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
Epidemiology and Surveillance

In Vitro Activity of Eravacycline against Gram-Negative Bacilli Isolated in Clinical Laboratories Worldwide from 2013 to 2017

Ian Morrissey, Melanie Olesky, Stephen Hawser, Sibylle H. Lob, James A. Karlowsky, G. Ralph Corey, Matteo Bassetti, Corey Fyfe
Ian Morrissey
aIHMA Europe Sàrl, Monthey, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Melanie Olesky
bTetraphase Pharmaceuticals, Watertown, Massachusetts, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen Hawser
aIHMA Europe Sàrl, Monthey, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sibylle H. Lob
cInternational Health Management Associates, Inc., Schaumburg, Illinois, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James A. Karlowsky
dDepartment of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G. Ralph Corey
eDuke University Medical Center, Durham, North Carolina, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matteo Bassetti
fInfectious Diseases Clinic, Department of Medicine, University of Udine, Udine, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Corey Fyfe
bTetraphase Pharmaceuticals, Watertown, Massachusetts, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/AAC.01699-19
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

Eravacycline is a novel, fully synthetic fluorocycline antibiotic developed for the treatment of serious infections, including those caused by multidrug-resistant (MDR) pathogens. Here, we evaluated the in vitro activities of eravacycline and comparator antimicrobial agents against a global collection of frequently encountered clinical isolates of Gram-negative bacilli. The CLSI broth microdilution method was used to determine MIC data for isolates of Enterobacterales (n = 13,983), Acinetobacter baumannii (n = 2,097), Pseudomonas aeruginosa (n = 1,647), and Stenotrophomonas maltophilia (n = 1,210) isolated primarily from respiratory, intra-abdominal, and urinary specimens by clinical laboratories in 36 countries from 2013 to 2017. Susceptibilities were interpreted using both CLSI and EUCAST breakpoints. Multidrug-resistant (MDR) isolates were defined by resistance to agents from ≥3 different antimicrobial classes. The MIC90s ranged from 0.25 to 1 μg/ml for Enterobacteriaceae and were 1 μg/ml for A. baumannii and 2 μg/ml for S. maltophilia, Proteus mirabilis, and Serratia marcescens. Eravacycline’s potency was up to 4-fold greater than that of tigecycline against genera/species of Enterobacterales, A. baumannii, and S. maltophilia. The MIC90s for five of six individual genera/species of Enterobacterales and A. baumannii were within 2-fold of the MIC90s for their respective subsets of MDR isolates, while the MDR subpopulation of Klebsiella spp. demonstrated 4-fold higher MIC90s. Eravacycline demonstrated potent in vitro activity against the majority of clinical isolates of Gram-negative bacilli, including MDR isolates, collected over a 5-year period. This study further underscores the potential benefit of eravacycline in the treatment of infections caused by MDR Gram-negative pathogens.

INTRODUCTION

Gram-negative pathogens causing serious infections are becoming an increasing clinical concern (1–5). Important antimicrobial-resistant Gram-negative pathogens include extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae; carbapenemase-producing, fluoroquinolone-resistant, and multidrug-resistant (MDR) Enterobacterales; as well as carbapenem-resistant and MDR Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia (1–5). In fact, many of these pathogens have recently been highlighted among Gram-negative MDR pathogens classified as urgent/critical or serious/high public health threats by the Centers for Disease Control and Prevention (CDC) (1) and the World Health Organization (WHO) (6).

Eravacycline is a novel, fully synthetic fluorocycline antibiotic developed for the treatment of serious infections, including those caused by MDR pathogens (5, 7; https://clinicaltrials.gov/ct2/show/NCT01844856). Eravacycline is comprised of a tetracycline core with two novel modifications, a fluorine atom at the C-7 position and a pyrrolidinoacetamido group at the C-9 position, both of which are on the D ring (7, 9). These novel modifications confer enhanced in vitro activity compared to that of other tetracyclines against resistant Gram-negative and Gram-positive bacteria, and the pyrrolidinoacetamido group allows for increased ribosomal binding and steric hindrance to avoid ribosome protection-based tetracycline resistance.

Eravacycline inhibits bacterial protein synthesis (i.e., acyl-tRNA transfer) by binding to the 30S ribosomal subunit (10). Eravacycline demonstrates potent broad-spectrum activity against Gram-negative bacilli (except for P. aeruginosa and Burkholderia spp.) and Gram-positive cocci, including anaerobes, as well as atypical bacterial pathogens and Neisseria gonorrhoeae (5, 11–16), and does not exhibit a loss of antibacterial activity against isolates expressing tetracycline ribosomal protection genes or most tetracycline efflux resistance genes (10, 11, 14).

