Br J Ophthalmol: first published as 10.1136/bjo.72.3.206 on 1 March 1988. Downloaded from

British Journal of Ophthalmology, 1988, 72, 206-209

Effect of preoperative on the normal eyelid and conjunctival bacterial flora

PETER B TAYLOR, KHALID F TABBARA, AND EILEEN M BURD From the Department ofOphthalmology, College ofMedicine, King Saud University and the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia

SUMMARY A randomised trial comparing the topical application of 1% fusidic acid with 0*3% solution in the reduction of the normal preoperative lid and conjunctival microbial flora was performed. Forty patients awaiting cataract surgery were randomly divided into two groups consisting of 20 patients each. The first group received a 1% microcrystalline suspension of fusidic acid, the second 0.3% gentamicin to the preoperative eye every two hours between 0600 and 2400 daily for 48 hours preoperatively. Cultures were obtained from both the lid margins and the conjunctival sac of both groups prior to therapy and again in the operating theatre before surgery. Microbiological identification and colony counts were performed by standard laboratory methods. epidermidis was the commonest micro-organism isolated. Statistical analysis revealed no significant differences in the ability of a 1% microcrystalline suspension of fusidic acid and 0.3% gentamicin in eliminating or reducing the normal preoperative conjunctival or lid flora.

Postoperative , especially endophthalmitis, from the products of the are serious complications of intraocular surgery. The Fusidium coccineum. It is chemically related to http://bjo.bmj.com/ aetiological agents of postoperative infections are P, but it has no cross-reactivity with often introduced intraocularly from the patient's own any other commonly used . Fusidic acid normal eyelid and/or conjunctival bacterial flora was introduced in Europe in 1962 and has been during surgical manipulation.'2 To minimise the risk effective against a wide range of Gram-positive of postoperative infections prophylactic topical anti- organisms, with low activity against Gram-negative microbial therapy is usually administered prior to organisms and fungi, in the concentration range of intraocular surgery. the relatively low blood levels acquired with the on September 28, 2021 by guest. Protected copyright. Bactericidal antibiotics are usually preferred for recommended systemic doses.3 It has the greatest use in prophylaxis. To ensure protection from both antistaphylococcal (both IP lactamase positive Gram-positive and Gram-negative micro-organisms and negative) activity of any agent a broad-spectrum antibiotic such as gentamicin or currently available.' , or a combination of and The topical ophthalmic fusidic acid preparation polymyxin, are frequently used in prophylaxis. The (Fucithalmic) would be expected to be effective choice of a topical prophylactic antibiotic should be against a wide range of Gram-positive organisms347 based on its efficacy against the causative agent, its and some Gram-negative organisms34' in view of its low toxicity, low risk of systemic sensitisation, and minimal inhibitory and minimal bactericidal concen- reasonable cost. trations. Fusidic acid can penetrate avascular tissue It has been well established that Gram-positive even in large collections of pus.9 The topical prep- organisms, particularly staphylococci, are the main aration has little or no epithelial toxicity and covers constituents of the normal ocular flora and are also organisms such as spp. that are missed the predominant cause of postoperative infections.2 by other traditionally used prophylactic aminoglyco- Fusidic acid (Fucidin) is a steroidal antibiotic isolated sides. The following trial was undertaken to compare Correspondence to Khalid F Tabbara, MD, King Khaled Eye the efficacy of Fucithalmic with gentamicin in the Specialist Hospital, PO Box 7191, Riyadh 11462, Saudi Arabia. preoperative prophylactic reduction of ocular flora. 206 Br J Ophthalmol: first published as 10.1136/bjo.72.3.206 on 1 March 1988. Downloaded from

Effect ofpreoperative fusidic acid on the normal eyelid and conjunctival bacterialfiora20207

Material and methods Table 1 Conjunctival isolatesfrom cultures taken before and after treatment withfusidic acid orgentamicin

