Clinical Benefit of Empiric High-dose Levofloxacin Therapy for Adults With Community-onset Enterobacteriaceae Bacteremia

Ching Chi Lee, Chao-Yung Yang, Chung Hsun Lee, Chih-Chia Hsieh, Ming-Yuan Hong, Hung Jen Tang, Wen-Chien Ko

Research output: Contribution to journalArticle

Abstract

Purpose: Levofloxacin is commonly prescribed to treat varied community-acquired gram-negative infections; knowledge of the therapeutic efficacies of high-dose (HD) administration is helpful to improve patient care. Methods: In this 6-year cohort, adults with community-onset Enterobacteriaceae bacteremia were retrospectively studied in 2 hospitals. To overcome the confounding factors in the dosage choice of empiric administration, patients receiving empiric intravenous HD (750 mg/d) therapy were matched with those receiving the conventional dose (CD; 500 mg/d) by using individual propensity scores, calculated by the independent predictors of 30-day crude mortality. Findings: Initially, more patients with critical illness (Pitt bacteremia score [PBS] ≥4) at bacteremia onset and comorbid malignancies and the higher 15- and 30-day mortality rate were recorded in 136 patients receiving HD therapy, compared to 103 receiving CD therapy. After appropriate matching, differences in patient demographic and clinical characteristics between the HD (n = 103) and CD (n = 103) groups were nonsignificant. Consequently, crude mortality rates at 3, 15, or 30 days after onset of bacteremia did not differ. However, the period of time to defervescence, total intravenous antimicrobial administration, and hospital stay was shorter in the HD group than in the CD group. Similarly, regardless if patients had more critical illness (PBS ≥2) or stabilized illness (PBS <2), the advantage of empiric HD therapy on defervescence remained significant. Within 60 days after discontinuation of intravenous levofloxacin therapy, the proportion of recurrent bacteremia, posttreatment overall infections, and posttreatment crude mortality was similar between the HD and CD groups. Implications: For adults with community-onset Enterobacteriaceae bacteremia, empiric administration of HD levofloxacin was as effective as CD levofloxacin in reducing mortality and, notably, led to more rapid defervescence compared with CD administration. (Clin Ther. 2019; 41:XXX–XXX)

Original languageEnglish
JournalClinical Therapeutics
DOIs
Publication statusAccepted/In press - 2019 Jan 1

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Levofloxacin
Enterobacteriaceae
Bacteremia
Mortality
Therapeutics
Critical Illness
Propensity Score
Infection
Intravenous Administration
Length of Stay
Patient Care
Demography

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

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title = "Clinical Benefit of Empiric High-dose Levofloxacin Therapy for Adults With Community-onset Enterobacteriaceae Bacteremia",
abstract = "Purpose: Levofloxacin is commonly prescribed to treat varied community-acquired gram-negative infections; knowledge of the therapeutic efficacies of high-dose (HD) administration is helpful to improve patient care. Methods: In this 6-year cohort, adults with community-onset Enterobacteriaceae bacteremia were retrospectively studied in 2 hospitals. To overcome the confounding factors in the dosage choice of empiric administration, patients receiving empiric intravenous HD (750 mg/d) therapy were matched with those receiving the conventional dose (CD; 500 mg/d) by using individual propensity scores, calculated by the independent predictors of 30-day crude mortality. Findings: Initially, more patients with critical illness (Pitt bacteremia score [PBS] ≥4) at bacteremia onset and comorbid malignancies and the higher 15- and 30-day mortality rate were recorded in 136 patients receiving HD therapy, compared to 103 receiving CD therapy. After appropriate matching, differences in patient demographic and clinical characteristics between the HD (n = 103) and CD (n = 103) groups were nonsignificant. Consequently, crude mortality rates at 3, 15, or 30 days after onset of bacteremia did not differ. However, the period of time to defervescence, total intravenous antimicrobial administration, and hospital stay was shorter in the HD group than in the CD group. Similarly, regardless if patients had more critical illness (PBS ≥2) or stabilized illness (PBS <2), the advantage of empiric HD therapy on defervescence remained significant. Within 60 days after discontinuation of intravenous levofloxacin therapy, the proportion of recurrent bacteremia, posttreatment overall infections, and posttreatment crude mortality was similar between the HD and CD groups. Implications: For adults with community-onset Enterobacteriaceae bacteremia, empiric administration of HD levofloxacin was as effective as CD levofloxacin in reducing mortality and, notably, led to more rapid defervescence compared with CD administration. (Clin Ther. 2019; 41:XXX–XXX)",
author = "Lee, {Ching Chi} and Chao-Yung Yang and Lee, {Chung Hsun} and Chih-Chia Hsieh and Ming-Yuan Hong and Tang, {Hung Jen} and Wen-Chien Ko",
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T1 - Clinical Benefit of Empiric High-dose Levofloxacin Therapy for Adults With Community-onset Enterobacteriaceae Bacteremia

