Optimizing antibiotic use in culture-negative healthcare-associated infection with a 'stop' policy: a descriptive analytical study.

BACKGROUND AND OBJECTIVES: Many sick neonates receive antibiotics for the clinical diagnosis of probable/possible sepsis. Reports suggest rampant antibiotic use in culture-negative sepsis. We introduced an antibiotic stop policy (ASP), by defining 'completed course duration of antibiotics' in the setting of culture-negative suspected healthcare-associated infection (HAI). Antibiotic overuse days (AOD) before antibiotic stop policy (BASP) and after antibiotic stop policy (AASP) were compared. METHODS: This descriptive analytical study was conducted to measure the change in AOD after implementing ASP in culture-negative HAI. We also sought to evaluate situations in which antibiotic overuse is likely (lower gestation, ventilation, central lines) and safety of the ASP, measured as not having to restart antibiotics in the week following completed course. RESULTS: A total of 126 neonates were initiated on a new antibiotic (started or changed) for suspected HAI. Of these, 43 were excluded. Patient days of 5175 and 5208 were analyzed in BASP and AASP, respectively. Implementation of an ASP reduced AOD (from 14.49 to 3.26 AOD per 1000 patient days; p value <0.01). Safety was ensured; the number of babies who had to be restarted on antibiotics within 1 week of stopping therapy was similar in both groups. All-cause mortality and relevant morbidities were comparable between groups. CONCLUSIONS: A significant decrease in AOD after the introduction of an ASP was noted, in neonates with culture-negative suspected HAI. This difference was noted even in the most vulnerable extreme preterm babies and those requiring ventilation and central lines.

Every treasured drop! Blood transfusion requirements in very preterm neonates after implementation of blood conservation strategies: an observational analytical study.

BACKGROUND: Certain morbidities are inevitable in preterm infants; the challenge lies in minimizing them. Anemia of prematurity is multifactorial. Therapy largely depends on adult red blood cell transfusions (RBCT); which inherently, are not without problems. Most literature in this respect are retrospective or evaluate individual stratagems to reduce RBCT. METHODS: This observational analytical study was planned to compare need for RBCT, before and after institution of blood conservation strategies (BCS). All those ≤30 weeks gestation at birth during two-time epochs were included (Before BCS: retrospective; After BCS: prospective). BCS constituted of delayed cord clamping (DCC), strict sampling indications, micro-sampling with point-of-care testing (MS-POCT) and adherence to RBCT thresholds. RESULTS: Of 45 enrolled neonates in each group, proportion of those requiring even 1 RBCT was significantly reduced after BCS [51.1% vs. 26.7%, p = 0.02, OR 0.35, 95%CI (0.14, 0.84)]. Calculated cumulative blood volume losses (35.3 ml vs. 21.9 ml) and loss per kilogram birth weight (35.3 ml/kg vs. 20.12 ml/kg) were significantly lower after BCS (p = 0.0036). Need for >1 RBCT, mean lowest Hb, mean maximum-hemoglobin drop, need for arterial lines were reduced. Adherence to RBCT thresholds were acceptably good in both time epochs. However, the compliance to DCC was low in both groups, identifying one area of focus with scope for massive improvement. CONCLUSIONS: Need for RBCT transfusions largely attributable to reduced blood losses for lab analysis were reduced after BCS. Installation of in-house MS-POCT seemed to be the pivotal factor. Units that care for very preterm infants must make attempts to procure MS-POCT equipment.

• Institution of a conglomerate of blood conservation strategies (BCS) is an effective strategy to reduce red blood cell transfusion requirements in very preterm infants. • The need for multiple transfusions, calculated cumulative blood volume losses, number of venous samples drawn are also reduced with BCS. • The most important component of BCS is the availability of micro-sampling-point-of-care-testing technology. This facility will benefit centers which care for these high-risk infants.

Incidence of Metabolic Bone Disease After Implementation of Bone Protective Nutritional Strategies: A Prospective Cohort Study.