To evaluate the potential use of fusidic acid for Therapy Pretreatment Post-treatment proph' axis prior to intraocular surgery 40 consecu- tive patients awaiting cataract surgery were randomly Staphylococcus Other* Staphylococcus Other* divided into two groups of 20 patients each. The first species species group received topical 1% fusidic acid microcrystal- Fusidic acid 13/20 8/20 1/20 0/20 line suspension (Fucithalmic) and the second group (65%) (40%) (5%) (0%) received 0-3% gentamicin ophthalmic solution in the Gentamicin 9/20 3/20 1/20 1/20 preoperative eye. The drops were administered one (45%) (15%) (5%) (5%) drop every two hours beginning at 0600 until 2400 for *Other includes cultures with more than one organism isolated. 48 hours prior to surgery, the last dose being given at midnight the night before surgery. Phisohex face scrubs were given the evening before and scant growth of Citrobacter diversus. Of the remain- again on the morning of surgery as part of the ing 18 patients one had only light growth of Strepto- standard preoperative procedure. coccus acidominimus, one grew mixed scant to light To assess the antimicrobial effectiveness of the Str. morbillorum and Corynebact~erium species; 16 of prophylactic medication cultures for bacteriological the 40 patients (40%) showed no growth prior to evaluation were taken before beginning prophylactic initiation of therapy. treatment and again in the operating room just prior Following treatment only one eye in each of the to preparation for surgery. Cultures of the eyelids antibiotic treatment groups showed growth of were obtained by rubbing a sterile cotton-tipped Staphylococcus epidermidis. In both of these cases swab moistened in trypticase soy broth from the the organism was resistant to the antibiotic used for canthal eyelid margin of the lower eyelid to the that eye. In the fusidic-acid-treated eyes the quantity temporal margin and back again. Conjunctival of growth decreased from a pretreatment of light to a cultures were taken in a similar manner while pulling post-treatment of scant growth. In the gentamicin- down on the lower eyelid with care to avoid the lid treated eye no organisms were found before treat- margins and lashes. The specimens were streaked on ment; but moderate growth of Staph. epidermidis was to 5% sheep blood agar and chocolate agar plates. found after treatment. The other organisms (Coryne- Cultures were incubated at 370C and observed at 24 bacterium and M. morganii) found before treatment and 48 hours. in the patients using fusidic acid were completely http://bjo.bmj.com/ The number of bacterial colonies growing were eliminated, as were the organisms (Streptococcus counted and quantitated with findings of less than 50 species, Staph. aureus, and Citrobacter diversus) in colonies graded as scant to light growth, 50 to 149 as the gentamicin-treated patients. moderate, and 150 or more as heavy growth. The In one gentamicin-treated patient, however, bacteria were identified by standard bacteriological cultures after treatment revealed 94 colonies of techniques. Antimicrobial sensitivity testing was Micrococcus species resistant to gentamicin which

done by the modified Kirby-Bauer disc diffusion were isolated from the eye of a pretreatment- on September 28, 2021 by guest. Protected copyright. method using Mueller Hinton agar. Statistical negative patient (Table 1). analysis of the data was performed by the Wilcoxon signed rank test and the hinominal test for propor- L ID MARGINS tions to evaluate the significance of the results. The eyelids of all patients showed bacterial growth before treatment. Of the 40 eyes 37 (93%) revealed Results moderate to heavy growth of Staphylococcus epidermidis. Of those with positive cultures for CONJUNCTIVA Staph. epidermidis 9 (24%) had concomitant growth The cultures of the conjunctivae from 22 of the 40 of other organisms. Of those eyelids giving a mixed patients (55%) revealed moderate pretreatment growth one gave a moderate growth of M. morganii growth of Staphylococcus epidermidis; six of 22 and species, one scant growth (27%) had concomitant growth of other organisms. of Bacillus species, one scant to light growth of Of the mixed growth cultures, two included light and Corynebacterium species, growth of Corynebacterium species, one with light one moderate growth of Corynebacterium species, growth of a streptococcus (alphahemolytic), one with one moderate growth of C. diversus, one scant light to moderate growth of both Morganella growth of Str. morbillorum, Enterobacter morganii and Corynebacterium species, one with agglomerans, and heavy growth of Corynebacterium light growth of , and one had species, one moderate growth of Moraxella species, Br J Ophthalmol: first published as 10.1136/bjo.72.3.206 on 1 March 1988. Downloaded from

208 Peter B Taylor, Khalid F Tabbara, and Eileen M Burd

Table 2 Lid margin isolatesfrom cultures taken before and after treatment withfusidic acid orgentamicin Therapy Pretreatment Post-treatment Staphylococcus Other* Staphylococcus Other* species species A B Ct A B Ct Fusidic acid 2/20 2/20 16/20 4/20 7/20 0/20 1/20 0/20 (10%) (10%) (80%) (20%) (35%) (0%) (5%) (0%) Gentamicin 2/20 8/20 9/20 6/20 3/20 1/20 0/20 1/20 (10%) (40%) (45%) (30%) (15%) (5%) (0%) (5%)

