Antibiotics are indicated for critically ill children with bacterial infections but are not without risk. Antibiotics incur additional expense, may require invasive catheters for administration, affect antibiotic resistance, and alter the child’s microbiome (1–3). One of the most common reasons for antibiotic use in the PICU is suspected ventilator-associated infection (VAI), a term that includes ventilator-associated pneumonia (VAP) and ventilator-associated tracheitis (4–6). Prudent antibiotic usage in children with suspected VAI is challenging because there are no gold standards for the diagnosis. In the case of VAP, agreement by experts is often little better than chance (7–9) and autopsy findings often conflict with the clinical diagnosis (10–12). In the absence of accurate diagnostic methods, novel approaches to guide antibiotic usage for children with suspected VAI are needed to reduce unnecessary usage, improve care, and minimize adverse effects (13).
Current antibiotic practices for suspected VAI are clinician dependent and highly variable, and there is poor correlation between duration of antibiotics and outcomes (514). Several clinical and laboratory findings may prompt antibiotic initiation, including fever, radiographic changes, leukocytosis, and escalation of mechanical ventilator settings (15). Our previous studies have demonstrated, however, that pediatric intensivists rely heavily on the results of respiratory secretion cultures to decide about antibiotic continuation (51416). Unfortunately, respiratory secretion cultures have significant bacterial growth in up to 80% of children mechanically ventilated for greater than 3 days and do not reliably distinguish between infection and colonization (17). Longer duration of mechanical ventilation (MV) prior to the culture collection and use of in-line suction catheters both markedly influence culture results. Additionally, a positive culture bears no clear relationship to outcomes or to other signs of VAI (517). The initial Ventilator-Associated INfection (VAIN) study demonstrated that antibiotic treatment for greater than or equal to 3 days in children with suspected VAI was not associated with improvements in mortality, PICU length of stay, or duration of MV, regardless of respiratory secretion culture results (5).
Given the uncertainty of the diagnosis, the variability in practice, and the common use of prolonged antibiotics for suspected VAI, we convened a group of interested experts to develop and test a guideline for antibiotic treatment. The a priori focus of this project was not on the diagnosis of VAI, but rather on decreasing antibiotic use by developing a scoring system to guide the continuation or discontinuation of antibiotics on the third day of treatment (i.e., after a “48-hr rule out” ). This article explains the methodology used to develop the scoring system and guideline and evaluates associations between our novel scoring system and clinical outcomes in a prospective cohort of children with suspected VAI.
After participating in the initial VAIN study (5), 29 investigators from 27 institutions agreed to develop and test the scoring system and guideline. The VAIN 2 study was divided into phase 1, prospective data collection in children with suspected VAI; phase 2, development of the scoring system and guideline; and phase 3, implementation of the guideline and assessment of guideline compliance, antibiotic use, and outcomes (currently underway). All participating hospitals granted Institutional Review Board approval and waived the need for informed consent. Data were collected using Research Electronic Data Capture (Vanderbilt University, Nashville, TN) housed at Virginia Commonwealth University. The funding agency (Gerber Foundation) limited the study to children less than 3 years old but played no other role in study design, guideline development, data analysis, or article preparation.
