Differences in suppression of regrowth and resistance despite similar initial bacterial killing for meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli

Phillip J. Bergen, Jürgen B. Bulitta, Fekade B. Sime, Jeffrey Lipman, Megan J. McGregor, Nada Millen, David L. Paterson, Carl M.J. Kirkpatrick, Jason A. Roberts, Cornelia B. Landersdorfer

Research output: Contribution to journalArticleResearchpeer-review

Abstract

We described bacterial killing and resistance emergence at various fixed concentrations of meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli. Time-kill studies were conducted utilizing nine isolates and a large range of concentrations. Within each strain and antibiotic, initial killing was similar, with concentrations ≥2×MIC. At many (strain-specific) concentrations causing substantial initial killing, regrowth occurred at 24-48h. For remaining concentrations, growth typically remained suppressed (<5-log10 cfu/mL). The concentrations of meropenem required to suppress regrowth ranged from 2–8×MIC for P. aeruginosa and 2–64×MIC for E. coli. For piperacillin/tazobactam, the equivalent concentrations ranged from 8–16×MIC for P. aeruginosa and 4–16×MIC for E. coli. The number of less-susceptible bacteria increased with rising concentrations before decreasing at even higher concentrations. Suppression of regrowth and resistance was substantially improved with higher concentrations (typically ≥8×MIC), suggesting a benefit of higher β-lactam concentrations beyond those required for maximum initial killing.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalDiagnostic Microbiology and Infectious Disease
Volume91
Issue number1
DOIs
Publication statusPublished - 1 May 2018

Keywords

  • Bacterial killing
  • beta-Lactam antibiotics
  • In vitro studies
  • Resistance

Cite this

Bergen, Phillip J. ; Bulitta, Jürgen B. ; Sime, Fekade B. ; Lipman, Jeffrey ; McGregor, Megan J. ; Millen, Nada ; Paterson, David L. ; Kirkpatrick, Carl M.J. ; Roberts, Jason A. ; Landersdorfer, Cornelia B. / Differences in suppression of regrowth and resistance despite similar initial bacterial killing for meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli. In: Diagnostic Microbiology and Infectious Disease. 2018 ; Vol. 91, No. 1. pp. 69-76.
@article{f2646d869ac84858b2449be5a03b0885,
title = "Differences in suppression of regrowth and resistance despite similar initial bacterial killing for meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli",
abstract = "We described bacterial killing and resistance emergence at various fixed concentrations of meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli. Time-kill studies were conducted utilizing nine isolates and a large range of concentrations. Within each strain and antibiotic, initial killing was similar, with concentrations ≥2×MIC. At many (strain-specific) concentrations causing substantial initial killing, regrowth occurred at 24-48h. For remaining concentrations, growth typically remained suppressed (<5-log10 cfu/mL). The concentrations of meropenem required to suppress regrowth ranged from 2–8×MIC for P. aeruginosa and 2–64×MIC for E. coli. For piperacillin/tazobactam, the equivalent concentrations ranged from 8–16×MIC for P. aeruginosa and 4–16×MIC for E. coli. The number of less-susceptible bacteria increased with rising concentrations before decreasing at even higher concentrations. Suppression of regrowth and resistance was substantially improved with higher concentrations (typically ≥8×MIC), suggesting a benefit of higher β-lactam concentrations beyond those required for maximum initial killing.",
keywords = "Bacterial killing, beta-Lactam antibiotics, In vitro studies, Resistance",
author = "Bergen, {Phillip J.} and Bulitta, {J{\"u}rgen B.} and Sime, {Fekade B.} and Jeffrey Lipman and McGregor, {Megan J.} and Nada Millen and Paterson, {David L.} and Kirkpatrick, {Carl M.J.} and Roberts, {Jason A.} and Landersdorfer, {Cornelia B.}",
year = "2018",
month = "5",
day = "1",
doi = "10.1016/j.diagmicrobio.2017.12.019",
language = "English",
volume = "91",
pages = "69--76",
journal = "Diagnostic Microbiology and Infectious Disease",
issn = "0732-8893",
publisher = "Elsevier",
number = "1",

}

Differences in suppression of regrowth and resistance despite similar initial bacterial killing for meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli. / Bergen, Phillip J.; Bulitta, Jürgen B.; Sime, Fekade B.; Lipman, Jeffrey; McGregor, Megan J.; Millen, Nada; Paterson, David L.; Kirkpatrick, Carl M.J.; Roberts, Jason A.; Landersdorfer, Cornelia B.

In: Diagnostic Microbiology and Infectious Disease, Vol. 91, No. 1, 01.05.2018, p. 69-76.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Differences in suppression of regrowth and resistance despite similar initial bacterial killing for meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli

AU - Bergen, Phillip J.

AU - Bulitta, Jürgen B.

AU - Sime, Fekade B.

AU - Lipman, Jeffrey

AU - McGregor, Megan J.

AU - Millen, Nada

AU - Paterson, David L.

AU - Kirkpatrick, Carl M.J.

AU - Roberts, Jason A.

AU - Landersdorfer, Cornelia B.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - We described bacterial killing and resistance emergence at various fixed concentrations of meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli. Time-kill studies were conducted utilizing nine isolates and a large range of concentrations. Within each strain and antibiotic, initial killing was similar, with concentrations ≥2×MIC. At many (strain-specific) concentrations causing substantial initial killing, regrowth occurred at 24-48h. For remaining concentrations, growth typically remained suppressed (<5-log10 cfu/mL). The concentrations of meropenem required to suppress regrowth ranged from 2–8×MIC for P. aeruginosa and 2–64×MIC for E. coli. For piperacillin/tazobactam, the equivalent concentrations ranged from 8–16×MIC for P. aeruginosa and 4–16×MIC for E. coli. The number of less-susceptible bacteria increased with rising concentrations before decreasing at even higher concentrations. Suppression of regrowth and resistance was substantially improved with higher concentrations (typically ≥8×MIC), suggesting a benefit of higher β-lactam concentrations beyond those required for maximum initial killing.

AB - We described bacterial killing and resistance emergence at various fixed concentrations of meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli. Time-kill studies were conducted utilizing nine isolates and a large range of concentrations. Within each strain and antibiotic, initial killing was similar, with concentrations ≥2×MIC. At many (strain-specific) concentrations causing substantial initial killing, regrowth occurred at 24-48h. For remaining concentrations, growth typically remained suppressed (<5-log10 cfu/mL). The concentrations of meropenem required to suppress regrowth ranged from 2–8×MIC for P. aeruginosa and 2–64×MIC for E. coli. For piperacillin/tazobactam, the equivalent concentrations ranged from 8–16×MIC for P. aeruginosa and 4–16×MIC for E. coli. The number of less-susceptible bacteria increased with rising concentrations before decreasing at even higher concentrations. Suppression of regrowth and resistance was substantially improved with higher concentrations (typically ≥8×MIC), suggesting a benefit of higher β-lactam concentrations beyond those required for maximum initial killing.

KW - Bacterial killing

KW - beta-Lactam antibiotics

KW - In vitro studies

KW - Resistance

UR - http://www.scopus.com/inward/record.url?scp=85041180193&partnerID=8YFLogxK

U2 - 10.1016/j.diagmicrobio.2017.12.019

DO - 10.1016/j.diagmicrobio.2017.12.019

M3 - Article

VL - 91

SP - 69

EP - 76

JO - Diagnostic Microbiology and Infectious Disease

JF - Diagnostic Microbiology and Infectious Disease

SN - 0732-8893

IS - 1

ER -