Empiric Acyclovir Research Articles

EPSTEIN-BARR–POSITIVE ULCERS OF THE ORAL CAVITY ASSOCIATED WITH IMMUNOSUPPRESSION IN A PATIENT WITH CANCER

A 24-year-old man with synovial sarcoma was hospitalized for neutropenic fever after chemotherapy, complaining of gingival pain for 1 day. No lymph node involvement was detected during neck palpation. Intraoral exam revealed a purple lesion involving the attached gingiva on the maxilla and mandible, of increased size and with a detachable overlying white plaque. There was rapid evolution to ulcerated lesions, causing an inability to feed. We performed an incisional biopsy and referred the patient for anatomopathologic examination, polymerase chain reaction (PCR), and culture for fungi and bacteria, a prescription of chlorhexidine 0.12%, and empiric fluconazole and acyclovir. PCR was positive for Epstein-Barr virus (EBV) with 1095 copies, so the patient was maintained on acyclovir for 15 days. The patient had significant improvement in pain and the oral lesions regressed after this period. This case demonstrated that EBV commonly occurs in immunosuppressed patients and underscores the importance of dentists in the diagnosis and control of oral complications in the multiprofessional hospital team. A 24-year-old man with synovial sarcoma was hospitalized for neutropenic fever after chemotherapy, complaining of gingival pain for 1 day. No lymph node involvement was detected during neck palpation. Intraoral exam revealed a purple lesion involving the attached gingiva on the maxilla and mandible, of increased size and with a detachable overlying white plaque. There was rapid evolution to ulcerated lesions, causing an inability to feed. We performed an incisional biopsy and referred the patient for anatomopathologic examination, polymerase chain reaction (PCR), and culture for fungi and bacteria, a prescription of chlorhexidine 0.12%, and empiric fluconazole and acyclovir. PCR was positive for Epstein-Barr virus (EBV) with 1095 copies, so the patient was maintained on acyclovir for 15 days. The patient had significant improvement in pain and the oral lesions regressed after this period. This case demonstrated that EBV commonly occurs in immunosuppressed patients and underscores the importance of dentists in the diagnosis and control of oral complications in the multiprofessional hospital team.

2587. Etiology and Outcome of Acute Neonatal Infectious Encephalitis

BackgroundThere are very few studies on acute encephalitis with onset during the neonatal period. The objectives of this study were to investigate the etiology and salient clinical features of neonatal encephalitis.MethodsNeonates with possible infectious encephalitis (IE) were prospectively enrolled. Inclusion criteria included encephalopathy (altered/fluctuating level of consciousness ≥24 hours) plus ≥2 of: fever/temperature instability; seizure(s); focal neurologic findings; CSF pleocytosis; EEG abnormalities consistent with encephalitis; neuroimaging abnormalities consistent with encephalitis. Neonates with a clear diagnosis of post-perinatal asphyxial encephalopathy or culture proven bacterial meningitis were excluded. Results shown as absolute numbers, proportions or medians [interquartile range] as appropriate.ResultsFifty-nine neonates fulfilled the inclusion/exclusion criteria (June 2013–November 2018). Empiric acyclovir was initiated in 49 (83.1%) cases. An infectious etiology was identified in 25 (42.4%): enteroviruses (n = 15), HSV (n = 5), HHV6 (n = 2), parainfluenza 3 (n = 1), influenza A (n = 1), CMV (n = 1). A noninfectious cause was confirmed in 20 (33.9%): missed hypoxic-ischemic encephalopathy (n = 10), genetic/metabolic disorders (n = 7), ischemic/hemorrhagic stroke (n = 3). No specific etiology was identified in 14 (23.7%). Thirteen (52%) neonates with IE either died (n = 7) or suffered neurologic sequelae (n = 6). Deaths were attributable to HSV (n = 4), enteroviruses (n = 2) and HHV6 (n = 1). Neurocognitive sequelae were documented in one case each of enterovirus, HSV2, HHV6, CMV, parainfluenza 3 and influenza A. Differences between neonates with and without IE, respectively, included age in days of symptom onset (7 [6, 10] vs. 1 [0, 3]; P < 0.001), gestational age (37.0 [36.0, 39.0] vs. 38.6 [37.6, 40.0]; P = 0.045), peripheral leukocyte count (10.5 [IQR 5.9, 14.6] vs. 14.3 [IQR 10.7, 21.7]; P = 0.008) and CSF glucose (2.80 [IQR 2.3, 3.2] vs. 3.10 [2.8, 3.8]; P = 0.003).ConclusionEnteroviruses and HSV are the predominant causes of neonatal IE. Outcome of neonatal IE is poor with approximately half dying or suffering neurologic sequelae.Disclosures All authors: No reported disclosures.

