Mycoplasma hominis meningitis in an extremely preterm newborn: a case report.

BACKGROUND: Mycoplasma Hominis is a micro-organism which is a part of the human genitourinary tract flora. Neonates are susceptible to acquire this pathogen either in utero or through vertical transmission. In rare cases, it may cause central nervous system infections with severe morbidity and mortality in preterm and term neonates. CASE PRESENTATION: We present a case of Mycoplasma Hominis meningitis in an extremely preterm neonate who presented with lethargy, tachycardia and seizures on day 7 of life. There was no history of maternal systemic or genitourinary infection during pregnancy and at the time of delivery. Empirical antibiotic therapy for neonatal meningitis was commenced after sending blood and cerebrospinal fluid cultures. Cerebrospinal fluid analysis showed pleocytosis with neutrophilic predominance, but no bacteria was identified on gram staining. Blood culture yielded no growth of any bacterial pathogen. However, growth of Mycoplasma Hominis was suspected in cerebrospinal fluid culture which was confirmed by 16S ribosomal ribonucleic acid (RNA) polymerase chain reaction analysis. Subsequently, antibiotics were changed to Moxifloxacin and Doxycycline which were given for a total duration of 6 weeks. Multiple cerebrospinal fluid cultures were performed during this treatment. No growth of any pathogen was identified on any of these cerebrospinal fluid cultures. CONCLUSIONS: We report a rare case of Mycoplasma Hominis meningitis in an extremely preterm neonate which was successfully treated with a combination therapy of Moxifloxacin and Doxycycline. It is important to consider the possibility of Mycoplasma Hominis meningitis in neonates who present with clinical signs and pleocytosis in cerebrospinal fluid but negative gram staining and no growth on conventional culture media.

Regional variation in cost of neonatal intensive care for extremely preterm infants.

BACKGROUND: Regional variation in cost of neonatal intensive care for extremely preterm infant is not documented. We sought to evaluate regional variation that may lead to benchmarking and cost saving. METHODS: An analysis of a Canadian national costing data from the payor perspective. We included all liveborn 23-28-week preterm infants in 2011-2015. We calculated variation in costs between provinces using non-parametric tests and a generalized linear model to evaluate cost variation after adjustment for gestational age, survival, and length of stay. RESULTS: We analysed 6932 infant records. The median total cost for all infants was $66,668 (Inter-Quartile Range (IQR): $4920-$125,551). Medians for the regions varied more than two-fold and ranged from $48,144 in Ontario to $122,526 in Saskatchewan. Median cost for infants who survived the first 3 days of life was $91,000 (IQR: $56,500-$188,757). Median daily cost for all infants was $1940 (IQR: $1518-$2619). Regional variation was significant after adjusting for survival more than 3 days, length of stay, gestational age, and year (pseudo-R2 = 0.9, p < 0.01). Applying the model on the second lowest-cost region to the rest of the regions resulted in a total savings of $71,768,361(95%CI: $65,527,634-$81,129,451) over the 5-year period ($14,353,672 annually), or over 11% savings for the total program cost of $643,837,303 over the study period. CONCLUSION: Costs of neonatal intensive care are high. There is large regional variation that persists after adjustment for length of stay and survival. Our results can be used for benchmarking and as a target for focused cost optimization, savings, and investment in healthcare.

Development, evaluation and validation of a screening tool for late onset bacteremia in neonates - a pilot study.

