Epidemiology and Etiology of Invasive Bacterial Infection in Infants ≤60 Days Old Treated in Emergency Departments.

2018

2018 May 18

1097-6833

OBJECTIVES: To help guide empiric treatment of infants ≤60 days old with suspected invasive bacterial infection by describing pathogens and their antimicrobial susceptibilities.

STUDY DESIGN: Cross-sectional study of infants ≤60 days old with invasive bacterial infection (bacteremia and/or bacterial meningitis) evaluated in the emergency departments of 11 children's hospitals between July 1, 2011 and June 30, 2016. Each site's microbiology laboratory database or electronic medical record system was queried to identify infants from whom a bacterial pathogen was isolated from either blood or cerebrospinal fluid. Medical records of these infants were reviewed to confirm the presence of a pathogen and to obtain demographic, clinical, and laboratory data.

RESULTS: Of the 442 infants with invasive bacterial infection, 353 (79.9%) had bacteremia without meningitis, 64 (14.5%) had bacterial meningitis with bacteremia, and 25 (5.7%) had bacterial meningitis without bacteremia. The peak number of cases of invasive bacterial infection occurred in the second week of life; 364 (82.4%) infants were febrile. Group B streptococcus was the most common pathogen identified (36.7%), followed by Escherichia coli (30.8%), Staphylococcus aureus (9.7%), and Enterococcus spp (6.6%). Overall, 96.8% of pathogens were susceptible to ampicillin plus a third-generation cephalosporin, 96.0% to ampicillin plus gentamicin, and 89.2% to third-generation cephalosporins alone.

CONCLUSIONS: For most infants ≤60 days old evaluated in a pediatric emergency department for suspected invasive bacterial infection, the combination of ampicillin plus either gentamicin or a third-generation cephalosporin is an appropriate empiric antimicrobial treatment regimen. Of the pathogens isolated from infants with invasive bacterial infection, 11% were resistant to third-generation cephalosporins alone.

10.1016/j.jpeds.2018.04.033

J. Pediatr.

29784512

Time to Pathogen Detection for Non-ill Versus Ill-Appearing Infants ≤60 Days Old With Bacteremia and Meningitis.

2018

2018 Jun 28

2154-1663

OBJECTIVES: We sought to determine the time to pathogen detection in blood and cerebrospinal fluid (CSF) for infants ≤60 days old with bacteremia and/or bacterial meningitis and to explore whether time to pathogen detection differed for non-ill-appearing and ill-appearing infants.

METHODS: We included infants ≤60 days old with bacteremia and/or bacterial meningitis evaluated in the emergency departments of 10 children's hospitals between July 1, 2011, and June 30, 2016. The microbiology laboratories at each site were queried to identify infants in whom a bacterial pathogen was isolated from blood and/or CSF. Medical records were then reviewed to confirm the presence of a pathogen and to extract demographic characteristics, clinical appearance, and the time to pathogen detection.

RESULTS: Among 360 infants with bacteremia, 316 (87.8%) pathogens were detected within 24 hours and 343 (95.3%) within 36 hours. A lower proportion of non-ill-appearing infants with bacteremia had a pathogen detected on blood culture within 24 hours compared with ill-appearing infants (85.0% vs 92.9%, respectively; = .03). Among 62 infants with bacterial meningitis, 55 (88.7%) pathogens were detected within 24 hours and 59 (95.2%) were detected within 36 hours, with no difference based on ill appearance.

CONCLUSIONS: Among infants ≤60 days old with bacteremia and/or bacterial meningitis, pathogens were commonly identified from blood or CSF within 24 and 36 hours. However, clinicians must weigh the potential for missed bacteremia in non-ill-appearing infants discharged within 24 hours against the overall low prevalence of infection.

10.1542/hpeds.2018-0002

Hosp Pediatr

29954839

Risk Stratification of Febrile Infants ≤60 Days Old Without Routine Lumbar Puncture.

2018

2018 Nov 13

1098-4275

: media-1vid110.1542/5840460609001PEDS-VA_2018-1879 OBJECTIVES: To evaluate the Rochester and modified Philadelphia criteria for the risk stratification of febrile infants with invasive bacterial infection (IBI) who do not appear ill without routine cerebrospinal fluid (CSF) testing.

METHODS: We performed a case-control study of febrile infants ≤60 days old presenting to 1 of 9 emergency departments from 2011 to 2016. For each infant with IBI (defined as a blood [bacteremia] and/or CSF [bacterial meningitis] culture with growth of a pathogen), controls without IBI were matched by site and date of visit. Infants were excluded if they appeared ill or had a complex chronic condition or if data for any component of the Rochester or modified Philadelphia criteria were missing.

