Management Options for Propionibacterium acnes Endophthalmitis WILLIAM ZAMBRANO, MD, HARRY W. FLYNN, Jr., MD, STEPHEN C. PFLUGFELDER, MD, THOMAS J. ROUSSEL, MD, WILLIAM W. CULBERTSON, MD, SIMON HOLLAND, MD, DARLENE MILLER, MA

Abstract: The authors reviewed the management of nine culture-proven cases of Propionibacterium acnes endophthalmitis which presented at an average of 4 months after extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens (PC IOL) implantation. The initial signs included a white intra­capsular plaque (9/9), vitritis (9/9), granulomatous uveitis (4/9), nongranuloma­tous uveitis (5/9), hypopyon (4/9), beaded fibrin strands in the anterior chamber (3/9), and diffuse intraretinal hemorrhages (2/9). A variety of management schemes were used in these patients, including the following: topical and intra­venous antibiotics alone; intraocular and topical antibiotic administration; pars plana vitrectomy with capsulectomy and intraocular antibiotic administration; and removal of all capsular remnants with PC IOL removal or exchange. The final visual acuities ranged from 20/20 to 20/60 in six eyes and 2o;2oo to 20/400 in three eyes. This review suggests that a variety of management op­tions for P. acnes endophthalmitis appear to be successful. Based on the authors' experience, an algorithm for future treatment is offered. Ophthalmology 96:1100-11 05, 1989

Propionibacterium acnes is a gram-positive anaerobic pleomorphic rod which has been implicated in a wide variety ofocular and periocular infections. 1Recent studies have focused on the association of P. acnes with a syn­drome of delayed onset postoperative endophthalmitis after extracapsular cataract extraction (ECCE) and pos­terior chamber intraocular lens (PC IOL) implanta­tion.Z-11 Currently, 16 cases ofchronic Propionibacterium­associated endophthalmitis after ECCE have been re­ported and a variety of treatment options have been dis-

Originally received: October 8, 1988. Revision accepted: March 28, 1989.

From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami.

Presented at the American Academy of Ophthalmology Annual Meeting, Las Vegas, October 1988.

Supported in part by Research to Prevent Blindness, Inc, New York, New York.

Reprint requests to Harry W. Flynn, Jr., MD, Bascom Palmer Eye Institute, 900 N.W. 17th St, Miami, FL 33136.

cussed. 11 We reviewed the management of nine cases of culture-proven P. acnes endophthalmitis and discuss the multiple treatment options successful in its management in this largest clinical series.

PATIENTS AND METHODS

We performed a retrospective review of the microbio­logical laboratory files and corresponding clinical records of all patients who were seen by the full-time faculty at the Bascom Palmer Eye Institute from 1984 to 1988 with a diagnosis of P. acnes endophthalmitis (Table 1). Nine cases were identified on basis of these records. No poly­microbial infections occurred in these cases. Both Acti­nomyces israeli and P. acnes were cultured from the vit­reous specimen of one outside case. This case was treated by physicians at another hospital and was excluded be­cause of inadequate information regarding the clinical course and treatment. Another case occurred with his­topathologic identification of organisms suggestive of P. acnes within the lens capsule but was excluded because

1100

ZAMBRANO et al • PROPIONIBACTERIUM AGNES ENDOPHTHALMITIS

Table 1. Clinical Features colate broth from the aqueous or vitreous plus the pres­

Interval to Onset of Culture Presenting

Case No./ Inflammation Diagnosis Signs at the Age (yrs)/ (mas after (mas after Time of Culture

Sex cataract surgery) cataract surgery) Diagnosis

1/70/M 10.00 38.0 WP, V, GU, H 2/68/M* 2.50 10.0 WP, V, NGU, H 3/81/M 12.00 13.0 WP, V, GU, BFS, DIH 4/60/M* 3.50 210 WP, V, NGU 5/60/Ft 2.50 6.0 WP, V, GU, BFS 6/63/F 1.25 1.5 WP, V, NGU, H 7/76/M 025 1.25 WP, V, NGU, H 8/82/F 0.25 0.5 WP, V, NGU 9/76/F 2.00 13.0 WP, V, GU, BFS, DIH

WP = white intracapsular plaque; V = vitritis; GU = granulomatous uveitis; H = hypopyon; NGU = nongranulomatous uveitis; BFS = beaded fibrin strands; DIH = diffuse intraretinal hemorrhages.