BACKGROUND: Clinical and laboratory parameters can aid in the early identification of neonates at risk for bacteremia before clinical deterioration occurs. However, current prediction models have poor diagnostic capabilities. The objective of this study was to develop, evaluate and validate a screening tool for late onset (> 72 h post admission) neonatal bacteremia using common laboratory and clinical parameters; and determine its predictive value in the identification of bacteremia. METHODS: A retrospective chart review of neonates admitted to a neonatal intensive care unit (NICU) between March 1, 2012 and January 14, 2015 and a prospective evaluation of all neonates admitted between January 15, 2015 and March 30, 2015 were completed. Neonates with late-onset bacteremia (> 72 h after NICU admission) were eligible for inclusion in the bacteremic cohort. Bacteremic patients were matched to non-infected controls on several demographic parameters. A Pearson's Correlation matrix was completed to identify independent variables significantly associated with infection (p < 0.05, univariate analysis). Significant parameters were analyzed using iterative binary logistic regression to identify the simplest significant model (p < 0.05). The predictive value of the model was assessed and the optimal probability cut-off for bacteremia was determined using a Receiver Operating Characteristic curve. RESULTS: Maximum blood glucose, heart rate, neutrophils and bands were identified as the best predictors of bacteremia in a significant binary logistic regression model. The model's sensitivity, specificity and accuracy were 90, 80 and 85%, respectively, with a false positive rate of 20% and a false negative rate of 9.7%. At the study bacteremia prevalence rate of 51%, the positive predictive value, negative predictive value and negative post-test probability were 82, 89 and 11%, respectively. CONCLUSION: The model developed in the current study is superior to currently published neonatal bacteremia screening tools. Validation of the tool in a historic data set of neonates from our institution will be completed.

The representation of vulnerable populations in quality improvement studies.

PURPOSE: A mapping review to quantify representation of vulnerable populations, who suffer from disparity and often inequitable healthcare, in quality improvement (QI) research. DATA SOURCES: Studies published in 2004-2014 inclusive from Medline, Embase and Cochrane databases for English language research with the terms 'quality improvement' or 'quality control' or 'QI' and 'plan-do-study-act' or 'PDSA' in the years 2004-2014 inclusively. STUDY SELECTION: Published clinical research that was a QI-themed, as identified by its declared search terms, MESH terms, abstract or title. DATA EXTRACTION: Three reviewers identified the eligible studies independently. Excluded were publications that were not trials, evaluations or analyses. RESULTS OF DATA SYNTHESIS: Of 2039 results, 1660 were eligible for inclusion. There were 586 (33.5%) publications that targeted a specific vulnerable population: children (184, 10.54%), mental health patients (125, 7.16%), the elderly (100, 5.73%), women (57, 3.27%), the poor (30, 1.72%), rural residents (29, 1.66%), visible minorities (27, 1.55%), the terminally ill (17, 0.97%), adolescents (16, 0.92%) and prisoners (1 study). Seventy-four articles targeted two or more vulnerable populations, and 11 targeted three population categories. On average, there were 158 QI research studies published per year, increasing from 69 in 2004 to 396 in 2014 (R2 = 0.7, P < 0.001). The relative representation of vulnerable populations had a mean of 33.58% and was stable over the time period (standard deviation (SD) = 5.9%, R2 = 0.001). Seven countries contributed to over 85% of the publications targeting vulnerable populations, with the USA contributing 62% of the studies. CONCLUSIONS: Over 11 years, there has been a marked increase in QI publications. Roughly one-third of all published QI research is on vulnerable populations, a stable proportion over time. Nevertheless, some vulnerable populations are under-represented. Increased education, resources and attention are encouraged to improve the health of vulnerable populations through focused QI initiatives.

Prophylactic Interventions in Neonatology: How Do They Fare in Real Life?

