Affiliations
Division of Pharmacy, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
Given name(s)
Camille
Family name
Graham
Degrees
MD

Pneumonia Guideline Therapy Outcomes

Article Type
Changed
Sun, 05/21/2017 - 13:32
Display Headline
Hospital outcomes associated with guideline‐recommended antibiotic therapy for pediatric pneumonia

Community‐acquired pneumonia (CAP) is a common and serious infection in children. With more than 150,000 children requiring hospitalization annually, CAP is the fifth most prevalent and the second most costly diagnosis of all pediatric hospitalizations in the United States.[1, 2, 3]

In August 2011, the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) published an evidence‐based guideline for the management of CAP in children. This guideline recommended that fully immunized children without underlying complications who require hospitalization receive an aminopenicillin as first‐line antibiotic therapy.[4] Additionally, the guideline recommends empirically adding a macrolide to an aminopenicillin when atypical pneumonia is a diagnostic consideration.

This recommendation was a substantial departure from practice for hospitals nationwide, as a multicenter study of children's hospitals (20052010) demonstrated that <10% of patients diagnosed with CAP received aminopenicillins as empiric therapy.[5] Since publication of the PIDS/IDSA guidelines, the use of aminopenicillins has increased significantly across institutions, but the majority of hospitalized patients still receive broad‐spectrum cephalosporin therapy for CAP.[6]

At baseline, 30% of patients hospitalized with CAP received guideline‐recommended antibiotic therapy at our institution. Through the use of quality‐improvement methods, the proportion of patients receiving guideline‐recommended therapy increased to 100%.[7] The objective of this study was to ensure that there were not unintended negative consequences to guideline implementation. Specifically, we sought to identify changes in length of stay (LOS), hospital costs, and treatment failures associated with use of guideline‐recommended antibiotic therapy for children hospitalized with uncomplicated CAP.

METHODS

Study Design and Study Population

This retrospective cohort study included children age 3 months to 18 years, hospitalized with CAP, between May 2, 2011 and July 30, 2012, at Cincinnati Children's Hospital Medical Center (CCHMC), a 512‐bed free‐standing children's hospital. The CCHMC Institutional Review Board approved this study with a waiver of informed consent.

Patients were eligible for inclusion if they were admitted to the hospital for inpatient or observation level care with a primary or secondary International Classification of Disease, 9th Revision discharge diagnosis code of pneumonia (480.02, 480.89, 481, 482.0, 482.30‐2, 482.41‐2, 482.83, 482.8990, 483.8, 484.3, 485, 486, 487.0) or effusion/empyema (510.0, 510.9, 511.01, 511.89, 513).[8] Patients with complex chronic conditions[9] were excluded. Medical records of eligible patients (n=260) were reviewed by 2 members of the study team to ensure that patients fell into the purview of the guideline. Patients who did not receive antibiotics (n=11) or for whom there was documented concern for aspiration (n=1) were excluded. Additionally, patients with immunodeficiency (n=1) or who had not received age‐appropriate vaccinations (n=2), and patients who required intensive care unit admission on presentation (n=17) or who had a complicated pneumonia, defined by presence of moderate or large pleural effusion at time of admission (n=8), were also excluded.[7] Finally, for patients with multiple pneumonia admissions, only the index visit was included; subsequent visits occurring within 30 days of discharge were considered readmissions.

Treatment Measure

The primary exposure of interest was empiric antibiotic therapy upon hospital admission. Antibiotic therapy was classified as guideline recommended or nonguideline recommended. Guideline‐recommended therapy was defined as follows:

  1. For children without drug allergies: ampicillin (200 mg/kg/day intravenously) or amoxicillin (90 mg/kg/day orally);
  2. For children with penicillin allergy: ceftriaxone (50100 mg/kg/day intravenously or intramuscularly) or cefdinir (14 mg/kg/day orally);
  3. For children with penicillin and cephalosporin allergy: clindamycin (40 mg/kg/day orally or intravenously); and
  4. Or azithromycin (10 mg/kg/day orally or intravenously on day 1) in combination with antibiotic category 1 or 2 or 3 above.

 

Outcome Measures

The primary outcomes examined were hospital LOS, total cost of hospitalization, and inpatient pharmacy costs. LOS was measured in hours and defined as the difference in time between departure from and arrival to the inpatient unit. Total cost of index hospitalization included both direct and indirect costs, obtained from the Centers for Medicare & Medicaid Services' Relative Value Units data for Current Procedural Terminology codes.[10]

Secondary outcomes included broadening of antibiotic therapy during the hospital course, pneumonia‐related emergency department (ED) revisits within 30 days, and pneumonia‐related inpatient readmissions within 30 days. Broadening of antibiotic therapy was defined as addition of a second antibiotic (eg, adding azithromycin on day 3 of hospitalization) or change in empiric antibiotic to a class with broader antimicrobial activity (eg, ampicillin to ceftriaxone) at any time during hospitalization. As our study population included only patients with uncomplicated pneumonia at the time of admission, this outcome was used to capture possible treatment failure. ED revisits and inpatient readmissions were reviewed by 3 investigators to identify pneumonia‐related visits. To encompass all possible treatment failures, all respiratory‐related complaints (eg, wheezing, respiratory distress) were considered as pneumonia‐related. Disagreements were resolved by group discussion.

Covariates

Severity of illness on presentation was evaluated using the Emergency Severity Index version 4,[11] abnormal vital signs on presentation (as defined by Pediatric Advanced Life Support age‐specific criteria[12]), and need for oxygen in the first 24 hours of hospitalization. Supplemental oxygen is administered for saturations <91% per protocol at our institution. The patient's highest Pediatric Early Warning Scale score[13] during hospitalization was used as a proxy for disease severity. Exam findings on presentation (eg, increased respiratory effort, rales, wheezing) were determined through chart review. Laboratory tests and radiologic imaging variables included complete blood cell count, blood culture, chest radiograph, chest ultrasound, and chest computed tomography. Abnormal white blood cell count was defined as <5000 or >15,000 cells/mL, the defined reference range for the CCHMC clinical laboratory.

Data Analysis

Continuous variables were described using median and interquartile range (IQR) and compared across groups using Wilcoxon rank sum test due to non‐normal distributions. Categorical variables were described by counts and frequencies and compared using the 2 test.

Multivariable linear regression analysis was performed to assess the independent effect of receipt of empiric guideline‐recommended antibiotic therapy on outcomes of LOS and costs while adjusting for covariates. As LOS and costs were non‐normally distributed, we logarithmically transformed these values to use as the dependent variables in our models. The resulting coefficients were back‐transformed to reflect the percent change in LOS and costs incurred between subjects who received empiric guideline therapy compared with those who did not.[14] Covariates were chosen a priori due to their clinical and biological relevance to the outcomes of LOS (eg, wheezing on presentation and need for supplemental oxygen), total cost of hospitalization (eg, LOS and need for repeat imaging), and inpatient pharmacy costs (eg, LOS and wheezing on presentation) (Table 1).

Cohort Characteristics
CharacteristicOverall Cohort, n=220Guideline Therapy, n=166Nonguideline Therapy, n=54P Value
  • NOTE: Abbreviations: CT, computed tomography; IQR, interquartile range; PEWS, Pediatric Early Warning Scale. *P<0.05.

Age, y, median (IQR)2.9 (1.36.3)2.5 (1.35.2)5.6 (2.38.8)<0.01*
Male, no. (%)122 (55.5%)89 (53.6%)33 (61.1%)0.34
Emergency Severity Index, no. (%)0.11
290 (40.9%)73 (44.0%)17 (31.5%) 
3116 (52.7%)85 (51.2%)31 (57.4%) 
414 (6.4%)8 (4.8%)6 (11.1%) 
Abnormal vital signs on presentation, no. (%)
Fever99 (45.0%)80 (48.2%)19 (35.2%)0.10
Tachycardia100 (45.5%)76 (45.8%)24 (44.4%)0.86
Tachypnea124 (56.4%)100 (60.2%)24 (44.4%)0.04*
Hypotension000 
Hypoxia27 (12.3%)24 (14.5%)3 (5.6%)0.08
Physical exam on presentation, no. (%)
Increased respiratory effort146 (66.4%)111 (66.9%)35 (64.8%)0.78
Distressed110 (50.0%)86 (51.8%)24 (44.4%)0.35
Retraction103 (46.8%)81 (48.8%)22 (40.7%)0.30
Grunting17 (7.7%)14 (8.4%)3 (5.6%)0.49
Nasal flaring19 (8.6%)17 (10.2%)2 (3.7%)0.14
Rales135 (61.4%)99 (59.6%)36 (66.7%)0.36
Wheeze91 (41.4%)66 (39.8%)25 (46.3%)0.40
Decreased breath sounds89 (40.5%)65 (39.2%)24 (44.4%)0.49
Dehydration21 (9.6%)13 (7.8%)8 (14.8%)0.13
PEWS 5 during admission, no. (%)43 (19.6%)34 (20.5%)9 (16.7%)0.54
Oxygen requirement in first 24 hours, no. (%)114 (51.8%)90 (53.6%)24 (46.2%)0.35
Complete blood count obtained, no. (%)99 (45.0%)72 (43.4%)27 (50.0%)0.40
Abnormal white blood cell count35 (35.7%)23 (32.4%)12 (44.4%)0.27
Blood culture obtained, no. (%)104 (47.3%)80 (48.2%)24 (44.4%)0.63
Positive2 (1.9%)1 (1.3%)1 (4.2%)0.36
Chest radiograph available, no. (%)214 (97.3%)161 (97.0%)53 (98.2%)0.65
Infiltrate178 (83.2%)139 (86.3%)39 (73.6%)0.03*
Bilateral29 (16.3%)20 (14.4%)9 (23.1%)0.19
Multilobar46 (25.8%)33 (23.7%)13 (33.3%)0.23
Effusion24 (11.2%)16 (9.9%)8 (15.1%)0.30
Additional imaging, no. (%)    
Repeat chest radiograph26 (11.8%)17 (10.2%)9 (16.7%)0.20
Chest ultrasound4 (1.8%)3 (1.8%)1 (1.9%)0.98
Chest CT2 (0.9%)1 (0.6%)1 (1.9%)0.40
Antibiotic, no. (%)   <0.01*
Aminopenicillin140 (63.6%)140 (84.3%)0 (0%) 
Third‐generation cephalosporin37 (16.8%)8 (4.8%)29 (53.7%) 
Macrolide monotherapy18 (8.2%)0 (0%)18 (33.3%) 
Clindamycin2 (0.9%)1 (0.6%)1 (1.9%) 
Levofloxacin1 (0.5%)0 (0%)1 (1.9%) 
Aminopenicillin+macrolide16 (7.3%)16 (9.6%)0 (0%) 
Cephalosporin+macrolide6 (2.7%)1 (0.6%)5 (9.3%) 

Secondary outcomes of broadened antibiotic therapy, ED revisits, and hospital readmissions were assessed using the Fisher exact test. Due to the small number of events, we were unable to evaluate these associations in models adjusted for potential confounders.

