Differentiating Bacterial Conjunctivitis from Allergic and Viral Conjunctivitis

Rudolph S. Wagner, MD
Making a definitive diagnosis for a pediatric patient presenting with conjunctivitis can be difficult. Conjunctivitis in the pediatric patient can be mimicked by nasolacrimal duct (NLD) obstruction and caused by allergies, bacteria, and viruses. Because antimicrobial cultures take time and are not always accurate, the diagnosis and treatment of conjunctivitis are often based on the physician’s knowledge regarding the current literature on likely pathogens and clinical experience. Therefore, pediatricians must be aware of the clinical signs and symptoms that can provide a differential diagnosis of conjunctivitis, so that it can be properly treated.

Pediatricians must be aware of the clinical signs and symptoms that can provide a differential diagnosis of conjunctivitis, so that it can be properly treated.
— Rudolph S. Wagner, MD
Nasolacrimal Duct Obstruction
NLD obstruction is always in the differential diagnosis for conjunctivitis during the first year of life. Effort should be made to rule out NLD obstruction as the cause of the patient’s symptoms. With NLD obstruction, the child’s eyelids may be matted together or discharge may be seen along the lashes or down the child’s cheek. However, patients with NLD obstruction present with less conjunctival injection than patients with bacterial conjunctivitis. Also, if the child’s face has been cleaned to prepare the child to see the physician, signs will usually recur during the office visit.

A definitive diagnosis of NLD obstruction can be made by digital massage of the lacrimal sac. When massaged, the nasolacrimal duct will produce a reflux of mucous from the puncta. The fluorescein dye disappearance test is most helpful when the condition is unilateral. After fluorescein dye has been administered to each eye, the dye will take longer to clear from the eye with NLD obstruction.

Presentation of Allergic Conjunctivitis
The number of children presenting to the clinic with allergic conjunctivitis will vary according to the season. Allergic conjunctivitis is caused by an acute type I hypersensitivity to common allergens. Allergic conjunctivitis has a protracted course, with the severity of symptoms waxing and waning throughout the allergy season. This is another way to differentiate allergic conjunctivitis from other forms, as recurrences within a short period of time are unlikely with bacterial or viral conjunctivitis. Symptoms include itchy eyes, watery or stringy discharge, chemosis, eyelid edema, rhinitis, and an “allergic shiner.” Chemosis (swelling of the conjunctiva) can be marked and may cause the cornea to appear as if it is sitting in a depression. In addition to seasonal allergic conjunctivitis, there are vernal limbal or palpebral types. With vernal limbal conjunctivitis, there is an accumulation of eosinophils along the limbus; with vernal palpebral conjunctivitis, large papules form under the conjunctiva of the upper eyelid.

Presentation of Viral Conjunctivitis
Viral conjunctivitis is more common in older children and adults than it is in preschool-aged children. Viral conjunctivitis is highly contagious and is characterized by watery discharge. The amount of vascular injection can be variable. Viral conjunctivitis is usually caused by adenovirus, but can also be caused by other viruses such as herpes simplex virus (HSV).

HSV may be one of the most problematic causes of conjunctivitis. This virus can lead to herpetic keratitis and possibly loss of vision. Corticosteroids, sometimes used as palliative care in cases of viral conjunctivitis caused by other viruses, are contraindicated in conjunctivitis caused by HSV. The disease is almost always unilateral and monocular. Patients with herpetic conjunctivitis may complain of severe pain. The eyelids may also be involved — they can be red, edematous, and display multiple vesicles. The corneal reflex in a patient with herpetic conjunctivitis will be irregular, not be sharp and crisp. Upon close examination, dendrites or small opacities may be observed. Herpetic conjunctivitis should be in the differential whenever a patient is not responding to antibiotic therapy. Patients with conjunctivitis thought to be caused by HSV should always be referred to an ophthalmologist.

Acute hemorrhagic conjunctivitis (AHC) is most commonly caused by a picornavirus, usually Coxsackie A24 or enterovirus 70. The presentation of AHC is often dramatic. The eye will become acutely painful and possibly photophobic even before hemorrhages can be seen. The subconjunctival hemorrhages that characterize this disease begin as petechiae which then coalesce and can involve the entire subconjunctiva. While highly contagious, AHC is self-limiting and its complications are rare.

Presentation of Bacterial Conjunctivitis
Acute bacterial conjunctivitis is most frequently observed among infants, toddlers, and preschool-aged children. One in 8 children has an episode every year, and there are 5 million cases in the United States annually. Bacterial conjunctivitis is a self-limiting disease, typically lasting 7 to 10 days without antibiotic treatment.1-3 For example, in 1 study 83% of children diagnosed with bacterial cconjunctivitis treated with a vehicle washout drop containing no active medication had clinical cures at 7 days.1 Viral conjunctivitis usually lasts longer than bacterial conjunctivitis. If conjunctivitis does not resolve with antibiotics after 3 to 4 days, the physician should suspect that the infection is viral.