* Previously reported in reference 7. t Previously reported in reference 10.

no intraocular cultures were performed. This case re­sponded favorably to treatment consisting ofiOL removal, anterior vitrectomy, and no intraocular antibiotics.

The clinical charts of each of the nine patients were reviewed for epidemiologic data, clinical history, thera­peutic modalities, and outcome. All nine cases had ECCE primarily and eight of the nine had PC IOL implantation at the same operative procedure. One patient (case 7) had vitreous loss at the initial cataract extraction and no IOL was implanted. A secondary IOL was implanted in this case at a later time, and acute inflammation with a prom­inent white intracapsular plaque, vitreitis, and hypopyon occurred within 2 weeks of the secondary implant.

All nine cases clinically demonstrated vitritis and a prominent white plaque within the capsular bag (Fig 1). On serial observations, this plaque appeared to enlarge in three cases. Four of the nine cases presented with gran­ulomatous anterior uveitis (Fig 2), whereas five had non­granulomatous iridocyclitis. Two cases had progressive postoperative inflammation within 2 weeks ofsurgery but seven ofthe cases had a delay in onset ofthe inflammation. Four of the cases presented with hypopyon, and beaded fibrin strands extending across the anterior chamber were seen in three patients (Fig 3). At the time of initial pre­sentation, two cases (Table 1, cases 3 and 9) with severe granulomatous inflammation of long-standing duration were observed to have diffuse intraretinal hemorrhages consistent with a hemorrhagic central vein occlusion.

The mean age of the patients was 71 years (range, 60­82 years). Five of the patients were male and four were female. The interval between cataract surgery and the on­set of symptoms averaged 4 months (range, 1 week to 12 months). The interval between cataract surgery and mi­crobiologic confirmation of P. acnes infection averaged 12 months (range, 2 weeks to 38 months).

All cultures were obtained using previously published standard techniques. 12 All cases fulfilled one of the fol­lowing culture criteria: ( 1) growth of P. acnes in thiogly­

ence of organisms on stained cytology or histopathology specimens, (2) growth of the organism in thioglycolate broth from both the aqueous and vitreous, (3) growth of the organisms in thioglycolate broth plus anaerobic blood agar from the aqueous, or vitreous, or both.

Intraocular culture data are presented in Table 2. The interval between culture inoculation and growth averaged 7 days (range, 3-14 days). P. acnes was isolated from both thioglycolate broth and anaerobic blood agar in six of nine cases and in thioglycolate only in three of nine.

TREATMENT TECHNIQUES AND VISUAL RESULTS

Multiple management options were used in these cases based on the severity of the initial presentation and the individual surgeon's preference (Table 2). A capsulectomy performed at the time of vitrectomy was used to achieve a clinical cure in five of nine patients treated. The vitrec­tomy was performed via the pars plana in three patients and via the limbus in two patients. The original IOL was retained in six patients and exchanged in three. A favor­able clinical response to treatment was achieved in all nine cases, including five patients undergoing vitrectomy for removal of visible lens capsule and four patients man­aged without capsulectomy. The final visual acuities ranged from 20/20 to 20/60 in six eyes and from 20/200 to 20/400 in three eyes.

DISCUSSION

P. acnes is an inhabitant ofthe human sebaceous follicle and has been cultured in up to 43.8% of normal con­junctiva.13 P. acnes has been implicated as a causative organism in a wide variety of ocular and periocular in­fections ranging from conjunctivitis to periorbital cellu­litis.1 Forster and associates12 reported the first case of endophthalmitis secondary toP. acnes in 1976. Over the ensuing years, P. acnes has been described as the cause of postoperative endophthalmitis in a number of clinical series?-11

In December 1986, Meisler and associates4 reported a new syndrome of P. acnes endophthalmitis with delayed onset after ECCE with PC IOL. In their six patients, the interval between cataract surgery and the detection of postoperative inflammation ranged from 2 to 6 months. Their patients presented clinically with hypopyon in five of six patients and granulomatous keratic precipitates in three of six. Four patients were managed by pars plana vitrectomy without IOL removal, and in two patients, removal of the PC IOL with capsulectomy and anterior vitrectomy was performed.