Phase 1: Prospective Data Collection
Data were prospectively collected from March 1, 2017, to January 16, 2018, from children less than 3 years old with suspected VAI. Subjects were eligible if they: 1) had been on invasive MV in the hospital for at least 48 hours; 2) had respiratory secretion cultures obtained; and 3) had antibiotics initiated for suspected VAI. Exclusion criteria were: 1) a nonrespiratory positive culture being treated with antibiotics (e.g., bacteremia, bacteriuria) and 2) immunodeficiency. As in our prior study (5), data collected included demographics, primary indication for MV, comorbidities, respiratory secretion analysis results, and antibiotic usage. The duration of initial antibiotics was defined as the number of days the child was treated with the same antibiotic, starting with the day the culture was obtained. If more than one antibiotic was initiated, the antibiotic with the longest duration was used. The total number of antibiotic days from the day the culture was obtained until PICU discharge, death, or 28 days had elapsed was also collected. If two (or more) antibiotics were given on a calendar day, then each day counted as two (or more) antibiotic days (e.g., a child on three antibiotics for 5 d = 15 antibiotic days). Clinical data (laboratory results, respiratory secretion description, etc.) and MV settings (lowest Fio2, lowest positive end-expiratory pressure [PEEP], etc.) were obtained for the 24 hours leading up to collection of the respiratory secretion culture (termed “day 0”) and for the period 48–72 hours after collection of the sample (termed “day 3”). We calculated the admission Pediatric Risk of Mortality III score (19) and the PEdiatric Logistic Organ Dysfunction (PELOD) 2 score (20) on the day the culture was obtained.
Phase 2: Guideline Development
Prior to the first consensus conference, investigators were anonymously surveyed about their perceptions of the sensitivity and specificity of 24 variables, composed primarily of the Centers for Disease Control and Prevention (CDC) “PNU1” criteria (21) for VAI, and rated these variables for the diagnosis of VAI on a scale of 1 to 9, with a score of 5 equivocal. The authors (primarily S.L.S., D.F.W.) then developed a framework from which the expert panel would design the guideline, beginning with an in-person consensus conference at the September 2017 “Pediatric Acute Lung Injury and Sepsis Investigators” (PALISI) meeting. The goals of that meeting were to: 1) discuss the survey results; 2) discuss a proposed structure for the scoring system and achieve consensus on its design; and 3) divide investigators into one of five groups for subsequent work, each assigned to one criteria category (clinical findings, chest radiograph results, respiratory secretion analysis, laboratory results, and ventilator settings). Each variable (e.g., temperature day 3) in the proposed scoring system structure was to have three tiers: a criterion that supports discontinuing antibiotics awarded negative 1 points (e.g., 36.0–37.9°C); a criterion that supports continuing antibiotics awarded +1 point (e.g., fever [defined as > 38.3°C]) (22); and a criterion that strongly supports continuing antibiotics awarded +2 points (e.g., ≥ 39.0°C).
After the in-person meeting, each group reviewed pertinent literature and used phone/web-based meetings to propose specific criteria for each tier of the scoring system within their assigned category. Next, the proposed criteria were anonymously voted on by all investigators on a scale from 1 (complete disagreement) to 9 (complete agreement) in line with the Research ANd Development (RAND)/UCLA method (23). Criteria with an average score of less than 7 were returned to their respective group for refinement or possible elimination and the voting process repeated a second time with the refined criteria.
Criteria that scored greater than or equal to 7 in the second round of voting were assembled into a scoring system similar to the Clinical Pulmonary Infection Score (24). This “Draft Guideline” and the individual criteria were analyzed using phase 1 data, including associations between criteria and clinical outcomes or illness severity (PELOD 2), and revised via telephone/internet-based meetings and serial surveys. Investigators were encouraged to seek input from other pediatric critical care and infectious disease colleagues at their institution during this period of refinement, but not before all phase 1 data had been collected. The process ended with a second in-person consensus conference at the March 2018 PALISI meeting, at which time the “Final Guideline” and antibiotic recommendations were approved by consensus with a goal of reducing antibiotic use by ~25%, followed by initiation of phase 3.
