Neonatal Fungal Infections Research Articles

Neonatal candidosis: clinical picture, management controversies and consensus, and new therapeutic options.

Candida infections are increasingly being recognized as a major cause of septicaemia in neonatal intensive care units, and are associated with high morbidity (25%) and mortality (25-54%). Low birth weight pre-term infants are especially vulnerable to this devastating disease. The most frequently encountered fungal infections are caused by Candida albicans, Candida parapsilosis and, rarely, by Candida tropicalis. Amphotericin B (with or without flucytosine) is the treatment of choice for Candida infections in neonates. Conventional amphotericin B use is often limited by its severe side effects, although these tend to be fewer in neonates than in adults. Possible alternatives to amphotericin B include triazoles (such as fluconazole) and lipid preparations of amphotericin B. Liposomal encapsulation of amphotericin B has been shown to decrease the toxicity of the drug while maintaining its antifungal activity. The liposomal formulation AmBisome has proved to be effective in the treatment of severe fungal infections in adult and paediatric immunocompromised patients who fail to respond to conventional amphotericin B. The experience with AmBisome in the treatment of fungal infections in neonates is limited, and the drug has been used mainly in infants either failing conventional amphotericin B or having intolerable toxicity. Pharmacokinetic studies have not yet been performed in neonates. Three uncontrolled studies published between 1997 and 1998 on AmBisome (dose range 1-7 mg/kg/day) in the treatment of neonatal candidosis revealed that the drug was effective and safe. New information is accumulating on the safe use of high-dose AmBisome (5-7 mg/kg/day) in very low birth weight infants, and successful use of the drug as first-line therapy of neonatal candidosis. These promising results suggest a potential role for AmBisome as an additional first-line treatment of systemic candidosis in neonates.

Epidemiology of Fungal Infection in Neonates

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Renal tolerance with the use of intralipid-amphotericin B in low-birth-weight neonates.

Amphotericin B is still the first-line therapy for neonatal fungal infections. With several comparative trials of intralipid-based amphotericin B (IL-AmB) demonstrating its clinical effectiveness and reduced renal toxicity in adults, we examined the renal tolerance and infection outcome in low-birth-weight infants in our 48-bed NICU treated with IL-AmB. Over 2 years, 52 patients (58 courses) received > or = 10 days of IL-AmB. Nineteen charts (23 episodes) were randomly accessed and reviewed. Mean birthweight = 747 grams, gestational age = 25.6 weeks, total IL-AmB dosage = 19.8 +/- 3.3 mg/kg (n = 23); 20 of these episodes were fungal culture positive (9 fungemias). Only one patient (who died during therapy) had a rise in creatinine of > 0.3 mg/dL. Overall, serum creatinine decreased significantly after Day 10 of IL-AmB therapy, from 0.93 +/- 0.42 mg/dL at baseline, to 0.54 +/- 0.24 after 19 days of therapy (p < 0.0001). Serial urine output, serum potassium and potassium supplementation data showed no significant differences from baseline. No interruption of therapy nor infusion reactions occurred. Only one death occurred attributable to fungal infection. Intralipid-amphotericin B may provide an effective alternative in the antifungal therapy of low birthweight neonates, without nephrotoxicity. Further prospective, comparative trials are warranted.

Prospective study of fluconazole therapy in systemic neonatal fungal infection.

Standard neonatal systemic antifungal therapy with amphotericin B and flucytosine can be associated with toxicity, drug resistance and the need for prolonged venous access. There is consequently a need for alternative treatment options. To assess the efficacy and safety of fluconazole in the treatment of systemic neonatal fungal infections. Open, nonrandomized evaluation of fluconazole treatment in 20 consecutively enrolled neonates with systemic fungal infection. Clinical and microbiologic cure was achieved in 12 of 19 (63%) of infants treated. One additional infant received prior amphotericin B therapy and is included for assessment of side effects. One infant with Torulopsis glabrata infection failed treatment. Six infants died of Gram-negative bacterial infection and other intercurrent medical problems. Fluconazole appeared to be safe and effective for treatment of systemic candidal infection in the neonate although more data are required in very low birth weight infants.

Renal Tolerance With The Use Of Intralipid-Amphotericin B In Low Birthweight Neonates. ♦ 1311

Introduction: Amphotericin B (AmB) is still the first-line therapy for neonatal fungal infections. Recently, lower renal and hematologic toxicity profiles have been observed for Intralipid-based Amphotericin B(IL-AmB) in critically ill patients. Based on initial empirically observed benefits of this admixture in selected neonates, we reviewed the renal tolerance and infection outcome in low birthweight infants treated with IL-AmB in our NICU.

