Conjunctivitis is a commonly encountered disease characterized by conjunctival edema and hyperemia and usually accompanied by variable types of discharge.1 Bacterial conjunctivitis was reported as the second most common type of infectious conjunctivitis after viral infection,2–4 and the first cause of acute conjunctivitis in children representing 50% to 75% of cases.5,6
These cases are usually managed initially by general practitioners and the antibiotic treatment is empirically selected without preceding microbiological studies.7,8 The microbiological aspects of bacterial conjunctivitis were previously studied and many organisms were incriminated (eg, Staphylococcus aureus, Staphylococcus epidermidis, and Haemophilus influenzae).9,10 This prospective study was performed to analyze the microbiological aspects of infantile bacterial conjunctivitis resistant to initial empirical topical antibiotic therapy in Egypt.
Patients and Methods
This was a prospective study that included infants referred to the outpatient clinic of Tanta University Eye Hospital from January 2014 to December 2016, with a clinical diagnosis of bacterial conjunctivitis that failed to improve after 2 weeks of treatment with empirical topical antibiotic drops. The study followed the tenets of the Declaration of Helsinki, informed consents were obtained from the legal guardians of all participants, and the study was approved by the institutional ethical committee. Whenever possible, both the duration and the exact type of empirical antibiotic used prior to presentation and its dose were recorded. Thorough ophthalmological examination was done for all patients to exclude other types of conjunctivitis and other causes of red eye. Patients with conditions known to result in recurrent or persistent ocular discharge such as congenital nasolacrimal duct obstruction, congenital entropion, and epiblepharon were all excluded from the study.
The previous treatment was stopped for 48 hours and conjunctival swabs were obtained from all patients for bacterial culture and antibiotic sensitivity testing as follows. The skin around the eye was cleaned with sterile gauze moistened with sterile saline, then it was disinfected with povidone-iodine solution. The tip of a sterile swab was then passed over the lower fornix, avoiding the eyelashes and the eyelid margin. The swab was then wiped over the surface of the plates of the following culture media: (1) MacConkey agar for detection of Enterobacteriaceae; (2) blood agar for detection of staphylococci and streptococci; (3) chocolate agar for detection of Neisseria gonorrhoeae and Haemophilus influenzae; (4) Loffler's agar for detection of Moraxella species and other fastidious microorganisms; and (5) Sabouraud dextrose agar for detection of Candida and Aspergillus species.
The plates were incubated aerobically at 30°C to 35°C for 48 hours except chocolate agar, which was incubated in carbon dioxide condition at 30°C to 35°C for 48 hours. The plates for fungal growth were incubated at 20°C to 25°C for 72 hours.
After the specified incubation period, different forms of microbial growth, if any, were identified using the approved identification system. Sensitivity testing was performed on bacterial isolates using 36 different types of antibiotics.
To avoid distorting the results, the fellow eyes in bilateral cases were reported only if they revealed different bacterial growth.
The study included 92 eyes of 86 infants: 47 (54.65%) males and 39 (45.35%) females. The patients' ages ranged from 4 to 6 months. Thirty-nine patients (45.35%) revealed a history of using tobramycin eye drops without improvement, whereas 26 patients (30.23%) used fusidic acid and 21 patients (24.42%) could not tell which antibiotic was used. Fourteen cases had bilateral conjunctivitis and 72 cases had unilateral conjunctivitis. After 48 hours of incubation, 8 of the bilateral cases (57.1%) showed the presence of the same organism in both eyes, whereas in 6 cases (42.9%) each eye showed the presence of different organisms and was recorded as different isolates. Forty-five samples (48.9%) revealed the presence of a solitary organism, 35 samples (38%) showed mixed infection with two different organisms, 9 samples (9.8%) showed mixed infection with three different organisms, and 3 samples (3.3%) were sterile (negative cultures), with a total number of 142 identified bacterial growths. Staphylococcus aureus was the most commonly isolated organism either separately or in the course of a mixed infection (35 samples; 24.65%). The growth of Streptococcus pneumoniae was verified in 31 samples (21.83%), Pseudomonas aeruginosa in 18 samples (12.68%), and coagulase-positive Staphylococcus aureus in 13 samples (9.15%). Candida albicans was harvested in 14 samples (15.22%) (Table 1).