OBJECTIVE: This study aims to evaluate the association of prophylactic antenatal steroids, indomethacin, and phototherapy with extremely preterm infant outcomes in a pragmatic setting. STUDY DESIGN: Retrospective study of infants born at <28 weeks gestation and admitted to 26 Canadian Neonatal Network neonatal intensive care units between 2010 and 2012. Mortality, severe neurological injury, retinopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, nosocomial infection, and patent ductus arteriosus ligation rates were compared between infants who received antenatal steroids, prophylactic indomethacin, and/or prophylactic phototherapy and those who did not. RESULTS: Of 3,465 eligible infants, 2,900 (84%) received antenatal steroids, 269 (8%) prophylactic indomethacin, and 403 (12%) prophylactic phototherapy. Associations were observed between antenatal steroids and mortality (adjusted odds ration [aOR] 0.47 [0.33-0.66]) and severe neurological injury (aOR 0.60 [0.46-0.77]), indomethacin and ductus arteriosus ligations (aOR 0.52 [0.31-0.87]), but not severe neurological injury (aOR 1.12 [0.81-1.54]), but phototherapy was not associated with any of the neonatal outcomes despite reductions in bilirubin. CONCLUSION: Antenatal steroids were associated with reduced mortality and neurological injury, prophylactic indomethacin was not associated with reduction in neurological injury and phototherapy was not associated with any improvement in neonatal outcomes. In a pragmatic setting, outside randomized controlled trials, the effectiveness and safety of prophylactic interventions in extremely preterm neonates vary; ongoing monitoring is warranted.

Sustaining Improvement Initiatives: Challenges and Potential Tools.

Like many implemented organizational changes, quality improvement (QI) projects demonstrate frequent decline after implementation. Factors associated with successfully sustained change are leadership, change characteristics, system capacity for changes and the resources required, and processes to maintain, evaluate, and communicate results. This review uses lessons from change theory and behavioral sciences to discuss change and sustainment of improvement efforts, to list models to support maintenance, and to provide evidence-based practical suggestions to enable the sustainability of QI interventions.

The price of neonatal intensive care outcomes - in-hospital costs of morbidities related to preterm birth.

Background: Neonatal care for preterm babies is prolonged and expensive. Our aim was to analyze and report costs associated with common preterm diagnoses during NICU stay. Methods: We analyzed data from the Ontario healthcare data service. Diagnoses were collated by discharge ICD codes, and categorized by gestational age. We calculated typical non parametric statistics, and for each diagnosis we calculated median shifts and generalized linear mode. Results: We included data on 12,660 infants between 23 and 30 weeks gestation in 2005-2017. Calculated cost increment with diagnosis were: Intestinal obstruction: $94,738.08 (95%CI: $70,093.3, $117,294.2), Ventriculoperitoneal shunt: $86,456.60 (95%CI: $60,773.7, $111,552.2), Chronic Lung Disease $77,497.70 (95%CI: $74,937.2, $80,012.8), Intestinal perforation $57,997.15 (95%CI:$45,324.7, $70,652.6), Retinopathy of Prematurity: $55,761.80 (95%CI: $53,916.2, $57,620.1), Patent Ductus Arteriosus $53,453.70 (95%CI: $51,206.9, $55692.7, Post-haemorrhagic ventriculomegaly $41,822.50 (95%CI: $34,590.4, $48,872.4), Necrotizing Enterocolitis $39,785 (95%CI: $35,728.9, $43,879), Meningitis $38,871.85 (95%CI: $25,272.7, $52,224.4), Late onset sepsis $32,954.20 (95%CI: $30,403.7, 35.515), Feeding difficulties $24,820.90 (95%CI: $22,553.3, $27,064.7), Pneumonia $23,781.70 (95%CI: $18,623.8, $28,881.6), Grade >2 Intraventricular Haemorrhage $14,777.38 (95%CI: $9,821.7, $20,085.2). Adjusted generalized linear model of diagnoses as coefficients for cost confirmed significance and robustness of the model. Conclusion: Cost of care for preterm infant is expensive, and significantly increases with prematurity complication. Interventions to reduce those complications may enable resource allocation and better understanding of the needs of the neonatal health services.

A comparison of tertiary level NICU costs for infants born <1250 g supplemented with human versus bovine milk-based fortifiers.

