In host evolution of beta lactam resistance during active treatment for Pseudomonas aeruginosa bacteremia
Multidrug-resistant (MDR) Pseudomonas aeruginosa has been declared a serious threat by the United States Centers for Disease Control and Prevention. Here, we used whole genome sequencing (WGS) to investigate recurrent P. aeruginosa bloodstream infections in a severely immunocompromised patient. The...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-08-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1241608/full |
| _version_ | 1797730934011723776 |
|---|---|
| author | Natasha Spottiswoode Samantha Hao Samantha Hao Estella Sanchez-Guerrero Angela M. Detweiler Honey Mekonen Norma Neff Henriette Macmillan Brian S. Schwartz Joanne Engel Joseph L. DeRisi Joseph L. DeRisi Steven A. Miller Steven A. Miller Charles R. Langelier Charles R. Langelier |
| author_facet | Natasha Spottiswoode Samantha Hao Samantha Hao Estella Sanchez-Guerrero Angela M. Detweiler Honey Mekonen Norma Neff Henriette Macmillan Brian S. Schwartz Joanne Engel Joseph L. DeRisi Joseph L. DeRisi Steven A. Miller Steven A. Miller Charles R. Langelier Charles R. Langelier |
| author_sort | Natasha Spottiswoode |
| collection | DOAJ |
| description | Multidrug-resistant (MDR) Pseudomonas aeruginosa has been declared a serious threat by the United States Centers for Disease Control and Prevention. Here, we used whole genome sequencing (WGS) to investigate recurrent P. aeruginosa bloodstream infections in a severely immunocompromised patient. The infections demonstrated unusual, progressive increases in resistance to beta lactam antibiotics in the setting of active treatment with appropriate, guideline-directed agents. WGS followed by comparative genomic analysis of isolates collected over 44 days demonstrated in host evolution of a single P. aeruginosa isolate characterized by stepwise acquisition of two de-novo genetic resistance mechanisms over the course of treatment. We found a novel deletion affecting the ampC repressor ampD and neighboring gene ampE, which associated with initial cefepime treatment failure. This was followed by acquisition of a porin nonsense mutation, OprD, associated with resistance to carbapenems. This study highlights the potential for in-host evolution of P. aeruginosa during bloodstream infections in severely immunocompromised patients despite appropriate antimicrobial therapy. In addition, it demonstrates the utility of WGS for understanding unusual resistance patterns in the clinical context. |
| first_indexed | 2024-03-12T11:51:18Z |
| format | Article |
| id | doaj.art-2828eeef9fac42af85ebf115d386a7b2 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-03-12T11:51:18Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-2828eeef9fac42af85ebf115d386a7b22023-08-31T06:44:03ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-08-011310.3389/fcimb.2023.12416081241608In host evolution of beta lactam resistance during active treatment for Pseudomonas aeruginosa bacteremiaNatasha Spottiswoode0Samantha Hao1Samantha Hao2Estella Sanchez-Guerrero3Angela M. Detweiler4Honey Mekonen5Norma Neff6Henriette Macmillan7Brian S. Schwartz8Joanne Engel9Joseph L. DeRisi10Joseph L. DeRisi11Steven A. Miller12Steven A. Miller13Charles R. Langelier14Charles R. Langelier15Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, CA, United StatesJohns Hopkins School of Medicine, Baltimore, Maryland, MD, United StatesChan Zuckerberg Biohub, San Francisco, CA, United StatesChan Zuckerberg Biohub, San Francisco, CA, United StatesChan Zuckerberg Biohub, San Francisco, CA, United StatesChan Zuckerberg Biohub, San Francisco, CA, United StatesChan Zuckerberg Biohub, San Francisco, CA, United StatesDivision of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, CA, United StatesDivision of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, CA, United StatesDivision of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, CA, United StatesChan Zuckerberg Biohub, San Francisco, CA, United StatesDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, United StatesDelve Bio Inc., San Francisco, CA, United StatesDivision of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, CA, United StatesChan Zuckerberg Biohub, San Francisco, CA, United StatesMultidrug-resistant (MDR) Pseudomonas aeruginosa has been declared a serious threat by the United States Centers for Disease Control and Prevention. Here, we used whole genome sequencing (WGS) to investigate recurrent P. aeruginosa bloodstream infections in a severely immunocompromised patient. The infections demonstrated unusual, progressive increases in resistance to beta lactam antibiotics in the setting of active treatment with appropriate, guideline-directed agents. WGS followed by comparative genomic analysis of isolates collected over 44 days demonstrated in host evolution of a single P. aeruginosa isolate characterized by stepwise acquisition of two de-novo genetic resistance mechanisms over the course of treatment. We found a novel deletion affecting the ampC repressor ampD and neighboring gene ampE, which associated with initial cefepime treatment failure. This was followed by acquisition of a porin nonsense mutation, OprD, associated with resistance to carbapenems. This study highlights the potential for in-host evolution of P. aeruginosa during bloodstream infections in severely immunocompromised patients despite appropriate antimicrobial therapy. In addition, it demonstrates the utility of WGS for understanding unusual resistance patterns in the clinical context.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1241608/fullantimicrobial resistancewhole-genome sequencinggram-negative bacteriagram negativegram negative (G -) bacteriahospital epidemiology |
| spellingShingle | Natasha Spottiswoode Samantha Hao Samantha Hao Estella Sanchez-Guerrero Angela M. Detweiler Honey Mekonen Norma Neff Henriette Macmillan Brian S. Schwartz Joanne Engel Joseph L. DeRisi Joseph L. DeRisi Steven A. Miller Steven A. Miller Charles R. Langelier Charles R. Langelier In host evolution of beta lactam resistance during active treatment for Pseudomonas aeruginosa bacteremia Frontiers in Cellular and Infection Microbiology antimicrobial resistance whole-genome sequencing gram-negative bacteria gram negative gram negative (G -) bacteria hospital epidemiology |
| title | In host evolution of beta lactam resistance during active treatment for Pseudomonas aeruginosa bacteremia |
| title_full | In host evolution of beta lactam resistance during active treatment for Pseudomonas aeruginosa bacteremia |
| title_fullStr | In host evolution of beta lactam resistance during active treatment for Pseudomonas aeruginosa bacteremia |
| title_full_unstemmed | In host evolution of beta lactam resistance during active treatment for Pseudomonas aeruginosa bacteremia |
| title_short | In host evolution of beta lactam resistance during active treatment for Pseudomonas aeruginosa bacteremia |
| title_sort | in host evolution of beta lactam resistance during active treatment for pseudomonas aeruginosa bacteremia |
| topic | antimicrobial resistance whole-genome sequencing gram-negative bacteria gram negative gram negative (G -) bacteria hospital epidemiology |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1241608/full |
| work_keys_str_mv | AT natashaspottiswoode inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT samanthahao inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT samanthahao inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT estellasanchezguerrero inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT angelamdetweiler inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT honeymekonen inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT normaneff inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT henriettemacmillan inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT briansschwartz inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT joanneengel inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT josephlderisi inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT josephlderisi inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT stevenamiller inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT stevenamiller inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT charlesrlangelier inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia AT charlesrlangelier inhostevolutionofbetalactamresistanceduringactivetreatmentforpseudomonasaeruginosabacteremia |