RESULTS: Overall, 135 infants with IBI (118 [87.4%] with bacteremia without meningitis and 17 [12.6%] with bacterial meningitis) and 249 controls were included. The sensitivity of the modified Philadelphia criteria was higher than that of the Rochester criteria (91.9% vs 81.5%; = .01), but the specificity was lower (34.5% vs 59.8%; < .001). Among 67 infants >28 days old with IBI, the sensitivity of both criteria was 83.6%; none of the 11 low-risk infants had bacterial meningitis. Of 68 infants ≤28 days old with IBI, 14 (20.6%) were low risk per the Rochester criteria, and 2 had meningitis.

CONCLUSIONS: The modified Philadelphia criteria had high sensitivity for IBI without routine CSF testing, and all infants >28 days old with bacterial meningitis were classified as high risk. Because some infants with bacteremia were classified as low risk, infants discharged from the emergency department without CSF testing require close follow-up.

10.1542/peds.2018-1879

Pediatrics

30425130

A Prediction Model to Identify Febrile Infants ≤60 Days at Low Risk of Invasive Bacterial Infection.

2019

2019 Jun 05

1098-4275

OBJECTIVES: To derive and internally validate a prediction model for the identification of febrile infants ≤60 days old at low probability of invasive bacterial infection (IBI).

METHODS: We conducted a case-control study of febrile infants ≤60 days old who presented to the emergency departments of 11 hospitals between July 1, 2011 and June 30, 2016. Infants with IBI, defined by growth of a pathogen in blood (bacteremia) and/or cerebrospinal fluid (bacterial meningitis), were matched by hospital and date of visit to 2 control patients without IBI. Ill-appearing infants and those with complex chronic conditions were excluded. Predictors of IBI were identified with multiple logistic regression and internally validated with 10-fold cross-validation, and an IBI score was calculated.

RESULTS: We included 181 infants with IBI (155 [85.6%] with bacteremia without meningitis and 26 [14.4%] with bacterial meningitis) and 362 control patients. Twenty-three infants with IBI (12.7%) and 138 control patients (38.1%) had fever by history only. Four predictors of IBI were identified (area under the curve 0.83 [95% confidence interval (CI): 0.79-0.86]) and incorporated into an IBI score: age <21 days (1 point), highest temperature recorded in the emergency department 38.0-38.4°C (2 points) or ≥38.5°C (4 points), absolute neutrophil count ≥5185 cells per μL (2 points), and abnormal urinalysis results (3 points). The sensitivity and specificity of a score ≥2 were 98.8% (95% CI: 95.7%-99.9%) and 31.3% (95% CI: 26.3%-36.6%), respectively. All 26 infants with meningitis had scores ≥2.

CONCLUSIONS: Infants ≤60 days old with fever by history only, a normal urinalysis result, and an absolute neutrophil count <5185 cells per μL have a low probability of IBI.

10.1542/peds.2018-3604

Pediatrics

31167938

Febrile Infants ≤60 Days Old With Positive Urinalysis Results and Invasive Bacterial Infections.

2020

2020 Nov 25

2154-1671

OBJECTIVES: We aimed to describe the clinical and laboratory characteristics of febrile infants ≤60 days old with positive urinalysis results and invasive bacterial infections (IBI).

METHODS: We performed a planned secondary analysis of a retrospective cohort study of febrile infants ≤60 days old with IBI who presented to 11 emergency departments from July 1, 2011, to June 30, 2016. For this subanalysis, we included infants with IBI and positive urinalysis results. We analyzed the sensitivity of high-risk past medical history (PMH) (prematurity, chronic medical condition, or recent antimicrobial receipt), ill appearance, and/or abnormal white blood cell (WBC) count (<5000 or >15 000 cells/μL) for identification of IBI.

RESULTS: Of 148 febrile infants with positive urinalysis results and IBI, 134 (90.5%) had bacteremia without meningitis and 14 (9.5%) had bacterial meningitis (11 with concomitant bacteremia). Thirty-five infants (23.6%) with positive urinalysis results and IBI did not have urinary tract infections. The presence of high-risk PMH, ill appearance, and/or abnormal WBC count had a sensitivity of 53.4% (95% confidence interval: 45.0-61.6) for identification of IBI. Of the 14 infants with positive urinalysis results and concomitant bacterial meningitis, 7 were 29 to 60 days old. Six of these 7 infants were ill-appearing or had an abnormal WBC count. The other infant had bacteremia with cerebrospinal fluid pleocytosis after antimicrobial pretreatment and was treated for meningitis.

CONCLUSIONS: The sensitivity of high-risk PMH, ill appearance, and/or abnormal WBC count is suboptimal for identifying febrile infants with positive urinalysis results at low risk for IBI. Most infants with positive urinalysis results and bacterial meningitis are ≤28 days old, ill-appearing, or have an abnormal WBC count.