BACKGROUND: Human milk-based fortifiers (HMBF) are more costly than bovine milk-based fortifiers (BMBF); but, the efficacy of human or bovine fortification for infants born <1250 g has yet to be fully elucidated. Our objective was to determine the effect of fortifier source on tertiary neonatal costs. METHODS: Costs associated with tertiary neonatal care, including direct and indirect hospital expenditures, feed-related costs and physician billing were analysed retrospectively for participants of OptiMoM (NCT02137473), a blinded RCT comparing fortifier type for babies born <1250 g. A generalized linear model of cost according to fortifier type was created. RESULTS: Mean [95% confidence interval] daily costs per patient, adjusted for birth gestation and weight, was significantly greater in the human than the BMBF group ($3,452 [$3,186 - $3,740] Canadian dollars (CAD) versus $2,451 [$2,257 - $2,662] CAD) respectively, p < 0.0001). CONCLUSION: HMBF usage entails additional costs on NICU stay that should be considered with implementation.

Survival and characteristics of retinopathy of prematurity in micro-premature infants.

OBJECTIVE: To describe the risk and nature of retinopathy of prematurity (ROP) in micro-premature infants (≤26 weeks' gestational age [GA]). METHODS: Retrospective analysis of prospectively collected data from infants born at 22-26 weeks' GA over a 5-year period. RESULTS: A total of 502 infants were identified, of whom 414 survived to discharge (82.5%). The Vermont Oxford Network database documented clinical follow-up data and ROP outcomes for all 414 patients; complete ROP clinical records were available for 294 of the infants who survived (70.8%). Forty infants were born between 22 and 23 weeks' GA (group A, 13.6%), and 254 were born between 24 and 26 weeks' GA (group B, 86.4%). Survival for group A infants was worse than that of group B infants (66.2% vs 85.4%; p < 0.01). Survival of group A infants improved during the study period (R2 = 0.625). Overall, 59.9% of infants developed any ROP and 8.5% developed type 1 ROP. Group A infants were more likely to develop ROP (90.0% vs 48.6%; p < 0.01) and type 1 ROP (30.0% vs 5.1%; p < 0.01) than group B infants. Group A infants developed ROP at an earlier age (32 + 6 weeks vs 33 + 3 weeks; p = 0.02) and were more likely to have zone I disease on presentation (65.0% vs 20.5%; p < 0.01), but there was no difference in the corrected gestational age of peak severity of ROP (35 + 2 weeks vs 34 + 5 weeks; p = 0.36). CONCLUSION: The most premature infants, born at 22-23 weeks' GA, develop ROP at an earlier age, are more likely to present with posterior disease, and have a high risk of disease requiring treatment.

Targeted fluconazole prophylaxis for high-risk very low birth weight infants.

Antifungal prophylaxis is increasingly used in very low birth weight (VLBW) infants who are at risk for severe fungal infections. Our objective was to assess the effectiveness of targeted fluconazole prophylaxis for high-risk VLBW infants. A retrospective cohort study with historical controls was performed. During the period 2007-2008, all high-risk VLBW infants (birth weight, ≤1,000 g; gestational age, ≤28 weeks; seven antimicrobial therapy or additional risk factors present) received fluconazole prophylaxis until risk factors were not present. Treated infants were compared to a gestational age- and birth weight-matched untreated cohort. Statistical analyses used univariate and multivariate analyses. The main outcome variable was a breakthrough fungal bloodstream infection (BSI). The prophylaxis cohort of 130 VLBW infants was compared to 319 control infants. The rate of fungal infections was significantly lower in the fluconazole prophylaxis group (1 of 130 vs. 19 of 319, p = 0.016); however, they did not differ in mortality (16.2 vs. 15 %, p = 0.77) or complications of prematurity. Fluconazole prophylaxis was associated with a significant decrease in candidal BSI (odds ratio, 0.05; 95 % confidence interval, 0.005-0.523). Selective vs. nonselective prophylaxis reduced the number of infants treated from 247 to 130. Conclusion Targeted fluconazole prophylaxis in VLBW infants is effective in preventing fungal infections without increasing the risk of BSI among low-risk infants.