Eravacycline has successfully completed clinical trials for the treatment of complicated intra-abdominal infection (cIAI) (https://clinicaltrials.gov/ct2/show/NCT01844856) and has been approved for use by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Additionally, eravacycline has demonstrated in vivo efficacy as a treatment in murine models of systemic, thigh, and lung infection and pyelonephritis.

The objective of the current study was to determine the in vitro activity of eravacycline relative to that of other antimicrobial agents using a representative global collection of clinical isolates of Gram-negative bacilli.

RESULTS AND DISCUSSION

A total of 17,781 Gram-negative aerobic isolates collected between 2013 and 2017 were included in this study. Enterobacteriaceae accounted for the majority of these isolates (n = 10,531). The MIC distributions for these isolates and the cumulative percentage of isolates inhibited by eravacycline are shown in Table 1. The MIC90 for isolates of A. baumannii was 1 μg/ml, and it was 0.5 μg/ml for the four genera/species of Enterobacteriaceae combined and 2 μg/ml for S. maltophilia. Among the six genera/species of Enterobacterales tested, MIC90 values were as follows: E. coli, 0.25 μg/ml; Klebsiella spp. and Citrobacter spp., 0.5 μg/ml; Enterobacter spp., 1 μg/ml; and Proteus mirabilis and Serratia marcescens, 2 μg/ml. For MDR populations of these organisms, the MIC90 values of eravacycline remained within 2- to 4-fold of the MIC90s indicated above. Given eravacycline’s limited activity against P. aeruginosa (Table 1), concordant with this pathogen’s established intrinsic resistance to tetracyclines, it was excluded from further analyses (17).

View this table:
  • View inline
  • View popup
  • Download powerpoint
TABLE 1

Cumulative percentage of all clinical isolates of Enterobacteriaceae, individual genera/species of Enterobacterales, A. baumannii, P. aeruginosa, and S. maltophilia tested from 2013 to 2017 inhibited by eravacycline, by MIC

When isolates were allocated to their respective geographic regions, eravacycline MIC50s and MIC90s were within 1 doubling dilution for all Enterobacteriaceae combined, individual genera/species of Enterobacterales, A. baumannii, and S. maltophilia (see Table S1 in the supplemental material). Similarly, there were no significant differences (a >1-doubling-dilution increase or decrease in the MIC50s or MIC90s) observed in the in vitro activity of eravacycline for any genera/species of Gram-negative bacilli stratified by specimen source (Table S2) or stratified by study period (2013 to 2014, 2015, 2016, 2017) (Table S3). A detailed trend analysis could not be conducted, given that there were changes in participating laboratories and the panel of antimicrobial agents tested over the time period studied (2013 to 2017).

The in vitro activities of eravacycline and comparator agents against Enterobacterales, A. baumannii, and S. maltophilia isolates and their MDR counterparts are shown in Tables 2 and 3, respectively. The rates of susceptibility of Enterobacteriaceae spp. to eravacycline were high, with the susceptibility rates being 98.8% for E. coli, 90.6% for Klebsiella spp., 94.6% for Citrobacter spp., and 89.6% for Enterobacter spp. (Table 2) (18). For MDR organisms, the rates of susceptibility to eravacycline for E. coli remained high (97.5%) and ranged from 77 to 81.9% for the other Enterobacteriaceae (Table 3). Breakpoint interpretations were not available for eravacycline against the other organisms tested.

View this table:
  • View inline
  • View popup
  • Download powerpoint
TABLE 2

In vitro activity of eravacycline and comparator agents against Enterobacteriaceae, individual genera/species of Enterobacterales, A. baumannii, and S. maltophilia, cumulative 2013 to 2017 data

View this table:
  • View inline
  • View popup
  • Download powerpoint
TABLE 3

In vitro activity of eravacycline and comparator agents against MDR Enterobacteriaceae, individual genera/species of Enterobacterales, and A. baumannii, cumulative 2013 to 2017 data

With regard to the comparator agents tested, the rate of susceptibility among the Enterobacteriaceae by the use of CLSI criteria was the highest for amikacin (99.1%), tigecycline (96.8%), the carbapenems meropenem (97.9%) and ertapenem (94.2%), and gentamicin (91.2%) (Table 2). Similar susceptibility was observed using EUCAST guidelines, with exceptions existing, such as for minocycline and tetracycline, for which no EUCAST breakpoints are given, and for colistin (99.4% susceptible by the use of EUCAST breakpoints), for which CLSI breakpoints are not given. Also, by use of the EUCAST criteria, tigecycline susceptibility was reduced to 70.6%, whereas eravacycline susceptibility remained at 92.6%. Other Enterobacterales, P. mirabilis, and S. marcescens were distinct, with reduced susceptibility to the tetracycline class, especially when susceptibility was evaluated using EUCAST breakpoints (Table 2). Among the Enterobacteriaceae, 19.5% (n = 2,051) were defined as being MDR isolates using CLSI breakpoints and 20.8% (n = 2,186) were defined as being MDR isolates using EUCAST breakpoints. The rates of susceptibility to all other comparators except amikacin, colistin (EUCAST breakpoints only), ertapenem, gentamicin (EUCAST breakpoints only), imipenem, meropenem, and tigecycline (CLSI breakpoints only) were less than 60% for the MDR isolate population. These susceptibilities are similar to those seen in other global surveillance studies (19, 20).

