Improved Diagnostics in Bacterial Neonatal Meningitis Using a Next-Generation Sequencing Platform.

INTRODUCTION: Bacterial meningitis in infants is an infrequent but life-threatening condition. Empiric therapy should begin as soon as meningitis is thought likely. Consequently, the causative microorganisms may not always be detected using culturing techniques, as cerebrospinal fluid (CSF) cultures are influenced by antibiotics. Nucleic acid amplification tests, such as polymerase chain reaction (PCR) (multiplex panels), may overcome this limitation but require a priori knowledge of the likely pathogen present within the sample. With this in mind, we investigated to what extent a culture-free, broad-range 16S rRNA gene next-generation sequencing (NGS) platform (MYcrobiota) could add to the microbiological diagnosis of meningitis. METHODS: Retrospective cohort study at level III neonatal intensive care unit. Included were all infants with suspected meningitis admitted between 10 November 2017 and 31 December 2020. A comparison was made of the bacterial pathogen detection rate between MYcrobiota and conventional bacterial culture. RESULTS: In a 3-year period, 37 CSF samples (diagnostic and follow-up) from 35 infants with proven or possible meningitis were available for MYcrobiota testing. MYcrobiota detected the presence of bacterial pathogens in 11 samples (30%), in contrast with the conventional CSF culture, which detected bacteria in 2 of 36 samples (5.6%). CONCLUSION: Addition of 16S rRNA sequencing to conventional culturing greatly improved the identification of the aetiology of bacterial meningitis compared to culturing of CSF samples alone.

A longitudinal analysis of nosocomial bloodstream infections among preterm neonates.

Nosocomial bloodstream infections (NBSIs), commonly due to central-line associated bloodstream infections (CLABSI), contribute substantially to neonatal morbidity and mortality. We aimed to identify longitudinal changes in incidence of NBSI, microbiological-spectrum, and antibiotic exposure in a large cohort of preterm neonates admitted to the neonatal intensive care unit. We retrospectively assessed differences in annual rates of NBSI (per 1000 patient-days), CLABSI (per 1000 central-line days), and antibiotic consumption (per 1000 patient-days) among preterm neonates (< 32 weeks' gestation) hospitalized between January 2012 and December 2020. Multi-state Markov models were created to model states of progression of NBSI and infection risk given a central-line on days 0, 3, 7, and 10 of admission. Of 1547 preterm infants, 292 (19%) neonates acquired 310 NBSI episodes, 99 (32%) of which were attributed to a central-line. Over the years, a significant reduction in central-line use was observed (p < 0.001), although median dwell-time increased (p = 0.002). CLABSI incidence varied from 8.83 to 25.3 per 1000 central-line days, with no significant difference between years (p = 0.27). Coagulase-negative staphylococci accounted for 66% of infections. A significant decrease was found in antibiotic consumption (p < 0.001). Probability of NBSI decreased from 16% on day 3 to 6% on day 10. NBSI remains a common problem in preterm neonates. Overall antibiotic consumption decreased over time despite the absence of a significant reduction in infection rates. Further research aimed at reducing NBSI, in particular CLABSI, is warranted, particularly with regard to limiting central-line dwell-time and fine-tuning insertion and maintenance practices.

Comparison of neonatal morbidity and mortality between single-room and open-bay care: a retrospective cohort study.

OBJECTIVE: In response to the increasing focus on family-centred care, neonatal intensive care unit (NICU) environments have gradually shifted towards the single-room design. However, the assumed benefits of this emerging design remain a subject of debate. Our goal was to evaluate the impact of single-room versus open-bay care on the risk of neonatal morbidity and mortality in preterm neonates. DESIGN: Retrospective cohort study. SETTING: Level III NICU. PATIENTS: Neonates born <32 weeks' gestation between 15 May 2015 and 15 May 2019. MAIN OUTCOME MEASURES: Mortality and morbidities of a cohort of neonates admitted to a new, single-room unit (SRU) were compared with a historical cohort of neonates admitted to an open-bay unit (OBU). Group differences were evaluated and multivariable logistic regression analyses were performed. RESULTS: Three-hundred and fifty-six and 343 neonates were admitted to the SRU and OBU, respectively. No difference in neonatal morbidities and mortality were observed between cohorts (bronchopulmonary dysplasia: OR 1.08, 95% CI 0.73 to 1.58, p=0.44; retinopathy of the prematurity stage ≥2: OR 1.36, 95% CI 0.84 to 2.22, p=0.10; intraventricular haemorrhage: OR 0.89, 95% CI 0.59 to 1.34, p=0.86; mortality: OR 1.55, 95% CI 0.75 to 3.20, p=0.28). In adjusted regression models, single-room care was independently associated with a decreased risk of symptomatic patent ductus arteriosus (adjusted OR 0.54, 95% CI 0.31 to 0.95). No independent association between single-room care and any of the other investigated outcomes was observed. CONCLUSIONS: Implementation of single-rooms in our NICU did not lead to a significant reduction in neonatal morbidity and mortality outcomes.