Bacterial conjunctivitis is characterized by mucopurulent discharge with matting of the eyelids. Common clinical findings in acute bacterial conjunctivitis include burning and stinging. While bacterial conjunctivitis can present in only one eye, it is usually present in both eyes or will spread to the contralateral eye. Acute bacterial conjunctivitis can be associated with otitis media. When a patient presents with both conjunctivitis and otitis media, systemic antibiotics are indicated.4,5 Like viral conjunctivitis, bacterial conjunctivitis is highly contagious.

Differentiating Bacterial from Viral Conjunctivitis
Bacterial conjunctivitis can be differentiated from viral conjunctivitis based on discharge (mucopurulent vs. watery), age of the affected child (preschool-aged vs. school-aged children), and whether the infection is bilateral or unilateral (Table 1).

Table

Click here for larger version of this Table.

Ocular Pathogens in Bacterial Conjunctivitis
Studies have shown that pediatric acute conjunctivitis is most often caused by bacteria. Viruses and allergies are the second and third most common causes (Figure 1).6,7 The younger the patient, the higher the likelihood of a bacterial etiology of the conjunctivitis.

Figure

Click here for larger version of this Figure.

A variety of studies have been performed to determine the organisms responsible for conjunctivitis. In a study of 95 patients with acute conjunctivitis and 91 control children of similar age, specimens of the lid and conjunctiva were obtained for culture and conjunctival scrapings were stained with Giemsa and Gram stains. Bacterial infections were identified in 80% of patients, viral infections were identified in 13%, and allergies in 2%. No cause could be determined in 5% of patients. Of the patients with bacterial conjunctivitis, Haemophilus influenzae accounted for 58.1% of all bacterial cultures. Streptococcus pneumoniae was the second most common pathogen, accounting for 27.1% of bacteria cultures. Moraxella catarrhalis was isolated from cultures in 8.1% of patients. Staphylococci accounted for 4.1% of cultures and species included Staphylococcus epidermis (2.7%) and other coagulase-negative staphylococci (1.4%). Staphylococci, corynebacteria, and alpha-hemolytic streptococci were the predominant organisms recovered from the lids of control subjects.6

In a prospective study in a children’s hospital emergency department published in 2007, conjunctival swabs were obtained for bacterial culture from 111 patients aged 1 month to 18 years (mean age, 33 months) who presented with red or pink eye and/or the diagnosis of conjunctivitis. Bacterial cultures were positive in 78.4% of the patients tested. Nontypeable H influenzae accounted for 82% of positive cultures, S pneumoniae for 16%, and Staphylococcus aureus for 2%.7 The decrease in the proportion of isolates positive for S pneumoniae compared to the study published in 1993 may be due to pneumococcal conjugate vaccine immunizations.

A prospective observational cohort study at an urban pediatric emergency department was published in 2010. Conjunctival swabs were taken from children aged 6 months to 17 years who presented with conjunctival erythema, eye discharge, or both. The median age was 3 years. Patients were excluded from the study if they had a history of ocular trauma, were exposed to a noxious chemical, wore contact lenses, or had used antibiotics in the previous 5 days. Bacterial cultures were isolated from 64.7% of the 368 patients enrolled in the study. H influenzae accounted for 67.6% of positive cultures, S pneumoniae for 19.7%, and S aureus for 8.0% (Figure 2).8

Figure

Click here for larger version of this Figure.

This study also investigated how it could be determined that conjunctivitis is not likely to be of bacterial etiology. They determined 4 factors that were likely to be associated with cultures that were negative for bacteria:
  • > 6 years of age
  • Presentation in April through November
  • Watery or no discharge
  • No glued eye in the morning
In this study, 92.2% of patients with all of these factors had cultures that were negative for bacteria and 76.4% of those with 3 factors had negative cultures. These data can aid a physician in deciding whether or how to treat a patient in some cases.

While the data in these 3 studies are consistent and compelling, physicians must also remember that atypical outbreaks of bacterial conjunctivitis can occur. Two notable outbreaks of bacterial conjunctivitis have been caused by an atypical strain of S pneumoniae.

The outbreak at Dartmouth College in New Hampshire in 2002 is especially significant because outbreaks of conjunctivitis in college-aged students are usually viral in etiology. From January 1 through February 15, 197 students were diagnosed with conjunctivitis. A viral cause was initially suspected, but conjunctival swabs from 12 students grew S pneumoniae. Because of the high number of cases and the unusual bacterial etiology in college-aged students, an investigation was initiated. Specimens were sent to the Dartmouth-Hitchcock Medical Center for culture and identification. Subcultures of presumed S pneumoniae isolates were then sent to the CDC for further analysis.9

Results of the investigation demonstrated that between January 1, 2002 and April 12, 2002, 698 of the 5,060 students enrolled at Dartmouth College were diagnosed with conjunctivitis. During similar periods in 2000 and 2001, only 66 and 92 students, respectively, were diagnosed with conjunctivitis. During the 2002 outbreak, 34 students suffered repeated infections as defined by visits to the health center for conjunctivitis by the same student that occurred more than 14 days apart. The attack ratio among the 3,682 undergraduates and 1,378 graduate students was 18.7% and 2.5%, respectively. Of the positive cultures, 43.3% grew nonencapsulated pneumococci.9 This outbreak exemplifies that bacterial conjunctivitis can occur in young adults and conjunctivitis should not be assumed to be due to adenovirus in this age group.