All analyses were performed with SAS version 9.3 (SAS Institute, Cary, NC), and P values <0.05 were considered significant.

RESULTS

Of the 220 unique patients included, 122 (55%) were male. The median age was 2.9 years (IQR: 1.36.3 years). Empiric guideline‐recommended therapy was prescribed to 168 (76%) patients (Table 1). Aminopenicillins were the most common guideline‐recommended therapy, accounting for 84% of guideline‐recommended antibiotics. An additional 10% of patients received the guideline‐recommended combination therapy with an aminopenicillin and a macrolide. Nonguideline‐recommended therapy included third‐generation cephalosporin antibiotics (54%) and macrolide monotherapy (33%).

Those who received empiric guideline‐recommended antibiotic therapy were similar to those who received nonguideline‐recommended therapy with respect to sex, Emergency Severity Index, physical exam findings on presentation, oxygen requirement in the first 24 hours, abnormal laboratory findings, presence of effusion on chest radiograph, and need for additional imaging (Table 1). However, patients in the guideline‐recommended therapy group were significantly younger (median 2.5 years vs 5.6 years, P0.01), more likely to have elevated respiratory rate on presentation (60.2% vs 44.4%, P=0.04), and more likely to have an infiltrate on chest radiograph (86.3% vs 73.6%, P=0.03) (Table 1). Patients who received nonguideline‐recommended macrolide monotherapy had a median age of 7.4 years (IQR: 5.89.8 years).

Median hospital LOS for the total cohort was 1.3 days (IQR: 0.91.9 days) (Table 2). There were no differences in LOS between patients who received and did not receive guideline‐recommended therapy in the unadjusted or the adjusted model (Table 3).

Unadjusted Outcomes
OutcomeGuideline Therapy, n=166Nonguideline Therapy, n=54P Value
  • NOTE: Abbreviations: IQR, interquartile range.

Length of stay, d, median (IQR)1.3 (0.91.9)1.3 (0.92.0)0.74
Total costs, median, (IQR)$4118 ($2,647$6,004)$4045 ($2,829$6,200)0.44
Pharmacy total costs, median, (IQR)$84 ($40$179)$106 ($58$217)0.12
Broadened therapy, no. (%)10 (6.0%)4 (7.4%)0.75
Emergency department revisit, no. (%)7 (4.2%)2 (3.7%)1.00
Readmission, no. (%)1 (0.6%)1 (1.9%)0.43
Univariate and Multivariate Analyses of Receipt of Empiric Guideline‐Recommended Therapy With Length of Stay, Total Costs, and Pharmacy Costs
OutcomeUnadjusted Coefficient (95% CI)Adjusted Coefficient (95% CI)Adjusted % Change in Outcome (95% CI)*
  • NOTE: Abbreviations: CI, confidence interval. *Negative adjusted percent change indicates decrease in outcome associated with guideline‐recommended therapy; positive adjusted percent change indicates increase in outcome associated with guideline‐recommended therapy. Model is adjusted for age, fever on presentation, tachypnea on presentation, wheezing on presentation, need for supplemental oxygen, Pediatric Early Warning Score 5, chest radiograph findings, and need for repeat imaging. Model is adjusted for age, wheezing on presentation, need for supplemental oxygen, Pediatric Early Warning Score 5, need for repeat imaging, and length of stay. Model is adjusted for age, wheezing on presentation, and length of stay.

Length of stay0.06 (0.27 to 0.15)0.06 (0.25 to 0.12)5.8 (22.1 to 12.8)
Total costs0.18 (0.40 to 0.04)0.11 (0.32 to 0.09)10.9 (27.4 to 9.4)
Pharmacy total costs0.44 (0.46 to 0.02)0.16 (0.57 to 0.24)14.8 (43.4 to 27.1)

Median total costs of the index hospitalization for the total cohort were $4097 (IQR: $2657$6054), with median inpatient pharmacy costs of $92 (IQR: $40$183) (Table 2). There were no differences in total or inpatient pharmacy costs for patients who received guideline‐recommended therapy compared with those who did not in unadjusted or adjusted analyses. Fourteen patients (6.4%) had antibiotic therapy broadened during hospitalization, 10 were initially prescribed guideline‐recommended therapy, and 4 were initially prescribed nonguideline‐recommended therapy (Table 4).

Clinical Details of Patients Who Had Antibiotic Therapy Broadened During Initial Hospitalization
Initial TherapyReasons for Antibiotic Change Identified From Chart Review
Guideline=10Ampicillin to ceftriaxone:
1 patient with clinical worsening
1 patient with coincident urinary tract infection due to resistant organism
4 patients without evidence of clinical worsening or documentation of rationale
Addition of a macrolide:
3 patients without evidence of clinical worsening or documentation of rationale
Addition of clindamycin:
1 patient with clinical worsening
Nonguideline=4Ceftriaxone to clindamycin:
1 patient with clinical worsening
Addition of a macrolide:
1 patient with clinical worsening
1 patients without evidence of clinical worsening or documentation of rationale
Addition of clindamycin:
1 patient with clinical worsening

Of the 9 pneumonia‐related ED revisits within 30 days of discharge, 7 occurred in patients prescribed empiric guideline‐recommended therapy (Table 5). No ED revisit resulted in hospital readmission or antibiotic change related to pneumonia. Two ED revisits resulted in new antibiotic prescriptions for diagnoses other than pneumonia.

Clinical Details of Patients With an Emergency Department Revisit or Inpatient Readmission Following Index Hospitalization
RevisitInitial TherapyDay PostdischargeClinical Symptoms at Return VisitClinical DiagnosisAntibiotic Prescription
  • NOTE: Abbreviations: ED, emergency department; IV, intravenous.

EDGuideline3Poor oral intake and feverPneumoniaContinued prior antibiotic
EDGuideline8Recurrent cough and feverResolving pneumoniaContinued prior antibiotic
EDGuideline13Follow‐upResolved pneumoniaNo further antibiotic
EDGuideline16Increased work of breathingReactive airway diseaseNo antibiotic
EDGuideline20Persistent coughViral illnessNo antibiotic
EDGuideline22Recurrent cough and congestionSinusitisAugmentin
EDGuideline26Increased work of breathingReactive airway diseaseNo antibiotic
EDNonguideline16Recurrent feverAcute otitis mediaAmoxicillin
EDNonguideline20Recurrent cough and feverViral illnessNo antibiotic
AdmissionGuideline3Increased work of breathingPneumoniaIV ampicillin
AdmissionNonguideline9Refusal to take oral clindamycinPneumoniaIV clindamycin

Two patients were readmitted for a pneumonia‐related illness within 30 days of discharge; 1 had received guideline‐recommended therapy (Table 5). Both patients were directly admitted to the inpatient ward without an associated ED visit. Antibiotic class was not changed for either patient upon readmission, despite the decision to convert to intravenous form.

DISCUSSION

In this retrospective cohort study, patients who received empiric guideline‐recommended antibiotic therapy on admission for CAP had no difference in LOS, total cost of hospitalization, or inpatient pharmacy costs compared with those who received therapy that varied from guideline recommendations. Our study suggests that prescribing narrow‐spectrum therapy and, in some circumstances, combination therapy, as recommended by the 2011 PIDS/IDSA pneumonia guideline, did not result in negative unintended consequences.

In our study, children receiving guideline‐recommended therapy were younger, more likely to have elevated respiratory rate on presentation, and more likely to have an infiltrate on chest radiograph. We hypothesize the age difference is a reflection of common use of nonguideline macrolide monotherapy in the older, school‐age child, as macrolides are commonly used for coverage of Mycoplasma pneumonia in older children with CAP.[15] Children receiving macrolide monotherapy were older than those receiving guideline‐recommended therapy (median age of 7.4 years and 2.5 years, respectively). We also hypothesize that some providers may prescribe macrolide monotherapy to children deemed less ill than expected for CAP (eg, normal percutaneous oxygen saturation). This hypothesis is supported by the finding that 60% of patients who had a normal respiratory rate and received nonguideline therapy were prescribed macrolide monotherapy. We did control for the characteristics that varied between the two treatment groups in our models to eliminate potential confounding.

One prior study evaluated the effects of guideline implementation in CAP. In evaluation of a clinical practice guideline that recommended ampicillin as first‐line therapy for CAP, no significant difference was found following guideline introduction in the number of treatment failures (defined as the need to broaden therapy or development of complicated pneumonia within 48 hours or 30‐day inpatient readmission).[16] Our study builds on these findings by directly comparing outcomes between recipients of guideline and nonguideline therapy, which was not done in the prestudy or poststudy design of prior work.[16] We believe that classifying patients based on empiric therapy received rather than timing of guideline introduction thoroughly examines the effect of following guideline recommendations. Additionally, outcomes other than treatment failures were examined in our study including LOS, costs, and ED revisits.

Our results are similar to other observational studies that compared narrow‐ and broad‐spectrum antibiotics for children hospitalized with CAP. Using administrative data, Williams et al. found no significant difference in LOS or cost between narrow‐ and broad‐spectrum intravenous antibiotic recipients ages 6 months to 18 years at 43 children's hospitals.[17] Queen et al. compared narrow‐ and broad‐spectrum antibiotic therapy for children ages 2 months to 18 years at 4 children's hospitals.[18] Differences in average daily cost were not significant, but children who received narrow‐spectrum antibiotics had a significantly shorter LOS. Finally, an observational study of 319 Israeli children <2 years of age found no significant difference in duration of oxygen requirement, LOS, or need for change in antibiotic therapy between the 66 children prescribed aminopenicillins and the 253 children prescribed cefuroxime.[19] These studies suggest that prescribing narrow‐spectrum antimicrobial therapy, as per the guideline recommendations, results in similar outcomes to broad‐spectrum antimicrobial therapy.