652. Impact of FilmArray Meningitis Encephalitis Panel on HSV Testing and Acyclovir Use in Children Beyond the Neonatal Period

BackgroundTesting and empiric use of acyclovir for herpes simplex virus (HSV) in children beyond the neonatal period undergoing lumbar puncture for suspected central nervous system (CNS) infection doubled in the past decade, while the incidence of HSV CNS infection is unchanged. A new syndromic multiplex PCR panel (FilmArray Meningitis Encephalitis Panel [MEP]) rapidly detects 14 pathogens in cerebrospinal fluid (CSF), including HSV. The impact of MEP implementation on HSV testing and acyclovir use is unknown.MethodsWe retrospectively compared CSF testing and acyclovir use in the pre-MEP era January 1, 2007–January 22, 2017 to post-implementation era of MEP January 23, 2017–December 31, 2017 amongst children >60 days with a CSF specimen sent to the Children’s Hospital Colorado microbiology laboratory. HSV singleplex PCR testing was available in both the pre-MEP and MEP eras.ResultsThe proportion of CSF specimens from children with suspected CNS infection undergoing HSV testing (MEP or HSV PCR) doubled from 25% in the pre-MEP era to 54% in the MEP era (P < 0.01; Figure 1). In the MEP era, HSV testing was conducted by MEP in 96% of cases and HSV PCR in 8% of cases. In both eras, a majority of CSF specimens undergoing HSV testing had no pleocytosis (63% vs. 59%, P = 0.27). Children with negative HSV testing by MEP were less likely to be started on acyclovir than those with negative HSV testing by singleplex PCR (18% vs. 50%, P < 0.01) and, amongst those started, acyclovir was discontinued sooner, after a median 3 vs 5 doses (P = 0.05). Overall, however, a similar proportion of children with suspected CNS infection received acyclovir in the MEP and pre-MEP eras (13% vs. 12%), despite a low rate of HSV positivity (0.5% vs. 0%).ConclusionImplementation of MEP for syndromic CSF testing in children >60 days with suspected CNS infection doubled HSV testing without affecting the rate of empiric acyclovir initiation. Patients with negative HSV testing on MEP were less likely to be started on acyclovir, and if started, received fewer doses than those who tested negative on HSV singleplex PCR, likely due to more rapid turnaround time. However, increased MEP testing offset this, suggesting increased use of newer rapid syndromic tests will not cure creeping empiricism. Diagnostic stewardship targeting MEP use toward children with pleocytosis to decrease unnecessary test utilization are warranted. Disclosures All authors: No reported disclosures.

2283 Herpes Simplex Virus Hepatitis in Immunocompetent Hosts - A Case Series Demonstrating the Importance of Early Recognition and Empiric Antiviral Therapy

INTRODUCTION: Herpes simplex virus (HSV) is a highly prevalent virus but only rarely results in fulminant hepatitis. The prevalence of HSV1 and HSV2 are reportedly 53.9% and 15.7% in the general United States population. However, despite the high prevalence it is only responsible for 1% of all acute liver failure. Immunocompetent individuals represent only 24% of these cases. We present three cases of HSV hepatitis in the presumed immunocompetent host. CASE DESCRIPTION/METHODS: Case 1: A 70 y.o male with type II diabetes presented with high fevers. His transaminases peaked at AST 973 and ALT 1183. His INR and T Bili both peaked at 1.4. Due to the anicteric nature of his hepatitis, he was started on empiric acyclovir. He developed nonspecific encephalopathy, later attributed to hospital acquired delirium. Cerebrospinal fluid was negative for HSV. His HSV serum PCR was positive for HSV1 on day 8. He later developed painful oropharyngeal ulcers. His liver enzymes and mental status would normalize. Case 2: A 19 y.o female with osteogenesis imperfecta and lupus (treatment naive) presented after a sexual assault with fevers. She developed right upper quadrant pain and a pustular rash on upper extremities. Her liver enzymes peaked at AST 2,480 and ALT 824 on day five of admission. Her INR and total bilirubin peaked at 2.8 and 1.5, respectively. Due to the anicteric nature of her hepatitis, she was empirically treated with acyclovir. Her serum HSV PCR returned positive for HSV2 on day twenty. Liver enzymes improved and she was discharged on PO valganciclovir. Case 3: A 21 y.o female with history of chlamydial infection presented with a diffuse urticarial rash, fever and right upper quadrant pain. Her AST was 2389 and ALT 1896. Total bilirubin peaked at 1.3. Due to the anicteric nature of her hepatitis, she was empirically treated with acyclovir. PCR of an oral lesion was positive for HSV2 and her serum PCR was positive for HSV2. She recovered completely. DISCUSSION: Despite low occurrence rates, our cases demonstrate HSV hepatitis must be kept in the differential diagnosis of hepatitis in the immunocompetent host. Progression to acute liver failure (ALF) occurs in 74% of HSV hepatitis cases. ALF from HSV has a mortality rate of 90%. Therefore, high clinical suspicion must be maintained for favorable outcomes. Fortunately, our patients had resolution of their HSV hepatitis due to early recognition of anicteric hepatitis and treatment with empiric acyclovir.

