Journal of Perinatology (2007) 27, 392–394 r 2007 Nature Publishing Group All rights reserved. 0743-8346/07 $30 www.nature.com/jp PERINATAL/NEONATAL CASE PRESENTATION Endogenous group B streptococcal endophthalmitis in a preterm infant

JR Sparks1, FM Recchia2 and J-H Weitkamp3 1Vanderbilt University School of Medicine, Nashville, TN, USA; 2Division of Vitreoretinal Diseases and Surgery, Vanderbilt Eye Institute, Nashville, TN, USA and 3Department of Pediatrics, Division of Neonatology, Monroe Carell Jr Children’s Hospital at Vanderbilt, Nashville, TN, USA

experienced several episodes of apnea and tachycardia on DOL 22. Endogenous endophthalmitis is a rare complication of bacteremia. Proper He received a lumbar puncture and blood culture, both of which intervention is critical, as the majority of affected patients lose vision in the grew GBS. He was treated for GBS meningitis with 400 mg/kg/day infected eye. Treatment options include systemic antibiotics, intravitreous in four divided doses of intravenous ampicillin for 38 days from antibiotics and vitrectomy. We report a case of endogenous endophthalmitis DOL 22 to 60 and 4 mg/kg/day as a single daily dose of intravenous presenting as leukocoria in a premature neonate with group B streptococcal gentamicin for 7 days from DOL 22 to DOL 29. The course was meningitis. complicated by persistently positive CSF cultures for GBS. CSF Journal of Perinatology (2007) 27, 392–394; doi:10.1038/sj.jp.7211685 findings between DOL 22 and 30 are shown in Table 1. Keywords: Group B streptococcus; endogenous endophthalmitis; infant; On DOL 40, while on ampicillin therapy, right-sided leukocoria premature; meningitis; vitrectomy was discovered during the infant’s initial screening exam for retinopathy of prematurity, and the presumptive diagnosis of endogenous endophthalmitis of the right eye was made (Figure 1). Introduction On ophthalmic examination of the right eye, the anterior Group B streptococci (Streptococcus agalactiae, GBS) remain a segment was quiet without hypoyon. Dense white opacities major pathogen causing invasive bacterial infections in neonates occupied the vitreous cavity, giving a grey-white reflex and and young infants. Although endogenous GBS endophthalmitis has precluding visualization of the retina. Ultrasonography revealed been reported in adults,1 this complication is extremely rare in dense vitreous opacities and no retinal detachment. Vitreous biopsy infants.2–5 Because endophthalmitis can cause rapid and and intravitreal administration of vancomycin 0.5 mg were carried widespread destruction of the choroid and retina with poor visual out under sedation in the operating room on DOL 45. Vancomycin prognosis, early diagnosis and treatment is essential for better was chosen because of its proven efficacy against Gram-positive outcome.3 cocci and its safety as an intravitreal injection. Systemic antibiotic therapy with high doses of ampicillin was continued for more than 4 weeks after the first negative CSF culture. As the vitreous debris did not clear spontaneously and there was concern for possible Case report development of deprivational amblyopia, vitrectomy surgery was A 1580 g male twin infant was born at 29 weeks gestational age via performed on DOL 74 to clear the visual axis. Culture of undiluted cesarean section for placental insufficiency to a 28-year-old prima vitreous fluid was negative. One month following uncomplicated gravida with twin gestation. Prenatal laboratory test results were surgery, the infant displayed a reaction to light in both eyes. Three significant for a positive GBS urine culture; intrapartum months postvitrectomy, a cataract was noted, and the patient antimicrobial prophylaxis was not given. Cultures of blood and underwent cataract extraction. At most recent examination cerebrospinal fluid (CSF) were sterile, and antimicrobial therapy 6 months postvitrectomy, the media were clear, the retina was was not administered. completely attached, and there was retinal epithelial atrophy and This baby’s twin brother was diagnosed with GBS meningitis at scarring consistent with the previous infection. day of life (DOL 19), was treated successfully and released from the hospital in good condition. Subsequently, the patient reported here