BACKGROUND: Metabolic bone disease (MBD) is a morbidity of multifactorial etiology with a high incidence in very preterm infants. We planned to study the incidence of MBD after implementation of bone health focussed nutritional strategy (BNS) in those <30 weeks gestation at birth. METHODS: This prospective cohort study including preterm newborns (<30 weeks) who received nutrition that incorporated (a) Early initiation of intravenous potassium phosphate; (b) Early enteral supplementation with multicomponent human milk fortifier at enteral feed tolerance of 40 mL/kg/day feeds itself; and (c) Weekly phosphorus measurements with optimization of enteral intakes. Incidence of MBD at 4 weeks of postnatal age and beyond were analyzed. Other relevant safety and clinical outcomes were measured. RESULTS: Of the 67 included neonates receiving BNS, 20.9% were classified as MBD. There was a low rate of hyper-phosphatemia (4.5%) and hyperkalemia (2.9%). Full enteral feeds were achieved by median (IQR) of 6 (5,7) postnatal days. CONCLUSION: In preterm newborns (24-30 weeks) MBD incidence was 20.9% after BNS was implemented. Intravenous potassium salt of phosphorus and early use of HMF were safe and feasible.

Microvillus Inclusion Disease: A Rare Mutation of STX3 in Exon 9 Causing Fatal Congenital Diarrheal Disease.

Inherited diarrheal disorders cause serious morbidity resulting in dependence on intensive care and parenteral nutrition. Microvillus inclusion disease (MVID) has been classically described and results from mutations in the gene coding myosin Vb, which is responsible for enterocyte polarization. Newer reports of mutations resulting in truncated syntaxin 3 (STX3) and Munc18-2 (STXBP2) proteins have been elucidated as causative. To date, five cases of STX3 abnormalities resulting in MVID have been described. We report an infant who presented with congenital diarrhea and was determined to have a rare mutation of STX3. This new finding would be beneficial in future functional genotype-phenotype correlation studies.

Endotracheal Aspirate and Ventilator-Associated Pneumonia in Neonates: Revisiting an Age-Old Debate.

OBJECTIVES: To explore the utility of endotracheal aspirates (ETA) for analyzing microbiological yield, incidence, risk factors for VAP, and clinically relevant outcomes. METHODS: Ventilated neonates suspected to have VAP were studied prospectively; they were classified as "VAP" or "No VAP" based on a predefined combination of clinical, radiological, and laboratory criteria. The microbiological yield from blood and ETA cultures was analyzed. RESULTS: Of 165 neonates who were ventilated for > 48 h, 65 were suspected of having VAP. Thirty-six (22.9%) were classified as VAP. Microbiological agents could be identified in 31 cases (86.1%) by ETA/blood cultures. Acinetobacter sp was the common organism identified. Duration of ventilation, and a higher number of reintubations before suspicion of VAP were significant risk factors for VAP. Positive ETA culture was associated with a greater duration of oxygen therapy and ventilation days after suspicion of VAP. CONCLUSIONS: The commonest culture yield from ETA in those suspected to have VAP was gram-negative bacilli. Duration of ventilation and reintubations were identified as significant risk factors for VAP. These are potentially modifiable factors. Positive ETA culture was associated with longer needs for respiratory supports. Negative ETA culture might encourage clinicians to stop antibiotics. TRIAL REGISTRATION: Clinical Trials Registry of India No. CTRI/2019/03/017912,  www.ctri.nic.in.

Iron Status of the Moderate and Late Preterm Infant: A Prospective Cohort Study.

