Cornea 19(2): 243245, 2000.

2000 Lippincott Williams & Wilkins, Inc., Philadelphia

Delayed Onset and Recurrent Alcaligenes xylosoxidans Keratitis

Tim H. Pan, D.O., David G. Heidemann, M.D., Steven P. Dunn, M.D., Christopher Y.C. Chow, M.D., and David Gossage, D.O.

Alcaligenes xylosoxidans (formerly Achromobacter xylosoxidans) is an opportunistic aerobic gram-negative rod that is oxidase positive and nonlactose fermenting. It may be confused with other gram-negative bacteria such as Pseudomonas aeruginosa (1). The organism was first described and named in 1971 by Yabuuchi and Ohyama (2), who isolated the organism from purulent ear discharge of seven patients. It is frequently found in moist areas of hospitals and is resistant to many antimicrobial agents (3). Alcaligenes xylosoxidans is a transient colonizer of human gastrointestinal or respiratory tract in patients with cystic fibrosis (4). Its mode of transmission is often unknown, although it frequently involves exposure of debilitated patients to contaminated fluids or medical solutions (1,5,6). It has caused bacteremia, urinary tract infections, meningitis, wound infections, pneumonia, and peritonitis (6). To our knowledge, only five cases of A. xylosoxidans keratitis have been reported (Table 1). We report a case of posttraumatic A. xylosoxidans keratitis that recurred after apparent resolution.

CASE REPORT A 21-year-old tire technician was first seen on March 25, 1998, with left-eye irritation after a tire inner tube exploded. Visual acuity in the left eye was 20/100. Slitlamp examination demonstrated a partial-thickness (90% depth) central corneal laceration. No infiltrate was present. The anterior chamber was quiet. No evidence of intraocular foreign body was noted on gonioscopy, funduscopy, and computed tomography (CT) scan. The patient was treated with ofloxacin drops every hour. ExSubmitted March 12, 1999. Revision received May 24, 1999. Accepted June 1, 1999. From the Department of Ophthalmology, William Beaumont Hospital, Royal Oak (D.G.H., S.P.D., C.Y.C.C.), and Pontiac Osteopathic Hospital, Pontiac (T.H.P., D.G.), Michigan, U.S.A. Address correspondence and reprint requests to Dr. D.G. Heidemann, Michigan Cornea Consultants, Suite 201, Farmbrook Medical Building, 29829 Telegraph, Southfield, MI 48034, U.S.A.

amination the next day revealed a mild anterior chamber reaction, and 1% prednisolone acetate drops and oral ciprofloxacin were added. His vision improved to 20/40, and the anterior chamber reaction subsided. On April 3, 1998, the patient had an intact epithelium, a mild anterior chamber reaction, and a few fine keratic precipitates. The prednisolone acetate was increased to every 2 h, and tobramycin (14 mg/ml) every 30 min was added to the treatment regimen. Three days later, his condition worsened, and he was referred for corneal subspecialty evaluation. Examination on April 6, 1998, revealed 20/200 vision, a 1.5-mm central epithelial defect, a 1.0-mm posterior stromal infiltrate, diffuse corneal edema, and a 0.5-mm hypopyon (Fig. 1). B-scan ultrasonography revealed a normal posterior segment. The site of laceration was reopened with a no. 11 blade to obtain corneal scrapings from the posterior stromal infiltrate for cultures on thioglycolate broth, blood, chocolate, and Sabouraud agar. The patients treatment regimen was modified to topical tobramycin (14 mg/ml), vancomycin (50 mg/ml), and amphotericin B (1.5 mg/ml) every hour around the clock, and oral ciprofloxacin. The topical steroids were discontinued. On April 9, 1998, his vision worsened to count fingers. Cultures revealed moderate growth of A. xylosoxidans. The patient was treated with hourly ciprofloxacin (3 mg/ml), 10% sodium sulfacetamide, and tobramycin (14 mg/ml) drops. Sensitivities eventually revealed that the organism was resistant to tobramycin, intermediately sensitive to ciprofloxacin, and sensitive to sulfamethoxazole and piperacillin. On April 17, 1998, the patients vision was 20/50, with an intact epithelium, and a quiet anterior chamber. On April 24, 1998, the vision was 20/30, with complete resolution of the corneal infiltrate, and a 1.0-mm midstromal scar located in the visual axis. Over the next 2-week period, the topical medications were slowly tapered to twice-a-day dosage by May 7. On May 11, 1998, the eye remained quiet, with a small residual central corneal stromal scar, and the antibiotic drops were discontinued. 243

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TABLE 1. Reported cases of Alcaligenes xylosoxidans keratitis
Steroid use ? Yes Yes No Yes Yes Conventional treatment (topical) failed ? ? Gentamicin, amikacin Cefazolin, gentamicin Tobramycin, cefazolin (and i.v. trimethoprim/sulfa, gentamicin) Ofloxacin (and oral ciprofloxacin) Treatment required (topical) ? ? Carbenicillin Carbenicillin Piperacillin (and i.v. azlocillin) Sulfacetamide

Author, date Majekodunmi, 1975 Boisjoly et al., 1973 Newman et al., 1984 Fiscella et al., 1989 Siganos et al., 1993 Current case, 1999

Immunocompromise Concurrent Clostridium welchii infection Chronic herpes simplex keratitis Neovascular glaucoma Bullous keratopathy with bandage contact lens Penetrating keratoplasty Corneal laceration