Planned outcomes to evaluate were PICU-free days (PFD) at 28 days, ventilator-free days (VFDs) at 28 days, duration of initial antibiotics, total number of antibiotic days, mortality, and use of prolonged antibiotics (≥ 4 d) (2526). Nonsurvivors were scored as zero for both PFD and VFD. Raw data from phase 1 (e.g., maximum temperature day 3, positive vs negative cultures) were compared against PFDs and duration of antibiotics using Pearson correlation, unpaired Student t tests, and analysis of variance, as appropriate. After each variable was assigned the appropriate number of points (e.g., –1, 0, +1, +2) in the phase 2 process, associations with outcomes were analyzed using Pearson correlation (continuous outcomes) and Student t test (dichotomous outcomes). Multivariate regression models were created and included variables that were loosely associated (p < 0.2) with the outcome in univariate analyses, with the guideline score forced into the model as needed. All statistical analyses were done using IBM SPSS Statistics for Windows, Version 24 (IBM Corp., Armonk, NY) or GraphPad Prism 7 (GraphPad Software, La Jolla, CA), and a p value of less than 0.05 was considered significant. Data are shown as median (interquartile range).
Characteristics of Phase 1 Subjects
From March 1, 2017, to January 16, 2018, 281 subjects from 22 sites were enrolled. The median age was 8 months (4–16 mo), 55% of subjects were male, and 33% were ventilated via a tracheostomy (Table 1). The most common diagnostic category was pulmonary (35%) and 75% of subjects had at least one comorbidity. The median duration of initial antibiotic therapy was 5 days (3–8 d) and the median total number of antibiotic days was 13 days (8–23 d). Fewer than one-quarter (65/281 [23%]) of subjects initially received one antibiotic; 133 of 281 (47%) received two antibiotics; 54 of 281 (19%) received three antibiotics; and 29 of 281 (10%) received four or more antibiotics. Most subjects (92%) survived to PICU discharge.
Development and Refinement of the Guideline
Results of the initial phase 2 survey (n = 24 respondents) varied widely (Fig. 1). For 18 of the 24 criteria, at least one respondent rated the sensitivity a 7 or higher on the 1–9 scale, whereas another respondent rated the sensitivity a 3 or lower. Similarly, 21 criteria had both a maximum score of greater than or equal to 7 and a minimum score of less than or equal to 3 for perceived specificity. After reviewing those results, a fourth tier awarding zero points was added to the scoring system for situations where a criterion was not measured or where the results were considered equivocal for continuing antibiotics (e.g., 38.0–38.3°C). After consensus was achieved on the four-tier scoring system, each working group met briefly for planning purposes, and the conference concluded.
Each working group considered the survey data, reviewed pertinent literature, and conducted a series of remote meetings. Investigators were given access to one of the author’s (D.F.W.) large databases of pertinent references and encouraged to seek additional information as appropriate, but a specific search strategy was not mandated. The five groups proposed a total of 36 diagnostic criteria, which were submitted to the group at large; nine achieved an average score less than 7 and were returned to their respective group for revision. One approved criterion—“change in lung compliance”—was eliminated because there was consensus that measurement technique varied excessively across institutions. Several other criteria were consolidated and wording revised by the working groups. A total of 25 criteria in five categories were accepted after the second round of voting and formatted into the Initial Draft Guideline (Supplemental Fig. 1, Supplemental Digital Content 1, http://links.lww.com/PCC/A949; legend, Supplemental Digital Content 3, http://links.lww.com/PCC/A951) by the leaders of the five groups (S.L.S., A.B., T.K., E.P., K.M.T.) and the principal investigator (D.F.W.). It was decided that each category (clinical findings, chest radiograph results, etc.) would be scored as the highest criterion score within the category and the final score would then be the sum of the scores from each of the five categories. Thus, for the initial Draft Guideline potential scores ranged between –5 and +10.