In addition to the Enterobacterales, a large collection of Gram-negative nonfermenters was tested, including A. baumannii (n = 2,097) and S. maltophilia (n = 1,210). For A. baumannii, high rates of resistance to the majority of the comparators were seen, with the levels of susceptibility to colistin (95.1%) and minocycline (67.3%) being the highest. Among the few agents with a breakpoint for S. maltophilia, the rate of susceptibility to minocycline was the highest at 99.0%. Approximately 24% and 15.7% of the isolates were resistant to levofloxacin and trimethoprim-sulfamethoxazole, respectively, similar to the findings of a surveillance study looking at isolates from 1998 to 2008 in Taiwan (21).

In this surveillance study, eravacycline demonstrated improved potency, based on MIC90 values, over tigecycline, showing a 4-fold greater potency than tigecycline against populations of A. baumannii, Klebsiella spp., and P. mirabilis and a 2-fold greater potency against E. coli, Enterobacter spp., Citrobacter spp., and S. maltophilia. Eravacycline and tigecycline showed equivalent potency against S. marcescens. Previous in vitro studies comparing eravacycline and tigecycline have reported similar 2- to 4-fold improvements in the MIC90 values of eravacycline over those of tigecycline (7, 12, 13, 16, 22–26). The tigecycline MIC90s for Enterobacterales spp., A. baumannii, and S. maltophilia determined in this study were equivalent to the MIC90s of tigecycline determined in other global surveillance studies (27, 28).

In addition to greater potency, eravacycline presents additional potential advantages over tigecycline: higher concentrations in serum and tissue (especially in the lung) and improved tolerability (7, 29–31). Previous studies have demonstrated that the in vitro activity of eravacycline is not affected by the presence of many of the resistance mechanisms likely present in the current surveillance population. These include studies which looked at the in vitro activity of eravacycline against ESBL-producing isolates of E. coli and K. pneumoniae; fluoroquinolone-susceptible and fluoroquinolone-resistant isolates of E. coli (including those of the MDR sequence type 131 genotype); polymyxin-resistant (mcr-1-positive) Enterobacteriaceae; carbapenem-resistant Enterobacteriaceae, including KPC-, SME-, VIM-, IMP-, NDM-, and OXA-48-producing isolates; and MDR Enterobacteriaceae and A. baumannii (12, 13, 16, 22–24, 26).

Eravacycline is currently approved for use by both EMA and FDA for the treatment of complicated intra-abdominal infections. As previously described, eravacycline maintains an overall potency advantage over tigecycline across approved organisms. The adoption of restrictive breakpoint criteria for tigecycline and eravacycline in the EUCAST 2019 guidelines, in contrast to the broad, albeit decade-old, tigecycline breakpoints granted by the FDA, makes comparisons of susceptibility between the two agents difficult. While the FDA breakpoints for both agents are granted for Enterobacteriaceae, the clinical efficacy of eravacycline against E. coli, Enterobacter cloacae, Citrobacter freundii, and species of Klebsiella is noted. Current eravacycline breakpoints from EUCAST were published concurrently with a reduction in both the tigecycline breakpoint and the approved organism list. The disconnect between approved interpretative criteria and organism coverage for tigecycline and other agents across these regulatory agencies highlights the need for greater efforts toward the harmonization of breakpoints.

Treatment of complicated intra-abdominal infection (cIAI) involves a combination of surgery and empirical antimicrobial therapy. Antimicrobial therapy must be sufficient to encompass a wide range of pathogens, including Gram-positive and Gram-negative aerobic and anaerobic bacteria (32–34). In cIAI patients, the most commonly encountered Gram-negative pathogens include E. coli, Klebsiella spp., and Enterobacter spp. (35). A. baumannii is less common in cIAI infections but has been noted to be an increasing cause of postoperative infections in hospital settings (36–38).

Eravacycline demonstrated potent in vitro activity against the clinically important Gram-negative organisms associated with cIAIs in humans. For all organisms, including A. baumannii and S. maltophilia, the MIC90s of eravacycline were 2- to 4-fold lower than those of tigecycline. This global surveillance investigation highlights the broad-spectrum potency of eravacycline against Gram-negative bacteria, including MDR strains, and further underscores its potential benefit for the treatment of cIAIs and other polymicrobial infections caused by resistant pathogens.