VARICELLA PNEUMONIA IN AN IMMUNOCOMPETENT ADULT WITH INTERSTITIAL LUNG DISEASE (ILD) REQUIRING VENO-VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION (VV-ECMO)

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Pulmonary involvement of varicella-zoster virus (VZV) is uncommon in immunocompetent adults but is associated with up to a 24% mortality rate. In this report, we present a case of primary VZV pneumonia causing severe acute respiratory distress syndrome (ARDS) ultimately requiring veno-venous ECMO (VV-ECMO). CASE PRESENTATION: A 37-year-old male with a history of ILD, noncompliant with immunosuppression regimen, presented with fever and cough for one week. He was discharged on levofloxacin for presumed community-acquired pneumonia. Two days later, he developed dyspnea and a diffuse vesicular rash concerning for chicken pox and was admitted. He developed worsening tachypnea and hypoxemia requiring endotracheal intubation. Subsequent bronchoscopy revealed normal mucosa. Empiric antibiotics and acyclovir were started for presumed VZV pneumonia given the rash. Arterial blood gas on a FiO2 of 70% was pH 7.38, PCO2 51, and PaO2 80 (PaO2:FiO2 114). Varicella IgM was positive, and a culture of his skin lesion grew VZV. CT chest revealed diffuse ground-glass opacities (Fig 1). Despite heavy sedation, paralytics and prone positioning, he developed increasing oxygen requirements, higher plateau pressures and a worsening respiratory acidosis. The patient was placed on VV-ECMO for respiratory support. Repeat bronchoscopy revealed new diffuse, endobronchial vesicular lesions (Fig 2,3). Despite more than two weeks on ECMO, he remains on ECMO due to poor lung compliance and gas exchange. His circuit was changed to include two oxygenators in parallel to improve gas exchange and CO2 removal, which allowed him to be extubated and communicate with his family. DISCUSSION: VZV pneumonia is becoming an increasingly recognized cause of ARDS in adults. Risk factors for the development of VZV pneumonia include an immunocompromised state, male sex, smoking history and prior lung disease. Our patient was never vaccinated against VZV and did not have the infection as a child. His course echoes what is described in the literature - pneumonia-like symptoms prior to development of skin lesions followed by ARDS. The underlying ILD likely predisposed him to a more severe course despite being immunocompetent otherwise. The finding of vesicular lesions on upper airways is classic of VZV pneumonia. Interestingly, the development of airway lesions occurred after skin lesions in our patient, which may explain why there are varying bronchoscopy findings reported in the literature. The mainstays of treatment include IV acyclovir and respiratory support. CONCLUSIONS: VZV pneumonia should be on the differential for patients with a diffuse rash and pneumonia given its high mortality rate. VV-ECMO may offer further supportive options since these patients are often younger and healthier, thus having a higher likelihood of recovering. The various configurations of VV-ECMO can allow prolonged lung rest to promote healing in these patients. Reference #1: Mirouse, A. et. al. Severe varicella-zoster virus pneumonia: a multicenter cohort study. Crit Care. 2017 Jun 7;21(1):137. Reference #2: John, K.G., et. al. The outcome of severe varicella pneumonia with respiratory failure admitted to the intensive care unit for mechanical ventilation. Eur Respir J. 2018 Jul 4;52(1). DISCLOSURES: No relevant relationships by Lisa Chen, source=Web Response No relevant relationships by Jonathan Gong, source=Web Response stock relationship with Pfizer Please note: $1001 - $5000 Added 03/11/2019 by Zubair Hasan, source=Web Response, value=stock stock relationship with Stryker Please note: $1001 - $5000 Added 03/11/2019 by Zubair Hasan, source=Web Response, value=stock stock relationship with United Health Group Please note: $1001 - $5000 Added 03/11/2019 by Zubair Hasan, source=Web Response, value=stock No relevant relationships by Ayelet Hilewitz, source=Web Response No relevant relationships by Seth Koenig, source=Web Response No relevant relationships by Peter Nauka, source=Web Response