Several criteria were then modified based on univariate analyses of the associations between the proposed score criteria and outcomes from the phase 1 data. Fever on day 0 trended with PFDs (r = 0.16; p = 0.08) and correlated significantly with the duration of initial antibiotics (r = 0.12; p = 0.04), but fever on day 3 was not associated with outcomes. Despite the lack of correlation, it was decided that fever was a commonly accepted criterion for infection and eliminating it could decrease clinician acceptance. Instead, the “+2” criterion was revised to require two episodes of fever at least 24 hours apart, and a single temperature cutoff was used to reduce confusion. Hypothermia (< 36.0°C) was also eliminated because it was not significantly associated with PFDs or duration of antibiotics, and because its high frequency (24%) suggested contributing factors other than infection (e.g., environmental exposure, common use of axillary temperatures). The respiratory culture criterion score was also modified. In the phase 1 data a positive respiratory culture was actually associated with higher survival rates (odds ratio, 2.48; 95% CI, 1.001–5.60; p = 0.04) but, as with fever, elimination of the criterion was thought to risk poor adoption of the Guideline. Consequently, the +1 criterion was revised to require both leukocytes on Gram stain and bacterial growth in culture and the +2 criterion removed. The requirement for air bronchograms or cavitary lesions to diagnose infiltrates was removed because these descriptions were rarely observed in the phase 1 data. Additionally, the absence of a recent chest radiograph was changed from –1 points to 0 points. The +1 score for laboratory results was changed to use the same cutoff as the –1 score (12,000 leukocytes/mL) to improve ease of use of the guideline. Finally, it was decided that individual components (Fio2 and mean airway pressure) of the oxygenation saturation index (OSI) should be included since systemic oxygen saturation was noted to be frequently above 97% in the phase 1 data, which invalidates OSI calculations (27). Finally, lower cutoffs were added to the +1 score in the MV settings category to avoid clinically insignificant changes leading to a higher chance of antibiotic continuation. With these modifications, possible Guideline scores now ranged from –5 to +9 (Fig. 2).
Guideline Performance and Selection of Cutoff Score
After completion of the above modifications, one author (D.F.W.) calculated and assigned a Guideline score to each of the phase 1 subjects. The associations of the guideline score to outcomes from the phase 1 data were then tested in multivariate models that included age, primary diagnosis category, comorbid status, severity of illness scores, and respiratory culture results. As shown in Table 2, the Final Guideline score trended with fewer PFDs (p = 0.073) and was independently associated with longer duration of initial antibiotics (p < 0.001) after adjusting for covariates. Scores were also significantly associated with PELOD 2 scores in a multivariate model (p < 0.001). There were no statistically significant associations between the Final Guideline score and either mortality or VFDs in multivariate analysis. None of the five categories were associated with mortality, but both clinical findings and laboratory findings significantly correlated with PFDs and duration of initial antibiotics (Supplemental Table 1, Supplemental Digital Content 2, http://links.lww.com/PCC/A950).
The Final Guideline was approved at the second consensus conference convened during the March 2018 PALISI meeting. Next, the cutoff scores that would prompt recommendations to continue or discontinue antibiotics were discussed, with a goal of reducing antibiotic use by approximately 25%. Phase 1 data were used to evaluate possible cutoff scores to determine 1) the number of children in the phase 1 cohort who would have been given each recommendation and 2) the percentage of children in each recommendation category who received a long initial antibiotic treatment course, defined as greater than or equal to 4 days (Table 3). After extended discussion, the group recommended stopping antibiotics for a score of 2 or less. There were no differences in VFDs or PFDs in the 130 children with a score of less than or equal to 2 whether they received a short (n = 56; 43.1%) or long (n = 74; 56.9%) antibiotic course (Fig. 3). Although there were also no statistical differences in VFDs or PFDs for the 151 children with scores greater than 2, higher scores correlated with illness severity (PELOD 2) and duration of initial antibiotics. Erring on the side of caution, the consensus was to recommend continuing antibiotics for scores greater than or equal to 6 and to make no recommendations for score of 3, 4, or 5. These recommendations were then approved for implementation in phase 3 of the trial.
Using a predesigned framework that included literature review, investigator surveys, clinician input, serial discussions, and standardized voting, a group of experts in pediatric critical care and pediatric infectious diseases designed a novel scoring system to guide the decision to continue or discontinue antibiotics after 48–72 hours in children with suspected VAI. Using prospective data from 281 subjects with suspected VAI comparable to other published cohorts (2628), we found that the recommendation to discontinue antibiotics would have applied to 46% of subjects, over half (57%) of whom had actually received a long course of antibiotics that had no clear association with clinical outcomes. Based on these data, we estimated that prospective application of the guideline could safely reduce antibiotic exposure in one-fourth of children with suspected VAI. The guideline will be implemented in the third phase of this study to evaluate the acceptability, efficacy, and safety of these recommendations.