Our study adds to prior studies that compared narrow‐ and broad‐spectrum therapy by comparing outcomes associated with guideline‐recommended therapy to nonguideline therapy. We considered antibiotic therapy as guideline recommended if appropriately chosen per the guideline, not just by simple classification of antibiotic. For example, the use of a cephalosporin in a patient with aminopenicillin allergy was considered guideline‐recommended therapy. We chose to classify the exposure of empiric antibiotic therapy in this manner to reflect true clinical application of the guideline, as not all children are able to receive aminopenicillins. Additionally, as our study stemmed from our prior improvement work aimed at increasing guideline adherent therapy,[7] we have a higher frequency of narrow‐spectrum antibiotic use than prior studies. In our study, almost two‐thirds of patients received narrow‐spectrum therapy, whereas narrow‐spectrum use in prior studies ranged from 10% to 33%.[17, 18, 19] Finally, we were able to confirm the diagnosis of pneumonia via medical record review and to adjust for severity of illness using clinical variables including vital signs, physical exam findings, and laboratory and radiologic study results.

This study must be interpreted in the context of several limitations. First, our study population was defined through discharge diagnosis codes, and therefore dependent on the accuracy of coding. However, we minimized potential for misclassification through use of a previously validated approach to identify patients with CAP and through medical record review to confirm the diagnosis. Second, we may be unable to detect very small differences in outcomes given limited power, specifically for outcomes of LOS, ED revisits, hospital readmissions, and need to broaden antibiotic therapy. Third, residual confounding may be present. Although we controlled for many clinical variables in our analyses, antibiotic prescribing practices may be influenced by unmeasured factors. The potential of system level confounding is mitigated by standardized care for patients with CAP at our institution. Prior system‐level changes using quality‐improvement science have resulted in a high level of adherence with guideline‐recommended antimicrobials as well as standardized medical discharge criteria.[7, 20] Additionally, nonmedical factors may influence LOS, limiting its use as an outcome measure. This limitation was minimized in our study by standardizing medical discharge criteria. Prior work at our institution demonstrated that the majority of patients, including those with CAP, were discharged within 2 hours of meeting medical discharge criteria.[20] Fourth, discharged patients who experienced adverse outcomes may have received care at a nearby adult emergency department or at their pediatrician's office. Although these events would not have been captured in our electronic health record, serious complications due to treatment failure (eg, empyema) would require hospitalization. As our hospital is the only children's hospital in the Greater Cincinnati metropolitan area, these patents would receive care at our institution. Therefore, any misclassification of revisits or readmissions is likely to be minimal. Finally, study patients were admitted to a large tertiary academic children's hospital, warranting further investigation to determine if these findings can be translated to smaller community settings.

In conclusion, receipt of guideline‐recommended antibiotic therapy for patients hospitalized with CAP was not associated with increases in LOS, total costs of hospitalization, or inpatient pharmacy costs. Our findings highlight the importance of changing antibiotic prescribing practices to reflect guideline recommendations, as there was no evidence of negative unintended consequences with our local practice change.

Acknowledgments

Disclosures: Dr. Ambroggio and Dr. Thomson were supported by funds from the NRSA T32HP10027‐14. Dr. Shah was supported by funds from NIAID K01A173729. The authors report no conflicts of interest.

Files
References
  1. Kronman MP, Hersh AL, Feng R, Huang YS, Lee GE, Shah SS. Ambulatory visit rates and antibiotic prescribing for children with pneumonia, 1994–2007. Pediatrics. 2011;127(3):411418.
  2. Lee GE, Lorch SA, Sheffler‐Collins S, Kronman MP, Shah SS. National hospitalization trends for pediatric pneumonia and associated complications. Pediatrics. 2010;126(2):204213.
  3. Keren R, Luan X, Localio R, et al. Prioritization of comparative effectiveness research topics in hospital pediatrics. Arch Pediatr Adolesc Med. 2012;166(12):11551164.
  4. Bradley JS, Byington CL, Shah SS, et al. The management of community‐acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25e76.
  5. Brogan TV, Hall M, Williams DJ, et al. Variability in processes of care and outcomes among children hospitalized with community‐acquired pneumonia. Pediatr Infect Dis J. 2012;31(10):10361041.
  6. Ross RK, Hersh AL, Kronman MP, et al. Impact of IDSA/PIDS guidelines on treatment of community‐acquired pneumonia in hospitalized children. Clin Infect Dis. 2014;58(6):834838.
  7. Ambroggio L, Thomson J, Murtagh Kurowski E, et al. Quality improvement methods increase appropriate antibiotic prescribing for childhood pneumonia. Pediatrics. 2013;131(5):e1623e1631.
  8. Williams DJ, Shah SS, Myers A, et al. Identifying pediatric community‐acquired pneumonia hospitalizations: accuracy of administrative billing codes. JAMA Pediatr. 2013;167(9):851858.
  9. Feudtner C, Hays RM, Haynes G, Geyer JR, Neff JM, Koepsell TD. Deaths attributed to pediatric complex chronic conditions: national trends and implications for supportive care services. Pediatrics. 2001;107(6):E99.
  10. Centers for Medicare 2011.
  11. Kleinman ME, Chameides L, Schexnayder SM, et al. Pediatric advanced life support: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Pediatrics. 2010;126(5):e1361e1399.
  12. Tucker KM, Brewer TL, Baker RB, Demeritt B, Vossmeyer MT. Prospective evaluation of a pediatric inpatient early warning scoring system. J Spec Pediatr Nurs. 2009;14(2):7985.
  13. Vittinghoff E, Glidden DV, Shiboski SC, McCulloch CE. Regression Methods in Biostatistics: Linear, Logistic, Survival, and Repeated Measures Models. New York, NY: Springer; 2005.
  14. Biondi E, McCulloh R, Alverson B, Klein A, Dixon A. Treatment of mycoplasma pneumonia: a systematic review. Pediatrics. 2014;133(6):10811090.
  15. Newman RE, Hedican EB, Herigon JC, Williams DD, Williams AR, Newland JG. Impact of a guideline on management of children hospitalized with community‐acquired pneumonia. Pediatrics. 2012;129(3):e597e604.
  16. Williams DJ, Hall M, Shah SS, et al. Narrow vs broad‐spectrum antimicrobial therapy for children hospitalized with pneumonia. Pediatrics. 2013;132(5):e1141e1148.
  17. Queen MA, Myers AL, Hall M, et al. Comparative effectiveness of empiric antibiotics for community‐acquired pneumonia. Pediatrics. 2014;133(1):e23e29.
  18. Dinur‐Schejter Y, Cohen‐Cymberknoh M, Tenenbaum A, et al. Antibiotic treatment of children with community‐acquired pneumonia: comparison of penicillin or ampicillin versus cefuroxime. Pediatr Pulmonol. 2013;48(1):5258.
  19. White CM, Statile AM, White DL, et al. Using quality improvement to optimise paediatric discharge efficiency. BMJ Qual Saf. 2014;23(5):428436.
Article PDF
Issue
Journal of Hospital Medicine - 10(1)
Publications
Page Number
13-18
Sections
Files
Files
Article PDF
Article PDF

Community‐acquired pneumonia (CAP) is a common and serious infection in children. With more than 150,000 children requiring hospitalization annually, CAP is the fifth most prevalent and the second most costly diagnosis of all pediatric hospitalizations in the United States.[1, 2, 3]

In August 2011, the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) published an evidence‐based guideline for the management of CAP in children. This guideline recommended that fully immunized children without underlying complications who require hospitalization receive an aminopenicillin as first‐line antibiotic therapy.[4] Additionally, the guideline recommends empirically adding a macrolide to an aminopenicillin when atypical pneumonia is a diagnostic consideration.

This recommendation was a substantial departure from practice for hospitals nationwide, as a multicenter study of children's hospitals (20052010) demonstrated that <10% of patients diagnosed with CAP received aminopenicillins as empiric therapy.[5] Since publication of the PIDS/IDSA guidelines, the use of aminopenicillins has increased significantly across institutions, but the majority of hospitalized patients still receive broad‐spectrum cephalosporin therapy for CAP.[6]

At baseline, 30% of patients hospitalized with CAP received guideline‐recommended antibiotic therapy at our institution. Through the use of quality‐improvement methods, the proportion of patients receiving guideline‐recommended therapy increased to 100%.[7] The objective of this study was to ensure that there were not unintended negative consequences to guideline implementation. Specifically, we sought to identify changes in length of stay (LOS), hospital costs, and treatment failures associated with use of guideline‐recommended antibiotic therapy for children hospitalized with uncomplicated CAP.

METHODS

Study Design and Study Population

This retrospective cohort study included children age 3 months to 18 years, hospitalized with CAP, between May 2, 2011 and July 30, 2012, at Cincinnati Children's Hospital Medical Center (CCHMC), a 512‐bed free‐standing children's hospital. The CCHMC Institutional Review Board approved this study with a waiver of informed consent.

Patients were eligible for inclusion if they were admitted to the hospital for inpatient or observation level care with a primary or secondary International Classification of Disease, 9th Revision discharge diagnosis code of pneumonia (480.02, 480.89, 481, 482.0, 482.30‐2, 482.41‐2, 482.83, 482.8990, 483.8, 484.3, 485, 486, 487.0) or effusion/empyema (510.0, 510.9, 511.01, 511.89, 513).[8] Patients with complex chronic conditions[9] were excluded. Medical records of eligible patients (n=260) were reviewed by 2 members of the study team to ensure that patients fell into the purview of the guideline. Patients who did not receive antibiotics (n=11) or for whom there was documented concern for aspiration (n=1) were excluded. Additionally, patients with immunodeficiency (n=1) or who had not received age‐appropriate vaccinations (n=2), and patients who required intensive care unit admission on presentation (n=17) or who had a complicated pneumonia, defined by presence of moderate or large pleural effusion at time of admission (n=8), were also excluded.[7] Finally, for patients with multiple pneumonia admissions, only the index visit was included; subsequent visits occurring within 30 days of discharge were considered readmissions.

Treatment Measure

The primary exposure of interest was empiric antibiotic therapy upon hospital admission. Antibiotic therapy was classified as guideline recommended or nonguideline recommended. Guideline‐recommended therapy was defined as follows:

  1. For children without drug allergies: ampicillin (200 mg/kg/day intravenously) or amoxicillin (90 mg/kg/day orally);
  2. For children with penicillin allergy: ceftriaxone (50100 mg/kg/day intravenously or intramuscularly) or cefdinir (14 mg/kg/day orally);
  3. For children with penicillin and cephalosporin allergy: clindamycin (40 mg/kg/day orally or intravenously); and
  4. Or azithromycin (10 mg/kg/day orally or intravenously on day 1) in combination with antibiotic category 1 or 2 or 3 above.