Guidelines on micronutrient supplementation in moderate to late preterm infants (MLP) are mostly extrapolated from those for smaller preterms, largely due to lack of systematic studies on physiological status in this special group of infants. Actual practices vary widely. We prospectively studied iron status by measurement of serum ferritin (SF) and haematological indices at 4 months corrected age in infants born between 32 and 36 weeks gestation (MLP), after they received 2 mg/kg/day oral iron from 6 weeks of postnatal age. Proportion of MLP having normal iron status (iron replete), i.e., neither iron deficiency (ID) nor iron excess was measured. ID anaemia, growth and development, risk factors for ID were also analysed. Of the 82 infants studied, 78% babies were late preterm. Seventy-four (90.3%) were iron replete (no deficiency or excess) at 4 months. High variability in SF levels (minimum of 9.8 to maximum of 252.2 µg/l) with median (IQR) of 57.45 µg/l (37.02-98.85) was noted in the entire cohort; and also within those who were iron deficient with median (IQR) of 17.50 µg/l (11.70-18.90). There was no difference in haematological indices of ID infants when compared to those with normal iron status. Inspite of oral iron supplementation with reasonable compliance, 8.5% MLP were iron deficient at 4 months corrected age. The high variability noted in SF levels could justify the need for monitoring iron status in this group of preterm infants. This could quintessentially aid individualization of iron supplementation advice.

Duration of Caffeine for Apnea of Prematurity-A Randomized Controlled Trial.

OBJECTIVES: There is sufficient evidence to support use of caffeine therapy for apnea of prematurity, but practices vary widely when it comes to discontinuing therapy. This study was planned to compare 'recurrence of apnea of prematurity' (RAP); when 2 protocols were used to stop caffeine therapy. METHODS: Neonates delivered at 26-32 wk gestation on caffeine therapy for apnea of prematurity were randomized into 2 groups: Group 1-caffeine stopped at 7 d apnea-free period, and Group 2-continued for a prefixed period till at least 34 wk postmenstrual age (PMA). Proportion of infants in each group with RAP were analyzed. RESULTS: Each group consisted of 60 infants. Proportion of infants in each group with RAP, were not different (15% vs 13%); odds ratio (OR) 0.87; 95% confidence interval (CI) (0.31-2.43). Caffeine could be stopped earlier (33 vs 34 wk PMA); and cumulative duration of therapy was lesser (19.5 vs 33 d) when stopped at 7 d apnea-free period. Other studied outcomes were similar between the two groups. CONCLUSIONS: Mandatorily continuing caffeine therapy up to 34 wk PMA in select preterm groups does not seem to decrease risk of recurrence of apnea. Larger trials that specifically study extremely preterm infants are required to make robust recommendations on when to stop therapy. CLINICAL TRIALS REGISTRY OF INDIA NO: CTRI/2016/12/007559. http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=14195&EncHid=&modid=&compid=%27,%2714195det%27.

Disability Prediction by Early Hammersmith Neonatal Neurological Examination: A Diagnostic Study.

BACKGROUND AND OBJECTIVES: Hammersmith Neonatal Neurologic Examination (HNNE) is used to identify term and preterm infants at risk of neurodevelopmental disability. The test is recommended at corrected term age in preterm; and around 2 weeks postnatal age in term neonates. As the current trend is to discharge based on physiological stability, it may not be feasible to perform HNNE at recommended age. The authors investigated whether predictive ability of the test for neurodevelopmental disability remained unchanged if performed early (before discharge). METHODS: The authors enrolled preterm and at-risk term neonates. HNNE PE was performed before discharge in all infants. The test was repeated in preterm infants at 40 weeks postmenstrual age and in term neonates at 2 weeks of age (HNNE RA). Neurodevelopmental disability was assessed at 1 year of age. RESULTS: HNNE PE was done in 125 neonates (103 preterm, 22 term neonates). HNNE RA was done in 58% infants. Neurodevelopmental disability was assessed in 84 (67%) of infants. Neurodevelopmental disability was noted in 14/84 (16.6%) babies. The receiver operating characteristic curve of raw scores showed that area under the curve for HNNE PE (0.71) and HNNE RA (0.66) were similar. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for both the tests were similar for a cutoff optimality score of 32.5. HNNE PE could be performed up to 4 weeks earlier than HNNE RA with the same predictive ability for neurodevelopmental disability. CONCLUSIONS: HNNE PE was as reliable as HNNE RA in predicting neurodevelopmental disability at 1 year of age. Completion of the test is assured and provides several weeks lead time for early intervention.