The primary reason to diagnose VAI is to administer antibiotics to improve outcomes, but it is difficult to discriminate between VAI and noninfectious causes of similar clinical deterioration. Unfortunately, pediatric intensivists appear to prescribe antibiotics seemingly independent of published VAI criteria (25), and little guidance is offered by the recent pediatric and CDC expert panel on VAI; rather than devise recommendations for antibiotic use in suspected VAI, they chose to include antibiotic use as one criterion for the diagnosis of VAI (2729). In this study, we elected to focus on treatment, not diagnosis, and developed an objective system to attempt to identify children who may have antibiotics safely discontinued. Our data and those of others support that VAI is unlikely to have substantial, if any, attributable mortality in children (2930); thus, stopping antibiotics when guideline scores are low would appear reasonable and safe. Furthermore, because these children are cared for in a highly monitored environment, antibiotics can be restarted promptly should the child’s clinical status change. We believe the risks of antibiotics may outweigh the benefits in many of these children. Antibiotics are not necessarily benign: they are expensive, may require long-term catheters for administration, can have significant untoward effects, and induce bacterial resistance.
Pediatric antibiotic guidelines often exclude PICU patients, leaving indications, drug selection, and duration up to bedside clinicians (31–33). Unlike other conditions (e.g., urinary tract infection) for which evidence-based recommendations exist (31), however, VAI is a somewhat subjective diagnosis with little inter-clinician agreement. Consequently, a pragmatic and balanced approach was taken to develop these guidelines. We deemed it important to garner expert opinions from a large number of experienced investigators from diverse institutions and fields. Phase 1 data collected prior to the consensus conferences were used to adjust the score to best correlate with disease severity, employing favorable outcomes as a surrogate for sufficient physiologic reserve to tolerate a trial of monitored antibiotic discontinuation. When an approved variable (e.g., fever) did not associate with outcomes, an attempt was made to balance the discriminatory ability of the score with the acceptance of an antibiotic guideline without the criterion. Similarly, we retained the positive respiratory culture criterion in the guideline despite the association with improved outcome in order to facilitate clinician acceptance (51416). Finally, the cutoff score for recommending antibiotic discontinuation was chosen to be high enough to identify a sufficiently large population receiving prolonged antibiotics, but not so high as to risk clinicians becoming fatigued by the guideline frequently recommending a different practice than their norm. Future projects may similarly benefit from pragmatic, balanced consideration.
Strengths of this project include the inclusion of a large number of experts from various institutions, the use of RAND/UCLA voting for criteria selection, and assessment with prospective data. We believe this project can serve as a model to examine other PICU therapies with wide practice variation (e.g., gastric ulcer prophylaxis , daily chest radiographs , corticosteroids for bronchiolitis , ipratropium for critical asthma ). When uncertain, some clinicians may assume “more is better” despite treatment side effects, costs, and adverse outcomes that impact individual patients and the healthcare system as a whole. The variable and often nonsystematic use of antibiotics for suspected VAI may be the most egregious example since antibiotic side effects are often underestimated and development of antibiotic resistance can have long-lasting societal impact. We believe this project offers a rational approach to examining practice variation and, in the case of suspected VAI, decreasing unnecessary antibiotic use.
