Poor efficacy of the combination of clarithromycin, amikacin, and cefoxitin against Mycobacterium abscessus in the hollow fiber infection model
Abstract Background Mycobacterium abscessus (MABS) causes difficult-to-treat pulmonary and extra-pulmonary infections. A combination therapy comprising amikacin, cefoxitin, and a macrolide agent is recommended, but its antimicrobial activity and clinical efficacy is uncertain. Inducible resistance t...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Annals of Clinical Microbiology and Antimicrobials |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12941-025-00776-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571911777812480 |
|---|---|
| author | Etienne Vignaud Sylvain Goutelle Charlotte Genestet Jérôme Guitton Sabine Cohen Chloé Bourg Aurore Durand Laura Lebouteiller Albin Bernard Caroline Richet Oana Dumitrescu Elisabeth Hodille |
| author_facet | Etienne Vignaud Sylvain Goutelle Charlotte Genestet Jérôme Guitton Sabine Cohen Chloé Bourg Aurore Durand Laura Lebouteiller Albin Bernard Caroline Richet Oana Dumitrescu Elisabeth Hodille |
| author_sort | Etienne Vignaud |
| collection | DOAJ |
| description | Abstract Background Mycobacterium abscessus (MABS) causes difficult-to-treat pulmonary and extra-pulmonary infections. A combination therapy comprising amikacin, cefoxitin, and a macrolide agent is recommended, but its antimicrobial activity and clinical efficacy is uncertain. Inducible resistance to macrolides (macrolides-iR) has been associated with poor clinical response in pulmonary infections, whilst for extra-pulmonary infections data are scarce. Objectives Herein, the aim was to evaluate the effect of the amikacin, cefoxitin, and clarithromycin combination against macrolides-iR MABS in a hollow-fiber infection model. Methods The hollow-fiber system was inoculated with M. abscessus subsp. abscessus type strain ATCC 19977 and treated during 10 days with the antibiotics combination. Two level of macrolide concentrations were evaluated mimicking the pharmacokinetics profiles of free (i.e. unbound) drug in blood and lung. Results Using blood concentrations, the combination failed to prevent bacterial growth. Using lung concentrations, the combination had a limited but significant effect on bacterial growth from day 2 to day 10. Moreover, increasing clarithromycin concentrations stabilized the amikacin-tolerance level: amikacin minimal inhibitory concentration of amikacin-tolerant strains increased over time using blood concentrations while it remained stable using lung concentrations. Conclusions Our finding confirms the low activity of the amikacin, cefoxitin, and clarithromycin combination against macrolide-iR MABS infection, and suggest the influence of clarithromycin concentrations on response. The low concentration of clarithromycin in blood may hamper efficacy for the treatment of extra-pulmonary MABS infection. Consequently, it should not be considered as an active molecule in the chosen antibiotic combination, as recently recommended for pulmonary infections. |
| format | Article |
| id | doaj-art-149f66e121a54c98bc85751a4d79cc0e |
| institution | Kabale University |
| issn | 1476-0711 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Annals of Clinical Microbiology and Antimicrobials |
| spelling | doaj-art-149f66e121a54c98bc85751a4d79cc0e2025-02-02T12:12:27ZengBMCAnnals of Clinical Microbiology and Antimicrobials1476-07112025-01-012411710.1186/s12941-025-00776-wPoor efficacy of the combination of clarithromycin, amikacin, and cefoxitin against Mycobacterium abscessus in the hollow fiber infection modelEtienne Vignaud0Sylvain Goutelle1Charlotte Genestet2Jérôme Guitton3Sabine Cohen4Chloé Bourg5Aurore Durand6Laura Lebouteiller7Albin Bernard8Caroline Richet9Oana Dumitrescu10Elisabeth Hodille11Laboratoire des Mycobactéries, Institut des Agents Infectieux, Laboratoire de Biologie Médicale Multi-Site, Hôpital de la Croix Rousse, Hospices Civils de LyonService de Pharmacie, Groupement Hospitalier Nord, Hospices Civils de LyonLaboratoire des Mycobactéries, Institut des Agents Infectieux, Laboratoire de Biologie Médicale Multi-Site, Hôpital de la Croix Rousse, Hospices Civils de LyonUMR CNRS 5558, Laboratoire de Biométrie et Biologie Evolutive & ISPB, Faculté de Pharmacie de Lyon, Université Claude Bernard Lyon 1Laboratoire de Biochimie et de Pharmacologie-Toxicologie, Centre Hospitalier Lyon Sud, Hospices Civils de LyonLaboratoire des Mycobactéries, Institut des Agents Infectieux, Laboratoire de Biologie Médicale Multi-Site, Hôpital de la Croix Rousse, Hospices Civils de LyonLaboratoire des Mycobactéries, Institut des Agents Infectieux, Laboratoire de Biologie Médicale Multi-Site, Hôpital de la Croix Rousse, Hospices Civils de LyonLaboratoire des Mycobactéries, Institut des Agents Infectieux, Laboratoire de Biologie Médicale Multi-Site, Hôpital de la Croix Rousse, Hospices Civils de LyonLaboratoire des Mycobactéries, Institut des Agents Infectieux, Laboratoire de Biologie Médicale Multi-Site, Hôpital de la Croix Rousse, Hospices Civils de LyonLaboratoire de Biochimie, Hôpital de la Croix Rousse, Hospices Civils de LyonLaboratoire des Mycobactéries, Institut des Agents Infectieux, Laboratoire de Biologie Médicale Multi-Site, Hôpital de la Croix Rousse, Hospices Civils de LyonLaboratoire des Mycobactéries, Institut des Agents Infectieux, Laboratoire de Biologie Médicale Multi-Site, Hôpital de la