovirus.
Viney et al.	2006	New South Wales, Australia	Case-Control	68	Anesthetic drops, tonometry, dilating drops, optical coherence tomography associated with EKC.Adenovirus was recovered from dilating drops up to 21 days with no reduction in initial virus titerEpidemic was controlled by reducing clinic caseload, establishing routine environmental cleaning, utilizing smaller volume vials for multi-dose drops, cohorting patients and promoting hand hygiene among staff.
Hamada et al.	2007	Kurume, Japan	Environmental sampling	27	After environmental disinfection with alcohol and glutaraldehyde, 81% of environmental swabs were positive for adenovirus (slit lamp, glasses frame, eye drops, treatment room tap). After second disinfection, 38% of environmental swabs were positive.
Dart et al.	2009	London, United Kingdom	Observational	________	A reduction in nosocomial EKC cases was observed after implementation of new infection control measures. – 1998-1999, 48.4% of total cases were nosocomial: standard infection control measures (hand washing, local area surface cleaning, single-use eye-drops, avoidance of tonometry)- 2002-2003, 22.7% of total cases were nosocomial: following introduction of new infection control measures (segregating suspected EKC cases in a separate waiting area and examination room and expediting their examination)- 2003-2005, 3.4% of total cases were nosocomial: subsequent 24 months after introduction of new infection control measures.

Hand washing compliance has been infrequently measured in the ophthalmology setting, however all studies have found very low hand hygiene compliance. At least one study found that physicians in an ophthalmology clinic only washed their hands 74% of the time between routine patient visits. Another study in the UK by Sivaraj et al. found that ophthalmologists washed their hands 0.048 times per patient. Eighty five percent of the physicians surveyed admitted they did not wash their hands in between patients. Mensah et al. found that hand hygiene was 18% in glaucoma clinics and only increased to 28% after staff was aware their hand hygiene was being monitored.

What other information supports the conclusions of studies regarding eye infections, e.g., case-control studies and case series?

There is a large body of evidence shown by large-scale retrospective and prospective studies done in Europe indicating that intracameral cephalosporin use at the end of cataract surgery reduces rates of endophthalmitis.

Summary of current controversies.

In the United States, the use of intracameral antibiotics at the end of cataract surgery is not a commonly used technique though it is widely employed elsewhere in the world. The most common antibiotic drops used perioperatively in the United States are 4th generation fluoroquinolones. There has not been a large-scale randomized prospective trial comparing their use versus intracameral antibiotics.

Research regarding appropriate cleaning agents for equipment is limited. Rutala et al. found that out of the 4 agents recommended by the CDC for sterilizing tonometer tips (3% hydrogen peroxide, 5000 ppm chlorine, 70% ethyl alcohol, or 70% isopropyl alcohol) only 5000 ppm chlorine and 70% ethyl alcohol were effective in sufficiently reducing titers of adenovirus. Due to the simplicity, reusable equipment is often wiped with a 70% isopropyl alcohol swab in between patients. However, studies have mixed results on the effectiveness of this strategy in eliminating adenovirus.

The ophthalmology clinic is often mistakenly determined to be “clean” or “cleaner” than other medical clinics. Consistent hand hygiene compliance and disinfection of surfaces and instruments between patients is necessary in ophthalmology and should be strictly enforced.

What is the impact of control of eye infections relative to infections at other sites or from other specific pathogens?

The use of anti-infective eye drops or intracameral antibiotics creates negligible systemic levels of these drugs and therefore has little impact on sites remote to the eye. Similarly, it is thought that due to this lack of systemic levels of drug and the small area of the eye that Perioperative Infection Prophylaxis for Ophthalmic Surgery negligibly contributes to antibiotic resistance.

Overview of important clinical trials, meta-analyses, case control studies, case series, and individual case reports related to control of eye infections.

See Table II, Table III, Table IV, Table V, and Table VI for a summary of the research regarding eye infections.

Table II.

Study	Rate of Endophthalmitis	Intracameral antibiotic use	Number of surgeries
Javitt et al	0.080% (1988)	No	57,103
West et al	0.247% (2001)	No	61,077
Semmens et al	0.198% (1998)	No	32,355
Moshirfar et al	0.070% (2005)	No	20,013
Lundström et al	0.045% (2004)	Yes	223,156

Table III.