There were several limitations to this project. First, undoubtedly some children with a low score may actually have bacterial infection and might benefit from antibiotics. Our score is not intended to diagnose VAI, but to identify children who may safely undergo a trial of monitored antibiotic discontinuation. The correlation between our score and illness severity suggests that children with low scores may tolerate a period without antibiotics even if true bacterial infection is present, especially because treatment can be restarted should the child’s clinical status change. We anticipate these patients will be identified in phase 3 due to clinical worsening after antibiotics are discontinued, and revisions to the guideline may be needed to better identify these patients. Second, the guideline score was developed by consensus but underwent final refinement using phase 1 data. Consequently, its correlation to outcomes is at least in part attributable to this modification. Third, although data were collected prospectively, measurement of variables was not prescribed and only clinically obtained values were available. Similarly, our a priori definitions of certain variables (e.g., “lowest” PEEP) may not be the most accurate measurement of illness severity. Fourth, our study was limited by the funding agency to children less than 3 years old, and findings may not be generalizable to older children. Fifth, VFDs may not be a useful outcome given the large number of children on chronic ventilation; we believe PFDs are the more meaningful outcome for this patient population. Sixth, alternative statistical tests may have been more appropriate given the skewed distribution of many variables. However, because the primary aim of the article is to explain the methodology used to develop the score and guideline, we included the analyses used during the actual process and did not modify them after the fact. Prospective evaluation using appropriate statistical tests may be needed to better determine the clinical impact of our score and guideline. Seventh, although some prior studies measure antibiotic exposure by counting the number of days in which a subject gets at least one antibiotic (38), we factored the number of antibiotics given on each day into our measure of antibiotic days. Each dose of antibiotics increases costs and confers risk, so we think this is more appropriate for our cohort, especially since treatment with more than one agent was very common.
In conclusion, we achieved consensus on a novel scoring system to guide antibiotic decisions on the third day of therapy for suspected VAI. Low scores correlate with current inconsistent use of antibiotics and with favorable outcomes regardless of the actual treatment received, which suggests the ability to safely tolerate a trial of monitored antibiotic discontinuation. We estimate that use of the guideline could reduce antibiotic exposure in approximately one-quarter of children with suspected VAI. We are currently testing the acceptance of the guideline and its ability to reduce antibiotic exposure without worsening clinical outcomes.
1. Geissler A, Gerbeaux P, Granier I, et al. Rational use of antibiotics
in the intensive care unit: Impact on microbial resistance and costs. Intensive Care Med 2003; 29:49–54
2. Sommer MO, Dantas G. Antibiotics
and the resistant microbiome. Curr Opin Microbiol 2011; 14:556–563
3. Davis AL, Carcillo JA, Aneja RK, et al. American College of Critical Care Medicine clinical practice parameters for hemodynamic support of pediatric
and neonatal septic shock. Crit Care Med 2017; 45:1061–1093
4. Fischer JE, Ramser M, Fanconi S. Use of antibiotics
intensive care and potential savings. Intensive Care Med 2000; 26:959–966
5. Willson DF, Hoot M, Khemani R, et al.; Ventilator-Associated INfection (VAIN) Investigators and the Pediatric
