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Background Neonatal HSV infection is associated with substantial morbidity and mortality. Therefore, prompt identification and treatment of infected neonates is paramount. At Nationwide Children’s Hospital (NCH), Columbus, OH all neonates admitted in the first 2 weeks (up to 2010) and 4 weeks (since 2010) of age are evaluated for HSV infection in addition to routine bacterial and other viral infections. The frequency of co-infection with HSV and other potential pathogens is not fully known. Methods Retrospective review of the medical records of infants admitted to NCH with a diagnosis of neonatal HSV infection from 2001 to 2019. Patients less than 6 weeks of age were identified by review of the NCH Virology and Molecular Laboratory results for all positive HSV PCRs obtained from any body site as well as by discharge ICD-9 and ICD-10 codes for HSV infection. Medical records were reviewed for demographic, clinical, laboratory, outcome data, and maternal history of genital HSV lesions at or before delivery. Occurrence of positive bacterial and/or viral co-detection were identified. The data were managed using REDCap electronic data capture tools hosted at NCH. Results There were 93 infants with neonatal HSV infection (mean age, 9.5 days [IQR, 7-15]; 42%, HSV1; 53%, HSV-2). 32 infants had central nervous system infection (CNS) while 31 had Skin-Eye-Mouth (SEM) infection and 30 had Disseminated Disease. Mortality was 15% (n=14). Only 3 mothers had active genital HSV lesions at delivery. Of the 93 infants, 5 (5%) had bacterial (n=2) or viral (n=3) co-infections. All of the infants only had mucosal sites positive for HSV 1 (n=4) or 2 (n=1). Of the 2 infants with bacterial infection, 1 had bacteremia due to viridans streptococci while the other one had necrotizing enterocolitis and a positive blood culture for Clostridium butyricum. The 3 infants with viral co-detection also were full term and all had positive enterovovirus PCR tests (1, blood, throat; 1, blood and ceerebrospinal fluid (CSF); 1, CSF) Conclusion 5% of infants with neonatal HSV infection had bacterial or enteroviral co-infection. These findings have important implications in the management of neonates evaluated for possible sepsis. Disclosures Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Advisor or Review Panel member)

Objectives Extremely premature infants are at high risk of developing invasive candidiasis; fluconazole prophylaxis is safe and effective for reducing invasive candidiasis in this population but further study is needed. We sought to better understand the effect of prophylactic fluconazole on a selection of fluconazole-resistant Candida species. Methods We evaluated the susceptibility to fluconazole of Candida isolates from premature infants ( Results Three hundred and sixty-one infants received fluconazole (n = 188) or placebo (n = 173). After the baseline period, Candida colonization was significantly lower in the fluconazole group compared with placebo during periods 1 (5% versus 27%; P Conclusions Fluconazole prophylaxis decreased Candida albicans and ‘non-albicans’ Candida colonization and was associated with a slightly higher fluconazole MIC for colonizing Candida isolates.

Background The diagnosis of congenital cytomegalovirus (cCMV) infection requires that CMV be detected in a body fluid before 3 weeks of age. After 3 weeks, a diagnosis of cCMV infection is difficult since one cannot differentiate between prenatal, natal, and postnatal CMV acquisition. Infants who refer on the newborn hearing screen often are diagnosed with hearing loss after 3 weeks of age. Our objective was to describe the use of the newborn dried blood spot (DBS) for detection of CMV DNA in infants who are evaluated for sensorineural hearing loss (SNHL). Methods Retrospective review of the electronic health records of infants who were referred to the Neonatal Infectious Disease (NEO-ID) Clinic at Nationwide Children’s Hospital, Columbus, OH since 2015 for evaluation of SNHL. Demographic, clinical, laboratory, and radiographic data were reviewed. With maternal informed consent, the newborn DBS was obtained from the Ohio Department of Health for detection of CMV DNA by polymerase chain reaction (PCR) testing as previously described (Boppana et al. JAMA, 2010). Results Eighteen infants (gestational age [mean ± SD], 38 ± 4 weeks; birth weight, 3,094 ± 705 g) with SNHL were referred by Otolaryngology for evaluation of possible cCMV infection; 17 (94%) had referred on the newborn hearing screen. The 18 infants were first tested for CMV at 151 ± 124 days of age (mean ±SD; range, 21–521 days), and 3 (17%) had a positive CMV DBS. Fourteen (78%) of the 18 infants had a positive serum CMV IgG antibody while 5 (63%) of 8 infants had CMV DNA detected in urine by PCR. Of the 3 infants with a positive CMV DBS, 2 were tested for CMV DNA PCR in urine and both were positive. Of the 3 infants, 1 had a negative serum CMV IgG antibody test at 174 days of age but the urine CMV PCR test was positive. In comparison, of 54 infants with cCMV infection confirmed by a positive urine CMV PCR in the first 3 weeks of age, 37 (68%) had a positive CMV DBS. Conclusion DBS testing for CMV DNA by PCR testing identified a small minority of infants with SNHL and thus confirming congenital infection. However, the overall sensitivity of CMV DBS testing in our cohort was 68%, suggesting that some infants with SNHL due to congenital CMV infection are missed. Disclosures All authors: No reported disclosures.

