Evaluation of Efficacy of Topical Povidone-Iodine and Different Types of Fluoroquinolones in the Sterilization of Bacterial Flora on the Conjunctiva

Abstract

Purpose:

To compare the sterilization effectivity of topical povidone-iodine, ciprofloxacin, and ofloxacin on the conjunctival bacterial flora.

Methods:

One hundred sixty-four eyes of 164 patients scheduled for cataract surgery were prospectively analyzed. Conjunctival cultures were obtained 1 day before the surgery without any topical application in all patients. Conjunctival flora was examined in 53 eyes of 53 patients (Group I) 15 min after 5% topical povidone-iodine application on the day of the surgery. Fifty-four eyes of 54 patients (Group II) received 1 drop 0.3% ciprofloxacin at 12 pm 1 day before the operation and 4 drops at 15 min intervals on the day of the surgery. Another 57 eyes of 57 patients (Group III) received 0.3% ofloxacin in the same application mode as ciprofloxacin. Conjunctival cultures were taken in all patients 15 min after last drop of topical antibiotic application.

Results:

Only coagulase-negative staphylococci were isolated from 75.4% in Group I, 72.2% in Group II, and 59.6% in Group III on pretreatment culture. Different types of bacteria such as Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Proteus spp., Micrococcus spp. were identified in other patients. Pretreatment conjunctival flora of Group I and Group II were similar (P>0.05), but it was significantly different in Group III (P<0.05). After topical application no bacterial growth was observed in 77.3% in Group I, 92.5% in Group II, and 66.6% in Group III. The difference between Group I and III was insignificant (P>0.05), but bacterial eradication effectiveness was significantly higher in Group II than that of other groups (P<0.05). Post-treatment cultures showed same bacterial flora as pretreatment cultures in 14.9% in Group I, 1.8% in Group II, and 19.2% in Group III. The difference between Group I and Group III was statistically insignificant (P>0.05) and the difference between Group II and other groups was statistically significant (P<0.05). Four eyes (7.5%) showed different types of bacterial growth from pretreatment flora in Group I, which were seen in 3 eyes (5.5%) in Group II and in 8 eyes (14%) in Group III. The differences between groups were statistically insignificant (P>0.05).

Conclusion:

Ciprofloxacin seems to be more effective in conjunctival sterilization. In consideration with high variety of bacterial flora in pretreatment period in ofloxacin group, ofloxacin seems to be superior to povidone-iodine on the reduction of bacterial flora on the conjunctiva.

Introduction

Postoperative endophthalmitis is a rare but potentially blinding complication of intraocular surgery, leaving 35% to 54% of patients with a visual acuity of less than 20/400.^1–5 The incidence of endophthalmitis varies depending on the type of surgery ranging from 0.082% to 0.32%.^1–5 Many different sources of infection have been identified, including airborne contamination, surgical instruments solutions, intraocular implants, operative complications such as wound leaks,^1–5 and vitreous wicks, but in most cases, the organisms responsible for endophthalmitis have been shown to be identical to flora present on the ocular surface and adnexia of the infected patient.^4,6 Therefore, the most effective method to reduce the incidence of endophthalmitis is to eliminate the ocular and adnexial flora before the intraocular surgery.^2,7 The most common method to reduce bacterial flora on the ocular surface is achieved by treatment of the ocular surface with topical antibiotics or instillation of povidone-iodine 5% into the conjunctiva cul de sac before the surgery.²

The purpose of this prospective study was to investigate and compare the sterilization effectiveness of topical povidone-iodine 5%, ciprofloxacin 0.3%, and ofloxacin 0.3% on the conjunctival bacterial flora before intraocular surgery.

Methods

This study was conducted in accordance with the Declaration of Helsinki and informed consent was obtained.

This prospective, randomized, comparative study included 164 eyes of 164 patients undergoing cataract surgery. Patients receiving topical ophthalmic medications or systemic antibiotic therapy during the previous 72 h and known allergies to quinolone derivatives were excluded from the study. No patient had an ocular infection at the time of the study and no one had corneal irritation.

Pretreatment conjunctival cultures were obtained 1 day before the surgery without any topical application in all patients. The patient was asked to look up, and the moistened sterile swab was gently rolled few times across the inferior palpebral conjunctiva. The culture samples were immediately inoculated into the culture media.

