Refractory neonatal candidemia and high-dose micafungin pharmacotherapy.
OBJECTIVE
Preterm neonates with candidemia frequently have persistently positive blood cultures, despite the use of conventional antifungal therapy. Our institutional treatment protocol for invasive candidiasis incorporates lipid complex amphotericin B as initial therapy with the sequential addition of fluconazole and high-dose micafungin (10 mg kg(-1)) every 48 to 72 h, if cultures from a sterile site remain positive. Our study objectives were to compare the clinical profiles and outcomes of preterm neonates with candidemia that responded to or were refractory to conventional antifungals. We further evaluate the clinical efficacy of high-dose micafungin pharmacotherapy of refractory candidemia.


METHODS
A chart review was performed on preterm infants (n=29) with invasive candidiasis and demographic, microbiologic and outcome data abstracted. Proportions and continuous variables were compared between the groups using Fisher's exact two-tailed test and t-test.


RESULTS
The refractory (n=19) candidemia and early responder (n=10) groups had comparable mean (+/-s.d.) gestation, 27(+/-3.1) vs 27.8 (+/-2.7) weeks. The refractory group was administered antibiotics for a longer duration, 14.5 (+/-10.3) vs 7.1 (+/-5) days, had a preponderance of non-albicans infections, 11 (57.9%) vs 1 (10%) and were on enteral feeds > 20 ml kg(-1) day(-1) significantly less often (21 vs 70%). Mortality was significantly higher (53 vs 20%) and fungal clearance rates lower (63.1 vs 90%), with a longer duration to clearance in the group with refractory candidemia. Mean aspartate aminotransferase (AST) showed a statistically significant increase following micafungin treatment, although clinical significance remains unclear.


CONCLUSIONS
Candidemia refractory to conventional antifungals is associated with prolonged antibiotic use, lack of enteral nutritive feeds and non-albicans infection. Despite high-dose micafungin pharmacotherapy in combination with conventional antifungals, infants with refractory candidemia had high mortality and poor fungal clearance.
Natarajan
G
G
Division of Neonatology, Children's Hospital of Michigan and Hutzel Women's Hospital, Detroit, MI 48201, USA. gnatara@med.wayne.edu
Lulic-Botica
M
M
Aranda
J V
JV
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001219:Aspartate Aminotransferases / Q000097:blood; D002177:Candidiasis / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000008:administration & dosage* / Q000009:adverse effects; D004750:Enteral Nutrition; D005260:Female; D016469:Fungemia / Q000188:drug therapy* / Q000401:mortality; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000188:drug therapy* / Q000401:mortality; D055666:Lipopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D008134:Long-Term Care; D008297:Male; D000077551:Micafungin; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D001219:Aspartate Aminotransferases; D000077551:Micafungin