Clinical Pediatrics

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Bacterial Conjunctivitis in Children: Antibacterial Treatment Options in an Era of Increasing Drug

Resistance
Michael E. Pichichero
CLIN PEDIATR published online 19 August 2010
DOI: 10.1177/0009922810379045

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 CLIN PEDIATR OnlineFirst, published on September 13, 2010 as doi:10.1177/0009922810379045

Clinical Pediatrics

Bacterial Conjunctivitis in Children: XX(X) 1­–7

© The Author(s) 2010
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Antibacterial Treatment Options in sagepub.com/journalsPermissions.nav
DOI: 10.1177/0009922810379045

an Era of Increasing Drug Resistance http://clp.sagepub.com

Michael E. Pichichero, MD1

Abstract
Bacterial conjunctivitis, one of the most common eye diseases in children, is highly contagious and rapidly transmitted
in day-care centers and schools. Empiric treatment with a broad-spectrum, ocular topical antibiotic has been shown
to shorten the course of the disease and reduce the risk for contagion. However, recent studies have documented a
pattern of growing drug resistance among the pathogens that cause bacterial conjunctivitis. Because drug resistance
occurs to each of the classes of ocular antibiotics (aminoglycosides, polymyxin B combination therapies, macrolides,
and fluoroquinolones), the selection of an effective anti-infective agent has become very difficult.

Keywords
bacterial conjunctivitis, fluoroquinolones, antibiotics, bacterial resistance

Introduction As bacterial resistance to anti-infectives continues to

Conjunctivitis is one of the most frequently seen eye
disorders in the primary care and pediatric setting,1-3
accounting for an estimated 1% to 4% of visits.4 The
etiology can be bacterial, viral, allergic, or chemical, but
bacterial infections are the most common. Bacterial con-
junctivitis occurs more often in preschool children than
in older children and adults.2 The most common caus-
ative organisms in children are Haemophilus influenzae,
Streptococcus pneumoniae, Staphylococcus aureus, and
Moraxella catarrhalis (Table 1).5 Approximately one
third of children with bacterial conjunctivitis have con-
current otitis media.6
Bacterial conjunctivitis is highly contagious and rapidly
transmitted in day-care centers and classrooms.2,3,7 The
condition is typically self-limited, with clinical resolu-
tion usually apparent by 7 days without treatment.7 How-
ever, clearance of the infection can take up to 3 weeks.3
Treatment of acute bacterial conjunctivitis with an anti-
infective agent lessens contagion and duration of dis-
ease, alleviates patient discomfort, and facilitates earlier
resumption of normal activities.3 A meta-analysis of
5 double-blind, placebo-controlled clinical studies with
a total of 1034 children and adults concluded that anti-
bacterial agents have their greatest impact on clinical and
microbiological remission if begun within 2 to 5 days of
symptom onset.8
evolve, the selection of an ocular antibacterial has become
a challenge. Bacterial resistance to antibiotic therapy can
result from a number of factors.9 Nationwide surveillance
studies such as the Ocular Tracking Resistance in US
Today (TRUST) survey and The Surveillance Network
(TSN) have documented emerging resistance among ocu-
lar pathogens to ocular anti-infectives.10,11
In this review, the differential diagnosis of bacterial
conjunctivitis in children and the efficacy of currently
used and newer topical antibacterial treatments for acute
bacterial conjunctivitis in the preschool and school-aged
child will be presented in the context of increasing bac-
terial resistance.
Diagnosis of Acute
Bacterial Conjunctivitis
The history for conjunctivitis should include time of
onset of symptoms, precipitating events, progression,
and duration and severity of symptoms (i.e., acute,
1
Rochester General Hospital, Research Institute Rochester, NY, USA
Corresponding Author:
Michael E. Pichichero, Center for Infectious Disease and
Immunology, Rochester General Hospital, Research Institute
1425 Portland Avenue, Rochester, NY 14621, USA
Email: michael.pichichero@rochestergeneral.org