Background Many children born to HCV-infected mothers in the U.S. never receive recommended anti-HCV antibody (Ab) screening at age ≥ 18 months. Earlier testing by HCV-RNA PCR might facilitate increased screening, though prior studies using older PCR assays reported unacceptably low sensitivity of one-time PCR testing in infants. We hypothesized that testing at age 2–6 months using modern blood HCV-RNA PCR platforms with enhanced analytical sensitivity and reliability will adequately detect infected infants. Methods Medical records of vertically exposed infants tested for HCV-RNA at age 2–6 months at Nationwide Children’s Hospital from January 1, 2008 to December 31, 2017 were reviewed. HCV-RNA tests included qualitative (in-house) and quantitative (ARUP reference lab) Cobas Taqman RT-PCR assays (Roche) with lower limits of detection of 1.2–1.9 log10 IU/mL. Diagnostic performance of early PCR screening was determined using a composite gold standard: (1) infected children had ≥ 2 positive PCRs or persistently positive Ab after age 24 months; (2) uninfected children lacked these criteria and required documentation of a negative Ab at a point after age 18 months. Results During the study period, 639 vertically exposed infants underwent HCV-RNA testing at age 2–6 months. Of these, 24 (3.8%) tested positive, consistent with prior estimates of the vertical transmission rate. Blood HCV-RNA levels were high at screening (median 6.7 log10 IU/mL, range 5.2–7.8 log10 IU/mL), and confirmatory PCR tests were positive in all who had repeat testing (n = 22). Among 615 infants with negative PCR screening, 444 had reached age ≥ 18 months, of whom 144 had undergone Ab testing. Ab tests were negative in 142, while two children had low positive Ab results at 18 months. In both cases, repeat PCR and repeat Ab after age 24 months were negative, suggesting waning maternal Ab rather than true infection. Using the composite gold standard there were 22 true positive, 0 false-positive, 144 true negative, and 0 false negative cases, yielding a sensitivity of 100% (95% CI: 85–100% [Wilson-Brown]). Conclusion These findings demonstrate that modern blood HCV-RNA PCR assays have excellent sensitivity for detecting vertically infected infants as early as 2–6 months of age and may improve HCV surveillance given the substantial number of children lost to follow-up prior to 18 months Ab screening. Disclosures All authors: No reported disclosures.

Background There is a paucity of data relating to pediatric subacute or chronic hematogenous osteomyelitis (SCHO), non-hematogenous osteoarticular infections (NHO), and osteoarticular hardware infections (HI). A comparative analysis of the entire spectrum of pediatric osteoarticular infections was conducted to identify distinguishing clinical features and biological markers. Methods Using ICD9/10 code searches, we identified pediatric patients ≤18 years of age at Hasbro Children’s Hospital (2006–2016) and Nationwide Children’s Hospital (2015–2016) with osteoarticular infections. Cases of Lyme arthritis or ENT-related infections were excluded. Eligibility criteria were confirmed by reviewing medical records and clinical and laboratory data were collected systematically. Results 428 children met inclusion criteria: 211 (49%) had acute hematogenous osteomyelitis (AHO), 61 (14%) suppurative arthritis (SA), 42 (10%) SCHO, 60 (14%) NHO, and 54 (13%) HI. The age distribution differed significantly across the five infection types: AHO (median, 9.2 years), SA (5.0), SCHO (10.2), NHO (11.5), and HI (14.5); P < 0.001. Median initial CRP values were significantly higher (P < 0.001) in AHO (65 mg/dl) and SA (44) compared with SCHO (15), NHO (15) and HI (24). An ESR >19 mm/hours at presentation was more sensitive than a CRP >8.0 mg/dl in identifying SCHO (80% vs. 64%; P = 0.035). Bacteremia occurred more frequently in AHO (42%) and SA (25%) compared with SCHO (7%), NHOI (5%) and OHI (4%); P < 0.001. Patients with HI had significantly more complications as reflected by more ICU admissions (33% vs. ≤3% for other groups), and longer antibiotic treatment durations (median, 65 vs. ≤37 days for other groups); P < 0.001 for each comparison. S. aureus was the most common organism isolated for all infections, but the proportion of other Gram- and Gram-negative pathogens was significantly higher in SCHO, NHO, and HI compared with AHO and SA (P < 0.001). The ratio of MSSA to MRSA among isolates was 3:1, and did not differ significantly across the infection types. Conclusion SCHO, NHO, and HI commonly present with minimal evidence of inflammation, and differ in the spectrum of causative pathogens compared with AHO and SA. Further studies are required to optimize the diagnosis and management of non-acute, non-hematogenous osteoarticular infections. Disclosures All authors: No reported disclosures.