 

Outcome Measures

The primary outcomes examined were hospital LOS, total cost of hospitalization, and inpatient pharmacy costs. LOS was measured in hours and defined as the difference in time between departure from and arrival to the inpatient unit. Total cost of index hospitalization included both direct and indirect costs, obtained from the Centers for Medicare & Medicaid Services' Relative Value Units data for Current Procedural Terminology codes.[10]

Secondary outcomes included broadening of antibiotic therapy during the hospital course, pneumonia‐related emergency department (ED) revisits within 30 days, and pneumonia‐related inpatient readmissions within 30 days. Broadening of antibiotic therapy was defined as addition of a second antibiotic (eg, adding azithromycin on day 3 of hospitalization) or change in empiric antibiotic to a class with broader antimicrobial activity (eg, ampicillin to ceftriaxone) at any time during hospitalization. As our study population included only patients with uncomplicated pneumonia at the time of admission, this outcome was used to capture possible treatment failure. ED revisits and inpatient readmissions were reviewed by 3 investigators to identify pneumonia‐related visits. To encompass all possible treatment failures, all respiratory‐related complaints (eg, wheezing, respiratory distress) were considered as pneumonia‐related. Disagreements were resolved by group discussion.

Covariates

Severity of illness on presentation was evaluated using the Emergency Severity Index version 4,[11] abnormal vital signs on presentation (as defined by Pediatric Advanced Life Support age‐specific criteria[12]), and need for oxygen in the first 24 hours of hospitalization. Supplemental oxygen is administered for saturations <91% per protocol at our institution. The patient's highest Pediatric Early Warning Scale score[13] during hospitalization was used as a proxy for disease severity. Exam findings on presentation (eg, increased respiratory effort, rales, wheezing) were determined through chart review. Laboratory tests and radiologic imaging variables included complete blood cell count, blood culture, chest radiograph, chest ultrasound, and chest computed tomography. Abnormal white blood cell count was defined as <5000 or >15,000 cells/mL, the defined reference range for the CCHMC clinical laboratory.

Data Analysis

Continuous variables were described using median and interquartile range (IQR) and compared across groups using Wilcoxon rank sum test due to non‐normal distributions. Categorical variables were described by counts and frequencies and compared using the 2 test.

Multivariable linear regression analysis was performed to assess the independent effect of receipt of empiric guideline‐recommended antibiotic therapy on outcomes of LOS and costs while adjusting for covariates. As LOS and costs were non‐normally distributed, we logarithmically transformed these values to use as the dependent variables in our models. The resulting coefficients were back‐transformed to reflect the percent change in LOS and costs incurred between subjects who received empiric guideline therapy compared with those who did not.[14] Covariates were chosen a priori due to their clinical and biological relevance to the outcomes of LOS (eg, wheezing on presentation and need for supplemental oxygen), total cost of hospitalization (eg, LOS and need for repeat imaging), and inpatient pharmacy costs (eg, LOS and wheezing on presentation) (Table 1).

Cohort Characteristics
CharacteristicOverall Cohort, n=220Guideline Therapy, n=166Nonguideline Therapy, n=54P Value
  • NOTE: Abbreviations: CT, computed tomography; IQR, interquartile range; PEWS, Pediatric Early Warning Scale. *P<0.05.

Age, y, median (IQR)2.9 (1.36.3)2.5 (1.35.2)5.6 (2.38.8)<0.01*
Male, no. (%)122 (55.5%)89 (53.6%)33 (61.1%)0.34
Emergency Severity Index, no. (%)0.11
290 (40.9%)73 (44.0%)17 (31.5%) 
3116 (52.7%)85 (51.2%)31 (57.4%) 
414 (6.4%)8 (4.8%)6 (11.1%) 
Abnormal vital signs on presentation, no. (%)
Fever99 (45.0%)80 (48.2%)19 (35.2%)0.10
Tachycardia100 (45.5%)76 (45.8%)24 (44.4%)0.86
Tachypnea124 (56.4%)100 (60.2%)24 (44.4%)0.04*
Hypotension000 
Hypoxia27 (12.3%)24 (14.5%)3 (5.6%)0.08
Physical exam on presentation, no. (%)
Increased respiratory effort146 (66.4%)111 (66.9%)35 (64.8%)0.78
Distressed110 (50.0%)86 (51.8%)24 (44.4%)0.35
Retraction103 (46.8%)81 (48.8%)22 (40.7%)0.30
Grunting17 (7.7%)14 (8.4%)3 (5.6%)0.49
Nasal flaring19 (8.6%)17 (10.2%)2 (3.7%)0.14
Rales135 (61.4%)99 (59.6%)36 (66.7%)0.36
Wheeze91 (41.4%)66 (39.8%)25 (46.3%)0.40
Decreased breath sounds89 (40.5%)65 (39.2%)24 (44.4%)0.49
Dehydration21 (9.6%)13 (7.8%)8 (14.8%)0.13
PEWS 5 during admission, no. (%)43 (19.6%)34 (20.5%)9 (16.7%)0.54
Oxygen requirement in first 24 hours, no. (%)114 (51.8%)90 (53.6%)24 (46.2%)0.35
Complete blood count obtained, no. (%)99 (45.0%)72 (43.4%)27 (50.0%)0.40
Abnormal white blood cell count35 (35.7%)23 (32.4%)12 (44.4%)0.27
Blood culture obtained, no. (%)104 (47.3%)80 (48.2%)24 (44.4%)0.63
Positive2 (1.9%)1 (1.3%)1 (4.2%)0.36
Chest radiograph available, no. (%)214 (97.3%)161 (97.0%)53 (98.2%)0.65
Infiltrate178 (83.2%)139 (86.3%)39 (73.6%)0.03*
Bilateral29 (16.3%)20 (14.4%)9 (23.1%)0.19
Multilobar46 (25.8%)33 (23.7%)13 (33.3%)0.23
Effusion24 (11.2%)16 (9.9%)8 (15.1%)0.30
Additional imaging, no. (%)    
Repeat chest radiograph26 (11.8%)17 (10.2%)9 (16.7%)0.20
Chest ultrasound4 (1.8%)3 (1.8%)1 (1.9%)0.98
Chest CT2 (0.9%)1 (0.6%)1 (1.9%)0.40
Antibiotic, no. (%)   <0.01*
Aminopenicillin140 (63.6%)140 (84.3%)0 (0%) 
Third‐generation cephalosporin37 (16.8%)8 (4.8%)29 (53.7%) 
Macrolide monotherapy18 (8.2%)0 (0%)18 (33.3%) 
Clindamycin2 (0.9%)1 (0.6%)1 (1.9%) 
Levofloxacin1 (0.5%)0 (0%)1 (1.9%) 
Aminopenicillin+macrolide16 (7.3%)16 (9.6%)0 (0%) 
Cephalosporin+macrolide6 (2.7%)1 (0.6%)5 (9.3%) 

Secondary outcomes of broadened antibiotic therapy, ED revisits, and hospital readmissions were assessed using the Fisher exact test. Due to the small number of events, we were unable to evaluate these associations in models adjusted for potential confounders.

All analyses were performed with SAS version 9.3 (SAS Institute, Cary, NC), and P values <0.05 were considered significant.

RESULTS

Of the 220 unique patients included, 122 (55%) were male. The median age was 2.9 years (IQR: 1.36.3 years). Empiric guideline‐recommended therapy was prescribed to 168 (76%) patients (Table 1). Aminopenicillins were the most common guideline‐recommended therapy, accounting for 84% of guideline‐recommended antibiotics. An additional 10% of patients received the guideline‐recommended combination therapy with an aminopenicillin and a macrolide. Nonguideline‐recommended therapy included third‐generation cephalosporin antibiotics (54%) and macrolide monotherapy (33%).

Those who received empiric guideline‐recommended antibiotic therapy were similar to those who received nonguideline‐recommended therapy with respect to sex, Emergency Severity Index, physical exam findings on presentation, oxygen requirement in the first 24 hours, abnormal laboratory findings, presence of effusion on chest radiograph, and need for additional imaging (Table 1). However, patients in the guideline‐recommended therapy group were significantly younger (median 2.5 years vs 5.6 years, P0.01), more likely to have elevated respiratory rate on presentation (60.2% vs 44.4%, P=0.04), and more likely to have an infiltrate on chest radiograph (86.3% vs 73.6%, P=0.03) (Table 1). Patients who received nonguideline‐recommended macrolide monotherapy had a median age of 7.4 years (IQR: 5.89.8 years).

Median hospital LOS for the total cohort was 1.3 days (IQR: 0.91.9 days) (Table 2). There were no differences in LOS between patients who received and did not receive guideline‐recommended therapy in the unadjusted or the adjusted model (Table 3).

Unadjusted Outcomes
OutcomeGuideline Therapy, n=166Nonguideline Therapy, n=54P Value
  • NOTE: Abbreviations: IQR, interquartile range.

Length of stay, d, median (IQR)1.3 (0.91.9)1.3 (0.92.0)0.74
Total costs, median, (IQR)$4118 ($2,647$6,004)$4045 ($2,829$6,200)0.44
Pharmacy total costs, median, (IQR)$84 ($40$179)$106 ($58$217)0.12
Broadened therapy, no. (%)10 (6.0%)4 (7.4%)0.75
Emergency department revisit, no. (%)7 (4.2%)2 (3.7%)1.00
Readmission, no. (%)1 (0.6%)1 (1.9%)0.43
Univariate and Multivariate Analyses of Receipt of Empiric Guideline‐Recommended Therapy With Length of Stay, Total Costs, and Pharmacy Costs
OutcomeUnadjusted Coefficient (95% CI)Adjusted Coefficient (95% CI)Adjusted % Change in Outcome (95% CI)*
  • NOTE: Abbreviations: CI, confidence interval. *Negative adjusted percent change indicates decrease in outcome associated with guideline‐recommended therapy; positive adjusted percent change indicates increase in outcome associated with guideline‐recommended therapy. Model is adjusted for age, fever on presentation, tachypnea on presentation, wheezing on presentation, need for supplemental oxygen, Pediatric Early Warning Score 5, chest radiograph findings, and need for repeat imaging. Model is adjusted for age, wheezing on presentation, need for supplemental oxygen, Pediatric Early Warning Score 5, need for repeat imaging, and length of stay. Model is adjusted for age, wheezing on presentation, and length of stay.

