Urinary tract infections in very premature neonates: the definition dilemma.

BACKGROUND AND OBJECTIVES: Data on urinary tract infections (UTIs) in very preterm neonates (VPTNs) are scarce. We aimed to (i) describe the characteristics of UTIs in VPTNs and (ii) compare the diagnostic practices of neonatal clinicians to established pediatric guidelines. METHODS: All VPTNs (<29 weeks GA) with a suspected UTI at the CHU Sainte-Justine neonatal intensive care unit from January 1, 2014, and December 31, 2019, were included and divided into two definition categories: Possible UTI, and Definite UTI. RESULTS: Most episodes were Possible UTI (87%). Symptoms of UTIs and pathogens varied based on the definition category. A positive urinalysis was obtained in 25%. Possible UTI episodes grew 2 organisms in 62% of cases and <50,000 CFU/mL in 62% of cases. CONCLUSION: Characteristics of UTIs in VPTNs vary based on the definition category and case definitions used by clinicians differ from that of established pediatric guidelines.

Serratia marcescens Colonization in a Neonatal Intensive Care Unit Has Multiple Sources, with Sink Drains as a Major Reservoir.

Compelling evidence suggests a contribution of the sink environment to the transmission of opportunistic pathogens from the hospital environment to patients in neonatal intensive care units (NICU). In this study, the distribution of the opportunistic pathogen Serratia marcescens in the sink environment and newborns in a NICU was investigated. More than 500 sink drain and faucet samples were collected over the course of five sampling campaigns undertaken over 3 years. Distribution and diversity of S. marcescens were examined with a modified MacConkey medium and a high-throughput short-sequence typing (HiSST) method. Sink drains were an important reservoir of S. marcescens, with an average of 44% positive samples, whereas no faucet sample was positive. The genotypic diversity of S. marcescens was moderate, with an average of two genotypes per drain, while the spatial distribution of S. marcescens was heterogeneous. The genotypic profiles of 52 clinical isolates were highly heterogeneous, with 27 unique genotypes, of which 71% of isolates were found in more than one patient. S. marcescens acquisition during the first outbreaks was mainly caused by horizontal transmissions. HiSST analyses revealed 10 potential cases of patient-to-patient transmission of S. marcescens, five cases of patient-to-sink transmission, and one bidirectional transfer between sink and patient. Environmental and clinical isolates were found in sink drains up to 1 year after the first detection, supporting persisting drain colonization. This extensive survey suggests multiple reservoirs of S. marcescens within the NICU, including patients and sink drains, but other external sources should also be considered. IMPORTANCE The bacterium Serratia marcescens is an important opportunistic human pathogen that thrives in many environments, can become multidrug resistant, and is often involved in nosocomial outbreaks in neonatal intensive care units (NICU). We evaluated the role of sinks during five suspected S. marcescens outbreaks in a NICU. An innovative approach combining molecular and culture methods was used to maximize the detection and typing of S. marcescens in the sink environment. Our results indicate multiple reservoirs of S. marcescens within the NICU, including patients, sink drains, and external sources. These results highlight the importance of sinks as a major reservoir of S. marcescens and potential sources of future outbreaks.

Neonatal and Neurodevelopmental Outcomes Following Linezolid for Coagulase-negative Staphylococcal Infection: Real World Evidence.

BACKGROUND: Coagulase-negative staphylococci (CoNS) frequently causes late-onset sepsis in preterm infants. Vancomycin is the first-line therapy, but the emergence of reduced vancomycin-susceptibility strains has resulted in linezolid use, of which long-term safety in preterm infants is unknown. OBJECTIVE: Evaluate the association between linezolid exposure and neurodevelopmental impairment (NDI) or death at 18-21 months of corrected age, in preterm infants with CoNS sepsis. METHODS: Multicentric retrospective cohort study comparing long-term outcomes of preterm infants exposed to linezolid versus other antistaphylococcal antimicrobials. We included infants ≤28 weeks' gestational age (GA), with CoNS sepsis, admitted between January 2011 and June 2015 in 3 level-3 Canadian NICUs. Primary outcome was a composite of death or significant NDI (sNDI) at 18-21 months of corrected age. Secondary outcomes included NDI and individual components of the primary outcome. We assessed the relationship between linezolid exposure and outcomes using a multivariable logistic regression. RESULTS: Of 274 infants included, 67 (24.4%) were exposed to linezolid. Median GA was 26 weeks and clinical characteristics were similar between groups. There was no difference in composite outcome of death or sNDI among the infants of both groups, but significantly more death by 18-21 months in the linezolid group (29.9% vs. 17.6%; P = 0.01). CONCLUSIONS: Linezolid exposure was not associated with composite outcome of death or sNDI at 18-21 months. The association between linezolid and death may be due to indication bias. Further studies are warranted.

Rotavirus vaccination in the neonatal intensive care units: where are we? A rapid review of recent evidence.