Different Types of Microorganisms Identified in the Study
Antibiotic sensitivity testing was performed on all isolated bacterial colonies against 36 different antibiotics. Most bacterial growths showed high sensitivity to levofloxacin, which eradicated as many as 108 growths (76.1%). Ciprofloxacin, ofloxacin, and norfloxacin were highly effective against 105 (74%), 104 (73.2%), and 102 (71.8%) growths, respectively. Chloramphenicol was found to be highly effective against 100 growths (70.4%), vancomycin against 94 growths (66.2%), and amikacin against 93 growths (65.5%).
On the other hand, 130 (91.5%) growths were resistant to imipenem. Resistance to meropenem was reported in 128 (90.1%) growths, fusidic acid in 125 (88%) growths, piperacillin in 124 (87.3%) growths, and penicillin in 115 (81%) growths (Table 2).
Sensitivity of Identified Microorganisms to 36 Tested Antibiotics
Infective conjunctivitis is a common condition that is more commonly encountered in infants and school-aged children.11 Bacterial conjunctivitis is usually characterized by a purulent or, more commonly, a mucopurulent discharge.12 Many cases may be presented with nonspecific presentations, and the type of discharge may not lead to a correct diagnosis. Rietveld et al.13 reported that 35% of culture-proven cases of bacterial conjunctivitis had serous or no discharge. It was found that the combined presence of eyelid mattering, absence of itching, and lack of history of conjunctivitis is strong evidence of bacterial conjunctivitis.14 Bacterial conjunctivitis diagnosis is based mainly on clinical findings and microbiological examination is not needed routinely in clinically suspected cases.11 A conjunctival swab is recommended if treatment fails, and is preferred to be taken a few days after stopping the previously used medications.15
The most common organisms incriminated in bacterial conjunctivitis were reported in many studies. Seal et al.7 found that Staphylococcus aureus, Coliform species, Haemophilus influenzae, and Streptococcus viridians were the most commonly found causative organisms in infants 1 year old or younger. Mahajan16 found Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae more commonly isolated in their cases of bacterial conjunctivitis. Epling and Smucny17 reported that the causative organism in children is mainly Haemophilus influenzae, followed by Streptococcus pneumoniae and Moraxella catarrhalis.17 The microbiological aspects of resistant infantile bacterial conjunctivitis not responding to empirical antibiotic treatment were not studied before. In this study, the most commonly isolated organisms were coagulase-negative Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and coagulase-positive Staphylococcus aureus. Mixed infections by two different organisms were reported in 38% and by three organisms in 9.8% of cases.
Jefferis et al.18 found that acute conjunctivitis can be considered as a self-limiting condition that does not require antibiotic treatment. They found a significant benefit from antibiotic treatment among patients with purulent discharge or mild severity redness. Other studies reported that topical antibiotic treatment of bacterial conjunctivitis increases the cure rate in patients with positive cultures, decreases the risk of spreading infection, and shortens the course of the disease.11,19 In Egypt, infants and children with conjunctival discharge are usually prescribed empirical topical antibiotic eye drops such as tobramycin or fusidic acid to gain the benefits of shortening the course of the disease and limiting the spread of infection.
In many studies, no significant difference was found between broad-spectrum antibiotic drops in patients clinically diagnosed as having bacterial conjunctivitis.20,21 The choice of antibiotic drops is based on availability, patient allergy, side effects, and costs.8,11 According to sensitivity studies, some authors recommended the use of chloramphenicol, ciprofloxacin, tobramycin, fusidic acid, and gatifloxacin.10,22,23,24 Some clinical studies have reported better treatment compliance by using fusidic acid.21,23 Due to the risk of serious complications such as aplastic anemia, topical chloramphenicol is rarely prescribed in the United States.25 On the other hand, two international case–control studies involving a population of approximately 40 million people identified more than 400 cases of aplastic anemia, and none of them was using chloramphenicol eye drops.26 In a British general practice database review, Lancaster et al.27 found only a small risk of serious hematological side effects related to chloramphenicol eye drops (3 per 674,148 prescriptions) and concluded that the continued use of topical chloramphenicol is a safe clinical option.