Acute Lung Injury and Sepsis Investigator’s (PALISI) Network: Pediatric
ventilator-associated infections: The Ventilator-Associated INfection Study. Pediatr Crit Care Med 2017; 18:e24–e34
6. Raymond J, Aujard Y. Nosocomial infections in pediatric
patients: A European, multicenter prospective study. European Study Group. Infect Control Hosp Epidemiol 2000; 21:260–263
7. Klompas M. Interobserver variability in ventilator-associated pneumonia
surveillance. Am J Infect Control 2010; 38:237–239
8. Schurink CAM, Nieuwenhoven CAV, Jacobs JA, et al. Clinical pulmonary infection score for ventilator-associated pneumonia
: Accuracy and inter-observer variability. Intensive Care Med 2004; 30:217–224
9. Nussenblatt V, Avdic E, Berenholtz S, et al. Ventilator-associated pneumonia
: Overdiagnosis and treatment are common in medical and surgical intensive care units. Infect Control Hosp Epidemiol 2014; 35:278–284
10. Petersen IS, Aru A, Skødt V, et al. Evaluation of pneumonia diagnosis in intensive care patients. Scand J Infect Dis 1999; 31:299–303
11. Tejerina E, Esteban A, Fernández-Segoviano P, et al. Accuracy of clinical definitions of ventilator-associated pneumonia
: Comparison with autopsy findings. J Crit Care 2010; 25:62–68
12. Fàbregas N, Ewig S, Torres A, et al. Clinical diagnosis of ventilator associated pneumonia revisited: Comparative validation using immediate post-mortem lung biopsies. Thorax 1999; 54:867–873
13. Beardsley AL. Ventilator-associated infections need a new approach. Pediatr Crit Care Med 2016; 17:587
14. Willson DF, Webster A, Heidemann S, et al.; Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric
Critical Care Research Network (CPCCRN): Diagnosis and treatment of ventilator-associated infection: Review of the critical illness stress-induced immune suppression prevention trial data. Pediatr Crit Care Med 2016; 17:287–293
15. Kalanuria AA, Ziai W, Mirski M. Ventilator-associated pneumonia
in the ICU. Crit Care 2014; 18:208
16. Willson DF, Kirby A, Kicker JS. Respiratory secretion analyses in the evaluation of ventilator-associated pneumonia
: A survey of current practice in pediatric
critical care. Pediatr Crit Care Med 2014; 15:715–719
17. Willson DF, Conaway M, Kelly R, et al. The lack of specificity of tracheal aspirates in the diagnosis of pulmonary infection in intubated children. Pediatr Crit Care Med 2014; 15:299–305
18. Randolph AG, Reder L, Englund JA. Risk of bacterial infection in previously healthy respiratory syncytial virus-infected young children admitted to the intensive care unit. Pediatr Infect Dis J 2004; 23:990–994
19. Pollack MM, Patel KM, Ruttimann UE. PRISM III: An updated Pediatric
Risk of Mortality score. Crit Care Med 1996; 24:743–752
20. Leteurtre S, Duhamel A, Salleron J, et al.; Groupe Francophone de Réanimation et d’Urgences Pédiatriques (GFRUP): PELOD-2: An update of the PEdiatric
Logistic Organ Dysfunction score. Crit Care Med 2013; 41:1761–1773
22. Ahonkhai VI, Lukacs LJ, Jonas LC, et al. Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB): Clinical evaluation. Pediatrics 1990; 85:676–681
23. Bembea MM, Jouvet P, Willson D, et al. Methodology of the pediatric
acute lung injury consensus conference. Pediatr Crit Care Med 2015; 16(5 Suppl 1):S1–S5
24. Pugin J, Auckenthaler R, Mili N, et al. Diagnosis of ventilator-associated pneumonia
by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid. Am Rev Respir Dis 1991; 143:1121–1129
25. Beardsley AL, Nitu ME, Cox EG, et al. An evaluation of various ventilator-associated infection criteria in a PICU. Pediatr Crit Care Med 2016; 17:73–80
26. Cocoros NM, Priebe GP, Logan LK, et al. A pediatric
approach to ventilator-associated events surveillance. Infect Control Hosp Epidemiol 2017; 38:327–333
27. Khemani RG, Thomas NJ, Venkatachalam V, et al.; Pediatric
Acute Lung Injury and Sepsis Network Investigators (PALISI): Comparison of SpO2 to PaO2 based markers of lung disease severity for children with acute lung injury. Crit Care Med 2012; 40:1309–1316