Length of stay0.06 (0.27 to 0.15)0.06 (0.25 to 0.12)5.8 (22.1 to 12.8)
Total costs0.18 (0.40 to 0.04)0.11 (0.32 to 0.09)10.9 (27.4 to 9.4)
Pharmacy total costs0.44 (0.46 to 0.02)0.16 (0.57 to 0.24)14.8 (43.4 to 27.1)

Median total costs of the index hospitalization for the total cohort were $4097 (IQR: $2657$6054), with median inpatient pharmacy costs of $92 (IQR: $40$183) (Table 2). There were no differences in total or inpatient pharmacy costs for patients who received guideline‐recommended therapy compared with those who did not in unadjusted or adjusted analyses. Fourteen patients (6.4%) had antibiotic therapy broadened during hospitalization, 10 were initially prescribed guideline‐recommended therapy, and 4 were initially prescribed nonguideline‐recommended therapy (Table 4).

Clinical Details of Patients Who Had Antibiotic Therapy Broadened During Initial Hospitalization
Initial TherapyReasons for Antibiotic Change Identified From Chart Review
Guideline=10Ampicillin to ceftriaxone:
1 patient with clinical worsening
1 patient with coincident urinary tract infection due to resistant organism
4 patients without evidence of clinical worsening or documentation of rationale
Addition of a macrolide:
3 patients without evidence of clinical worsening or documentation of rationale
Addition of clindamycin:
1 patient with clinical worsening
Nonguideline=4Ceftriaxone to clindamycin:
1 patient with clinical worsening
Addition of a macrolide:
1 patient with clinical worsening
1 patients without evidence of clinical worsening or documentation of rationale
Addition of clindamycin:
1 patient with clinical worsening

Of the 9 pneumonia‐related ED revisits within 30 days of discharge, 7 occurred in patients prescribed empiric guideline‐recommended therapy (Table 5). No ED revisit resulted in hospital readmission or antibiotic change related to pneumonia. Two ED revisits resulted in new antibiotic prescriptions for diagnoses other than pneumonia.

Clinical Details of Patients With an Emergency Department Revisit or Inpatient Readmission Following Index Hospitalization
RevisitInitial TherapyDay PostdischargeClinical Symptoms at Return VisitClinical DiagnosisAntibiotic Prescription
  • NOTE: Abbreviations: ED, emergency department; IV, intravenous.

EDGuideline3Poor oral intake and feverPneumoniaContinued prior antibiotic
EDGuideline8Recurrent cough and feverResolving pneumoniaContinued prior antibiotic
EDGuideline13Follow‐upResolved pneumoniaNo further antibiotic
EDGuideline16Increased work of breathingReactive airway diseaseNo antibiotic
EDGuideline20Persistent coughViral illnessNo antibiotic
EDGuideline22Recurrent cough and congestionSinusitisAugmentin
EDGuideline26Increased work of breathingReactive airway diseaseNo antibiotic
EDNonguideline16Recurrent feverAcute otitis mediaAmoxicillin
EDNonguideline20Recurrent cough and feverViral illnessNo antibiotic
AdmissionGuideline3Increased work of breathingPneumoniaIV ampicillin
AdmissionNonguideline9Refusal to take oral clindamycinPneumoniaIV clindamycin

Two patients were readmitted for a pneumonia‐related illness within 30 days of discharge; 1 had received guideline‐recommended therapy (Table 5). Both patients were directly admitted to the inpatient ward without an associated ED visit. Antibiotic class was not changed for either patient upon readmission, despite the decision to convert to intravenous form.

DISCUSSION

In this retrospective cohort study, patients who received empiric guideline‐recommended antibiotic therapy on admission for CAP had no difference in LOS, total cost of hospitalization, or inpatient pharmacy costs compared with those who received therapy that varied from guideline recommendations. Our study suggests that prescribing narrow‐spectrum therapy and, in some circumstances, combination therapy, as recommended by the 2011 PIDS/IDSA pneumonia guideline, did not result in negative unintended consequences.

In our study, children receiving guideline‐recommended therapy were younger, more likely to have elevated respiratory rate on presentation, and more likely to have an infiltrate on chest radiograph. We hypothesize the age difference is a reflection of common use of nonguideline macrolide monotherapy in the older, school‐age child, as macrolides are commonly used for coverage of Mycoplasma pneumonia in older children with CAP.[15] Children receiving macrolide monotherapy were older than those receiving guideline‐recommended therapy (median age of 7.4 years and 2.5 years, respectively). We also hypothesize that some providers may prescribe macrolide monotherapy to children deemed less ill than expected for CAP (eg, normal percutaneous oxygen saturation). This hypothesis is supported by the finding that 60% of patients who had a normal respiratory rate and received nonguideline therapy were prescribed macrolide monotherapy. We did control for the characteristics that varied between the two treatment groups in our models to eliminate potential confounding.

One prior study evaluated the effects of guideline implementation in CAP. In evaluation of a clinical practice guideline that recommended ampicillin as first‐line therapy for CAP, no significant difference was found following guideline introduction in the number of treatment failures (defined as the need to broaden therapy or development of complicated pneumonia within 48 hours or 30‐day inpatient readmission).[16] Our study builds on these findings by directly comparing outcomes between recipients of guideline and nonguideline therapy, which was not done in the prestudy or poststudy design of prior work.[16] We believe that classifying patients based on empiric therapy received rather than timing of guideline introduction thoroughly examines the effect of following guideline recommendations. Additionally, outcomes other than treatment failures were examined in our study including LOS, costs, and ED revisits.

Our results are similar to other observational studies that compared narrow‐ and broad‐spectrum antibiotics for children hospitalized with CAP. Using administrative data, Williams et al. found no significant difference in LOS or cost between narrow‐ and broad‐spectrum intravenous antibiotic recipients ages 6 months to 18 years at 43 children's hospitals.[17] Queen et al. compared narrow‐ and broad‐spectrum antibiotic therapy for children ages 2 months to 18 years at 4 children's hospitals.[18] Differences in average daily cost were not significant, but children who received narrow‐spectrum antibiotics had a significantly shorter LOS. Finally, an observational study of 319 Israeli children <2 years of age found no significant difference in duration of oxygen requirement, LOS, or need for change in antibiotic therapy between the 66 children prescribed aminopenicillins and the 253 children prescribed cefuroxime.[19] These studies suggest that prescribing narrow‐spectrum antimicrobial therapy, as per the guideline recommendations, results in similar outcomes to broad‐spectrum antimicrobial therapy.

Our study adds to prior studies that compared narrow‐ and broad‐spectrum therapy by comparing outcomes associated with guideline‐recommended therapy to nonguideline therapy. We considered antibiotic therapy as guideline recommended if appropriately chosen per the guideline, not just by simple classification of antibiotic. For example, the use of a cephalosporin in a patient with aminopenicillin allergy was considered guideline‐recommended therapy. We chose to classify the exposure of empiric antibiotic therapy in this manner to reflect true clinical application of the guideline, as not all children are able to receive aminopenicillins. Additionally, as our study stemmed from our prior improvement work aimed at increasing guideline adherent therapy,[7] we have a higher frequency of narrow‐spectrum antibiotic use than prior studies. In our study, almost two‐thirds of patients received narrow‐spectrum therapy, whereas narrow‐spectrum use in prior studies ranged from 10% to 33%.[17, 18, 19] Finally, we were able to confirm the diagnosis of pneumonia via medical record review and to adjust for severity of illness using clinical variables including vital signs, physical exam findings, and laboratory and radiologic study results.

This study must be interpreted in the context of several limitations. First, our study population was defined through discharge diagnosis codes, and therefore dependent on the accuracy of coding. However, we minimized potential for misclassification through use of a previously validated approach to identify patients with CAP and through medical record review to confirm the diagnosis. Second, we may be unable to detect very small differences in outcomes given limited power, specifically for outcomes of LOS, ED revisits, hospital readmissions, and need to broaden antibiotic therapy. Third, residual confounding may be present. Although we controlled for many clinical variables in our analyses, antibiotic prescribing practices may be influenced by unmeasured factors. The potential of system level confounding is mitigated by standardized care for patients with CAP at our institution. Prior system‐level changes using quality‐improvement science have resulted in a high level of adherence with guideline‐recommended antimicrobials as well as standardized medical discharge criteria.[7, 20] Additionally, nonmedical factors may influence LOS, limiting its use as an outcome measure. This limitation was minimized in our study by standardizing medical discharge criteria. Prior work at our institution demonstrated that the majority of patients, including those with CAP, were discharged within 2 hours of meeting medical discharge criteria.[20] Fourth, discharged patients who experienced adverse outcomes may have received care at a nearby adult emergency department or at their pediatrician's office. Although these events would not have been captured in our electronic health record, serious complications due to treatment failure (eg, empyema) would require hospitalization. As our hospital is the only children's hospital in the Greater Cincinnati metropolitan area, these patents would receive care at our institution. Therefore, any misclassification of revisits or readmissions is likely to be minimal. Finally, study patients were admitted to a large tertiary academic children's hospital, warranting further investigation to determine if these findings can be translated to smaller community settings.

In conclusion, receipt of guideline‐recommended antibiotic therapy for patients hospitalized with CAP was not associated with increases in LOS, total costs of hospitalization, or inpatient pharmacy costs. Our findings highlight the importance of changing antibiotic prescribing practices to reflect guideline recommendations, as there was no evidence of negative unintended consequences with our local practice change.

Acknowledgments

Disclosures: Dr. Ambroggio and Dr. Thomson were supported by funds from the NRSA T32HP10027‐14. Dr. Shah was supported by funds from NIAID K01A173729. The authors report no conflicts of interest.

Community‐acquired pneumonia (CAP) is a common and serious infection in children. With more than 150,000 children requiring hospitalization annually, CAP is the fifth most prevalent and the second most costly diagnosis of all pediatric hospitalizations in the United States.[1, 2, 3]

In August 2011, the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) published an evidence‐based guideline for the management of CAP in children. This guideline recommended that fully immunized children without underlying complications who require hospitalization receive an aminopenicillin as first‐line antibiotic therapy.[4] Additionally, the guideline recommends empirically adding a macrolide to an aminopenicillin when atypical pneumonia is a diagnostic consideration.

