Managing microbial keratitis

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Managing microbial keratitis
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Diagnosis

• Microbial keratitis is rare in the absence of
  predisposing factors which include (1) contact
  lens wear, (2) ocular surface disease, eg (a)
  herpetic keratitis, (b) corneal-anaesthesia, (c)
  exposure and (d) bullous keratopathy and (3)
  trauma. Infection can present as an epithelial
  defect or corneal melt, without inflammation, in
  the immunocompromised or in those using topical
  steroids in whom corneal infiltration by
  leucocytes, the hallmark of microbial keratitis,
  may be absent.

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Corneal Exposure
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Corneal Melt
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Corneal Ulcer
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Initial Investigation

• Corneal scraping is indicated whenever microbial
  keratitis is suspected. It provides material for
  a microbiological diagnosis, debrides necrotic
  tissue and enhances antibiotic penetration.
  Endophthalmitis does not follow bacterial
  keratitis without corneal perforation (unlike
  fungal keratitis) so that anterior chamber and
  vitreous taps are not indicated when perforation
  is absent

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Corneal culture materials

• Corneal culture materials should be available in
  the emergency area and include, as a minimum, a
  slide for Gram staining and a blood agar plate
  for aerobic incubation. Most corneal isolates in
  temperate areas, including fungi, will grow on
  these media. Ocular specimens should be
  inoculated directly onto the media avoiding the
  use of transport or storage media. Some of the
  pathogens isolated from ocular infections may be
  considered to be normal flora by non-ocular
  microbiologists, so it is important that
  ophthalmologists liaise closely with the
  laboratory. A 21 gauge needle may be used to take
  the specimens.

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Hypopion Ulcer
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Treatment

• Therapy can be divided into a sterilisation phase
  and a healing phase with clearly defined
  endpoints for clinical review and decision
  making. Clinical signs may not indicate when
  corneal sterilisation has occurred, after
  starting intensive therapy, because sterilisation
  often precedes both epithelial healing and the
  resolution of inflammatory signs.

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Treatment

• These may also be delayed by preservative or
  agent related toxicity where intensive topical
  treatment is prolonged. Intensive antibiotic
  therapy is given for a limited period in the
  stetilisation phase and is followed by the
  healing phase, in which reduced therapy is aimed
  at (1) limiting further inflammatory damage, (2)
  preventing superinfection, and (3) promoting
  epithelial healing.

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Treatment

• Antibiotics should consist of broad spectrum
  topical antibacterial treatment because (1) a
  negative Gram stain does not exclude keratitis,
  (2) bacterial isolates are far more common than
  fungi or amoebae and (3) polymicrobial infections
  are common. This approach is continued unless the
  infecting agents are identified, with their
  antimicrobial sensitivities, enabling specific
  therapy to begin.

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Antibiotics

• The choice of antibiotics now hes between the
  standard regimen of topical, commercially
  unavailable, fortified aminoglycoside and
  fortified cephalosporin drops (ie gentamicin 1.5
  and cefuroxime 5) or the new regime of
  fluoroquinolone monotherapy with commercially
  available ciprofloxacin or ofloxacin 0.3.

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Broad spectrum cover against the majority of
bacterial pathogens

• Both the standard and new regimens offer broad
  spectrum cover against the majority of bacterial
  pathogens but fluoroquinolone monotherapy has
  advantages and has been shown to have equal
  efficacy in recent clinical trials.
• However, fluoroquinolones may not adequately
  treat streptococcal keratitis and comination
  therapy of a quinolone with a fortified
  cephalosporin may be advisable in patients with
  ocular surface disease or in children in whom
  streptococcal infection is more common.
• Currently both the standard and fluoroquinolone
  regimen encounter bacteriola resistance in about
  5 of cases.
• Neither regimen treats fungal or acanthamoeba
  infection.

