In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride
Background: Besifloxacin ophthalmic suspension 0.6% (<i>w</i>/<i>v</i>%) contains benzalkonium chloride (BAK) as a preservative. We evaluated the in vitro time-kill activity of besifloxacin, alone and in combination with BAK, against common bacteria implicated in ophthalmic i...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/14/6/517 |
| _version_ | 1797532402566823936 |
|---|---|
| author | Joseph Blondeau Heleen DeCory |
| author_facet | Joseph Blondeau Heleen DeCory |
| author_sort | Joseph Blondeau |
| collection | DOAJ |
| description | Background: Besifloxacin ophthalmic suspension 0.6% (<i>w</i>/<i>v</i>%) contains benzalkonium chloride (BAK) as a preservative. We evaluated the in vitro time-kill activity of besifloxacin, alone and in combination with BAK, against common bacteria implicated in ophthalmic infections. Methods: The activity of besifloxacin (100 µg/mL), BAK (10, 15, 20, and 100 µg/mL), and combinations of besifloxacin and BAK were evaluated against isolates of <i>Staphylococcus epidermidis</i> (<i>n</i> = 4), <i>Staphylococcus aureus</i> (<i>n</i> = 3), <i>Haemophilus influenzae</i> (<i>n</i> = 2), and <i>Pseudomonas aeruginosa</i> (<i>n</i> = 2) in time-kill experiments of 180 min duration. With the exception of one <i>S. aureus</i> isolate, all of the staphylococcal isolates were methicillin- and/or ciprofloxacin-resistant; one <i>P. aeruginosa</i> isolate was ciprofloxacin-resistant. The reductions in the viable colony counts (log<sub>10</sub> CFU/mL) were plotted against time, and the differences among the time–kill curves were evaluated using an analysis of variance. Areas-under-the-killing-curve (AUKCs) were also computed. Results: Besifloxacin alone demonstrated ≥3-log killing of <i>P. aeruginosa</i> (<5 min) and <i>H. influenzae</i> (<120 min), and approached 3-log kills of <i>S. aureus</i>. BAK alone demonstrated concentration-dependent killing of <i>S. epidermidis</i>, <i>S. aureus</i> and <i>H. influenzae</i>, and at 100 µg/mL produced ≥3-log kills in <5 min against these species. The addition of BAK (10, 15, and 20 µg/mL) to besifloxacin increased the rate of killing compared to besifloxacin alone, with earlier 3-log kills of all species except <i>P. aeruginosa</i> and a variable impact on <i>S. aureus</i>. The greatest reductions in AUKC were observed among <i>H. influenzae</i> (8-fold) and <i>S. epidermidis</i> (≥5-fold). Similar results were found when the isolates were evaluated individually by their resistance phenotype. Conclusions: In addition to confirming the activity of 100 µg/mL BAK as a preservative in the bottle, these data suggest that BAK may help besifloxacin to achieve faster time-kills on-eye in the immediate timeframe post-instillation before extensive dilution against bacterial species implicated in ophthalmic infections, including drug-resistant <i>S. epidermidis</i>. Greater killing activity may help prevent resistance development and/or help treat resistant organisms. |
| first_indexed | 2024-03-10T10:58:39Z |
| format | Article |
| id | doaj.art-861f07d9f7fc4b0aa386c538197b1546 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T10:58:39Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-861f07d9f7fc4b0aa386c538197b15462023-11-21T21:41:20ZengMDPI AGPharmaceuticals1424-82472021-05-0114651710.3390/ph14060517In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium ChlorideJoseph Blondeau0Heleen DeCory1Clinical Microbiology, Royal University Hospital, Saskatoon, SK S7N 0W8, CanadaBausch + Lomb, Rochester, NY 14609, USABackground: Besifloxacin ophthalmic suspension 0.6% (<i>w</i>/<i>v</i>%) contains benzalkonium chloride (BAK) as a preservative. We evaluated the in vitro time-kill activity of besifloxacin, alone and in combination with BAK, against common bacteria implicated in ophthalmic infections. Methods: The activity of besifloxacin (100 µg/mL), BAK (10, 15, 20, and 100 µg/mL), and combinations of besifloxacin and BAK were evaluated against isolates of <i>Staphylococcus epidermidis</i> (<i>n</i> = 4), <i>Staphylococcus aureus</i> (<i>n</i> = 3), <i>Haemophilus influenzae</i> (<i>n</i> = 2), and <i>Pseudomonas aeruginosa</i> (<i>n</i> = 2) in time-kill experiments of 180 min duration. With the exception of one <i>S. aureus</i> isolate, all of the staphylococcal isolates were methicillin- and/or ciprofloxacin-resistant; one <i>P. aeruginosa</i> isolate was ciprofloxacin-resistant. The reductions in the viable colony counts (log<sub>10</sub> CFU/mL) were plotted against time, and the differences among the time–kill curves were evaluated using an analysis of variance. Areas-under-the-killing-curve (AUKCs) were also computed. Results: Besifloxacin alone demonstrated ≥3-log killing of <i>P. aeruginosa</i> (<5 min) and <i>H. influenzae</i> (<120 min), and approached 3-log kills of <i>S. aureus</i>. BAK alone demonstrated concentration-dependent killing of <i>S. epidermidis</i>, <i>S. aureus</i> and <i>H. influenzae</i>, and at 100 µg/mL produced ≥3-log kills in <5 min against these species. The addition of BAK (10, 15, and 20 µg/mL) to besifloxacin increased the rate of killing compared to besifloxacin alone, with earlier 3-log kills of all species except <i>P. aeruginosa</i> and a variable impact on <i>S. aureus</i>. The greatest reductions in AUKC were observed among <i>H. influenzae</i> (8-fold) and <i>S. epidermidis</i> (≥5-fold). Similar results were found when the isolates were evaluated individually by their resistance phenotype. Conclusions: In addition to confirming the activity of 100 µg/mL BAK as a preservative in the bottle, these data suggest that BAK may help besifloxacin to achieve faster time-kills on-eye in the immediate timeframe post-instillation before extensive dilution against bacterial species implicated in ophthalmic infections, including drug-resistant <i>S. epidermidis</i>. Greater killing activity may help prevent resistance development and/or help treat resistant organisms.https://www.mdpi.com/1424-8247/14/6/517besifloxacinbenzalkonium chloridein vitrotime-kill studiesophthalmic infectionsantibacterial resistance |
| spellingShingle | Joseph Blondeau Heleen DeCory In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride Pharmaceuticals besifloxacin benzalkonium chloride in vitro time-kill studies ophthalmic infections antibacterial resistance |
| title | In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride |
| title_full | In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride |
| title_fullStr | In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride |
| title_full_unstemmed | In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride |
| title_short | In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride |
| title_sort | in vitro time kill of common ocular pathogens with besifloxacin alone and in combination with benzalkonium chloride |
| topic | besifloxacin benzalkonium chloride in vitro time-kill studies ophthalmic infections antibacterial resistance |
| url | https://www.mdpi.com/1424-8247/14/6/517 |
| work_keys_str_mv | AT josephblondeau invitrotimekillofcommonocularpathogenswithbesifloxacinaloneandincombinationwithbenzalkoniumchloride AT heleendecory invitrotimekillofcommonocularpathogenswithbesifloxacinaloneandincombinationwithbenzalkoniumchloride |