Nontypeable pneumococcus also caused an outbreak of bacterial conjunctivitis in Westbrook, Maine later in 2002. From September 20 to December 6, at the index elementary school, a total of 101 students (out of 361) had at least 1 episode of conjunctivitis. Eleven of 20 students tested (55%) had an episode of culture-confirmed pneumococcal conjunctivitis. Additionally, school nurses and child care staff in the community reported an additional 4% of students attending kindergarten through grade 12 at 4 schools, and 9% of children attending 3 community child care centers, having conjunctivitis during this time period.

Among the 53 students with conjunctivitis at other schools, 10 (19%) had a family member at the index school, and seven (29%) of 24 ill child care attendees had a sibling at the index school. Of 15 conjunctival specimens collected from students at other schools, 5 (33%) grew S pneumoniae. The CDC advises, “health care providers and public health officials should be aware that nontypeable S pneumoniae can cause outbreaks of conjunctivitis in school-aged children and college students; outbreaks should be reported to state health departments and the CDC.”10

Antibiotic Resistance and Bacterial Conjunctivitis
In a retrospective cross-sectional study, the microbiology records of all patients (adults and children) with bacterial conjunctivitis seeking treatment at Bascom Palmer Eye Institute in Miami from January 1, 1994 through December 31, 2003 were reviewed. For an eye to have been included in the study, conjunctival swabs must have resulted in a positive culture. Over this 10-year period in South Florida, the most common isolate from the 2,408 consecutive swabs was S aureus (37.6%). Children < 7 years of age were most likely to have gram-negative infections, most frequently H influenzae, but S aureus was the second most common isolate in children younger than 6 years of age. Of the S aureus isolates, 19.1% were resistant to methicillin. The incidence of methicillin-resistant S aureus (MRSA) increased over the decade. There were also 2-fold and 3-fold increases in resistance of gram-positive organisms to erythromycin and ciprofloxacin.11

Nosocomial and community-acquired MRSA infections have also been reported in children. Many neonatal intensive care units (NICUs) take weekly pharyngeal swabs of every neonate to test for MRSA colonization. Neonates who are colonized with MRSA may show no signs of infection but MRSA infections in neonates are possible. In 1 report, a 7-day-old neonate was referred to the ophthalmology team with a 1-day history of purulent conjunctivitis in the right eye. The conjunctival swab taken before any antibiotics were administered grew MRSA. Both parents were also found to be colonized by MRSA and likely transmitted it to their child.12 In addition, community-acquired MRSA has caused at least 1 case of orbital cellulitis in a non-immunocompromised child and at least 1 case of chronic dacryocystitis secondary to congenital NLD obstruction.13,14 Thus, healthy infants can harbor MRSA and pediatric community-acquired MRSA can occur.

H influenzae and S pneumoniae still account for between 85% and 98% of all cases of bacterial conjunctivitis.6-8 Nontypeable S pneumoniae is also the most common cause of atypical outbreaks of bacterial conjunctivitis. Therefore, when treating a patient empirically, fluoroquinolones are a reasonable choice. They are the only class of drugs effective against both H influenzae and S pneumoniae and against which neither organism has developed significant resistance.15 S pneumoniae is generally resistant to gentamicin, tobramycin, polymyxin B/trimethoprim, and azithromycin, and H influenzae has developed resistance against erythromycin. The fluoroquinolones are also effective against S aureus, a less common but still significant cause of bacterial conjunctivitis. However, methicillin resistance in S aureus isolates is a marker for multidrug resistance, including resistance to the fluoroquinolones. Of the antibiotics tested by Ocular TRUST, only trimethoprim retained high efficacy against MRSA in vitro; 95% of MRSA isolates were susceptible to trimethoprim.15

A potent, highly effective antibiotic eradicates pathogens quickly, reducing the length of time for bacteria to mutate and therefore develop resistance.
— Rudolph S. Wagner, MD
The idea that treating infections with the most potent antibiotic available can lead to drug resistance is inaccurate. A potent, highly effective antibiotic eradicates pathogens quickly, reducing the length of time for bacteria to mutate and therefore develop resistance. Rather, the use of inadequate doses or tapering of antibiotics in ophthalmic use contributes to the development of antibiotic resistance. Another factor in clinical practice is the inappropriate use of systemic antibiotics by physicians and nonadherence by patients. Other causes of the increase in antibiotic resistance are broad-spectrum therapies,16 widespread use of antibiotics in animal feed,17,18 and the spread of resistant organisms by increased international travel.19,20