This recommendation was a substantial departure from practice for hospitals nationwide, as a multicenter study of children's hospitals (20052010) demonstrated that <10% of patients diagnosed with CAP received aminopenicillins as empiric therapy.[5] Since publication of the PIDS/IDSA guidelines, the use of aminopenicillins has increased significantly across institutions, but the majority of hospitalized patients still receive broad‐spectrum cephalosporin therapy for CAP.[6]

At baseline, 30% of patients hospitalized with CAP received guideline‐recommended antibiotic therapy at our institution. Through the use of quality‐improvement methods, the proportion of patients receiving guideline‐recommended therapy increased to 100%.[7] The objective of this study was to ensure that there were not unintended negative consequences to guideline implementation. Specifically, we sought to identify changes in length of stay (LOS), hospital costs, and treatment failures associated with use of guideline‐recommended antibiotic therapy for children hospitalized with uncomplicated CAP.

METHODS

Study Design and Study Population

This retrospective cohort study included children age 3 months to 18 years, hospitalized with CAP, between May 2, 2011 and July 30, 2012, at Cincinnati Children's Hospital Medical Center (CCHMC), a 512‐bed free‐standing children's hospital. The CCHMC Institutional Review Board approved this study with a waiver of informed consent.

Patients were eligible for inclusion if they were admitted to the hospital for inpatient or observation level care with a primary or secondary International Classification of Disease, 9th Revision discharge diagnosis code of pneumonia (480.02, 480.89, 481, 482.0, 482.30‐2, 482.41‐2, 482.83, 482.8990, 483.8, 484.3, 485, 486, 487.0) or effusion/empyema (510.0, 510.9, 511.01, 511.89, 513).[8] Patients with complex chronic conditions[9] were excluded. Medical records of eligible patients (n=260) were reviewed by 2 members of the study team to ensure that patients fell into the purview of the guideline. Patients who did not receive antibiotics (n=11) or for whom there was documented concern for aspiration (n=1) were excluded. Additionally, patients with immunodeficiency (n=1) or who had not received age‐appropriate vaccinations (n=2), and patients who required intensive care unit admission on presentation (n=17) or who had a complicated pneumonia, defined by presence of moderate or large pleural effusion at time of admission (n=8), were also excluded.[7] Finally, for patients with multiple pneumonia admissions, only the index visit was included; subsequent visits occurring within 30 days of discharge were considered readmissions.

Treatment Measure

The primary exposure of interest was empiric antibiotic therapy upon hospital admission. Antibiotic therapy was classified as guideline recommended or nonguideline recommended. Guideline‐recommended therapy was defined as follows:

  1. For children without drug allergies: ampicillin (200 mg/kg/day intravenously) or amoxicillin (90 mg/kg/day orally);
  2. For children with penicillin allergy: ceftriaxone (50100 mg/kg/day intravenously or intramuscularly) or cefdinir (14 mg/kg/day orally);
  3. For children with penicillin and cephalosporin allergy: clindamycin (40 mg/kg/day orally or intravenously); and
  4. Or azithromycin (10 mg/kg/day orally or intravenously on day 1) in combination with antibiotic category 1 or 2 or 3 above.

 

Outcome Measures

The primary outcomes examined were hospital LOS, total cost of hospitalization, and inpatient pharmacy costs. LOS was measured in hours and defined as the difference in time between departure from and arrival to the inpatient unit. Total cost of index hospitalization included both direct and indirect costs, obtained from the Centers for Medicare & Medicaid Services' Relative Value Units data for Current Procedural Terminology codes.[10]

Secondary outcomes included broadening of antibiotic therapy during the hospital course, pneumonia‐related emergency department (ED) revisits within 30 days, and pneumonia‐related inpatient readmissions within 30 days. Broadening of antibiotic therapy was defined as addition of a second antibiotic (eg, adding azithromycin on day 3 of hospitalization) or change in empiric antibiotic to a class with broader antimicrobial activity (eg, ampicillin to ceftriaxone) at any time during hospitalization. As our study population included only patients with uncomplicated pneumonia at the time of admission, this outcome was used to capture possible treatment failure. ED revisits and inpatient readmissions were reviewed by 3 investigators to identify pneumonia‐related visits. To encompass all possible treatment failures, all respiratory‐related complaints (eg, wheezing, respiratory distress) were considered as pneumonia‐related. Disagreements were resolved by group discussion.

Covariates

Severity of illness on presentation was evaluated using the Emergency Severity Index version 4,[11] abnormal vital signs on presentation (as defined by Pediatric Advanced Life Support age‐specific criteria[12]), and need for oxygen in the first 24 hours of hospitalization. Supplemental oxygen is administered for saturations <91% per protocol at our institution. The patient's highest Pediatric Early Warning Scale score[13] during hospitalization was used as a proxy for disease severity. Exam findings on presentation (eg, increased respiratory effort, rales, wheezing) were determined through chart review. Laboratory tests and radiologic imaging variables included complete blood cell count, blood culture, chest radiograph, chest ultrasound, and chest computed tomography. Abnormal white blood cell count was defined as <5000 or >15,000 cells/mL, the defined reference range for the CCHMC clinical laboratory.

Data Analysis

Continuous variables were described using median and interquartile range (IQR) and compared across groups using Wilcoxon rank sum test due to non‐normal distributions. Categorical variables were described by counts and frequencies and compared using the 2 test.

Multivariable linear regression analysis was performed to assess the independent effect of receipt of empiric guideline‐recommended antibiotic therapy on outcomes of LOS and costs while adjusting for covariates. As LOS and costs were non‐normally distributed, we logarithmically transformed these values to use as the dependent variables in our models. The resulting coefficients were back‐transformed to reflect the percent change in LOS and costs incurred between subjects who received empiric guideline therapy compared with those who did not.[14] Covariates were chosen a priori due to their clinical and biological relevance to the outcomes of LOS (eg, wheezing on presentation and need for supplemental oxygen), total cost of hospitalization (eg, LOS and need for repeat imaging), and inpatient pharmacy costs (eg, LOS and wheezing on presentation) (Table 1).

Cohort Characteristics
CharacteristicOverall Cohort, n=220Guideline Therapy, n=166Nonguideline Therapy, n=54P Value
  • NOTE: Abbreviations: CT, computed tomography; IQR, interquartile range; PEWS, Pediatric Early Warning Scale. *P<0.05.

Age, y, median (IQR)2.9 (1.36.3)2.5 (1.35.2)5.6 (2.38.8)<0.01*
Male, no. (%)122 (55.5%)89 (53.6%)33 (61.1%)0.34
Emergency Severity Index, no. (%)0.11
290 (40.9%)73 (44.0%)17 (31.5%) 
3116 (52.7%)85 (51.2%)31 (57.4%) 
414 (6.4%)8 (4.8%)6 (11.1%) 
Abnormal vital signs on presentation, no. (%)
Fever99 (45.0%)80 (48.2%)19 (35.2%)0.10
Tachycardia100 (45.5%)76 (45.8%)24 (44.4%)0.86
Tachypnea124 (56.4%)100 (60.2%)24 (44.4%)0.04*
Hypotension000 
Hypoxia27 (12.3%)24 (14.5%)3 (5.6%)0.08
Physical exam on presentation, no. (%)
Increased respiratory effort146 (66.4%)111 (66.9%)35 (64.8%)0.78
Distressed110 (50.0%)86 (51.8%)24 (44.4%)0.35
Retraction103 (46.8%)81 (48.8%)22 (40.7%)0.30
Grunting17 (7.7%)14 (8.4%)3 (5.6%)0.49
Nasal flaring19 (8.6%)17 (10.2%)2 (3.7%)0.14
Rales135 (61.4%)99 (59.6%)36 (66.7%)0.36
Wheeze91 (41.4%)66 (39.8%)25 (46.3%)0.40
Decreased breath sounds89 (40.5%)65 (39.2%)24 (44.4%)0.49
Dehydration21 (9.6%)13 (7.8%)8 (14.8%)0.13
PEWS 5 during admission, no. (%)43 (19.6%)34 (20.5%)9 (16.7%)0.54
Oxygen requirement in first 24 hours, no. (%)114 (51.8%)90 (53.6%)24 (46.2%)0.35
Complete blood count obtained, no. (%)99 (45.0%)72 (43.4%)27 (50.0%)0.40
Abnormal white blood cell count35 (35.7%)23 (32.4%)12 (44.4%)0.27
Blood culture obtained, no. (%)104 (47.3%)80 (48.2%)24 (44.4%)0.63
Positive2 (1.9%)1 (1.3%)1 (4.2%)0.36
Chest radiograph available, no. (%)214 (97.3%)161 (97.0%)53 (98.2%)0.65
Infiltrate178 (83.2%)139 (86.3%)39 (73.6%)0.03*
Bilateral29 (16.3%)20 (14.4%)9 (23.1%)0.19
Multilobar46 (25.8%)33 (23.7%)13 (33.3%)0.23
Effusion24 (11.2%)16 (9.9%)8 (15.1%)0.30
Additional imaging, no. (%)    
Repeat chest radiograph26 (11.8%)17 (10.2%)9 (16.7%)0.20
Chest ultrasound4 (1.8%)3 (1.8%)1 (1.9%)0.98
Chest CT2 (0.9%)1 (0.6%)1 (1.9%)0.40
Antibiotic, no. (%)   <0.01*
Aminopenicillin140 (63.6%)140 (84.3%)0 (0%) 
Third‐generation cephalosporin37 (16.8%)8 (4.8%)29 (53.7%) 
Macrolide monotherapy18 (8.2%)0 (0%)18 (33.3%) 
Clindamycin2 (0.9%)1 (0.6%)1 (1.9%) 
Levofloxacin1 (0.5%)0 (0%)1 (1.9%) 
Aminopenicillin+macrolide16 (7.3%)16 (9.6%)0 (0%) 
Cephalosporin+macrolide6 (2.7%)1 (0.6%)5 (9.3%) 

Secondary outcomes of broadened antibiotic therapy, ED revisits, and hospital readmissions were assessed using the Fisher exact test. Due to the small number of events, we were unable to evaluate these associations in models adjusted for potential confounders.

All analyses were performed with SAS version 9.3 (SAS Institute, Cary, NC), and P values <0.05 were considered significant.