Background Congenital CMV infection is the leading cause of non-genetic sensorineural hearing loss in infancy. Antiviral therapy has been shown to improve hearing outcomes, and thus “targeted” CMV screening for newborns who do not pass the hearing screen has been recommended. Diagnosis of congenital CMV infection requires that the infant be tested for CMV in the first 3 weeks of age. Our objective was to determine when infants in the neonatal intensive care unit (NICU) have their first hearing screen performed and thus inform the practice of targeted screening for determination of CMV-related hearing loss. Methods Retrospective review of the electronic health records of all infants admitted to the Level 4 outborn NICU at Nationwide Children’s Hospital, Columbus, OH from August 2016 to May 2017. Demographic and clinical data were obtained, and the age that the first hearing screen was performed was assessed. Results During the 10 month study period, 362 infants were admitted to the NICU and had a first hearing screen performed. The majority of neonates (204, 56%) had a first hearing screen performed in the first 3 weeks of age. However, 158 (44%; median birth weight [IQR], 1072 g [747–1766]; median gestational age [IQR], 28 weeks [25–32]) infants received the first hearing screen at >3 weeks of age when a positive CMV PCR or culture cannot distinguish congenital infection from intrapartum/postnatal acquisition of CMV. Of the 158 infants, 20 (13%) did not pass the first hearing screen (13, unilateral; 7, bilateral), and subsequently, 9 of them did pass a second hearing screen. However, 11 of the 20 infants did not pass a second hearing screen and had urine CMV PCR testing, and 1 (9%) was positive. This latter infant’s newborn dried blood spot CMV DNA PCR was negative so a diagnosis of congenital CMV infection was not possible. Conclusion Targeted screening in the NICU for CMV-related hearing loss is problematic as a substantial number of infants do not have a hearing screen performed until after 21 days of age, thus representing a missed opportunity for diagnosis of congenital CMV infection and institution of antiviral therapy if indicated. Our findings support universal CMV screening of neonates on admission to the NICU. Disclosures O. Adunka, MED-EL Corporation: Consultant, Consulting fee, Educational grant and Research support; Advanced Bionics: Consultant, Consulting fee and Licensing agreement or royalty; Advanced Cochlear Diagnostics: President, Ownership interest; AGTC Corporation: Consultant, Consulting fee

Candidiasis carries a significant risk of death or neurodevelopmental impairment (NDI) in extremely low birth weight infants (ELBW;1000 g). We sought to determine the impact of candiduria in ELBW preterm infants.Our study was a secondary analysis of the Neonatal Research Network study Early Diagnosis of Nosocomial Candidiasis. Follow-up assessments included Bayley Scales of Infant Development examinations at 18-22 months of corrected age. Risk factors were compared between groups using exact tests and general linear modeling. Death, NDI, and death or NDI were compared using generalized linear mixed modeling.Of 1515 infants enrolled, 34 (2.2%) had candiduria only. Candida was isolated from blood only (69 of 1515 [4.6%]), cerebrospinal fluid (CSF) only (2 of 1515 [0.1%]), other sterile site only (not urine, blood, or CSF; 4 of 1515 [0.3%]), or multiple sources (28 of 1515 [2%]). Eleven infants had the same Candida species isolated in blood and urine within 3 days; 3 (27%) had a positive urine culture result first. Most urine isolates were Candida albicans (21 of 34 [62%]) or Candida parapsilosis (7 of 34 [29%]). Rate of death or NDI was greater among those with candiduria (50%) than among those with suspected but not proven infection (32%; odds ratio, 2.5 [95% confidence interval, 1.2-5.3]) after adjustment. No difference in death and death or NDI was noted between infants with candiduria and those with candidemia.These findings provide compelling evidence that ELBW infants with candiduria are at substantial risk of death or NDI. Candiduria in ELBW preterm infants should prompt a systemic evaluation (blood, CSF, and abdominal ultrasound) for disseminated Candida infection and warrants treatment.

Infants with Congenital CMV Infection: Is It Worth Doing the Lumbar Puncture? Christopher Ouellette, MD; Andrea Ronchi, MD; Asuncion Mejias, MD, PhD; Susana Chavez-Bueno, MD; Douglas Salamon, MB(ASCP)SV; Lorenza Pugni; Fabio Mosca; Pablo J. Sanchez MD, FIDSA; Pediatrics, Division of Infectious Diseases, Nationwide Children’s Hospital, Columbus, OH; Pediatrics, University of Texas Southwestern, Dallas, TX; Center for Vaccines and Immunity, The Research Institute at Nationwide Children’s Hospital, Columbus, OH; University of Oklahoma Health Sciences Center, Oklahoma City, OK; Department of Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH; Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, Universita degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy