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Rhodococcus globerulus keratitis after laser in situ keratomileusis
Rhodococcus globerulus keratitis after laser in situ keratomileusis Osvaldo H. Cuello, MD, M. Josefina Caorlin, MD, Victor E. Reviglio, MD, Lydia Carvajal, PhD, Claudio P. Juarez, MD, Esther Palacio de Guerra, PhD, Jose´ D. Luna, MD A healthy 20-year-old woman with myopia had uneventful bilateral laser in situ keratomileusis after which the uncorrected visual acuity was 20/20 in the right eye and 20/30 in the left eye. Fifteen days later, a stromal paraxial lesion was found in the right eye with a corresponding loss of visual acuity, pain, and photophobia. The flap was lifted and the infiltrate scraped for smears. Cultures showed that Rhodococcus globerulus was the infectious agent. Intensive topical antibiotic treatment was applied with good visual results. J Cataract Refract Surg 2002; 28:2235–2237 © 2002 ASCRS and ESCRS
L
aser in situ keratomileusis (LASIK) is currently one of the most frequently used refractive surgical procedures; therefore, microbial contamination and complications such as corneal infections have begun to be reported.1,2 Rhodococcus species is an uncommon intracellular aerobic gram-positive coccobacillus. Within this genus, species such as Rhodococcus luteus, Rhodococcus erythropolis, and Rhodococcus rhodochrous are known to cause ocular infection in humans. The first 2 species have been reported to cause endophthalmitis after intraocular lens implantation,3 and the third species has been reported to cause corneal ulcer infections.4,5 To our knowledge, Rhodococcus globerulus has not been reported as an agent responsible for ocular infection or any other human infectious disease. We present a case of Rhodococcus globerulus infectious corneal abscess after LASIK.
Case Report A 20-year-old Hispanic woman with a bilateral moderate myopia who had unsuccessfully worn contact lenses consulted
Accepted for publication November 26, 2001. From the Fundacio´n VER, Co´rdoba, Argentina. Reprint requests to Jose´ D. Luna, MD, PO Box 743, Correo Central, 5000 Co´rdoba, Argentina E-mail: [email protected]. © 2002 ASCRS and ESCRS Published by Elsevier Science Inc.
our corneal department for refractive surgery. The best spectacle-corrected visual acuity was 20/20 with ⫺5.75 ⫹1.50 ⫻ 75 in the right eye and 20/20 with ⫺4.50 ⫹2.25 ⫻ 90 in the left eye. On June 17, 1999, the patient had uneventful bilateral LASIK, in the right eye first. The same cutting blade was used in both eyes without resterilizing the microkeratome. Artificial tears and a mixture of chloramphenicol and dexamethasone were prescribed to be instilled 4 times daily after surgery. Twenty-four hours and 7 days after surgery, the slitlamp examination was normal in both eyes, showing a clear corneal stroma and no debris or infiltrates at the flap interface. The uncorrected visual acuity (UCVA) was 20/20 in the right eye and 20/30 in the left eye. Fifteen days later, the patient returned to the eye center reporting a foreign-body sensation and pain in the right eye. Visual acuity was 20/60, and a slitlamp examination showed mild edema involving the central and peripheral corneal flap. Forty-eight hours later, the symptoms were still present and visual acuity had decreased to hand motions. No history of trauma was found. A slitlamp examination showed a stromal, paraxial, round, white, 0.2 mm infiltrate with blurred edges surrounded by clear cornea and extending to approximately 50% of stromal thickness. There was also moderate flap edema and an epithelial defect of the flap edge extending from the 4 to 6 o’clock position. An anterior chamber reaction with 3⫹ flare and 3⫹ inflammatory cells with a 0.3 mm hypopyon was found. The posterior segment was normal. Under topical anesthesia, the corneal flap was lifted and the corneal stromal bed scraped for culture and sensitivity studies. The stromal bed was irrigated with povidone–iodine 5% solution and the flap placed in its original position. 0886-3350/02/$–see front matter PII S0886-3350(01)01347-5
CASE REPORTS: CUELLO