AU - Lee, Ching Chi

AU - Yang, Chao-Yung

AU - Lee, Chung Hsun

AU - Hsieh, Chih-Chia

AU - Hong, Ming-Yuan

AU - Tang, Hung Jen

AU - Ko, Wen-Chien

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: Levofloxacin is commonly prescribed to treat varied community-acquired gram-negative infections; knowledge of the therapeutic efficacies of high-dose (HD) administration is helpful to improve patient care. Methods: In this 6-year cohort, adults with community-onset Enterobacteriaceae bacteremia were retrospectively studied in 2 hospitals. To overcome the confounding factors in the dosage choice of empiric administration, patients receiving empiric intravenous HD (750 mg/d) therapy were matched with those receiving the conventional dose (CD; 500 mg/d) by using individual propensity scores, calculated by the independent predictors of 30-day crude mortality. Findings: Initially, more patients with critical illness (Pitt bacteremia score [PBS] ≥4) at bacteremia onset and comorbid malignancies and the higher 15- and 30-day mortality rate were recorded in 136 patients receiving HD therapy, compared to 103 receiving CD therapy. After appropriate matching, differences in patient demographic and clinical characteristics between the HD (n = 103) and CD (n = 103) groups were nonsignificant. Consequently, crude mortality rates at 3, 15, or 30 days after onset of bacteremia did not differ. However, the period of time to defervescence, total intravenous antimicrobial administration, and hospital stay was shorter in the HD group than in the CD group. Similarly, regardless if patients had more critical illness (PBS ≥2) or stabilized illness (PBS <2), the advantage of empiric HD therapy on defervescence remained significant. Within 60 days after discontinuation of intravenous levofloxacin therapy, the proportion of recurrent bacteremia, posttreatment overall infections, and posttreatment crude mortality was similar between the HD and CD groups. Implications: For adults with community-onset Enterobacteriaceae bacteremia, empiric administration of HD levofloxacin was as effective as CD levofloxacin in reducing mortality and, notably, led to more rapid defervescence compared with CD administration. (Clin Ther. 2019; 41:XXX–XXX)

AB - Purpose: Levofloxacin is commonly prescribed to treat varied community-acquired gram-negative infections; knowledge of the therapeutic efficacies of high-dose (HD) administration is helpful to improve patient care. Methods: In this 6-year cohort, adults with community-onset Enterobacteriaceae bacteremia were retrospectively studied in 2 hospitals. To overcome the confounding factors in the dosage choice of empiric administration, patients receiving empiric intravenous HD (750 mg/d) therapy were matched with those receiving the conventional dose (CD; 500 mg/d) by using individual propensity scores, calculated by the independent predictors of 30-day crude mortality. Findings: Initially, more patients with critical illness (Pitt bacteremia score [PBS] ≥4) at bacteremia onset and comorbid malignancies and the higher 15- and 30-day mortality rate were recorded in 136 patients receiving HD therapy, compared to 103 receiving CD therapy. After appropriate matching, differences in patient demographic and clinical characteristics between the HD (n = 103) and CD (n = 103) groups were nonsignificant. Consequently, crude mortality rates at 3, 15, or 30 days after onset of bacteremia did not differ. However, the period of time to defervescence, total intravenous antimicrobial administration, and hospital stay was shorter in the HD group than in the CD group. Similarly, regardless if patients had more critical illness (PBS ≥2) or stabilized illness (PBS <2), the advantage of empiric HD therapy on defervescence remained significant. Within 60 days after discontinuation of intravenous levofloxacin therapy, the proportion of recurrent bacteremia, posttreatment overall infections, and posttreatment crude mortality was similar between the HD and CD groups. Implications: For adults with community-onset Enterobacteriaceae bacteremia, empiric administration of HD levofloxacin was as effective as CD levofloxacin in reducing mortality and, notably, led to more rapid defervescence compared with CD administration. (Clin Ther. 2019; 41:XXX–XXX)

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