First name
Michael
Middle name
W
Last name
Kuzniewicz

Title

Time to positivity of blood cultures in neonatal late-onset bacteraemia.

Year of Publication

2022

Number of Pages

583-588

Date Published

11/2022

ISSN Number

1468-2052

Abstract

OBJECTIVE: To determine the time to positivity (TTP) of blood cultures among infants with late-onset bacteraemia and predictors of TTP >36 hours.

DESIGN: Retrospective cohort study.

SETTING: 16 birth centres in two healthcare systems.

PATIENTS: Infants with positive blood cultures obtained >72 hours after birth.

OUTCOME: The main outcome was TTP, defined as the time interval from specimen collection to when a neonatal provider was notified of culture growth. TTP analysis was restricted to the first positive culture per infant. Patient-specific and infection-specific factors were analysed for association with TTP >36 hours.

RESULTS: Of 10 235 blood cultures obtained from 3808 infants, 1082 (10.6%) were positive. Restricting to bacterial pathogens and the first positive culture, the median TTP (25th-75th percentile) for 428 cultures was 23.5 hours (18.4-29.9); 364 (85.0%) resulted in 36 hours. Excluding coagulase-negative staphylococci (CoNS), 275 of 294 (93.5%) cultures were flagged positive by 36 hours. In a multivariable model, CoNS isolation and antibiotic pretreatment were significantly associated with increased odds of TTP >36 hours. Projecting a 36-hour empiric duration at one site and assuming that all negative evaluations were associated with an empiric course of antibiotics, we estimated that 1164 doses of antibiotics would be avoided in 629 infants over 10 years, while delaying a subsequent antibiotic dose in 13 infants with bacteraemia.

CONCLUSIONS: Empiric antibiotic administration in late-onset infection evaluations (not targeting CoNS) can be stopped at 36 hours. Longer durations (48 hours) should be considered when there is pretreatment or antibiotic therapy is directed at CoNS.

DOI

10.1136/archdischild-2021-323416

Alternate Title

Arch Dis Child Fetal Neonatal Ed

PMID

35273079
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Title

Stratification of risk of early-onset sepsis in newborns ≥ 34 weeks' gestation.

Year of Publication

2014

Number of Pages

30-6

Date Published

2014 Jan

ISSN Number

1098-4275

Abstract

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.

DOI

10.1542/peds.2013-1689

Alternate Title

Pediatrics

PMID

24366992
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Title

Time to positivity of blood cultures in neonatal late-onset bacteraemia.

Year of Publication

2022

Number of Pages

Date Published

2022 Mar 10

ISSN Number

1468-2052

Abstract

<p><strong>OBJECTIVE: </strong>To determine the time to positivity (TTP) of blood cultures among infants with late-onset bacteraemia and predictors of TTP &gt;36 hours.</p>

<p><strong>DESIGN: </strong>Retrospective cohort study.</p>

<p><strong>SETTING: </strong>16 birth centres in two healthcare systems.</p>

<p><strong>PATIENTS: </strong>Infants with positive blood cultures obtained &gt;72 hours after birth.</p>

<p><strong>OUTCOME: </strong>The main outcome was TTP, defined as the time interval from specimen collection to when a neonatal provider was notified of culture growth. TTP analysis was restricted to the first positive culture per infant. Patient-specific and infection-specific factors were analysed for association with TTP &gt;36 hours.</p>

<p><strong>RESULTS: </strong>Of 10 235 blood cultures obtained from 3808 infants, 1082 (10.6%) were positive. Restricting to bacterial pathogens and the first positive culture, the median TTP (25th-75th percentile) for 428 cultures was 23.5 hours (18.4-29.9); 364 (85.0%) resulted in 36 hours. Excluding coagulase-negative staphylococci (CoNS), 275 of 294 (93.5%) cultures were flagged positive by 36 hours. In a multivariable model, CoNS isolation and antibiotic pretreatment were significantly associated with increased odds of TTP &gt;36 hours. Projecting a 36-hour empiric duration at one site and assuming that all negative evaluations were associated with an empiric course of antibiotics, we estimated that 1164 doses of antibiotics would be avoided in 629 infants over 10 years, while delaying a subsequent antibiotic dose in 13 infants with bacteraemia.</p>

<p><strong>CONCLUSIONS: </strong>Empiric antibiotic administration in late-onset infection evaluations (not targeting CoNS) can be stopped at 36 hours. Longer durations (48 hours) should be considered when there is pretreatment or antibiotic therapy is directed at CoNS.</p>

DOI

10.1136/archdischild-2021-323416

Alternate Title

Arch Dis Child Fetal Neonatal Ed

PMID

35273079
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Title

National Healthcare Safety Network 2018 Baseline Neonatal Standardized Antimicrobial Administration Ratios.