The samples were studied at the clinical microbiology laboratory. Gram staining showed the presence of polymorphonuclear leukocytes and isolated gram-positive rods as well as some short branching filaments, which raised the suspicion of the presence of an aerobic actinomycete (Figure 1). The modified Ziehl-Neelsen stain showed partial acid fastness. The culture was grown on sheep blood agar, chocolate agar, Sabouraud dextrose agar, and brain– heart infusion broth. It was incubated in aerobiosis and microaerophilia (5% carbon dioxide) at 37°C. Five days later, colonies had developed in all aerobiosis-incubated media. The colonies were round, nonhemolytic, and mucoid. Pigmentation was initially orange and became red over the following days. Culture studies included gram staining to observe morphology, Ziehl-Neelsen staining to rule out fast-growing micobacteria, and modified acid fast stain, which was positive and revealed partial acid fastness. Results of the identification tests are shown in Table 1. To complete the studies and confirm the suspected identification, the specimen was sent to Instituto Nacional de Enfermedades Infecciosas Dr. Carlos G. Malbra´n in Buenos Aires, Argentina. The institute identified the organism as Rhodococcus globerulus. Routine blood laboratory and HIV tests, requested later, were normal. The patient was started on a regimen of topical fortified vancomycin hydrochloride (25 mg/mL) alternating every half an hour with amikacin (14 mg/mL). Three days later, the patient had no epithelial defect and the stromal infiltrate had begun to organize. The drops were slowly tapered. Over the next week, the patient showed continued improvement of the corneal infiltrate with consolidation into a small inferotemporal paraxial stromal scar. Topical erythromycin continued to be instilled 4 times a day for 2 weeks, after which there were no clinical signs of a corneal ulcer. After a 4-month follow-up, the patient had no recurrence and the final UCVA in the right eye was 20/40.
Figure 1. (Cuello) A microscopic photograph of a smear shows intracellular gram-positive branched vegetative mycelium (arrow) (gram stain, original magnification ⫻1000).
2236
Table 1. Laboratory identification tests and results.6 Test
Result
Production of Catalase
⫹
Urea hydrolysis
⫹
SH2 (TSI)
–
Gelatinase
⫹
Decomposition of Adenine
–
Tyrosine
–
Growth on sole carbon source Citrate
⫹
Mannose
–
Inositol
–
Cellobiose
–
Maltose
⫹
Mannitol
–
Sorbitol
–
Sucrose
–
SH2 ⫽ hydrogen sulfide; TSI ⫽ triple sugar iron agar
Discussion Although it has been shown that the risk of infectious keratitis is greater when the corneal epithelium is ulcerated, in LASIK the corneal stroma can be exposed to infectious agents as well, risking infection. According to international experience, the incidence of this complication after LASIK is 1 in 5000.2 However, as this refractive procedure becomes more widely available, cases of postoperative infectious keratitis are beginning to be reported.1,2 Ocular infection with Rhodococcus species is rare.3,5 The genera Rhodococcus, Nocardia, Gordona, and Tsukamurella belong to Nocardiaciae family and are partially acid-fast aerobic actinomycetes. At present, it is known that the Rhodococcus genus consists of about 16 very diverse species in terms of biochemical characteristics and morphology. This organism is ubiquitous and causes lung infection by inhalation and cutaneous lesions resulting from wound contamination. The latter, attributed to Rhodococcus equi, occurs in healthy persons, frequently in children. Most reported Rhodococcus species infections in humans have been observed in immunocompromised patients, including those with AIDS.7
J CATARACT REFRACT SURG—VOL 28, DECEMBER 2002
CASE REPORTS: CUELLO
On gram stain, the rods vary in length, from cocci to long, curved, clubbed forms. Large, irregular, highly mucoid, pale-salmon colonies grow well on ordinary media. Because Rhodococcus species is a facultative intracellular pathogen, antimicrobial agents that concentrate intracellularly (eg, erythromycin) may be among the most effective treatments. Ocular infections caused by Rhodococcus species when inoculated into the eye have been described, including 2 cases of chronic postoperative endophthalmitis.3 However, to the best of our knowledge, this is the first report of R globerulus infection in humans and the first infectious keratitis after LASIK caused by this uncommon organism. Our patient was not immunocompromised and did not have AIDS or another disease that could alter her immune system. She was successfully treated with an intense topical regimen of fortified vancomycin, amikacin, and erythromycin, and good postoperative visual acuity was obtained. In cases of post-LASIK infectious keratitis located at the stromal interface in which there is usually a poor or no response to empiric antibiotic treatment, we strongly believe that it is advisable to lift the flap, scrape the stromal bed for microbiological studies, and then wash the area with an antiseptic solution. After this procedure, we recommend using a combination of fortified antibiotics until culture results are available. This option of a therapeutic workup has been used at our center for
the past 3 years after an experience with Mycobacterium chelonae keratitis.1 Clinical experience suggests that keratitis as a complication of LASIK is possible. Discussing this with patients before surgery is highly recommended.