Cost of neonatal intensive care for extremely preterm infants in Canada.

BACKGROUND: Neonatal intensive care is expensive and prolonged. Extremely preterm infants are routinely supported. The costs for this practice at the age of borderline viability are of interest to clinicians and policymakers. METHODS: We analyzed data from the Canadian national administrative database on total cost and length of hospital care from a public payor perspective for 23-28-week premature infants from 2011 to 2015. We also compared total and daily costs for 23-25-week newborns. Each comparison evaluated the total cohort and infants who lived more than 3 days. We used non-parametric tests, correlation tests, and generalized linear models for cost difference analysis, adjusting for survival, length of stay, and year. RESULTS: We analyzed 6,932 infants' cost records. For all infants, median length of hospital stay was 41 days (IQR, 1-77 days). For infants who survived the first 3 days, median length of stay was 61 days (IQR, 34-90 days). The median total cost was $66,669 (IQR, $4,920-$125,550). For infants who survived the first 3 days, median total cost was $91,137 (IQR, $56,596-$188,757). For infants who survived the first 3 days, median total costs were $147,835 (IQR, $44,711-$233,847) for 23-week infants, $154,736 (IQR, $61,160-$248,290) for 24-week infants, and $130,317 (IQR, $79,737-$229,058) for 25-week infants. These amounts did not differ (P>0.7). CONCLUSIONS: Total and daily costs of neonatal intensive care are high. Total cost was not different between surviving 23-25-week infants. These findings highlight the need for a funding strategy for the routine support of these fragile infants.

Therapeutic Drug Monitoring of Moxifloxacin to Guide Treatment of Mycoplasma hominis Meningitis in an Extremely Preterm Infant.

Mycoplasma hominis (M hominis) is a rare cause of neonatal bacterial meningitis. Treatment can be challenging because of M hominis' intrinsic antibiotic resistance and the difficulty in accessing antimicrobial susceptibility testing. In this report, we describe an extremely preterm male infant with seizures who had a subsequent diagnosis of M hominis meningitis. Because of severity of illness, doxycycline (4 mg/kg IV every 24 hours) and moxifloxacin (5 mg/kg IV every 24 hours) were started empirically. Repeat cerebrospinal fluid cultures were negative and showed decreasing pleiocytosis. Given the concentration-dependent killing of moxifloxacin and concern for endovascular infection from a concomitant cerebral venous sinus thrombosis, serum concentrations of moxifloxacin were obtained to estimate pharmacokinetic and pharmacodynamic parameters. These were compared to the targets described in other case reports of M hominis meningitis. The maximum serum concentration (Cmax) was 2.5 mg/L, volume of distribution was 2.2 L/kg, clearance was 0.18 L/kg/hr, terminal half-life was 8.6 hours, and area-under-the-concentration-time curve (AUC) was 28.1 mg•hr/L. Using the range of minimum inhibitory concentrations (MICs) reported in the literature, the estimated Cmax/MIC for this patient was 21 to 158 (target Cmax/MIC: >10) and AUC/MIC was 234 to 1757 (target AUC/MIC: ≥100). Doxycycline and moxifloxacin were continued for 6 weeks. No adverse events to moxifloxacin or doxycycline were observed in the NICU. This report describes the successful treatment of M hominis neonatal meningitis and adds to the knowledge of pharmacokinetic and pharmacodynamic parameters of moxifloxacin in neonates. Additional data will help to confirm the role for routine therapeutic drug monitoring of moxifloxacin in neonates.

A Quality Improvement Intervention to Reduce Necrotizing Enterocolitis in premature infants with Probiotic Supplementation.