Croix Rousse, Hospices Civils de LyonAbstract Background Mycobacterium abscessus (MABS) causes difficult-to-treat pulmonary and extra-pulmonary infections. A combination therapy comprising amikacin, cefoxitin, and a macrolide agent is recommended, but its antimicrobial activity and clinical efficacy is uncertain. Inducible resistance to macrolides (macrolides-iR) has been associated with poor clinical response in pulmonary infections, whilst for extra-pulmonary infections data are scarce. Objectives Herein, the aim was to evaluate the effect of the amikacin, cefoxitin, and clarithromycin combination against macrolides-iR MABS in a hollow-fiber infection model. Methods The hollow-fiber system was inoculated with M. abscessus subsp. abscessus type strain ATCC 19977 and treated during 10 days with the antibiotics combination. Two level of macrolide concentrations were evaluated mimicking the pharmacokinetics profiles of free (i.e. unbound) drug in blood and lung. Results Using blood concentrations, the combination failed to prevent bacterial growth. Using lung concentrations, the combination had a limited but significant effect on bacterial growth from day 2 to day 10. Moreover, increasing clarithromycin concentrations stabilized the amikacin-tolerance level: amikacin minimal inhibitory concentration of amikacin-tolerant strains increased over time using blood concentrations while it remained stable using lung concentrations. Conclusions Our finding confirms the low activity of the amikacin, cefoxitin, and clarithromycin combination against macrolide-iR MABS infection, and suggest the influence of clarithromycin concentrations on response. The low concentration of clarithromycin in blood may hamper efficacy for the treatment of extra-pulmonary MABS infection. Consequently, it should not be considered as an active molecule in the chosen antibiotic combination, as recently recommended for pulmonary infections.https://doi.org/10.1186/s12941-025-00776-wMycobacterium abscessusHollow-fiber systemHollow-fiber infection modelClarithromycinAmikacinCefoxitin |
| spellingShingle | Etienne Vignaud Sylvain Goutelle Charlotte Genestet Jérôme Guitton Sabine Cohen Chloé Bourg Aurore Durand Laura Lebouteiller Albin Bernard Caroline Richet Oana Dumitrescu Elisabeth Hodille Poor efficacy of the combination of clarithromycin, amikacin, and cefoxitin against Mycobacterium abscessus in the hollow fiber infection model Annals of Clinical Microbiology and Antimicrobials Mycobacterium abscessus Hollow-fiber system Hollow-fiber infection model Clarithromycin Amikacin Cefoxitin |
| title | Poor efficacy of the combination of clarithromycin, amikacin, and cefoxitin against Mycobacterium abscessus in the hollow fiber infection model |
| title_full | Poor efficacy of the combination of clarithromycin, amikacin, and cefoxitin against Mycobacterium abscessus in the hollow fiber infection model |
| title_fullStr | Poor efficacy of the combination of clarithromycin, amikacin, and cefoxitin against Mycobacterium abscessus in the hollow fiber infection model |
| title_full_unstemmed | Poor efficacy of the combination of clarithromycin, amikacin, and cefoxitin against Mycobacterium abscessus in the hollow fiber infection model |
| title_short | Poor efficacy of the combination of clarithromycin, amikacin, and cefoxitin against Mycobacterium abscessus in the hollow fiber infection model |
| title_sort | poor efficacy of the combination of clarithromycin amikacin and cefoxitin against mycobacterium abscessus in the hollow fiber infection model |
| topic | Mycobacterium abscessus Hollow-fiber system Hollow-fiber infection model Clarithromycin Amikacin Cefoxitin |
| url | https://doi.org/10.1186/s12941-025-00776-w |
| work_keys_str_mv | AT etiennevignaud poorefficacyofthecombinationofclarithromycinamikacinandcefoxitinagainstmycobacteriumabscessusinthehollowfiberinfectionmodel AT sylvaingoutelle poorefficacyofthecombinationofclarithromycinamikacinandcefoxitinagainstmycobacteriumabscessusinthehollowfiberinfectionmodel AT charlottegenestet poorefficacyofthecombinationofclarithromycinamikacinandcefoxitinagainstmycobacteriumabscessusinthehollowfiberinfectionmodel AT jeromeguitton poorefficacyofthecombinationofclarithromycinamikacinandcefoxitinagainstmycobacteriumabscessusinthehollowfiberinfectionmodel AT sabinecohen poorefficacyofthecombinationofclarithromycinamikacinandcefoxitinagainstmycobacteriumabscessusinthehollowfiberinfectionmodel AT chloebourg poorefficacyofthecombinationofclarithromycinamikacinandcefoxitinagainstmycobacteriumabscessusinthehollowfiberinfectionmodel AT auroredurand poorefficacyofthecombinationofclarithromycinamikacinandcefoxitinagainstmycobacteriumabscessusinthehollowfiberinfectionmodel AT lauralebouteiller poorefficacyofthecombinationofclarithromycinamikacinandcefoxitinagainstmycobacteriumabscessusinthehollowfiberinfectionmodel AT albinbernard poorefficacyofthecombinationofclarithromycinamikacinandcefoxitinagainstmycobacteriumabscessusinthehollowfiberinfectionmodel AT carolinerichet poorefficacyofthecombinationofclarithromycinamikacinandcefoxitinagainstmycobacteriumabscessusinthehollowfiberinfectionmodel AT oanadumitrescu poorefficacyofthecombinationofclarithromycinamikacinandcefoxitinagainstmycobacteriumabscessusinthehollowfiberinfectionmodel AT elisabethhodille poorefficacyofthecombinationofclarithromycinamikacinandcefoxitinagainstmycobacteriumabscessusinthehollowfiberinfectionmodel |