References 1. Reviglio V, Rodriguez ML, Picotti GS, et al. Mycobacterium chelonae keratitis following laser in situ keratomileusis. J Refract Surg 1998; 14:357–360 2. Machat J. Excimer Laser Refractive Surgery; Practice and Principles. Thorofare, NJ, Slack, Inc., 1996; 359 – 400 3. Wenkel H, Rummelt V, Knorr H, Naumann GO. Chronic postoperative endophthalmitis following cataract extraction and intraocular lens implantation: report on nine patients. Ger J Ophthalmol 1993; 2:419 –425 4. Gopaul D, Ellis C, Maki A Jr, Joseph MG. Isolation of Rhodococcus rhodochrous from a chronic corneal ulcer. Diagn Microbiol Infect Dis 1988; 10:185–90 5. Broadway D, Duguid G, Matheson M, et al. Rhodococcus keratitis [letter]. Br J Ophthalmol 1998; 82:198 –199 6. Brown JM, McNeil MM, Desmond EP. Nocardia, Rhodococcus, Gordona, Actinomadura, Streptomyces, and other actinomycetes of medical importance. In: Murray PR, Baron EJ, Pfaller MA, et al, eds, Manual of Clinical Microbiology, 7th ed. Washington, DC, ASM Press, 1999; 370 –398 7. Jones MR, Neale TJ, Say PJ, Home JG. Rhodococcus equi: an emerging opportunistic pathogen? Aust NZ J Med 1989; 19:103–107
J CATARACT REFRACT SURG—VOL 28, DECEMBER 2002
2237
L
aser in situ keratomileusis (LASIK) is currently one of the most frequently used refractive surgical procedures; therefore, microbial contamination and complications such as corneal infections have begun to be reported.1,2 Rhodococcus species is an uncommon intracellular aerobic gram-positive coccobacillus. Within this genus, species such as Rhodococcus luteus, Rhodococcus erythropolis, and Rhodococcus rhodochrous are known to cause ocular infection in humans. The first 2 species have been reported to cause endophthalmitis after intraocular lens implantation,3 and the third species has been reported to cause corneal ulcer infections.4,5 To our knowledge, Rhodococcus globerulus has not been reported as an agent responsible for ocular infection or any other human infectious disease. We present a case of Rhodococcus globerulus infectious corneal abscess after LASIK.
Case Report A 20-year-old Hispanic woman with a bilateral moderate myopia who had unsuccessfully worn contact lenses consulted
Accepted for publication November 26, 2001. From the Fundacio´n VER, Co´rdoba, Argentina. Reprint requests to Jose´ D. Luna, MD, PO Box 743, Correo Central, 5000 Co´rdoba, Argentina E-mail: [email protected]. © 2002 ASCRS and ESCRS Published by Elsevier Science Inc.
