Posaconazole activity against Candida glabrata after exposure to caspofungin or amphotericin B.
We evaluated the effects of sequential therapy with caspofungin (CAS) or amphotericin B (AMB) followed by posaconazole (POS) against Candida glabrata. The susceptibilities to POS of yeast cells pre-exposed to CAS or AMB were identical to those of untreated cells as shown by standard Clinical and Laboratory Standards Institute broth dilution, cell viability, and disk diffusion methods. We then investigated the activity of sequential regimens in an experimental model of disseminated candidiasis. CAS given at 1 mg/kg/day for 2 days followed by POS at either 15 or 30 mg/kg/day significantly reduced the counts compared to the controls, but this treatment was not superior to the use of CAS alone. Also, sequential regimens with AMB given at 1 mg/kg/day for 2 days followed by POS (AMB/POS) were effective at reducing the fungal burden against the controls. In addition, AMB/POS with both doses of the triazole were significantly more effective than AMB alone. Overall, our data showed that there is no therapeutic advantage in using CAS followed by POS, whereas an induction therapy with AMB followed by a maintenance regimen with POS might be a suitable strategy in managing C. glabrata infections.
Istituto di Malattie Infettive e Medicina Pubblica, Università Politecnica delle Marche, Azienda Ospedaliera-Universitaria, Ospedali Riuniti, Umberto I-G.M. Lancisi-G. Salesi, Via Conca 60020, Torrette di Ancona, Ancona, Italy. f.barchiesi@univpm.it
Elisabetta
E
Spreghini
Carmelo Massimo
CM
Maida
Maria Eleonora
ME
Milici
Giorgio
G
Scalise
Francesco
F
Barchiesi
D000666:Amphotericin B / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D041221:Candida glabrata / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D000077336:Caspofungin; D015169:Colony Count, Microbial; D004334:Drug Administration Schedule; D054714:Echinocandins / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007668:Kidney / Q000382:microbiology; D055666:Lipopeptides; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000592:standards; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D014230:Triazoles; C101425:posaconazole; D000666:Amphotericin B; D000077336:Caspofungin