A Comparison of AmBisome® to Amphotericin B for Treatment of Systemic Candidiasis in Very Low Birth Weight Infants

Abstract

PurposeAmphotericin B is considered the treatment of choice for systemic candidiasis, but adverse effects may limit its use. An alternative option for the treatment of candidiasis includes lipid preparations of amphotericin B. This study investigated the safety and efficacy of AmBisome®, a lipid formulation of amphotericin B containing liposomal structures, for the treatment of systemic candidiasis in very low birth weight infants (VLBWI).Materials and MethodsData from 26 VLBWI treated with AmBisome® in the study group (AmBisome group) from October 2003 to July 2006 were compared with data from 20 VLBWI treated with amphotericin B as a historical control (Amphotericin group). This study was a prospective, historical control, multi-center trial.ResultsCandida spp. was isolated in 73% (19/26) of the cases for the AmBisome group and 90% (18/20) of the cases for the Amphotericin group. The fungal eradication rate and the time to eradication was 84% (16/19) and 9 ± 8 days in the AmBisome group, and 89% (16/18) and 10 ± 9 days in the Amphotericin group, respectively (p = 0.680 vs p = 0.712). The major adverse effects were lower in the AmBisome group (renal toxicity, 21% vs 55%, p = 0.029; hepatotoxity, 25% vs 65%, p = 0.014, AmBisome group vs Amphotericin group, respectively). There was no significant difference in mortality attributed to systemic candidiasis (12% in the AmBisome group, 10% in the Amphotericin group, p = 0.868).ConclusionAmBisome® is effective and safe for treating systemic fungal infections in VLBWI.

Amphotericin B in neonates: deoxycholate or lipid formulation as first-line therapy – is there a ‘right’ choice?

“…The two studies that compared DAMB and lipid formulations showed no difference in overall survival rate or in the time of resolution of fungaemia [41,42]. One of them used DAMB group as historical control [42]. Overall neonatal survival rate in invasive candidiasis treated with DAMB alone in studies published after 1997 varies from 74 to 94% (see Table 2 [21] showed that treatment with high doses of LAMB is effective and well tolerated with an eradication rate of 95%.…”

“…Some studies used combination therapy with flucytosine (5-FC) or added fluconazole, which may have influenced the effect of therapy. The two studies that compared DAMB and lipid formulations showed no difference in overall survival rate or in the time of resolution of fungaemia [41,42]. One of them used DAMB group as historical control [42].…”

“…Adler-Shohet et al [48], Ló pez Sastre et al Oliguria defined as urine output less than 1 ml/kg/h for more than 18 or 24 h. 5 Hypokalaemia was defined as K <3 mmol/l or K<3 mEq/l. 6 Hepatotoxicity defined differently in the studies: rise of ALT or AST>30-60 U/l; two-fold rise of ALT or AST or GGT (Driessen 1996), 100% rise of ALT or AST (Jeon 2007 Values available or calculated from the available data in the reports: 7a in eight out of 13 studies;…”

“…Studies with more than five neonates were reviewed 3. Different thresholds of serum creatinine rise and/or BUN were used: BUN >16-30 mg/dl and/or Cr>0.8-1.5 mg/dl; 50% rise in Cr(Jeon 2007); rise of Cr of 0.4 mg/dl(Le 2009). 4 …”

Challenging issues in neonatal candidiasis

“…Data are limited in standard dosing, starting with Fungal infections are associated with the greatest decrease (50%) in platelet counts, similar to gram-negative infections (Guida, 2003) the highest safe dose on day 1 of treatment, and use with prompt CVC removal with fungemia. A-II evidence supports AmB deoxycholate starting at 1 mg/kg per day, with a recent study demonstrating safety when increasing up to 1.5 mg/kg if needed 32 . Lipid preparations need a similar approach, starting at 5 mg/kg so underdosing does not affect efficacy, and one study has examined increasing to 7 mg/kg 33,34 .…”