ENDOGENOUS ENDOPHTHALMITIS DUE TO CLINICALLY VANCOMYCINRESISTANT STAPHYLOCOCCUS AUREUS Vaidehi S. Dedania, MD,* Benjamin P. Hale, MD,† Pawan Bhatnagar, MD†
Purpose: To report a case of clinically vancomycin-resistant Staphylococcus aureus endophthalmitis. Methods: This is an observational case report of a patient referred for decreased vision during an admission for methicillin-resistant S. aureus bacteremia. Results: A 48-year-old woman with methicillin-resistant S. aureus bacteremia presented with decreased vision in one eye. Best-corrected visual acuity at presentation was 20/25 in the right eye and hand motion in the left eye. Biomicroscopic examination revealed evidence of endophthalmitis in both eyes. After a period of deterioration despite treatment with intravenous and intravitreal vancomycin and intravitreal ceftazidime—20/200− in the right eye and light perception in the left eye, an alternative treatment regimen with intravenous daptomycin and intravitreal clindamycin and amikacin led to clinical improvement in both eyes, with quiescence of anterior chamber cell and vitritis. Best-corrected visual acuity at 3 weeks of follow-up had improved to 20/40 in the right eye and remained light perception in the left eye. Conclusion: In cases of endogenous endophthalmitis secondary to methicillin-resistant S. aureus not responsive to intravenous and intravitreal vancomycin, particularly with borderline sensitivities, consideration to clinical resistance should be entertained. RETINAL CASES & BRIEF REPORTS 9:59–60, 2015
From the *Department of Ophthalmology, Albany Medical Center, Lions Eye Institute, Albany, New York; and †Retina Consultants PLLC, Department of Ophthalmology, Division of Vitreoretinal Surgery, Albany Medical College, Slingerlands, New York.
Case Report A 48-year-old woman with history of hypertension, Type II diabetes mellitus, and end-stage renal disease on hemodialysis was admitted for the treatment of methicillin-resistant S. aureus bacteremia with intravenous vancomycin. While inpatient, she developed pain and rapidly progressive vision loss in both eyes with a best-corrected visual acuity of 20/25 in the right eye and hand motion in the left eye. Anterior chamber examination revealed 4+ leukocytes and a fibrinous reaction in both eyes, with a layered hypopyon in the left eye. Dilated examination of the right eye revealed 1+ vitritis and focal retinitis in the temporal equator. The fundus was not visible in the left eye, where B-scan ultrasonography revealed dense vitreous debris and an attached retina. Endogenous endophthalmitis secondary to methicillin-resistant S. aureus was diagnosed. Vitreous tap of the left eye and injection of vancomycin (1 mg per 0.1 mL) and ceftazidime (2.25 mg per 0.1 mL) into both eyes were performed. Despite intravitreal and intravenous vancomycin, deterioration of vision to 20/200− in the right eye and light perception in the left eye, with the development of a hypopyon in the right eye and increasing hypopyon in the left eye, was noted 2 days later. Vitreous culture confirmed methicillinresistant S. aureus. Microbiological testing revealed a minimum inhibitory concentration (MIC) of 2 mg/mL for vancomycin. The laboratory at Albany Medical Center uses the broth microdilution test for assessing susceptibilities of S. aureus. Notably, the
R
ecently, systemic infections due to Staphylococcus aureus strains with decreased sensitivity to vancomycin have emerged and pose a significant clinical concern.1 To date, vancomycin-resistant S. aureus has not been reported as a cause of endogenous endophthalmitis. Here, we describe a case of severe bilateral endogenous endophthalmitis due to S. aureus that was clinically resistant to vancomycin.
None of the authors have any financial/conflicting interests to disclose. Reprint requests: Vaidehi S. Dedania, MD, Department of Ophthalmology, Albany Medical Center, 1220 New Scotland Road, Slingerlands, NY 12159; e-mail: [email protected]
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microbiology laboratory documented that an MIC $2 was possible evidence of the development of vancomycin resistance. Because of worsening despite therapy and a borderline MIC, vancomycin resistance was suspected. Systemic therapy was changed to intravenous daptomycin and intravitreal injections of clindamycin 1 mg per 0.1 mL (MIC #0.5 [susceptible]) and amikacin 400 mg per 0.1 mL (MIC = 16 [susceptible]) were administered. Within 24 hours of changing therapy, both eyes clinically improved with quiescence of anterior chamber cell and vitritis. At 3 weeks of follow-up, best-corrected visual acuity was 20/40 in the right eye and light perception in the left eye with a resolved retinal infiltrate in the right eye. The left eye developed a total retinal detachment.
