MYCOBACTERIUM CHELONEI KERATITIS:

A CASE REPORT AND REVIEW OF PREVIOUSLY

REPORTED CASES

DAVID C. BROADWAY I MA LCOLM G. KERR-MUIRI, SUSANNAH J. EYKYN2 and

,
HOSEP PAMBAKIAN'
London

SUMMARY mild exophthalmos and superior limbic keratoconjunctiv­

A 56-year-old woman who wore hard contact lenses itis, all of which subsequently improved.
developed a keratitis due to Mycobacterium chelonei. The With the onset of the painful left eye, she ceased wear­
organism was only sensitive to imipenem and partially to ing her contact lenses and was treated for 'conjunctivitis'
ciprofloxacin and erythromycin. After an initial response with G. neomycin 0.5%/hydrocortisone 1.5%. After initial
to topical therapy with these antibiotics the infection improvement. the condition relapsed and I month later the
relapsed and a penetrating keratoplasty was performed, treatment was changed to G. chloramphenicol 0.5% q.d.s.
with resulting cure. M. chelonei has not previously been The corrected (-\0.00 DS) left visual acuity was 6/18.
reported as a cause of keratitis associated with hard con­ the eye was red with a small inferior corneal ulcer plugged
tact lens wear; neither has its treatment with imipenem with mucoid material. The lesion was debrided, treated
and/or ciprofloxacin. A detailed photographic record with Oc. betamethasone 0.1 %/neomycin 0.5% and pad­
showing the natural history of the keratitis is presented. ded. Initial improvement was followed by relapse. A
Previously reported cases of M. chelonei keratitis are chalky anterior stromal infiltrate with associated epithelial
reviewed.
defect developed. Surrounding epithelial oedema, local­
ised stromal oedema and a few small keratic precipitates
Mycohacterium chelonei keratitis is rare. Only 2 cases
.e (KPs) were evident. The patient was admitted for corneal
have previously been reported in the United Kingdom. I
scraping and treated with hourly topical G. gentamicin
13 in the United States and Canada,l-Il.l� 2 in Chinal1 and I
(USIc and G. methicillin 2%. The following day the con­
in Australia.12 In these cases the organism was multi­
dition was thought to resemble staphylococcal corneal
resistant to antimicrobials but where specified was sensi­
disease and treatment was changed to G. methicillin 2%
tive ill vitro, or showed a clinical response to amikacin. A
2-hourly and G. prednisolone 0.3% q.d.s. Three days later
further II cases have recently been reported in the United
bacteriological culture revealed growth of an atypical
States, but clinical details are not available. I)
mycobacterium (later identified as M. chelonei) sensitive
Delay in diagnosis and multiresistance mean that
to gentamicin. However, since the condition was improv­
medical therapy alone is frequently unsuccessful in the
ing the patient was discharged with no change in
management of M. chelollei keratitis.
treatment.
Four days later she returned; the infiltrate was thicker,
CASE REPORT
the KPs larger and there was mild iritis. Treatment was
A 56-year-old woman with high myopia who had worn
changed to G. gentamicin 0.3% 2-hourly and G. pred­
hard contact lenses for 18 years presented with a red pain­
nisolone 0.3% q.d.s. Four days later the condition had
ful left eye of 2 days' duration.
deteriorated further and the visual acuity was 6/24-1. Cor­
At the age of 17 years she had mild dysthyroid eye
neal sensation was normal but the lesion was now thought
disease and her corrected visual acuities were 6/9. N5 in
to look herpetic. Oc. acyclovir 3% 5x/day was added.
each eye. Clinical signs included lid retraction. lid lag.
Again there was an initial clinical improvement but this
From: 'Department of Ophthalmology. 'Department of Microbiology was not sustained. After a further 6 weeks of treatment the
and )Department of Histopathology. St Thomas' HospitaL London. UK. patient was referred to St Thomas' Hospital.
COlTespondence to: Mr David Broadway. Department of Clinical
Science. Institute of Ophthalmology. 17-25 Cayton Street. London The patient's best corrected (-12.00 DS) left visual
ECIV 9AT. UK. acuity was 6/18. The eye was injected and the corneal

Eye (1994) 8,134-142 © 1994 Royal College of Ophthalmologists

MYCOBACTERIUM CHELONEI KERATITIS 135

Fig. 1. The left eye at presentation to St Thomas' Hospital. ((I) The corneal lesion. (b) The lesion stained withfiuorescein. There is a
craggy, opaque, central and anterior corneal plaque measuring 5 x 4 mm (a) Ivith associated epithelial staining defects (b). Beneath
this were several discrete but faint stromal lesions with surrounding satellite lesions and adjacent deeper stromal infiltrate. The lesions
were mainly globular, although some had a spicule or crystal-like appearance. A separate, small deep-stromal satellite lesion 0.75 mm
(rom the main lesion can be seen superonasally (arrmv).