The US Public Health Service, the CDC, and in-hospital antibiotic monitoring teams disseminate policies to help reduce the spread of antibiotic resistance. However, they can only monitor antibiotic use in humans. The use of antibiotics in agriculture has not been regulated. Food animals receive between 40% and 80% of antimicrobials in the United States each year. Many of these antibiotics are the same or similar to antibiotics that are used in humans. Most of these antibiotics, however, are not used to treat disease. Healthy animals receive low doses of antimicrobial agents in their feed over prolonged periods of time to promote growth, to increase feed efficiency, and to prevent disease. Because resistance genes are bred and transferred within environmental reservoirs that contain bacteria and antibacterial agents in less than bactericidal concentrations, this nontherapeutic use of antibiotics is likely to select for organisms with genes conferring resistance to those antibiotics. Exposure to low dosages of antibiotics over long periods of time creates selective pressure for organisms to mutate, develop resistance genes, and transfer these genes horizontally to other organisms.17,18

While bacteria spread genes for antibiotic resistance to other bacteria, humans disseminate antibiotic resistant strains of bacteria internationally. Global travel increases the biodiversity of organisms. When bacteria are introduced to a region where they were previously absent, reduced natural selection leads to increased genetic drift and increases the number and variety of strains that develop from that species of bacteria. Certain strains of S aureus were already resistant to methicillin before methicillin was ever used as an antibiotic. These strains have increased in number and diversity. New strains can initially be unique to a geographic region until person-to-person contact spreads these strains across from country to country and across oceans.19,20

Bacterial Resistance to Fluoroquinolones
Because fluoroquinolones are usually the initial therapy for bacterial conjunctivitis before the results of cultures are obtained (if conjunctival swabs for cultures are, in fact, obtained), preventing the development of fluoroquinolone resistance and increasing fluoroquinolone activity are important goals. The mechanism of action for all newer fluoroquinolones is 2-fold: they target DNA gyrase and topoisomerase IV. The probability of an organism developing 2 simultaneous resistant mutations is extremely low.21 Furthermore, topical fluoroquinolones can eradicate bacteria from the eye quickly in the concentration and dosages in which they are prescribed, greatly reducing the opportunity for mutations to occur.22 Studies have shown that newer fluoroquinolones did not contribute to resistance of isolates from the conjunctiva, nose, throat, or cheeks.22,23 However, because of the high level of in vitro MRSA resistance, the Ocular TRUST study suggests considering alternatives to fluoroquinolones when MRSA is a likely pathogen (Table 2).15

Table

Click here for larger version of this Table.

In summary, conjunctivitis can have a bacterial, viral, or allergic etiology. Bacteria are the most common cause of conjunctivitis in children, but the possibility of conjunctivitis in adolescents and older children should not be ruled out. Clinicians should be mindful of the likely source of conjunctivitis when deciding how to treat their patients.