Discussion The first clinical isolate of vancomycin-resistant S. aureus was reported in 2002 from an indwelling catheter tip.2 The Center for Disease Control (CDC) currently defines vancomycin-susceptible S. aureus as having an MIC of #2 mg/mL, vancomycinintermediate S. aureus as having an MIC of 4 to 8 mg/mL, and vancomycin-resistant S. aureus as having an MIC of $16 mg/mL.3,4 These definitions have recently been questioned because infections with high MICs in the susceptible range (MIC = 1–2 mg/mL) have shown decreased vancomycin susceptibility and higher rates of treatment failure.1 In addition to a higher likelihood of clinical treatment failure, the attainment of target serum levels of vancomycin in patients with S. aureus isolates with an MIC $2 mg/mL may be less likely and has necessitated the use of alternative antibiotic regimens.5 Furthermore, reports suggest that the treatment of S. aureus bacteremia with vancomycin in isolates with an MIC of 1 mg/mL to 2 mg/mL may have decreased success and/or require higher doses of medication.6 Vancomycin-resistant S. aureus endophthalmitis is very rare, with only 3 reported cases, all occurring postoperatively.7 These cases were treated with varying combinations of intravitreal quinupristin/dalfopristin, ceftazidime and amikacin, and systemic linezolid, rifampin, and minocycline.7 Additionally, daptomycin has emerged as an alternative to vancomycin for the treatment of methicillin-resistant S. aureus and has been found to reach therapeutic concentrations in the vitreous after intravenous administration.8 In this patient, despite intravenous and intravitreal vancomycin, profound clinical deterioration was noted. A vitrectomy was not able to be performed after this initial poor response because the patient had comorbid conditions and her medical status during this admission precluded surgical treatment. Although the CDC parameters for resistance to vancomycin were not met, there was definitive clinical evidence of
reduced susceptibility of this “high MIC” strain of S. aureus to vancomycin. Furthermore, after switching treatment to intravenous daptomycin along with intravitreal injections of clindamycin and amikacin, clinical improvement was noted within 24 hours. This rapid response to an alternate antibiotic regimen, in conjunction with the previous lack of response to vancomycin therapy, serves to support the diagnosis of a vancomycin-resistant strain of S. aureus. Endogenous bacterial endophthalmitis caused by clinically vancomycin-resistant S. aureus has not previously been reported. In this case of S. aureus-induced endogenous endophthalmitis, there was significant clinical worsening on the previous regimen, and microbiological evaluation showed borderline sensitivity. Fortunately, intravenous daptomycin with intravitreal clindamycin and amikacin were successful in inducing quiescence. In cases of S. aureus endophthalmitis not responsive to vancomycin, particularly with borderline sensitivities, alternative antibiotics should be considered. Key words: endogenous endophthalmitis, Staphylococcus aureus, vancomycin-resistant. References 1. Holmes NE, Johnson PD, Howden BP. Relationship between vancomycin-resistant Staphylococcus aureus, vancomycinintermediate S. aureus, high vancomycin MIC, and outcome in serious S. aureus infections. J Clin Microbiol 2012;50:2548–2552. 2. Chang S, Sievert DM, Hageman JC, et al. Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene. N Engl J Med 2003;348:1342–1347. 3. Clinical and Laboratory Standards Institute (CLSI). Methods for Diluation Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard—Seventh edition. CLSI Document M07-a7. Wayne, Philadelphia, PA: CLSI; 2006. 4. Hageman JC, Patel JB, Carey RC, et al. Investigation and control of vancomycin-intermediate and -resistant Staphylococcus aureus: a guide for health departments and infection control personnel. Atlanta, GA. 2006. Available at: http://www.cdc.gov/ hai/pdfs/visa_vrsa/visa_vrsa_guide.pdf. 5. Ryback MJ, Lomaestro BM, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Disease Society of America, and the Society of Infectious Disease Pharmacists. Pharmacotherapy 2009;29:1275–1279. 6. Sakoulas G, Moise-Broder PA, Schentag J, et al. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J Clin Microbiol 2004;42:2398–2402. 7. Stroh EM. Quinupristin/dalfopristin in vancomycin-resistant Staphylococcus aureus endophthalmitis. Arch Ophthalmol 2012;130:1323–1324. 8. Sheridan KR, Potoski BA, Shields RK, et al. Presence of adequate intravitreal concentrations of daptomycin after systemic intravenous administration in a patient with endogenous endophthalmitis. Pharmacotherapy 2010;30:1247–1251.
