Karen M. Puopolo

Interpreting complete blood counts soon after birth in newborns at risk for sepsis.

BACKGROUND: A complete blood count (CBC) with white blood cell differential is commonly ordered to evaluate newborns at risk for sepsis. OBJECTIVES: To quantify how well components of the CBC predict sepsis in the first 72 hours after birth. METHODS: For this retrospective cross-sectional study we identified 67 623 term and late-preterm (≥34 weeks gestation) newborns from 12 northern California Kaiser hospitals and 1 Boston, Massachusetts hospital who had a CBC and blood culture within 1 hour of each other at <72 hours of age. We compared CBC results among newborns whose blood cultures were and were not positive and quantified discrimination by using receiver operating characteristic curves and likelihood ratios. RESULTS: Blood cultures of 245 infants (3.6 of 1000 tested newborns) were positive. Mean white blood cell (WBC) counts and mean absolute neutrophil counts (ANCs) were lower, and mean proportions of immature neutrophils were higher in newborns with infection; platelet counts did not differ. Discrimination improved with age in the first few hours, especially for WBC counts and ANCs (eg, the area under the receiver operating characteristic curve for WBC counts was 0.52 at <1 hour and 0.87 at ≥4 hours). Both WBC counts and ANCs were most informative when very low (eg, the likelihood ratio for ANC < 1000 was 115 at ≥4 hours). No test was very sensitive; the lowest likelihood ratio (for WBC count ≥ 20 000 at ≥4 hours) was 0.16. CONCLUSION: Optimal interpretation of the CBC requires using interval likelihood ratios for the newborns age in hours.

Stratification of Risk of Early-Onset Sepsis in Newborns ≥34 Weeks’ Gestation

OBJECTIVE: To define a quantitative stratification algorithm for the risk of early-onset sepsis (EOS) in newborns ≥34 weeks’ gestation. METHODS: We conducted a retrospective nested case-control study that used split validation. Data collected on each infant included sepsis risk at birth based on objective maternal factors, demographics, specific clinical milestones, and vital signs during the first 24 hours after birth. Using a combination of recursive partitioning and logistic regression, we developed a risk classification scheme for EOS on the derivation dataset. This scheme was then applied to the validation dataset. RESULTS: Using a base population of 608 014 live births ≥34 weeks’ gestation at 14 hospitals between 1993 and 2007, we identified all 350 EOS cases <72 hours of age and frequency matched them by hospital and year of birth to 1063 controls. Using maternal and neonatal data, we defined a risk stratification scheme that divided the neonatal population into 3 groups: treat empirically (4.1% of all live births, 60.8% of all EOS cases, sepsis incidence of 8.4/1000 live births), observe and evaluate (11.1% of births, 23.4% of cases, 1.2/1000), and continued observation (84.8% of births, 15.7% of cases, incidence 0.11/1000). CONCLUSIONS: It is possible to combine objective maternal data with evolving objective neonatal clinical findings to define more efficient strategies for the evaluation and treatment of EOS in term and late preterm infants. Judicious application of our scheme could result in decreased antibiotic treatment in 80 000 to 240 000 US newborns each year.

Seven-Year Experience With a Surveillance Program to Reduce Methicillin-Resistant Staphylococcus aureus Colonization in a Neonatal Intensive Care Unit