PURPOSE OF REVIEW: Rotavirus is a leading cause of viral acute gastroenteritis in infants. Neonates hospitalized in neonatal intensive care units (NICUs) are at risk of rotavirus infections with severe outcomes. The administration of rotavirus vaccines is only recommended, in the United States and Canada, upon discharge from the NICU despite rotavirus vaccines being proven well tolerated and effective in these populations, because of risks of live-attenuated vaccine administration in immunocompromised patients and theoretical risks of rotavirus vaccine strains shedding and transmission.We aimed to summarize recent evidence regarding rotavirus vaccine administration in the NICU setting and safety of rotavirus vaccines in preterm infants. METHODS: We conducted a rapid review of the literature from the past 10 years, searching Medline and Embase, including all study types except reviews, reporting on rotavirus vaccines 1 and 5; NICU setting; shedding or transmission; safety in preterm. One reviewer performed data extraction and quality assessment. RECENT FINDINGS: Thirty-one articles were analyzed. Vaccine-derived virus shedding following rotavirus vaccines existed for nearly all infants, mostly during the first week after dose 1, but with rare transmission only described in the household setting. No case of transmission in the NICU was reported. Adverse events were mild to moderate, occurring in 10-60% of vaccinated infants. Extreme premature infants or those with underlying gastrointestinal failure requiring surgery presented with more severe adverse events. SUMMARY: Recommendations regarding rotavirus vaccine administration in the NICU should be reassessed in light of the relative safety and absence of transmission of rotavirus vaccine strains in the NICU.

Development of a GAL4-VP16/UAS trans-activation system for tissue specific expression in Medicago truncatula.

Promoters with tissue-specific activity are very useful to address cell-autonomous and non cell autonomous functions of candidate genes. Although this strategy is widely used in Arabidopsis thaliana, its use to study tissue-specific regulation of root symbiotic interactions in legumes has only started recently. Moreover, using tissue specific promoter activity to drive a GAL4-VP16 chimeric transcription factor that can bind short upstream activation sequences (UAS) is an efficient way to target and enhance the expression of any gene of interest. Here, we developed a collection of promoters with different root cell layers specific activities in Medicago truncatula and tested their abilities to drive the expression of a chimeric GAL4-VP16 transcription factor in a trans-activation UAS: ß-Glucuronidase (GUS) reporter gene system. By developing a binary vector devoted to modular Golden Gate cloning together with a collection of adapted tissue specific promoters and coding sequences we could test the activity of four of these promoters in trans-activation GAL4/UAS systems and compare them to "classical" promoter GUS fusions. Roots showing high levels of tissue specific expression of the GUS activity could be obtained with this trans-activation system. We therefore provide the legume community with new tools for efficient modular Golden Gate cloning, tissue specific expression and a trans-activation system. This study provides the ground work for future development of stable transgenic lines in Medicago truncatula.

Fetal and Postnatal Head Circumference Growth: Synergetic Factors for Neurodevelopmental Outcome at 2 Years of Age for Preterm Infants.

Preterm infants present higher risk of non-optimal neurodevelopmental outcome. Fetal and postnatal growth, in particular head circumference (HC), is associated with neurodevelopmental outcome. OBJECTIVES: We aimed to calculate the relationship between HC at birth, HC delta Z-score (between birth and hospital discharge), and non-optimal neurodevelopmental outcome at 2 years of corrected age in preterm infants. METHODS: Surviving infants born ≤34 weeks of gestation were included in the analysis. The relationship between the risk of being non-optimal at 2 years and both HC at birth and HC growth was assessed. The 2 Z-scores were considered first independently and then simultaneously to investigate their effect on the risk of non-optimality using a generalized additive model. RESULTS: A total of 4,046 infants with both HC measures at birth and hospital discharge were included. Infants with small HC at birth (Z-score <-2 SD), or presenting suboptimal HC growth (dZ-score <-2 SD), are at higher risk of non-optimal neurodevelopmental outcome at 2 years (respectively OR 1.7 [95% CI 1.4-2] and OR 1.4 [95% CI 1.2-1.8]). Interestingly, patients cumulating small HC Z-score at birth (-2 SD) and presenting catch-down growth (HC dZ-score [-2 SD]) have a significantly increased risk for neurocognitive impairment (OR >2) while adjusting for gestational age, twin status, sex, and socioeconomic information. CONCLUSIONS: HC at birth and HC dZ-score between birth and hospital discharge are synergistically associated to neurodevelopmental outcome at 2 years of corrected age, in a population-based prospective cohort of preterm infants born ≤34 weeks of gestation.

Pharmacokinetics of linezolid treatment using intravenous and oral administrations in extremely premature infants.

INTRODUCTION: Vancomycin is the usual antibiotic treatment in coagulase-negative staphylococcus sepsis in premature infants but causes renal toxicity. As linezolid is effective in Gram-positive cocci infection, and devoid of renal side-effects, it has been used in Nantes neonatal intensive care units and linezolid plasma concentrations were monitored. AIM: The aims of this study are to report data on linezolid concentrations in premature infants, describe clinical and bacteriological evolution during treatment, and determine potential side effects. METHODS: A retrospective observational study of premature infants treated with linezolid in Nantes Hospital from January 2008 through November 2011 was conducted. Linezolid plasma concentrations, possible side effects due to linezolid, and clinical response to linezolid treatment were collected from folder review. RESULTS: Twenty-four linezolid plasma concentrations were monitored in 16 premature patients, at steady state for continuous intravenous administration or 7 ± 1.5 h after last oral administration. Except for one case, linezolid plasma concentrations were ≥minimal inhibition concentration (MIC) for linezolid for both parenteral and oral administrations. We observed three cases of thrombocytopenia, two of leukopenia, three of neutropenia, and one of severe hyperlactacidemia, resolving after discontinuation of treatment. Clinical signs of infection resolved in 13/16 cases. Bacteria were coagulase-negative Staphylococci in 12/16 cases and were eradicated in 9/12 evaluable cases. CONCLUSIONS: This study reports an adequate linezolid plasma concentration with regard to the linezolid MIC in extremely premature infants. However, considering adverse events reported, its use should be cautious and may concern only oral administration during the late phase of infection, to limit paradoxical catheter use to treat nosocomial infections. Moreover, safe and efficient anti-Staphylococcus therapies should be identified to treat this vulnerable population.