In vitro
                    efficacy of sulbactam/durlobactam combined with β-lactam antibiotics in Australian
                    Mycobacterium abscessus
                    isolates

Kirby Patterson-Fahy; Robyn Carter; Scott C Bell; Ieuan E S Evans; Andrew John Burke; Rachel M Thomson

doi:10.1093/jac/dkaf441

journal article Open Access Dec 12, 2025

In vitro efficacy of sulbactam/durlobactam combined with β-lactam antibiotics in Australian Mycobacterium abscessus isolates

Kirby Patterson-Fahy

Robyn Carter Scott C Bell Ieuan E S Evans Andrew John Burke

Rachel M Thomson

Journal of Antimicrobial Chemotherapy Vol. 81 No. 1 · Oxford University Press (OUP)

View at Publisher Save 10.1093/jac/dkaf441

Abstract

Abstract

Background and objectives
Mycobacterium abscessus has extensive innate and acquired antibiotic resistance resulting in limited antibiotic treatment options and poor clinical outcomes. Currently, the only β-lactam antibiotics with efficacy against M. abscessus are imipenem and cefoxitin. Durlobactam is a β-lactamase inhibitor that may overcome intrinsic resistance mechanisms and enable the use of alternative oral β-lactam antibiotics. The objective of this study was to determine whether sulbactam/durlobactam increases the susceptibility of M. abscessus to alternative β-lactam antibiotics.

Material and methods
Antibiotic susceptibility testing was performed for durlobactam, meropenem, cefuroxime/amoxicillin alone, and sulbactam/durlobactam alone and in combination with meropenem and cefuroxime/amoxicillin according to Clinical Laboratory Standards Institute (CLSI) standards. These results were then compared with imipenem susceptibility with and without relebactam.

Results
Sulbactam/durlobactam significantly lowered the MICs of M. abscessus to meropenem, cefuroxime and cefuroxime/amoxicillin to MICs comparable to those of imipenem and imipenem/relebactam. The culture medium used had a significant impact on MIC, with Middlebrook 7H9 having significantly lower MICs for all combinations containing durlobactam compared with CLSI standard CAMHB media.

Conclusion
Sulbactam/durlobactam significantly increased susceptibility to oral and intravenous β-lactam antibiotics in the form of cefuroxime, cefuroxime/amoxicillin and meropenem against clinical isolates of M. abscessus. This study also found significant differences in susceptibility to β-lactam antibiotics dependent on the culture media used, highlighting that the optimal culture methods for determining MIC in M. abscessus remains uncertain. Future in vivo studies are required to determine whether the in vitro efficacy of the β-lactam combinations studied could result in clinical efficacy for M. abscessus disease.

Topics

No keywords indexed for this article. Browse by subject →

References

47

[1]

Thomson "Influence of climate variables on the rising incidence of nontuberculous mycobacterial (NTM) infections in Queensland, Australia 2001–2016" Sci Total Environ (2020) 10.1016/j.scitotenv.2020.139796

[2]

Johansen "Non-tuberculous mycobacteria and the rise of Mycobacterium abscessus" Nat Rev Microbiol (2020) 10.1038/s41579-020-0331-1

[3]

Chen "Clinical efficacy and adverse effects of antibiotics used to treat Mycobacterium abscessus pulmonary disease" Front Microbiol (2019) 10.3389/fmicb.2019.01977

[4]

Kwak "Mycobacterium abscessus pulmonary disease: individual patient data meta-analysis" Eur Respir J (2019) 10.1183/13993003.01991-2018

[5]

Haworth "British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD)" Thorax (2017) 10.1136/thoraxjnl-2017-210927

[6]

Floto "US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis" Thorax (2016) 10.1136/thoraxjnl-2015-207360

[7]

Daley "Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline" Eur Respir J (2020) 10.1183/13993003.00535-2020

[8]

β-Lactams and β-Lactamase Inhibitors: An Overview

KAREN BUSH, Patricia A. Bradford

Cold Spring Harbor Perspectives in Medicine 2016 10.1101/cshperspect.a025247

[9]

Lavollay "The peptidoglycan of Mycobacterium abscessus is predominantly cross-linked by L,D-transpeptidases" J Bacteriol (2011) 10.1128/jb.00606-10

[10]

Machowski "Comparative genomics for mycobacterial peptidoglycan remodelling enzymes reveals extensive genetic multiplicity" BMC Microbiol (2014) 10.1186/1471-2180-14-75

[11]

Sayed "First penicillin-binding protein occupancy patterns for 15 β-lactams and β-lactamase inhibitors in Mycobacterium abscessus" Antimicrob Agents Chemother (2020) 10.1128/aac.01956-20

[12]

Dousa "Insights into the L,D-transpeptidases and D,D-carboxypeptidase of Mycobacterium abscessus: ceftaroline, imipenem, and novel diazabicyclooctane inhibitors" Antimicrob Agents Chemother (2020) 10.1128/aac.00098-20