Necrotizing Enterocolitis (NEC) is a severe intestinal inflammatory disease due to multifactorial causes that present in preterm infants. Compared with similar neonatal intensive care units, our NEC rate was increasing and prompted reduction by a quality improvement (QI) intervention. METHODS: We aimed to reduce NEC rate by 30% by the end of 2016. We used the Institute of Healthcare Improvement model and typical QI tools, including teamwork, process organizing tools, and evidence-based review, to assist in our selection of supplementation of Lactobacillus reuteri probiotic. We used education, process mapping, process control statistics, and forcing mechanism to implement the changes. In addition to reducing NEC rates, our additional outcome measures were sepsis, mortality, sepsis evaluations, feeding intolerance, growth, days of both antimicrobials, and parenteral nutrition use. Process measures were compliance with probiotics supplementation policy and balancing measures were sepsis rates and feeding intolerance. RESULTS: NEC rates decreased from 4.4% to the current 1.7%, and in a pre/post-intervention analysis, the results were significant in all patient subcategories. We did not demonstrate a reduction in mortality. No adverse events occurred. Feeding intolerance episodes and days nil-per-os decreased with no differences in growth at discharge. These results continued over 2 years, and this practice has already spread to several neonatal intensive care units in Ontario, Canada. CONCLUSIONS: We utilized QI methods and tools to implement a successful practice change of routine probiotic supplementation to reduce NEC rates in preterm infants. We suggest considering this intervention as a successful means to prevent this serious illness.

Impact of Stewardship on Inhaled Nitric Oxide Utilization in a Neonatal ICU.

OBJECTIVES: Inhaled nitric oxide (iNO) remains the "gold standard" therapy for hypoxemic respiratory failure in newborns. Despite good quality evidence to guide iNO use in this population, we observed considerable practice variation, particularly in timing and rate of weaning. To promote evidence-based practice, we launched an iNO stewardship program in April 2013. Our objective was to determine whether iNO stewardship led to changes in iNO utilization and weaning. METHODS: We conducted a quality improvement project in an outborn quaternary NICU, targeting improved iNO guideline compliance. We compared patterns of iNO utilization between 2 cohorts: prestewardship (April 2011-March 2013; retrospective data collection) and poststewardship (April 2013-March 2015; prospective data collection). RESULTS: Eighty-seven neonates received 88 courses of iNO in the 2 years prestewardship, and 64 neonates received 64 courses of iNO in the 2 years poststewardship. There were no significant differences (P > .05) in patient demographics, in the proportion of patients receiving iNO "off-label," in proportion initiated at the referring hospital, or in outcomes (death or extracorporeal membrane oxygenation). There were significant (P < .05) reductions in median total hours on iNO per patient (47 vs 20; P < .001), in iNO hours per patient from maximum dose to initial wean (28 vs 9; P < .01), and in hours from initial wean to discontinuation (14 vs 8; P < .05). CONCLUSIONS: The introduction of iNO stewardship was associated with improved adherence to evidence-based guidelines and an overall reduction in total and per-patient iNO use.

In utero oxcarbazepine and a withdrawal syndrome, anomalies, and hyponatremia.

Oxcarbazepine is an antiepileptic agent that has been used during pregnancy, although its safety during pregnancy has not been sufficiently established. This article presents an infant born with renal and cardiac malformations who developed a withdrawal syndrome and hyponatremia following in utero exposure to oxcarbazepine. The infant was born at 35 weeks' gestation by urgent cesarean section to a mother in status epilepticus who had been treated with oxcarbazepine throughout her pregnancy. Evaluation for congenital anomalies identified mild aortic stenosis, a bicuspid aortic valve, patent foramen ovale, patent ductus arteriosus, and severe left hydronephrosis due to left ureteropelvic junction stenosis. On the third day of life the infant developed clinical signs of a withdrawal syndrome, which peaked on day 7 and resolved by day 12. Transient hyponatremia resolved by day 8 of life. Follow-up showed normal development at 15 months. The association of a withdrawal syndrome with oxcarbazepine exposure has not been previously reported. The hyponatremia is consistent with adult reports. The possible association of oxcarbazepine with renal and cardiac malformations requires further confirmation.