Multicenter Collaborative Study of the Interaction of Antifungal Combinations against <i>Candida</i> Spp. by Loewe Additivity and Bliss Independence-Based Response Surface Analysis
Combination antifungal therapy is widely used but not well understood. We analyzed the spectrophotometric readings from a multicenter study conducted by the New York State Department of Health to further characterize the in vitro interactions of the major classes of antifungal agents against <i&g...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/8/9/967 |
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| author | Joseph Meletiadis David R. Andes Shawn R. Lockhart Mahmoud A. Ghannoum Cindy C. Knapp Luis Ostrosky-Zeichner Michael A. Pfaller Vishnu Chaturvedi Thomas J. Walsh |
| author_facet | Joseph Meletiadis David R. Andes Shawn R. Lockhart Mahmoud A. Ghannoum Cindy C. Knapp Luis Ostrosky-Zeichner Michael A. Pfaller Vishnu Chaturvedi Thomas J. Walsh |
| author_sort | Joseph Meletiadis |
| collection | DOAJ |
| description | Combination antifungal therapy is widely used but not well understood. We analyzed the spectrophotometric readings from a multicenter study conducted by the New York State Department of Health to further characterize the in vitro interactions of the major classes of antifungal agents against <i>Candida</i> spp. Loewe additivity-based fractional inhibitory concentration index (FICi) analysis and Bliss independence-based response surface (BIRS) analysis were used to analyze two-drug inter- and intraclass combinations of triazoles (AZO) (voriconazole, posaconazole), echinocandins (ECH) (caspofungin, micafungin, anidulafungin), and a polyene (amphotericin B) against <i>Candida albicans</i>, <i>C. parapsilosis</i>, and <i>C. glabrata</i>. Although mean FIC indices did not differ statistically significantly from the additivity range of 0.5–4, indicating no significant pharmacodynamic interactions for all of the strain–combinations tested, BIRS analysis showed that significant pharmacodynamic interactions with the sum of percentages of interactions determined with this analysis were strongly associated with the FIC indices (Χ<sup>2</sup> 646, <i>p</i> < 0.0001). Using a narrower additivity range of 1–2 FIC index analysis, statistically significant pharmacodynamic interactions were also found with FICi and were in agreement with those found with BIRS analysis. All ECH+AB combinations were found to be synergistic against all <i>Candida</i> strains except <i>C. glabrata</i>. For the AZO+AB combinations, synergy was found mostly with the POS+AB combination. All AZO+ECH combinations except POS+CAS were synergistic against all <i>Candida</i> strains although with variable magnitude; significant antagonism was found for the POS+MIF combination against <i>C. albicans</i>. The AZO+AZO combination was additive for all strains except for a <i>C. parapsilosis</i> strain for which antagonism was also observed. The ECH+ECH combinations were synergistic for all <i>Candida</i> strains except <i>C. glabrata</i> for which they were additive; no antagonism was found. |
| first_indexed | 2024-03-09T23:30:29Z |
| format | Article |
| id | doaj.art-ad3d59ee98f34271bd5930d1d702fd84 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-09T23:30:29Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-ad3d59ee98f34271bd5930d1d702fd842023-11-23T17:10:03ZengMDPI AGJournal of Fungi2309-608X2022-09-018996710.3390/jof8090967Multicenter Collaborative Study of the Interaction of Antifungal Combinations against <i>Candida</i> Spp. by Loewe Additivity and Bliss Independence-Based Response Surface AnalysisJoseph Meletiadis0David R. Andes1Shawn R. Lockhart2Mahmoud A. Ghannoum3Cindy C. Knapp4Luis Ostrosky-Zeichner5Michael A. Pfaller6Vishnu Chaturvedi7Thomas J. Walsh8Clinical Microbiology Laboratory, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, GreeceDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53726, USAMycotic Diseases Branch, Centers for Diseases C, Atlanta, GA 30333, USACenter for Medical Mycology, Case Western Reserve University, Cleveland, OH 44106, USATrek Diagnostics System, Cleveland, OH 44131, USADivision of Infectious Diseases, University of Texas Health Science Center, Houston, TX 77030, USAMedical Microbiology Division, Department of Pathology, The University of