Marie Wang

All Publications

• Testing for Meningitis in Febrile Well-Appearing Young Infants With a Positive Urinalysis. Pediatrics Wang, M. E., Biondi, E. A., McCulloh, R. J., Garber, M. D., Natt, B. C., Lucas, B. P., Schroeder, A. R. 2019

  Abstract

  To determine factors associated with cerebrospinal fluid (CSF) testing in febrile young infants with a positive urinalysis and assess the probability of delayed diagnosis of bacterial meningitis in infants treated for urinary tract infection (UTI) without CSF testing.We performed a retrospective cohort study using data from the Reducing Excessive Variability in Infant Sepsis Evaluation quality improvement project. A total of 20 570 well-appearing febrile infants 7 to 60 days old presenting to 124 hospitals from 2015 to 2017 were included. A mixed-effects logistic regression was conducted to determine factors associated with CSF testing. Delayed meningitis was defined as a new diagnosis of bacterial meningitis within 7 days of discharge.Overall, 3572 infants had a positive urinalysis; 2511 (70.3%) underwent CSF testing. There was wide variation by site, with CSF testing rates ranging from 64% to 100% for infants 7 to 30 days old and 10% to 100% for infants 31 to 60 days old. Factors associated with CSF testing included: age 7 to 30 days (adjusted odds ratio [aOR]: 4.6; 95% confidence interval [CI]: 3.8-5.5), abnormal inflammatory markers (aOR: 2.2; 95% CI: 1.8-2.5), and site volume >300 febrile infants per year (aOR: 1.8; 95% CI: 1.2-2.6). Among 505 infants treated for UTI without CSF testing, there were 0 (95% CI: 0%-0.6%) cases of delayed meningitis.There was wide variation in CSF testing in febrile infants with a positive urinalysis. Among infants treated for UTI without CSF testing (mostly 31 to 60-day-old infants), there were no cases of delayed meningitis within 7 days of discharge, suggesting that routine CSF testing of infants 31 to 60 days old with a positive urinalysis may not be necessary.

  View details for DOI 10.1542/peds.2018-3979

  View details for PubMedID 31395621

• A Prediction Model to Identify Febrile Infants ≤60 Days at Low Risk of Invasive Bacterial Infection. Pediatrics Aronson, P. L., Shabanova, V., Shapiro, E. D., Wang, M. E., Nigrovic, L. E., Pruitt, C. M., DePorre, A. G., Leazer, R. C., Desai, S., Sartori, L. F., Marble, R. D., Rooholamini, S. N., McCulloh, R. J., Woll, C., Balamuth, F., Alpern, E. R., Shah, S. S., Williams, D. J., Browning, W. L., Shah, N., Neuman, M. I. 2019

  Abstract

  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).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.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.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.

  View details for DOI 10.1542/peds.2018-3604

  View details for PubMedID 31167938

• Parenteral Antibiotic Therapy Duration in Young Infants With Bacteremic Urinary Tract Infections. Pediatrics Desai, S., Aronson, P. L., Shabanova, V., Neuman, M. I., Balamuth, F., Pruitt, C. M., DePorre, A. G., Nigrovic, L. E., Rooholamini, S. N., Wang, M. E., Marble, R. D., Williams, D. J., Sartori, L., Leazer, R. C., Mitchell, C., Shah, S. S. 2019

  Abstract

  To determine the association between parenteral antibiotic duration and outcomes in infants ≤60 days old with bacteremic urinary tract infection (UTI).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).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: -5.8 to 12.7) or 30-day all-cause reutilization (risk difference: 3%; 95% confidence interval: -14.5 to 20.6).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.

  View details for DOI 10.1542/peds.2018-3844

  View details for PubMedID 31431480

• Epidemiology and Etiology of Invasive Bacterial Infection in Infants ≤60 Days Old Treated in Emergency Departments. The Journal of pediatrics Woll, C., Neuman, M. I., Pruitt, C. M., Wang, M. E., Shapiro, E. D., Shah, S. S., McCulloh, R. J., Nigrovic, L. E., Desai, S., DePorre, A. G., Leazer, R. C., Marble, R. D., Balamuth, F., Feldman, E. A., Sartori, L. F., Browning, W. L., Aronson, P. L. 2018

  Abstract

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

  View details for PubMedID 29784512

• Factors Associated with Adverse Outcomes among Febrile Young Infants with Invasive Bacterial Infections. The Journal of pediatrics Pruitt, C. M., Neuman, M. I., Shah, S. S., Shabanova, V., Woll, C., Wang, M. E., Alpern, E. R., Williams, D. J., Sartori, L., Desai, S., Leazer, R. C., Marble, R. D., McCulloh, R. J., DePorre, A. G., Rooholamini, S. N., Lumb, C. E., Balamuth, F., Shin, S., Aronson, P. L. 2018

  Abstract

  To determine factors associated with adverse outcomes among febrile young infants with invasive bacterial infections (IBIs) (ie, bacteremia and/or bacterial meningitis).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.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 < .001). On adjusted analysis, bacterial meningitis (aOR 16.3, 95% CI 6.5-41.0; P < .001), prematurity (aOR 7.1, 95% CI 2.6-19.7; P < .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.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.