MATERIALS AND METHODS

Bacterial isolates.From 2013 through 2017, clinical isolates of Enterobacterales (n = 13,983), A. baumannii (n = 2,097), P. aeruginosa (n = 1,647), and S. maltophilia (n = 1,210) were collected by laboratories in 36 countries (in the Asia-Pacific region, Australia, Hong Kong, Japan, South Korea, Malaysia, New Zealand, Philippines, Singapore, Taiwan, Thailand, and Vietnam; in Europe, Austria, Belgium, Croatia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Netherlands, Poland, Portugal, Romania, Russia, Serbia, Spain, Sweden, Switzerland, Turkey, and the United Kingdom; and in North America [the United States]). In the Asia-Pacific region, isolates were collected only in 2015 through 2017, and some other countries also did not participate in all years.

Table S1 in the supplemental material summarizes the numbers of isolates of Enterobacteriaceae, A. baumannii, and S. maltophilia collected by geographic region. For the Enterobacteriaceae and A. baumannii, approximately 40 to 45% of the isolates came from North America and Europe and 15% came from the Asia-Pacific region. For S. maltophilia, approximately 50% of the isolates came from Europe, 30% came from North America, and 20% came from the Asia-Pacific region. In total, there were 6,559, 5,667, 5,305, and 1,406 isolates, respectively, from respiratory, intra-abdominal, urinary, and other specimen sources.

The identity of each isolate was confirmed using matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (Bruker Biotyper; Bruker Daltonics, Bremen, Germany). Isolates were limited to one per patient, determined by the participating laboratory algorithms to be clinically significant, and collected irrespective of their antimicrobial susceptibility profile and independently of patient gender or age. The study was not designed to directly compare the prevalence of antimicrobial-resistant pathogens across specific geographic locations but, rather, was designed to evaluate the in vitro activities of eravacycline and comparator antimicrobial agents against a global collection of frequently encountered clinical isolates of Gram-negative bacilli collected from 2013 to 2017.

Antimicrobial susceptibility testing.The in vitro susceptibilities of isolates were determined using the CLSI-defined broth microdilution method in 96-well broth microdilution panels (17, 39). The antimicrobial agents used in panel production were acquired as laboratory-grade powders from their respective manufacturers or from a commercial source. The list of antimicrobial agents tested in each of the four study periods varied slightly, in that some agents, in addition to those tested in the 2013 to 2014 period, were included in the 2015 to 2017 testing periods. Ten antimicrobial agents (aztreonam, cefepime, ceftazidime, ceftriaxone, eravacycline, gentamicin, levofloxacin, piperacillin-tazobactam, tetracycline, and tigecycline) were tested against all isolates in each study period from 2013 to 2017. Of note, imipenem was tested in 2013 and 2014, while ertapenem and meropenem were tested in 2015 to 2017; colistin was tested against Enterobacteriaceae only in 2013 and 2014; amoxicillin-clavulanate was tested only in 2015; ampicillin-sulbactam was tested only in 2015 and 2016; and cefotaxime, minocycline, and trimethoprim-sulfamethoxazole were tested only in 2015 to 2017. The eravacycline MICs for Gram-negative bacilli were read following the current CLSI standard for dilution method testing; MIC endpoints were read following panel incubation at 35°C in ambient air for 16 to 20 h (Enterobacteriaceae, P. aeruginosa) or 20 to 24 h (A. baumannii, S. maltophilia) (17). Quality control testing for eravacycline and other antimicrobial agents was performed on each day of testing as specified by the CLSI (39) using the CLSI-defined control strains E. coli ATCC 25922 and P. aeruginosa ATCC 27853.

MICs were interpreted using 2019 CLSI MIC breakpoints (17) and 2019 EUCAST MIC breakpoints (18), with the following exceptions: FDA MIC interpretative breakpoints for eravacycline and tigecycline (29) were used in place of CLSI MIC breakpoints, which are not currently published for these agents. Additionally, tigecycline breakpoints were lowered with the 2019 EUCAST MIC guidelines, while simultaneously, the label was restricted to E. coli and Citrobacter koseri from the Enterobacteriaceae; in order to perform a more accurate and complete comparison between eravacycline and tigecycline susceptibilities, the current breakpoints for both eravacycline and tigecycline were applied to susceptibility percentages for all Enterobacteriaceae species.

