Comparison of mortality between nosocomial and community-acquired febrile neutropenia patients treated initially with cefazolin plus tobramycin: retrospective chart review

Abstract

Cefazolin plus tobramycin have been determined to be effective for community-acquired FN, but have not been evaluated in the treatment of nosocomial FN. This study compared the incidence of mortality from 2002 to 2004 with 2008 to 2009 in patients with nosocomial FN treated with cefazolin plus tobramycin and compared characteristics of patients with nosocomially acquired FN to community acquired FN. A retrospective chart review of 45 nosocomial FN episodes from 2008 to 2009, and 54 episodes from 2002 to 2004 treated with cefazolin plus tobramycin was conducted. Data on the community acquired FN episodes was obtained from our previous research. Nosocomial FN mortality increased from 4% in 2002–2004 to 13% in 2008–2009 (p = 0.08). The nosocomial cohort was at higher risk of medical complications and mortality than the community-acquired cohort based on several variables (neutrophil nadir, duration of neutropenia and fever, hematological malignancy, MASCC and Talcott score; p < 0.05). As a result, the nosocomial cohort was treated with longer courses of antibiotic therapy (14 days vs 7 days; p < 0.0001) and were more likely to require broader spectrum antibiotics (64 out of 99 vs 34 out of 96; p < 0.0001). There was an observed increased risk of mortality from 2002 to 2004 compared with 2008 to 2009 in patients treated with cefazolin plus tobramycin for nosocomial FN, this was notable despite not attaining statistical significance. Therefore, this regimen is not appropriate for nosocomial FN.

Appendices

Appendix 1. Data collected for each episode reviewed

• Age

• Gender

• Cancer-related diagnosis

• Chemotherapy most recently received

• Intent of chemotherapy (palliative, adjunctive or curative)

• Date of most recent cycle of chemotherapy

• Date of admission

• Neutrophil count on day of admission

• Maximum oral temperature on day of admission

• Date of FN diagnosis

• Neutrophil count on day of diagnosis with FN

• Maximum oral temperature on day of diagnosis with FN

• Start and stop dates for cefazolin and tobramycin

• Initial cefazolin and tobramycin dosing received by the patient

• Other antimicrobials administered with start and stop dates

• Number of febrile days before becoming consistently afebrile for at least 24 h or discharge/death

• Number of afebrile days until discharge or death

• Neutrophil count at nadir

• Date that nadir occurred

• Number of days to nadir

• Total number of days on antimicrobial therapy overall

• Date that neutrophil count recovered to ≥ 0.5 ×10⁹/L

• Number of days for neutrophil count recovery to ≥ 0.5 ×10⁹ /L from nadir

• Chest X-ray results (i.e., pneumonia present or absent)

• Microbiological cultures and sensitivity results

• Identification of an infection due to Gram-positive or Gram-negative bacteria

• Documentation of any identified source of infection

• Number of days from admission to positive culture

• Comorbidities in addition to cancer (e.g., chronic obstructive pulmonary disease, myocardial infarction, heart failure, peripheral vascular disease, cerebrovascular disease, pulmonary embolism, dementia, connective tissue disease, peptic ulcer disease, liver disease, diabetes, diabetes with organ damage, hemiplegia, AIDS)

• Serum creatinine on admission and peak during tobramycin therapy

• Use of prophylaxis antibiotics

• Use of granulocyte colony-stimulating factor (G-CSF)

• Occurrence of previous FN episodes

• Death during admission

• Death attributable to antimicrobial failure (defined as death during treatment for FN)

• If patient was followed by the infectious diseases consult service (yes/no; nosocomial cohort only)

Appendix 2. Definitions

• Chemotherapy classification:

  • Curative—chemotherapy administered with the intent to cure the underlying disease. High-intensity chemotherapy prior to stem cell or bone marrow transplantation was classified as curative.

  • Adjuvant—chemotherapy administered following a definitive treatment intervention to decrease risk of reoccurrence

  • Palliative—chemotherapy administered without curative intent to decrease tumor load and increase life expectancy

• Burden of illness used in MASCC score:

  • Mild or no symptoms—asymptomatic patients

  • Severe symptoms—systemically ill patients with hemodynamic instability were classified as severe (patients with a heart rate greater than 100 beats per minute or systolic blood pressure less than 90 mmHg who require admission to an Intensive Care Unit).

  • Moderate symptoms—all other patients (examples include: patients with severe chills, pain, unable to work for the past few days, some signs and symptoms of infection, but not sepsis, etc.).

• Date of most recent chemotherapy:

  • Recorded as the first day of the cycle for regimens consisting of more than 1 day of therapy.

  • Recorded as the day therapy was initiated for patients receiving daily chemotherapy

• Time to nadir:

  • Calculated as the number of days from the first day of chemotherapy to the lowest documented neutrophil count, inclusive.

• Number of days before becoming afebrile until discharge:

  • Calculated as the number of days until documentation of consecutive temperatures ≤ 38°C until discharge.

• Broadened antibiotic coverage:

  • Agents prescribed for the purpose of broadening therapy to cover pathogens not adequately covered by cefazolin plus tobramycin alone for the management of febrile neutropenia, included both antibiotic and antifungal agents.

  • Modifying therapy to oral antibiotics in a stable patient and narrowing therapy once an infection had been identified were not considered indicators of failure with cefazolin plus tobramycin.

  • Fluconazole <200 mg orally daily and antiviral agents were not considered to be broadened therapy, since they were presumed to be prescribed for oral thrush or viral infections respectively, and not specifically associated with continued fever of febrile neutropenia.

• The total number of days of therapy overall:

  • Calculated as the number of days from initiation of cefazolin plus tobramycin to the last day of therapy with any antibiotic for the treatment of febrile neutropenia while in hospital, inclusive.

  • If the patient was discharged or died before recovery, time to discharge or death was used.