[13]

Kumar "Mycobacterium abscessus L,D-transpeptidases are susceptible to inactivation by carbapenems and cephalosporins but not penicillins" Antimicrob Agents Chemother (2017) 10.1128/aac.00866-17

[14]

Longo "Dual β-lactams for the treatment of Mycobacterium abscessus: a review of the evidence and a call to act against an antibiotic nightmare" J Antimicrob Chemother (2024) 10.1093/jac/dkae288

[15]

Nguyen "“One-two punch”: synergistic ß-lactam combinations for Mycobacterium abscessus and target redundancy in the inhibition of peptidoglycan synthesis enzymes" Clin Infect Dis (2021) 10.1093/cid/ciab535

[16]

Comprehensive stability analysis of 13 β-lactams and β-lactamase inhibitors in in vitro media, and novel supplement dosing strategy to mitigate thermal drug degradation

Jieqiang Zhou, Yuli Qian, Yinzhi Lang et al.

Antimicrobial Agents and Chemotherapy 2024 10.1128/aac.01399-23

[17]

Pozuelo Torres "Dual β-lactam therapy to improve treatment outcome in Mycobacterium abscessus disease" Clin Microbiol Infect (2024) 10.1016/j.cmi.2024.03.019

[18]

Ripoll "Non mycobacterial virulence genes in the genome of the emerging pathogen Mycobacterium abscessus" PLoS ONE (2009) 10.1371/journal.pone.0005660

[19]

Characterization of broad-spectrum Mycobacterium abscessus class A -lactamase

D. Soroka, V. Dubée, O. Soulier-Escrihuela et al.

Journal of Antimicrobial Chemotherapy 2014 10.1093/jac/dkt410

[20]

Lefebvre "Inhibition of the β-lactamase BlaMab by avibactam improves the in vitro and in vivo efficacy of imipenem against Mycobacterium abscessus" Antimicrob Agents Chemother (2017) 10.1128/aac.02440-16

[21]

Le Run "Impact of relebactam-mediated inhibition of Mycobacterium abscessus BlaMab β-lactamase on the in vitro and intracellular efficacy of imipenem" J Antimicrob Chemother (2020) 10.1093/jac/dkz433

[22]

Burke "In vitro susceptibility testing of imipenem-relebactam and tedizolid against 102 Mycobacterium abscessus isolates" Int J Antimicrob Agents (2023) 10.1016/j.ijantimicag.2023.106938

[23]

Dousa "Synergistic effects of sulopenem in combination with cefuroxime or durlobactam against Mycobacterium abscessus" mBio (2024) 10.1128/mbio.00609-24

[24]

Inhibiting Mycobacterium abscessus Cell Wall Synthesis: Using a Novel Diazabicyclooctane β-Lactamase Inhibitor To Augment β-Lactam Action

Khalid M. Dousa, David C. Nguyen, Sebastian G. Kurz et al.

mBio 2022 10.1128/mbio.03529-21

[25]

Durlobactam to boost the clinical utility of standard of care β-lactams against Mycobacterium abscessus lung disease

Dereje A. Negatu, Wassihun Wedajo Aragaw, Tewodros T. Gebresilase et al.

Antimicrobial Agents and Chemotherapy 2024 10.1128/aac.01046-24

[26]

Durlobactam in combination with β-lactams to combat Mycobacterium abscessus

Eunjeong Shin, Khalid M. Dousa, Magdalena A. Taracila et al.

Antimicrobial Agents and Chemotherapy 2024 10.1128/aac.01174-24

[27]

CLSI

[28]

CLSI

[29]

Russo "Approaches to testing novel β-lactam and β-lactam combination agents in the clinical laboratory" Antibiotics (2023) 10.3390/antibiotics12121700

[30]

Rodvold "Plasma and intrapulmonary concentrations of ETX2514 and sulbactam following intravenous administration of ETX2514SUL to healthy adult subjects" Antimicrob Agents Chemother (2018) 10.1128/aac.01089-18

[31]

Mullard "FDA approves new antibiotic combination for drug-resistant pneumonia" Nat Rev Drug Discov (2023) 10.1038/d41573-023-00096-8

[32]

Lopeman "Effect of amoxicillin in combination with imipenem-relebactam against Mycobacterium abscessus" Sci Rep (2020) 10.1038/s41598-020-57844-8

[33]

Park "Impact of susceptibility to injectable antibiotics on the treatment outcomes of Mycobacterium abscessus pulmonary disease" Open Forum Infect Dis (2021) 10.1093/ofid/ofab215

[34]

Misawa "In vitro effects of diazabicyclooctane β-lactamase inhibitors relebactam and nacubactam against three subspecies of Mycobacterium abscessus complex" Int J Antimicrob Agents (2022) 10.1016/j.ijantimicag.2022.106669

[35]

