Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Antimicrobial Agents and Chemotherapy
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Letter to the Editor

Outcomes of Patients with Bloodstream Infections Caused by Ampicillin-Susceptible but Penicillin-Resistant Enterococcus faecalis: Caution in Interpreting the Results

Nicolo L. Cabrera, Alexandre E. Malek, Samuel L. Aitken, Cesar A. Arias
Nicolo L. Cabrera
aDepartment of Internal Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas, USA
bDepartment of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nicolo L. Cabrera
Alexandre E. Malek
aDepartment of Internal Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas, USA
bDepartment of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Samuel L. Aitken
cDivision of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Samuel L. Aitken
Cesar A. Arias
aDepartment of Internal Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas, USA
dCenter for Antimicrobial Resistance and Microbial Genomics, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas, USA
eCenter for Infectious Diseases, The University of Texas Health Science Center at Houston, School of Public Health, Houston, Texas, USA
fMolecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogota, Colombia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/AAC.02387-19
  • Article
  • Info & Metrics
  • PDF
Loading

LETTER

We read with great interest the article by Kim et al. published in Antimicrobial Agents and Chemotherapy on the clinical prognoses of ampicillin-susceptible but penicillin-resistant (ASPR) Enterococcus faecalis infections (1). This phenotype appeared to confer an increased risk of 30-day mortality among patients with E. faecalis bloodstream infections (BSI), particularly those treated with ampicillin (AMP) or piperacillin-tazobactam (TZP). The findings raised concern for an increased risk of mortality despite the use of appropriate therapy guided by in vitro susceptibilities.

We believe that uncertainties in this study make the results difficult to interpret. First, piperacillin (PIP) or TZP in vitro susceptibilities of study isolates were not reported, likely as the Clinical and Laboratory Standards Institute accepts AMP in vitro susceptibility as a surrogate for non-β-lactamase-producing isolates (2). However, a concerning rate of discordance between these susceptibility phenotypes has been described. Conceição et al. reported on 34 non-β-lactamase-producing ASPR E. faecalis isolates, of which 9 were susceptible to PIP by disk diffusion but none were by broth dilution (BD) or gradient strip testing (3). Similarly, Tan et al. reported that among 3 E. faecalis isolates confirmed to be ASPR, 2 isolates were found to have PIP resistance (by broth microdilution and gradient strip testing) (4). All isolates were negative for β-lactamase production. Furthermore, Infante et al. found that among 21 ASPR E. faecalis isolates, 19% were resistant to PIP (BD and disk diffusion) and an amino acid substitution (D573E) was identified in PBP4 (5). Conceivably, pbp4 mutations associated with the ASPR phenotype may contribute to PIP resistance, though this has yet to be directly investigated. These findings cast doubt on the reliability of in vitro AMP susceptibility as a surrogate marker for TZP.

Second, patients who received AMP or TZP were combined into one group. In this group, patients with ASPR isolates had increased mortality compared to that of patients infected with a non-ASPR isolate. This difference was not observed among patients treated with glycopeptide-containing regimens. These results raise the possibility that the ASPR phenotype was associated with a poor clinical response to β-lactams even if their administration was deemed appropriate by in vitro susceptibility testing. However, it is crucial to specify the number of patients treated with TZP rather than ampicillin, as it is possible that TZP was an inactive therapy but not correctly identified as such by in vitro AMP susceptibility testing.

Third, combined ampicillin and ceftriaxone therapy is the regimen favored by many clinicians to treat serious high-inoculum BSI caused by E. faecalis (6). In the study by Kim et al., arguably lower-risk sources of BSI (e.g., urinary tract [11.2%], central line [1.7%]) comprised only a small fraction of the cohort. Notably, 33.9% of patients required intensive care (1). With serious infections, rates of combination therapy and specific second agents used in patients who received AMP or TZP without a glycopeptide versus those who received glycopeptide-containing regimens are important data for interpreting the results.

Kim et al. raise an important clinical question. However, conclusions need to be taken with caution, and further data are required to support the findings and optimize the treatment and clinical care of patients infected with these organisms.

ACKNOWLEDGMENTS

We have no potential conflicts of interest to disclose.

There were no sources of funding.

