Infection Control & Hospital Epidemiology
and prolonged mechanical ventilation compared with matched patients without pediatric VAE.3–5 A previous cohort study found that pediatric AVAC criteria were met in 44% of pediatric VAC cases.5 We reasoned that the wide variability in the frac- tion of VACs that meet AVAC criteria and who get laboratory testing may indicate potential opportunities to improve anti- microbial stewardship and to improve laboratory testing prac- tices. We sought to characterize variability in antimicrobial use and laboratory testing for infections associated with pediatric AVAC and pediatric PVAP across various ICU types and hospitals.
Methods Study design and population
We identified VAE cases from a previous cohort of children ≤18 years of age who had been ventilated for≥1 day in pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), or neonatal intensive care units (NICUs) at 6 US hospitals: Beth Israel Deaconess Medical Center, Boston Chil- dren’sHospital, Children’s Hospital of Philadelphia, Rainbow Babies and Children’s Hospital, Rush University Medical Center, and University of Utah Healthcare. The 6 hospitals included 3 CICUs, 5 PICUs, and 5 NICUs. The study period varied by hospital (ranging from 8 to 66 months), based on the timing of availability of electronic data for ventilator parameters. The earliest start date was February 5, 2008; for all hospitals, the study period ended June 30, 2013. Each pediatric VAC case was matched 1:1 with subjects without pediatric VAC by hospital, ICU type on admission, age±50% (unless the pediatric VAC subject was <8 days old, in which case comparison subjects were matched within 2 days of age), gestational age in weeks (for NICU patients only; matched±1 week), presence of congenital heart disease (based on International Classification of Disease, Ninth Revision [ICD-9] diagnosis and procedure codes, excluding patent ductus arteriosus), and the number of venti- lation days prior to the pediatric VAC event plus 1 day. Case patients who did not have VAC based on adjudication and their corresponding controls were excluded from the analysis. ICU type was defined as the ICU location at the start of the venti- lation episode. Underlying chronic comorbidities were identified by chart review using a standardized chart abstraction tool described previously.6
Definitions for pediatric VAC, AVAC, and PVAP
Pediatric VAC was defined as worsening oxygenation, expressed by an increase in minimum daily fraction of inspired oxygen (FIO2)by≥0.25 or mean airway pressure (MAP) by≥4cm H2O for≥2 days following a period of stability or improvement on the ventilator. The VAE window period was defined as the 2 days before, the day of, and the 2 days after the VAC onset date, as long as all of the days were on or after the third day of mechanical ventilation. Criteria for pediatric AVAC weremet if a new antimicrobial agent was started within the VAE window, continued for≥4 days, and had not been given in the 2 days preceding the start date. AVAC patients with positive respiratory diagnostic tests in the VAE window were defined as having pediatric PVAP. Criteria for PVAP, including qualifying patho- gens for PVAP, definitions for threshold values for cultured specimens meeting PVAP, and definitions for “purulent
Results
From an initial cohort of 9,025 patients who experienced 10,377 hospital admissions and 12,167 mechanical ventilation episodes, our final cohort included 192 VAC cases (43 in the CICU, 70 in the PICU, and 79 in the NICU) with 192 matched controls. Characteristics of patients with VAC are described in Table 1. VAC cases were more likely to have underlying immunosup- pression or renal disease than controls, while more controls had underlying neurologic conditions or were tracheostomy and/or ventilator dependent. Differences in underlying comorbidities were notable between ICU types. A higher proportion of VAC cases with underlying immunosuppression were located in the PICU (29%) at the time of ventilation onset than in the CICU (7%) or NICU (1%).
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respiratory secretions” (ie, secretions from lung, bronchi, or trachea containing≥25 neutrophils and≤10 squamous epithe- lial cells per low power field [lpx, ×100]), were defined in accordance with CDC NHSN VAE definitions.1 “Invasive” respiratory diagnostic testing was defined as positive samples from bronchoalveolar lavage (BAL), protected specimen brush (PSB), lung tissue, or pleural fluid, whereas “noninvasive” sam- ples included those from sputum or endotracheal aspirate. Viral diagnostic results were available from 3 hospitals. Lung pathol- ogy data were available from 2 hospitals.
Antimicrobial spectrum and duration
Based on a previously published study, the antimicrobial spectrum was classified into the following 5 groups: Class 1 agents included penicillin, oxacillin, nafcillin, dicloxacillin, ampicillin, amoxicillin, cefazolin, cephalexin, and nitrofurantoin. Class 2 agents included tetracyclines, macrolides, trimethoprim- sulfamethoxazole, cefoxitin, cefuroxime, and clindamycin. Class 3 agents included amoxicillin-clavulanate, ampicillin-sulbactam, and ceftriaxone. Class 4 agents included aminoglycosides, fluoroquinolones, aztreonam, ceftazidime, cefepime, ceftaroline, ertapenem, and vancomycin. Class 5 agents included imipenem, meropenem, piperacillin-tazobactam, colistin, daptomycin, and linezolid.7 For the purposes of this study, we classified metro- nidazole as a class 2 agent. Antimicrobial duration was defined in accordance with CDC definitions for qualifying antimicrobial days (QADs).1 Anti- microbial administration data were extracted from both case and control patients throughout their hospitalization. Eligible anti- microbials were defined by CDC NHSN criteria for VAE.1 An antimicrobial was considered “new” if it was initiated on or after the third day of mechanical ventilation and within the VAE window period and had not been administered in the preceding 2 days. Cases were classified as being on antimicrobials at the time of the VAC event, regardless of the date of intubation, if they were on an antimicrobial agent 3 or more days prior to the VAC event on day −3.
Statistical analysis
Statistical analyses were performed using STATA version 12.1 software (StataCorp, College Station, TX). This study was approved by the institutional review boards at Harvard Pilgrim Health Care and each of the participating hospitals with waivers of informed consent.
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