Granulocyte colony-stimulating factor as a marker for bacterial infection in neonates

OBJECTIVE: To evaluate granulocyte colony-stimulating factor (G-CSF) as an early marker of bacterial or fungal infection in neonates. STUDY DESIGN: We measured G-CSF levels in infants of varying gestational and postnatal ages. We separated the infants into three groups: group 1, positive bacterial or fungal blood culture result; group 2, negative blood culture result but evidence of clinical sepsis; and group 3, negative blood culture result and no or weak evidence of sepsis. Comparison of mean G-CSF levels by group was accomplished by an analysis of variance. RESULTS: One hundred seventy-six evaluations for sepsis were done for 156 infants with gestational ages ranging from 24 to 43 weeks; 50% of these infants were less than 35 weeks of gestational age. The mean G-CSF levels of groups 1 and 2 were significantly higher than those of group 3. The mean G-CSF level of each group was 2278 pg/ml (group 1), 1873 pg/ml (group 2), and 280 pg/ml (group 3) ( p <0.001). On the basis of a cutoff level of 200 pg/ml, the sensitivity of the test was 95%, specificity 73%, positive predictive value 40%, and negative predictive value 99%. CONCLUSION: G-CSF levels represent a sensitive marker of infection in neonates of all gestational ages. (J P EDIATR 1996;128:765-9)

Systemic fungal infections in neonates

Systemic fungal infections, previously considered to be a rare complication, are now frequently diagnosed in VLBW infants receiving intensive care. Confirming the diagnosis by laboratory tests is difficult and a high index of suspicion is required. Prompt and aggressive use of antifungal treatment is justified in a clinically septic neonate, especially those with a raised serum concentration of C reactive protein, who do not show a satisfactory response to antibiotics. The newer generation of liposomal amphotericin and azole antifungal drugs appear to be safe, effective, and well tolerated. With increasing awareness, prompt treatment, and better neonatal intensive care, the outcome of systemic fungal infection in preterm infants should improve.

Antifungal agents and their renal implications in the neonate

The incidence of superficial or systemic fungal infections has been increasing in neonates. The cause of this increased susceptibility to fungal infections is due to the increased use of mechanical ventilation, indwelling catheters, broad-spectrum antibiotic therapy, parenteral nutrition, and steroid therapy. The most common organism encountered in neonatal infections is Candida species. This article will cover the etiology, signs, symptoms, diagnosis, and treatment of the usual neonatal fungal infections. Each of the antifungal agents used to treat neonates will be discussed with regard to its mechanism of action, pharmacokinetics, indications, normal and renal functional impairment dosing, and adverse effects.

Distinct mechanisms of epithelial adhesion for Candida albicans and Candida tropicalis. Identification of the participating ligands and development of inhibitory peptides.

The yeast Candida albicans is the leading cause of disseminated fungal infection in neonates, immunocompromised hosts, diabetics, and postoperative patients; Candida tropicalis is the second most frequent isolate. Because the integrin analogue in C. albicans shares antigenic, structural, and functional homologies with the beta 2-integrin subunits alpha M and alpha X, we investigated the role of integrin analogues in epithelial adhesion of C. albicans and C. tropicalis. On flow cytometry with the monoclonal antibody (mAb) OKM1, surface fluorescence was highest for C. albicans and significantly reduced for C. tropicalis (P < 0.001). However, adhesion to the human epithelial cell line HeLa S3 did not differ for these two candidal species: specific adhesion was highest for C. albicans at 44.0 +/- 1.8%, and only slightly lower for C. tropicalis at 38.8 +/- 3.6% (P = NS). The disparity between expression of the integrin analogue and epithelial adhesion suggested distinct mechanisms for this process in C. albicans versus C. tropicalis. Preincubation of C. albicans with anti-alpha M mAbs, with purified iC3b (the RGD ligand for the integrin analogue), or with 9-15-mer RGD peptides from iC3b all inhibited epithelial adhesion significantly (P < 0.001-0.04). Purified fibronectin or fibronectin-RGD peptides failed to block C. albicans adhesion. In contrast, epithelial adhesion of C. tropicalis was significantly inhibited by purified fibronectin and its RGD peptides (P < or = 0.021), but not by iC3b nor the iC3b-RGD peptides. Both iC3b and fibronectin were identified on the surface of epithelial cells after growth in serum-free medium. A polyclonal antibody to C3 inhibited C. albicans adhesion while a control antibody to fibronectin was ineffective; the converse was true for C. tropicalis. These results indicate that the pathogenic yeasts C. albicans and C. tropicalis recognize distinct RGD ligands present at the surface of the epithelial cell and that these interactions can be differentially inhibited by defined RGD peptides containing appropriate flanking sequences.

Fungal infection in neonates

Fungal infection in neonates