Safety and Effectiveness of Piperacillin/Tazobactam (Zosyn®) in the Treatment of Pediatric Hospital Acquired Pneumonia (HAP): A Retrospective Cohort Study

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Retrospective study

Study drug and medical condition

• Medicinal product name, other:
  Zosyn
• Medical condition to be studied:
  Pneumonia

Population studied

• Short description of the study population:
  The study population involved pediatric patients aged 2 months to <18 years diagnosed with hospital acquired pneumonia (HAP) received treatment with piperacillin/tazobactam identified from the Pediatric Health Information System (PHIS) between January 01, 2003 and June 30, 2016.; Inclusion criteria:;  Hospital admission between January 1, 2003 and June 30, 2016,;  Aged between 2 months and 18 years at the time of hospital admission,;  Presence of at least one discharge ICD-9-CM code consistent with bacterial pneumonia (Table 1), and;  Received at least 1 dose of P/T or comparator HAP appropriate antibiotic during the hospitalization.; ; Exclusion criteria:;  Patients who have received an antibiotic(s) consistent with treatment of CAP (i.e., 2nd or 3rd Generation cephalosporins, ampicillin/amoxicillin, amoxicillin/clavulanic acid, ampicillin/sulbactam, azithromycin, clindamycin, or penicillin) during the first two days of hospitalization,;  Patients with a diagnosis of cystic fibrosis based on ICD-9 CM codes (Table 2); these patients will be excluded because they are frequently admitted for cystic fibrosis pulmonary exacerbations and receive similar antibiotic therapy but likely do not have HAP, ;  Patients who were started on two HAP appropriate antibiotics simultaneously (within one day). These patients will be excluded because they will likely to be clinically different than patients started on monotherapy, ;  Patients who received P/T or comparator antibiotics for other infection(s) prior to the diagnosis of HAP, or,;  Patients with missing pharmacy data in PHIS
• Age groups:
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
• Special population of interest:
  Other
• Special population of interest, other:
  Hospital acquired pneumonia patients
• Estimated number of subjects:
  450

Study design details

• Main study objective:
  The main objective of the study is to assess safety and effectiveness of piperacillin/Tazobactam for the treatment of hospital acquired pneumonia (HAP) in pediatric patients.
• Outcomes:
  To estimate the risk of serious events including mortality among pediatric patients with HAP in the US, comparing Piperacillin/Tazobactam to comparator HAP appropriate antibiotics (i.e. ticarcillin-clavulanate, carbapenems, ceftazidime, cefepime, or ciprofloxacin). To evaluate effectiveness of the antibiotic therapy (using binary treatment outcome “patient clinically improved” or patient clinically did not improve”) in pediatric patients with HAP in the US, comparing Piperacillin/Tazobactam to comparator HAP appropriate antibiotic therapies.
• Data analysis plan:
  Descriptive statistics will be performed to describe patient characteristics such as age, sex, race/ethnicity, geographical location, length of hospital stay, presence of co-morbid conditions at the time of hospital admission, concomitant medication use and ventilator support in the P/T exposed and comparator groups. For each of the serious events outcomes, one or more events that occur during the follow-up time will be counted for each patient. Each outcome will be analyzed using a Poisson model with an offset for person-time at risk and robust variance estimate. Results will be presented by group (P/T, comparator) for the:• Total number of events, • Cumulative person-time at risk, • Model adjusted event rate per 1,000 person years with corresponding 95% CI, and• Model adjusted incidence rate ratio (IRR) with corresponding 95% CI.