Predicting Neonatal Early Onset Sepsis: A 14-Year Cohort Study.

BACKGROUND: In many infants, treatment is started for suspicion of early onset sepsis (EOS), of whom the majority do not have an infection. Early prediction of the absence of a culture-proven sepsis (CPS) would significantly reduce the time of antibiotic treatment and hospitalization. Our objective was to analyze 3 criteria in infants with CPS: positive blood culture (BC) at 24 hours after the onset of suspicion of EOS (OSEOS), C-reactive protein (CRP) ≥10 mg/L and clinical signs of infection, so we can consequently consider to stop antibiotic treatment in infants without these criteria. METHODS: We included all infants with suspicion of EOS from 2007 until 2020. The proportion was calculated of (1) infants with CPS with, at 24 hours, a positive BC and/or CRP ≥10 mg/L and/or clinical signs of infection and (2) infants without CPS with CRP <10 mg/L between 12 and 24 hours after OSEOS. RESULTS: The BC showed growth of a pathogenic microorganism in 50 of 4120 included infants (1.2%). Time to positivity was ≥24 hours in 8 (16%) infants, of whom 7 infants had a raised CRP and/or clinical symptoms of infection within 24 hours. In 1095 (74%) of infants without CPS in whom CRP was measured between 12 and 24 hours after OSEOS, CRP was <10 mg/L. CONCLUSION: A combination of BC, CRP, and clinical signs of infection can diagnose 98% (49/50) of infants with CPS 24 hours after OSEOS. Based on normal CRP and the absence of a positive BC, the decision to stop antibiotics could have been brought forward to 24 hours in 74% of infants.

The Effect of Single-Room Care Versus Open-Bay Care on the Incidence of Bacterial Nosocomial Infections in Pre-Term Neonates: A Retrospective Cohort Study.

INTRODUCTION: Nosocomial infections (NIs) are a major source of iatrogenic harm in neonatal intensive care units (NICUs). The influence of the infrastructure of NICUs on NIs is not well documented. This study aims to examine the effect of single-room units (SRU) versus open-bay units (OBU) on the incidence of NIs, including central-line-associated bloodstream infections (CLABSI), in preterm neonates. METHODS: All preterm neonates (< 32 weeks gestational age) admitted to our NICU were included. Two study periods were compared: one prior to (May 2015-May 2017) and one following (May 2017-May 2019) transition from OBU to SRU. Incidence density (number of infections per 1000 patient-days) and cumulative incidence (number of infections per 100 neonates) for NIs were calculated. CLABSIs were calculated per 1000 central-line days. U chart analysis was performed to determine special-cause variation in quarterly CLABSI and NI rates. Multivariate competing risk regression was performed to identify independent NI risk factors. RESULTS: Of the 712 included infants, 164 (23%) infants acquired ≥ 1 NIs. No differences were found in incidence density (13.68 vs. 12.62, p = 0.62) or cumulative incidence of NI (23.97 vs. 22.02, p = 0.59) between OBU and SRU. CLABSIs showed a similar non-significant reduction after the move (14.00 vs. 10.59, p = 0.51). U chart analysis did not identify unit transition as a potential source of special-cause variation for CLABSI and NI. Competing risks regression analysis revealed longer duration of invasive mechanical ventilation as a significant risk factor for NI (subhazards ratio: 1.03 per day on ventilation, p = 0.01). CONCLUSION: Single-rooms are not associated with a significant reduction in NIs in the NICU. This study therefore does not add evidence that could support the transition to SRUs if based only on a large multimodal infection control strategy. Recommendations to build SRUs would require a wider justification, also taking into account other SRU benefits.

The Effect of Single-Room Care Versus Open-Bay Care on the Incidence of Bacterial Nosocomial Infections in Pre-Term Neonates: A Retrospective Cohort Study.