There have been several additional reports of delayed onset endophthalmitis due to P. acnes since Meisler's original description of the syndrome. s-II Similar to other reports, our patients presented with an episode of intra­

1101

OPHTHALMOLOGY • JULY 1989 • VOLUME 96 • NUMBER 7

Fig 1. Top left, white plaque within the capsular bag. Fig 2. Bottom , chronic granulomatous inflammation with pigmented keratic pre­cipitates on the corneal endothelium. Fig 3. Top right, beaded fibrin strands across the anterior chamber and a white plaque at the 12­

o'clock position.

ocular inflammation at an average of 4 months postop­ proaches were used in this retrospective series. There are several reasons for these differing approaches. First, theeratively, although two patients presented with signs of delayed onset clinical syndrome had not been recognizedendophthalmitis within 2 weeks of cataract surgery.

All patients in our series had a prominent white intra­ at the time of presentation in several of the earlier cases capsular plaque suggesting that this sign may be the most (Table l, cases land 2). Second, the endophthalmitis cases distinguishing clinical feature ofP. acnes endophthalmitis. in this retrospective series were handled by a number of The white intracapsular plaque noted in these patients different physicians based on their personal experience suggests that the organism is sequestered within the cap­ and individual preference. Third, there was variable se­sular bag having survived from the time of the cataract verity of presenting signs and symptoms of infection. surgery. Organisms have been demonstrated histologically All patients in this series who underwent either partial within the lens capsule in several reports. 8•9 or attempted total capsulectomy (5/9) were subsequently

Vitritis was present in all nine patients indicating that cured of their disease as observed clinically without in­the inflammation was not limited to the anterior segment. flammation and without the use oftopical steroids. It must Beaded fibrin strands extending across the anterior cham­ be noted, however, that four patients responded to a non­ber were seen in three patients. Although similar fibrin surgical approach including either topical, intraocular, strands have previously been noted in association with and/or intravenous antibiotics. This nonsurgical approach sarcoidosis, 14 fungal endophthalmitis, 15 and toxoplas­ has been previously reported by Brady et al 10 in a case mosis, 16 this sign has not been reported in P. acnes en­ treated by anterior chamber paracentesis, and topical, dophthalmitis. This nonspecific fibrin manifestation along periocular, and systemic antibiotics alone. Although suc­with chronic recurrent granulomatous uveitis and a cessful therapy may require surgical intervention in some

cases, other cases may respond to less invasive therapy.prominent white plaque within the capsular bag should raise the suspicion of P. acnes endophthalmitis in eyes Based on our experience with these nine culture-proven with delayed onset inflammation after cataract surgery. cases, we have devised a management approach for P.

Because controversy exists regarding the optimal initial acnes endophthalmitis which we plan to use in future treatment of this entity,3

-11 a variety of management ap- cases (Table 3). In a clinical setting with mild initial pre­

1102

Table

2. T

reat

men

t Res

ults

Visu

al A

cuity

Re

curre

nce

at T

ime

Cultu

re R

esul

ts o

fof

Cul

ture

In

itial D

iagn

ostic

Da

ysCa

se

Diag

nosis

Pr

oced

ure

to

Visu

al

Follo

w-u

pNo

. (e

ye)

(day

s to

gro

wth

) In

itial T

reat

men

t No

. Cu

lture

Dat

a Su

bseq

uent

The

rapy

G

rowt

h O

utco

me

(mos

) Co

mm

ents

4/20

0 (O

D)

NP

IOL

exch

ange

; pa

rtial

cap

sulo

tom

y;

1 C

ultu

re-p

ositiv

e*

Topi

cal a

nd in

traoc

ular

5

20/3

0 15

In

itially

not

bel

ieve

dan

d an

terio

r vitr

ecto

my;

no

AB (

V, T

) to

be

infe

cted

intra

ocul

ar A

B 2

Cul

ture

-neg

ative

Pa

rs p

lana

vitr

ecto

my;

parti

al c

apsu

loto

my;

subc

onju

nctiv

al (

C, G

)an

d in

traoc

ular

AB

(C)