Hedin "A rough colony morphology of Mycobacterium abscessus is associated with cavitary pulmonary disease and poor clinical outcome" J Infect Dis (2023) 10.1093/infdis/jiad007

[36]

Rominski "Effect of β-lactamase production and β-lactam instability on MIC testing results for Mycobacterium abscessus" J Antimicrob Chemother (2017) 10.1093/jac/dkx284

[37]

Kaushik "In vitro activity of the new β-lactamase inhibitors relebactam and vaborbactam in combination with β-lactams against Mycobacterium abscessus complex clinical isolates" Antimicrob Agents Chemother (2019) 10.1128/aac.02623-18

[38]

Shrivastava "Sulbactam-durlobactam improves cephalosporin and carbapenem susceptibility and time-kill effect against Mycobacterium abscessus" Microbiol Spectr (2025) 10.1128/spectrum.01492-25

[39]

Baker "Cystic fibrosis sputum media induces an overall loss of antibiotic susceptibility in Mycobacterium abscessus" NPJ Antimicrob Resist (2024) 10.1038/s44259-024-00054-3

[40]

Greendyke "Differential antibiotic susceptibility of Mycobacterium abscessus variants in biofilms and macrophages compared to that of planktonic bacteria" Antimicrob Agents Chemother (2008) 10.1128/aac.00986-07

[41]

Oschmann-Kadenbach "Impact of Mycobacteroides abscessus colony morphology on biofilm formation and antimicrobial resistance" Int J Med Microbiol (2024) 10.1016/j.ijmm.2024.151603

[42]

Negatu "Strongly bactericidal all-oral β-lactam combinations for the treatment of Mycobacterium abscessus lung disease" Antimicrob Agents Chemother (2022) 10.1128/aac.00790-22

[43]

Efficacy and safety of sulbactam–durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii–calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK)

Keith S Kaye, Andrew F Shorr, Richard G Wunderink et al.

The Lancet Infectious Diseases 2023 10.1016/s1473-3099(23)00184-6

[44]

Singh 10.1101/2025.08.05.668504

[45]

Dartois "Preclinical murine models for the testing of antimicrobials against Mycobacterium abscessus pulmonary infections: current practices and recommendations" Tuberculosis (2024) 10.1016/j.tube.2024.102503

[46]

Shimamura "Successful treatment of macrolide-resistant Mycobacterium abscessus infection using multi-drug regimens including dual β-lactams and phage therapy: case reports in two children" ASM Case Rep (2025) 10.1128/asmcr.00087-24

[47]

Jong "Finding the optimal regimen for Mycobacteroides abscessus treatment (FORMaT) in people with Mycobacteroides abscessus pulmonary disease: a multicentre, randomised, multi-arm, adaptive platform trial" BMJ Open (2025) 10.1136/bmjopen-2024-096188

Metrics

1

Citations

47

References

Details

Published: Dec 12, 2025
Vol/Issue: 81(1)
License: View

Authors

K

Kirby Patterson-Fahy

The University of Queensland, Greenslopes Clinical School, Gallipoli Medical Research , Greenslopes, QLD ,

R

Robyn Carter

The University of Queensland, Greenslopes Clinical School, Gallipoli Medical Research , Greenslopes, QLD ,

S

Scott C Bell

Department of Thoracic Medicine, The Prince Charles Hospital , Chermside, Brisbane, QLD ,; Child Health Research Centre, The University of Queensland , South Brisbane, QLD ,; Department of Respiratory Medicine, Gold Coast University Hospital , Southport, QLD ,; School of Medicine and Dentistry, Health Group, Griffith University , Southport, QLD ,

I

Ieuan E S Evans

Department of Thoracic Medicine, The Prince Charles Hospital , Chermside, Brisbane, QLD ,; Faculty of Medicine, The University of Queensland, Mayne Medical School , Herston, Brisbane ,

A

Andrew John Burke

Faculty of Medicine, The University of Queensland, Mayne Medical School , Herston, Brisbane ,; Department of Infectious Disease, The Prince Charles Hospital , Chermside, Brisbane, QLD ,

R

Rachel M Thomson

The University of Queensland, Greenslopes Clinical School, Gallipoli Medical Research , Greenslopes, QLD ,; Department of Thoracic Medicine, The Prince Charles Hospital , Chermside, Brisbane, QLD ,; MetroSouth Clinical TB Service, Princess Alexandra Hospital , Brisbane ,

Funding

Gallipoli Medical Research

Cite This Article

Kirby Patterson-Fahy, Robyn Carter, Scott C Bell, et al. (2025). In vitro efficacy of sulbactam/durlobactam combined with β-lactam antibiotics in Australian Mycobacterium abscessus isolates. Journal of Antimicrobial Chemotherapy, 81(1). https://doi.org/10.1093/jac/dkaf441

In vitro efficacy of sulbactam/durlobactam combined with β-lactam antibiotics in Australian Mycobacterium abscessus isolates

You May Also Like