Year of Publication

2022

Number of Pages

Date Published

2022 Jan 24

ISSN Number

2154-1671

Abstract

<p><strong>BACKGROUND: </strong>The microbiologic etiologies, clinical manifestations, and antimicrobial treatment of neonatal infections differ substantially from infections in adult and pediatric patient populations. In 2019, the Centers for Disease Control and Prevention developed neonatal-specific (Standardized Antimicrobial Administration Ratios SAARs), a set of risk-adjusted antimicrobial use metrics that hospitals participating in the National Healthcare Safety Network's (NHSN's) antimicrobial use surveillance can use in their antibiotic stewardship programs (ASPs).</p>

<p><strong>METHODS: </strong>The Centers for Disease Control and Prevention, in collaboration with the Vermont Oxford Network, identified eligible patient care locations, defined SAAR agent categories, and implemented neonatal-specific NHSN Annual Hospital Survey questions to gather hospital-level data necessary for risk adjustment. SAAR predictive models were developed using 2018 data reported to NHSN from eligible neonatal units.</p>

<p><strong>RESULTS: </strong>The 2018 baseline neonatal SAAR models were developed for 7 SAAR antimicrobial agent categories using data reported from 324 neonatal units in 304 unique hospitals. Final models were used to calculate predicted antimicrobial days, the SAAR denominator, for level II neonatal special care nurseries and level II/III, III, and IV NICUs.</p>

<p><strong>CONCLUSIONS: </strong>NHSN's initial set of neonatal SAARs provides a way for hospital ASPs to assess whether antimicrobial agents in their facility are used at significantly higher or lower rates compared with a national baseline or whether an individual SAAR value is above or below a specific percentile on a given SAAR distribution, which can prompt investigations into prescribing practices and inform ASP interventions.</p>

DOI

10.1542/hpeds.2021-006253

Alternate Title

Hosp Pediatr

PMID

35075483
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Title

Antibiotic stewardship for early-onset sepsis.

Year of Publication

2020

Number of Pages

151325

Date Published

2020 Oct 12

ISSN Number

1558-075X

Abstract

<p>Antibiotics are administered to the vast majority of preterm newborns and to a substantial proportion of term infants in the hours after birth due to risk for early-onset sepsis. The approaches taken to determine which newborns should be evaluated for early-onset sepsis, and what type and duration of antibiotics are administered, are important elements of neonatal antibiotic stewardship. The use of multivariate prediction models for sepsis risk assessment among infants born ≥35 weeks' gestation can safely reduce the use of empiric antibiotic therapy. Approaches incorporating serial physical examination may also contribute to decreasing empiric antibiotic exposure among such infants. Among infants born &lt;35 weeks' gestation, delivery characteristics can be used to identify preterm infants at low enough risk of early infection that empiric therapies are not required. Data informing the epidemiology, microbiology and antibiotic susceptibility patterns of early-onset sepsis pathogens can be used to optimize antibiotic choice for empiric and targeted antibiotic therapy to ensure that effective therapies are administered, while decreasing the risks associated with broad-spectrum antibiotic exposure. Optimal use of blood culture and time to positivity data can also contribute to decreasing the risks associated with prolonged antibiotic administration in the face of sterile cultures.</p>

DOI

10.1016/j.semperi.2020.151325

Alternate Title

Semin Perinatol

PMID

33221072
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Title

Time to Positivity of Neonatal Blood Cultures for Early-onset Sepsis.

Year of Publication

2020

Number of Pages

Date Published

2020 May 05

ISSN Number

1532-0987

Abstract

<p><strong>BACKGROUND: </strong>In newborns at risk for early-onset sepsis, empiric antibiotics are often initiated while awaiting the results of blood cultures. The duration of empiric therapy can be guided by the time to positivity (TTP) of blood cultures. The objective of the study was to determine the TTP of neonatal blood cultures for early-onset sepsis and the factors which may impact TTP.</p>

<p><strong>METHODS: </strong>Observational study of blood cultures growing pathogenic species obtained within 72 hours of birth from infants born at 23-42 weeks gestation, at 19 hospitals in Northern California, Boston, and Philadelphia. TTP was defined as the time from blood culture collection to the time organism growth was reported by the microbiology laboratory.</p>