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2 Clinical Pediatrics XX(X)
Table 1. Common Pathogens of Bacterial Conjunctivitis5
Neonates
<1 week Neisseria gonorrhoeae
1-2 weeks Chlamydia trachomatis
Haemophilus influenzae
Streptococcus pneumoniae
Older infants and toddlers (1-5 years)
Without otitis
H influenzae
S pneumoniae
Moraxella catarrhalis
Staphylococcus aureus
With otitis
H influenzae
S pneumoniae
School-aged children/adolescents
S aureus
H influenzae
S pneumoniae
hyperacute, or chronic).5 Exposure to other children/
adults at home, school, or day care with similar symp-
toms should be noted, as should a history of allergies
and whether the conjunctivitis is unilateral or bilateral.
The physical exam should include an assessment of
the external structural parts of the eye (eyelids, lashes)
as well as the cornea and bulbar palpebral conjunctiva.
The surrounding skin should be examined and
enlarged regional lymph nodes should be noted. In addi-
tion, patients should be checked for comorbid otitis
media.
Signs and symptoms specific to allergic conjunctivi-
tis include itching, stringy or ropy discharge, lid edema,
chemosis, red, hyperemic conjunctiva, and comorbid
allergic rhinitis. Viral conjunctivitis is characterized by
watery discharge and conjunctival injection. The pres-
ence of preauricular and/or submandibular lymphade-
nopathy can confirm viral conjunctivitis. Children with
viral conjunctivitis may be febrile and/or have associ-
ated pharyngitis.
Acute bacterial conjunctivitis begins abruptly with
early symptoms of irritation or foreign body sensation
and tearing. Mucopurulent or purulent discharge, fre-
quently occurring with morning crusting, swelling, and
comorbid otitis media are the most common indicators
of acute bacterial conjuctivitis.2,6
Cultures may be used to confirm or deny the etiology;
however, these are rarely obtained, unless the conjunc-
tivitis is recurrent or severe. In children, nontypeable H
influenzae is the predominant organism in acute bacterial
conjunctivitis followed by S pneumoniae.3,12 Figure 1
depicts an algorithm for evaluating conjunctivitis based
on the age of the child.5
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Treatment of acute bacterial conjunctivitis with a broad-
spectrum, preferably bactericidal, antibacterial is often
initiated empirically because the rapid kill of bacteria
shortens the time to recovery1,2,13; limits the spread of
disease2; relieves a financial burden by speeding up a
child’s return to day care or school and, consequently,
the parents’ return to work; and reduces the risk of
sight-threatening complications. For acute bacterial
conjunctivitis with otitis media, treatment with an oral
antibiotic is recommended.14 For uncomplicated acute
bacterial conjunctivitis, topical ophthalmic agents are
preferred over systemic agents because the concentra-
tion of antibiotic achieved on the eye following topical
administration is higher than that achieved in the blood
following oral administration and systemic side effects
of orally administered antibiotics are avoided. Also, the
concentration of antibiotic achieved on the surface of
the eye following topical administration is expected
to exceed both the minimum inhibitory concentration
(MIC) required to inhibit 90% of tested isolates (MIC90)
and the minimum bactericidal concentration at the target
tissue site.15 To date there has only been one study com-
paring the efficacy of oral treatment with that of topical
treatment. Wald et al16 showed that oral cefixime and
topical polymyxin B/bacitracin were equally effective
in achieving clinical cure in children aged 2 months to
6 years with acute bacterial conjunctivitis. From this study
one might infer that an effective oral antibiotic with activ-
ity against ocular pathogens should be sufficient therapy
and the addition of an ocular antibiotic unnecessary. when
both conjunctivitis and otitis media are present.
Considerations in choosing the appropriate topi-
cal antibiotic for bacterial conjunctivitis include broad
coverage of ocular Gram-positive and Gram-negative
bacteria,17 rapid kill rate, low bacterial resistance, mini-
mal toxicity to the eye, patient comfort, and a convenient
dosing schedule to encourage patient adherence. Cur-
rently, the most commonly used topical ophthalmic anti-
infective options are from one of the following classes:
aminoglycosides, polymyxin B combination therapies,
macrolides, or fluoroquinolones.9 Sulfonamides and
chloramphenicol are no longer favored in the United
States because of tolerability/safety concerns of severe
stinging on instillation with sulfonamides and aplastic
anemia with chloramphenicol and are not addressed in
this review. Table 2 presents a brief summary of the
currently used topical anti-infectives for bacterial con-
junctivitis with their dosage regimens. Most of these
antibiotics are approved for children 1 year and older.
Aminoglycosides
Aminoglycosides (gentamicin, tobramycin, neomycin) are
most active against Gram-negative bacteria, particularly
Pichichero 3

Child with conjunctivitis

Older infant School-aged child

Neonate
Toddler Adolescent

Gram stain Otitis Otitis Hyperacute

<24 hours old and culture media media Gram stain Viral Allergic
present absent and culture

Gram-negative Presume H. influenzae Gram- Antihistamines,

Topical
Chemical cocci, chlamydia, nontypeable, negative Eye irrigation Decongestants,
antibiotics
N. gonorrhea Oral Oral antibiotics cocci NSAID’ s,
erythromycin H1 receptor
antagonists, Mast
Systemic Systemic
Systemic cell stabilizers
Observation antibiotics, antibiotics,
antibiotics,
Eye irrigation Eye irrigation
Eye irritation

Figure 1. Algorithm for evaluating conjunctivitis5

Abbreviation: NSAIDS, nonsteroidal anti-inflammatory drugs.
Source: Modified from current citation.