2 20

/100

(OD

) AC

neg

, vii

neg

Subc

onju

nctiv

al AB

(C)

; int

raoc

ular

1

Cul

ture

-pos

itive

IOL

exch

ange

; tot

al

5 20

/200

7

Post

oper

ative

cys

toic

AB (C

, G);

topi

cal A

B (C

) ca

psul

e ca

psul

otom

y;

mac

ular

ede

ma

subc

onju

nctiv

al A

B(C

, G)

3 2/

200

(OS)

AC

neg

, vii

pos

(9)

Subc

onju

nctiv

al A

B (C

, G);

1 C

ultu

re-p

ositiv

e Pa

rs p

lana

vitr

ecto

my;

14

20

/200

12

DI

H be

fore

and

afte

rin

traoc

ular

AB

(V, T

); to

pica

l AB

parti

al c

apsu

loto

my;

tre

atm

ent

(C, T

); in

trave

nous

AB

(CTX

) in

traoc

ular

AB

(V,

G);

subc

onju

nctiv

al A

B(V

, G)

4 20

/200

(OS

) AC

NP,

vii

pos

(7)

IOL

exch

ange

, par

tial c

apsu

loto

my;

No

ne

20/2

5 13

ante

rior v

itrec

tom

y;su

bcon

junc

tival

AB

(G)

5 3/

200

(OD)

AC

pos

(4)

, vii

NP

Intra

veno

us A

B (C

TX);

topi

cal A

B 1

Cultu

re N

P To

pica

l AB

and

POAB

(C)

20/2

0 12

(C)

6 20

/200

(OD

) AC

pos

, vit

pos,

(7)

Intra

ocul

ar A

B (V

, T);

None

20

/40

6su

bcon

junc

tival

AB

(V,

T);

intra

veno

us A

B (C

TX)

7 2/

200

(OS)

AC

neg

, vi

i neg

In

traoc

ular

AB

(V,

T);

Cultu

re-p

ositiv

e To

pica

l AB

(V);

12

20/2

5 10

subc

onju

nctiv

al A

B (V

, T)

intra

ocul

ar a

ndsu

bcon

junc

tival

AB

(V, T

)8

HM (

OS)

AC p

os, v

ii po

s (7

) In

traoc

ular

AB

(V,

T)

None

20

/60

5 YA

G ca

psul

otom

y4

mos

afte

rtre

atm

ent w

ith n

ore

curre

nce

9 HM

(OS

) AC

neg

, vi

i pos

(7)

Pa

rs p

lana

vitr

ecto

my;

par

tial

None

20

/400

8

DIH

befo

re a

nd a

fter

caps

ulot

omy;

intra

ocul

ar A

B (V

) tre

atm

ent

00 =

righ

t ey

e; N

P =

not

perfo

rmed

; IOL

= in

traoc

ular

lens

; AB

= an

tibio

tics;

V =

van

com

ycin

; T =

tobr

amyc

in; A

C =

ante

rior

cham

ber;

Vii

= vit

reou

s; C

= c

efaz

olin

; G =

gen

tam

icin

; OS

= le

ftey

e; CT

X =

ceftr

iaxo

ne; D

IH =

diffu

se in

trare

tinal

hem

orrh

ages

; PO

AB =

ora

l ant

ibio

tics;

HM

= h

and

mot

ions

.*A

nter

ior

cham

ber

and

vitre

ous

tap

perfo

rmed

; org

anism

was

cul

ture

d fro

m t

he v

itreo

us o

nly.

- - ....,0

OPHTHALMOLOGY • JULY 1989 • VOLUME 96 • NUMBER 7

Table 3. Treatment Strategies in Suspected Propionibacterium acnes Cases

Initial Treatment Follow-up Treatment (if initial failure)

Milder cases Better initial visual acuity, less lntravitreal vancomycin (1 mg) (1) Pars plana vitrectomy, capsulectomy, intravitreal

inflammation, better view of fundus (±topical and intravenous AB) vancomycin (1 mg) (2) Removal of all capsular remnants, IOL removal or

exchange, intravitreal vancomycin (1 mg) Advanced cases

Poorer initial visual acuity, more lntravitreal vancomycin (1 mg) Removal of all capsular remnants, IOL removal or exchange, inflammation, less view of fundus (±topical and intravenous AB) intravitreal vancomycin (1 mg)

or pars plana vitrectomy, capsulectomy, intravitreal vancomycin (1 mg)

