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 Microbial
keratitis results from the interaction of a broad spectrum of pathogens
and a diverse range of host responses. Uncertainty about treatment
endpoints sometimes leads to toxic levels of antibiotic therapy
and unnecessarily frequent clinical review. This article draws on
a comprehensive review that can be referred to for further detail.1
It outlines a simplified management strategy that is successful
for the majority of cases and identifies the point of failure when
referral may be indicated.
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.
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. 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.
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.
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.
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.
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%.
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.2,3,4 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.
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.4
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.
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.
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.
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.
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,
If
slow healing is occurring patients can continue with the healing
phase regimen until resolution is complete.
JKG
Dart FRCOphth
References
1.
Allan DS, Kart JKG (1995). Strategies for the management of
microbial keratitis. Br J Ophthalmol 1995; 79; 777-86.
2.
O'Brien TP. Maguire MG, Fink NE, Alfonso E, McDonnell P (1995).
Efficacy of ofloxacin vs cefazolin and tobramycin in the therapy
for bacterial keratitis. Report from the Bacterial Keratitis Study
research Group. Arch-Ophthalmol 1995; 113; 1257-65.
3.
Hyndiuk RA, Eiferman RA, Caldwell DR, Rosenwasser GO, Santos CI,
Katz HR, Badrinath SS, Reddy MK, Adenis JP, Klauss V. Comparison
of ciprofloxacin ophthalmic solution 0.3% to fortified tobramycin-cefazolin
in treating bacterial corneal ulcers. Ciprofloxacin Bacterial keratitis
Study Group. Ophthalmology 1996; 103; 1854-62.
4.
The Ofloxacin Study Group (1997). Ofloxacin monotherapy for
the primary treatment of microbial keratitis: a double-masked randomised
controlled trial with conventional dual therapy. Ophthalmology
1997; in press.
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