<p><strong>RESULTS: </strong>A total of 594 blood cultures growing pathogenic bacteria were identified. Group B Streptococcus and Escherichia coli accounted for 74% of blood culture isolates. Median TTP was 21.0 hours (interquartile range, 17.1-25.3 hours). Blood cultures were identified as positive by 24 hours after they were obtained in 68% of cases; by 36 hours in 94% of cases; and by 48 hours in 97% of cases. Neither the administration of maternal intrapartum antibiotic prophylaxis, gestational age &lt;35 weeks, nor blood culture system impacted median TTP.</p>

<p><strong>CONCLUSIONS: </strong>Pathogens are isolated by 36 hours after blood culture collection in 94% of neonatal early blood cultures, regardless of maternal antibiotic administration. TTP information can inform decisions regarding the duration of empiric neonatal antibiotic therapies.</p>

DOI

10.1097/INF.0000000000002632

Alternate Title

Pediatr. Infect. Dis. J.

PMID

32379197
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Title

A Quantitative, Risk-Based Approach to the Management of Neonatal Early-Onset Sepsis.

Year of Publication

2017

Number of Pages

Date Published

2017 Feb 20

ISSN Number

2168-6211

Abstract

<p><strong>Importance: </strong>Current algorithms for management of neonatal early-onset sepsis (EOS) result in medical intervention for large numbers of uninfected infants. We developed multivariable prediction models for estimating the risk of EOS among late preterm and term infants based on objective data available at birth and the newborn's clinical status.</p>

<p><strong>Objectives: </strong>To examine the effect of neonatal EOS risk prediction models on sepsis evaluations and antibiotic use and assess their safety in a large integrated health care system.</p>

<p><strong>Design, Setting, and Participants: </strong>The study cohort includes 204 485 infants born at 35 weeks' gestation or later at a Kaiser Permanente Northern California hospital from January 1, 2010, through December 31, 2015. The study compared 3 periods when EOS management was based on (1) national recommended guidelines (baseline period [January 1, 2010, through November 31, 2012]), (2) multivariable estimates of sepsis risk at birth (learning period [December 1, 2012, through June 30, 2014]), and (3) the multivariable risk estimate combined with the infant's clinical condition in the first 24 hours after birth (EOS calculator period [July 1, 2014, through December 31, 2015]).</p>

<p><strong>Main Outcomes and Measures: </strong>The primary outcome was antibiotic administration in the first 24 hours. Secondary outcomes included blood culture use, antibiotic administration between 24 and 72 hours, clinical outcomes, and readmissions for EOS.</p>

<p><strong>Results: </strong>The study cohort included 204 485 infants born at 35 weeks' gestation or later: 95 343 in the baseline period (mean [SD] age, 39.4 [1.3] weeks; 46 651 male [51.0%]; 37 007 white, non-Hispanic [38.8%]), 52 881 in the learning period (mean [SD] age, 39.3 [1.3] weeks; 27 067 male [51.2%]; 20 175 white, non-Hispanic [38.2%]), and 56 261 in the EOS calculator period (mean [SD] age, 39.4 [1.3] weeks; 28 575 male [50.8%]; 20 484 white, non-Hispanic [36.4%]). In a comparison of the baseline period with the EOS calculator period, blood culture use decreased from 14.5% to 4.9% (adjusted difference, -7.7%; 95% CI, -13.1% to -2.4%). Empirical antibiotic administration in the first 24 hours decreased from 5.0% to 2.6% (adjusted difference, -1.8; 95% CI, -2.4% to -1.3%). No increase in antibiotic use occurred between 24 and 72 hours after birth; use decreased from 0.5% to 0.4% (adjusted difference, 0.0%; 95% CI, -0.1% to 0.2%). The incidence of culture-confirmed EOS was similar during the 3 periods (0.3% in the baseline period, 0.3% in the learning period, and 0.2% in the EOS calculator period). Readmissions for EOS (within 7 days of birth) were rare in all periods (5.2 per 100 000 births in the baseline period, 1.9 per 100 000 births in the learning period, and 5.3 per 100 000 births in the EOS calculator period) and did not differ statistically (P = .70). Incidence of adverse clinical outcomes, including need for inotropes, mechanical ventilation, meningitis, and death, was unchanged after introduction of the EOS calculator.</p>

<p><strong>Conclusions and Relevance: </strong>Clinical care algorithms based on individual infant estimates of EOS risk derived from a multivariable risk prediction model reduced the proportion of newborns undergoing laboratory testing and receiving empirical antibiotic treatment without apparent adverse effects.</p>

DOI

10.1001/jamapediatrics.2016.4678

Alternate Title

JAMA Pediatr

PMID

28241253
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