2312 Using Serum Transaminase Ratios to Recognize Herpes Simplex Hepatitis

INTRODUCTION: Herpes simplex virus (HSV) hepatitis is an uncommon cause of acute liver failure (ALF). HSV hepatitis accounts for less than 2% of all cases of viral ALF. The clinical presentation is non-specific including encephalopathy, leukopenia, and fever. Typical HSV skin manifestations are present in less than 50% of cases. Diagnosis is challenging due to the lack of timely and reliable serologic testing. Liver biopsy can help with diagnosis however is not always available. Reported mortality is 88% for untreated HSV hepatitis. Early treatment with acyclovir reduces mortality to 51%. Current guidelines recommend starting acyclovir if HSV hepatitis is suspected (1). CASE DESCRIPTION/METHODS: A 67 year-old female presented with a four day history of nausea, vomiting, diarrhea, and progressive weakness. On admission, she was hemodynamically stable with a fever of 102.8F. Physical exam revealed RUQ tenderness. No labial or genital lesions were present. Laboratory testing revealed WBC 2500 IU/L, platelets 108,000/mm3, AST 3038 IU/L, ALT 696 IU/L, ALP 181 IU/L, TB 0.2 mg/dL, and INR 1.5. Viral hepatitis serologies were negative. CT abdomen revealed a 4.9 × 3.7 × 3.5 cm enhancing lesion in the liver dome. Liver biopsy of lesion showed multifocal non-zonal massive necrosis consistent with HSV hepatitis. The patient was started on IV acyclovir at 7mg/kg/8hr on hospital day twelve for a total of fourteen days. The patient improved and liver enzymes normalized prior to discharge. DISCUSSION: A prior review of sixteen case reports described HSV hepatitis presenting with a hepatocellular liver injury pattern of AST significantly more elevated than ALT (2). This case presented similarly, with the AST:ALT ratio being nearly 5:1. Despite this pattern previously being recognized, it is not regularly described in review articles or practice guidelines. Early treatment with acyclovir lowers mortality of HSV hepatitis, yet there are no clear recommendations on when we should suspect HSV hepatitis. Clinicians should consider early empiric acyclovir for ALF when traditional viral hepatitis serologies are negative and give special consideration for hepatocellular liver injuries with significantly elevated AST:ALT ratios as this may represent a pattern for HSV hepatitis.

Factors Associated With HSV PCR CSF Testing and Empiric Acyclovir Therapy in Young Febrile Infants.

Herpes simplex virus (HSV) infection in infants is a devastating disease with an often subtle presentation. We examined cerebrospinal fluid (CSF) HSV PCR (polymerase chain reaction) testing and empiric acyclovir therapy in young febrile infants. Chart review identified hospitalized infants aged ≤60 days with fever ≥38°C who had undergone lumbar puncture. Previously published criteria were used to define patients at high risk for HSV. Primary outcomes were CSF HSV PCR testing and empiric acyclovir therapy. Of 536 febrile infants, 23% had HSV testing; empiric acyclovir was started in 15%. HSV testing and therapy were associated with younger age, seizure, maternal vaginal lesions, postnatal HSV contact, vesicles, poor tone, CSF pleocytosis, and enteroviral testing. Sixty-two percent of high-risk infants did not undergo HSV testing, and 75% did not receive acyclovir. High-risk infants were untested and untreated at relatively high rates. Evidence-based criteria to guide HSV testing and treatment are needed.