In this study, the microorganisms isolated from infants not improving with initial empirical treatment were found to be highly sensitive to fluoroquinolones (levofloxacin, ciprofloxacin, ofloxacin, and norfloxacin), followed by chloramphenicol, vancomycin, and amikacin. The use of fluoroquinolones in children is controversial due to safety concerns. The possible occurrence of musculoskeletal complications (even if reported as low as 2% or less) resulted in limited use of this group in children.28 It was reported that arthralgia and arthropathy rarely occur in children using systemic fluoroquinolones and resolve completely after drug cessation without any long-term complications.29 On the other hand, other authors reported that topical fluoroquinolone eye drops such as ciprofloxacin, levofloxacin, and ofloxacin are safe and effective in children with bacterial conjunctivitis.30,31
The isolated pathogens were found to be resistant to carbapenems (imipenem and meropenem), fusidic acid, piperacillin, and penicillin. Increased resistance to fusidic acid was reported previously and explained by the long-term topical use.32,33 The currently used in vitro sensitivity tests use lower antibiotic concentrations than that delivered in the conjunctiva through topical use, which may explain the clinical improvement despite in vitro resistance.11 The resistance to fusidic acid found in this study can be explained by the previously mentioned factors in addition to the antibiotic misuse patterns.
Increased bacterial resistance to antibiotics such as tobramycin, gentamycin, chloramphenicol, and fluoroquinolones has been reported.5,6,34 It was previously recommended that fluoroquinolones and aminoglycosides should be used only in cases of bacterial conjunctivitis not responding to fusidic acid or chloramphenicol initial treatment.11 According to the results of antibiotic sensitivity found in this study, it is recommended to change the current empirical antibiotic eye drops used in infantile conjunctivitis in Egypt from tobramycin or fusidic acid to other agents such as chloramphenicol, which is safe, inexpensive, readily available, and more effective. These results also provide strong evidence that fluoroquinolones can be reserved for resistant cases of bacterial conjunctivitis as long as other safe and effective agents are available.
- Leibowitz HM. The red eye. N Engl J Med. 2000;343:345–351. doi:10.1056/NEJM200008033430507 [CrossRef]
- Stenson S, Newman R, Fedukowicz H. Laboratory studies in acute conjunctivitis. Arch Ophthalmol. 1982;100:1275–1277. doi:10.1001/archopht.1982.01030040253009 [CrossRef]
- Woodland RM, Darougar S, Thaker U, et al. Causes of conjunctivitis and keratoconjunctivitis in Karachi, Pakistan. Trans R Soc Trop Med Hyg. 1992;86:317–320. doi:10.1016/0035-9203(92)90328-A [CrossRef]