Fig. 2. The corneal biopsy. (a) There is ulceration of the surface epithelium and stromal infiltration with a moderate number of poly­
morphs. (b) In the slough (){the ulcer base there are numerous acid-alcohol fast bacilli (AAFB) (Ziehl-Neelsen stain).

lesion consisted of a large diffuse sub-epithelial infiltrate sidered necessary in view of the anterior chamber (AC)
below which a number of more focal opacities were pres­ activity and to prevent steroid withdrawal rebound iritis.
ent. A satellite lesion was identified supranasally (Fig. 1). Over the subsequent week a subjective improvement
There was mild iritis. Treatment was stopped for 2 days occurred, the eye became less injected and reduction in
and a corneal biopsy taken. Gram stain showed pus cells corneal stromal oedema revealed pigmented KPs. There
only, and no acid-alcohol fast bacilli (AAFB) were was only mild AC activity, with no hypopyon. The corneal
detected with auramine stain. A fungal keratitis was sus­ lesion and visual acuity, however, remained unchanged.
pected and treated with G. miconazole 1 % 2-hourly and G. The topical antibiotics were subsequently administered at
atropine 1% q.d. s. Deterioration occurred with extension longer intervals.
of the keratitis and development of a fibrinous iritis and Ten days later the corneal stromal lesion was more dis­
small hypopyon. crete, but the individual opacities, at various depths
Meanwhile histopathological examination of the cor­ throughout the stroma, began to change in character
neal specimen showed numerous AAFB in the slough of (Fig. 3).
the ulcer base (Fig. 2) and after 5 days' incubation a light The M. chelonei was reported sensitive to imipenem
growth of AAFB was obtained on blood agar and Low­ and partially sensitive to erythromycin and ciprofioxacin.
enstein-lensen medium. The organism was later identi­ It was resistant to amikacin.
fied by the Regional Tuberculosis Centre (Dulwich Public The patient was then admitted for intensive topical ther­
Health Laboratory) as M. chelonei. Pending the results of apy with G. imipenem 0. 5% I-hourly/day and 2-hourly/
in vitro sensitivity tests treatment was changed to G. ami­ night, G. ciprofioxacin 0. 2% I-hourly/day and 2-hourly/
kacin 2.5% lh-hourly/day and I-hourly/night, G. dexame­ night, Oc. erythromycin 5x/day, G. atropine 1 % b. d. and
thasone 0. 1 % I-hourly/day and 2-hourly/night with G. G. dexamethasone 0. 1 % t. d.s.
atropine 1% q. d. s. Intensive steroid therapy was con- After 2 days there was subjective improvement but little
136 D. C. BROADWAY ET AL.

Fig. 3. The corneal lesioll q H'eeks after presentation. (a)

Localised opacities withill the main lesion. (h) The upper-nasal
satellite lesiolls. (c) The upper-temporal qlladrallf of the main
corneal lesion showillg some otrhe localised stromal opacities.
Discrete. dense. deep stromal lesions han' appeared within the
main lesioll, Two satellite lesiolls cal1 he identified supcrol1asal
to the lIIail1 lesioll. the original olle hm'illg cnlarged. the secolld.
situated at thc edge of the maill lesioll. heillg small and neH'. A
grollp olsil7lilar lesiolls can he seell ar the upper-temporal edge
o/the main lesioll. The lesiolls were illitiallv glohular ill nature
with 110 adjacelll cellular actil'itv, The corneal epithelium was
intact at this stage. Four dars later sOllie of the glohular opac­
ities were lIoted to hare migrated to rhe mid-stroma. hecome
stellate shaped alld to show polychromatic arhorisatiol1,