OBJECTIVES. The objectives of this study were to determine the incidence rates of neonatal methicillin-resistant Staphylococcus aureus colonization and infection after the implementation of a NICU methicillin-resistant S aureus surveillance and isolation program and to describe the characteristics of infants with methicillin-resistant S aureus colonization and invasive disease. METHODS. From August 2000 through August 2007, all infants admitted to the study NICU were screened for methicillin-resistant S aureus colonization with weekly nasal/rectal swabs; colonized or infected infants were isolated and cared for as a cohort. The annual incidence rates of methicillin-resistant S aureus colonization and infection were monitored, and characteristics of methicillin-resistant S aureus-colonized and -infected infants were compared. Data were collected from infant, maternal, and hospital laboratory records. RESULTS. During the study period, 7997 infants were admitted to the NICU and 102 methicillin-resistant S aureus-colonized or -infected infants (1.3%) were identified. The incidence of methicillin-resistant S aureus decreased progressively from 1.79 cases per 1000 patient-days in 2000 to 0.15 cases per 1000 patient-days in 2005, but the incidence then increased to 1.26 cases per 1000 patient-days in 2007. Fifteen of the 102 case infants (14.7%) had invasive infections; no significant differences between infected and colonized infants were identified. Methicillin-resistant S aureus isolates with 14 different antibiograms were found during the study period. There was a shift from isolates predominantly likely to be hospital-associated in 2000–2004 to those likely to be community-associated in 2006–2007. CONCLUSIONS. A continuous program of weekly methicillin-resistant S aureus surveillance cultures and isolation of affected infants was associated with a variable incidence of methicillin-resistant S aureus colonization over a 7-year study period. Methicillin-resistant S aureus was not eradicated from this tertiary-care NICU, and our data suggest that infants were colonized by multiple different methicillin-resistant S aureus strains during the study period.

Prevention and management of procedural pain in the neonate: An update

The prevention of pain in neonates should be the goal of all pediatricians and health care professionals who work with neonates, not only because it is ethical but also because repeated painful exposures have the potential for deleterious consequences. Neonates at greatest risk of neurodevelopmental impairment as a result of preterm birth (ie, the smallest and sickest) are also those most likely to be exposed to the greatest number of painful stimuli in the NICU. Although there are major gaps in knowledge regarding the most effective way to prevent and relieve pain in neonates, proven and safe therapies are currently underused for routine minor, yet painful procedures. Therefore, every health care facility caring for neonates should implement (1) a pain-prevention program that includes strategies for minimizing the number of painful procedures performed and (2) a pain assessment and management plan that includes routine assessment of pain, pharmacologic and nonpharmacologic therapies for the prevention of pain associated with routine minor procedures, and measures for minimizing pain associated with surgery and other major procedures.

No Change in the Incidence of Ampicillin-Resistant, Neonatal, Early-Onset Sepsis Over 18 Years

OBJECTIVE: The objective of this study was to assess the effect of maternal antibiotic exposure on neonatal early-onset sepsis (EOS) rates over an 18-year period. METHODS: A review was performed of infant and maternal records for all culture- proven cases of EOS in infants delivered at the Brigham and Womens Hospital (Boston, MA) in 1990–2007. RESULTS: Data were analyzed from 335 EOS cases over periods that differed with respect to hospital policy for intrapartum antibiotic prophylaxis against group B Streptococcus (GBS): 1990–1992 (no prophylaxis); 1993–1996 (risk-based); and 1997–2007 (screening-based). The overall incidence of EOS decreased over these periods (3.70 vs 2.23 vs 1.59 cases per 1000 live births; P < .0001). No change in the incidence of infection with ampicillin-resistant organisms was observed overall or among very low birth weight infants. However, an increased proportion of infections were caused by ampicillin- resistant organisms. Mothers of infants with ampicillin-resistant infections were more likely to have been treated with ampicillin (P = .0001). Overall peripartum antibiotic use increased during the study period primarily because of increased use of penicillin G and clindamycin, with no significant change in the use of ampicillin. CONCLUSIONS: Predominant use of penicillin G for GBS prophylaxis resulted in decreased incidence of EOS. No change in the incidence of ampicillin-resistant EOS was observed, but resistant cases were associated with peripartum ampicillin exposure. These findings suggest that obstetricians should consider preferential use of penicillin G for GBS prophylaxis.

Effectiveness of a guideline to reduce vancomycin use in the neonatal intensive care unit.