- Fitch CP, Rapoza PA, Owens S, et al. Epidemiology and diagnosis of acute conjunctivitis at an inner-city hospital. Ophthalmology. 1989;96:1215–1220. doi:10.1016/S0161-6420(89)32749-7 [CrossRef]
- Block SL, Hedrick J, Tyler R, et al. Increasing bacterial resistance in pediatric acute conjunctivitis (1997–1998). Antimicrob Agents Chemother. 2000;44:1650–1654. doi:10.1128/AAC.44.6.1650-1654.2000 [CrossRef]
- Buznach N, Dagan R, Greenberg D. Clinical and bacterial characteristics of acute bacterial conjunctivitis in children in the antibiotic resistance era. Pediatr Infect Dis J. 2005;24:823–828. doi:10.1097/01.inf.0000178066.24569.98 [CrossRef]
- Seal DV, Barrett SP, McGill JI. Aetiology and treatment of acute bacterial infection of the external eye. Br J Ophthalmol. 1982;66:357–360. doi:10.1136/bjo.66.6.357 [CrossRef]
- Azari AA, Barney NP. Conjunctivitis: a systematic review of diagnosis and treatment. JAMA. 2013;310:1721–1729. doi:10.1001/jama.2013.280318 [CrossRef]
- Seibel W, Ruprecht KW. Bacteriological findings in conjunctival smears [article in German]. Klin Monbl Augenheilkd. 1983;183:60–62. doi:10.1055/s-2008-1054875 [CrossRef]
- Hørven I. Acute conjunctivitis: a comparison of fusidic acid viscous eye drops and chloramphenicol. Acta Ophthalmol (Copenh). 1993;71:165–168. doi:10.1111/j.1755-3768.1993.tb04983.x [CrossRef]
- Høvding G. Acute bacterial conjunctivitis. Acta Ophthalmol. 2008;86:5–17. doi:10.1111/j.1600-0420.2007.01006.x [CrossRef]
- Rubenstein JB, Jick SL. Disorders of the conjunctiva and limbus. In: Yannof J, Duker JS (eds.). Ophthalmology, 2nd ed. St. Louis: Mosby; 2004:397–412.
- Rietveld RP, ter Riet G, Bindels PJ, Sloos JH, van Weert HC. Predicting bacterial cause in infectious conjunctivitis. BMJ. 2004;329:206–210. doi:10.1136/bmj.38128.631319.AE [CrossRef]
- Rietveld RP, van Weert HC, ter Riet G, Bindels PJ. Diagnostic impact of signs and symptoms in acute infectious conjunctivitis: systematic literature search. BMJ. 2003;327:789. doi:10.1136/bmj.327.7418.789 [CrossRef]
- Mannis MJ, Plotnik RD. Bacterial conjunctivitis. In: Tasman M, Jaeger EA (eds.). Duane's Clinical Ophthalmology, vol. 4. Philadelphia: Lippincott, Williams & Wilkins; 2005:1–11.
- Mahajan VM. Aetiology and treatment of acute bacterial infection of the external eye. Br J Ophthalmol. 1983;67:191–194. doi:10.1136/bjo.67.3.191 [CrossRef]
- Epling J, Smucny J. Bacterial conjunctivitis. Clin Evid. 2005;2:756–761.
- Jefferis J, Perera R, Everitt H, et al. Acute infective conjunctivitis in primary care: who needs antibiotics? An individual patient data meta-analysis. Br J Gen Pract. 2011;61:e542–e548. doi:10.3399/bjgp11X593811 [CrossRef]
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- Wall AR, Sinclair N, Adenis JP. Comparison of Fucithalmic (fusidic acid viscous eye drops 1%) and Noroxin (norfloxacin ophthalmic solution 0.3%) in the treatment of acute bacterial conjunctivitis. J Drug Assess. 1998;1:549–558.