113 A case of suspected autoimmune encephalitis secondary to nivolumab

ObjectiveTo describe a case of suspected immune encephalitis following nivolumab for metastatic melanoma.MethodsRetrospective review of clinical records and diagnostic tests.ResultsA 78-year-old man with cerebral and lung melanoma metastases was treated with nivolumab, the newly developed monoclonal antibody which inhibits PD-1 deactivation of T-cells. He showed good radiological response.Three months after ceasing nivolumab, he presented to ED with acute confusion, aphasia, left-sided weakness and neglect as a stroke call. MRI demonstrated no evidence of stroke or acute encephalitis. EEG showed diffuse slowing. Lumbar puncture was not performed as he was therapeutically anticoagulated and had begun to improve on empirical antibiotics and acyclovir. One week later, he suddenly deteriorated with fevers and reduced level of consciousness. Acyclovir was restarted. Repeat EEG revealed periodic epileptic discharges over the right hemisphere and MRI demonstrated hyperintense signal and diffusion restriction of the right mesial temporal lobe suggestive of encephalitis. Subsequent lumbar puncture was negative for HSV, VZV, enterovirus, and autoimmune encephalitis antibodies.The patient’s oncology team had been in support of a course of methylprednisone on suspicion of autoimmune encephalitis, but by the time the lumbar puncture results returned he was again improving. A diagnosis of suspected nivolumab-induced encephalitis was made based on exclusion of other possible diagnoses.ConclusionsThe rising use of immune checkpoint inhibitors heralds an array of new and unexpected neurological complications including autoimmune encephalitis. A nationwide registry of possible cases may be helpful in improving our currently limited understanding of these emerging complications.

Prevalence of herpes simplex virus-1 in hospitalized adult patients with clinical diagnosis of meningoencephalitis using real-time polymerase chain reaction: A single-center, cross-sectional study.

Background:Early diagnosis of herpes simplex virus-1 (HSV-1) meningoencephalitis is very important because antiviral therapy significantly decreases mortality and morbidity. Polymerase chain reaction (PCR) is a reliable method with high sensitivity and specificity in detection of HSV-1. The aim of this study is to determine the prevalence of HSV-1 in patients with diagnosis of meningoencephalitis using real-time PCR.Materials and Methods:The cerebrospinal fluid samples were collected from 126 patients with clinical diagnosis of HSV-1 meningoencephalitis in Alzahra Referral Hospital in Isfahan, Iran. After deoxyribonucleic acid (DNA) extraction, real-time PCR was performed by fluorescence resonance energy transfer assay and participants underwent brain magnetic resonance imaging, as well.Results:Among 126 patients, 68.3% were male and 31.7% were female. The mean age of the participants was 41.96 ± 22.36 years. Most of the participants were in the age group of 20–29 years. Three patients (2.4%) had positive and 123 patients (97.6%) had negative HSV-1 DNA test. Among three positive cases, two were in the age group of 20–29 years and one in the age group of ≥80 years. No HSV-2 DNA was detected.Conclusion:According to the estimated prevalence of HSV-1 meningoencephalitis in the current study, it seems that the prevalence of HSV-1 meningoencephalitis is not too high in our community; therefore, initial empiric acyclovir therapy is frequently overused.

343. Compliance to Standard of Care in the Diagnosis and Management of Suspected Encephalitis

BackgroundEncephalitis is associated with death or neurological disability in 50% with the majority of the patients having an unknown etiology. The IDSA guidelines on the management of encephalitis were published in August 2008 but compliance with their recommendations is unknown.MethodsA retrospective study was conducted at 17 hospitals in the Great Houston area from August 2008 through July 2015. All cases met the definition for possible or probable encephalitis as per the international encephalitis consortium recommendations. Data extraction from the medical record was done utilizing a standardized form. Extracted data included information on demographics, clinical presentation, diagnostic testing, and treatment.ResultsA total of 264 adults and children with encephalitis were enrolled. Compliance with IDSA guidelines was excellent for obtaining an MRI of the brain (92%), an electroencephalogram (92%) and obtaining a cerebrospinal fluid (CSF) bacterial culture (86.7%). Empirical antibiotic and acyclovir therapy was started in about 65% of patient with a CSF HSV PCR being done in 78.8%. A CSF VZV PCR was only done in 31.4% while an arboviral serology was done in 57.1% of patients. Compliance was lowest in ordering a CSF N-methyl-d-aspartate receptor antibody (NMDA) and voltage-gated potassium channel (VGKC) antibodies (19.3% and 5.6%, respectively). The tests with the highest yield were a CSF NMDA receptor antibody (39.2%) and a CSF VZV PCR (13.2%).ConclusionDiagnostic evaluation of patients with encephalitis and compliance with IDSA guidelines is suboptimal.Disclosures All authors: No reported disclosures.