FOOTNOTES

  • For the author reply, see https://doi.org/10.1128/AAC.02513-19.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

REFERENCES

  1. 1.↵
    1. Kim D,
    2. Lee H,
    3. Yoon E-J,
    4. Hong JS,
    5. Shin JH,
    6. Uh Y,
    7. Shin KS,
    8. Shin JH,
    9. Kim YA,
    10. Park YS,
    11. Jeong SH
    . 2019. Prospective observational study of the clinical prognoses of patients with bloodstream infections caused by ampicillin-susceptible but penicillin-resistant Enterococcus faecalis. Antimicrob Agents Chemother 63:e00291-19. doi:10.1128/AAC.00291-19.
    OpenUrlAbstract/FREE Full Text
  2. 2.↵
    Clinical and Laboratory Standards Institute. 2019. Performance standards for antimicrobial susceptibility testing, 29th ed. CLSI supplement M100. Clinical and Laboratory Standards Institute, Wayne, PA.
  3. 3.↵
    1. Conceição N,
    2. De Oliveira C,
    3. Da Silva LEP,
    4. De Souza LRC,
    5. De Oliveira AG
    . 2012. Ampicillin susceptibility can predict in vitro susceptibility of penicillin-resistant, ampicillin-susceptible Enterococcus faecalis isolates to amoxicillin but not to imipenem and piperacillin. J Clin Microbiol 50:3729–3731. doi:10.1128/JCM.01246-12.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Tan YE,
    2. Ng LSY,
    3. Tan TY
    . 2014. Evaluation of Enterococcus faecalis clinical isolates with “penicillin-resistant, ampicillin-susceptible” phenotype as reported by Vitek-2 Compact system. Pathology 46:544–550. doi:10.1097/PAT.0000000000000146.
    OpenUrlCrossRef
  5. 5.↵
    1. Infante VHP,
    2. Conceição N,
    3. de Oliveira AG,
    4. Darini ALDC
    . 2016. Evaluation of polymorphisms in pbp4 gene and genetic diversity in penicillin-resistant, ampicillin-susceptible Enterococcus faecalis from hospitals in different states in Brazil. FEMS Microbiol Lett 363:fnw044. doi:10.1093/femsle/fnw044.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Beganovic M,
    2. Luther MK,
    3. Rice LB,
    4. Arias CA,
    5. Rybak MJ,
    6. LaPlante KL
    . 2018. A review of combination antimicrobial therapy for Enterococcus faecalis bloodstream infections and infective endocarditis. Clin Infect Dis 67:303–309. doi:10.1093/cid/ciy064.
    OpenUrlCrossRef
PreviousNext
Back to top
Download PDF
Citation Tools
Outcomes of Patients with Bloodstream Infections Caused by Ampicillin-Susceptible but Penicillin-Resistant Enterococcus faecalis: Caution in Interpreting the Results
Nicolo L. Cabrera, Alexandre E. Malek, Samuel L. Aitken, Cesar A. Arias
Antimicrobial Agents and Chemotherapy Mar 2020, 64 (4) e02387-19; DOI: 10.1128/AAC.02387-19

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Antimicrobial Agents and Chemotherapy article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Outcomes of Patients with Bloodstream Infections Caused by Ampicillin-Susceptible but Penicillin-Resistant Enterococcus faecalis: Caution in Interpreting the Results
(Your Name) has forwarded a page to you from Antimicrobial Agents and Chemotherapy
(Your Name) thought you would be interested in this article in Antimicrobial Agents and Chemotherapy.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Outcomes of Patients with Bloodstream Infections Caused by Ampicillin-Susceptible but Penicillin-Resistant Enterococcus faecalis: Caution in Interpreting the Results
Nicolo L. Cabrera, Alexandre E. Malek, Samuel L. Aitken, Cesar A. Arias
Antimicrobial Agents and Chemotherapy Mar 2020, 64 (4) e02387-19; DOI: 10.1128/AAC.02387-19
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • LETTER
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Info & Metrics
  • PDF

KEYWORDS

Enterococcus faecalis
ampicillin-susceptible but penicillin-resistant (ASPR) phenotype
ampicillin susceptible
beta-lactam
penicillin resistant

Related Articles

Cited By...

About

  • About AAC
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • AAC Podcast
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #AACJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0066-4804; Online ISSN: 1098-6596