Purpose: To report a case of clinically vancomycin-resistant Staphylococcus aureus endophthalmitis. Methods: This is an observational case report of a patient referred for decreased vision during an admission for methicillin-resistant S. aureus bacteremia. Results: A 48-year-old woman with methicillin-resistant S. aureus bacteremia presented with decreased vision in one eye. Best-corrected visual acuity at presentation was 20/25 in the right eye and hand motion in the left eye. Biomicroscopic examination revealed evidence of endophthalmitis in both eyes. After a period of deterioration despite treatment with intravenous and intravitreal vancomycin and intravitreal ceftazidime—20/200− in the right eye and light perception in the left eye, an alternative treatment regimen with intravenous daptomycin and intravitreal clindamycin and amikacin led to clinical improvement in both eyes, with quiescence of anterior chamber cell and vitritis. Best-corrected visual acuity at 3 weeks of follow-up had improved to 20/40 in the right eye and remained light perception in the left eye. Conclusion: In cases of endogenous endophthalmitis secondary to methicillin-resistant S. aureus not responsive to intravenous and intravitreal vancomycin, particularly with borderline sensitivities, consideration to clinical resistance should be entertained. RETINAL CASES & BRIEF REPORTS 9:59–60, 2015
From the *Department of Ophthalmology, Albany Medical Center, Lions Eye Institute, Albany, New York; and †Retina Consultants PLLC, Department of Ophthalmology, Division of Vitreoretinal Surgery, Albany Medical College, Slingerlands, New York.
Case Report A 48-year-old woman with history of hypertension, Type II diabetes mellitus, and end-stage renal disease on hemodialysis was admitted for the treatment of methicillin-resistant S. aureus bacteremia with intravenous vancomycin. While inpatient, she developed pain and rapidly progressive vision loss in both eyes with a best-corrected visual acuity of 20/25 in the right eye and hand motion in the left eye. Anterior chamber examination revealed 4+ leukocytes and a fibrinous reaction in both eyes, with a layered hypopyon in the left eye. Dilated examination of the right eye revealed 1+ vitritis and focal retinitis in the temporal equator. The fundus was not visible in the left eye, where B-scan ultrasonography revealed dense vitreous debris and an attached retina. Endogenous endophthalmitis secondary to methicillin-resistant S. aureus was diagnosed. Vitreous tap of the left eye and injection of vancomycin (1 mg per 0.1 mL) and ceftazidime (2.25 mg per 0.1 mL) into both eyes were performed. Despite intravitreal and intravenous vancomycin, deterioration of vision to 20/200− in the right eye and light perception in the left eye, with the development of a hypopyon in the right eye and increasing hypopyon in the left eye, was noted 2 days later. Vitreous culture confirmed methicillinresistant S. aureus. Microbiological testing revealed a minimum inhibitory concentration (MIC) of 2 mg/mL for vancomycin. The laboratory at Albany Medical Center uses the broth microdilution test for assessing susceptibilities of S. aureus. Notably, the
R
ecently, systemic infections due to Staphylococcus aureus strains with decreased sensitivity to vancomycin have emerged and pose a significant clinical concern.1 To date, vancomycin-resistant S. aureus has not been reported as a cause of endogenous endophthalmitis. Here, we describe a case of severe bilateral endogenous endophthalmitis due to S. aureus that was clinically resistant to vancomycin.
None of the authors have any financial/conflicting interests to disclose. Reprint requests: Vaidehi S. Dedania, MD, Department of Ophthalmology, Albany Medical Center, 1220 New Scotland Road, Slingerlands, NY 12159; e-mail: [email protected]
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microbiology laboratory documented that an MIC $2 was possible evidence of the development of vancomycin resistance. Because of worsening despite therapy and a borderline MIC, vancomycin resistance was suspected. Systemic therapy was changed to intravenous daptomycin and intravitreal injections of clindamycin 1 mg per 0.1 mL (MIC #0.5 [susceptible]) and amikacin 400 mg per 0.1 mL (MIC = 16 [susceptible]) were administered. Within 24 hours of changing therapy, both eyes clinically improved with quiescence of anterior chamber cell and vitritis. At 3 weeks of follow-up, best-corrected visual acuity was 20/40 in the right eye and light perception in the left eye with a resolved retinal infiltrate in the right eye. The left eye developed a total retinal detachment.