  View details for PubMedID 30297292

• Risk Stratification of Febrile Infants ≤60 Days Old Without Routine Lumbar Puncture. Pediatrics Aronson, P. L., Wang, M. E., Shapiro, E. D., Shah, S. S., DePorre, A. G., McCulloh, R. J., Pruitt, C. M., Desai, S., Nigrovic, L. E., Marble, R. D., Leazer, R. C., Rooholamini, S. N., Sartori, L. F., Balamuth, F., Woll, C., Neuman, M. I. 2018

  Abstract

  : media-1vid110.1542/5840460609001PEDS-VA_2018-1879Video Abstract 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.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.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.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.

  View details for PubMedID 30425130

• Time to Pathogen Detection for Non-ill Versus Ill-Appearing Infants ≤60 Days Old With Bacteremia and Meningitis. Hospital pediatrics Aronson, P. L., Wang, M. E., Nigrovic, L. E., Shah, S. S., Desai, S., Pruitt, C. M., Balamuth, F., Sartori, L., Marble, R. D., Rooholamini, S. N., Leazer, R. C., Woll, C., DePorre, A. G., Neuman, M. I. 2018

  Abstract

  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.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.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; P = .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.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.

  View details for PubMedID 29954839

• Trends in the incidence of possible severe bacterial infection and case fatality rates in rural communities in Sub-Saharan Africa, South Asia and Latin America, 2010-2013: a multicenter prospective cohort study. Reproductive health Hibberd, P. L., Hansen, N. I., Wang, M. E., Goudar, S. S., Pasha, O., Esamai, F., Chomba, E., Garces, A., Althabe, F., Derman, R. J., Goldenberg, R. L., Liechty, E. A., Carlo, W. A., Hambidge, K. M., Krebs, N. F., Buekens, P., McClure, E. M., Koso-Thomas, M., Patel, A. B. 2016; 13 (1): 65

  Abstract

  Possible severe bacterial infections (pSBI) continue to be a leading cause of global neonatal mortality annually. With the recent publications of simplified antibiotic regimens for treatment of pSBI where referral is not possible, it is important to know how and where to target these regimens, but data on the incidence and outcomes of pSBI are limited.We used data prospectively collected at 7 rural community-based sites in 6 low and middle income countries participating in the NICHD Global Network's Maternal and Newborn Health Registry, between January 1, 2010 and December 31, 2013. Participants included pregnant women and their live born neonates followed for 6 weeks after delivery and assessed for maternal and infant outcomes.In a cohort of 248,539 infants born alive between 2010 and 2013, 32,088 (13 %) neonates met symptomatic criteria for pSBI. The incidence of pSBI during the first 6 weeks of life varied 10 fold from 3 % (Zambia) to 36 % (Pakistan), and overall case fatality rates varied 8 fold from 5 % (Kenya) to 42 % (Zambia). Significant variations in incidence of pSBI during the study period, with proportions decreasing in 3 sites (Argentina, Kenya and Nagpur, India), remaining stable in 3 sites (Zambia, Guatemala, Belgaum, India) and increasing in 1 site (Pakistan), cannot be explained solely by changing rates of facility deliveries. Case fatality rates did not vary over time.In a prospective population based registry with trained data collectors, there were wide variations in the incidence and case fatality of pSBI in rural communities and in trends over time. Regardless of these variations, the burden of pSBI is still high and strategies to implement timely diagnosis and treatment are still urgently needed to reduce neonatal mortality.The study was registered at ClinicalTrials.gov ( NCT01073475 ).

  View details for DOI 10.1186/s12978-016-0177-1

  View details for PubMedID 27221099

• Risk factors for possible serious bacterial infection in a rural cohort of young infants in central India. BMC public health Wang, M. E., Patel, A. B., Hansen, N. I., Arlington, L., Prakash, A., Hibberd, P. L. 2016; 16 (1): 1097

  Abstract

  Possible 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.We 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.Two 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 2(nd)/3(rd) trimester (RR 1.46, 95 % CI 1.08-1.98) compared to 1(st) 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).Infants 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.This trial is registered at ClinicalTrials.gov ( NCT01073475 ).

  View details for DOI 10.1186/s12889-016-3688-3

  View details for PubMedID 27760543

• Immune Reconstitution Inflammatory Syndrome in Human Immunodeficiency Virus-Infected Children in Peru PEDIATRIC INFECTIOUS DISEASE JOURNAL Wang, M. E., Castillo, M. E., Montano, S. M., Zunt, J. R. 2009; 28 (10): 900-903

  Abstract

  Immune reconstitution inflammatory syndrome (IRIS) after initiating highly active antiretroviral therapy (HAART) has not been widely studied in children, especially in resource-poor settings.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.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.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.

  View details for DOI 10.1097/INF.0b013e3181a4b7fa

  View details for Web of Science ID 000270407800009

  View details for PubMedID 19687769

  View details for PubMedCentralID PMC3514443

• Changes in health insurance coverage during the economic downturn: 2000-2002. Health affairs Holahan, J., Wang, M. 2004: W4-31 42

  Abstract

  Using Current Population Survey data from 2000-2002, this paper documents the changes that led the uninsured population to grow by 3.8 million during that time period. All of the increase in the uninsured occurred among adults, and two-thirds was among low-income adults. The extent to which the loss of employer coverage resulted in people becoming uninsured depended on their access to public programs: Children were more likely than adults to gain public coverage; women more likely than men; and parents more likely than nonparents. Middle- and higher-income Americans were also affected because many lost income and because rates of employer coverage were lower.

  View details for PubMedID 15451962