References
  1. Rose PW, Harnden A, Brueggemann AB, et al. Chloramphenicol treatment for acute infective conjunctivitis in children in primary care: a randomised double-blind placebo-controlled trial. Lancet. 2005;366(9479):37-43.
  2. Kowalski RP, Dhaliwal DK. Ocular bacterial infections: current and future treatment options. Expert Rev Anti Infect Ther. 2005;3(1):131-139.
  3. Høvding G. Acute bacterial conjunctivitis. Acta Ophthalmol. 2008;86(1):5-17.
  4. Bodor FF, Marchant CD, Shurin PA, Barenkamp SJ. Bacterial etiology of conjunctivitis-otitis media syndrome. Pediatrics. 1985;76(1):26-28.
  5. Block SL, Hedrick J, Tyler R, et al. Increasing bacterial resistance in pediatric acute conjunctivitis (1997-1998). Antimicrob Agents Chemother. 2000;44(6):1650-1654.
  6. Weiss A, Brinser JH, Nazar-Stewart V. Acute conjunctivitis in childhood. J Pediatr. 1993;122(1):10-14.
  7. Patel PB, Diaz MC, Bennett JE, Attia MW. Clinical features of bacterial conjunctivitis in children. Acad Emerg Med. 2007;14(1):1-5.
  8. Meltzer JA, Kunkov S, Crain EF. Identifying children at low risk for bacterial conjunctivitis. Arch Pediatr Adolesc Med. 2010;164(3):263-267.
  9. Martin M, Turco JH, Zegans ME, et al. An outbreak of conjunctivitis due to atypical Streptococcus pneumoniae. N Engl J Med. 2003;348(12):1112-1121.
  10. Centers for Disease Control and Prevention (CDC). Pneumococcal conjunctivitis at an elementary school — Maine, September 20 - December 6, 2002. MMWR Morb Mortal Wkly Rep. 2003;52(4):64-66.
  11. Cavuoto K, Zutshi D, Karp CL, Miller D, Feuer W. Update on bacterial conjunctivitis in South Florida. Ophthalmology. 2008;115(1):51-56.
  12. Sahu DN, Thomson S, Salam A, Morton G, Hodgkins P. Neonatal methicillin-resistant Staphylococcus aureus conjunctivitis. Br J Ophthalmol. 2006;90(6):794-795.
  13. Vazan DF, Kodsi SR. Community-acquired methicillin-resistant Staphylococcus aureus orbital cellulitis in a non-immunocompromised child. J AAPOS. 2008;12(2):205-206.
  14. Kodsi S. Community-acquired methicillin-resistant Staphylococcus aureus in association with chronic dacryocystitis secondary to congenital nasolacrimal duct obstruction. J AAPOS. 2006;10(6):583-584.
  15. Asbell P, et al. Presented at: Annual Meeting of the American Society of Cataract and Refractive Surgery; April 3-8, 2009; San Francisco, CA.
  16. Schlech BA, Blondeau J. Future of ophthalmic anti-infective therapy and the role of moxifloxacin ophthalmic solution 0.5% (VIGAMOX). Surv Ophthalmol. 2005;50(suppl 1):S64-S67.
  17. Shea KM. Antibiotic resistance: what is the impact of agricultural uses of antibiotics on children's health? Pediatrics. 2003;112(1 Pt 2):253-258.
  18. Shea KM; American Academy of Pediatrics Committee on Environmental Health; American Academy of Pediatrics Committee on Infectious Diseases. Nontherapeutic use of antimicrobial agents in animal agriculture: implications for pediatrics. Pediatrics. 2004;114(3):862-868.
  19. Hershberg R, Lipatov M, Small PM, et al. High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography. PLoS Biol. 2008;6(12):e311.
  20. Ayliffe GA. The progressive intercontinental spread of methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 1997;24(suppl 1):S74-S79.
  21. Comstock TL, Karpecki PM, Morris TW, Zhang JZ. Besifloxacin: a novel anti-infective for the treatment of bacterial conjunctivitis. Clin Ophthalmol. 2010;4:215-225.
  22. Nafziger AN, Bertino JS Jr. Besifloxacin ophthalmic suspension for bacterial conjunctivitis. Drugs Today (Barc). 2009;45(8):577-588.
  23. Lichtenstein SJ, et al. Paper presented at: American Association for Pediatric Ophthalmology and Strabismus (AAPOS) 36th Annual Meeting; April 14-18, 2010; Orlando, FL.
Making a definitive diagnosis for a pediatric patient presenting with conjunctivitis can be difficult. Conjunctivitis in the pediatric patient can be mimicked by nasolacrimal duct (NLD) obstruction and caused by allergies, bacteria, and viruses. Because antimicrobial cultures take time and are not always accurate, the diagnosis and treatment of conjunctivitis are often based on the physician’s knowledge regarding the current literature on likely pathogens and clinical experience. Therefore, pediatricians must be aware of the clinical signs and symptoms that can provide a differential diagnosis of conjunctivitis, so that it can be properly treated.

Pediatricians must be aware of the clinical signs and symptoms that can provide a differential diagnosis of conjunctivitis, so that it can be properly treated.
— Rudolph S. Wagner, MD
Nasolacrimal Duct Obstruction
NLD obstruction is always in the differential diagnosis for conjunctivitis during the first year of life. Effort should be made to rule out NLD obstruction as the cause of the patient’s symptoms. With NLD obstruction, the child’s eyelids may be matted together or discharge may be seen along the lashes or down the child’s cheek. However, patients with NLD obstruction present with less conjunctival injection than patients with bacterial conjunctivitis. Also, if the child’s face has been cleaned to prepare the child to see the physician, signs will usually recur during the office visit.

A definitive diagnosis of NLD obstruction can be made by digital massage of the lacrimal sac. When massaged, the nasolacrimal duct will produce a reflux of mucous from the puncta. The fluorescein dye disappearance test is most helpful when the condition is unilateral. After fluorescein dye has been administered to each eye, the dye will take longer to clear from the eye with NLD obstruction.

Presentation of Allergic Conjunctivitis
The number of children presenting to the clinic with allergic conjunctivitis will vary according to the season. Allergic conjunctivitis is caused by an acute type I hypersensitivity to common allergens. Allergic conjunctivitis has a protracted course, with the severity of symptoms waxing and waning throughout the allergy season. This is another way to differentiate allergic conjunctivitis from other forms, as recurrences within a short period of time are unlikely with bacterial or viral conjunctivitis. Symptoms include itchy eyes, watery or stringy discharge, chemosis, eyelid edema, rhinitis, and an “allergic shiner.” Chemosis (swelling of the conjunctiva) can be marked and may cause the cornea to appear as if it is sitting in a depression. In addition to seasonal allergic conjunctivitis, there are vernal limbal or palpebral types. With vernal limbal conjunctivitis, there is an accumulation of eosinophils along the limbus; with vernal palpebral conjunctivitis, large papules form under the conjunctiva of the upper eyelid.