RESULTS

Of the 220 unique patients included, 122 (55%) were male. The median age was 2.9 years (IQR: 1.36.3 years). Empiric guideline‐recommended therapy was prescribed to 168 (76%) patients (Table 1). Aminopenicillins were the most common guideline‐recommended therapy, accounting for 84% of guideline‐recommended antibiotics. An additional 10% of patients received the guideline‐recommended combination therapy with an aminopenicillin and a macrolide. Nonguideline‐recommended therapy included third‐generation cephalosporin antibiotics (54%) and macrolide monotherapy (33%).

Those who received empiric guideline‐recommended antibiotic therapy were similar to those who received nonguideline‐recommended therapy with respect to sex, Emergency Severity Index, physical exam findings on presentation, oxygen requirement in the first 24 hours, abnormal laboratory findings, presence of effusion on chest radiograph, and need for additional imaging (Table 1). However, patients in the guideline‐recommended therapy group were significantly younger (median 2.5 years vs 5.6 years, P0.01), more likely to have elevated respiratory rate on presentation (60.2% vs 44.4%, P=0.04), and more likely to have an infiltrate on chest radiograph (86.3% vs 73.6%, P=0.03) (Table 1). Patients who received nonguideline‐recommended macrolide monotherapy had a median age of 7.4 years (IQR: 5.89.8 years).

Median hospital LOS for the total cohort was 1.3 days (IQR: 0.91.9 days) (Table 2). There were no differences in LOS between patients who received and did not receive guideline‐recommended therapy in the unadjusted or the adjusted model (Table 3).

Unadjusted Outcomes
OutcomeGuideline Therapy, n=166Nonguideline Therapy, n=54P Value
  • NOTE: Abbreviations: IQR, interquartile range.

Length of stay, d, median (IQR)1.3 (0.91.9)1.3 (0.92.0)0.74
Total costs, median, (IQR)$4118 ($2,647$6,004)$4045 ($2,829$6,200)0.44
Pharmacy total costs, median, (IQR)$84 ($40$179)$106 ($58$217)0.12
Broadened therapy, no. (%)10 (6.0%)4 (7.4%)0.75
Emergency department revisit, no. (%)7 (4.2%)2 (3.7%)1.00
Readmission, no. (%)1 (0.6%)1 (1.9%)0.43
Univariate and Multivariate Analyses of Receipt of Empiric Guideline‐Recommended Therapy With Length of Stay, Total Costs, and Pharmacy Costs
OutcomeUnadjusted Coefficient (95% CI)Adjusted Coefficient (95% CI)Adjusted % Change in Outcome (95% CI)*
  • NOTE: Abbreviations: CI, confidence interval. *Negative adjusted percent change indicates decrease in outcome associated with guideline‐recommended therapy; positive adjusted percent change indicates increase in outcome associated with guideline‐recommended therapy. Model is adjusted for age, fever on presentation, tachypnea on presentation, wheezing on presentation, need for supplemental oxygen, Pediatric Early Warning Score 5, chest radiograph findings, and need for repeat imaging. Model is adjusted for age, wheezing on presentation, need for supplemental oxygen, Pediatric Early Warning Score 5, need for repeat imaging, and length of stay. Model is adjusted for age, wheezing on presentation, and length of stay.

Length of stay0.06 (0.27 to 0.15)0.06 (0.25 to 0.12)5.8 (22.1 to 12.8)
Total costs0.18 (0.40 to 0.04)0.11 (0.32 to 0.09)10.9 (27.4 to 9.4)
Pharmacy total costs0.44 (0.46 to 0.02)0.16 (0.57 to 0.24)14.8 (43.4 to 27.1)

Median total costs of the index hospitalization for the total cohort were $4097 (IQR: $2657$6054), with median inpatient pharmacy costs of $92 (IQR: $40$183) (Table 2). There were no differences in total or inpatient pharmacy costs for patients who received guideline‐recommended therapy compared with those who did not in unadjusted or adjusted analyses. Fourteen patients (6.4%) had antibiotic therapy broadened during hospitalization, 10 were initially prescribed guideline‐recommended therapy, and 4 were initially prescribed nonguideline‐recommended therapy (Table 4).

Clinical Details of Patients Who Had Antibiotic Therapy Broadened During Initial Hospitalization
Initial TherapyReasons for Antibiotic Change Identified From Chart Review
Guideline=10Ampicillin to ceftriaxone:
1 patient with clinical worsening
1 patient with coincident urinary tract infection due to resistant organism
4 patients without evidence of clinical worsening or documentation of rationale
Addition of a macrolide:
3 patients without evidence of clinical worsening or documentation of rationale
Addition of clindamycin:
1 patient with clinical worsening
Nonguideline=4Ceftriaxone to clindamycin:
1 patient with clinical worsening
Addition of a macrolide:
1 patient with clinical worsening
1 patients without evidence of clinical worsening or documentation of rationale
Addition of clindamycin:
1 patient with clinical worsening

Of the 9 pneumonia‐related ED revisits within 30 days of discharge, 7 occurred in patients prescribed empiric guideline‐recommended therapy (Table 5). No ED revisit resulted in hospital readmission or antibiotic change related to pneumonia. Two ED revisits resulted in new antibiotic prescriptions for diagnoses other than pneumonia.

Clinical Details of Patients With an Emergency Department Revisit or Inpatient Readmission Following Index Hospitalization
RevisitInitial TherapyDay PostdischargeClinical Symptoms at Return VisitClinical DiagnosisAntibiotic Prescription
  • NOTE: Abbreviations: ED, emergency department; IV, intravenous.

EDGuideline3Poor oral intake and feverPneumoniaContinued prior antibiotic
EDGuideline8Recurrent cough and feverResolving pneumoniaContinued prior antibiotic
EDGuideline13Follow‐upResolved pneumoniaNo further antibiotic
EDGuideline16Increased work of breathingReactive airway diseaseNo antibiotic
EDGuideline20Persistent coughViral illnessNo antibiotic
EDGuideline22Recurrent cough and congestionSinusitisAugmentin
EDGuideline26Increased work of breathingReactive airway diseaseNo antibiotic
EDNonguideline16Recurrent feverAcute otitis mediaAmoxicillin
EDNonguideline20Recurrent cough and feverViral illnessNo antibiotic
AdmissionGuideline3Increased work of breathingPneumoniaIV ampicillin
AdmissionNonguideline9Refusal to take oral clindamycinPneumoniaIV clindamycin

Two patients were readmitted for a pneumonia‐related illness within 30 days of discharge; 1 had received guideline‐recommended therapy (Table 5). Both patients were directly admitted to the inpatient ward without an associated ED visit. Antibiotic class was not changed for either patient upon readmission, despite the decision to convert to intravenous form.

DISCUSSION

In this retrospective cohort study, patients who received empiric guideline‐recommended antibiotic therapy on admission for CAP had no difference in LOS, total cost of hospitalization, or inpatient pharmacy costs compared with those who received therapy that varied from guideline recommendations. Our study suggests that prescribing narrow‐spectrum therapy and, in some circumstances, combination therapy, as recommended by the 2011 PIDS/IDSA pneumonia guideline, did not result in negative unintended consequences.

In our study, children receiving guideline‐recommended therapy were younger, more likely to have elevated respiratory rate on presentation, and more likely to have an infiltrate on chest radiograph. We hypothesize the age difference is a reflection of common use of nonguideline macrolide monotherapy in the older, school‐age child, as macrolides are commonly used for coverage of Mycoplasma pneumonia in older children with CAP.[15] Children receiving macrolide monotherapy were older than those receiving guideline‐recommended therapy (median age of 7.4 years and 2.5 years, respectively). We also hypothesize that some providers may prescribe macrolide monotherapy to children deemed less ill than expected for CAP (eg, normal percutaneous oxygen saturation). This hypothesis is supported by the finding that 60% of patients who had a normal respiratory rate and received nonguideline therapy were prescribed macrolide monotherapy. We did control for the characteristics that varied between the two treatment groups in our models to eliminate potential confounding.

One prior study evaluated the effects of guideline implementation in CAP. In evaluation of a clinical practice guideline that recommended ampicillin as first‐line therapy for CAP, no significant difference was found following guideline introduction in the number of treatment failures (defined as the need to broaden therapy or development of complicated pneumonia within 48 hours or 30‐day inpatient readmission).[16] Our study builds on these findings by directly comparing outcomes between recipients of guideline and nonguideline therapy, which was not done in the prestudy or poststudy design of prior work.[16] We believe that classifying patients based on empiric therapy received rather than timing of guideline introduction thoroughly examines the effect of following guideline recommendations. Additionally, outcomes other than treatment failures were examined in our study including LOS, costs, and ED revisits.

Our results are similar to other observational studies that compared narrow‐ and broad‐spectrum antibiotics for children hospitalized with CAP. Using administrative data, Williams et al. found no significant difference in LOS or cost between narrow‐ and broad‐spectrum intravenous antibiotic recipients ages 6 months to 18 years at 43 children's hospitals.[17] Queen et al. compared narrow‐ and broad‐spectrum antibiotic therapy for children ages 2 months to 18 years at 4 children's hospitals.[18] Differences in average daily cost were not significant, but children who received narrow‐spectrum antibiotics had a significantly shorter LOS. Finally, an observational study of 319 Israeli children <2 years of age found no significant difference in duration of oxygen requirement, LOS, or need for change in antibiotic therapy between the 66 children prescribed aminopenicillins and the 253 children prescribed cefuroxime.[19] These studies suggest that prescribing narrow‐spectrum antimicrobial therapy, as per the guideline recommendations, results in similar outcomes to broad‐spectrum antimicrobial therapy.

Our study adds to prior studies that compared narrow‐ and broad‐spectrum therapy by comparing outcomes associated with guideline‐recommended therapy to nonguideline therapy. We considered antibiotic therapy as guideline recommended if appropriately chosen per the guideline, not just by simple classification of antibiotic. For example, the use of a cephalosporin in a patient with aminopenicillin allergy was considered guideline‐recommended therapy. We chose to classify the exposure of empiric antibiotic therapy in this manner to reflect true clinical application of the guideline, as not all children are able to receive aminopenicillins. Additionally, as our study stemmed from our prior improvement work aimed at increasing guideline adherent therapy,[7] we have a higher frequency of narrow‐spectrum antibiotic use than prior studies. In our study, almost two‐thirds of patients received narrow‐spectrum therapy, whereas narrow‐spectrum use in prior studies ranged from 10% to 33%.[17, 18, 19] Finally, we were able to confirm the diagnosis of pneumonia via medical record review and to adjust for severity of illness using clinical variables including vital signs, physical exam findings, and laboratory and radiologic study results.