Discussion The first clinical isolate of vancomycin-resistant S. aureus was reported in 2002 from an indwelling catheter tip.2 The Center for Disease Control (CDC) currently defines vancomycin-susceptible S. aureus as having an MIC of #2 mg/mL, vancomycinintermediate S. aureus as having an MIC of 4 to 8 mg/mL, and vancomycin-resistant S. aureus as having an MIC of $16 mg/mL.3,4 These definitions have recently been questioned because infections with high MICs in the susceptible range (MIC = 1–2 mg/mL) have shown decreased vancomycin susceptibility and higher rates of treatment failure.1 In addition to a higher likelihood of clinical treatment failure, the attainment of target serum levels of vancomycin in patients with S. aureus isolates with an MIC $2 mg/mL may be less likely and has necessitated the use of alternative antibiotic regimens.5 Furthermore, reports suggest that the treatment of S. aureus bacteremia with vancomycin in isolates with an MIC of 1 mg/mL to 2 mg/mL may have decreased success and/or require higher doses of medication.6 Vancomycin-resistant S. aureus endophthalmitis is very rare, with only 3 reported cases, all occurring postoperatively.7 These cases were treated with varying combinations of intravitreal quinupristin/dalfopristin, ceftazidime and amikacin, and systemic linezolid, rifampin, and minocycline.7 Additionally, daptomycin has emerged as an alternative to vancomycin for the treatment of methicillin-resistant S. aureus and has been found to reach therapeutic concentrations in the vitreous after intravenous administration.8 In this patient, despite intravenous and intravitreal vancomycin, profound clinical deterioration was noted. A vitrectomy was not able to be performed after this initial poor response because the patient had comorbid conditions and her medical status during this admission precluded surgical treatment. Although the CDC parameters for resistance to vancomycin were not met, there was definitive clinical evidence of
reduced susceptibility of this “high MIC” strain of S. aureus to vancomycin. Furthermore, after switching treatment to intravenous daptomycin along with intravitreal injections of clindamycin and amikacin, clinical improvement was noted within 24 hours. This rapid response to an alternate antibiotic regimen, in conjunction with the previous lack of response to vancomycin therapy, serves to support the diagnosis of a vancomycin-resistant strain of S. aureus. Endogenous bacterial endophthalmitis caused by clinically vancomycin-resistant S. aureus has not previously been reported. In this case of S. aureus-induced endogenous endophthalmitis, there was significant clinical worsening on the previous regimen, and microbiological evaluation showed borderline sensitivity. Fortunately, intravenous daptomycin with intravitreal clindamycin and amikacin were successful in inducing quiescence. In cases of S. aureus endophthalmitis not responsive to vancomycin, particularly with borderline sensitivities, alternative antibiotics should be considered. Key words: endogenous endophthalmitis, Staphylococcus aureus, vancomycin-resistant. References 1. Holmes NE, Johnson PD, Howden BP. Relationship between vancomycin-resistant Staphylococcus aureus, vancomycinintermediate S. aureus, high vancomycin MIC, and outcome in serious S. aureus infections. J Clin Microbiol 2012;50:2548–2552. 2. Chang S, Sievert DM, Hageman JC, et al. Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene. N Engl J Med 2003;348:1342–1347. 3. Clinical and Laboratory Standards Institute (CLSI). Methods for Diluation Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard—Seventh edition. CLSI Document M07-a7. Wayne, Philadelphia, PA: CLSI; 2006. 4. Hageman JC, Patel JB, Carey RC, et al. Investigation and control of vancomycin-intermediate and -resistant Staphylococcus aureus: a guide for health departments and infection control personnel. Atlanta, GA. 2006. Available at: http://www.cdc.gov/ hai/pdfs/visa_vrsa/visa_vrsa_guide.pdf. 5. Ryback MJ, Lomaestro BM, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Disease Society of America, and the Society of Infectious Disease Pharmacists. Pharmacotherapy 2009;29:1275–1279. 6. Sakoulas G, Moise-Broder PA, Schentag J, et al. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J Clin Microbiol 2004;42:2398–2402. 7. Stroh EM. Quinupristin/dalfopristin in vancomycin-resistant Staphylococcus aureus endophthalmitis. Arch Ophthalmol 2012;130:1323–1324. 8. Sheridan KR, Potoski BA, Shields RK, et al. Presence of adequate intravitreal concentrations of daptomycin after systemic intravenous administration in a patient with endogenous endophthalmitis. Pharmacotherapy 2010;30:1247–1251.