An MDR phenotype was defined as resistance to one or more agents from three or more antimicrobial agent classes recommended for testing for a specific pathogen or pathogen family (Enterobacteriaceae) and possessing MIC interpretative breakpoints published by CLSI (17) or EUCAST (18). Eravacycline and tigecycline were excluded from the list of agents used for the MDR determination. Because the list of antimicrobial agents tested in each study year varied slightly, the identified MDR populations also varied slightly in each study year. Identification of MDR isolates of S. maltophilia was excluded from the analysis because of the very limited number of antimicrobial agents with either CLSI (17) or EUCAST (18) MIC breakpoints for that species. Resistance to levofloxacin and trimethoprim-sulfamethoxazole was captured for this organism, as these represent the current treatment of choice and a proposed alternative, respectively (40).

ACKNOWLEDGMENTS

We thank all laboratories participating in this eravacycline global surveillance study for their contributions, as well as Sophie Magnet for her coordination of the laboratory work.

Funding for this research was provided by Tetraphase Pharmaceuticals, Inc., Watertown, MA, USA, which also included compensation fees for services in relation to preparing the manuscript.

C.F. and M.O. are employees of Tetraphase Pharmaceuticals. I.M. and S.H. and are employees of IHMA Europe Sàrl. S.H.L. works for IHMA, Inc. Both IHMA laboratories have received research funding from Tetraphase Pharmaceuticals, Inc. J.A.K. is a consultant to IHMA, Inc. The authors employed by IHMA and J.A.K. do not have personal financial interests in the sponsor of this paper (Tetraphase Pharmaceuticals, Inc.). M.B. has participated in advisory boards and/or received speaker honoraria from Achaogen, Angelini, Astellas, AstraZeneca, Bayer, Basilea, Cidara, Gilead, Menarini, MSD, Nabriva, Paratek, Pfizer, The Medicines Company, Tetraphase, and Vifor. G.R.C. has received consulting fees from Cempra Pharmaceuticals, PRA International, Furiex Pharmaceuticals, Inimex Pharmaceuticals, Dr. Reddy’s Laboratories, Cerexa/Forest Laboratories, AstraZeneca, GlaxoSmithKline, Merck, ContraFect, Theravance, and Astellas; has received research grants from Theravance, Innocoll, and The Medicines Company; and has served on the advisory boards of Pfizer, Polymedix, Tetraphase Pharmaceuticals, Seachaid Pharmaceuticals, BioCryst Pharmaceuticals, Durata, Achaogen, ContraFect, and Nabriva.

FOOTNOTES

    • Received 22 August 2019.
    • Returned for modification 8 October 2019.
    • Accepted 9 December 2019.
    • Accepted manuscript posted online 16 December 2019.
  • Supplemental material is available online only.

  • Copyright © 2020 Morrissey et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

