Persistently positive cultures and outcome in invasive neonatal candidiasis

Background. A persistently positive culture >24 h after starting antibiotic therapy has been correlated with adverse outcome in several invasive bacte rial infections, but few reports address persistent positivity and outcome in infections caused by fungi and other pathogens that replicate more slowl y and therefore may succumb less quickly to therapy. Methods. To assess whether positive culture >24 h after achieving target do ses (amphotericin greater than or equal to 0.5 mg/kg/day or fluconazole gre ater than or equal to 6 mg/kg/day) of systemic antifungal therapy predicts focal infectious complication(s) or death from infection, we compared neona tal intensive care unit infants who had persistent (P+) or nonpersistent (P -) positive cultures with invasive candidiasis (clinical signs of infection and recovery of Candida from a normally sterile site) at this center from January 1, 1981, through June 30, 1999. Infants who died less than or equal to 24 h after attaining target dosing, recovered without therapy, had a fo cal infectious complication already present at the time target dosing was a chieved or were diagnosed with invasive candidiasis only postmortem were ex cluded. Results. We identified 58 P+ (29, 12 and 7 had positive cultures for >7, >1 4 and greater than or equal to 21 days, respectively) and 38 P- infants. No differences were found between P+ and P- for birth weight; gestational age ; gender; onset age; central vascular catheters; necrotizing enterocolitis, surgery or bacterial sepsis; or duration of parenteral nutrition, antibiot ics, tracheal intubation or postnatal steroids. PS were more likely to have blood or cerebrospinal fluid involvement (68 vs. 45%, P = 0.03). Distribut ion of Candida species was similar (albicans in 53 vs. 63% for P+ vs. P-). P+ were significantly more likely to develop later "fungus ball" uropathy ( 16 of 56 vs. 2 of 32, P = 0.01), to develop renal infiltration (11 of 56 vs . 1 of 32, P = 0.03) and to die from invasive candidiasis (11 of 58 vs. 0 o f 38, P = 0.003) than P-. P+ were also more likely to develop endocarditis, abscess, ventriculitis and invasive dermatitis, although P > 0.05. Focal c omplication increased as duration of P+ increased (48, 55, 67 and 71% at >1 , >7, >14 and greater than or equal to 21 days, P = 0.06). When comparing o nly those with positive blood and/or cerebrospinal fluid culture, similar p atterns were observed, although only death and focal complication or death from invasive candidiasis attained significance. Conclusions. These observations suggest that in neonatal invasive candidias is: (1) cultures usually remain positive >24 h after attaining target antif ungal doses; (2) aggressive imaging for focal complications may be reserved for infants with persistently positive cultures after several days of anti fungal therapy at target doses or have signs strongly suggestive of focal c omplication; (3) focal complications and/or death from candidiasis increase with persistence; (4) focal complications increase with duration of persis tence; (5) serial culture of infected site(s) helps predict outcome and the need for aggressive surveillance and intervention for focal complications.