Outbreak of Gram Positive Bacterial Keratitis Associated with Epidemic Keratoconjunctivitis in Neonates and Infants

1
Outbreak of Gram Positive Bacterial Keratitis
Associated with Epidemic Keratoconjunctivitis in
Neonates and Infants
Joo Hoon Kim1, Mee Kum Kim1, Joo Youn Oh1, Ki
Cheol Jang1, Won Ryang Wee1, Jin Hak
Lee2 Department of Ophthalmology, Seoul National
University College of Medicine, Seoul,
Korea1 Department of Ophthalmology, Seoul
National University Bundang Hospital, Seongnam,
Gyeonggi-do, Korea2 All authors in this study
declare no financial interest.
2

• The outbreak of Epidemic Keratoconjunctivitis(EKC)
  
• In a community, yearly
• In a health care unit (HCU), not uncommon
• Neonatal intensive care unit (workers, patients)
• Nursing home

• The outbreak of EKC in NICU at SNUH in 2007

• There is only 1 case of bacterial keratitis
  after EKC
• Alcaligenes Xylosoxidans (gram-negative rod)
• Oh et al. Korean J Ophthalmol. 2005 Sep19(3)

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Purpose

• To report the clinical characteristics of
  bacterial keratitis associated with outbreak of
  EKC
• To evaluate the risk factors for the development
  of bacterial keratitis in eyes with EKC

Design

• Retrospective case-control study with hospital
  based case series

Participants

• 108 patients (45 adults and 63 children)
  diagnosed as EKC in a tertiary eye-care center
  from July 2007 to August 2007
• 9 out of 108 patients who were treated with
  bacterial keratitis after an episode of EKC

4
Methods

• (1) Clinical aspects of bacterial keratitis after
  EKC
• Demographic data sex, age at infection,
  HCU-association
• Microbiological profile, onset of keratitis after
  EKC, corneal findings and classification
• Treatment outcome
• (2) Risk factors assessment for bacterial
  keratitis
• Definition
• Bacterial keratitis Any Infective corneal lesion
  with bacterial corneal cultures () or
  conjunctival bacterial swap culture ()
• EKC Clinical signs (follicular hypertrophy,
  exudative membrane, lacrimal swelling, mucoid
  discharge, redness and no other identified cause
  of conjunctivitis) and if possible, () result of
  Adenovirus Immunofluoresence assay (IFA) or
  culture
• Risk factors (statistical analysis)
• Use of steroid at early EKC period (Fishers
  test)
• Interval of F/U at early EKC period (Mann-Whitney
  test)
• MRSA colonization in conjunctiva and other part
  of body (Fishers test)
• Gestational age (Mann-Whitney test)
• Body Weight at infection (Mann-Whitney test)
• Duration of hospitalization (Mann-Whitney test)

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Result

• Epidemiology of EKC, Bacterial keratitis and
  Microbiological Features
• The incidence of bacterial keratitis (Table 1)
• Most bacterial keratitis(88) neonates and
  infants
• Significantly higher in HCU-based inpatients or
  children compared with population-based patients
  or adults
• Causative organism of bacterial keratitis (Table
  2)
• Methicilline resistant Staphylococcus
  aureus(MRSA)
• Most frequently found (7 cases)
• Coinfected with Staphylococcus epidermidis and
  Pseudomonas aeruginosa (1 case)
• Streptococcus pyogenes (1case)

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• Principle treatment of keratitis

• Onset of ketatitis after EKC (Table 2)
• Mean 8.8 days (3-12days)
• Treatment

• Initial Tx at EKC
• Topical ecolicin with or without topical
  steroid
• Initial Tx at Keratitis
• Discontinuation of steroid
• Systemic antibiotics IV Vancomycin, Amikin
• Local treatment
• 3.1 Vancomycin sol. q 1hr, 2 Amikin sol. q 1hr
• Change according to the reported sensitivity test
• If unresponsive to treatment
• 5 T-vanco ointment 6/d, 0.5 moxifloxacin sol. q
  2hr
• Surgical treatment 1 case (due to impending
  perforation) (Fig 1E)
• Amniotic membrane transplantation (Fig 1F, G, H)

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• Clinical manifestation of bacterial keratitis and
  Outcome of treatment (Table 2)

