Adjunctive Use of Phage Sb-1 in Antibiotics Enhances Inhibitory Biofilm Growth Activity versus Rifampin-Resistant <i>Staphylococcus aureus</i> Strains
Effective antimicrobials are crucial for managing <i>Staphylococcus aureus</i> implant-associated bone infections (IABIs), particularly for infections due to rifampin-resistant <i>S. aureus</i> (RRSA). Failure to remove the implant results in persistent infection; thus, prolo...
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doaj-7b5276197d3b4b33a5300e4dcb38216e2020-11-25T04:06:11ZengMDPI AGAntibiotics2079-63822020-10-01974974910.3390/antibiotics9110749Adjunctive Use of Phage Sb-1 in Antibiotics Enhances Inhibitory Biofilm Growth Activity versus Rifampin-Resistant <i>Staphylococcus aureus</i> StrainsLei Wang0Tamta Tkhilaishvili1Andrej Trampuz2Center for Musculoskeletal Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 13353 Berlin, GermanyCenter for Musculoskeletal Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 13353 Berlin, GermanyCenter for Musculoskeletal Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 13353 Berlin, GermanyEffective antimicrobials are crucial for managing <i>Staphylococcus aureus</i> implant-associated bone infections (IABIs), particularly for infections due to rifampin-resistant <i>S. aureus</i> (RRSA). Failure to remove the implant results in persistent infection; thus, prolonged suppressive antibiotic therapy may be a reasonable alternative. However, a high incidence of adverse events can necessitate the discontinuation of therapy. In this scenario, commercial <i>Staphylococcal</i> bacteriophage Sb-1 combined with antibiotics is an option, showing a promising synergistic activity to facilitate the treatment of biofilm infections. Therefore, we evaluated the efficacy of the inhibitory activity of five antibiotics (doxycycline, levofloxacin, clindamycin, linezolid, and rifampin) alone or combined with phage Sb-1 (10<sup>6</sup> PFU/mL) in a simultaneous and staggered manner, to combat five clinical RRSA strains and the laboratory strain MRSA ATCC 43300 in 72 h by isothermal microcalorimetry. The synergistic effects were observed when phage Sb-1 (10<sup>6</sup> PFU/mL) combined with antibiotics had at least 2 log-reduction lower concentrations, represented by a fractional biofilm inhibitory concentration (FBIC) of <0.25. Among the antibiotics that we tested, the synergistic effect of all six strains was achieved in phage/doxycycline and phage/linezolid combinations in a staggered manner, whereas a distinctly noticeable improvement in inhibitory activity was observed in the phage/doxycycline combination with a low concentration of doxycycline. Moreover, phage/levofloxacin and phage/clindamycin combinations also showed a synergistic inhibitory effect against five strains and four strains, respectively. Interestingly, the synergistic inhibitory activity was also observed in the doxycycline-resistant and levofloxacin-resistant profile strains. However, no inhibitory activity was observed for all of the combinations in a simultaneous manner, as well as for the phage/rifampin combination in a staggered manner. These results have implications for alternative, combined, and prolonged suppressive antimicrobial treatment approaches.https://www.mdpi.com/2079-6382/9/11/749rifampin-resistant <i>Staphylococcus aureus</i>biofilm infectionantibiotic-phage combinationsynergismsuppression therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lei Wang Tamta Tkhilaishvili Andrej Trampuz |
spellingShingle |
Lei Wang Tamta Tkhilaishvili Andrej Trampuz Adjunctive Use of Phage Sb-1 in Antibiotics Enhances Inhibitory Biofilm Growth Activity versus Rifampin-Resistant <i>Staphylococcus aureus</i> Strains Antibiotics rifampin-resistant <i>Staphylococcus aureus</i> biofilm infection antibiotic-phage combination synergism suppression therapy |
author_facet |
Lei Wang Tamta Tkhilaishvili Andrej Trampuz |
author_sort |
Lei Wang |
title |
Adjunctive Use of Phage Sb-1 in Antibiotics Enhances Inhibitory Biofilm Growth Activity versus Rifampin-Resistant <i>Staphylococcus aureus</i> Strains |
title_short |
Adjunctive Use of Phage Sb-1 in Antibiotics Enhances Inhibitory Biofilm Growth Activity versus Rifampin-Resistant <i>Staphylococcus aureus</i> Strains |
title_full |
Adjunctive Use of Phage Sb-1 in Antibiotics Enhances Inhibitory Biofilm Growth Activity versus Rifampin-Resistant <i>Staphylococcus aureus</i> Strains |
title_fullStr |
Adjunctive Use of Phage Sb-1 in Antibiotics Enhances Inhibitory Biofilm Growth Activity versus Rifampin-Resistant <i>Staphylococcus aureus</i> Strains |
title_full_unstemmed |
Adjunctive Use of Phage Sb-1 in Antibiotics Enhances Inhibitory Biofilm Growth Activity versus Rifampin-Resistant <i>Staphylococcus aureus</i> Strains |
title_sort |
adjunctive use of phage sb-1 in antibiotics enhances inhibitory biofilm growth activity versus rifampin-resistant <i>staphylococcus aureus</i> strains |
publisher |
MDPI AG |
series |
Antibiotics |
issn |
2079-6382 |
publishDate |
2020-10-01 |
description |
Effective antimicrobials are crucial for managing <i>Staphylococcus aureus</i> implant-associated bone infections (IABIs), particularly for infections due to rifampin-resistant <i>S. aureus</i> (RRSA). Failure to remove the implant results in persistent infection; thus, prolonged suppressive antibiotic therapy may be a reasonable alternative. However, a high incidence of adverse events can necessitate the discontinuation of therapy. In this scenario, commercial <i>Staphylococcal</i> bacteriophage Sb-1 combined with antibiotics is an option, showing a promising synergistic activity to facilitate the treatment of biofilm infections. Therefore, we evaluated the efficacy of the inhibitory activity of five antibiotics (doxycycline, levofloxacin, clindamycin, linezolid, and rifampin) alone or combined with phage Sb-1 (10<sup>6</sup> PFU/mL) in a simultaneous and staggered manner, to combat five clinical RRSA strains and the laboratory strain MRSA ATCC 43300 in 72 h by isothermal microcalorimetry. The synergistic effects were observed when phage Sb-1 (10<sup>6</sup> PFU/mL) combined with antibiotics had at least 2 log-reduction lower concentrations, represented by a fractional biofilm inhibitory concentration (FBIC) of <0.25. Among the antibiotics that we tested, the synergistic effect of all six strains was achieved in phage/doxycycline and phage/linezolid combinations in a staggered manner, whereas a distinctly noticeable improvement in inhibitory activity was observed in the phage/doxycycline combination with a low concentration of doxycycline. Moreover, phage/levofloxacin and phage/clindamycin combinations also showed a synergistic inhibitory effect against five strains and four strains, respectively. Interestingly, the synergistic inhibitory activity was also observed in the doxycycline-resistant and levofloxacin-resistant profile strains. However, no inhibitory activity was observed for all of the combinations in a simultaneous manner, as well as for the phage/rifampin combination in a staggered manner. These results have implications for alternative, combined, and prolonged suppressive antimicrobial treatment approaches. |
topic |
rifampin-resistant <i>Staphylococcus aureus</i> biofilm infection antibiotic-phage combination synergism suppression therapy |
url |
https://www.mdpi.com/2079-6382/9/11/749 |
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