change on examination. The main lesion developed an ological examination revealed numerous AAFB. Cultures
irregular surface and became thinned centrally. The dis­ were unfortunately contaminated. Thus, a left penetrating
crete globular and stellate stromal lesions (including the keratoplasty (PK) was performed about 10 months after
satellites) persisted (Fig. 4). Over the next 3 weeks the cor­ onset of the initial symptoms. Histopathological examin­
neal lesion changed. The central components of the main ation of the corneal button (Fig. 8) demonstrated clear sur­
lesion were extruded; the satellites remained (Fig. 5). gical margins.
Topical antimicrobial therapy was reduced to 3-hourly Two years later the graft remains clear and corrected
and the steroid increased to 4-hourly. visual acuity is 6/12.
For 5 weeks there was a reduction in inflammation and
an increase in visual acuity to 6/12 + I. Over the sub­
DISCUSSION
sequent 10 days a new satellite lesion appeared temporally
(Fig. 6), the upper-nasal lesions disappeared and AC The atypical mycobacterium M, che/onei was first identi­
activity increased. Steroid administration was increased to fied by Freidmann in 1903 when he cultured AAFB from
2-hourly. Ten days later a new focal globular opacity was two Berlin Zoo sea turtles (Che/ona corticata) which had
evident within the central part of the main lesion. Over 2 developed pulmonary disease. Distribution of the organ­
weeks this opacity enlarged and simultaneously the upper­ ism within the environment remains unknown, Ib but it was
temporal lesion became less feathery, more anteriorly tirst recognised as a human pathogen in 1953 by Moore
situated and associated with a small epithelial defect and and Frerichs 17 who isolated it from an infected knee joint.
localised stromal oedema which responded to hourly G. Since then it has been increasingly reported as a pathogen
dexamethasone 0.1%. Both lesions were eventually in a variety of human diseases.6lblX '5 M. che/onei keratitis
extruded in the same manner. is rare. We have identified 18 casesl . l" summarised in
Over the following month the condition remained stable Table L and a further I I of which there are no clinical
with no further development of focal stromal opacities, details. I)
although the central opacification had increased to 5 x M che/onci is an opportunistic pathogen and most
8 mm in area (Fig. 7). After I I weeks of specific treatment patients with this infection have had predisposing injury
the condition worsened. Visual acuity fell to 6/36. there (including surgery). Others have been immunocompro­
was central epithelial loss and new peripheral satellite mised or worn extended-wear contact lenses. Preceding
lesions appeared. local trauma had occurred in 16 of the 17 reported cases of
A further corneal biopsy was performed and histopalh- M. che/ollei keratitis where relevant details were provided
MYCOBACTERIUM CHELONEI KERATITIS 137

Fig. 4. The corneal lesion 7 \\'eeks after presentation A mix­

tllre or glolmlar and stellate stromal lesions can he seen.

Fig. 5. The corneal lesion 10 weeks after presentation. (a) The lefi ere. (h) The corneal lesion (e) The lipper-nasal satellite lesiol1s.
(d) The opacity at the upper-temjJoral margin or the main lesion. Each of'the discreTe opacities \\'ithin the main lesion migrated for­
wards within the cornea, passing throllgh a transient stellate appearance in the mid-stroma. Finally, each was extruded to disappear
and leave b ehind an epithelial erosion. The tll'O salellile lesions Ie) and one on the lipper-temporal margin oj'the main lesion (d)
remained, b ecoming larger and more .flllff.'· or/eatherr.

(see Table I). In this case the patient had worn hard contact should alert the clinician to seek expert laboratory assist­
lenses for 18 years and had mild dysthyroid eye disease ance. Most microbiology laboratories do not perform
which may have predisposed to the infection. special staining for AAFB on corneal specimens unless
In most of the reported cases there was a latent period of specifically requested, and most specimens are incubated
2-8 weeks after corneal insult before the keratitis pre­ for only 48 hQurs - an inadequate time for M. chelonei to
sented. The condition is characterised by a long delay grow. The first indication of this unusual infection may
between presentation and correct diagnosis for a number well come from a histology report.
of reasons: the keratitis is rare and readily mistaken (as in Descriptions of the M. chelollei lesions from previous
this case) for herpetic, fungal or other bacterial disease. reports are similar to this case, the characteristic lesion
Repeated failure of a variety of therapeutic regImens being an irregular infiltrate with radiating projections. the
 .......
w
00

Table I. Cases of Mycobacterium che/onei keratitis

Interval Method of
Age between Initial diagnosis and Definitive
and Insult injury and antimicrobial in vitro antimicrobial Duration
Noyefl Date sex to cornea keratitis treatment Steroid sensitivities treatment Surgery of disease Result

1131 1978 39 F Dendritic ulcer Not specified Idoxuridine Corneal scrape and Kanamycin, erythromycin, PK (for 2 months Clear graft
culture; gentamicin gentamicin failure of 16 months
medical later
treatment)
2141 1982 35 M Metal FB 6-8 weeks Prednisolone! + Corneal scrape and Amikacin (condition PK 4-5 months Not
(welding) sulphacetamide, neomycin/ culture; amikacin improved but could not be specified
polymyxin B, amphotericin eradicated)
B, bacitracin

