A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study

Background: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. Methods: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. Findings: On July 1, 2019, 26 of infants (580/2,265; range, 0�100; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received �1 antimicrobial agent (92, antibacterial; 19, antifungal; 4, antiviral). The most common reasons for antibiotic therapy were �rule-out� sepsis (32) and �culture-negative� sepsis (16) with ampicillin (40), gentamicin (35), amikacin (19), vancomycin (15), and meropenem (9) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26), amikacin (20), and meropenem (16) were the most prescribed agents. Length of therapy for culture-positive and �culture-negative� infections was 12 days (median; IQR, 8�14) and 7 days (median; IQR, 5�10), respectively. Mortality was 6 (42, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0·02). Interpretation: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. Funding: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship © 2021 The Author

Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect.

Background: Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1) - critical for lung, thyroid and central nervous system morphogenesis and function - causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant.Methods: The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH). Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC) were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled 2H 2O and 13C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry 2H and 13C enrichment curves. Six intubated infants with no primary lung disease were used as controls.Results: Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human and was not found in two healthy controls and in five ABCA3 mutation carriers. Kinetic studies demonstrated a marked reduction of SP-B synthesis (43.2 vs. 76.5 ± 24.8%/day); conversely, DSPC synthesis was higher (12.4 vs. 6.3 ± 0.5%/day) compared to controls, although there was a marked reduction of DSPC content in tracheal aspirates (29.8 vs. 56.1 ± 12.4% of total phospholipid content).Conclusion: Defective TTF-1 signaling may result in profound surfactant homeostasis disruption and neonatal/pediatric diffuse lung disease. Heterozygous ABCA3 missense mutations may act as disease modifiers in other genetic surfactant defects

Porous carbons from ionic liquid precursors confined within nanoporous silicas

We propose Vycor® porous glass and various types of enhanced pore size Vycor® (hereafter referred to eps-Vycor®) as hard templates for the development of micro-mesoporous N-doped carbons via nanocasting/thermolytic treatment of 1-alkyl-3-methylimidazolium tricyanomethanide Ionic Liquids (ILs). Vycor® is less costly than mesoporous ordered silicas of the type SBA-15 and MCM-41 which are sometimes employed for the development of micro-mesoporous carbons (CMK-3) as inverse replicas from the solid matrix; in addition Vycor® and eps-Vycor® can also be used in the form of sheets or tubes, thus opening the road for the development of composite carbon/silica substrate membranes with molecular sieving characteristics. We find that the nitrile functional groups in the anion of the IL lead to enhanced carbon yield while nanocasting and nanoconfinement are decisive for producing functional carbons with high levels of microporosity. In addition, the developed functional carbons exhibited extended mesoporosity with characteristic H2 or H1 types of hysteresis in their N2 adsorption isotherms (77 K), solely in the cases when eps-Vycor® was applied as the hard template. The widening of the Vycor® pores, especially of the pore constrictions by treatment in HF for varying periods led to the formation of thicker carbon nanodomains that exhibited the required mechanical stability to retain the inverse structure (replica) upon dissolution of the hard template

Zeolite imidazolate framework-Ionic liquid hybrid membranes for highly selective CO2 separation

Zeolitic imidazolate framework ZIF-69 membranes were grown on porous a-alumina substrates via seeded secondary growth and further functionalized by a CO2-selective tricyanomethanide anion/alkylmethylimidazolium cation-based ionic liquid (IL) to plug the gaps between the ZIF crystals yet leave the framework pores open for gas diffusion. In this configuration, ZIF intergrain boundaries and defects were repaired by a medium that exhibits high selectivity for CO2. As a result, the selectivity of the hybrid membrane was significantly higher than that of as-grown ZIF membranes and, because of the existence of the ZIF channels, the permeability was higher than that corresponding to bulk IL. Specifically, CO2 permeated 20 times faster than N2 through the intact ZIF pores and 65 times faster than through the bulk IL phase. The developed membranes at room temperature and under a 2 bar transmembrane pressure exhibited CO2 permeance of 5.6 × 10–11 and 3.7 × 10–11 mol m–2 s–1 Pa–1 and real CO2/N2 selectivities of 44 and 64 for CO2/N2 mixtures consisting of 44% and 75% (v/v) CO2, respectively. In addition, on the basis of the experimental evidence from the hybrid membranes, predictions were made on the expected performance of an ideal, crack-free, and homogeneous ZIF-69 membrane. This work provides a promising solution to the challenges associated with defect formation experienced during growth not only of ZIFs but also of other zeolite and inorganic membranes used for CO2 separation

Zeolite imidazolate framework-Ionic liquid hybrid membranes for highly selective CO2 separation

Zeolitic imidazolate framework ZIF-69 membranes were grown on porous a-alumina substrates via seeded secondary growth and further functionalized by a CO2-selective tricyanomethanide anion/alkylmethylimidazolium cation-based ionic liquid (IL) to plug the gaps between the ZIF crystals yet leave the framework pores open for gas diffusion. In this configuration, ZIF intergrain boundaries and defects were repaired by a medium that exhibits high selectivity for CO2. As a result, the selectivity of the hybrid membrane was significantly higher than that of as-grown ZIF membranes and, because of the existence of the ZIF channels, the permeability was higher than that corresponding to bulk IL. Specifically, CO2 permeated 20 times faster than N2 through the intact ZIF pores and 65 times faster than through the bulk IL phase. The developed membranes at room temperature and under a 2 bar transmembrane pressure exhibited CO2 permeance of 5.6 × 10–11 and 3.7 × 10–11 mol m–2 s–1 Pa–1 and real CO2/N2 selectivities of 44 and 64 for CO2/N2 mixtures consisting of 44% and 75% (v/v) CO2, respectively. In addition, on the basis of the experimental evidence from the hybrid membranes, predictions were made on the expected performance of an ideal, crack-free, and homogeneous ZIF-69 membrane. This work provides a promising solution to the challenges associated with defect formation experienced during growth not only of ZIFs but also of other zeolite and inorganic membranes used for CO2 separation