Background <p>Multidrug-resistant (MDR) <i>Acinetobacter</i> spp. bloodstream infection (BSI) is concerning in hematologic patients, but integrated clinical and genomic analyses are scarce.</p> Methods <p>We retrospectively analyzed 62 hematologic patients with <i>Acinetobacter</i> spp. BSI over 13 years, including 30 MDR and 32 non-MDR cases. Whole-genome sequence (WGS) was conducted on 23 MDR isolates. Checkerboard assays evaluated the in vitro activity of eravacycline combined with sulbactam, meropenem, cefoperazone–sulbactam, polymyxin B, and levofloxacin.</p> Results <p>Female (66.67% vs. 34.38%, <i>P</i> = 0.022) and adult (≥ 14 years; 80.00% vs. 53.12%, <i>P</i> = 0.049) patients were more common in the MDR group. Prior carbapenem exposure, prolonged neutropenia, and respiratory tract colonization were associated with MDR-BSI. The majority of MDR cases did not receive appropriate empirical therapy within 24&#xa0;h (40.00% vs. 90.62%, <i>P</i> &lt; 0.001). The overall 30-day mortality was 38.71%, significantly higher in MDR than non-MDR patients (53.33% vs. 25.00%, <i>P</i> = 0.043). Among MDR subgroup, 30-day non-survivors had more profound cytopenias and higher inflammatory markers at BSI onset (<i>P</i> &lt; 0.05). WGS revealed diverse sequence types and capsular loci across the isolates, including 14 non-<i>A.baumannii</i> and 9 <i>A.baumannii</i> strains. Among 20 carbapenemase-positive isolates, <i>bla</i><sub>OXA−23</sub> (<i>n</i> = 9) predominated in <i>A.baumannii</i>, while <i>bla</i><sub>OXA−58</sub> (<i>n</i> = 7) and <i>bla</i><sub>NDM−1</sub> (<i>n</i> = 7) were restricted to non-<i>A.baumannii</i> isolates. Eravacycline demonstrated potent in vitro activity (MIC<sub>50/90</sub>=0.125/0.5&#xa0;mg/L) and showed synergy with sulbactam (52.17%), meropenem (43.48%), and cefoperazone–sulbactam (39.13%), while combinations with polymyxin B (86.96%) and levofloxacin (69.57%) were primarily additive.</p> Conclusions <p>Eravacycline exhibited strong in vitro activity and favorable synergy with sulbactam, supporting its potential role in treating MDR <i>Acinetobacter</i> spp. infections in this high-risk population.</p>

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Multidrug-resistant Acinetobacter spp. bloodstream infections in hematologic patients: clinical characteristics, genomic features, and eravacycline-based combination therapy

  • Wenjing Guo,
  • Jia Li,
  • Nuobing Yang,
  • Sisi Zhen,
  • Tingting Zhang,
  • Qingsong Lin,
  • Yigeng Cao,
  • Wenbin Cao,
  • Aiming Pang,
  • Donglin Yang,
  • Xin Chen,
  • Rongli Zhang,
  • Jialin Wei,
  • Qiaoling Ma,
  • Weihua Zhai,
  • Yi He,
  • Yizhou Zheng,
  • Erlie Jiang,
  • Mingzhe Han,
  • Sizhou Feng

摘要

Background

Multidrug-resistant (MDR) Acinetobacter spp. bloodstream infection (BSI) is concerning in hematologic patients, but integrated clinical and genomic analyses are scarce.

Methods

We retrospectively analyzed 62 hematologic patients with Acinetobacter spp. BSI over 13 years, including 30 MDR and 32 non-MDR cases. Whole-genome sequence (WGS) was conducted on 23 MDR isolates. Checkerboard assays evaluated the in vitro activity of eravacycline combined with sulbactam, meropenem, cefoperazone–sulbactam, polymyxin B, and levofloxacin.

Results

Female (66.67% vs. 34.38%, P = 0.022) and adult (≥ 14 years; 80.00% vs. 53.12%, P = 0.049) patients were more common in the MDR group. Prior carbapenem exposure, prolonged neutropenia, and respiratory tract colonization were associated with MDR-BSI. The majority of MDR cases did not receive appropriate empirical therapy within 24 h (40.00% vs. 90.62%, P < 0.001). The overall 30-day mortality was 38.71%, significantly higher in MDR than non-MDR patients (53.33% vs. 25.00%, P = 0.043). Among MDR subgroup, 30-day non-survivors had more profound cytopenias and higher inflammatory markers at BSI onset (P < 0.05). WGS revealed diverse sequence types and capsular loci across the isolates, including 14 non-A.baumannii and 9 A.baumannii strains. Among 20 carbapenemase-positive isolates, blaOXA−23 (n = 9) predominated in A.baumannii, while blaOXA−58 (n = 7) and blaNDM−1 (n = 7) were restricted to non-A.baumannii isolates. Eravacycline demonstrated potent in vitro activity (MIC50/90=0.125/0.5 mg/L) and showed synergy with sulbactam (52.17%), meropenem (43.48%), and cefoperazone–sulbactam (39.13%), while combinations with polymyxin B (86.96%) and levofloxacin (69.57%) were primarily additive.

Conclusions

Eravacycline exhibited strong in vitro activity and favorable synergy with sulbactam, supporting its potential role in treating MDR Acinetobacter spp. infections in this high-risk population.