Antibiotics for Aspiration Pneumonia in Neurologically Impaired Children

Exclusion Criteria

Children transferred from another hospital were excluded as records from their initial presentation, including treatment and outcomes, were not available. We also excluded children with tracheostomy^15,16 or chronic ventilator dependence,¹⁷ those with a diagnosis of human immunodeficiency virus or tuberculosis, and children who received chemotherapy during hospitalization given expected differences in etiology, treatment, and outcomes.¹⁸

Exposure

The primary exposure was antibiotic therapy received in the first two days of admission. Antibiotics were classified by their antimicrobial spectra of activity as defined by The Sanford Guide to Antimicrobial Therapy¹⁹ against the most commonly recognized pathogens of aspiration pneumonia: anaerobes, Gram-negatives, and P. aeruginosa (Appendix Table 1).^10,20 For example, penicillin G and clindamycin were among the antibiotics classified as providing anaerobic coverage alone, whereas ceftriaxone was classified as providing Gram-negative coverage alone and ampicillin-sulbactam or as combination therapy with clindamycin and ceftriaxone were classified as providing anaerobic and Gram-negative coverage. Piperacillin-tazobactam and meropenem were classified as providing anaerobic, Gram-negative, and P. aeruginosa coverage. We excluded antibiotics that do not provide coverage against anaerobes, Gram-negative, or P. aeruginosa (eg, ampicillin, azithromycin) or that provide coverage against Gram-negative and P. aeruginosa, but not anaerobes (eg, cefepime, tobramycin), as these therapies were prescribed for <5% of the cohort. We chose not to examine the coverage for Streptococcus pneumonia or Staphylococcus aureus as antibiotics included in this analysis covered these bacteria for 99.9% of our cohort.

Outcomes included acute respiratory failure during hospitalization, intensive care unit (ICU) transfer, and hospital length of stay (LOS). Acute respiratory failure during hospitalization was defined as the presence of Clinical Transaction Classification (CTC) or ICD-9 procedure code for noninvasive or invasive mechanical ventilation on day two or later of hospitalization, with or without the need for respiratory support on day 0 or day 1 (Appendix Table 2). Given the variability in hospital policies that may drive ICU admission criteria for complex patients, our outcome of ICU transfer was defined as the requirement for ICU level care on day two or later of hospitalization without ICU admission. Acute respiratory failure and ICU care occurring within the first two hospital days were not classified as outcomes because these early events likely reflect illness severity at presentation rather than outcomes attributable to treatment failure; these were included as markers of severity in the models.

Patient Demographics and Clinical Characteristics

Demographic and clinical characteristics that might influence antibiotic choice and/or hospital outcomes were assessed. Clinical characteristics included complex chronic conditions,^21-23 medical technology assistance,²⁴ performance of diagnostic testing, and markers of severe illness on presentation. Diagnostic testing included bacterial cultures (blood, respiratory, urine) and chest radiograph performance in the first two days of hospitalization. Results of diagnostic testing are not available in the PHIS. Illness severity on presentation included acute respiratory failure, pleural drainage, receipt of vasoactive agents, and transfusion of blood products in the first two days of hospitalization (Appendix Table 2).^17,25,26

Continuous data were described with median and interquartile ranges (IQR) due to nonnormal distribution. Categorical data were described with frequencies and percentages. Patient demographics, clinical characteristics, and hospital outcomes were stratified by empiric antimicrobial coverage and compared using chi-square and Kruskal–Wallis tests as appropriate.