Study Group	Rate of Total Endophthalmitis	Rate of Proven Endophthalmitis	Number of surgeries
No perioperative antibiotic prophylaxis	0.345% (0.119-0.579)	0.247% (0.118-0.453)	4,054
Intracameral cefuroxime only	0.074% (0.015-0.216)	0.049% (0.006-0.178)	4,056
Topical levofloxacin only	0.247% (0.119-0.454)	0.173% (0.070-0.356)	4,049
Both intracameral cefuroxime and topical levofloxacin	0.049% (0.006-0.178)	0.025% (0.001-0.137)	4,052

Table IV.

Organism	Percentage of cases
Streptococcus pneumoniae	2 (6.8%)
Streptococcus salivarius	2 (6.8%)
Streptococcus suis	1 (3.4%)
Streptococcus mitis	1 (3.4%)
Streptococcus sanguinis	1 (3.4%)
Streptococcus oralis	1 (3.4%)
Staphylococcus aureus	2 (6.8%)
Staphylococcus epidermidis	9 (31.0%)
Staphylococcushominis/haemolyticus	1 (3.4%)
Staphylococcus warneri	1 (3.4%)
Propionibacterium acnes	2 (6.8%)
Non-proven	9 (31.0%)

Table V.

Organism	Percentage of cases
Coagulase-negative Staphylococcus	50 (68.4%)
Staphylococcus aureus	5 (6.8%)
Miscellaneous gram-positive organisms	5 (6.8%)
Gram-negative species	7 (9.6%)

Table VI.

Component	Strength of evidence
Povidone iodine 5% solution decreases risk for ocular infections postoperatively	Conclusive (Level 1)
Perioperative antibiotic drops decrease bacterial counts on the eye surface	Conclusive (Level 1)
Intracameral antibiotic use decreases the risk for endophthalmitis	Conclusive (Level 1)

Evaluating all the existing evidence regarding Perioperative Infection Prophylaxis for Ophthalmic Surgery, one can conclude that this intervention is effective.

Controversies in detail.

In summary, there is scientific plausibility for Perioperative Infection Prophylaxis for Ophthalmic Surgery to decrease the rate of postoperative ocular infections. The use of Povidone iodine 5% solution as a prep agent before ocular surgery is simple, inexpensive, safe, and efficacious. The use of antibiotic drops in the perioperative period is nearly universal amongst cataract surgeons. It is safe and efficacious though expensive (depending on the drug used) and somewhat burdensome to patients. The use of intracameral antibiotics is simple and efficacious though a bit more risky than using drops while costs vary depending on the drug used. Most European ophthalmic surgeons use intracameral antibiotics at the end of cataract surgery in addition to the other methods mentioned while most American surgeons do not.

Controversies regarding Perioperative Infection Prophylaxis for Ophthalmic Surgery:

(1) The use of intracameral antibiotics has not been widely adopted by American ophthalmic surgeons. Many American surgeons criticize the large prospective European clinical trial that showed a benefit of this approach due to the high baseline rate of endophthalmitis and the topical antibiotic that was used (levofloxacin was studied, not the later generation fluoroquinolones gatifloxacin or moxifloxacin). There is also no commercially available preparation of antibiotics for use intracamerally in the United States. This means that to use intracameral antibiotic solutions similar to those used in the European trial, one would need for the drug to be mixed by a pharmacist or other health care worker. This raises the risk of causing toxic anterior segment syndrome (TASS) if an inappropriate drug, concentration, or diluents were to be used. Also it is not well established which antibiotics and in what concentrations should be used intracamerally. For example, the use of gentamicin in this manner can cause immediate and severe intraocular damage. Some surgeons have advocated the use of moxifloxacin from the eye drop bottle as the currently available preparation used in the United States (Vigamox from Alcon Laboratories) is non-preserved, isotonic, and pH neutral.