Presentation of Viral Conjunctivitis
Viral conjunctivitis is more common in older children and adults than it is in preschool-aged children. Viral conjunctivitis is highly contagious and is characterized by watery discharge. The amount of vascular injection can be variable. Viral conjunctivitis is usually caused by adenovirus, but can also be caused by other viruses such as herpes simplex virus (HSV).

HSV may be one of the most problematic causes of conjunctivitis. This virus can lead to herpetic keratitis and possibly loss of vision. Corticosteroids, sometimes used as palliative care in cases of viral conjunctivitis caused by other viruses, are contraindicated in conjunctivitis caused by HSV. The disease is almost always unilateral and monocular. Patients with herpetic conjunctivitis may complain of severe pain. The eyelids may also be involved — they can be red, edematous, and display multiple vesicles. The corneal reflex in a patient with herpetic conjunctivitis will be irregular, not be sharp and crisp. Upon close examination, dendrites or small opacities may be observed. Herpetic conjunctivitis should be in the differential whenever a patient is not responding to antibiotic therapy. Patients with conjunctivitis thought to be caused by HSV should always be referred to an ophthalmologist.

Acute hemorrhagic conjunctivitis (AHC) is most commonly caused by a picornavirus, usually Coxsackie A24 or enterovirus 70. The presentation of AHC is often dramatic. The eye will become acutely painful and possibly photophobic even before hemorrhages can be seen. The subconjunctival hemorrhages that characterize this disease begin as petechiae which then coalesce and can involve the entire subconjunctiva. While highly contagious, AHC is self-limiting and its complications are rare.

Presentation of Bacterial Conjunctivitis
Acute bacterial conjunctivitis is most frequently observed among infants, toddlers, and preschool-aged children. One in 8 children has an episode every year, and there are 5 million cases in the United States annually. Bacterial conjunctivitis is a self-limiting disease, typically lasting 7 to 10 days without antibiotic treatment.1-3 For example, in 1 study 83% of children diagnosed with bacterial cconjunctivitis treated with a vehicle washout drop containing no active medication had clinical cures at 7 days.1 Viral conjunctivitis usually lasts longer than bacterial conjunctivitis. If conjunctivitis does not resolve with antibiotics after 3 to 4 days, the physician should suspect that the infection is viral.

Bacterial conjunctivitis is characterized by mucopurulent discharge with matting of the eyelids. Common clinical findings in acute bacterial conjunctivitis include burning and stinging. While bacterial conjunctivitis can present in only one eye, it is usually present in both eyes or will spread to the contralateral eye. Acute bacterial conjunctivitis can be associated with otitis media. When a patient presents with both conjunctivitis and otitis media, systemic antibiotics are indicated.4,5 Like viral conjunctivitis, bacterial conjunctivitis is highly contagious.

Differentiating Bacterial from Viral Conjunctivitis
Bacterial conjunctivitis can be differentiated from viral conjunctivitis based on discharge (mucopurulent vs. watery), age of the affected child (preschool-aged vs. school-aged children), and whether the infection is bilateral or unilateral (Table 1).

Table

Click here for larger version of this Table.

Ocular Pathogens in Bacterial Conjunctivitis
Studies have shown that pediatric acute conjunctivitis is most often caused by bacteria. Viruses and allergies are the second and third most common causes (Figure 1).6,7 The younger the patient, the higher the likelihood of a bacterial etiology of the conjunctivitis.

Figure

Click here for larger version of this Figure.

A variety of studies have been performed to determine the organisms responsible for conjunctivitis. In a study of 95 patients with acute conjunctivitis and 91 control children of similar age, specimens of the lid and conjunctiva were obtained for culture and conjunctival scrapings were stained with Giemsa and Gram stains. Bacterial infections were identified in 80% of patients, viral infections were identified in 13%, and allergies in 2%. No cause could be determined in 5% of patients. Of the patients with bacterial conjunctivitis, Haemophilus influenzae accounted for 58.1% of all bacterial cultures. Streptococcus pneumoniae was the second most common pathogen, accounting for 27.1% of bacteria cultures. Moraxella catarrhalis was isolated from cultures in 8.1% of patients. Staphylococci accounted for 4.1% of cultures and species included Staphylococcus epidermis (2.7%) and other coagulase-negative staphylococci (1.4%). Staphylococci, corynebacteria, and alpha-hemolytic streptococci were the predominant organisms recovered from the lids of control subjects.6

In a prospective study in a children’s hospital emergency department published in 2007, conjunctival swabs were obtained for bacterial culture from 111 patients aged 1 month to 18 years (mean age, 33 months) who presented with red or pink eye and/or the diagnosis of conjunctivitis. Bacterial cultures were positive in 78.4% of the patients tested. Nontypeable H influenzae accounted for 82% of positive cultures, S pneumoniae for 16%, and Staphylococcus aureus for 2%.7 The decrease in the proportion of isolates positive for S pneumoniae compared to the study published in 1993 may be due to pneumococcal conjugate vaccine immunizations.