28. Gupta S, Boville BM, Blanton R, et al. A multicentered prospective analysis of diagnosis, risk factors, and outcomes associated with pediatric ventilator-associated pneumonia
. Pediatr Crit Care Med 2015; 16:e65–e73
29. Almuneef M, Memish ZA, Balkhy HH, et al. Ventilator-associated pneumonia
in a pediatric
intensive care unit in Saudi Arabia: A 30-month prospective surveillance. Infect Control Hosp Epidemiol 2004; 25:753–758
30. Elward AM, Warren DK, Fraser VJ. Ventilator-associated pneumonia
intensive care unit patients: Risk factors and outcomes. Pediatrics 2002; 109:758–764
31. Roberts KB; Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management: Urinary tract infection: Clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics 2011; 128:595–610
32. Wald ER, Applegate KE, Bordley C, et al.; American Academy of Pediatrics: Clinical practice guideline for the diagnosis and management of acute bacterial sinusitis in children aged 1 to 18 years. Pediatrics 2013; 132:e262–e280
33. Shulman ST, Bisno AL, Clegg HW, et al.; Infectious Diseases Society of America: Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis 2012; 55:e86–e102
34. Costarino AT, Dai D, Feng R, et al. Gastric acid suppressant prophylaxis in pediatric
intensive care: Current practice as reflected in a large administrative database. Pediatr Crit Care Med 2015; 16:605–612
35. Quasney MW, Goodman DM, Billow M, et al. Routine chest radiographs in pediatric
intensive care units. Pediatrics 2001; 107:241–248
36. Pierce HC, Mansbach JM, Fisher ES, et al. Variability of intensive care management for children with bronchiolitis. Hosp Pediatr 2015; 5:175–184
37. Shein SL, Farhan O, Morris N, et al. Adjunctive pharmacotherapies in children with asthma exacerbations requiring continuous albuterol therapy: Findings from The Ohio Pediatric
Asthma Repository. Hosp Pediatr 2018; 8:89–95
38. Gerber JS, Newland JG, Coffin SE, et al. Variability in antibiotic use at children’s hospitals. Pediatrics 2010; 126:1067–1073
PEDIATRIC ACUTE LUNG INJURY AND SEPSIS INVESTIGATOR (PALISI) NETWORK
Christopher L. Carroll, MD, Connecticut Children’s Medical Center (Hartford, CT); Ranjit S. Chima, MD, Cincinnati Children’s Hospital Medical Center (Cincinnati, OH); Samuel Davila, MD, UT Southwestern Medical Center (Dallas, TX); Theodore Demartini, MD, Penn State Health (Hershey, PA); Heidi Flori, MD, University of Michigan C.S. Mott Children’s Hospital (Ann Arbor, MI); Patricia Fontela, MD, PhD, Montreal Children’s Hospital (Montreal, QC); Rainer Gedeit, MD, Children’s Hospital of Wisconsin (Milwaukee, WI); Denise Goodman, MD, Ann & Robert H. Lurie Children’s Hospital of Chicago (Chicago, IL); Amanda B. Hassinger, MD, MS, John R. Oishei Children’s Hospital (Buffalo, NY); Asumthia Jeyapalan, DO, Holtz Children’s Hospital/Jackson Memorial Hospital (Miami, FL); Philippe Jouvet, MD, PhD, MBA, CHU Sainte-Justine (Montreal, QC); Robinder Khemani, MD, Children’s Hospital of Los Angeles (Los Angeles, CA); Aileen Kirby, MD, Doernbecher Children’s Hospital (Portland, OR); John C. Lin, MD, St. Louis Children’s Hospital (St. Louis, MO); Sholeen Nett, MD, PhD, Dartmouth–Hitchcock Medical Center (Hanover, NH); Jason Newland, MD, MEd, St. Louis Children’s Hospital (St. Louis, MO); Akira Nishisaki, MD, MSCE, Children’s Hospital of Philadelphia (Philadelphia, PA); Ronald Sanders, MD, Arkansas Children’s Hospital (Little Rock, AR); Adam Schwarz, MD, Children’s Hospital of Orange County (Mission Viejo, CA); Lincoln Smith, MD, Seattle Children’s Hospital (Seattle, WA); Edward Truemper, MD, Children’s Hospital and Medical Center (Omaha, NE); and Katri Typpo, MD, MPH, University of Arizona (Tucson, AZ).
antibiotics; mechanical ventilation; pediatric; ventilator-associated pneumonia
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