our corneal department for refractive surgery. The best spectacle-corrected visual acuity was 20/20 with ⫺5.75 ⫹1.50 ⫻ 75 in the right eye and 20/20 with ⫺4.50 ⫹2.25 ⫻ 90 in the left eye. On June 17, 1999, the patient had uneventful bilateral LASIK, in the right eye first. The same cutting blade was used in both eyes without resterilizing the microkeratome. Artificial tears and a mixture of chloramphenicol and dexamethasone were prescribed to be instilled 4 times daily after surgery. Twenty-four hours and 7 days after surgery, the slitlamp examination was normal in both eyes, showing a clear corneal stroma and no debris or infiltrates at the flap interface. The uncorrected visual acuity (UCVA) was 20/20 in the right eye and 20/30 in the left eye. Fifteen days later, the patient returned to the eye center reporting a foreign-body sensation and pain in the right eye. Visual acuity was 20/60, and a slitlamp examination showed mild edema involving the central and peripheral corneal flap. Forty-eight hours later, the symptoms were still present and visual acuity had decreased to hand motions. No history of trauma was found. A slitlamp examination showed a stromal, paraxial, round, white, 0.2 mm infiltrate with blurred edges surrounded by clear cornea and extending to approximately 50% of stromal thickness. There was also moderate flap edema and an epithelial defect of the flap edge extending from the 4 to 6 o’clock position. An anterior chamber reaction with 3⫹ flare and 3⫹ inflammatory cells with a 0.3 mm hypopyon was found. The posterior segment was normal. Under topical anesthesia, the corneal flap was lifted and the corneal stromal bed scraped for culture and sensitivity studies. The stromal bed was irrigated with povidone–iodine 5% solution and the flap placed in its original position. 0886-3350/02/$–see front matter PII S0886-3350(01)01347-5
CASE REPORTS: CUELLO
The samples were studied at the clinical microbiology laboratory. Gram staining showed the presence of polymorphonuclear leukocytes and isolated gram-positive rods as well as some short branching filaments, which raised the suspicion of the presence of an aerobic actinomycete (Figure 1). The modified Ziehl-Neelsen stain showed partial acid fastness. The culture was grown on sheep blood agar, chocolate agar, Sabouraud dextrose agar, and brain– heart infusion broth. It was incubated in aerobiosis and microaerophilia (5% carbon dioxide) at 37°C. Five days later, colonies had developed in all aerobiosis-incubated media. The colonies were round, nonhemolytic, and mucoid. Pigmentation was initially orange and became red over the following days. Culture studies included gram staining to observe morphology, Ziehl-Neelsen staining to rule out fast-growing micobacteria, and modified acid fast stain, which was positive and revealed partial acid fastness. Results of the identification tests are shown in Table 1. To complete the studies and confirm the suspected identification, the specimen was sent to Instituto Nacional de Enfermedades Infecciosas Dr. Carlos G. Malbra´n in Buenos Aires, Argentina. The institute identified the organism as Rhodococcus globerulus. Routine blood laboratory and HIV tests, requested later, were normal. The patient was started on a regimen of topical fortified vancomycin hydrochloride (25 mg/mL) alternating every half an hour with amikacin (14 mg/mL). Three days later, the patient had no epithelial defect and the stromal infiltrate had begun to organize. The drops were slowly tapered. Over the next week, the patient showed continued improvement of the corneal infiltrate with consolidation into a small inferotemporal paraxial stromal scar. Topical erythromycin continued to be instilled 4 times a day for 2 weeks, after which there were no clinical signs of a corneal ulcer. After a 4-month follow-up, the patient had no recurrence and the final UCVA in the right eye was 20/40.
Figure 1. (Cuello) A microscopic photograph of a smear shows intracellular gram-positive branched vegetative mycelium (arrow) (gram stain, original magnification ⫻1000).