Correspondence: Dr J-H Weitkamp, Pediatrics/Neonatology, Monroe Carell Jr Children’s Discussion Hospital at Vanderbilt, 11111 Doctor’s Office Tower, Nashville, TN 37232-9544, USA. E-mail: [email protected] Endogenous endophthalmitis as a complication of late-onset GBS Received 3 October 2006; revised 23 January 2007; accepted 1 February 2007 disease in infants has been reported very rarely, and to our Endogenous group B strep endophthalmitis JR Sparks et al 393 knowledge, this is the first report of a premature infant with this is a concern. Complete ophthalmic examination and complication. We found only four other reports of neonatal ultrasonography can be necessary to establish the diagnosis. Some endophthalmitis associated with GBS disease in the literature.2–5 recommend that all infants with sepsis should be subjected to a In these four described cases, all but one5 were associated with GBS thorough ophthalmic examination.8 Although organisms can be bacteremia and meningitis, similar to this patient. Late-onset GBS occasionally cultured from a vitreous biopsy or a vitrectomy disease usually occurs from 1 week to 3 months after delivery and cassette,9 the diagnosis is established most frequently from blood presents with meningitis as the predominant clinical finding. cultures. In a recent review of endogenous bacterial Premature infants, such as in this case, are at increased risk for endophthalmitis, blood cultures were positive in 94% and vitreous late-onset GBS sepsis, most likely due to decreased levels of cultures in only 56%.1 In the case presented here, both blood and maternal antibodies.6 In this setting, bacteria leaving the CSF cultures were positive for GBS; however, a vitreous aspirate and bloodstream enter the CSF space and initiate an inflammatory a vitrectomy specimen were both negative, most likely because the cascade. The initial inflammatory response leads to cerebral blood vitreous aspirate was taken after the infant had already received flow alteration and impairment of the retinal blood flow. Group B systemic antibiotics, and the vitrectomy was performed after streptococcal meningitis significantly impairs eye blood flow administration of intravitreal antibiotics. Polymerase chain autoregulation and may contribute to increased risk of retinal reaction and DNA sequencing of samples from vitreous or aqueous damage in infants with meningitis.7 fluid have been reported and these methods promise to be useful Endogenous endophthalmitis can be initially misdiagnosed and diagnostic tools for culture-negative samples, although speciation can result in poor visual prognosis if treatment is delayed. In is not always possible.10,11 neonates, typical examination features that the neonatologist can Endogenous bacterial endophthalmitis, irrespective of etiology, see include a reduced or absent red reflex and a limited view of the relates to amount and duration of inoculum. The ongoing positive fundus (Figure 1). The differential diagnosis of leukocoria in this CSF cultures despite optimal therapy are a clue not only to age group includes cataract, retinoblastoma or retinal detachment, intracranial complications but also to endophthalmitis, making especially in premature infants in whom retinopathy of prematurity daily eye examinations crucial to early diagnosis and good outcome. Early systemic antibiotic therapy remains the cornerstone of Table 1 Cerebrospinal fluid findings by hospital day treatment; however, patients can develop endogenous endophthalmitis while on appropriate therapy with therapeutic Day of life 22 24 26 30 blood levels. The role of intravitreal antibiotics is controversial. Glucose (mg/dl) 0 5 8 23 Some experts advocate combined vitreous biopsy and intravitreal Protein (mg/dl) 373 306 339 396 injection of vancomycin or ceftazidime for most Gram stain 1,9 Leukocytes (mlÀ1) 5520 1020 1270 210 positive or Gram stain negative organisms, respectively. Polymorphonuclear leukocytes (%) 78 63 81 64 Vitrectomy can be therapeutic, but, in the absence of randomized Gram stain 2+ Gram-pos. cocci in pairs Neg. Neg. Neg. trials studying patients with endogenous endophthalmitis, no clear Culture GBS GBS GBSa Neg. recommendations regarding its use can be made. In such cases Abbreviation: GBS, group B streptococci. affecting adults, vitrectomy can be associated with improved aGBS grew on one plate after 3 days of incubation. outcome.1 Given the significantly higher ocular and systemic

Figure 1 (a) External photograph of the right eye showing a quiet anterior segment and an irregular white reflex. The lens is clear, and the white reflex is due to dense vitreous opacities. (b) Wide-field fundus photograph of the right eye showing diffuse vitreous debris with no visualization of the retina.

Journal of Perinatology Endogenous group B strep endophthalmitis JR Sparks et al 394 morbidity of vitrectomy in a young premature infant, vitrectomy is 4 Greenwald MJ, Wohl LG, Sell CH. Metastatic bacterial endophthalmitis. usually reserved for cases with more severe infection, in cases with A contemporary reappraisal. Surv Ophthalmol 1986; 31: 81–101. associated retinal detachment, or in cases in which clearing of 5 Wu Z, Uzcategui N, Chung M, Song J, Lim JI. Group B streptococcal optical media is necessary for visual development. endogenous endophthalmitis in a neonate. Retina 2006; 26: 472–473. The outcome of endogenous endophthalmitis is generally poor. 6 Lin FY, Weismann LE, Troendle J, Adams K. Prematurity is the major risk However, with prompt diagnosis and treatment, maintenance of factor for late-onset group B streptococcus disease. J Infect Dis 2003; 188: vision is possible. 267–271. 7 Bottoli I, Beharry K, Modanlou HD, Norris K, Ling E, Noya F et al. Effect of group B streptococcal meningitis on retinal blood and choroidal blood flow in newborn pigs. Invest Ophtalmol Vis Sci 1995; 36: Acknowledgments 1231–1239. We thank Dr William Walsh for review of this paper and helpful discussion. 8 Matasova K, Hudecova J, Zibolen M. Bilateral endogenous endophthalmitis as a complication of late-onset sepsis in a premature infant. Eur J Pediatr 2003; 162: 346–347. References 9 Donahue SP, Kowalski RP, Jewart BH, Friberg TR. Vitreous cultures in 1 Jackson TL, Eykyn SJ, Graham EM, Stanford MR. Endogenous bacterial suspected endophthalmitis. Biopsy or vitrectomy? Ophthalmology 1993; 100: endophthalmitis: a 17-year prospective series and review of 267 reported 452–455. cases. Surv Opthalmol 2003; 48: 403–423. 10 Okhravi N, Adamson P, Carroll N, Dunlop A, Matheson MM, Towler HMA 2 Greene GR, Carroll WL, Morozumi PA, Ching FC. Endophthalmitis et al. PCR-based evidence of bacterial involvement in eyes with suspected associated with group-B streptococcal meningitis in an infant. Am J Dis intraocular infection. Invest Ophthalmol Vis Sci 2000; 41: 3474–3479. Child 1979; 133: 752–753. 11 Okhravi N, Adamson P, Matheson MM, Towler HM, Lightman S. PCR-RFLP- 3 Berger BB. Endophthalmitis complicating neonatal group B streptococcal mediated detection and speciation of bacterial sepsis causing endophthal- septicemia. Am J Ophthalmol 1982; 92: 681–684. mitis. Invest Ophthalmol Vis Sci 2000; 41: 1438–1447.

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