10.1542/hpeds.2020-000638

Hosp Pediatr

33239319

Characteristics of Afebrile Infants ≤60 Days of Age With Invasive Bacterial Infections.

2021

100-105

2021 Jan

2154-1671

OBJECTIVES: To describe the characteristics and outcomes of afebrile infants ≤60 days old with invasive bacterial infection (IBI).

METHODS: We conducted a secondary analysis of a cross-sectional study of infants ≤60 days old with IBI presenting to the emergency departments (EDs) of 11 children's hospitals from 2011 to 2016. We classified infants as afebrile if there was absence of a temperature ≥38°C at home, at the referring clinic, or in the ED. Bacteremia and bacterial meningitis were defined as pathogenic bacterial growth from a blood and/or cerebrospinal fluid culture.

RESULTS: Of 440 infants with IBI, 78 (18%) were afebrile. Among afebrile infants, 62 (79%) had bacteremia without meningitis and 16 (20%) had bacterial meningitis (10 with concomitant bacteremia). Five infants (6%) died, all with bacteremia. The most common pathogens were (35%), (16%), and (16%). Sixty infants (77%) had an abnormal triage vital sign (temperature <36°C, heart rate ≥181 beats per minute, or respiratory rate ≥66 breaths per minute) or a physical examination abnormality (ill appearance, full or depressed fontanelle, increased work of breathing, or signs of focal infection). Forty-three infants (55%) had ≥1 of the following laboratory abnormalities: white blood cell count <5000 or >15 000 cells per μL, absolute band count >1500 cells per μl, or positive urinalysis. Presence of an abnormal vital sign, examination finding, or laboratory test result had a sensitivity of 91% (95% confidence interval 82%-96%) for IBI.

CONCLUSIONS: Most afebrile young infants with an IBI had vital sign, examination, or laboratory abnormalities. Future studies should evaluate the predictive ability of these criteria in afebrile infants undergoing evaluation for IBI.

10.1542/hpeds.2020-002204

Hosp Pediatr

33318052

Height of fever and invasive bacterial infection.

2020

2020 Aug 20

1468-2044

<p><strong>OBJECTIVE: </strong>We aimed to evaluate the association of height of fever with invasive bacterial infection (IBI) among febrile infants &lt;=60 days of age.</p>

<p><strong>METHODS: </strong>In a secondary analysis of a multicentre case-control study of non-ill-appearing febrile infants &lt;=60 days of age, we compared the maximum temperature (at home or in the emergency department) for infants with and without IBI. We then computed interval likelihood ratios (iLRs) for the diagnosis of IBI at each half-degree Celsius interval.</p>

<p><strong>RESULTS: </strong>The median temperature was higher for infants with IBI (38.8°C; IQR 38.4-39.2) compared with those without IBI (38.4°C; IQR 38.2-38.9) (p&lt;0.001). Temperatures 39°C-39.4°C and 39.5°C-39.9°C were associated with a higher likelihood of IBI (iLR 2.49 and 3.40, respectively), although 30.4% of febrile infants with IBI had maximum temperatures &lt;38.5°C.</p>

<p><strong>CONCLUSIONS: </strong>Although IBI is more likely with higher temperatures, height of fever alone should not be used for risk stratification of febrile infants.</p>

10.1136/archdischild-2019-318548

Arch. Dis. Child.

32819913

Parenteral Antibiotic Therapy Duration in Young Infants With Bacteremic Urinary Tract Infections.

2019

2019 Aug 20

1098-4275

<p><strong>OBJECTIVES: </strong>To determine the association between parenteral antibiotic duration and outcomes in infants ≤60 days old with bacteremic urinary tract infection (UTI).</p>

<p><strong>METHODS: </strong>This multicenter retrospective cohort study included infants ≤60 days old who had concomitant growth of a pathogen in blood and urine cultures at 11 children's hospitals between 2011 and 2016. Short-course parenteral antibiotic duration was defined as ≤7 days, and long-course parenteral antibiotic duration was defined as &gt;7 days. Propensity scores, calculated using patient characteristics, were used to determine the likelihood of receiving long-course parenteral antibiotics. We conducted inverse probability weighting to achieve covariate balance and applied marginal structural models to the weighted population to examine the association between parenteral antibiotic duration and outcomes (30-day UTI recurrence, 30-day all-cause reutilization, and length of stay).</p>

<p><strong>RESULTS: </strong>Among 115 infants with bacteremic UTI, 58 (50%) infants received short-course parenteral antibiotics. Infants who received long-course parenteral antibiotics were more likely to be ill appearing and have growth of a non- organism. There was no difference in adjusted 30-day UTI recurrence between the long- and short-course groups (adjusted risk difference: 3%; 95% confidence interval: -5.8 to 12.7) or 30-day all-cause reutilization (risk difference: 3%; 95% confidence interval: -14.5 to 20.6).</p>

<p><strong>CONCLUSIONS: </strong>Young infants with bacteremic UTI who received ≤7 days of parenteral antibiotics did not have more frequent recurrent UTIs or hospital reutilization compared with infants who received long-course therapy. Short-course parenteral therapy with early conversion to oral antibiotics may be considered in this population.</p>

10.1542/peds.2018-3844

Pediatrics

31431480

Factors Associated with Adverse Outcomes among Febrile Young Infants with Invasive Bacterial Infections.

