Empirical third-generation cephalosporin therapy for adults with community-onset Enterobacteriaceae bacteraemia: Impact of revised CLSI breakpoints

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Abstract

Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients (n = 409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR) = 19.96; P < 0.001]; high Pitt bacteraemia score (≥4) at bacteraemia onset (OR = 13.91; P < 0.001); bacteraemia because of pneumonia (OR = 5.45; P = 0.007); de-escalation after empirical therapy (OR = 0.28; P = 0.03); and isolates with a CTX MIC ≤ 1 mg/L (OR = 0.17; P = 0.02). Of note, isolates with a CTX MIC ≤ 8 mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC (γ = 1.00; P = 0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC ≤ 1 mg/L.

Original languageEnglish
Pages (from-to)297-303
Number of pages7
JournalInternational journal of antimicrobial agents
Volume47
Issue number4
DOIs
Publication statusPublished - 2016 Apr

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Cefotaxime
Enterobacteriaceae
Cephalosporins
Bacteremia
Odds Ratio
Ceftriaxone
Therapeutics
Mortality
Medical Records
Pneumonia
Anti-Bacterial Agents
Morbidity

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

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title = "Empirical third-generation cephalosporin therapy for adults with community-onset Enterobacteriaceae bacteraemia: Impact of revised CLSI breakpoints",
abstract = "Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients (n = 409) were categorised into de-escalation (260; 63.6{\%}), no switch (115; 28.1{\%}) and escalation (34; 8.3{\%}) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR) = 19.96; P < 0.001]; high Pitt bacteraemia score (≥4) at bacteraemia onset (OR = 13.91; P < 0.001); bacteraemia because of pneumonia (OR = 5.45; P = 0.007); de-escalation after empirical therapy (OR = 0.28; P = 0.03); and isolates with a CTX MIC ≤ 1 mg/L (OR = 0.17; P = 0.02). Of note, isolates with a CTX MIC ≤ 8 mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC (γ = 1.00; P = 0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC ≤ 1 mg/L.",
author = "Hsieh, {Chih Chia} and Lee, {Chung Hsun} and Li, {Ming Chi} and Hong, {Ming Yuan} and Chi, {Chih Hsien} and Lee, {Ching Chi}",
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language = "English",
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T1 - Empirical third-generation cephalosporin therapy for adults with community-onset Enterobacteriaceae bacteraemia

T2 - Impact of revised CLSI breakpoints

AU - Hsieh, Chih Chia

AU - Lee, Chung Hsun

AU - Li, Ming Chi

AU - Hong, Ming Yuan

AU - Chi, Chih Hsien

AU - Lee, Ching Chi

PY - 2016/4

Y1 - 2016/4

N2 - Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients (n = 409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR) = 19.96; P < 0.001]; high Pitt bacteraemia score (≥4) at bacteraemia onset (OR = 13.91; P < 0.001); bacteraemia because of pneumonia (OR = 5.45; P = 0.007); de-escalation after empirical therapy (OR = 0.28; P = 0.03); and isolates with a CTX MIC ≤ 1 mg/L (OR = 0.17; P = 0.02). Of note, isolates with a CTX MIC ≤ 8 mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC (γ = 1.00; P = 0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC ≤ 1 mg/L.

AB - Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients (n = 409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR) = 19.96; P < 0.001]; high Pitt bacteraemia score (≥4) at bacteraemia onset (OR = 13.91; P < 0.001); bacteraemia because of pneumonia (OR = 5.45; P = 0.007); de-escalation after empirical therapy (OR = 0.28; P = 0.03); and isolates with a CTX MIC ≤ 1 mg/L (OR = 0.17; P = 0.02). Of note, isolates with a CTX MIC ≤ 8 mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC (γ = 1.00; P = 0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC ≤ 1 mg/L.

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