Strong Homology Between Colonizing and Bloodstream Carbapenem-Resistant Acinetobacter Spp.: Implications for Empiric Antibiotic Therapy in Hematological Patients

Abstract

Objective

This study aimed to assess the impact of colonization status on the outcomes of Acinetobacter spp. bloodstream infection (BSI) and investigate the homology and within-host evolution between colonizing and bloodstream carbapenem-resistant Acinetobacter spp. (CRA) to inform antibiotic therapeutic decisions.

Methods

We analyzed clinical outcomes of 46 hematological patients with Acinetobacter spp. BSI and performed whole-genome sequencing on the remaining CRA isolates.

Results

Among the patients, 39.1% (n=18) had prior Acinetobacter spp. colonization. Colonized patients had higher rates of polymicrobial BSI (50.0% vs 21.4%, P=0.044) and CRA BSI (72.2% vs 17.9%, P<0.001), resulting in elevated inflammatory markers and increased 30-day mortality. Each of the eight pairs of the remaining respiratory colonizing and bloodstream CRA strains belonged to the same genomospecies. Each pair exhibited definitive agreement in at least 21 of the 22 most representative antibiotic susceptibility tests. The minimum spanning tree based on multilocus sequence typing (MLST) and phylogenetic trees based on MLST and single nucleotide polymorphism (SNP) all indicated that each pair shared the same minimum branch. Very few non-synonymous SNPs in genic regions were identified during the transition from respiratory colonization to bloodstream infection, with minimal changes in virulence genes. Homology analysis suggested that CRA BSI originated from colonizing isolates in the respiratory tract.

Conclusion

Strict infection control measures are needed to manage Acinetobacter spp. colonisation in hematological patients. Appropriate empirical therapy can be administered for suspected CRA BSI based on the antimicrobial minimum inhibitory concentration of CRA colonising the respiratory tract.

Keywords:

• Acinetobacter
• colonization
• bloodstream infections
• homology
• therapy
• carbapenem-resistant

Patient Consent Statement

We have obtained written informed consent from the patient or patient’s parent/guardian.

Data Sharing Statement

The datasets generated and/or analysed during the current study are available in the GenBank repository. You can access them through the following web link: https://www.ncbi.nlm.nih.gov/nuccore/?term=PRJNA883531, and the accession number is PRJNA883531.

Ethics Approval Statement

The study design was approved by the Ethics Committee of the Blood Diseases Hospital, Chinese Academy of Medical Sciences. Lot number: IIT2022071-EC-1. Please refer to the attached file.

Acknowledgments

Thanks are due to Fupin Hu and Siquan Shen for bioinformatics analysis.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (grant numbers 2021-I2M-1-017, 2021-I2M-C&T-B-080), and the Tianjin Municipal Science and Technology Commission Grant (grant number 21JCZDJC01170).