Kawasaki Disease in the neonate: case report and literature review

BackgroundKawasaki Disease (KD), the leading cause of acquired heart disease in children in the developed world, is extremely rare in neonates. We present a case of incomplete KD in a neonate and a review of the literature on neonatal KD.Case presentationA previously healthy full term 15 day old Caucasian male with an unremarkable antenatal and perinatal history, presented on Day 2 of illness with fever, rash, irritability, and poor feeding. Examination revealed fever (39.6C), tachycardia, tachypnea, extreme irritability, and a generalized maculopapular rash, but was otherwise normal. His complete blood count, CRP and ESR were normal. Empiric intravenous antibiotics and acyclovir resulted in no improvement. On day 4, he had ongoing fever and developed recurrent apnea, required supplemental oxygen, and was transferred to the pediatric intensive care unit. On day 6, he developed bilateral non-purulent conjunctivitis, palmar erythema, bilateral non-pitting edema and erythema of his feet, and arthritis. His full septic work-up and viral studies were negative. On Day 7 he was treated with intravenous immunoglobulin, and over the next 48 h his symptoms including extremity edema resolved, he no longer required supplemental oxygen, and fever did not recur. On day 9 of illness he had marked thrombocytosis. Subsequently, he developed distal extremity desquamation. Repeated echocardiograms excluded the presence of coronary artery aneurysms (CAA).ConclusionsWe believe this to be a rare case of incomplete KD in a neonate, in which timely IVIG administration led to resolution of the acute illness and may have prevented CAA. A comprehensive English-language medical literature review of KD presenting in the neonatal period revealed only fifteen case reports. Cases often presented with incomplete KD, and a number had atypical laboratory features including a normal CRP in the acute phase, similar to what was seen in our patient. This case and our literature review should increase awareness that KD can rarely occur in neonates, often presenting atypically. Recognizing KD in a neonate enables appropriate treatment that can result in resolution of symptoms and may decrease the risk of cardiac complications.

Neonatal HSV Disease: Balancing the Low Incidence With the Need to Treat Promptly.

* Abbreviations: ED — : emergency department HSV — : herpes simplex virus LP — : lumbar puncture PCR — : polymerase chain reaction In this issue of Pediatrics , Cruz et al1 address the following clinical question: what is the probability that an infant <60 days of age presenting to the emergency department (ED) who receives a lumbar puncture (LP) for concern of meningitis has a herpes simplex virus (HSV) infection? To answer this question, Cruz et al1 conducted a retrospective observational study and report on the incidence of HSV in infants <60 days old who had cerebrospinal fluid bacterial culture testing performed at 1 of 23 North American, tertiary-care, pediatric EDs over a 9-year period. There were 112 infants who had HSV identified, which amounts to 0.42%, or 42 of 10 000 (95% confidence interval, 35–51 of 10 000) infants evaluated. This estimate serves as the pretest probability of HSV infection in infants presenting to the ED who receive an LP for meningitis. On average, EDs saw ∼1 infant with HSV infection per year. Of neonatal HSV cases, 89.3% occurred in the first 6 weeks, with a median age of presentation of 14 days. Cruz et al1 also bring attention to an important issue on the state of affairs of hospital management of HSV in young infants: there is substantial variation in HSV testing and acyclovir administration across EDs. HSV testing ranged from 14% to 72%, and empirical acyclovir administration ranged from 4% to 53% across EDs. … Address correspondence to Sanjay Mahant, MD, Department of Paediatrics, Hospital for Sick Children, 555 University Ave, Toronto, ON, Canada M5G1X8. E-mail: sanjay.mahant{at}sickkids.ca

During the Emergency Department Evaluation of a Well-Appearing Neonate with Fever, Should Empiric Acyclovir Be Initiated?

BackgroundHerpes simplex virus (HSV) infection represents significant morbidity and mortality in the neonatal period. Although clear guidelines exist on the evaluation and management of the otherwise well-appearing febrile neonate pertaining to occult serious bacterial infections, there is no standardized approach regarding when to initiate testing and treatment for HSV infection. It is vital we establish a unified guideline based on available clinical research to aid in our decision to evaluate and initiate therapy for this disease. MethodsA PubMed search was performed using the keywords “neonate AND fever AND HSV” and “neonate AND fever AND acyclovir.” The time period for the search was May 1982 to May 2016. Identified articles underwent further selection based on relevance to the clinical question. Selected articles then underwent detailed review and structured analysis. ResultsOur search identified 93 articles, of which 18 were found to be relevant to our clinical question. Recommendations were then made based on thorough review and analysis of the selected articles. ConclusionsNeonatal HSV infection carries significant morbidity and mortality if left untreated. High-quality clinical evidence on when to evaluate and treat for possible HSV infection is lacking. Based on available research, HSV infection in the febrile neonate should be strongly considered if age is < 21 days, or if presenting with concerning clinical features. If testing is performed, empiric treatment with high-dose acyclovir should be initiated. Additional research is needed to further clarify which cases mandate evaluation and treatment for HSV, and to better define treatment protocols.

