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 mL (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 mL have a low probability of IBI. WHAT'S KNOWN ON THIS SUBJECT: Commonly used risk-stratification criteria for febrile infants were either developed .2 decades ago in studies that included relatively few infants with bacteremia and/or bacterial meningitis or include procalcitonin, which is not readily available in some hospitals. WHAT THIS STUDY ADDS: A newly derived score is highly sensitive for the identification of non-ill-appearing febrile infants #60 days old with invasive bacterial infection. Infants with fever by history only, normal urinalysis results, and an absolute neutrophil count ,5185 cells per mL had a low probability of infection.

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%; P = .01), but the specificity was lower (34.5% vs 59.8%; P < .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.

Background Immune reconstitution inflammatory syndrome (IRIS) after initiating highly active antiretroviral therapy (HAART) has not been widely studied in children, especially in resource-poor settings. Methods Retrospective cohort study of HIV-infected children initiating HAART between 2001 and 2006 at a tertiary pediatric hospital in Lima, Peru. Charts were reviewed for 1 year after HAART initiation. IRIS was defined as a HAART-associated adverse event caused by an infectious or inflammatory condition in patients with documented virologic or immunologic success. Results Ninety-one children (52% female) received HAART for at least 1 year. Median age at initiation was 5.7 years; 91% were ART naive and 73% had CDC stage C disease. The incidence of IRIS was 19.8 events per 100 person years (95% CI: 11.5–28.0). Median time to IRIS was 6.6 weeks after HAART initiation (range: 2–32 weeks). There were 18 IRIS events, 11 unmasking and 7 paradoxical. These included associations with Mycobacterium tuberculosis in 4 cases, Bacillus Calmette Guerin lymphadenitis in 1 case, varicella zoster virus in 6 cases and herpes simplex labialis in 6 cases. Children who developed IRIS had a higher baseline HIV viral load (P = 0.02) and an indicator of malnutrition (P = 0.007) before HAART initiation. Conclusion IRIS occurred in 20% of HIV-infected children starting HAART in Peru and was associated with more advanced disease and malnutrition. Future research is needed to examine specific risk factors associated with pediatric IRIS to allow prompt identification and treatment of IRIS.

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.

OBJECTIVES:To determine the association between parenteral antibiotic duration and outcomes in infants #60 days old with bacteremic urinary tract infection (UTI).METHODS: 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 .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).RESULTS: 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-Escherichia coli 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: 25.8 to 12.7) or 30-day all-cause reutilization (risk difference: 3%; 95% confidence interval: 214.5 to 20.6).CONCLUSIONS: 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.WHAT'S KNOWN ON THIS SUBJECT: Infants #60 days old with bacteremic urinary tract infection often receive prolonged courses of parenteral antibiotics. The safety of short-course parenteral antibiotic therapy has not been established in this population. WHAT THIS STUDY ADDS:In this multicenter study of infants #60 days old with bacteremic urinary tract infection, infants receiving #7 days of parenteral antibiotics did not experience more frequent UTI recurrence or hospital reutilization compared with infants receiving .7 days of parenteral therapy.

OBJECTIVES: To describe the initial clinical response and care escalation needs for children with urinary tract infections (UTIs) resistant to third-generation cephalosporins while on discordant antibiotics. METHODS: We performed a retrospective study of children &lt;18 years old presenting to an acute care setting of 5 children’s hospitals and a large managed care organization from 2012 to 2017 with third-generation cephalosporin-resistant UTIs (defined as the growth of ≥50 000 colony-forming units per mL of Escherichia coli or Klebsiella spp. nonsusceptible to ceftriaxone with a positive urinalysis). We included children started on discordant antibiotics who had follow-up when culture susceptibilities resulted. Outcomes were escalation of care (emergency department visit, hospital admission, or ICU transfer while on discordant therapy) and clinical response at follow-up (classified as improved or not improved). RESULTS: Of the 316 children included, 78% were girls and the median age was 2.4 years (interquartile range 0.6–6.5). Children were evaluated in the emergency department (56%) or clinic (43%), and 90% were started on a cephalosporin. A total of 7 of 316 children (2.2%; 95% confidence interval 0.8%–4.5%) experienced escalation of care. For the 230 children (73%) with clinical response recorded, 192 of 230 (83.5%; 95% confidence interval 78.0%–88.0%) experienced clinical improvement. In children with repeat urine testing while on discordant therapy, pyuria improved or resolved in 16 of 19 (84%) and urine cultures sterilized in 11 of 17 (65%). CONCLUSIONS: Most children with third-generation cephalosporin-resistant UTIs started on discordant antibiotics experienced initial clinical improvement, and few required escalation of care. Our findings suggest that narrow-spectrum empiric therapy is appropriate while awaiting final urine culture results.

BackgroundPossible serious bacterial infection (PBSI) is a major cause of neonatal mortality worldwide. We studied risk factors for PSBI in a large rural population in central India where facility deliveries have increased as a result of a government financial assistance program.MethodsWe studied 37,379 pregnant women and their singleton live born infants with birth weight ≥ 1.5 kg from 20 rural primary health centers around Nagpur, India, using data from the 2010–13 population-based Maternal and Newborn Health Registry supported by NICHD’s Global Network for Women’s and Children’s Health Research. Factors associated with PSBI were identified using multivariable Poisson regression.ResultsTwo thousand one hundred twenty-three infants (6 %) had PSBI. Risk factors for PSBI included nulliparity (RR 1.13, 95 % CI 1.03–1.23), parity > 2 (RR 1.30, 95 % CI 1.07–1.57) compared to parity 1–2, first antenatal care visit in the 2nd/3rd trimester (RR 1.46, 95 % CI 1.08–1.98) compared to 1st trimester, administration of antenatal corticosteroids (RR 2.04, 95 % CI 1.60–2.61), low birth weight (RR 3.10, 95 % CI 2.17–4.42), male sex (RR 1.20, 95 % CI 1.10–1.31) and lack of early initiation of breastfeeding (RR 3.87, 95 % CI 2.69–5.58).ConclusionInfants who are low birth weight, born to mothers who present late to antenatal care or receive antenatal corticosteroids, or born to nulliparous women or those with a parity > 2, could be targeted for interventions before and after delivery to improve early recognition of signs and symptoms of PSBI and prompt referral. There also appears to be a need for a renewed focus on promoting early initiation of breastfeeding following delivery in facilities.Trial registrationThis trial is registered at ClinicalTrials.gov (NCT01073475).Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-016-3688-3) contains supplementary material, which is available to authorized users.

Objective To determine factors associated with adverse outcomes among febrile young infants with invasive bacterial infections (IBI), i.e., bacteremia and/or bacterial meningitis. Study design 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. Results 350 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: 29/71 (40.8%) with bacterial meningitis vs. 13/279 (4.7%) with bacteremia without meningitis (36.2% difference, 95% CI 25.1% to 48.0%; P < .001). On adjusted analysis, bacterial meningitis (adjusted odds ratio [aOR] 16.3, 95% CI 6.5 to 41.0; P<0.001), prematurity (aOR 7.1, 95% CI2.6 to 19.7; P<0.001), and ill appearance (aOR 3.8, 95% CI 1.6 to 9.1; P=0.002) were associated with adverse outcomes. Among infants who were born at term, not ill appearing, and had bacteremia without meningitis, only 2/184 (1.1%) had adverse outcomes, and there were no deaths. Conclusions 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.