REFERENCES

  1. 1.↵
    Centers for Disease Control and Prevention. 2013. Antibiotic resistance threats in the United States, 2013. Centers for Disease Control and Prevention, Atlanta, GA. https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf.
  2. 2.↵
    1. Bassetti M,
    2. Poulakou G,
    3. Ruppe E,
    4. Bouza E,
    5. Van Hal SJ,
    6. Brink A
    . 2017. Antimicrobial resistance in the next 30 years, humankind, bugs and drugs: a visionary approach. Intensive Care Med 43:1464–1475. doi:10.1007/s00134-017-4878-x.
    OpenUrlCrossRef
  3. 3.↵
    1. Kollef MH,
    2. Bassetti M,
    3. Francois B,
    4. Burnham J,
    5. Dimopoulos G,
    6. Garnacho-Montero J,
    7. Lipman J,
    8. Luyt CE,
    9. Nicolau DP,
    10. Postma MJ,
    11. Torres A,
    12. Welte T,
    13. Wunderink RG
    . 2017. The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship. Intensive Care Med 43:1187–1197. doi:10.1007/s00134-017-4682-7.
    OpenUrlCrossRef
  4. 4.↵
    1. Bassetti M,
    2. Russo A,
    3. Carnelutti A,
    4. La Rosa A,
    5. Righi E
    . 2018. Antimicrobial resistance and treatment: an unmet clinical safety need. Expert Opin Drug Saf 17:669–680. doi:10.1080/14740338.2018.1488962.
    OpenUrlCrossRef
  5. 5.↵
    1. Falagas ME,
    2. Mavroudis AD,
    3. Vardakas KZ
    . 2016. The antibiotic pipeline for multi-drug resistant Gram-negative bacteria: what can we expect? Expert Rev Anti Infect Ther 14:747–763. doi:10.1080/14787210.2016.1204911.
    OpenUrlCrossRef
  6. 6.↵
    World Health Organization. 2017. WHO publishes list of bacteria for which new antibiotics are urgently needed. http://www.who.int/news-room/detail/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed.
  7. 7.↵
    1. Zhanel GG,
    2. Cheung D,
    3. Adam H,
    4. Zelenitsky S,
    5. Golden A,
    6. Schweizer F,
    7. Gorityala B,
    8. Lagacé-Wiens PR,
    9. Walkty A,
    10. Gin AS,
    11. Hoban DJ,
    12. Karlowsky JA
    . 2016. Review of eravacycline, a novel fluorocycline antibacterial agent. Drugs 76:567–588. doi:10.1007/s40265-016-0545-8.
    OpenUrlCrossRefPubMed
  8. 8.
    Reference deleted.
  9. 9.↵
    1. Xiao X-Y,
    2. Hunt DK,
    3. Zhou J,
    4. Clark RB,
    5. Dunwoody N,
    6. Fyfe C,
    7. Grossman TH,
    8. O'Brien WJ,
    9. Plamondon L,
    10. Rönn M,
    11. Sun C,
    12. Zhang W-Y,
    13. Sutcliffe JA
    . 2012. Fluorocyclines. 1. 7-Fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: a potent broad spectrum antibacterial agent. J Med Chem 55:597–605. doi:10.1021/jm201465w.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Grossman TH,
    2. Starosta AL,
    3. Fyfe C,
    4. O'Brien W,
    5. Rothstein DM,
    6. Mikolajka A,
    7. Wilson DN,
    8. Sutcliffe JA
    . 2012. Target and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic. Antimicrob Agents Chemother 56:2559–2564. doi:10.1128/AAC.06187-11.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Sutcliffe JA,
    2. O’Brien W,
    3. Fyfe C,
    4. Grossman TH
    . 2013. Antibacterial activity of eravacycline (TP-434), a novel fluorocycline against hospital and community pathogens. Antimicrob Agents Chemother 59:5548–5558. doi:10.1128/AAC.01288-13.
    OpenUrlCrossRef
  12. 12.↵
    1. Abdallah M,
    2. Olafisoye O,
    3. Cortes C,
    4. Urban C,
    5. Landman D,
    6. Quale J
    . 2015. Activity of eravacycline against Enterobacteriaceae and Acinetobacter baumannii, including multidrug-resistant isolates from New York City. Antimicrob Agents Chemother 59:1802–1805. doi:10.1128/AAC.04809-14.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    1. Johnson JR,
    2. Porter SB,
    3. Johnston BD,
    4. Thuras P
    . 2015. Activity of eravacycline against Escherichia coli clinical isolates collected from U.S. veterans in 2011 in relation to coresistance phenotype and sequence type 131 genotype. Antimicrob Agents Chemother 60:1888–1891. doi:10.1128/AAC.02403-15.
    OpenUrlCrossRef
  14. 14.↵
    1. Bassetti M,
    2. Righi E
    . 2014. Eravacycline for the treatment of intra-abdominal infections. Expert Opin Invest Drugs 23:1575–1584. doi:10.1517/13543784.2014.965253.
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Lagacé-Wiens PRS,
    2. Adam HJ,
    3. Laing NM,
    4. Baxter MR,
    5. Martin I,
    6. Mulvey MR,
    7. Karlowsky JA,
    8. Hoban DJ,
    9. Zhanel GG
    . 2017. Antimicrobial susceptibility of clinical isolates of Neisseria gonorrhoeae to alternative antimicrobials with therapeutic potential. J Antimicrob Chemother 72:2273–2277. doi:10.1093/jac/dkx147.