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Sterilisation Phase

• Hourly administration of topical antibiotic
  therapy for five days leaves a wide rnargin of
  safety for most bacterial infections and compares
  well with a gradual reduction of high dose
  antibiotic treatment.
• Most cases can be managed successfully as
  outpatients with initial review after forty eight
  hours. Admission may be necessary where good
  compliance is unlikely or for overnight treatment
  in severe infections (axial lesions, lesions 6mm
  or more in diameter, or with 50, or more stromal
  thinning). Systemic antibiotics (ie ciprofloxacin
  750mg bd) ire indicated where the ulcer is close
  to the limbus. This may help protect from
  contiguous spread of infection to the sclera and
  enhance antibiotic delivery to peripheral
  lesions. Adjunctive treatment at this stige may
  include (1) dilating drops, (2) analgesic
  medication or (3) hypotensive agents for
  secondary glaucoma. Subconjunctival injections
  should be avoided.

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Sterilisation Phase

• Amoebic and fungal kerititis are rarely rapidly
  progressive and may be exacerbated by bacterial
  superinfection. Specific investigations and
  treatment regimens, involving a much more
  prolonged sterilisation phase, are required for
  both and lie outside the scope of this review.
  However, unless there is clear clinical evidence
  (or a Gram stain) suggesting non-bacteriid
  infection, it is appropriate to commence
  treatment with intensive broad spectrum
  antiibiotics for a defined initial period.

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Interpretation of Culture

• Whilst cultures should be incubated for a
  minimum of 14 days before being reported as
  culture negative, growth of most pathogens can be
  expected ifter 48 hours.
• Sensitivity Testing
• If clinical progress is satisfactory, there is no
  indication for altering antibiotic therapy. But
  sensitivity testing can be invaluable in guiding
  the choice of a more appropriate antibiotic where
  bacterial keratitis is progressive.
• Review at one week is necessary to determine
  whether the disease is progressive or resolving.
  Clear evidence of poor compliance or, in culture
  positive cases, resistance to the initial
  antibiotic choice are indications for re-entering
  the sterilization phase using appropriate
  specific therapy. Deteriorating or static cases
  should be referred, whereas cases in which
  resolution is partial but incomplete may safely
  enter a second phase of treatment directed at
  encouraging healing.

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Initial Review

• Early review at two days is to detect rapidly
  progressive cases and assess the culture results.
  Daily review can be confusing as the inflammatory
  reaction may be enhanced by endotoxin release
  within the first 48 hours.
•  
• However definite progression at this stage
  (increased stromal thinning or a clear expansion
  of the ulcer) is unusual, and implies that
  patients are either insensitive to, or not
  complying with, antimicrobial therapy.
•  
• This rapid early progression can be treated by
  admitting patients to ensure compliance and
  reviewing the microbiology results. Unless these
  indicate resistance to the primary therapy, with
  a change to a more appropriate antibiotic, then
  continue initial broad spectrum antibiotic
  therapy until two days of hourly treatment day
  and night have been followed by a further three
  days of hourly treatment during the day. Further
  progression after this point is then an
  indication for specialist referral.
• Threatened or actual perforation indicate urgent
  referral as emergency penetrating keritoplasties
  in these circumstances carry a poor prognosis for
  vision, are difficult to perform well, and can
  often be avoided even after a perforation.

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Healing Phase

• Healing is commonly retarded by persisting
  inflammation, treatment toxicity or untreated
  underlying ocular surface disease. Antibiotic
  treatment should be reduced to prophylactic
  levels at this stage to avoid toxicity and
  unpreserved medication used where possible.
• Ocular surface disorders (ie dry eyes, exposure,
  entropion and blepharitis) must be treated.
  Complete resolution of anterior chamber and
  comeal inflammatory signs is normal in microbial
  keratitis without steroid treatment. However,
  topical steroids may speed re-epithelisation and
  resolution of the inflammatory response although
  their use will enhance fungal or herpetic
  infection and may increase the risk of
  perforation by inhibiting wound healing. In
  corneal graft recipients, without evidence of
  fungal infection, steroid therapy should be
  introduced at the outset to protect against a
  rejection episode.
• At review after one week of the healing phase (ie
  week 3 after presentation), referral may be
  indicated as indolent ulceration may be due to
  unusual organisms, usually of low virulence, with
  continued disease progression