AB = antibiotics; IOL = intraocular lens.

sentation (better visual acuity, less intraocular inflam­mation, better view of fundus details), we would first per­form intraocular cultures. At the same time that cultures are obtained, we recommend intravitreal vancomycin ( 1 mg) for eyes with these characteristic features of delayed onset endophthalmitis. Vancomycin has been reported to be effective against P. acnes, 17 although other antibiotics including methicillin and the cephalosporins may also be effective. Vancomycin offers the advantage that it is the first line of treatment for other indolent gram-positive organisms such as the coagulase-negative staphylococci associated with delayed onset endophthalmitis. 18 Since P. acnes and other anaerobic bacteria show relative resistance to aminoglycosides, 17 we do not recommend these anti­biotics in the management of this entity. By using only vancomycin in these delayed onset cases, the well-docu­mented retinal toxicity of aminoglycosides can be avoided. 19·20 Additional therapy includes intensive topical and systemic antibiotics in selected cases.

If the initial nonsurgical management is unsuccessful, we recommend pars plana vitrectomy with excision of the white intracapsular plaque while maintaining sufficient zonular integrity to support the intraocular lens. Repeat intraocular antibiotics based on prior antibiotic sensitivity testing are injected at this time. In cases with more severe initial presentation (poorer initial visual acuity, more in­traocular inflammation, less view of fundus details), the surgeon may elect to initiate primary capsulectomy and pars plana vitrectomy as a more effective means of re­moving the sequestered organisms and inflammatory de­bris. Our series suggests that a more aggressive initial ap­proach in these advanced cases may be warranted, since cases with intense granulomatous iritis and vitreitis of prolonged duration had a worse visual prognosis (cases 3 and 9). In both of these patients, the decreased vision was due to diffuse intraretinal hemorrhages noted at the time ofpresentation and persisting after treatment. We believe that this complication may be a result of either P. acnes or the inflammation it incites. If the pars plana vitrectomy and partial capsulectomy approach fails to eliminate the infection, the surgeon can then elect to perform IOL re­moval, attempt removal of all capsular lens remnants, and possible IOL exchange.

Because anaerobic cultures were not routinely obtained, many reported cases of phacoanaphylactic endophthal­mitis21 in the literature may actually represent delayed onset P. acnes endophthalmitis, which were cured by re­moval of the IOL and capsular remnants. Case 1 in this series was treated in 1984 before the recognition of the delayed onset syndrome ofP. acnes endophthalmitis. The presumed diagnosis of phacoanaphylactic endophthal­mitis was made and no cultures were obtained initially. After a recurrence of inflammation in this case, positive intraocular cultures were obtained and a successful visual outcome was achieved with two additional treatments (Table 2, case 1).

As a greater number of organisms are identified as a cause ofdelayed onset postoperative infection after ECCE with PC IOL implantation, 12·18 it is important to establish culture criteria for these infections such as those used in our cases. Since recovery of P. acnes from thioglycolate broth alone may be a contaminant, more than one an­aerobic media should be used to confirm endophthalmitis caused by this organism. As recommended for acute onset postoperative endophthalmitis, we advocate both the aqueous and vitreous since three of our nine cases (Table 2, cases 1, 3, and 9) had positive vitreous cultures, whereas the aqueous culture was negative. Cultures should be spe­cifically held for a minimum of 14 days in order to yield a higher frequency of positive anaerobic cultures. We be­lieve that adherence to strict culture criteria for anaerobic organisms is essential in future reports comparing various treatment regimens for anaerobic endophthalmitis.

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15. Pflugfelder SC, Flynn HW Jr, Zwickey TH, et al. Exogenous fungal endophthalmitis. Ophthalmology 1988; 95:19-30.

16. Schlaegel TF Jr. "Wet snow." Arch Ophthalmol1973; 89:169-70. 17. Wang WLL, Everett ED, Johnson M, Dean E. Suspectibility of Pro­

pionibacterium acnes to seventeen antibiotics. Antimicrob Agents Chemother 1977; 11:171-3.

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