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Adenovirus and "Culture-Negative Sepsis" in a Preterm Neonate.

ABSTRACT: Background?Respiratory viral infections remain an underrecognized cause of morbidity and mortality among preterm infants in the neonatal intensive care unit (NICU). Case Report?An eight day old, 650 gram birth weight, 23 weeks' gestational age female developed "culture-negative" sepsis manifested by respiratory deterioration, hypoxia, leukocytosis, and thrombocytopenia. She was diagnosed with pneumonia and hepatitis due to adenovirus HAdV-D (H29F9) by polymerase chain reaction (PCR) testing, but died at the age of 18 days despite treatment with cidofovir and immune globulin intravenous. Conclusion?As the ability to diagnosis respiratory viral infections in the NICU has improved greatly with the use of PCR testing, the impact and contribution of these viruses to neonatal disease is now being recognized and the notion of "culture-negative" sepsis needs reassessment. The diagnosis of these infections in high risk infants is important not only for etiologic and epidemiologic reasons but ultimately for informing antimicrobial stewardship efforts.

SUBMITTER: Moallem M

PROVIDER: S-EPMC5138071 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Adenovirus and "Culture-Negative Sepsis" in a Preterm Neonate.

Moallem Mohannad M Song Eunkyung E Jaggi Preeti P Conces Miriam R MR Kajon Adriana E AE Sánchez Pablo J PJ

AJP reports 20161001 4

<b>Background</b> Respiratory viral infections remain an underrecognized cause of morbidity and mortality among preterm infants in the neonatal intensive care unit (NICU). <b>Case Report</b> An eight day old, 650 gram birth weight, 23 weeks' gestational age female developed "culture-negative" sepsis manifested by respiratory deterioration, hypoxia, leukocytosis, and thrombocytopenia. She was diagnosed with pneumonia and hepatitis due to adenovirus HAdV-D (H29F9) by polymerase chain reaction (PCR ...[more]

PMID: 27924246

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Project description:BACKGROUND:The primary objective of this study was to compare the characteristics of culture-positive and culture-negative status in septic patients. We also determined whether culture status is associated with mortality and whether unique variables are associated with mortality in culture-positive and culture-negative patients separately. METHODS:Utilizing patient records from intensive care units, emergency department, and general care wards in a large academic medical center, we identified adult patients with suspected infection and ≥2 systemic inflammatory response syndrome criteria between January 1, 2007, and May 31, 2014. We compared the characteristics between culture-positive and culture-negative patients and used binary logistic regression to identify variables independently associated with culture status and mortality. We also did sensitivity analyses using patients with Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria for sepsis. RESULTS:The study population included 9288 culture-negative patients (89%) and 1105 culture-positive patients (11%). Culture-negative patients received more antibiotics during the 48 hours preceding diagnosis but otherwise demonstrated similar characteristics as culture-positive patients. After adjusting for illness severity, a positive culture was not independently associated with mortality (odds ratio = 1.01 [95% CI, 0.81-1.26]; P = .945). The models predicting mortality separately in culture-negative and culture-positive patients demonstrated very good and excellent discrimination (C-statistic ± SD, 0.87 ± 0.01 and 0.92 ± 0.01), respectively. In the sensitivity analyses using patients with sepsis by Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria, after adjustments for illness severity, positive cultures were still not associated with mortality (odds ratio = 1.13 [95% CI, 0.86-1.43]; P = .303; and odds ratio = 1.05 [95% CI, 0.83-1.33]; P = .665), respectively. In all models, physiological derangements were associated with mortality. CONCLUSIONS:While culture status is important for tailoring antibiotics, culture-negative and culture-positive patients with sepsis demonstrate similar characteristics and, after adjusting for severity of illness, similar mortality. The most important factor associated with negative cultures is receipt of antibiotics during the preceding 48 hours. The risk of death in patients suspected of having an infection is most associated with severity of illness. This is aligned with the Sepsis-3 definition using Sequential Organ Failure Assessment score to better identify those suspected of infection at highest risk of a poor outcome.

Project description:Background: Preterm birth can lead to brain injury and currently there are no targeted therapies to promote postnatal brain development and protect these vulnerable neonates. We have previously shown that the neurosteroid-analogue ganaxolone promotes white matter development and improves behavioural outcomes in male juvenile guinea pigs born preterm. Adverse side effects in this previous study necessitated this current follow-up dosing study, where a focus was placed upon physical wellbeing during the treatment administration and markers of neurodevelopment at the completion of the treatment period. Methods: Time-mated guinea pigs delivered preterm (d62) by induction of labour or spontaneously at term (d69). Preterm pups were randomized to receive no treatment (Prem-CON) or ganaxolone at one of three doses [0.5 mg/kg ganaxolone (low dose; LOW-GNX), 1.0 mg/kg ganaxolone (mid dose; MID-GNX), or 2.5 mg/kg ganaxolone (high dose; HIGH-GNX) in vehicle (45% β-cyclodextrin)] daily until term equivalence age. Physical parameters including weight gain, ponderal index, supplemental feeding, and wellbeing (a score based on respiration, activity, and posture) were recorded throughout the preterm period. At term equivalence, brain tissue was collected, and analysis of hippocampal neurodevelopment was undertaken by immunohistochemistry and RT-PCR. Results: Low and mid dose ganaxolone had some impacts on early weight gain, supplemental feeding, and wellbeing, whereas high dose ganaxolone significantly affected all physical parameters for multiple days during the postnatal period when compared to the preterm control neonates. Deficits in the preterm hippocampus were identified using neurodevelopmental markers including mRNA expression of oligodendrocyte lineage cells (CSPG4, MBP), neuronal growth (INA, VEGFA), and the GABAergic/glutamatergic system (SLC32A1, SLC1A2, GRIN1, GRIN2C, DLG4). These deficits were not affected by ganaxolone at the doses used at the equivalent of normal term. Conclusion: This is the first study to investigate the effects of a range of doses of ganaxolone to improve preterm brain development. We found that of the three doses, only the highest dose of ganaxolone (2.5 mg/kg) impaired key indicators of physical health and wellbeing over extended periods of time. Whilst it may be too early to see improvements in markers of neurodevelopment, further long-term study utilising the lower doses are warranted to assess functional outcomes at ages when preterm birth associated behavioural disorders are observed.

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Adenovirus and "Culture-Negative Sepsis" in a Preterm Neonate.

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Adenovirus and "Culture-Negative Sepsis" in a Preterm Neonate.

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