A prospective observational cohort study at an urban pediatric emergency department was published in 2010. Conjunctival swabs were taken from children aged 6 months to 17 years who presented with conjunctival erythema, eye discharge, or both. The median age was 3 years. Patients were excluded from the study if they had a history of ocular trauma, were exposed to a noxious chemical, wore contact lenses, or had used antibiotics in the previous 5 days. Bacterial cultures were isolated from 64.7% of the 368 patients enrolled in the study. H influenzae accounted for 67.6% of positive cultures, S pneumoniae for 19.7%, and S aureus for 8.0% (Figure 2).8

Figure

Click here for larger version of this Figure.

This study also investigated how it could be determined that conjunctivitis is not likely to be of bacterial etiology. They determined 4 factors that were likely to be associated with cultures that were negative for bacteria:
  • > 6 years of age
  • Presentation in April through November
  • Watery or no discharge
  • No glued eye in the morning
In this study, 92.2% of patients with all of these factors had cultures that were negative for bacteria and 76.4% of those with 3 factors had negative cultures. These data can aid a physician in deciding whether or how to treat a patient in some cases.

While the data in these 3 studies are consistent and compelling, physicians must also remember that atypical outbreaks of bacterial conjunctivitis can occur. Two notable outbreaks of bacterial conjunctivitis have been caused by an atypical strain of S pneumoniae.

The outbreak at Dartmouth College in New Hampshire in 2002 is especially significant because outbreaks of conjunctivitis in college-aged students are usually viral in etiology. From January 1 through February 15, 197 students were diagnosed with conjunctivitis. A viral cause was initially suspected, but conjunctival swabs from 12 students grew S pneumoniae. Because of the high number of cases and the unusual bacterial etiology in college-aged students, an investigation was initiated. Specimens were sent to the Dartmouth-Hitchcock Medical Center for culture and identification. Subcultures of presumed S pneumoniae isolates were then sent to the CDC for further analysis.9

Results of the investigation demonstrated that between January 1, 2002 and April 12, 2002, 698 of the 5,060 students enrolled at Dartmouth College were diagnosed with conjunctivitis. During similar periods in 2000 and 2001, only 66 and 92 students, respectively, were diagnosed with conjunctivitis. During the 2002 outbreak, 34 students suffered repeated infections as defined by visits to the health center for conjunctivitis by the same student that occurred more than 14 days apart. The attack ratio among the 3,682 undergraduates and 1,378 graduate students was 18.7% and 2.5%, respectively. Of the positive cultures, 43.3% grew nonencapsulated pneumococci.9 This outbreak exemplifies that bacterial conjunctivitis can occur in young adults and conjunctivitis should not be assumed to be due to adenovirus in this age group.

Nontypeable pneumococcus also caused an outbreak of bacterial conjunctivitis in Westbrook, Maine later in 2002. From September 20 to December 6, at the index elementary school, a total of 101 students (out of 361) had at least 1 episode of conjunctivitis. Eleven of 20 students tested (55%) had an episode of culture-confirmed pneumococcal conjunctivitis. Additionally, school nurses and child care staff in the community reported an additional 4% of students attending kindergarten through grade 12 at 4 schools, and 9% of children attending 3 community child care centers, having conjunctivitis during this time period.

Among the 53 students with conjunctivitis at other schools, 10 (19%) had a family member at the index school, and seven (29%) of 24 ill child care attendees had a sibling at the index school. Of 15 conjunctival specimens collected from students at other schools, 5 (33%) grew S pneumoniae. The CDC advises, “health care providers and public health officials should be aware that nontypeable S pneumoniae can cause outbreaks of conjunctivitis in school-aged children and college students; outbreaks should be reported to state health departments and the CDC.”10

Antibiotic Resistance and Bacterial Conjunctivitis
In a retrospective cross-sectional study, the microbiology records of all patients (adults and children) with bacterial conjunctivitis seeking treatment at Bascom Palmer Eye Institute in Miami from January 1, 1994 through December 31, 2003 were reviewed. For an eye to have been included in the study, conjunctival swabs must have resulted in a positive culture. Over this 10-year period in South Florida, the most common isolate from the 2,408 consecutive swabs was S aureus (37.6%). Children < 7 years of age were most likely to have gram-negative infections, most frequently H influenzae, but S aureus was the second most common isolate in children younger than 6 years of age. Of the S aureus isolates, 19.1% were resistant to methicillin. The incidence of methicillin-resistant S aureus (MRSA) increased over the decade. There were also 2-fold and 3-fold increases in resistance of gram-positive organisms to erythromycin and ciprofloxacin.11

Nosocomial and community-acquired MRSA infections have also been reported in children. Many neonatal intensive care units (NICUs) take weekly pharyngeal swabs of every neonate to test for MRSA colonization. Neonates who are colonized with MRSA may show no signs of infection but MRSA infections in neonates are possible. In 1 report, a 7-day-old neonate was referred to the ophthalmology team with a 1-day history of purulent conjunctivitis in the right eye. The conjunctival swab taken before any antibiotics were administered grew MRSA. Both parents were also found to be colonized by MRSA and likely transmitted it to their child.12 In addition, community-acquired MRSA has caused at least 1 case of orbital cellulitis in a non-immunocompromised child and at least 1 case of chronic dacryocystitis secondary to congenital NLD obstruction.13,14 Thus, healthy infants can harbor MRSA and pediatric community-acquired MRSA can occur.