2018

2018 Oct 05

1097-6833

<p><strong>OBJECTIVE: </strong>To determine factors associated with adverse outcomes among febrile young infants with invasive bacterial infections (IBIs) (ie, bacteremia and/or bacterial meningitis).</p>

<p><strong>STUDY DESIGN: </strong>Multicenter, retrospective cohort study (July 2011-June 2016) of febrile infants ≤60 days of age with pathogenic bacterial growth in blood and/or cerebrospinal fluid. Subjects were identified by query of local microbiology laboratory and/or electronic medical record systems, and clinical data were extracted by medical record review. Mixed-effect logistic regression was employed to determine clinical factors associated with 30-day adverse outcomes, which were defined as death, neurologic sequelae, mechanical ventilation, or vasoactive medication receipt.</p>

<p><strong>RESULTS: </strong>Three hundred fifty infants met inclusion criteria; 279 (79.7%) with bacteremia without meningitis and 71 (20.3%) with bacterial meningitis. Forty-two (12.0%) infants had a 30-day adverse outcome: 29 of 71 (40.8%) with bacterial meningitis vs 13 of 279 (4.7%) with bacteremia without meningitis (36.2% difference, 95% CI 25.1%-48.0%; P &lt; .001). On adjusted analysis, bacterial meningitis (aOR 16.3, 95% CI 6.5-41.0; P &lt; .001), prematurity (aOR 7.1, 95% CI 2.6-19.7; P &lt; .001), and ill appearance (aOR 3.8, 95% CI 1.6-9.1; P = .002) were associated with adverse outcomes. Among infants who were born at term, not ill appearing, and had bacteremia without meningitis, only 2 of 184 (1.1%) had adverse outcomes, and there were no deaths.</p>

<p><strong>CONCLUSIONS: </strong>Among febrile infants ≤60 days old with IBI, prematurity, ill appearance, and bacterial meningitis (vs bacteremia without meningitis) were associated with adverse outcomes. These factors can inform clinical decision-making for febrile young infants with IBI.</p>

10.1016/j.jpeds.2018.08.066

J. Pediatr.

30297292

Empiric Antibiotic Use and Susceptibility in Infants With Bacterial Infections: A Multicenter Retrospective Cohort Study.

2017

2017 Jul 20

2154-1663

<p><strong>OBJECTIVES: </strong>To assess hospital differences in empirical antibiotic use, bacterial epidemiology, and antimicrobial susceptibility for common antibiotic regimens among young infants with urinary tract infection (UTI), bacteremia, or bacterial meningitis.</p>

<p><strong>METHODS: </strong>We reviewed medical records from infants &lt;90 days old presenting to 8 US children's hospitals with UTI, bacteremia, or meningitis. We used the Pediatric Health Information System database to identify cases and empirical antibiotic use and medical record review to determine infection, pathogen, and antimicrobial susceptibility patterns. We compared hospital-level differences in antimicrobial use, pathogen, infection site, and antimicrobial susceptibility.</p>

<p><strong>RESULTS: </strong>We identified 470 infants with bacterial infections: 362 (77%) with UTI alone and 108 (23%) with meningitis or bacteremia. Infection type did not differ across hospitals (P = .85). Empirical antibiotic use varied across hospitals (P &lt; .01), although antimicrobial susceptibility patterns for common empirical regimens were similar. A third-generation cephalosporin would have empirically treated 90% of all ages, 89% in 7- to 28-day-olds, and 91% in 29- to 89-day-olds. The addition of ampicillin would have improved coverage in only 4 cases of bacteremia and meningitis. Ampicillin plus gentamicin would have treated 95%, 89%, and 97% in these age groups, respectively.</p>

<p><strong>CONCLUSIONS: </strong>Empirical antibiotic use differed across regionally diverse US children's hospitals in infants &lt;90 days old with UTI, bacteremia, or meningitis. Antimicrobial susceptibility to common antibiotic regimens was similar across hospitals, and adding ampicillin to a third-generation cephalosporin minimally improves coverage. Our findings support incorporating empirical antibiotic recommendations into national guidelines for infants with suspected bacterial infection.</p>

10.1542/hpeds.2016-0162

Hosp Pediatr

28729240