2236
Table 1. Laboratory identification tests and results.6 Test
Result
Production of Catalase
⫹
Urea hydrolysis
⫹
SH2 (TSI)
–
Gelatinase
⫹
Decomposition of Adenine
–
Tyrosine
–
Growth on sole carbon source Citrate
⫹
Mannose
–
Inositol
–
Cellobiose
–
Maltose
⫹
Mannitol
–
Sorbitol
–
Sucrose
–
SH2 ⫽ hydrogen sulfide; TSI ⫽ triple sugar iron agar
Discussion Although it has been shown that the risk of infectious keratitis is greater when the corneal epithelium is ulcerated, in LASIK the corneal stroma can be exposed to infectious agents as well, risking infection. According to international experience, the incidence of this complication after LASIK is 1 in 5000.2 However, as this refractive procedure becomes more widely available, cases of postoperative infectious keratitis are beginning to be reported.1,2 Ocular infection with Rhodococcus species is rare.3,5 The genera Rhodococcus, Nocardia, Gordona, and Tsukamurella belong to Nocardiaciae family and are partially acid-fast aerobic actinomycetes. At present, it is known that the Rhodococcus genus consists of about 16 very diverse species in terms of biochemical characteristics and morphology. This organism is ubiquitous and causes lung infection by inhalation and cutaneous lesions resulting from wound contamination. The latter, attributed to Rhodococcus equi, occurs in healthy persons, frequently in children. Most reported Rhodococcus species infections in humans have been observed in immunocompromised patients, including those with AIDS.7
J CATARACT REFRACT SURG—VOL 28, DECEMBER 2002
CASE REPORTS: CUELLO
On gram stain, the rods vary in length, from cocci to long, curved, clubbed forms. Large, irregular, highly mucoid, pale-salmon colonies grow well on ordinary media. Because Rhodococcus species is a facultative intracellular pathogen, antimicrobial agents that concentrate intracellularly (eg, erythromycin) may be among the most effective treatments. Ocular infections caused by Rhodococcus species when inoculated into the eye have been described, including 2 cases of chronic postoperative endophthalmitis.3 However, to the best of our knowledge, this is the first report of R globerulus infection in humans and the first infectious keratitis after LASIK caused by this uncommon organism. Our patient was not immunocompromised and did not have AIDS or another disease that could alter her immune system. She was successfully treated with an intense topical regimen of fortified vancomycin, amikacin, and erythromycin, and good postoperative visual acuity was obtained. In cases of post-LASIK infectious keratitis located at the stromal interface in which there is usually a poor or no response to empiric antibiotic treatment, we strongly believe that it is advisable to lift the flap, scrape the stromal bed for microbiological studies, and then wash the area with an antiseptic solution. After this procedure, we recommend using a combination of fortified antibiotics until culture results are available. This option of a therapeutic workup has been used at our center for
the past 3 years after an experience with Mycobacterium chelonae keratitis.1 Clinical experience suggests that keratitis as a complication of LASIK is possible. Discussing this with patients before surgery is highly recommended.
References 1. Reviglio V, Rodriguez ML, Picotti GS, et al. Mycobacterium chelonae keratitis following laser in situ keratomileusis. J Refract Surg 1998; 14:357–360 2. Machat J. Excimer Laser Refractive Surgery; Practice and Principles. Thorofare, NJ, Slack, Inc., 1996; 359 – 400 3. Wenkel H, Rummelt V, Knorr H, Naumann GO. Chronic postoperative endophthalmitis following cataract extraction and intraocular lens implantation: report on nine patients. Ger J Ophthalmol 1993; 2:419 –425 4. Gopaul D, Ellis C, Maki A Jr, Joseph MG. Isolation of Rhodococcus rhodochrous from a chronic corneal ulcer. Diagn Microbiol Infect Dis 1988; 10:185–90 5. Broadway D, Duguid G, Matheson M, et al. Rhodococcus keratitis [letter]. Br J Ophthalmol 1998; 82:198 –199 6. Brown JM, McNeil MM, Desmond EP. Nocardia, Rhodococcus, Gordona, Actinomadura, Streptomyces, and other actinomycetes of medical importance. In: Murray PR, Baron EJ, Pfaller MA, et al, eds, Manual of Clinical Microbiology, 7th ed. Washington, DC, ASM Press, 1999; 370 –398 7. Jones MR, Neale TJ, Say PJ, Home JG. Rhodococcus equi: an emerging opportunistic pathogen? Aust NZ J Med 1989; 19:103–107
J CATARACT REFRACT SURG—VOL 28, DECEMBER 2002
2237