    OpenUrlCrossRef
  16. 16.↵
    1. Zhanel GG,
    2. Baxter MR,
    3. Adam HJ,
    4. Sutcliffe J,
    5. Karlowsky JA
    . 2018. In vitro activity of eravacycline against 2,213 Gram-negative and 2,424 Gram-positive bacterial pathogens isolated in Canadian hospital laboratories: CANWARD surveillance study 2014–2015. Diagn Microbiol Infect Dis 91:55–62. doi:10.1016/j.diagmicrobio.2017.12.013.
    OpenUrlCrossRef
  17. 17.↵
    Clinical and Laboratory Standards Institute. 2019. Performance standards for antimicrobial susceptibility testing, 29th ed. M100. Clinical and Laboratory Standards Institute, Wayne, PA.
  18. 18.↵
    European Committee on Antimicrobial Susceptibility Testing. 2019. Breakpoint tables for interpretation of MICs and zone diameters, version 9.0. http://www.eucast.org.
  19. 19.↵
    1. Hoban DJ,
    2. Reinert RR,
    3. Bouchillon SK,
    4. Dowzicky MJ
    . 2015. Global in vitro activity of tigecycline and comparator agents: Tigecycline Evaluation and Surveillance Trial 2004–2013. Ann Clin Microbiol Antimicrob 14:27. doi:10.1186/s12941-015-0085-1.
    OpenUrlCrossRefPubMed
  20. 20.↵
    1. Giammanco A,
    2. Calà C,
    3. Fasciana T,
    4. Dowzicky MJ,
    5. Giammanco A,
    6. Calà C,
    7. Fasciana T,
    8. Dowzicky MJ
    . 2017. Global assessment of the activity of tigecycline against multidrug resistant Gram-negative pathogens between 2004 and 2014 as part of the Tigecycline Evaluation and Surveillance Trial. mSphere 2:e00310-16. doi:10.1128/mSphere.00310-16.
    OpenUrlAbstract/FREE Full Text
  21. 21.↵
    1. Wu H,
    2. Wang JT,
    3. Shiau YR,
    4. Wang HY,
    5. Lauderdale TL,
    6. Chang SC, TSAR Hospitals
    . 2012. A multicenter surveillance of antimicrobial resistance on Stenotrophomonas maltophilia in Taiwan. J Microbiol Immunol Infect 45:120–126. doi:10.1016/j.jmii.2011.09.028.
    OpenUrlCrossRefPubMed
  22. 22.↵
    1. Seifert H,
    2. Stefanik D,
    3. Sutcliffe JA,
    4. Higgins PG
    . 2018. In-vitro activity of the novel fluorocycline eravacycline against carbapenem non-susceptible Acinetobacter baumannii. Int J Antimicrob Agents 51:62–64. doi:10.1016/j.ijantimicag.2017.06.022.
    OpenUrlCrossRef
  23. 23.↵
    1. Fyfe C,
    2. LeBlanc G,
    3. Close B,
    4. Nordmann P,
    5. Dumas J,
    6. Grossman TH
    . 2016. Eravacycline is active against bacterial isolates expressing the polymyxin resistance gene mcr-1. Antimicrob Agents Chemother 60:6989–6990. doi:10.1128/AAC.01646-16.
    OpenUrlFREE Full Text
  24. 24.↵
    1. Livermore DM,
    2. Mushtaq S,
    3. Warner M,
    4. Woodford N
    . 2016. In vitro activity of eravacycline against carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii. Antimicrob Agents Chemother 60:3840–3844. doi:10.1128/AAC.00436-16.
    OpenUrlAbstract/FREE Full Text
  25. 25.↵
    1. Monogue ML,
    2. Thabit AK,
    3. Hamada Y,
    4. Nicolau DP
    . 2016. Antibacterial efficacy of eravacycline in vivo against Gram-positive and Gram-negative organisms. Antimicrob Agents Chemother 60:5001–5005. doi:10.1128/AAC.00366-16.
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. Zhang Y,
    2. Lin X,
    3. Bush K
    . 2016. In vitro susceptibility of β-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE) to eravacycline. J Antibiot (Tokyo) 69:600–604. doi:10.1038/ja.2016.73.
    OpenUrlCrossRef
  27. 27.↵
    1. Mayne A,
    2. Dowzicky MJ
    . 2012. In vitro activity of tigecycline and comparators against organisms associated with intra-abdominal infections collected as part of TEST (2004–2009). Diagn Microbiol Infect Dis 74:151–157. doi:10.1016/j.diagmicrobio.2012.05.032.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Pfaller MA,
    2. Huband MD,
    3. Streit JM,
    4. Flamm RK,
    5. Sader HS
    . 2018. Surveillance of tigecycline activity tested against clinical isolates from a global (North America, Europe, Latin America and Asia-Pacific) collection (2016). Int J Antimicrob Agents 51:848–853. doi:10.1016/j.ijantimicag.2018.01.006.
    OpenUrlCrossRef
  29. 29.↵
    Wyeth Pharmaceuticals Inc. 2016. Tygacil (tigecycline)—tigecycline injection, powder, lyophilized, for solution, prescribing information. Wyeth Pharmaceuticals Inc, Philadelphia, PA.
  30. 30.↵
    1. Zhanel GG,
    2. Karlowsky JA,
    3. Rubinstein E,
    4. Hoban DJ
    . 2006. Tigecycline: a novel glycylcycline antibiotic. Expert Rev Anti Infect Ther 4:9–25. doi:10.1586/14787210.4.1.9.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Solomkin JS,