Background: The Centers for Disease Control and Prevention recommend hospitals develop guidelines for the appropriate use of vancomycin as part of comprehensive antimicrobial stewardship. The objective of this study was to evaluate the effectiveness and safety of a guideline to restrict vancomycin use in the neonatal intensive care unit (NICU). Methods: A vancomycin use guideline was introduced in 2 tertiary care NICUs with low incidences of methicillin-resistant Staphylococcus aureus infections. We compared all infants >72 hours of age who were evaluated for late-onset infection before and after implementation of this guideline. Results: Vancomycin start rates were reduced from 6.9 to 4.5 per 1000 patient-days (35% reduction; P = 0.01) at Brigham and Womens Hospital, and from 17 to 6.4 per 1000 patient-days (62% reduction; P < 0.0001) at Massachusetts General Hospital. The number of infants exposed to vancomycin decreased from 5.2 to 3.1 per 1000 patient-days (40% reduction; P = 0.008) at Brigham and Womens Hospital, and 10.8 to 5.5 per 1000 patient-days (49% reduction; P = 0.009) at Massachusetts General Hospital. Causes of infection, duration of bacteremia, and incidence of complications or deaths attributable to late-onset infection did not change significantly at either institution. Conclusions: Implementation of a NICU vancomycin use guideline significantly reduced exposure of newborns to vancomycin without adversely affecting short-term patient safety. Further studies are required to evaluate the long-term effect of vancomycin restriction on NICU patient safety and microbial ecology, particularly among institutions with higher rates of methicillin-resistant Staphylococcus aureus infections.

Patent Ductus Arteriosus in Preterm Infants.

Despite a large body of basic science and clinical research and clinical experience with thousands of infants over nearly 6 decades,1 there is still uncertainty and controversy about the significance, evaluation, and management of patent ductus arteriosus in preterm infants, resulting in substantial heterogeneity in clinical practice. The purpose of this clinical report is to summarize the evidence available to guide evaluation and treatment of preterm infants with prolonged ductal patency in the first few weeks after birth.

Risk Assessment in Neonatal Early Onset Sepsis

The incidence of neonatal early onset sepsis has declined with the widespread use of intrapartum antibiotic therapies, yet early onset sepsis remains a potentially fatal condition, particularly among very low birth-weight infants. Clinical signs of neonatal infection are nonspecific and may be absent in the immediate postnatal period. Maternal and infant clinical characteristics, as well as infant laboratory values, have been used to identify newborns at risk and to administer empiric antibiotic therapy to prevent progression to more severe illness. Such approaches result in the evaluation of approximately 15% of asymptomatic term and late preterm infants and of nearly all preterm infants. The development of multivariate predictive models may provide more accurate methods of identifying newborns at highest risk and allow for more limited newborn antibiotic exposures.

The apgar score

The Apgar score provides an accepted and convenient method for reporting the status of the newborn infant immediately after birth and the response to resuscitation if needed. The Apgar score alone cannot be considered as evidence of, or a consequence of, asphyxia; does not predict individual neonatal mortality or neurologic outcome; and should not be used for that purpose. An Apgar score assigned during resuscitation is not equivalent to a score assigned to a spontaneously breathing infant. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists encourage use of an expanded Apgar score reporting form that accounts for concurrent resuscitative interventions.

Neonatal early-onset sepsis evaluations among well-appearing infants: projected impact of changes in CDC GBS guidelines

Objective:To determine (a) the proportion of asymptomatic infants born at ⩾35 weeks gestation evaluated for early-onset sepsis (EOS) and exposed to postnatal antibiotics; (b) reasons for and outcomes of the evaluations, and (c) anticipated changes when applying the Centers for Disease Control and Prevention (CDC) 2010 guidelines to this study population.Study Design:Retrospective cohort study of infants born at ⩾35 weeks gestation in 2008–2009 in a large maternity center.Result:Out of the 7226 infants that met the study criteria: 1062 (14.7%) were evaluated for EOS and half of those evaluated, received empiric antibiotics. 70.4% of evaluations were performed owing to maternal intrapartum fever, but 23% were prompted by inadequate Group B Streptococcus (GBS) prophylaxis alone. Three cases of blood culture-proven infection were identified.Conclusion:Improved approaches are needed to identify asymptomatic infants who are at risk for EOS to decrease unnecessary evaluations and antibiotic exposure. Transition to the 2010 CDC GBS guidelines may eliminate a quarter of EOS evaluations among these infants.