ArticleAntimicrobial agents and chemotherapy2015
The strength of synergistic interaction between posaconazole and caspofungin depends on the underlying azole resistance mechanism of Aspergillus fumigatus.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Synergistic activity of caspofungin and posaconazole againstMicrobiology spectrum · 2026Article
- In Vitro Interactions Between Bacteriophages and Antibacterial Agents of Various Classes Against Multidrug-Resistant Metallo-β-Lactamase-ProducingPharmaceuticals (Basel, Switzerland) · 2025Article
- A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi.Nature communications · 2023Article
- Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Heterogeneity in the transcriptional response of the human pathogen Aspergillus fumigatus to the antifungal agent caspofungin.Genetics · 2022Article
- Article
- Cell-Cycle-Associated Expression Patterns Predict Gene Function in Mycobacteria.Current biology : CB · 2020Article
- In vitro interaction of isavuconazole and anidulafungin against azole-susceptible and azole-resistant Aspergillus fumigatus isolates.The Journal of antimicrobial chemotherapy · 2020Article
- A Collaborative Tale of Diagnosing and Treating Chronic Pulmonary Aspergillosis, from the Perspectives of Clinical Microbiologists, Surgical Pathologists, and Infectious Disease Clinicians.Journal of fungi (Basel, Switzerland) · 2020Review
- Posaconazole Alone and in Combination with Caspofungin for Treatment of ExperimentalJournal of fungi (Basel, Switzerland) · 2020Article
- Article
- Echinocandins for the Treatment of Invasive Aspergillosis: from Laboratory to Bedside.Antimicrobial agents and chemotherapy · 2019Review
- Article
- A Cationic Polymer That Shows High Antifungal Activity against Diverse Human Pathogens.Antimicrobial agents and chemotherapy · 2017Article
- Dirhamnolipids secreted from Pseudomonas aeruginosa modify anjpegungal susceptibility of Aspergillus fumigatus by inhibiting β1,3 glucan synthase activity.The ISME journal · 2017Article
- Fungal Infections, Treatment and Antifungal Resistance: The Sub-Saharan African Context.Therapeutic advances in infectious diseaseReview
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5 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
The majority of azole resistance mechanisms in Aspergillus fumigatus correspond to mutations in the cyp51A gene. As azoles are less effective against infections caused by multiply azole-resistant A. fumigatus isolates, new therapeutic options are warranted for treating these infections. We therefore investigated the in vitro combination of posaconazole (POSA) and caspofungin (CAS) against 20 wild-type and resistant A. fumigatus isolates with 10 different resistance mechanisms. Fungal growth was assessed with the XTT [2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt] method. Pharmacodynamic interactions were assessed with the fractional inhibitory concentration (FIC) index (FICi) on the basis of 10% (FICi-0), 25% (FICi-1), or 53 0% (FICi-2) growth, and FICs were correlated with POSA and CAS concentrations. Synergy and antagonism were concluded when the FICi values were statistically significantly (t test, P < 0.05) lower than 1 and higher than 1.25, respectively. Significant synergy was found for all isolates with mean FICi-0 values ranging from 0.28 to 0.75 (median, 0.46). Stronger synergistic interactions were found with FICi-1 (median, 0.18; range, 0.07 to 0.47) and FICi-2 (0.31; 0.07 to 0.6). The FICi-2 values of isolates with tandem-repeat-containing mutations or codon M220 were lower than those seen with the other isolates (P < 0.01). FIC-2 values were inversely correlated with POSA MICs (rs = -0.52, P = 0.0006) and linearly with the ratio of drug concentrations in combination over the MIC of POSA (rs = 0.76, P < 0.0001) and CAS (rs = 0.52, P = 0.0004). The synergistic effect of the combination of POSA and CAS (POSA/CAS) against A. fumigatus isolates depended on the underlying azole resistance mechanism. Moreover, the drug combination synergy was found to be increased against isolates with elevated POSA MICs compared to wild-type isolates.
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