26 Use of acyclovir in infants aged less than six weeks at a Canadian tertiary care centre: too much or too little?
Bibliographic record
Abstract
Herpes simplex virus (HSV) infection carries major morbidity and mortality in the neonatal period. HSV infection in neonates may present with multiple clinical presentations, including localized skin, eye, and mouth (SEM), central nervous system (CNS) or disseminated disease. Current practices are not standardized regarding when to initiate treatment for suspected HSV infection as opposed to guidelines that exist on the management of the febrile infants. Previous research has shown that Canadian pediatric emergency physicians rarely empirically administer acyclovir to febrile neonates without risk factors. In contrast, some American pediatric hospitals strongly recommend considering acyclovir in all febrile neonates less than 21 days of age. The Canadian Paediatric Society (CPS) supports that infants up to 42 days of age should be fully evaluated for HSV when clinical features are consistent with such infection. The primary aim of this study was to describe current practices in the use of acyclovir in infants less than six weeks of age at a tertiary Canadian pediatric hospital. Secondary aims were to assess the prevalence of HSV infection in this cohort as well as the diagnostic work-up performed and the therapeutic management of those patients. We performed a retrospective observational cohort study of infants aged less than six weeks of age who were treated with acyclovir based on fever and/or clinical symptoms suggestive of possible HSV infection (such as seizure, shock, cutaneous vesicles or neonatal conjunctivitis). All infants were evaluated by a pediatrician in a single pediatric tertiary care centre between January 1st 2015 and December 31st 2017. Infants were admitted under general pediatrics or in the neonatal or pediatric intensive care unit. Chart review was performed and multiples variables were included in the analysis. Patients with insufficient chart data, already hospitalized at the time of acyclovir initiation or transferred to another hospital prior to discharge were excluded. 109 patients were included. Most patients were born by vaginal delivery (84%) and without instrument assistance (85%). Most pregnant women (97%) had no history of HSV. At the time of presentation in the emergency department, the mean age was 20 ± 11 days. Most patients presented with fever (64%) while only three presented with cutaneous vesicles. 62 patients (57%) received intravenous fluid bolus therapy. All patients were admitted, with a mean hospital stay of 5.2 ± 4.5 days. Patients were treated with acyclovir for 2.1 ± 2.2 days. Most patients had a baseline CBC (n=108), C-reactive protein (n=98), creatinine (n=96) and ALT (n=67) levels. With regards to investigations for HSV, 103 patients (94%) had a lumbar puncture (LP) with cerebrospinal fluid (CSF) HSV PCR (n=100) or viral culture (n=66). Only 12 patients underwent skin or mucous membrane swab and 14 blood HSV PCR. A minority of patients with an elevated ALT level on admission had a blood HSV PCR. Among all, only two patients had a confirmed HSV infection, one with isolated ocular involvement (keratitis) and the other with SEM and disseminated infection. Both had family members with HSV, the latter with confirmed maternal postnatal primary infection. Both patients were afebrile at presentation. Only two patients were found with HSV infection. Both were afebrile and had family members with active lesions. Despite neonatal HSV presenting with three clinical forms, most clinicians relied on CSF alone to rule out HSV infection, even with a normal LP. A limited number of patients underwent blood PCR or swabs of mucous membranes, even in cases of elevated serum transaminases. Fever alone as a screening symptom for HSV infection appears to be insufficient. Further research is needed to define optimal management.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".