This study must be interpreted in the context of several limitations. First, our study population was defined through discharge diagnosis codes, and therefore dependent on the accuracy of coding. However, we minimized potential for misclassification through use of a previously validated approach to identify patients with CAP and through medical record review to confirm the diagnosis. Second, we may be unable to detect very small differences in outcomes given limited power, specifically for outcomes of LOS, ED revisits, hospital readmissions, and need to broaden antibiotic therapy. Third, residual confounding may be present. Although we controlled for many clinical variables in our analyses, antibiotic prescribing practices may be influenced by unmeasured factors. The potential of system level confounding is mitigated by standardized care for patients with CAP at our institution. Prior system‐level changes using quality‐improvement science have resulted in a high level of adherence with guideline‐recommended antimicrobials as well as standardized medical discharge criteria.[7, 20] Additionally, nonmedical factors may influence LOS, limiting its use as an outcome measure. This limitation was minimized in our study by standardizing medical discharge criteria. Prior work at our institution demonstrated that the majority of patients, including those with CAP, were discharged within 2 hours of meeting medical discharge criteria.[20] Fourth, discharged patients who experienced adverse outcomes may have received care at a nearby adult emergency department or at their pediatrician's office. Although these events would not have been captured in our electronic health record, serious complications due to treatment failure (eg, empyema) would require hospitalization. As our hospital is the only children's hospital in the Greater Cincinnati metropolitan area, these patents would receive care at our institution. Therefore, any misclassification of revisits or readmissions is likely to be minimal. Finally, study patients were admitted to a large tertiary academic children's hospital, warranting further investigation to determine if these findings can be translated to smaller community settings.

In conclusion, receipt of guideline‐recommended antibiotic therapy for patients hospitalized with CAP was not associated with increases in LOS, total costs of hospitalization, or inpatient pharmacy costs. Our findings highlight the importance of changing antibiotic prescribing practices to reflect guideline recommendations, as there was no evidence of negative unintended consequences with our local practice change.

Acknowledgments

Disclosures: Dr. Ambroggio and Dr. Thomson were supported by funds from the NRSA T32HP10027‐14. Dr. Shah was supported by funds from NIAID K01A173729. The authors report no conflicts of interest.

References
  1. Kronman MP, Hersh AL, Feng R, Huang YS, Lee GE, Shah SS. Ambulatory visit rates and antibiotic prescribing for children with pneumonia, 1994–2007. Pediatrics. 2011;127(3):411418.
  2. Lee GE, Lorch SA, Sheffler‐Collins S, Kronman MP, Shah SS. National hospitalization trends for pediatric pneumonia and associated complications. Pediatrics. 2010;126(2):204213.
  3. Keren R, Luan X, Localio R, et al. Prioritization of comparative effectiveness research topics in hospital pediatrics. Arch Pediatr Adolesc Med. 2012;166(12):11551164.
  4. Bradley JS, Byington CL, Shah SS, et al. The management of community‐acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25e76.
  5. Brogan TV, Hall M, Williams DJ, et al. Variability in processes of care and outcomes among children hospitalized with community‐acquired pneumonia. Pediatr Infect Dis J. 2012;31(10):10361041.
  6. Ross RK, Hersh AL, Kronman MP, et al. Impact of IDSA/PIDS guidelines on treatment of community‐acquired pneumonia in hospitalized children. Clin Infect Dis. 2014;58(6):834838.
  7. Ambroggio L, Thomson J, Murtagh Kurowski E, et al. Quality improvement methods increase appropriate antibiotic prescribing for childhood pneumonia. Pediatrics. 2013;131(5):e1623e1631.
  8. Williams DJ, Shah SS, Myers A, et al. Identifying pediatric community‐acquired pneumonia hospitalizations: accuracy of administrative billing codes. JAMA Pediatr. 2013;167(9):851858.
  9. Feudtner C, Hays RM, Haynes G, Geyer JR, Neff JM, Koepsell TD. Deaths attributed to pediatric complex chronic conditions: national trends and implications for supportive care services. Pediatrics. 2001;107(6):E99.
  10. Centers for Medicare 2011.
  11. Kleinman ME, Chameides L, Schexnayder SM, et al. Pediatric advanced life support: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Pediatrics. 2010;126(5):e1361e1399.
  12. Tucker KM, Brewer TL, Baker RB, Demeritt B, Vossmeyer MT. Prospective evaluation of a pediatric inpatient early warning scoring system. J Spec Pediatr Nurs. 2009;14(2):7985.
  13. Vittinghoff E, Glidden DV, Shiboski SC, McCulloch CE. Regression Methods in Biostatistics: Linear, Logistic, Survival, and Repeated Measures Models. New York, NY: Springer; 2005.
  14. Biondi E, McCulloh R, Alverson B, Klein A, Dixon A. Treatment of mycoplasma pneumonia: a systematic review. Pediatrics. 2014;133(6):10811090.
  15. Newman RE, Hedican EB, Herigon JC, Williams DD, Williams AR, Newland JG. Impact of a guideline on management of children hospitalized with community‐acquired pneumonia. Pediatrics. 2012;129(3):e597e604.
  16. Williams DJ, Hall M, Shah SS, et al. Narrow vs broad‐spectrum antimicrobial therapy for children hospitalized with pneumonia. Pediatrics. 2013;132(5):e1141e1148.
  17. Queen MA, Myers AL, Hall M, et al. Comparative effectiveness of empiric antibiotics for community‐acquired pneumonia. Pediatrics. 2014;133(1):e23e29.
  18. Dinur‐Schejter Y, Cohen‐Cymberknoh M, Tenenbaum A, et al. Antibiotic treatment of children with community‐acquired pneumonia: comparison of penicillin or ampicillin versus cefuroxime. Pediatr Pulmonol. 2013;48(1):5258.
  19. White CM, Statile AM, White DL, et al. Using quality improvement to optimise paediatric discharge efficiency. BMJ Qual Saf. 2014;23(5):428436.
References
  1. Kronman MP, Hersh AL, Feng R, Huang YS, Lee GE, Shah SS. Ambulatory visit rates and antibiotic prescribing for children with pneumonia, 1994–2007. Pediatrics. 2011;127(3):411418.
  2. Lee GE, Lorch SA, Sheffler‐Collins S, Kronman MP, Shah SS. National hospitalization trends for pediatric pneumonia and associated complications. Pediatrics. 2010;126(2):204213.
  3. Keren R, Luan X, Localio R, et al. Prioritization of comparative effectiveness research topics in hospital pediatrics. Arch Pediatr Adolesc Med. 2012;166(12):11551164.
  4. Bradley JS, Byington CL, Shah SS, et al. The management of community‐acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25e76.
  5. Brogan TV, Hall M, Williams DJ, et al. Variability in processes of care and outcomes among children hospitalized with community‐acquired pneumonia. Pediatr Infect Dis J. 2012;31(10):10361041.
  6. Ross RK, Hersh AL, Kronman MP, et al. Impact of IDSA/PIDS guidelines on treatment of community‐acquired pneumonia in hospitalized children. Clin Infect Dis. 2014;58(6):834838.
  7. Ambroggio L, Thomson J, Murtagh Kurowski E, et al. Quality improvement methods increase appropriate antibiotic prescribing for childhood pneumonia. Pediatrics. 2013;131(5):e1623e1631.
  8. Williams DJ, Shah SS, Myers A, et al. Identifying pediatric community‐acquired pneumonia hospitalizations: accuracy of administrative billing codes. JAMA Pediatr. 2013;167(9):851858.
  9. Feudtner C, Hays RM, Haynes G, Geyer JR, Neff JM, Koepsell TD. Deaths attributed to pediatric complex chronic conditions: national trends and implications for supportive care services. Pediatrics. 2001;107(6):E99.
  10. Centers for Medicare 2011.
  11. Kleinman ME, Chameides L, Schexnayder SM, et al. Pediatric advanced life support: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Pediatrics. 2010;126(5):e1361e1399.
  12. Tucker KM, Brewer TL, Baker RB, Demeritt B, Vossmeyer MT. Prospective evaluation of a pediatric inpatient early warning scoring system. J Spec Pediatr Nurs. 2009;14(2):7985.
  13. Vittinghoff E, Glidden DV, Shiboski SC, McCulloch CE. Regression Methods in Biostatistics: Linear, Logistic, Survival, and Repeated Measures Models. New York, NY: Springer; 2005.
  14. Biondi E, McCulloh R, Alverson B, Klein A, Dixon A. Treatment of mycoplasma pneumonia: a systematic review. Pediatrics. 2014;133(6):10811090.
  15. Newman RE, Hedican EB, Herigon JC, Williams DD, Williams AR, Newland JG. Impact of a guideline on management of children hospitalized with community‐acquired pneumonia. Pediatrics. 2012;129(3):e597e604.
  16. Williams DJ, Hall M, Shah SS, et al. Narrow vs broad‐spectrum antimicrobial therapy for children hospitalized with pneumonia. Pediatrics. 2013;132(5):e1141e1148.
  17. Queen MA, Myers AL, Hall M, et al. Comparative effectiveness of empiric antibiotics for community‐acquired pneumonia. Pediatrics. 2014;133(1):e23e29.
  18. Dinur‐Schejter Y, Cohen‐Cymberknoh M, Tenenbaum A, et al. Antibiotic treatment of children with community‐acquired pneumonia: comparison of penicillin or ampicillin versus cefuroxime. Pediatr Pulmonol. 2013;48(1):5258.
  19. White CM, Statile AM, White DL, et al. Using quality improvement to optimise paediatric discharge efficiency. BMJ Qual Saf. 2014;23(5):428436.
Issue
Journal of Hospital Medicine - 10(1)
Issue
Journal of Hospital Medicine - 10(1)
Page Number
13-18
Page Number
13-18
Publications
Publications
Article Type
Display Headline
Hospital outcomes associated with guideline‐recommended antibiotic therapy for pediatric pneumonia
Display Headline
Hospital outcomes associated with guideline‐recommended antibiotic therapy for pediatric pneumonia
Sections
Article Source

© 2014 Society of Hospital Medicine

Disallow All Ads
Correspondence Location
Address for correspondence and reprint requests: Joanna Thomson, MD, Division of Hospital Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML 9016, Cincinnati, OH, 45220; Telephone: 513‐803‐8092; Fax: 13‐803‐9244; E‐mail: joanna.thomson@cchmc.org
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Article PDF Media
Media Files