Pseudomonas aeruginosa (with the exception of neo-
mycin), and are active against methicillin-sensitive S
aureus (MSSA) but offer little coverage of streptococci
and methicillin-resistant S aureus (MRSA).18 Studies of
tobramycin 0.3% and gentamicin 0.3% in patients of all
ages found clinical cure rates ranging from 46% to 77%
and 39% to 70%, respectively.7 One study demonstrated
significantly improved clinical cure rates with tobramy-
cin compared with gentamicin (P = .038).19 Results of a
study in children (<20 years) demonstrated bacterial
eradication rates identical to those in patients of all ages
with bacterial eradication rates of 85% and 65% for
tobramycin and gentamicin, respectively.20
Resistance to Aminoglycosides
Studies of bacterial conjunctivitis isolates conducted from
the late 1990s through the mid-2000s have shown an
increasing degree of resistance to gentamicin and tobra-
mycin among Gram-positive pathogens. The first annual
survey of Ocular TRUST, describing data collected from
October 2005 through June 2006 showed 65.3% resis-
tance among S pneumoniae isolates to tobramycin.10
Tobramycin was active against MSSA, but 63.6% of
MRSA were resistant to tobramycin. Additional analysis
of archived isolates of S pneumoniae and H influenzae
obtained between 1999 and 2006 further showed 59.9%
of penicillin-sensitive S pneumoniae (PSSP) isolates were
resistant to tobramycin compared with 73.1% of peni-
cillin-nonsusceptible S pneumoniae (PNSP) isolates. Of
note, little to no aminoglycoside resistance was seen in
H influenzae.10
Polymyxin B Combination Therapy
Polymyxin B exerts activity against Gram-negative organ-
isms only and is, therefore, administered in combination
with other antibiotics with complementary modes of
action to provide a broader spectrum of coverage. Com-
monly used polymyxin B combination products include
polymyxin B/trimethoprim, polymyxin B/bacitracin,
and polymyxin B/neomycin/bacitracin. Trimethoprim
has activity against most staphylococci, streptococci,
and some Gram-negatives such as Haemophilus. Most
staphylococci and streptococci are susceptible to bacitra-
cin. Double-masked, randomized comparisons did not
identify any significant differences between the poly-
myxin B combination regimens in clinical resolution
or bacterial eradication rates when tested in patients of
all ages.12
Resistance to Polymyxin B
Combination Therapy
In 2000, a pediatric surveillance study by Block et al12
showed that polymyxin B was ineffective against both
PSSP and PNSP isolates. Although both polymyxin B/
neomycin and polymyxin B/trimethoprim combinations
were more active against S pneumoniae isolates than
polymyxin B, only the combination of polymyxin B/

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4 Clinical Pediatrics XX(X)

Table 2. Summary of Commonly Used Topical Antimicrobial Agents for Bacterial Conjunctivitis

