Treatment of candidemia and invasive candidiasis in the intensive care unit: post hoc analysis of a randomized, controlled trial comparing micafungin and liposomal amphotericin B.
BACKGROUND
Invasive candidiasis and candidemia are life-threatening nosocomial infections in intensive care patients.


METHODS
A post hoc analysis of a phase 3 trial assessing micafungin (100 mg/day for subjects > 40 kg; 2 mg/kg/day for subjects <or= 40 kg) versus liposomal amphotericin B (3 mg/kg/day). Subgroups were defined according to the type of ward on the first day of treatment: intensive care unit (ICU) or non-ICU. Multivariate regression was performed to identify factors associated with treatment success at end of therapy and all-cause mortality at days 8 and 30.


RESULTS
In non-ICU subjects, treatment success was significantly higher for micafungin versus liposomal amphotericin B (85% (n = 108/127) versus 72.1% (n = 98/136); P = 0.0113). However, for ICU subjects, treatment success rates for micafungin versus liposomal amphotericin B were similar (62.5% (n = 75/120) versus 66.4% (n = 73/110); P = 0.5828). Overall, treatment success was significantly lower in ICU subjects compared with non-ICU subjects (64.3% (n = 148/230) versus 78.3% (n = 206/263); P = 0.0006). Multivariate regression analysis revealed a lower likelihood of treatment success for: ICU versus non-ICU subjects; persistent neutropenia; and high versus low Acute Physiology and Chronic Health Evaluation (APACHE) II scores. However, when interactions between potential explanatory factors were included in the analysis model, ICU status no longer emerged as a significant associated variable but the association between APACHE II score and treatment outcome remained. Further analyses indicated that the likelihood of mortality at day 8 and day 30 was lower for subjects with lower APACHE II scores. Renal function was significantly better in micafungin versus liposomal amphotericin B subjects: a difference (liposomal amphotericin B - micafungin in mean peak change in estimated glomerular filtration rate (ml/minute/1.73 m2) of -18.2 (P < 0.0001) and -17.7 (P = 0.0124) in non-ICU and ICU subjects, respectively.


CONCLUSIONS
Overall, ICU subjects had lower treatment success rates than non-ICU subjects for both liposomal amphotericin B and micafungin. Multivariate regression after controlling for potential confounding factors suggested the APACHE II score remained a potential explanatory factor associated with treatment success, mortality at day 8, and mortality at day 30.


BACKGROUND
Post hoc analysis--clinicaltrials.gov trial NCT00106288.
Université Paris Descartes, Hôpital Necker-Enfants Malades, Centre d'Infectiologie Necker-Pasteur, 149 rue de Sevres, 75015 Paris, France. bertrand.dupont@nck.aphp.fr
Bertrand F
BF
Dupont
Olivier
O
Lortholary
Luis
L
Ostrosky-Zeichner
Flavie
F
Stucker
Vijay
V
Yeldandi
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002177:Candidiasis / Q000188:drug therapy*; D003428:Cross Infection / Q000188:drug therapy; D054714:Echinocandins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D055666:Lipopeptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D000077551:Micafungin; D008875:Middle Aged; D015999:Multivariate Analysis
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; C068538:liposomal amphotericin B; D000666:Amphotericin B; D000077551:Micafungin