3111 1983 84 F FB (raking leaves); �5 weeks Idoxuridine, trifluoridine, + Corneal scrape and culture; Amikacin and erythromycin PK 5 months Clear graft
dendritic ulcer? prednisolone/ amikacin (condition improved but 6 months
sulphacetamide, could not be eradicated) later
phenylephrine, erythromycin,
polymyxin B/neomycin!
gramicidine

4161 1983 60 M Suture abscess 3 months Not specified + Corneal scrape and culture; Amikacin Not specified Resolution
(post triple no sensitivities specified
procedure)

5171 1984 68 M Suture removal 3 weeks Various antibiotics including + Corneal scrape and culture; Erythromycin (10 days), 5 months Resolution
(post PK) natamycin amikacin, erythromycin Amikacin (5 months) (with
residual
scarring)
6171 1984 78 F Needle PC 2 weeks Various antimicrobials + Corneal button culture; Various antimicrobials PK (for 3 months Clear graft
(unspecified) amikacin, erythromycin (unspecified) failure of
medical,
treatment)
7171 1984 82 F Needle PC 2.5 weeks Gentamicin, + Corneal button culture; Tobramycin PK and Not specified Clear graft
chloramphenicol amikacin, tobramycin, vitrectomy
erythromycin (for failure
of medical
treatment)
8181 1986 37 F RK 2 weeks Various antibiotics including + Corneal biopsy and culture; Amikacin (condition PK 6 months Clear graft
cefazolin, tobramycin and amikacin improved but could not be
bacitracin eradicated)
9181 1986 33 F RK 2 weeks Various antibiotics and anti- + Corneal biopsy and culture; Amikacin >6 weeks Resolution
fungal drugs (unspecified) not specified

(Continues)
Table I. (Continlled)

Interval Method of
Age between Initial diagnosis and Definitive
and Insult injury and antimicrobial in vitro antimicrobial Duration
No.I"'1 Date sex to cornea keratitis treatment Steroid sensitivities treatment Surgery of disease Result

10111 1987 65F PK (x2) and 6 weeks (after Methicillin, gentamicin, + Corneal scape and culture; Amikacin, 6 months Resolution
extended-wear second PK) penicillin, chloramphenicol, ethionamide, gentamicin erythromycin (with
contact lens use polymyxin Blbacitracin, (resistant later) residual
cephaloridine, tetracycline scarring)
IIIYI 1987 60 M PK 2 months Various topical medications Corneal scrape and culture; Amikacin (condition PK 1-2 months Clear graft
(unspecified) amikacin improved but could not be 14 months
eradicated) later

121101 1987 41F PK 3 months Isoniazid, rifampicin, Corneal scrape and culture; Erythromycin, gentamicin, 2 months Resolution
ethambutol, pyridoxine, amikacin, erythromycin, tetracyline, rifampicin,
streptomycin streptomycin, tetracycline streptomycin

131111 1988 29F Extended-wear Unknown Prednisolone! + Corneal biopsy and culture; Amikacin 9 months Resolution
contact lens use sulphacetamide, idoxuridine, not specified (with
vidarabine residual
scarring)

141121 1 989 77F ECCE + IOL 6 months Not specified + Corneal scrape and culture; Amikacin. PK (for >6 weeks Clear graft
amikacin, cefoxitin, oxytetracycline failure of 8 months
erythromycin medical later
treatment)
151131 1989 ? Corneal trauma Not specified Not specified Corneal scrape and culture; Various antimicrobials 2-3 months Not
not specified specified
161131 1989 ? Corneal trauma Not specified Not specified Corneal scrape and culture; Various antimicrobials 2-3 months Not
not specified specified

171'1 1990 -F Not specified Not specified Not specified ') Not specified; not specified Not specified Not specified Not
specified

181141 1990 64M FB (mowing lawn) ",I month Tobramycin, natamycin and Corneal biopsy and culture; Amikacin II months Resolution
ketoconazole with various not specified (with
antimicrobials (unspecified) residual
scarring)

This 1991 56F Hard contact Unknown Various antibiotics (see text), + Corneal biopsy and culture; Imipenem, ciproftoxacin, PK (for 10 months Clear graft
case lens wear acyclovir, miconazole imipenem, ciproftoxacin erythromycin failure of 24 months
(partial), erythromycin medical later
(partial) treatment)

Abbreviations: PK, penetrating keratoplasty; RK, radial keratotomy; PC, posterior capsulotomy; ECCE, extracapsular cataract extraction; IOL, intraocular lens;FB, foreign body.