Antimicrobial Agent Dosage Comments

Aminoglycosides
Gentamicin 0.3% solution and
ointment
Tobramycin 0.5% solution and
ointment
Macrolides
Erythromycin 0.5% ointment
Azithromycin 1% suspension
Polymyxin B combinations
Polymyxin B/trimethoprim
sulfate solution 10 000 U/mL,
1 mg/mL
Polymyxin B/bacitracin ointment
10 000 U/g, 500 U/g
Polymyxin B/neomycin/
bacitracin ointment
10 000 U/g, 0.35%, 400 U/g
Fluoroquinolones
Ciprofloxacin 0.3% solution or
ointment
Ofloxacin 0.3% solution
Levofloxacin 0.5% solution
Gatifloxacin 0.3% solution
Moxifloxacin 0.5% solution
Besifloxacin 0.6% suspension
Source: Merck Manual 2009-2010 Merck Sharp & Dohme Corp. http://www.merck.com/mmpe/sec09/ch101/ch101c.html. Accessed February 15,
2010. Tasman W, Jaeger AE. In: Duane’s Ophthalmology. Philadelphia, PA: Lippincott Williams & Wilkins; 2009. Online edition.
Solution: instill 1-2 drops every 2-4 hours
up to 2 drops every hour for severe
infections
Ointment: instill 0.5-inch ribbon 2-3
times/day to every 3-4 hours
Instill 0.5-inch ribbon 2-6 times/day
Instill 1 drop twice a day for 2 days then
daily for 5 days
Instill 1-2 drops every 4-6 hours
Instill 0.5-inch ribbon every 3-4 hours for
acute infections or 2-3 per day for mild
to moderate infections for 7-10 days
Instill 0.5-inch ribbon every 3-4 hours for
acute infections or 2-3 per day for mild
to moderate infections for 7-10 days
Solution: instill 1-2 drops every 2 hours
for 2 days, up to 8 times/day, then 4
times/day for 5 days (class labeling)
Ointment: instill 0.5-inch ribbon 3 times/
day for 2 days followed by twice daily
for 5 days
Same as above (class labeling)
Same as above (class labeling)
Same as above (class labeling)
Instill 3 times/day for 7 days
Instill 3 times/day for 7 days
Resistance among Gram-positive organisms,
particularly Streptococci. May cause
hyperemia or keratopathy
Generally bacteriostatic. Staphylococcus species
have become resistant to erythromycin;
resistance to both erythromycin and
azithromycin among Haemophilus influenzae.
Azithromycin’s long half-life is a risk factor
for resistance
Effective against H influenzae and penicillin-
susceptible Staphylococcus pneumoniae. Not
reliably bactericidal. Clinical cure may take
as long as a week
Reports of contact dermatitis of the
periocular area with bacitracin
Ocular allergic reactions seen with neomycin
and contact dermatitis with bacitracin
Effective against a broad spectrum of
Gram-negative and Gram-positive
organisms. However, resistance has emerged
among S pneumoniae
Drug precipitates with frequent dosing
reported with ciprofloxacin
Highly effective against a broad spectrum of
Gram-negative and Gram-positive organisms
Highly effective against a broad spectrum of
Gram-negative and Gram-positive organisms
Of the fluoroquinolones, the only one that
does not contain benzalkonium chloride as
a preservative
Developed only for topical ophthalmic use;
potent in vitro efficacy against bacterial
strains resistant to other fluoroquinolones,
but clinical relevance not known

trimethoprim achieved MIC90 values considered predic-
tive of clinical efficacy and then only against penicillin-
susceptible S pneumoniae.12 In contrast, most strains of
H influenzae remained susceptible to polymyxin B
alone or in combination with neomycin or trimethoprim
regardless of β-lactamase status. Ocular TRUST 1 data
reported 100% resistance among S pneumoniae and
MSSA to polymyxin B, but no resistance by H influenzae.10
Trimethoprim was effective against PSSP, but 74% of
PNSP were resistant to trimethoprim.10
Macrolides
Macrolides are active primarily against Gram-positive
cocci with the exception of enterococci and are generally
bacteriostatic. Erythromycin has been used as an ocular

