Real‑World Effectiveness of Ceftazidime-Avibactam for Gram‑Negative Infections

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23 Jan, 26

Introduction

Multidrugresistant Gramnegative bacteria, especially carbapenemresistant strains, are spreading globally and limiting effective treatment options. Ceftazidime–avibactam (CAZ-AVI) offers important activity against many resistant organisms, though its effectiveness varies across Asia where resistance mechanisms differ and realworld data remain limited.

Aim

To investigate the clinical characteristics, microbiology, and outcomes of patients treated with CAZ-AVI for Gram-negative bacterial infection

Patient Profile

  • N=472 (≥ 20-year-old) with culture confirmed Gram-negative infection and received ≥ 24 hours of CAZ- AVI 
  • Infections in participants:
    1. respiratory tract infections (46.2%)
    2. complicated urinary tract infections (22%)
    3. complicated intra-abdominal infections (14%)
    4. primary bacteremia (10%)
    5. secondary bacteremia (11.7%)
    6. polymicrobial infections (10%)
  • Most participants were 
    1. Elderly (mean age: 70.6 years old)
    2. High SOFA score (mean 8.4)
    3. High Charlson Comorbidity Index score (≥ 4 in 73.1 %) with median of 5

Methods

  • Multicenter retrospective cohort study 
  • 90 % of CAZ-AVI used as targeted therapy for pathogens including 
    1. Klebsiella pneumoniae (64.4 %)
    2. Pseudomonas aeruginosa (17.8 %)
    3. Escherichia coli (8.3 %)
    4. Enterobacter spp. (2.3 %)
    5. Carbapenem resistant (73.7%)
  • Nearly half (47.2%) received combination therapy, often with colistin or tigecycline
  • Median CAZAVI duration: 11 days (mean 11 ± 6.3)

Study endpoints

Primary: In-hospital mortality

Secondary: Clinical success (symptom resolution or significant improvement)

Results

Clinical Outcomes

  • CAZAVI achieved a meaningful rate of overall clinical improvement (58.1%) among patients with severe Gramnegative infections
  • Clinical success was more frequently observed when CAZAVI was administered as monotherapy rather than in combination regimens

Table 1: Primary and Secondary Outcomes

Outcome

Percentage of study participants (N=472)

Clinical success

58.1%

Inhospital mortality

41.1%

Success with monotherapy

67.5%

Success with combination therapy

52.2%

 

Time of Initiation

  • Starting CAZAVI within 24–48 hours after sampling resulted in:
    1. Higher clinical success (OR 4.096)
    2. Survival benefit compared with initiation after >72 hours (p < 0.05)

Risk Factors for In-Hospital Mortality

Table 2: Independent predictors of mortality 

Risk Factor

HR (95% CI)

pvalue

Immunomodulator use (past 30 days) 

2.641 

(1.046–6.669)

0.040

SOFA score

1.159 

(1.094–1.227)

<0.001

First CAZAVI dose in ICU

1.417 

(1.004–2.000)

0.047

Enterobacter spp. Infection

2.854 

(1.321–6.166)

0.008 

Conclusion

  • Most patients receiving CAZ-AVI as targeted therapy had characteristics of older age, high SOFA scores, and high Charlson comorbidity index scores
  • Receiving immunomodulators, higher SOFA score, and Enterobacter spp. infections were significant factors associated with in-hospital mortality
  • Early initiation of CAZ-AVI treatment and CAZ-AVI monotherapy were associated with better outcome

Reference

J Infect Public Health. 2025 Jun;18(6):102735