Implementation of In-house PCR Testing for Herpes Simplex Virus Encephalitis: Impact on Patient Acyclovir Exposure

BackgroundHSV encephalitis is a life-threatening disease process that requires prompt treatment. Diagnosis is often dependent upon nucleic acid studies of CNS samples. We introduced the Film Array Meningitis/Encephalitis (ME) Panel, a qualitative multiplexed nucleic acid-based diagnostic test for a variety of CNS pathogens, including HSV, in June 2016. It replaced an equivalent reference laboratory nucleic acid amplification test. The intent was to provide a more timely result and decrease unnecessary drug exposure to the patient.MethodsWe conducted a retrospective chart review of adult patients (>18 yo) admitted between June-September 2015 and June-September 2016 who underwent CSF testing for HSV and received empiric acyclovir. The aim was to determine whether the newly available test resulted in fewer doses of acyclovir in those who tested negative for a herpes virus as compared with those tested with the previously available assay. We excluded those found to be positive for HSV-1, HSV-2, or VZV in the CSF. We defined a dose as any administration of acyclovir or valacyclovir to the patient.ResultsResults of the diagnostic assay returned significantly faster after institution of the ME panel (4.9 days (118 hours) vs .09 days (2.25 hours)). Due to the non-normal distribution of acyclovir dosing, comparisons were made with the Wilcoxson Rank-sum. The institution of the ME panel for all CSF studies significantly impacted our use of acyclovir, as patients with negative tests for HSV PCR in the CSF received fewer doses of acyclovir after implementation of the ME panel (median (25th–75th percentiles) 6 (2–13.5) vs 3 (1–6), P = .018).ConclusionImplementation of a rapid diagnostic PCR based test for HSV 1 and HSV 2 in 2016 significantly reduced the number of empiric acyclovir doses administered during the summer of 2016 compared with the summer of 2015 in patients testing negative for the condition.Disclosures All authors: No reported disclosures.

CSF HSV PCR Testing in Adults and Children with Meningitis and Encephalitis

BackgroundHerpes simplex virus (HSV) is a common treatable cause of meningitis and encephalitis. Delayed antiviral therapy is associated with worse clinical outcomes in HSV encephalitis.ObjectivesTo determine the utilization of a cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) and identify predictors for a positive HSV PCR result.MethodsA retrospective review of 751 adults and children with meningitis and encephalitis at 9 hospitals in Houston TX from January 1 2005 to December 31 2010.ResultsOf 751 patients, 331 (44%) underwent CSF HSV PCR testing. Adults were more commonly tested than children (84% vs. 69%, P <0.0001). Additionally, patients with more comorbidities and clinical findings of encephalitis (e.g., altered mental status, focal neurological findings, seizures) were more commonly tested for HSV (P <0.001). Patients tested for HSV were also more likely to be evaluated for West Nile Virus, receive empiric acyclovir and have worse outcomes (P < 0.001). In total, 48 of 331 (14.5%) patients tested had a positive CSF HSV PCR. Predictors for a positive CSF HSV PCR on logistic regression analysis were stiff neck (odds ratio [OR], 2.181 [1.090–4.366]; P = 0.028, lymphocytic pleocytosis >50% lymphocytes (OR, 6.187 [1.412–27.11] P = 0.016, and CSF protein > 100mg/dl (OR, 3.279 [1.105–9.731] P = 0.032.ConclusionCSF HSV PCR is underutilized in community acquired meningitis and encephalitis and is done more frequently in adults and in those with an encephalitis presentation.Disclosures R. Hasbun, Biomeriaux: Consultant, Consulting fee Biofire: Speaker’s Bureau, Speaker honorarium Merck: Speaker’s Bureau, Speaker honorarium Pfizer: Speaker’s Bureau, Speaker honorarium Medicine’s Co: Speaker’s Bureau, Speaker honorarium