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Pichichero 5
antibiotic for more than 25 years as a 0.5% ointment.
However, resistance among Staphylococcus species and
poor activity against H influenzae have relegated eryth-
romycin to a marginal role in the treatment of bacterial
conjunctivitis.17
Azithromycin is a newer macrolide topical ophthal-
mic antibiotic. Abelson et al21 reported rates of clinical
resolution and bacterial eradication of 63.1% and 88.5%,
respectively, at day 6 or 7 following treatment initiation
with azithromycin 1% in children and adults with bacte-
rial conjunctivitis.
Resistance to Macrolides
The Ocular TRUST 1 survey (2005-2006) showed a
22.4% resistance rate to azithromycin among S pneu-
moniae isolates, 45.7% resistance among MSSA isolates,
and 90.9% resistance among MRSA isolates.10 A study
from 32 centers in the United States evaluating conjunc-
tival isolates collected in 2006 and 2007 identified
20% resistance to azithromycin among S pneumoniae
isolates and 30% resistance among S aureus isolates
from 625 patients with bacterial conjunctivitis.22 Resis-
tance to azithromycin among 76% of H influenzae iso-
lates was reported.
Fluoroquinolones
Fluoroquinolones offer broad-spectrum coverage against
both Gram-positive and Gram-negative organisms.23 The
initial topical ophthalmic fluoroquinolones ofloxacin and
ciprofloxacin were introduced in the 1990s but have been
largely replaced by the newer fluoroquinolones levo-
floxacin, moxifloxacin, and besifloxacin because of their
improved activity against Gram-positive organisms.
Several randomized, double-masked, controlled clin-
ical trials in children and adults with bacterial conjunc-
tivitis demonstrated rates of clinical cure ranging from
approximately 66% to 96% and microbial eradication
ranging from approximately 84% to 96% for the newer
fluoroquinolones.24
Besifloxacin, the latest topical ophthalmic fluoro-
quinolone, received US Food and Drug Administration
approval in May 2009 for the treatment of bacterial con-
junctivitis. Treatment of children and adults with bacte-
rial conjunctivitis with besifloxacin 0.6% resulted in
clinical resolution rates of 45% to 73% and bacterial
eradication rates of 88% to 91%.25,26 The efficacy and
safety of besifloxacin in children and adolescents aged
1 to 17 years (N = 447 with culture confirmed conjunc-
tivitis) were recently reported in a post hoc analysis
and were found to be consistent with the overall study
population.27
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Resistance to Fluoroquinolones
Development of resistance to a fluoroquinolone is often
achieved through one or more mutations in the genes
encoding these enzymes. The newer fluoroquinolones
(eg, moxifloxacin and besifloxacin) exhibit balanced
dual binding of these enzymes and require multistep
mutations, whereas resistance to the older fluoroquino-
lones (eg, ciprofloxacin, ofloxacin), which typically target
one enzyme in preference to the other, may require only
a single such mutation.10,28
Surveillance data thus far has failed to show resis-
tance of S pneumoniae or H influenzae isolates to either
the older or newer fluoroquinolones.10,12,22 In contrast,
there is documented resistance to both older and newer
ophthalmic fluoroquinolones among S aureus. From
2004 to 2006 it was reported that 90% to 92% of MSSA
isolates, but only 27% to 32% of MRSA isolates,
were susceptible to the fluoroquinolones tested (cipro-
floxacin, levofloxacin, and moxifloxacin) and a con-
sistent annual 2.5% increase in MRSA as a cause of
ocular infections was identified.16 Another study
reported an increase in resistance to ciprofloxacin by
S aureus isolates from 13.3% to 36.0% and the preva-
lence of methicillin resistance among these isolates
increased concurrently from 4.4% to 42.9%.17 More
recently, a study of bacterial conjunctivitis isolates
found that 65% of MRSA isolates were resistant to
ciprofloxacin.29
Safety of Topical Ophthalmic
Antibiotics for Bacterial Conjunctivitis
The topical ophthalmic antibiotics for the treatment of
bacterial conjunctivitis are generally safe and well toler-
ated with few exceptions. Because systemic exposure fol-
lowing topical administration is minimal, adverse events
are mostly mild and transient and limited to ocular adverse
events. Topical aminoglycosides have been associated
with corneal and conjunctival toxicity, especially when
used frequently. Superficial punctate lesions have been
reported with tobramycin, and ocular allergic reactions
have been reported with tobramycin, gentamicin, and
neomycin.30 Bacitracin has been associated with cases
of contact dermatitis in the periocular area.31 Local
irritation may occur in patients treated with polymyxin
B/trimethoprim sulfate combination regimens, whereas
allergic sensitization reactions may occur with polymyxin
B/bacitracin/neomycin combination regimens. Macrolides
are associated with minor ocular irritations, redness,
and hypersensitivity reactions. Fluoroquinolone oph-
thalmic solutions have been well tolerated and are asso-
ciated with less toxicity (eg, burning/stinging, chemosis,
6 Clinical Pediatrics XX(X)
photophobia, negative effects on corneal epithelium) than
other ophthalmic antibacterial classes.18,32,33
Choosing an Appropriate Ophthalmic
Antibiotic for Bacterial Conjunctivitis
The ideal topical anti-infective for the treatment of acute
bacterial conjunctivitis should be a well-tolerated, broad-
spectrum, highly potent, and a bactericidal agent with a
high concentration on the ocular surface and rapid kill
time. Although there are many classes of topical antibiotic
treatment options available to primary care physicians, dif-
ferences among them as well as emerging bacterial resis-
tance should be considered in selecting the appropriate
antibiotic. In addition, agents with convenient dosing regi-
mens are likely to promote treatment compliance. When
local antibiotic resistance to ocular pathogens warrants
the increased cost, use of newer fluoroquinolones might
be considered.
Declaration of Conflicting Interests
The author(s) declared no conflicts of interest with respect to
the authorship and/or publication of this article.
Funding
The author(s) received no financial support for the research
and/or authorship of this article.
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