Familial Hemophagocytic Lymphohistiocytosis: A Rare Mutation of STXBP2 in Exon 19.

Familial hemophagocytic lymphohistiocytosis (FHLH) is a fulminant rapidly progressive disorder characterized by uncontrolled immune system activation. Over the last decade, STXBP2 mutations have been reported as causative. We report a baby with typical clinical features and supportive laboratory findings, who had a homozygous missense variation in exon 19 of STXBP2 that results in an amino acid substitution of aspartic acid for glycine. Adding to the currently scant literature on this variation may contribute to the database pool and help to confirm assertion of pathogenicity in FHLH.

Exclusive Breast Milk vs. Hybrid Milk Feeding for Preterm Babies-A Randomized Controlled Trial Comparing Time to Full Feeds.

When breastmilk is insufficient to meet planned feed volumes, neonatologists need to continue parenteral nutrition (PN) or use formula. This trial conducted at a tertiary care unit in South India between August 2014 and April 2016 compared time to full feeds in preterms fed 'mother's milk alone(MM)' vs. 'hybrid feed-mother's milk supplemented with formula(HF)'. We also compared time to regain birth weights, duration of PN, feed intolerance, Necrotizing Enterocolitis stage 2 or more, all-cause mortality, Extrauterine growth restriction, Healthcare associated infections, exclusive breast milk feeding rates at discharge, Retinopathy of prematurity requiring laser therapy, abnormal neurosonogram and oxygen dependency at 28 days. Neonates between 27 and 32 weeks were randomized into MM/HF when breast milk was insufficient. HF received formula to reach targeted feed volumes. MM received more PN to meet fluid requirements. 54 babies were analyzed in MM and 58 in HF. Time to full feeds were similar-MM (14.1 ± 4 days); HF (13.5 ± 4 days), p = 0.45. Exclusive breast milk feeding rates at discharge were higher in MM when compared to HF (74% vs. 51%). Other secondary outcomes were similar between groups. When mother's milk is unavailable in sufficient quantities, preterm babies may receive hybrid feeds. (Clinical trials registry of India no. REF/2016/02/006622).

Outcome of Very Preterm Infants With Early Optimal Nutrition Strategy: A Comparative Cohort Study.

BACKGROUND: Aggressive nutrition may benefit early growth; nevertheless, effects on neurodevelopmental outcomes are unclear. We planned a descriptive analytical study to compare survival without neurodevelopment disability (NDD) at 1 year in 2 groups during 2 time epochs-before and after implementation of early optimal nutrition strategies. NDD was defined as any one of the following: mental and/or motor development quotient < 85 at 12 months of age, corrected for prematurity; Denver Developmental Screening Test abnormal/suspect in even 1 domain out of the 4 domains; seizures; requirement of hearing aid; or blindness in 1 or both eyes. We also compared mortality, survival without bronchopulmonary dysplasia, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), intraventricular hemorrhage, periventricular leukomalacia, sepsis, metabolic bone disease (MBD), and extrauterine growth restriction (EUGR). METHODS: Preterm neonates born between 27 and 32 weeks' gestation were included. The prospective study group (AO) was recruited after implementation of early optimal nutrition policy. The comparative retrospective cohort (BO) received nutrition based on clinicians' decisions. Both groups were followed up using a structured plan till 1 year corrected age. RESULTS: 137 neonates were enrolled in AO and 151 in the BO cohort. There was no statistically significant difference in survival without NDD at 1 year-75.5% in AO vs 72.1% in BO, odds ratio 0.84 (95% CI 0.5-1.6). Babies who received early optimal nutrition had less NEC, EUGR, and ROP requiring laser therapy but more MBD. CONCLUSION: There was no difference in survival without NDD in early optimal nutrition cohort compared to the cohort before implementation of the nutrition strategy. Short-term benefits themselves may justify the need for early optimal nutrition.