    2. Ramesh MK,
    3. Cesnauskas G,
    4. Novikovs N,
    5. Stefanova P,
    6. Sutcliffe JA,
    7. Walpole SM,
    8. Horn PT
    . 2014. Phase 2 randomized double blind study of the efficacy and safety of two dose regimens of eravacycline versus ertapenem for adult community-acquired complicated intra-abdominal infections. Antimicrob Agents Chemother 58:1847–1854. doi:10.1128/AAC.01614-13.
    OpenUrlAbstract/FREE Full Text
  32. 32.↵
    1. Reygaert WC
    . 2010. Antibiotic optimization in the difficult-to-treat patient with complicated intra-abdominal or complicated skin and skin structure infections: focus on tigecycline. Ther Clin Risk Manag 6:419–430. doi:10.2147/tcrm.s9117.
    OpenUrlCrossRefPubMed
  33. 33.↵
    1. Sartelli M
    . 2010. A focus on intra-abdominal infections. World J Emerg Surg 5:9. doi:10.1186/1749-7922-5-9.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Weigelt JA
    . 2007. Empiric treatment options in the management of complicated intraabdominal infections. Cleve Clin J Med 74:S29–S37. doi:10.3949/ccjm.74.Suppl_4.S29.
    OpenUrlAbstract/FREE Full Text
  35. 35.↵
    1. Solomkin JS,
    2. Mazuski JE,
    3. Bradley JS,
    4. Rodvold KA,
    5. Goldstein EJC,
    6. Baron EJ,
    7. O'Neill PJ,
    8. Chow AW,
    9. Dellinger EP,
    10. Eachempati SR,
    11. Gorbach S,
    12. Hilfiker M,
    13. May AK,
    14. Nathens AB,
    15. Sawyer RG,
    16. Bartlett JG
    . 2010. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 50:133–164. doi:10.1086/649554.
    OpenUrlCrossRefPubMedWeb of Science
  36. 36.↵
    1. Li G,
    2. Ren J,
    3. Wu Q,
    4. Hu D,
    5. Wang G,
    6. Wu X,
    7. Liu S,
    8. Wu Y,
    9. Gu G,
    10. Li J
    . 2015. Bacteriology of spontaneous intra-abdominal abscess in patients with Crohn disease in China: risk of extended-spectrum beta-lactamase-producing bacteria. Surg Infect (Larchmt) 16:461–465. doi:10.1089/sur.2013.181.
    OpenUrlCrossRef
  37. 37.↵
    1. Jang JY,
    2. Lee SH,
    3. Shim H,
    4. Choi JY,
    5. Yong D,
    6. Lee JG
    . 2015. Epidemiology and microbiology of secondary peritonitis caused by viscus perforation: a single-center retrospective study. Surg Infect (Larchmt) 16:436–442. doi:10.1089/sur.2014.148.
    OpenUrlCrossRef
  38. 38.↵
    1. Augustin P,
    2. Kermarrec N,
    3. Muller-Serieys C,
    4. Lasocki S,
    5. Chosidow D,
    6. Marmuse JP,
    7. Valin N,
    8. Desmonts JM,
    9. Montravers P
    . 2010. Risk factors for multidrug resistant bacteria and optimization of empirical antibiotic therapy in postoperative peritonitis. Crit Care 14:R20. doi:10.1186/cc8877.
    OpenUrlCrossRefPubMed
  39. 39.↵
    Clinical and Laboratory Standards Institute. 2018. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 11th ed. Approved standard M07-A11. Clinical and Laboratory Standards Institute, Wayne, PA.
  40. 40.↵
    1. Wang YL,
    2. Scipione MR,
    3. Dubrovskaya Y,
    4. Papadopoulos J
    . 2014. Monotherapy with fluoroquinolone or trimethoprim-sulfamethoxazole for treatment of Stenotrophomonas maltophilia infections. Antimicrob Agents Chemother 58:176–182. doi:10.1128/AAC.01324-13.
    OpenUrlAbstract/FREE Full Text
View Abstract
PreviousNext
Back to top
Download PDF
Citation Tools
In Vitro Activity of Eravacycline against Gram-Negative Bacilli Isolated in Clinical Laboratories Worldwide from 2013 to 2017
Ian Morrissey, Melanie Olesky, Stephen Hawser, Sibylle H. Lob, James A. Karlowsky, G. Ralph Corey, Matteo Bassetti, Corey Fyfe
Antimicrobial Agents and Chemotherapy Feb 2020, 64 (3) e01699-19; DOI: 10.1128/AAC.01699-19

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.
In Vitro Activity of Eravacycline against Gram-Negative Bacilli Isolated in Clinical Laboratories Worldwide from 2013 to 2017
(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
In Vitro Activity of Eravacycline against Gram-Negative Bacilli Isolated in Clinical Laboratories Worldwide from 2013 to 2017
Ian Morrissey, Melanie Olesky, Stephen Hawser, Sibylle H. Lob, James A. Karlowsky, G. Ralph Corey, Matteo Bassetti, Corey Fyfe
Antimicrobial Agents and Chemotherapy Feb 2020, 64 (3) e01699-19; DOI: 10.1128/AAC.01699-19
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • INTRODUCTION
    • RESULTS AND DISCUSSION
    • MATERIALS AND METHODS
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

eravacycline
multidrug resistant
MDR
Gram negative
Enterobacteriaceae
Acinetobacter

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