*Other includes those cultures with more than one organism isolated. tA=colonies quantitated at scant to light growth (1-49 colonies). B=moderate growth (50-149 colonies). C= heavy growth (150 colonies or more). and two eyes gave scant and heavy growth of Staph. found in 10-5% of gentamicin-treated eyes and 28% aureus. The lids of three of the 40 eyes (7%) gave of Fucithalmic-treated eyes. One lid margin was pure growths of other organisms, two with heavy found to have heavy growth of resistant Staph. aureus growth of Staph. aureus and one with moderate to organisms that were completely eliminated by topical heavy mixed growth of Staph. acidominimus and Fucithalmic. Other bacteria, including a-haemolytic Corynebacterium species. streptococcus, Bacillus spp, Klebsiella pneumoniae, Post-treatment lid margin cultures of those with and Morganella morganii which demonstrated resist- pretreatment Staph. epidermidis showed complete ance in vitro were eliminated from the eyelids and elimination (no growth) in 10 of the 18 (55%) conjunctiva by Fucithalmic. Resistance testing in patients receiving fusidic acid and in 15 of the 19 vitro is based on projected levels achieved by (79%) receiving gentamicin. Of the remainder of systemic antibiotic administration and frequently those with post-treatment Staph. epidermidis, only 14 does not correlate with susceptibility of the organism of the 37 (38%) showed a significant reduction in to topically applied drugs. However, such testing growth quantity for the two different antibiotics provides useful information on the antibiotic to (Table 2). which the organism is most sensitive. Coryne-

All other organisms found in pretreatment cultures bacterium spp. were also eliminated, though suscept- http://bjo.bmj.com/ were completely eliminated in cultures taken after ibility testing in vitro was not performed. treatment. However, in one patient receiving gentamicin a Micrococcus species resistant to Discussion gentamicin was isolated that was not present in pretreatment cultures. The choice of antibiotic to be used for prevention of Statistical analysis comparing pretreatment and postsurgical infections should be based on knowledge post-treatment counts using Staphylococcus species of the bacteria usually involved and their general growth as a sample showed significant reduction in patterns of susceptibility to antibiotics. This know- on September 28, 2021 by guest. Protected copyright. bacterial flora for both conjunctiva and lid margins ledge is difficult for any one institution to have whether treated by fusidic acid or gentamicin (Tables because of the relatively few cases encountered; we 1 and 2) (conjunctiva: fusidic acid, p=0-0005, therefore depend on reports of retrospective studies gentamicin, p=0-0117; lid margin: fusidic acid, for such information. Many of the early series p=O-OOOl, gentamicin, p=0.0007). No significant reporting postoperative ocular infections did not differences (eyelids, p=0-478; conjunctiva, p=097) mention the causative organisms or implicated were found when comparing post-treatment colony organisms from improperly sterilised surgical instru- counts of fusidic-acid-treated versus gentamicin- ments, contaminated solutions, or bacteria from skin treated eyes. or nasal mucosa of surgeon or operating room staff. With improvements in sterile technique, sterilisation SUMMARY OF RESULTS of surgical instruments, and strict quality control of In the present study fusidic acid either eliminated or solutions and medications, the normal ocular flora reduced the colonies of Staph. epidermidis present in have been implicated as the source of postoperative all but one of the eyes studied. The one case in which in most cases"-' and bacteriophage typing there was an increase in the number of Staph. of strains has confirmed this suspicion in one epidermidis colonies along the lid margins involved a study. 4 resistant strain. Resistance of Staph. epidermidis was Antibiotics used topically as prophylaxis before Br J Ophthalmol: first published as 10.1136/bjo.72.3.206 on 1 March 1988. Downloaded from