(2) The rates of endophthalmitis in the United States rose significantly between 1994 and 2001. Some researchers suggest the cause of this trend was the switch to clear corneal incisions and away from the sclerocorneal incisions that were popular prior to the late 1990’s. Other advantages to the clear corneal incision (rapidity and ease of construction, improved ergonomics during phacoemulsification) make it unlikely that surgeons will abandon this approach. This has led to closer attention to techniques of clear corneal incision construction as some authors report very low rates of endophthalmitis using this approach.

(3) Neither the use of perioperative antibiotic drops nor the use of intracameral antibiotics at the end of surgery for the prophylaxis of infection is an FDA-approved indication for these drugs. To date, definitive data suggesting a decrease in post-cataract extraction endophthalmitis risk due to peri-operative antibiotic drop use is lacking. In most American communities, the use of perioperative antibiotic eye drops is considered standard of care, however. These eye drops are typically indicated for treating ocular surface infections though they are prescribed millions of times per year in the United States for infection prophylaxis.

Many people are allergic to iodine or iodine-containing products, so the use of povidone iodine 5% solution for ocular surgical prep is problematic. There is not a good alternative for the eye surface as most other substances such as alcohol and chlorhexidine that are used for skin prep are toxic to the cornea and other ocular tissues. Most surgeons will proceed without an eye surface prep if the patient is allergic to iodine (though they are likely to prep the periocular skin with alcohol). Additional drops of antibiotics prior to surgery may also be employed.

Are there national and international eye infection guidelines?

The American Academy of Ophthalmology recommends the use of a 5% solution of povidone iodine in the conjunctival cul de sac to prevent infection. This organization also concludes that it is incumbent on the surgeon to assure that all incisions are closed in a watertight fashion at the end of the procedure. The European Society of Cataract and Refractive Surgeons recommends the use of intracameral cefuroxime in routine cataract surgery.

References

“American Academy of Ophthalmology. Cataract in the Adult Eye, Preferred Practice Pattern”. 2006.

Aizman, A, Stein, JD, Stenson, SM. “A survey of patterns of physician hygiene in ophthalmology clinic patient encounters”. Eye & Contact Lens: Science & Clinical Practice. vol. 29. 2003. pp. 221-2.

Dart, JK, El-Amir, AN, Maddison, T. “Identification and control of nosocomial adenovirus keratoconjunctivitis in an ophthalmic department”. Br J Ophthalmol. vol. 93. 2009. pp. 18-20.

Hamada, N, Gotoh, K, Hara, K. “Nosocomial outbreak of epidemic keratoconjunctivitis accompanying environmental contamination with adenoviruses”. J Hosp Infect. vol. 68. 2008. pp. 262-8.

Lee, AG. “Hand washing in ophthalmology”. Can J Ophthalmol. vol. 42. 2007. pp. 791-2.

Mensah, E, Murdoch, IE, Binstead, K, Rotheram, C, Franks, W. “Hand hygiene in routine glaucoma clinics”. Br J Ophthalmol. vol. 89. 2005. pp. 1541-2.

Montessori, V, Scharf, S, Holland, S, Werker, DH, Roberts, FJ, Bryce, E. “Epidemic keratoconjunctivitis outbreak at a tertiary referral eye care clinic”. Am J Infect Control. vol. 26. 1998. pp. 399-405.

Rutala, WA, Peacock, JE, Gergen, MF, Sobsey, MD, Weber, DJ. “Efficacy of hospital germicides against adenovirus 8, a common cause of epidemic keratoconjunctivitis in health care facilities”. Antimicrob Agents Chemother. vol. 50. 2006. pp. 1419-24.

Rutala, WA. “Weber DJ, and the Healthcare Infection Control Practices Advisory Committee”. Guideline for disinfection and sterilization in healthcare facilities. 2008. pp. 1-158.

Sivaraj, RR, Evans, R, Rauz, S, Murray, PI. “Hand hygiene practices among ophthalmologists”. J Hosp Infect. vol. 63. 2006. pp. 352-4.

Uchio, E, Ishiko, H, Aoki, K, Ohno, S. “Adenovirus detected by polymerase chain reaction in multidose eyedrop bottles used by patients with adenoviral keratoconjunctivitis”. Am J Ophthalmol. vol. 134. 2002. pp. 618-9.

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