Evaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia

CANDIPOP Project from GEIH-GEMICOMED (SEIMC) and REIPI: B. Padilla, P. Muñoz, J. Guinea, J. R. Paño Pardo, J. García-Rodríguez, C. García Cerrada, J. Fortún, P. Martín, E. Gómez, P. Ryan, C. Campelo, I. de los Santos Gil, V. Buendía, B. P. Gorricho, M. Alonso, F. S. Sanz, J. M. Aguado, P. Merino, F. González Romo, M. Gorgolas, I. Gadea, J. E. Losa, A. Delgado-Iribarren, A. Ramos, Y. Romero, I. Sánchez Romero, O. Zaragoza, M. Cuenca-Estrella, J. Rodriguez-Baño, A. Isabel Suarez, A. Loza, A. I. Aller García, E. Martín-Mazuelos, M. R. Pérez de Pipaón, J. Garnacho, C. Ortiz, M. Chávez, F. L. Maroto, M. Salavert, J. Pemán, J. Blanquer, D. Navarro, J. J. Camarena, R. Zaragoza, V. Abril, C. Gimeno, S. Hernáez, G. Ezpeleta, E. Bereciartua, J. L. Hernández Almaraz, M. Montejo, R. A. Rivas, R. Ayarza, A. M. Planes, I. R. Camps, B. Almirante, J. Mensa, M. Almela, M. Gurgui, F. Sánchez-Reus, J. Martinez-Montauti, M. Sierra, J. P. Horcajada, L. Sorli, J. Gómez, A. Gené, M. Urrea, M. Valerio, A. Díaz-Martín, F. Puchades, A. Mularoni.[Objective] Paradoxical growth (PG) and trailing effect (TE) are frequently observed during antifungal susceptibility testing (AFST). These two phenomena interfere with the determination of the minimal inhibitory concentration (MIC). The aim of this study was to assess the clinical impact of TE and PG.[Methods] We analysed the frequency of TE and PG of 690 Candida isolates collected from a population-based study performed in Spain (CANDIPOP) and correlated the results with clinical outcome of the patients.[Results] Around 70% (484/690) of the isolates exhibited TE to azoles. Candida tropicalis showed the highest presence of TE (39/53 isolates exhibited residual growth >25% of control). No TE was seen in most of the isolates from the psilosis complex. PG was mainly associated with echinocandins. In patients treated with fluconazole within the first 48 hours after blood sampling (n = 221), the presence of TE to azoles tended to be associated with lower 30-day mortality (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25–1.00) but not with clinical failure (OR 0.85, 95% CI 0.45–1.54). In the subgroup of 117 patients treated with echinocandins, the presence of PG was not associated with patient's response to antifungal treatment (OR for 30-day mortality 1.63, 95% CI 0.76–4.03; OR for clinical failure 1.17, 95% CI 0.53–2.70).[Conclusions] TE or PG are widely expressed among Candida spp., although they do not seem to influence clinical outcome.C. Rueda was funded by a Sara Borrell contract from the Fondo de Investigaciones Sanitarias (FIS, reference number CD11/00110). O. Zaragoza was funded by grant SAF2014-54336-R from the Spanish Ministry for Economics and Competitivity. The CANDIPOP study was funded by research grants from Gilead, MSD, Astellas and Pfizer and by funding from the Fundacion SEIMC-GESIDA and the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund ‘A way to achieve Europe’ ERDF and the Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). MC-E has received grant support from Astellas Pharma, bioMerieux, Gilead Sciences, Merck Sharp & Dohme, Pfizer, Schering-Plough, Soria Melguizo SA, Ferrer International, the Europea Union, the ALBAN program, the Spanish Agency for International Cooperation, the Spanish Ministry of Culture and Education, the Spanish Health Research Fund, the Instituto de Salud Carlos III (Spanish Ministry of Economy and Competitiveness), the Ramón Areces Foundation and the Mutua Madrileña Foundation