Iowa College of Medicine, Iowa City, IA 52242, USAWestchester Medical Center, New York Medical College, Valhalla, NY 10595, USATransplantation-Oncology Infectious Diseases, Weill Cornell Medicine of Cornell University, New York, NY 10065, USACombination antifungal therapy is widely used but not well understood. We analyzed the spectrophotometric readings from a multicenter study conducted by the New York State Department of Health to further characterize the in vitro interactions of the major classes of antifungal agents against <i>Candida</i> spp. Loewe additivity-based fractional inhibitory concentration index (FICi) analysis and Bliss independence-based response surface (BIRS) analysis were used to analyze two-drug inter- and intraclass combinations of triazoles (AZO) (voriconazole, posaconazole), echinocandins (ECH) (caspofungin, micafungin, anidulafungin), and a polyene (amphotericin B) against <i>Candida albicans</i>, <i>C. parapsilosis</i>, and <i>C. glabrata</i>. Although mean FIC indices did not differ statistically significantly from the additivity range of 0.5–4, indicating no significant pharmacodynamic interactions for all of the strain–combinations tested, BIRS analysis showed that significant pharmacodynamic interactions with the sum of percentages of interactions determined with this analysis were strongly associated with the FIC indices (Χ<sup>2</sup> 646, <i>p</i> < 0.0001). Using a narrower additivity range of 1–2 FIC index analysis, statistically significant pharmacodynamic interactions were also found with FICi and were in agreement with those found with BIRS analysis. All ECH+AB combinations were found to be synergistic against all <i>Candida</i> strains except <i>C. glabrata</i>. For the AZO+AB combinations, synergy was found mostly with the POS+AB combination. All AZO+ECH combinations except POS+CAS were synergistic against all <i>Candida</i> strains although with variable magnitude; significant antagonism was found for the POS+MIF combination against <i>C. albicans</i>. The AZO+AZO combination was additive for all strains except for a <i>C. parapsilosis</i> strain for which antagonism was also observed. The ECH+ECH combinations were synergistic for all <i>Candida</i> strains except <i>C. glabrata</i> for which they were additive; no antagonism was found.https://www.mdpi.com/2309-608X/8/9/967pharmacodynamic interactionsLoewe additivityBliss independencesynergyantagonism<i>Candida</i> |
| spellingShingle | Joseph Meletiadis David R. Andes Shawn R. Lockhart Mahmoud A. Ghannoum Cindy C. Knapp Luis Ostrosky-Zeichner Michael A. Pfaller Vishnu Chaturvedi Thomas J. Walsh Multicenter Collaborative Study of the Interaction of Antifungal Combinations against <i>Candida</i> Spp. by Loewe Additivity and Bliss Independence-Based Response Surface Analysis Journal of Fungi pharmacodynamic interactions Loewe additivity Bliss independence synergy antagonism <i>Candida</i> |
| title | Multicenter Collaborative Study of the Interaction of Antifungal Combinations against <i>Candida</i> Spp. by Loewe Additivity and Bliss Independence-Based Response Surface Analysis |
| title_full | Multicenter Collaborative Study of the Interaction of Antifungal Combinations against <i>Candida</i> Spp. by Loewe Additivity and Bliss Independence-Based Response Surface Analysis |
| title_fullStr | Multicenter Collaborative Study of the Interaction of Antifungal Combinations against <i>Candida</i> Spp. by Loewe Additivity and Bliss Independence-Based Response Surface Analysis |
| title_full_unstemmed | Multicenter Collaborative Study of the Interaction of Antifungal Combinations against <i>Candida</i> Spp. by Loewe Additivity and Bliss Independence-Based Response Surface Analysis |
| title_short | Multicenter Collaborative Study of the Interaction of Antifungal Combinations against <i>Candida</i> Spp. by Loewe Additivity and Bliss Independence-Based Response Surface Analysis |
| title_sort | multicenter collaborative study of the interaction of antifungal combinations against i candida i spp by loewe additivity and bliss independence based response surface analysis |
| topic | pharmacodynamic interactions Loewe additivity Bliss independence synergy antagonism <i>Candida</i> |
| url | https://www.mdpi.com/2309-608X/8/9/967 |
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