On May 13, 1998, the patient had an acute worsening of symptoms. He had vision of count fingers, a 2.0-mm epithelial defect, a 1.5-mm stromal infiltrate with surrounding stromal edema, and a 0.5-mm hypopyon. Repeated corneal cultures were taken. The patient was treated with tobramycin (14 mg/ml), vancomycin (33 mg/ml), and 10% sodium sulfacetamide drops. Over the next 2-week period, the keratitis resolved. Cultures again yielded a moderate growth of A. xylosoxidans on blood and chocolate agar, with the same sensitivity pattern as the previous cultures. On June 16, 1998, the patients vision was 20/30, and there was no evidence of infection. Treatment with tobramycin and sodium sulfacetamide drops was maintained for 2 months. Six months later, his eye remained quiet, with 20/40 visual acuity. DISCUSSION The first reported ocular infection by A. xylosoxidans was in 1977, when it was isolated from the infected orbit of a patient who had lost the globe after a perforating injury from shrapnel (3). It was implicated in a case of chronic bacterial endophthalmitis in a 63-year-old women after cataract surgery (4). To our knowledge, there have been five reported cases of A. xylosoxidans

FIG. 1. Posterior stromal corneal infiltrate at laceration site, with diffuse stromal edema and small hypopyon.

corneal infection (Table 1). Our case was similar in some aspects to these reported cases. All patients had a compromised cornea and did not respond to conventional antimicrobial therapy. Our patient sustained a partialthickness corneal laceration from a tire explosion and was treated with topical steroids and antibiotics. It is unclear if the previous reported cases of A. xylosoxidans keratitis were late onset. Our patient did not develop an infiltrate until 10 days after injury. As in the previously reported cases, our patient did not respond to conventional broad-spectrum antibiotics. He was taking ofloxacin and fortified tobramycin drops when the ulcer initially developed. The previously reported ineffective regimens included topical gentamicin, amikacin, cefazolin, and tobramycin. Alcaligenes xylosoxidans is usually resistant to aminoglycosides and firstgeneration cephalosporins. In the previously reported cases, resolution of the keratitis was achieved only after the initiation of carbenicillin, ticarcillin, piperacillin, and/or azlocillin drops. The -carboxypenicillins (e.g., carbenicillin, ticarcillin) and the acylaminopenicillins (e.g., azlocillin, mezlocillin) are effective both in vitro and in vivo against A. xylosoxidans (9,12). Our patient responded well to topical ciprofloxacin and sodium sulfacetamide drops after the discontinuation of topical corticosteroids. Alcaligenes xylosoxidans has many similarities to Pseudomonas. As with Pseudomonas keratitis, steroids may have been a risk factor in exacerbation of A. xylosoxidans keratitis. In our patients treatment regimen, only sulfamethaxozole, a bacteriostatic agent, received a sensitive rating. The organism was only intermediately sensitive to ciprofloxacin and was resistant to aminoglycosides. It appears that the discontinuation of steroids and addition of sodium sulfacetamide was sufficient to cure the infection. Our patient differs from the previous reported cases in that the keratitis recurred after an apparent resolution. Viable organisms were most likely still present at the original ulcer site. In each instance, corneal cultures yielded a moderate growth of A. xylosoxidans on blood and chocolate agar. The infection resolved permanently after prolonged treatment with topical sodium sulfacetamide. In retrospect, treatment with carbenicillin or piper-

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ALCALIGENES XYLOSOXIDANS KERATITIS acillin may have been more effective at eradicating the infection. In conclusion, A. xylosoxidans should be considered a potential pathogen in compromised or traumatized corneas. The infection may be late onset and exacerbated by steroids. It does not respond to conventional broadspectrum antimicrobial therapy and may be difficult to eradicate. REFERENCES
1. Forbes, Weissfeld. Bailey and Scotts diagnostic microbiology. St. Louis: Mosby, 1998:47685. 2. Yabuuchi E, Ohyama A. Achromobacter xylosoxidans from human ear discharge. Jpn J Microbiol 1971;15:47781. 3. Holmes B, Snell JJ, Lapage SP. Strains of Achromobacter xylosoxidans from clinical material. J Clin Pathol 1977;30:595601. 4. Ficker L, Meridith TA, Wilson LA, Kaplan JK, Kozarsky AM. Chronic bacterial endophthalmitis. Am J Ophthalmol 1987;103: 7458.

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5. McGuckin MB, Thorpe RJ, Koch KM, Alavi A, Staum M, Abrutyn E. An outbreak of Achromobacter xylosoxidans related to diagnostic tracer procedures. Am J Epidemiol Infect Dis 1982;1:24256. 6. Reverdy ME, Freney J, Fleurette J, et al. Nosocomial colonization and infection by Achromobacter xylosoxidans. J Clin Microbiol 1984;19:1403. 7. Majekodunmi S, Odugbemi T. Clostridium welchii corneal ulcer: a case report. Can J Ophthalmol 1975;10:2902. 8. Boisjoly HM, Paven-Langston D, Kenyon KR, Sullivan Baker A. Superinfections in herpes simplex keratitis. Am J Ophthalmol 1983;96:35461. 9. Newman PE, Hider P, Waring GO III, Wilson LA, Harbin TS. Corneal ulcer due to Achromobacter xylosoxidans. Br J Ophthalmol 1984;68:4724. 10. Fiscella R, Noth J. Achromobacter xylosoxidans corneal ulcer in a therapeutic soft contact lens wearer. Cornea 1989;8:2679. 11. Siganos DS, Tselentis IG, Papatzanaki ME, Tsilimbaris MK, Pallikaris IG. Achromobacter xylosoxidans keratitis following penetrating keratoplasty. Refract Corneal Surg 1993;9:713. 12. Igra-Siegman Y, Chmel H, Cobbs C. Clinical and laboratory characteristics of Achromobacter xylosoxidans infection. J Clin Microbiol 1980;11:1415.

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