Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus.

Tricyclic pyrrolopyrimidines (TPPs) are a new class of antibacterials inhibiting the ATPase of DNA gyrase. TPP8, a representative of this class, is active against Mycobacterium abscessus in vitro. Spontaneous TPP8 resistance mutations mapped to the ATPase domain of M. abscessus DNA gyrase, and the compound inhibited DNA supercoiling activity of recombinant M. abscessus enzyme. Further profiling of TPP8 in macrophage and mouse infection studies demonstrated proof-of-concept activity against M. abscessus ex vivo and in vivo.

A trial comparing continuous positive airway pressure (CPAP) devices in preterm infants.

OBJECTIVE: To test the hypothesis that infants born <30 weeks' gestation supported by Seattle-PAP will have lower rates of continuous positive airway pressure (CPAP) failure than infants supported with conventional, Fisher&Paykel-CPAP (FP-CPAP). STUDY DESIGN: Randomized trial (3/2017-01/2019) at 5 NICUs. The primary outcome was CPAP failure; subgroup analyses (gestational age, receipt antenatal corticosteroids) were performed. RESULTS: A total of 232 infants were randomized. Infants in the Seattle-PAP and FP-CPAP groups had mean gestational ages of 27.0 and 27.2 weeks, respectively. We observed no differences in rates of treatment failure between Seattle-PAP (40/112, 35.7%) and FP-CPAP (38/120, 31.7%; risk difference, 4.1%; 95% CI, -8.1-16.2; P = 0.51). Subgroup analysis indicated no differences in rates of CPAP failure. We observed no differences between the two groups in frequencies of adverse events or duration of respiratory support. CONCLUSIONS: Among infants born <30 weeks' gestation, rates of CPAP failure did not differ between Seattle-PAP and FP-CPAP.

Quality Improvement Initiative to Reduce the Necrotizing Enterocolitis Rate in Premature Infants.

OBJECTIVE: To reduce the incidence of necrotizing enterocolitis (NEC) among very low birth weight (VLBW) infants admitted to 8 intensive care nurseries from a 2010 baseline of 8.0% to <4.0% by 2012 and sustain for 6 months using quality improvement (QI) methodology. METHODS: A multidisciplinary NEC QI team used the Vermont Oxford Network definition of NEC and the Institute for Healthcare Improvement model. The specific aims were evidenced based and included (1) standardized early human milk feedings, (2) conservative feeding guidelines during blood transfusions and indomethacin treatment, and (3) restriction of ranitidine use in VLBW infants. Inclusion criteria included VLBW infants admitted within the study period without NEC. Exclusion criteria included established NEC or spontaneous intestinal perforation unrelated to NEC. The incidence of NEC and NEC-related surgery were tracked using statistical process control methodology. RESULTS: The baseline NEC rate in 2010 was 8% (27 NEC cases in 335 VLBW infants). After initiation of early human-milk feeding and conservative feeds during blood transfusions guidelines in November 2011, only 3.1% (19 of 606 VLBW infants) had developed NEC through December 2013 (P = .001). Special cause variation was noted in June 2012 establishing a new centerline at 3.1%. NEC-related mortality decreased from a 2010 baseline mean of 2.7% to a new baseline mean of 0.9% from January 2011 to December 2013. CONCLUSIONS: Implementation of QI initiatives decreased the NEC rate from 8.0% to <4.0%. Early human milk feedings and conservative feeding during blood transfusion policies appear to have significant impact on NEC reduction.

Surveillance of ventilator-associated pneumonia in very-low-birth-weight infants.

BACKGROUND: Surveillance of ventilator-associated pneumonia (VAP) is an essential part of quality patient care. Very-low-birth-weight (VLBW) infants, many with tracheal microbial colonization and bronchopulmonary dysplasia (BPD), comprise a difficult group in whom to make a diagnosis of pneumonia with the Centers for Disease Control and Prevention (CDC) criteria for infants younger than 1 year. OBJECTIVE: Our objective was to retrospectively compare VAP surveillance diagnoses made by the hospital infection control practitioner (ICP) with those made by a panel of experts with the same clinical and laboratory evidence and supportive radiologic data. A secondary objective was to compare radiologic diagnosis of pneumonia made by the general hospital radiologists, by the panel of experts, and by a pediatric radiologist from another hospital. STUDY POPULATION: Thirty-seven VLBW infants identified as at risk for VAP by the ICP on the basis of a positive bacterial tracheal culture and the application of CDC criteria for the definition of pneumonia were studied. METHODS: Clinical and laboratory evidence and routine radiologic reports made by the general radiologist were reviewed independently by a panel of experts composed of 3 experienced neonatologists. Chest x-rays from the day before, day of, and day after the surveillance date were reviewed separately by the 3 neonatologists and also by a pediatric radiologist. RESULTS: After inter-reader reliability was found satisfactory (kappa's coefficient, 0.47-0.75; P <.05), the panel of neonatologists determined that the 37 VLBW infants represented 4 distinct clinical categories. Group 1 comprised 12 airway-colonized infants, aged 14 to 30 days, who on the surveillance date, albeit intubated, were asymptomatic, not treated with antibiotics, and survived. Group 2 comprised 11 airway-colonized infants, aged 7 to 42 days, who presented with equivocal clinical, laboratory, or radiologic signs of VAP and survived. Group 3 comprised 7 airway-colonized infants, aged 14 to 21 days, who were acutely ill (3 died) and had clinical and laboratory evidence of nosocomial bloodstream infection (BSI) but no radiologic signs of pneumonia. Group 4 comprised 7 infants, aged 14 to 28 days, who were acutely ill (4 died) and had clinical and laboratory evidence of infection and radiologic changes consistent with VAP. Radiologic Findings: General radiologists, neonatologists, and the pediatric radiologist agreed that none of the asymptomatic airway-colonized infants (Group 1) had VAP. General radiologists reported signs suggestive of pneumonia in 8 of 11 infants (Group 2), a finding not corroborated by the others. Everybody agreed on the absence of radiologic pneumonia in 6 of 7 patients with nosocomial BSI (Group 3) and on the presence of signs consistent with pneumonia in the remaining 7 infants (Group 4). CONCLUSION: Surveillance diagnosis of VAP in VLBW infants is difficult because current CDC definitions are not specific for this population. Isolated positive tracheal culture alone does not distinguish between bacterial colonization and respiratory infection. Clinical and laboratory signs of VAP, mostly nonspecific, can be found in other conditions such as bronchopulmonary dysplasia and nosocomial BSI. Routine radiologic reports suggestive of pneumonia in airway-colonized infants without definitive clinical and laboratory evidence of infection could be misleading. To improve accuracy, surveillance diagnosis of VAP in special populations such as VLBW infants should be reformulated; meanwhile, ICPs should seek consultation with experienced clinicians for interpretation of data.