P180 Unusual causes of genital ulceration presenting to genitourinary medicine clinic – a case series

IntroductionGenital ulceration presents frequently at GUM clinics, with herpes simplex (HSV) infection a common aetiology. A diagnosis of HSV is distressing with possible implications for relationships and future pregnancies. It is therefore important to consider other causes if atypical presentation or negative HSV PCR from area of active ulceration.MethodCase review of uncommon aetiologies of ulceration.ResultsCase 1: 25 year old. Prodromal sore throat and flu-like symptoms. Examination revealed deep ulcers on vulva and oral mucosa without eye or skin involvement. CRP 120, ESR 80, ASOT titre 400, negative autoimmune screen, monospot negative. Developed anterior uveitis and erythema nodosum 24 hours later. Diagnosed with Behcet’s disease requiring prednisolone and mycophenolate mofitil.Case 2: 28 year old. Prodromal sore throat and headache. Sexual history atypical for HSV. Known Graves’ disease, on propylthiouracil. On examination, patient looked unwell. Shallow vulval ulceration noted. Neutrophils 0.1, ESR 31. Diagnosed with apthous ulceration secondary to neutropenia and admitted for neutropenic-sepsis treatment. Required thyroidectomy with pathology revealing papillary carcinoma.Case 3: 13 year old referred by SARC. No history of sexual contact or features of child sexual exploitation. Prodromal flu-like illness. Of note, mother Influenza A positive.No response to empirical acyclovir. HSV PCR negative. Nasopharyngeal swab confirmed Influenza A. Case subsequently closed with SARC and Social Services.DiscussionThis case series highlights less common but important causes of genital ulceration. Full systemic history and clinical assessment remains essential in those where alternate diagnoses to HSV are being considered.

Criteria to Screen Molecular Tests for the Diagnosis of Herpes Simplex Virus in the Central Nervous System have no Propensity to Harm

Objectives: Investigators have ruled out herpes simplex virus (HSV) infection without the detection of herpes simplex deoxyribonucleic acid in cerebrospinal fluid (CSF) (i.e., HSV polymerase chain reaction [PCR]) by laboratory (normal CSF white blood cell count and protein) and clinical criteria (age ≥2 years, no history of human immunodeficiency virus or solid-organ transplant). Compared to HSV PCR of all samples, the algorithm saves money in test costs and may decrease exposure to acyclovir by illustrating the low probability that the patient has HSV. Concern exists that algorithm use may cause harm through alteration of empiric acyclovir treatment in patients with true HSV central nervous system infection. Methods: All Department of Veterans Affair's patients with a positive HSV PCR of the CSF between 2000 and 2013 were identified and their medical records reviewed to determine the extent and possible impact of omitted HSV PCR testing by the algorithm. Results: Of 6357 total results, 101 patients had a positive CSF HSV PCR in the study period. Among the positive CSF HSV PCR results, the algorithm excluded 7 (7%) from PCR testing. Record review indicated these seven patients not tested by the algorithm with a positive CSF HSV PCR were considered by their attending physician not to have active HSV. Conclusion: The algorithm to screen HSV tests had no propensity to harm.

Persistent Gaps in Appropriate Use of Empiric Acyclovir in Neonates.

The use of empiric acyclovir for suspected neonatal herpes simplex virus (HSV) infection has been debated for years. To identify the gap in the decision to initiate empiric acyclovir, we performed a retrospective chart review and administered a survey to pediatricians to assess current practices regarding evaluation for possible HSV infection. Seventy infants received empiric acyclovir over a 1-year period; of these, 3 infants (4.3%) had positive HSV testing. Fourteen infants were identified as "high-risk" for HSV infection; of these, 13 infants had incomplete testing. Survey results revealed uncertainty in the decision to initiate acyclovir and in the composition of complete diagnostic testing. This study confirmed the clinical uncertainty in the decision to initiate empiric acyclovir. Using this chart review and survey as a baseline, future efforts will focus on a quality improvement project to reduce empiric acyclovir use in low-risk infants and to ensure complete diagnostic evaluation in high-risk infants.

Perinatally-acquired herpes simplex virus infection and empiric acyclovir therapy

Perinatally-acquired herpes simplex virus infection and empiric acyclovir therapy

Use of Empiric Acyclovir for Infants Compared With Published Recommendations

Use of Empiric Acyclovir for Infants Compared With Published Recommendations