Effect ofpreoperativefusidic acid on the normal eyelid and conjunctivalbacterialfiora 209 intraocular surgery do not always completely eradi- tive in preoperative prophylactic antimicrobial cate the indigenous eyelid and conjunctival flora.'56 therapy. However, a review ofthe literature clearly shows that The topical fusidic acid 1% viscodrops were kindly supplied by Leo the incidence of postsurgical endophthalmitis was Pharmaceuticals Ltd, Denmark. markedly reduced from an average of 1-3% (range, We thank Robert L Phillips, PhD, and William Greer, PhD, of 0 44% to 3-16%) in patients not given prophylactic King Faisal Specialist Hospital and Research Centre for the help antibiotics, to an average of0335% (range, 0 00% to with statistical analysis of the data. 0.57%) in patients who did receive prophylactic References antibiotics.2 The organisms most commonly recovered in cases 1 Debnath SC, Talukder MAS, Bartlett FW. Effect of pre- operative antibiotics on bacterial colony counts of the con- of postsurgical endophthalmitis include primarily junctival sac. J Ocul Ther Surg 1985; 4: 122-4. Staph. aureus and Staph. epidermidis. Streptococcus 2 Starr MB. Prophylactic antibiotics for ophthalmic surgery. Surv spp., Proteus spp., and spp. are also Ophthalmol 1983; 27: 353-73. commonly seen, although less frequently."-'4 17 3 Godtfredson WO, Roholt K, Tybring L. Fucidin: a new orally active antibiotic. Lancet 1962, ii: 137-48. Studies of the efficacy of topical antibiotics in 4 Barber M, Waterworth P. Antibacterial activity in vitro of reducing normal ocular bacterial flora have shown fucidin. Lancet 1962; i: 931-2. that antibiotics vary widely in their ability to reduce 5 Newmann RL, Bhat KM, Hackney R, et al. Fusidic acid: or eliminate the normal ocular flora. Although laboratory and clinical assessment. Br Med J 1962; ii: 1645-7. 6 King K, Brady LM, Harkness JL. Gentamicin-resistant staphy- various dosage schedules were used, the superiority lococci. Lancet 1981; ii: 698-9. of gentamicin 0.3% solution over the following other 7 Tabbara KF, Lawson NA, Burd EM. In vitro susceptibility to agents has been clearly demonstrated: chloram- fusidic acid ofclinically significant isolates from ocular infections. phenicol 05% solution;' "8"9 sulphacethamide 30% Saudi MedJ 1987; 8(2): 167-70. 8 Jacobsen J. The sensitivity of eye towards solution;2 sulphametiazole 4% solution; bacitracin fucidin, , and given as MIC values. 1%- 0-5% solution; neomycin-polymyxin- Bacteriologic Department, Leo Pharmaceuticals Ltd: May 1980. B-gramicidin solution; ristocetin sulphate 05%- 9 Taylor G, Bloor K. Antistaphylococcal activity of fucidin. 025% solution; Lancet 1962; i: 935-7. 10 Crosbie RB. Treatment of staphylococcal infections with chloride 3%-polymyxin B 0-1% ointment;'6 sofra- Fucidin. Br Med J 1963; i: 788-94. mycin 0-5% solution; and sulphate 10% 11 Valenton MJ, Brubaker RF, Allen HF. Staphylococcus epider- solution.'9 In addition, gentamicin 03% ointment midis (albus) endophthalmitis. Arch Ophthalmol 1973; 89: 94-6. was as effective as gentamicin 0-3% solution in one 12 Baum JL, Rao G. Treatment of post-cataract endophthalmitis with periocular and systemic antibiotics and . http://bjo.bmj.com/ study.'8 Gentamicin is an antibiotic whose anti- Ophthalmology 1976; 81: 151-7. bacterial spectrum includes most normal ocular flora, 13 Forster RK, Abbott RL, Gelender H. Management of infectious particularly staphylococci. endophthalmitis. Ophthalmology 1980; 87: 313-8. The present study showed that fusidic acid 1% 14 Locatcher-Khorazo D, Sullivan N, Gutierrez E. Staphylococcus aureus isolated from normal and infected eyes. Arch Ophthalmol microcyrstalline suspension was as effective as genta- 1967; 77: 370-7. micin in reducing or eliminating Staph. epidermidis 15 Whitney CR, Anderson RP, Allansmith MR. Preoperatively present on the lid margin or in the conjunctival fornix administered antibiotics: their effect on bacteria counts of the of presurgical cataract patients when administered eyelids. Arch Ophthalmol 1972; 87: 155-60. on September 28, 2021 by guest. Protected copyright. two 16 Fahmy JA. Bacterial flora in relation to cataract extraction: V. every hours from 0600 to 2400 for 48 hours prior Effects of topical antibiotics on the preoperative conjunctival to surgery. Fusidic acid applied topically penetrates flora. Acta Ophthalmol (Kbh) 1980; 58: 567-75. the cornea well (Taylor and colleagues, unpublished 17 Allen HF, Mangiaracine AB. Bacterial endophthalmitis after data) and is bactericidal in concentrations close to the cataract extraction: II. Incidence in 36000 consecutive opera- tions with special reference to preoperative topical antibiotics. minimal inhibitory concentration. When topically Arch Ophthalmol 1974; 91: 3-7. applied, this microcrystalline suspension of fusidic 18 Burns RP, Oden M. Antibiotic prophylaxis in cataract surgery. acid is effective against most Gram-positive bacteria Trans Am Ophthalmol Soc 1972; 70: 43-57. such as Streptococcus spp. which can be missed by 19 Burns RP. Effectiveness study ofantibiotics. In: Leopold IH, ed. more traditional preoperative Symposium on ocular therapy St Louis: Mosby, 1972; 5: 105-12. therapy. This antibiotic may provide another alterna- Acceptedforpublication 8 January 1987.