• Shallow infiltrations with epithelial defect
  (n2) (Fig.1A)
• Mean healing time 95.6 days (range 5-13 days)
• Corneal sequels after 3 mo (-)
• Stromal infiltrates underlying epithelial defects
  (n7)(Fig.1B, C)
• Mean healing time 25.616.7 days (range 10-51
  days)
• Corneal sequels after 3 mo
• Diffuse stromal new vessle 83.3(5/6)
• Corneal opacity 67.7(4/6) (Fig 1D)
• Though bacterial keratitis had been resolved in
  all of the patients, 44.4 (4/9) of bacterial
  keratitis patients have been requiring corneal
  transplantation due to dense central opacity (3
  months follow-up)

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• Risk factors assessment for bacterial keratitis

• Incidence of bacterial keratitis
• Significantly higher in HCU stayed patients and
  children (especially in neonate and infants)
  (Table 1)
• Using topical steroid in early EKC
• Not significantly different in HCU-based
  (3016/54) and population-based (4625/54) EKC
  patients (p0.07, ?2 test)
• In the HCU stayed children
• Factors significantly higher in bacterial
  keratitis group
• Culture positive rate of MRSA in conjunctiva
  (Table 3)
• Incidence of using topical steroid in early EKC
  period (Table 3)
• Longer interval of follow-up examinations in
  early EKC period (Table 4)
• Factors with no difference between bacterial
  keratitis and EKC group (Table 4)
• () Results for either adenoviral IFA or culture
• MRSA colonization of other parts of body
• Gestational age
• Duration of hospitalization

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Conclusion

• Infants including neonates show high tendency of
  MRSA keratitis accompanied with EKC, especially
  in HCU stayed inpatients
• MRSA colonization in conjunctiva, use of topical
  steroid and longer interval of follow-up for EKC
  can be a risk factor in development of MRSA
  keratitis

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Discussion

• Why bacterial keratitis after EKC in neonate and
  young infant?

• Weak physical barrier in the premature1
• epidermal barrier mature around the 32nd or
  34th week of gestation
• Weak mucosal membrane immunity2
• lower the sIgA in preterm infants at the age of 3
  to 8 postnatal months
• Weak innate and specific immunity to pathogen2
• Unable to complain

EKC destruction of corneal integrity
Compromised surface
Highly susceptible of infection
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• Why MRSA keratitis in health care unit?

• MRSA infection3
• 12 community-associated, 85 health
  care-associated
• MRSA nares colonization4
• MRSA colonization in nares 25 of MRSA infection
  rate compared with 2.0 of the uncolonized
• MRSA ocular surface colonization and nasal
  carriage5
• Conjunctival MRSA () Anterior nares of MRSA
  78
• Conjunctival MRSA (-) Anterior nares of MRSA
  11
• SNUH NICU6
• 10.4neonates became colonized for MRSA in
  nasal/ inguinal cultures
• The mean time to acquire MRSA colonization was
  17.1 days (1-471days)

Compromised surface with EKC may elicit MRSA
keratitis!! Risk factor MRSA colonization,
Topical steroid use, Long interval of F/U
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References

• 1. Cartlidge P. The epidermal barrier. Semin
  Neonatol. 20005273-80.
• 2. Adkins B, Leclerc C, Marshall-Clarke S.
  Neonatal adaptive immunity comes of age. Nat Rev
  Immunol 20044553-64.
• 3. Naimi TS, LeDell KH, Como-Sabetti K et al.
  Comparison of community- and health
  care-associated methicillin-resistant
  Staphylococcus aureus infection. JAMA
  20032902976-84.
• 4. Davis KA, Stewart JJ, Crouch HK et al.
  Methicillin-resistant staphylococcus aureus
  (MRSA) nares colonization at hospital admission
  and its effect on subsequent MRSA Infection. Clin
  Infect Dis. 200439776-82.
• 5. Kimura N, Sotozono C, Higashihara H et al.
  Relationship between ocular surface infection or
  colonization of methicillin-resistant
  Staphylococcus aureus and nasal carriage. Nippon
  Ganka Gakkai Zasshi. 2007111504-8.
• 6. Kim YH, Chang SS, Kim YS et al. Clinical
  outcomes in methicillin-resistant Staphylococcus
  aureus-colonized neonates in the neonatal
  intensive care unit. Neonatology 200791241-7.