Full-strength (10%) povidone-iodine solution was diluted to half strength with sterile saline before topical application in 53 eyes (Group I). Bacterial isolates were identified 15 min after 5% topical povidone-iodine application on the day of the surgery.

Fifty-four eyes (Group II) received 1 drop of 0.3% ciprofloxacin (Ciloxan^®; Alcon) at 12 pm 1 day before the surgery and 4 drops at 15-min intervals on the day of the surgery.

Another 57 eyes (Group III) received 0.3% ofloxacin (Exocin^®; Allergan) in the same application mode. The post-treatment conjunctival cultures were taken from all patients 15 min after the last drop of the topical antibiotic application.

All specimens were coded before sending to microbiology department; therefore, the microbiologist did not know whether a given specimen was taken before or after the topical application and whether it was obtained from the eye that received povidone-iodine, ciprofloxacin, or ofloxacin. After obtaining conjunctival cultures for this study, all patients underwent phacoemulsification surgery with standard sterilization and premedication technique.

As statistical analysis we used the SPSS 11.0 for Windows package software (SPSS, Inc.). Kruskal–Wallis and Mann–Whitney tests were used for statistical comparisons and a p-value less than 0.05 was accepted as significant statistical difference.

Results

One hundred sixty-four eyes of 164 patients were included in the study. From these, povidone-iodine solution was applied to 53 eyes (Group I), ciprofloxacin to 54 eyes (Group II), and ofloxacin to 57 eyes (Group III). The patients demographic data are shown in the Table 1. There was no difference regarding age and sex between groups (P>0.05).

Table 1.

Demographic Data of Patients

	n	Age±SD (year)	Gender (M/F)
Group I (5% povidone-iodine)	53	58.24±5.32	28/25
Group II (0.3% ciprofloxacin)	54	60.45±4.42	27/27
Group III (0.3% ofloxacin)	57	59.62±6.23	29/28

In our study we found 163/164 positive (99.3%) conjunctival cultures in prepreparation period. Coagulase-negative Staphylococcus (CNS) species were the most commonly cultured organisms in all prepreparation specimens. Only Staphylococcus epidermidis was isolated from 75.4% (40 eyes) in Group I, 72.2% (39 eyes) in Group II, and 59.6% (34 eyes) in Group III on the prepreparation cultures.

Seven isolates of Staphylococcus aureus (13.2%), 3 isolates of Bacillus species (5.6%), 1 Micrococcus species, 1 Klebsiella pneumoniae, and 1 isolate of combined S. aureus with Proteus species cultured in Group I in prepreparation period (Table 2).

Table 2.

Prepreparation Cultures of Conjunctival Flora

	n	Staphylococcus epidermidis	Staphylococcus Aureus	Bacillus species	Escherichia coli	Other
Group I (5% povidone-iodine)	53	40 (75.4%)	7 (13.2%)	3 (5.6%)	—	1 eye Micrococcus species 1 eye Klebsiella pneumoniae 1 eye S. aureus with Proteus species
Group II (0.3% ciprofloxacin)	54	39 (72.2%)	11 (20.3%)	1 (1.8%)	1 (1.8%)	1 eye Enterobacteria 1 eye S. epidermidis with Streptococci
Group III (0.3% ofloxacin)	57	34 (59.6%)	15 (26.3%)	3 (5.2%)	1 (1.7%)	1 eyes S. aureus with Streptococci 1 eyes S. aureus with Bacillus species 1 eye S. aureus with Corinobacterium diphtheria

In Group II, S. aureus were identified in 11 eyes (20.3%). Bacillus species, Enterobacteria, and Escherichia coli were cultured in 1 eye of each and 1 isolate of combined 1 eye S. epidermidis with Streptococci cultured in Group II in prepreparation period (Table 2).

In Group III, S. aureus was isolated in 15 eyes (26.3%), Bacillus species was in 3 (5.2%), and E. coli was isolated in 1 (1.7%) cultures as a single organism. Three eyes had mixed contaminating organisms such as S. aureus with Streptococci, S. aureus with Corynebacterium diphtheria, and S. aureus with Bacillus species in prepreparation in Group III (Table 2). Prepreparation conjunctival flora of Group I and Group II were similar (P>0.05), but they were significantly different than that of Group III (P<0.05).