.......
VJ
\0
140 D. C. BROADWAY ET AL.

Fig. 6. The corneal lesion J 7 weeks afier presentation show­ Fig. 7. The corneal lesion 22 weeks after presentation. No
ing the new temporal satellite lesion (arrow!.lnitiallr g!o)J/I!ar /ilca! opacities are present in the corneal lesion. which has
and located in the deep stroma, the new satellite lesion grudll­ increased in si:e hI' incorporation of the regions /Jrel'iously
allyincreased in size, its appearance hecoming more feather\' as occllpied hy the satellite lesions.
it migrated into the mid-stroma. In COl1lrast, Ol'er the same
period of time the two older satellite lesions hecame confillent
and less feathery hefore heing extruded. this heing associated
with epithelial loss and increased discomf(JrI. The lIpper-tem­
poral opacitycontinued to increase in si:e. maintaining a feath­
eryappearance.

. .....

Fig. 8. The penetrating keratoplastv corneal 171111011. (a) There is a celllralmid-stromal carit)' containillg a colon.'>' of microorganisms
associated with some granillar material. There is a 1I00iceahle ahsellce IIfillfiammatilll1 ill the specimell. (h) The colony oj'microorgan­
isms consists of numerous AAFB (Ziehl-Neelsen staill).

lesion margins having an indistinct, fluffy or feathery eventually the lesion or part of it would become extruded
appearance. The lesions can involve all levels of the with associated epithelial loss.
stroma with a predilection for the mid to deep stroma. In this case definitive diagnosis was by corneal biopsy
They have been described as 'snow-flakes' x or to have a and culture. The method of diagnosis in 15 previously
'cracked windshield' appearance5 - this latter appearance reported cases was corneal biopsy,7.x.11.14 scrape 3-5.7.9-1.1 or
has also been described in M.fortuitum keratitis."O Satel­ re-scrape 1.6 and culture. In 2 of the cases reported by New­
lite lesions, a prominent feature in this case, are also man et a/7 the diagnosis was made after penetrating ker­
.. 2
reported. 1 9 11.1 An associated epithelial defect appears to atoplasty by culture of corneal buttons.
be universal. M. che/onei is resistant to conventional anti-mycobac­
In none of the previous reports has the natural history of terial agents but often sensitive ill I'ilro to amikacin27
the corneal lesions been discussed. In this case focal which has thus emerged as the drug of choice. Sensitivity
lesions appeared initially in the deeper stroma and were testing of atypical mycobacteria is technically difficult
globular in shape. These then moved forward in the cor­ and in I'irro results are poor predictors of clinical response.
nea, the margins becoming indistinct and feathery, giving In 9 of the reported cases of M. che/onei keratitis the
small lesions a stellate appearance. This appearance organism was reported sensitive to amikacin.4j.7-lo.12 In 2
diminished as the lesions reached the anterior stroma and of these cases7.X treatment with amikacin was successful.
MYCOBACTERIUM CHELONEI KERATITIS 14 1

In another 5 cases"'S'J12 there \vas an initial improvement M. che/onei keratitis is a rare infection and diagnostic
with amikacin but the infection could not be eradicated. delay is virtually inevitable. Persistent failure with
and all were eventually managed by penetrating kerLl­ assorted therapeutic regimens should alert the clinician to
toplasty. Amikacin sensitivity was not specified in 7 the presence of an unusual microbe and expert microbio­
cases2.1.6XI,I" but in 3 of these there was a favourable clini­ logical and histopathological help should be sought. Oph­
cal response to amikacin.6K.," In2 cases.1 11 although ill vit­ thalmologists should be particularly aware of the
ro resistance to amikacin was reported. the keratitis possibility of mycobacterial corneal infections after sur­
responded to amikacin used alone" or in combination gery or ocular trauma. Once suspected there should be an
with erythromycin.I These cases indicate that ill \'itro test­ aggressive approach directed to obtaining adequate cor­
ing toM. chelonei can be unreliable. neal tissue for staining and culture. Corneal biopsy rather
In this case there was no evidence of ill I'itro sensitivity than scraping is ideal. In addition, pathology departments
or clinical response to amikacin. but there was in vitro sen­ should be provided with adequate clinical information
sitivity to imipenem and partial sensitivity to ciproHoxa­ since routine cultures may be discarded before mycobac­
cin and erythromycin. Treatment with these drugs teria have had time to grow.
produced an initial response. but the improvement was not
Key words: Ciprofioxacin. Imipenem, Keratitis, Mycobacterilllll
maintained. dll'/ollei.
Erythromycin has been used successfully to treat M.
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