INTRODUCTION: Nosocomial infections (NIs) are a major source of iatrogenic harm in neonatal intensive care units (NICUs). The influence of the infrastructure of NICUs on NIs is not well documented. This study aims to examine the effect of single-room units (SRU) versus open-bay units (OBU) on the incidence of NIs, including central-line-associated bloodstream infections (CLABSI), in preterm neonates. METHODS: All preterm neonates (< 32 weeks gestational age) admitted to our NICU were included. Two study periods were compared: one prior to (May 2015-May 2017) and one following (May 2017-May 2019) transition from OBU to SRU. Incidence density (number of infections per 1000 patient-days) and cumulative incidence (number of infections per 100 neonates) for NIs were calculated. CLABSIs were calculated per 1000 central-line days. U chart analysis was performed to determine special-cause variation in quarterly CLABSI and NI rates. Multivariate competing risk regression was performed to identify independent NI risk factors. RESULTS: Of the 712 included infants, 164 (23%) infants acquired ≥ 1 NIs. No differences were found in incidence density (13.68 vs. 12.62, p = 0.62) or cumulative incidence of NI (23.97 vs. 22.02, p = 0.59) between OBU and SRU. CLABSIs showed a similar non-significant reduction after the move (14.00 vs. 10.59, p = 0.51). U chart analysis did not identify unit transition as a potential source of special-cause variation for CLABSI and NI. Competing risks regression analysis revealed longer duration of invasive mechanical ventilation as a significant risk factor for NI (subhazards ratio: 1.03 per day on ventilation, p = 0.01). CONCLUSION: Single-rooms are not associated with a significant reduction in NIs in the NICU. This study therefore does not add evidence that could support the transition to SRUs if based only on a large multimodal infection control strategy. Recommendations to build SRUs would require a wider justification, also taking into account other SRU benefits. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40121-020-00380-9.

Two cases of Emergomyces pasteurianus infection in immunocompromised patients in the Netherlands.

We report two cases of Emergomyces pasteurianus infection in the Netherlands. Both patients were immunocompromised and had pulmonary symptoms. The first patient died due to a pulmonary infection with Es. pasteurianus, concomitant listeriosis, Pseudomonas aeruginosa sepsis and invasive pulmonary aspergillosis. The second patient had pulmonary and subcutaneous lesions, and recovered completely after treatment with posaconazole for 14 months. In both cases, diagnosis of Es. pasteurianus was made with internal transcribed spacer rRNA PCR and culture.

Higher Tinzaparin Dosing Is Needed to Achieve Target Anti-Xa Levels in Pediatric Cardiac Intensive Care Patients.

OBJECTIVES: This study was conducted to evaluate tinzaparin dosing and therapeutic drug monitoring. DESIGN: Retrospective study. SETTING: Single tertiary-level PICU. PATIENTS: Tinzaparin doses and anti-Xa levels from all children admitted to a PICU (from October 1, 2010, to December 31, 2013) were retrospectively analyzed. Thirty-nine children, median age of 13 months (interquartile range, 73 mo), with 46 episodes of newly started therapeutic tinzaparin were identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Local hospital policy is to determine the first anti-Xa level after 3-4 doses, 4 hours post dose, targeting 0.5-1.0 IU/mL for therapeutic dosing. First anti-Xa levels were determined after 3.8 (± 2.4; range, 1-14) doses and were below the target range in 37 of 46 episodes (76%) of tinzaparin use: mean, 0.30 (± 0.11) IU/mL. Tinzaparin was then increased by 23% (± 19) in 23 of 37 episodes (62%), and further anti-Xa levels were determined. In 14 episodes, further levels were not available because of cessation of tinzaparin therapy. Target anti-Xa levels, 0.69 (± 0.24) IU/mL, were eventually reached in the PICU in 22 patients after a mean of 8.8 (± 7.3) doses. In the entire cohort, the dose required to achieve target anti-Xa levels was significantly higher (+51 [± 62] U/kg; p = 0.003) than the recommended starting dose. CONCLUSIONS: Target anti-Xa levels were reached with tinzaparin dosing in PICU patients after more than 8 doses, warranting further dose-effect research. Especially in the younger age group, substantially higher dose requirements than proposed in the internationally used guidelines are required. With the results of our study, we suggest a different therapeutic drug monitoring approach than that currently used.