- Jackson WB, Low DE, Dattani D, Whitsitt PF, Leeder RG, MacDougall R. Treatment of acute bacterial conjunctivitis: 1% fusidic acid viscous drops vs. 0.3% tobramycin drops. Can J Ophthalmol. 2002;37:228–237. doi:10.1016/S0008-4182(02)80114-4 [CrossRef]
- Miller IM, Wittreich JM, Cook T, Vogel R. The safety and efficacy of topical norfloxacin compared with chloramphenicol for the treatment of external ocular bacterial infections. The Norfloxacin-Chloramphenicol Ophthalmic Study Group. Eye (Lond). 1992;6:111–114. doi:10.1038/eye.1992.23 [CrossRef]
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- Yee RW, Tepedino M, Bernstein P, et al. A randomized, investigator-masked clinical trial comparing the efficacy and safety of gatifloxacin 0.3% administered BID versus QID for the treatment of acute bacterial conjunctivitis. Curr Med Res Opin. 2005;21:425–431. doi:10.1185/030079905X30699 [CrossRef]
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- Wiholm BE, Kelly JP, Kaufman D, et al. Relation of aplastic anaemia to use of chloramphenicol eye drops in two international case-control studies. BMJ. 1998;316:666. doi:10.1136/bmj.316.7132.666 [CrossRef]
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Different Types of Microorganisms Identified in the Study
|Microorganism||No. of Samples in Which It Was Identified|
|Coagulase-negative Staphylococcus aureus||35|
|Coagulase-positive Staphylococcus aureus||13|
Sensitivity of Identified Microorganisms to 36 Tested Antibiotics
|Antibiotic||No. of Organisms Highly Sensitive to It (%)||No. of Organisms Moderately Sensitive to It (%)||No. of Organisms Resistant to It (%)|
|1. Levofloxacin||108 (76.1)||7 (4.9)||27 (19)|
|2. Ciprofloxacin||105 (74)||17 (12)||20 (14)|
|3. Ofloxacin||104 (73.2)||18 (12.7)||20 (14.1)|
|4. Norfloxacin||102 (71.8)||19 (13.4)||21 (14.8)|
|5. Chloramphenicol||100 (70.4)||7 (4.9)||35 (24.7)|
|6. Vancomycin||94 (66.2)||0 (0)||48 (33.8)|
|7. Amikacin||93 (65.5)||31 (21.8)||18 (12.7)|
|8. Cefepime||92 (64.8)||9 (6.3)||41 (28.9)|
|9. Gatifloxacin||90 (63.4)||17 (12)||35 (24.6)|
|10. Linezolid||83 (58.5)||2 (1.4)||57 (40.1)|
|11. Cefoperazone||79 (55.6)||13 (9.2)||50 (35.2)|
|12. Bacitracin||76 (53.5)||5 (3.5)||61 (43)|
|13. Rifampicin||72 (50.7)||18 (12.7)||52 (36.6)|
|14. Tobramycin||69 (48.6)||47 (33.1)||26 (18.3)|
|15. Clindamycin||69 (48.6)||5 (3.5)||68 (47.9)|
|16. Gentamycin||68 (47.9)||37 (26.05)||37 (26.05)|
|17. Ceftazidime||63 (44.4)||25 (17.6)||54 (38)|
|18. Ceftriaxone||62 (43.7)||23 (16.2)||57 (40.1)|
|19. Azithromycin||53 (37.3)||12 (8.5)||77 (54.2)|
|20. Erythromycin||52 (36.6)||11 (7.8)||79 (55.6)|
|21. Cefotaxime||51 (35.9)||17 (12)||74 (52.1)|
|22. Clarithromycin||50 (35.2)||8 (5.6)||84 (59.2)|
|23. Cefoxitin||48 (33.8)||16 (11.3)||78 (54.9)|
|24. Cefuroxime||44 (31)||23 (16.2)||75 (52.8)|
|25. Cefaclor||42 (29.6)||6 (4.2)||94 (66.2)|
|26. Neomycin||39 (27.5)||46 (32.4)||57 (40.1)|
|27. Cefixime||37 (26.1)||4 (2.8)||101 (71.1)|
|28. Oxytetracycline||28 (19.7)||18 (12.7)||96 (67.6)|
|29. Ampicillin||27 (19)||5 (3.5)||110 (77.5)|
|30. Aztreonam||25 (17.6)||6 (4.2)||111 (78.2)|
|31. Penicillin||25 (17.6)||2 (1.4)||115 (81)|
|32. Tetracycline||24 (16.9)||26 (18.3)||92 (64.8)|
|33. Piperacillin||15 (10.6)||3 (2.1)||124 (87.3)|
|34. Fusidic acid||13 (9.2)||4 (2.8)||125 (88)|
|35. Meropenem||13 (9.2)||1 (0.7)||128 (90.1)|
|36. Imipenem||12 (8.5)||0 (0)||130 (91.5)|