After topical application of povidone-iodine, ofloxacin, or ciprofloxacin, 41 eyes (77.3%) showed no bacterial growth in Group I, 50 eyes (92.5%) in Group II, and 38 eyes (66.6%) in Group III (Table 3). The difference between Group I and Group III was insignificant (P>0.05), but bacterial eradication effectiveness was significantly higher in Group II than that of other groups (P<0.05).

Table 3.

Numbers of Eyes That Showed No Bacterial Growth in Postpreparation Conjunctival Flora

	n	No bacterial growth
Group I (5% povidone-iodine)	53	41 eyes (77.3%)
Group II (0.3% ciprofloxacin)	54	50 eyes (92.5%)
Group III (0.3% ofloxacin)	57	38 eyes (66.6%)

Postpreparation cultures showed the same bacterial flora as prepreparation cultures in 8 eyes (14.9%) in Group I, in 1 eye (1.8%) in Group II, and 11 eyes (19.2%) in Group III (Table 4). The differences between Group II and other 2 groups were statistically significant (P<0.05). S. aureus was isolated both in pre- and postpreparation flora in 6 eyes (11.3%) in Group I, CNS in 1 eye (1.8%), and Bacillus species in 1 eye (1.8%) in patient treated with povidone-iodine. CNS was isolated in 1 eye (1.8%) both pre- and postpreparation period in Group II (Table 4).

Table 4.

Postpreparation Cultures of Conjunctival Flora

		Same bacterial flora
	n	S. Epidermidis	S. aureus	Bacillus species	Different bacterial flora
Group I (5% povidone-iodine)	53	1 (1.8%)	6 (11.3%)	1 (1.8%)	4 (7.5%)
Group II (0.3% ciprofloxacin)	54	1 (1.8%)	—	—	3 (5.5%)
Group III (0.3% ofloxacin)	57	4 (7.0%)	7 (12.2%)	—	8 (14.0%)

S. aureus was cultured in 7 eyes (12.2%) and CNS was isolated in 4 eyes (7%) in patients treated with ofloxacin in both pre- and postpreparation period (Table 4).

Four eyes (7.5%) showed bacterial growth different type from prepreparation flora in Group I, which were seen 3 eyes (5.5%) in Group II and in 8 eyes (14%) in Group III (Table 4). The difference between groups was statistically insignificant (P>0.05).

Of the 164 eyes, only 1 (0.7%) showed no bacterial growth in prepreparation period, in which Klebsiella was isolated in postpreparation culture that ciprofloxacin was used as medication.

Discussion

The incidence of positive conjunctival cultures in normal eyes has been reported to be 60.9% to 100% in different series.^8,9 External ocular flora plays an important role in the pathogenesis of acute postoperative endophthalmitis.^2,7 Bacteria of the conjunctival flora consist of mainly S. epidermidis, S. aureus, Streptococcus spp., and other more virulent organisms such as Streptococcus pneumonia, diphtheroids, and haemophilus and Pseudomonas aeruginosa, which are the most common causes of postoperative endophthalmitis.^1–11 In our study we found 163/164 positive conjunctival cultures in prepreparation period. The most common organisms in prepreparation cultures were Gram-positive cocci, particularly CNS (59.6% to 75.4%) and S. aureus in all of the 3 groups in our series. Ariyosu et al.⁴ had isolated CNS in 62% of eyes and S. aureus in 31% of eyes. Synder-Perlmutter et al.² also found that 89%–94% of colonies were CNS and 6%–11% was S. aureus in their series. Result of conjunctival flora in our series was similar to other authors' reports. Reduction in the ocular surface flora is the best method to prevent postoperative endophthalmitis.

Many techniques can be used to eliminate or at least minimize the number of micro-organisms on the skin and ocular surface. The 2 main techniques to reduce bacterial flora are treatment of the ocular surface with topical antibiotics before the surgery and instillation of povidone-iodine 5% into the conjunctival cul de sac before the surgery. Povidone-iodine (polyvinylpyrrolidone) is a high-molecular-weight water-soluble polymer that is a safe periocular skin and conjunctival antiseptic effective against bacteria, viruses, fungi, protozoa, and spores.^12,13 On contact with the micro-organism it disrupts the cell membranes, resulting in the death of the micro-organism.¹ Antiseptics such as povidone-iodine have a rapid onset of action; most bacteria are killed within 30 s.² Apt et al.¹⁴ showed that after application of povidone-iodine, bacterial colonies were reduced by 91% and the number of species by 50%. Dereklis¹² founded a reduction in the positive conjunctival cultures from 66% to 30% in eyes after instillation of 1 drop of 5% povidone-iodine. Caldwell et al.⁸ reported that positive conjunctival culture incidences reduced to 9.6% in 225 surgical cases after povidone-iodine application. We found that there were no bacterial growth in cultures taken 15 min after conjunctival irrigation with povidone-iodine. This confirms the effectiveness of povidone-iodine for conjunctival sterilization. In our series 77.3% of eyes showed no bacterial growth of the application of povidone-iodine, which was very similar to Dereklis and other authors finding.^8,12