H influenzae and S pneumoniae still account for between 85% and 98% of all cases of bacterial conjunctivitis.6-8 Nontypeable S pneumoniae is also the most common cause of atypical outbreaks of bacterial conjunctivitis. Therefore, when treating a patient empirically, fluoroquinolones are a reasonable choice. They are the only class of drugs effective against both H influenzae and S pneumoniae and against which neither organism has developed significant resistance.15 S pneumoniae is generally resistant to gentamicin, tobramycin, polymyxin B/trimethoprim, and azithromycin, and H influenzae has developed resistance against erythromycin. The fluoroquinolones are also effective against S aureus, a less common but still significant cause of bacterial conjunctivitis. However, methicillin resistance in S aureus isolates is a marker for multidrug resistance, including resistance to the fluoroquinolones. Of the antibiotics tested by Ocular TRUST, only trimethoprim retained high efficacy against MRSA in vitro; 95% of MRSA isolates were susceptible to trimethoprim.15

A potent, highly effective antibiotic eradicates pathogens quickly, reducing the length of time for bacteria to mutate and therefore develop resistance.
— Rudolph S. Wagner, MD
The idea that treating infections with the most potent antibiotic available can lead to drug resistance is inaccurate. A potent, highly effective antibiotic eradicates pathogens quickly, reducing the length of time for bacteria to mutate and therefore develop resistance. Rather, the use of inadequate doses or tapering of antibiotics in ophthalmic use contributes to the development of antibiotic resistance. Another factor in clinical practice is the inappropriate use of systemic antibiotics by physicians and nonadherence by patients. Other causes of the increase in antibiotic resistance are broad-spectrum therapies,16 widespread use of antibiotics in animal feed,17,18 and the spread of resistant organisms by increased international travel.19,20

The US Public Health Service, the CDC, and in-hospital antibiotic monitoring teams disseminate policies to help reduce the spread of antibiotic resistance. However, they can only monitor antibiotic use in humans. The use of antibiotics in agriculture has not been regulated. Food animals receive between 40% and 80% of antimicrobials in the United States each year. Many of these antibiotics are the same or similar to antibiotics that are used in humans. Most of these antibiotics, however, are not used to treat disease. Healthy animals receive low doses of antimicrobial agents in their feed over prolonged periods of time to promote growth, to increase feed efficiency, and to prevent disease. Because resistance genes are bred and transferred within environmental reservoirs that contain bacteria and antibacterial agents in less than bactericidal concentrations, this nontherapeutic use of antibiotics is likely to select for organisms with genes conferring resistance to those antibiotics. Exposure to low dosages of antibiotics over long periods of time creates selective pressure for organisms to mutate, develop resistance genes, and transfer these genes horizontally to other organisms.17,18

While bacteria spread genes for antibiotic resistance to other bacteria, humans disseminate antibiotic resistant strains of bacteria internationally. Global travel increases the biodiversity of organisms. When bacteria are introduced to a region where they were previously absent, reduced natural selection leads to increased genetic drift and increases the number and variety of strains that develop from that species of bacteria. Certain strains of S aureus were already resistant to methicillin before methicillin was ever used as an antibiotic. These strains have increased in number and diversity. New strains can initially be unique to a geographic region until person-to-person contact spreads these strains across from country to country and across oceans.19,20

Bacterial Resistance to Fluoroquinolones
Because fluoroquinolones are usually the initial therapy for bacterial conjunctivitis before the results of cultures are obtained (if conjunctival swabs for cultures are, in fact, obtained), preventing the development of fluoroquinolone resistance and increasing fluoroquinolone activity are important goals. The mechanism of action for all newer fluoroquinolones is 2-fold: they target DNA gyrase and topoisomerase IV. The probability of an organism developing 2 simultaneous resistant mutations is extremely low.21 Furthermore, topical fluoroquinolones can eradicate bacteria from the eye quickly in the concentration and dosages in which they are prescribed, greatly reducing the opportunity for mutations to occur.22 Studies have shown that newer fluoroquinolones did not contribute to resistance of isolates from the conjunctiva, nose, throat, or cheeks.22,23 However, because of the high level of in vitro MRSA resistance, the Ocular TRUST study suggests considering alternatives to fluoroquinolones when MRSA is a likely pathogen (Table 2).15

Table

Click here for larger version of this Table.

In summary, conjunctivitis can have a bacterial, viral, or allergic etiology. Bacteria are the most common cause of conjunctivitis in children, but the possibility of conjunctivitis in adolescents and older children should not be ruled out. Clinicians should be mindful of the likely source of conjunctivitis when deciding how to treat their patients.

References
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