Evaluation of disk diffusion method compared to broth microdilution for antifungal susceptibility testing of 3 echinocandins against Aspergillus spp.

We tested the susceptibility of caspofungin, micafungin, and anidulafungin against Aspergillus spp. isolates by the new Clinical and Laboratory Standards Institute M51-A disk diffusion (DD) and the broth microdilution methods. A total of 65 clinical isolates of Aspergillus spp. were evaluated. The DD assay was performed on nonsupplemented Müeller-Hinton agar using caspofungin 2-µg, micafungin 1-µg, and anidulafungin 2-µg disks. Echinocandin minimal effective concentrations (MECs) and inhibition zones (IZs) were read after 24 to 48 (A. terreus) h at 35 °C. Caspofungin MECs for all Aspergillus spp. strains tested were ≤ 0.25 µg/mL; IZs were ≥ 15 mm for most species except for A. terreus (11-22 mm). Both micafungin and anidulafungin MECs were ≤ 0.015 µg/mL, but micafungin IZs were ≥ 14 mm while anidulafungin IZs were ≥ 22 mm. As for caspofungin, the DD method could be a useful method for susceptibility testing of micafungin and anidulafungin against Aspergillus spp.

[Virological response to adefovir dipivoxil predicts the long-term development of resistance in previously untreated patients with HBeAg-negative chronic hepatitis B]. / La respuesta virológica al tratamiento con adefovir dipivoxil predice el desarrollo de resistencias a largo plazo en pacientes con hepatitis crónica B HBeAg negativo previamente no tratados.

BACKGROUND AND OBJECTIVE: Adefovir dipivoxil monotherapy in lamivudine-resistant patients is associated with more frequent development of resistance than in naïve patients. The virological response during treatment predicts the risk of developing resistance. The aims of this study were to assess the efficacy of adefovir dipivoxil treatment in naïve and lamivudine-resistant patients and to determine whether virological response predicts the development of adefovir resistance. PATIENTS AND METHOD: This study included 82 patients with HBeAg-negative chronic hepatitis B (CHB) who received adefovir dipivoxil therapy. During active treatment, HBV-DNA values were determined by polymerase chain reaction; in addition, the presence of adefovir resistance-associated mutations was studied in cases of virological breakthrough. RESULTS: Virological response at 12 and 24 months was 59% and 73% in naive patients compared with 40% and 67% in lamivudine-resistant patients, whereas virological breakthrough at 24 months was 9.5% in naïve patients compared with 20% in lamivudine-resistant patients. A small percentage (4%) of patients with virological response at 12 months showed virological breakthrough between 12 and 40 months versus 29.4% of patients without virological response (P=.03). In lamivudine-resistant patients, virological response at 12 months was not a predictive factor for the development of virological breakthrough. CONCLUSIONS: Adefovir dipivoxil monotherapy in lamivudine-resistant patients is associated with an increased tendency to develop virological breakthrough, which cannot be predicted by virological response at 12 months of treatment. In naive patients, an undetectable viral load at 12 months of treatment ensures the absence of virological breakthrough at 40 months of treatment.

La respuesta virológica al tratamiento con adefovir dipivoxil predice el desarrollo de resistencias a largo plazo en pacientes con hepatitis crónica B HBeAg negativo previamente no tratados / Virological response to adefovir dipivoxil predicts the long-term development of resistance in previously untreated patients with HBeAg-negative chronic hepatitis B

Fundamento y objetivo La monoterapia con adefovir dipivoxil en pacientes resistentes a lamivudina se asocia con mayor desarrollo de resistencias que en naive. La respuesta virológica durante el tratamiento predice el riesgo de resistencias. Los objetivos de este estudio son evaluar la eficacia del tratamiento con adefovir dipivoxil en pacientes naive y resistentes a lamivudina y valorar si la respuesta virológica predice el desarrollo de resistencias a adefovir. Pacientes y metodo Se ha incluido a 82 pacientes con hepatitis crónica B (HCB) HBeAg negativo tratados con adefovir dipivoxil. Durante el tratamiento se determinó ADNVHB por reacción en cadena de la polimerasa y en los casos de breakthrough virológico, se estudió la presencia de mutaciones asociadas a resistencia a adefovir. Resultados La respuesta virológica a los 12 y 24 meses fue del 59 y el 73% en naive y del 40 y el 67% en resistentes a lamivudina. El breakthrough virológico a los 24 meses fue del 9,5% en naive y el 20% en resistentes a lamivudina. El 4% de los naive con respuesta virológica a los 12 meses presentó breakthrough virológico entre 12 y 40 meses de tratamiento frente al 29,4% de los pacientes sin respuesta virológica (p=0,03). En resistentes a lamivudina la respuesta virológica a los 12 meses no predijo el breakthrough virológico. Conclusiones La monoterapia con adefovir dipivoxil en pacientes resistentes a lamivudina se asocia con mayor tendencia al desarrollo de breakthrough virológico no predecible por la respuesta virológica a los 12 meses de tratamiento. En pacientes naive la carga viral no detectable a los 12 meses de tratamiento predice la ausencia de breakthrough virológico hasta los 40 meses de tratamiento (AU)

Background and objective Adefovir dipivoxil monotherapy in lamivudine-resistant patients is associated with more frequent development of resistance than in naïve patients. The virological response during treatment predicts the risk of developing resistance. The aims of this study were to assess the efficacy of adefovir dipivoxil treatment in naïve and lamivudine-resistant patients and to determine whether virological response predicts the development of adefovir resistance. Patients and method This study included 82 patients with HBeAg-negative chronic hepatitis B (CHB) who received adefovir dipivoxil therapy. During active treatment, HBV-DNA values were determined by polymerase chain reaction; in addition, the presence of adefovir resistance-associated mutations was studied in cases of virological breakthrough. Results Virological response at 12 and 24 months was 59% and 73% in naive patients compared with 40% and 67% in lamivudine-resistant patients, whereas virological breakthrough at 24 months was 9.5% in naïve patients compared with 20% in lamivudine-resistant patients. A small percentage (4%) of patients with virological response at 12 months showed virological breakthrough between 12 and 40 months versus 29.4% of patients without virological response (P=.03). In lamivudine-resistant patients, virological response at 12 months was not a predictive factor for the development of virological breakthrough. Conclusions Adefovir dipivoxil monotherapy in lamivudine-resistant patients is associated with an increased tendency to develop virological breakthrough, which cannot be predicted by virological response at 12 months of treatment. In naive patients, an undetectable viral load at 12 months of treatment ensures the absence of virological breakthrough at 40 months of treatment (AU)