The ideal antibiotic to reduce the ocular surface flora should have broad-spectrum, high tear-film concentration and low corneal toxicity, and at the same time it should be bactericidal and potent. Fluoroquinolone antibiotics are among the most frequently used topical antibiotics in endophthalmitis prophylaxis. They are bactericidal and work by inhibiting bacterial DNA gyrase, resulting in irreversible damage to bacterial DNA in both Gram-positive and Gram-negative bacteria.^2,3 Main fluoroquinolones available for use in ophthalmology are ciprofloxacin, ofloxacin, and norfloxacin. To et al.³ found that many Gram-positive ocular isolates were highly susceptible to all 3 types of fluoroquinolones. Ciprofloxacin and ofloxacin are highly potent against a broad spectrum of organisms that are the main causes of ophthalmic infection. Therefore, some ophthalmologists advocate using them for endophthalmitis prophylaxis and we preferred to evaluate their effectiveness in sterilization of conjunctival flora.

Synder-Perlmutter et al.² reported that the reduction in bacterial colony achieved by ciprofloxacin was significantly greater than that of ofloxacin. In our study we found that after topical application of ciprofloxacin, negative conjunctival culture was obtained in 92.5% of eyes, whereas it was only 66.6% in ofloxacin application group. In our comparative study ciprofloxacin seems to be more effective in the conjunctival sterilization than both ofloxacin and povidone-iodine. We did not find significantly different conjunctival sterilization effectiveness between povidone-iodine and ofloxacin, but in our series, prepreparation conjunctival flora was more variable in ofloxacin group than that of ciprofloxacin and povidone-iodine group and different types of bacteria rather than CNS were found. Diamond et al.¹⁵ found that intracorneal concentration of ofloxacin was significantly higher than that of ciprofloxacin and greater potency of ciprofloxacin offsets superior penetration of ofloxacin. We did not studied corneal penetration capability of chemicals in this study.

When we consider high variety of bacterial types in preparation eyes managed with ofloxacin, ofloxacin seems to be superior to povidone-iodine for reduction of bacterial flora on the conjunctiva.

To et al.³ reported that 15% and 16% of cultured CNS species were resistant to ciprofloxacin and ofloxacin, respectively. In their series, 29% of cultured S. aureus was found to be resistant to both fluoroquinolones. Pinna et al.¹⁶ reported that 29% of CNS isolates were multiresistant organisms, defined as resistant to 3 or more antibiotics. In their series 7% of isolates were found to be resistant to ciprofloxacin. Postpreparation cultures have the same bacterial isolates as pretreatment cultures in 14.9% of eyes managed with povidone-iodine in our series, which was 1.8% and 19.2% in ciprofloxacin and ofloxacin, respectively. Our results confirm the data published by other authors.

Antibiotic-resistant bacteria, mainly CNS, the most common organisms colonizing the eye, are an important problem, especially in the nosocomial infections. Actually, multiresistant bacteria such as CNS colonize the skin of the hospitalized patients and hospital personnel.¹⁷ Skin colonization serves as a potential reservoir for multiresistant isolates that can cause infections. We found that 5.5%–14% of eyes had different types of isolates in postpreparation period than prepreparation cultures. This should be due to the contamination with resistant bacteria either from the subject conjunctiva or the specimens during sampling and handling.

The goal of the surgical prophylaxis should be to eliminate or reduce the ocular surface flora perioperatively. In our study we observed that ciprofloxacin seems to be more effective in conjunctival bacterial eradication than both ofloxacin and povidone-iodine, but higher ocular penetrance of ofloxacin and effectiveness of povidone-iodine against all fungi, viruses, and spores are their advantages for preoperative preparation for ophthalmic surgery.

Footnotes

Author Disclosure Statement

None of the authors has a financial or proprietary interest in any material or method mentioned.

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